Xiaodong Wang - Dalian Institute of Chemical Physics

Xiaodong Wang
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Name
Xiaodong Wang
Affiliation
Dalian Institute of Chemical Physics
Country
China

Publications Authored By Xiaodong Wang

2017Jan
J. Med. Chem.
J Med Chem 2017 Jan 5. Epub 2017 Jan 5.
National Institute of Biological Sciences , No. 7 Science Park Road, Zhongguancun Life Science Park, Changping District, Beijing 102206, China.

On the basis of its essential role in driving inflammation and disease pathology, cell necrosis has gradually been verified as a promising therapeutic target for treating atherosclerosis, systemic inflammatory response syndrome (SIRS), and ischemia injury, among other diseases. Most necrosis inhibitors targeting receptor-interacting protein 1 (RIP1) still require further optimization because of weak potency or poor metabolic stability. We conducted a phenotypic screen and identified a micromolar hit with novel amide structure.Read More

Medicinal chemistry efforts yielded a highly potent, selective, and metabolically stable drug candidate, compound 56 (RIPA-56). Biochemical studies and molecular docking revealed that RIP1 is the direct target of this new series of type III kinase inhibitors. In the SIRS mice disease model, 56 efficiently reduced tumor necrosis factor alpha (TNFα)-induced mortality and multiorgan damage. Compared to known RIP1 inhibitors, 56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies.

2017Jan
Org. Lett.
Org Lett 2017 Jan 27;19(1):218-221. Epub 2016 Dec 27.
College of Chemistry & Materials Engineering, Wenzhou University , Wenzhou, Zhejiang 325035, P. R. China.

The first example of the palladium-catalyzed sequential nucleophilic addition followed by an intramolecular cyclization of functionalized nitriles with arylboronic acids has been achieved, providing an efficient synthetic pathway to access structurally diverse isoquinolines and isoquinolones. This methodology has also been successfully applied to the total synthesis of the topoisomerase I inhibitor CWJ-a-5 (free base).Read More

2017Jan
ChemSusChem
ChemSusChem 2017 Jan 3. Epub 2017 Jan 3.
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, CHINA.

For the first time, a series of renewable C9-C12 triketones with repeating [COCH2CH2] units were synthesized in high carbon yields (~90%) by the aqueous phase hydrogenation of the aldol condensation products of 5-hydroxylmethylfurfural (HMF) and ketones over the Au/TiO2 catalyst. Compared with the reported routes, this new route has many advantages such as environmental friendly, fewer steps, using a cheaper easier separation and reusable catalyst, etc..Read More

The triketones as obtained can be used as feedstocks in the production of conducting or semi-conducting polymers. By the solvent-free intramolecular aldol condensation over solid base catalysts, these triketones were selectively converted to diketones which can be used as the intermediates in synthesis of useful chemicals or polymers. As another application, the triketones and diketones can also be utilized as precursors for the synthesis of jet fuel range branched cycloalkanes which have low freezing points (224-250 K) and high densities (~0.81 g mL-1).

2017Jan
Proc. Natl. Acad. Sci. U.S.A.
Proc Natl Acad Sci U S A 2017 Jan 17. Epub 2017 Jan 17.
Department of Plant Sciences, University of California, Davis, CA 95616;

Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. Young polyploid species such as wheat, which was domesticated less than 10,000 y ago, have high levels of sequence identity among subgenomes that mask the effects of recessive alleles. Such redundancy reduces the probability of selection of favorable mutations during natural or human selection, but also allows wheat to tolerate high densities of induced mutations.Read More

Here we exploited this property to sequence and catalog more than 10 million mutations in the protein-coding regions of 2,735 mutant lines of tetraploid and hexaploid wheat. We detected, on average, 2,705 and 5,351 mutations per tetraploid and hexaploid line, respectively, which resulted in 35-40 mutations per kb in each population. With these mutation densities, we identified an average of 23-24 missense and truncation alleles per gene, with at least one truncation or deleterious missense mutation in more than 90% of the captured wheat genes per population. This public collection of mutant seed stocks and sequence data enables rapid identification of mutations in the different copies of the wheat genes, which can be combined to uncover previously hidden variation. Polyploidy is a central phenomenon in plant evolution, and many crop species have undergone recent genome duplication events. Therefore, the general strategy and methods developed herein can benefit other polyploid crops.

2016Dec
Nanoscale Res Lett
Nanoscale Res Lett 2016 Dec 27;11(1):38. Epub 2016 Jan 27.
Institute of Fundamental and Frontier Science, State Key Laboratory of Electronic Thin Film and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, 610054, People's Republic of China.

Ordered nanodroplet arrays and aligned nanodroplet chains are fabricated using ion-beam-directed self-organization. The morphological evolution of nanodroplets formed on GaAs (100) substrates under ion beam bombardment is characterized by scanning electron microscopy and atomic force microscopy. Ordered Ga nanodroplets are self-assembled under ion beam bombardment at off-normal incidence angles.Read More

The uniformity, size, and density of Ga nanodroplets can be tuned by the incident angles of ion beam. The ion beam current also plays a critical role in the self-ordering of Ga nanodroplets, and it is found that the droplets exhibit a similar droplet size but higher density and better uniformity with increasing the ion beam current. In addition, more complex arrangements of nanodroplets are achieved via in situ patterning and ion-beam-directed migration of Ga atoms. Particularly, compared to the destructive formation of nanodroplets through direct ion beam bombardment, the controllable assembly of nanodroplets on intact surfaces can be used as templates for fabrication of ordered semiconductor nanostructures by droplet epitaxy.

This open-label, multicenter, phase Ib study assessed the safety and preliminary activity of duligotuzumab, a dual-action antibody that blocks ligand binding to human epidermal growth factor receptor 3 (HER3) and epidermal growth factor receptor, in combination with chemotherapy, in the first-line treatment of patients with recurrent/metastatic squamous cell cancer of the head and neck.
On day 1, duligotuzumab at a dose of 1650 mg intravenously was combined with cisplatin at a dose of 100 mg/m(2) and 5-fluorouracil at a dose of 1000 mg/m(2) /day on days 1 to 4 in treatment arm A, or carboplatin (area under the curve, 6 mg/mL/min) and paclitaxel (at a dose of 200 mg/m(2) ) in treatment arm B. Up to 6 cycles (21 days/cycle) were followed by duligotuzumab maintenance until disease progression or intolerable toxicity occurred.Read More


Nine patients in arm A and 15 patients in arm B received a median of 6 cycles of chemotherapy, and a median of 11 cycles (arm A) and 9 cycles (arm B) of duligotuzumab. Dose-limiting toxicities occurred in 3 patients in arm A and 1 patient in arm B. Grade ≥ 3 treatment-related adverse events (graded according to graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]) in ≥ 3 patients were neutropenia (5 patients), hypokalemia (4 patients), dehydration (3 patients), anemia (3 patients), and diarrhea (3 patients) in arm A, and neutropenia (8 patients), anemia (5 patients), febrile neutropenia (4 patients), leukopenia (3 patients), thrombocytopenia (3 patients), and hypomagnesemia (3 patients) in arm B. The chemotherapy dose was reduced in 19 of 24 patients. Sixteen patients (67%) demonstrated objective responses regardless of human papillomavirus status or neuregulin 1 (NRG1) mRNA expression (arm A: 2 confirmed complete responses and 4 confirmed partial responses; arm B: 2 confirmed complete responses and 8 confirmed partial responses).
Duligotuzumab in combination with cisplatin/5-fluorouracil or carboplatin/paclitaxel demonstrated encouraging activity in patients with recurrent/metastatic squamous cell cancer of the head and neck; an association with increased frequency and severity of select adverse events relative to historical data was suggestive of the potentiation of chemotherapy-related adverse events. Cancer 2016;122:3803-3811. © 2016 American Cancer Society.

2016Dec
Angew. Chem. Int. Ed. Engl.
Angew Chem Int Ed Engl 2016 Dec 9;55(52):16054-16058. Epub 2016 Nov 9.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Homogeneous catalysts generally possess superior catalytic performance compared to heterogeneous catalysts. However, the issue of catalyst separation and recycling severely limits their use in practical applications. Single-atom catalysts have the advantages of both homogeneous catalysts, such as "isolated sites", and heterogeneous catalysts, such as stability and reusability, and thus would be a promising alternative to traditional homogeneous catalysts.Read More

In the hydroformylation of olefins, single-atom Rh catalysts supported on ZnO nanowires demonstrate similar efficiency (TON≈40000) compared to that of homogeneous Wilkinson's catalyst (TON≈19000). HAADF-STEM and infrared CO chemisorption experiments identified isolated Rh atoms on the support. XPS and XANES spectra indicate that the electronic state of Rh is almost metallic. The catalysts are about one or two orders of magnitude more active than most reported heterogeneous catalysts and can be reused four times without an obvious decline in activity.

2016Dec
Mol. Plant Microbe Interact.
Mol Plant Microbe Interact 2016 Dec 4;29(12):977-989. Epub 2017 Jan 4.
1 Department of Plant Science, University of California, Davis, CA 95616, U.S.A.

In Arabidopsis, NPR1 is a key transcriptional coregulator of systemic acquired resistance. Upon pathogen challenge, NPR1 translocates from the cytoplasm to the nucleus, in which it interacts with TGA-bZIP transcription factors to activate the expression of several pathogenesis-related (PR) genes. In a screen of a yeast two-hybrid library from wheat leaves infected with Puccinia striiformis f.Read More

sp. tritici, we identified a conserved rust protein that interacts with wheat NPR1 and named it PNPi (for Puccinia NPR1 interactor). PNPi interacts with the NPR1/NIM1-like domain of NPR1 via its C-terminal DPBB_1 domain. Using bimolecular fluorescence complementation assays, we detected the interaction between PNPi and wheat NPR1 in the nucleus of Nicotiana benthamiana protoplasts. A yeast three-hybrid assay showed that PNPi interaction with NPR1 competes with the interaction between wheat NPR1 and TGA2.2. In barley transgenic lines overexpressing PNPi, we observed reduced induction of multiple PR genes in the region adjacent to Pseudomonas syringae pv. tomato DC3000 infection. Based on these results, we hypothesize that PNPi has a role in manipulating wheat defense response via its interactions with NPR1.

2016Dec
PLoS ONE
PLoS One 2016 16;11(12):e0167994. Epub 2016 Dec 16.
Department of Electrical Engineering, Columbia University, New York, New York, United States of America.

Exploring linkage disequilibrium (LD) patterns among the single nucleotide polymorphism (SNP) sites can improve the accuracy and cost-effectiveness of genomic association studies, whereby representative (tag) SNPs are identified to sufficiently represent the genomic diversity in populations. There has been considerable amount of effort in developing efficient algorithms to select tag SNPs from the growing large-scale data sets. Methods using the classical pairwise-LD and multi-locus LD measures have been proposed that aim to reduce the computational complexity and to increase the accuracy, respectively.Read More

The present work solves the tag SNP selection problem by efficiently balancing the computational complexity and accuracy, and improves the coverage in genomic diversity in a cost-effective manner. The employed algorithm makes use of mutual information to explore the multi-locus association between SNPs and can handle different data types and conditions. Experiments with benchmark HapMap data sets show comparable or better performance against the state-of-the-art algorithms. In particular, as a novel application, the genome-wide SNP tagging is performed in the 1000 Genomes Project data sets, and produced a well-annotated database of tagging variants that capture the common genotype diversity in 2,504 samples from 26 human populations. Compared to conventional methods, the algorithm requires as input only the genotype (or haplotype) sequences, can scale up to genome-wide analyses, and produces accurate solutions with more information-rich output, providing an improved platform for researchers towards the subsequent association studies.

2016Dec
ACS Med Chem Lett
ACS Med Chem Lett 2016 Dec 13;7(12):1044-1049. Epub 2016 Sep 13.
Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States; Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States; Meryx, Inc., 450 West Dr., Chapel Hill, North Carolina 27599, United States.

Mer tyrosine kinase (MerTK) is aberrantly elevated in various tumor cells and has a normal anti-inflammatory role in the innate immune system. Inhibition of MerTK may provide dual effects against these MerTK-expressing tumors through reducing cancer cell survival and redirecting the innate immune response. Recently, we have designed novel and potent macrocyclic pyrrolopyrimidines as MerTK inhibitors using a structure-based approach.Read More

The most active macrocycles had an EC50 below 40 nM in a cell-based MerTK phosphor-protein ELISA assay. The X-ray structure of macrocyclic analogue 3 complexed with MerTK was also resolved and demonstrated macrocycles binding in the ATP binding pocket of the MerTK protein as anticipated. In addition, the lead compound 16 (UNC3133) had a 1.6 h half-life and 16% oral bioavailability in a mouse PK study.

2016Dec
Sci Rep
Sci Rep 2016 Dec 21;6:39598. Epub 2016 Dec 21.
National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.

As new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance.Read More

We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo, without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).

2016Dec
Int J Nanomedicine
Int J Nanomedicine 2016;11:6781-6794. Epub 2016 Dec 14.
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy.

Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro.Read More

In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections.

2016Dec
Biochim. Biophys. Acta
Biochim Biophys Acta 2016 Dec 23. Epub 2016 Dec 23.
University of Victoria-Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101-4464 Markham St., Victoria, BC V8Z 7X8, Canada; Department of Biochemistry and Microbiology, University of Victoria, Petch Building Room 207, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada. Electronic address:

In this work, we combined the use of two MALDI matrices (quercetin and 9-aminoacridine), a recently developed new matrix coating technique - matrix coating assisted by an electric field (MCAEF), and matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) to detect and image endogenous compounds in the cancerous and non-cancerous regions of three human prostate cancer (stage II) tissue specimens. After three rounds of imaging data acquisitions (i.e.Read More

, quercetin for positive and negative ion detection and 9-aminoacridine for negative ion detection), and metabolite identification, a total of 1091 metabolites including 1032 lipids and 59 other metabolites were routinely detected and successfully localized. Of these compounds, 250 and 217 were only detected in either the cancerous or the non-cancerous regions respectively, although we cannot rule out the presence of these metabolites at concentrations below the detection limit. In addition, 152 of the other 624 metabolites showed differential distributions (p<0.05, t-test) between the two regions of the tissues. Further studies on a larger number of clinical specimens will need to be carried out to confirm this large number of apparently cancer-related metabolites. The successful determination of the spatial locations and abundances of these endogenous biomolecules indicated significant metabolism abnormalities - e.g., increased energy charge and under-expression of neutral acyl glycerides, in the prostate cancer samples. To our knowledge, this work has resulted in MALDI-MS imaging of the largest group of metabolites in prostate cancer thus far and demonstrated the importance of using complementary matrices for comprehensive metabolomic imaging by MALDI-MS. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

2016Dec
ChemMedChem
ChemMedChem 2016 Dec 28. Epub 2016 Dec 28.
Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Macrocycles have attracted significant attention in drug discovery recently. In fact, a few de novo designed macrocyclic kinase inhibitors are currently in clinical trials with good potency and selectivity for their intended target. In this study, we successfully engaged a structure-based drug design approach to discover macrocyclic pyrimidines as potent Mer tyrosine kinase (MerTK)-specific inhibitors.Read More

An enzyme-linked immunosorbent assay (ELISA) in 384-well format was employed to evaluate the inhibitory activity of macrocycles in a cell-based assay assessing tyrosine phosphorylation of MerTK. Through structure-activity relationship (SAR) studies, analogue 11 [UNC2541; (S)-7-amino-N-(4-fluorobenzyl)-8-oxo-2,9,16-triaza-1(2,4)-pyrimidinacyclohexadecaphane-1-carboxamide] was identified as a potent and MerTK-specific inhibitor that exhibits sub-micromolar inhibitory activity in the cell-based ELISA. In addition, an X-ray structure of MerTK protein in complex with 11 was resolved to show that these macrocycles bind in the MerTK ATP pocket.

2016Dec
ChemSusChem
ChemSusChem 2016 Dec 29. Epub 2016 Dec 29.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, P.R. China.

For the first time, we demonstrated two integrated processes for the direct synthesis of dodecanol or 2,4,8-trimethylnonane (a jet fuel range C12 -branched alkane) using methyl isobutyl ketone (MIBK) that can be derived from lignocellulose. The reactions were carried out in dual-bed continuous flow reactors. In the first bed, MIBK was selectively converted to a mixture of C12 alcohol and ketone.Read More

Over the Pd-modified magnesium- aluminium hydrotalcite (Pd-MgAl-HT) catalyst, a high total carbon yield (73.0 %) of C12 oxygenates can be achieved under mild conditions. In the second bed, the C12 oxygenates generated in the first bed were hydrogenated to dodecanol over a Ru/C catalyst or hydrodeoxygenated to 2,4,8-trimethylnonane over a Cu/SiO2 catalyst. The as-obtained dodecanol can be used as feedstock in the production of sodium dodecylsulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS), which are widely used as surfactants or detergents. The asobtained 2,4,8-trimethylnonane can be blended into conventional jet fuel without hydroisomerization.

2016Nov
Mitochondrial DNA A DNA Mapp Seq Anal
Mitochondrial DNA A DNA Mapp Seq Anal 2016 Nov 8;27(6):4586-4587. Epub 2016 Sep 8.
a College of Animal Science, Guizhou University , Guiyang , P.R. China.

In this study, we cloned and sequenced the complete mitochondrial DNA (mtDNA) of Synechogobius hasta to characterize and compare their mitochondrial genomes. The total length of the mitochondrial genome is 16,655 bp with an accession number KM891736. The organization of the mitochondrial genomes was similar to those reported from other fish mitochondrial genomes containing 37 genes (13 protein-coding genes, 2 ribosomal RNA and 22 transfer RNAs) and a major non-coding control region.Read More

Except for ND6 and 8 tRNAs, all other genes are encoded on the heavy strand. The base composition of the 13 mitochondrial protein-coding genes in the third position was relatively low (9.7%). The complete mitogenome may provide important date set for the study of genetic mechanism of S. hasta.

2016Nov
Arch. Gynecol. Obstet.
Arch Gynecol Obstet 2016 Nov 22;294(6):1219-1226. Epub 2016 Aug 22.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Renmin South Road, Section 3, Chengdu, 610041, Sichuan, China.

Hypoxia inducible factor-1α (HIF-1α), regulated in development and DNA damage response-1 (REDD1), and mammalian target of rapamycin (mTOR) play distinct roles in response to hypoxia. The aim of this study was to evaluate whether the HIF-1α-REDD1-mTOR-mediated hypoxic stress response also operates normally in estrogen-induced cholestasis.
Pregnant rats were administered with ethinylestradiol (EE) to induce cholestasis and then were subjected to feto-placental ischemia reperfusion (IR); as controls, one group received neither EE nor IR, and another two groups received only EE or IR.Read More


Giving rats either EE alone or IR alone increased placental levels of HIF-1α, REDD1, glucose transporter-1 (GLUT1), and phosphoglycerate kinase-1 (PGK1), and decreased placental mTOR and lactic dehydrogenase A (LDHA) expression compared with the control rats. Subjecting EE-treated rats to IR did not further alter placental levels of REDD1 or mTOR, while it did elevate placental HIF-1α, GLUT1, and PGK1 expression, and decline LDHA expression. By contrast, mRNA levels did not differ significantly among the four groups for any of the proteins analyzed.
This study manifested that placental HIF-1α and its downstream glucose metabolism effectors can effectively react to hypoxia in EE-induced cholestasis rats. However, hypoxia-induced REDD1 and mTOR alternation, which responds efficiently in normal placentas, was impaired in EE-induced cholestasis placentas.

2016Nov
Radiology
Radiology 2016 Nov 7:160572. Epub 2016 Nov 7.
From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.).

Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters.Read More

HAI consisted of infusions of oxaliplatin 40 mg/m(2) for 2 hours, followed by 5-fluorouracil 800 mg/m(2) for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. (©) RSNA, 2016.

2016Nov
Biomed Res Int
Biomed Res Int 2016 17;2016:5682851. Epub 2016 Oct 17.
School of Information Sciences and Technology, Northwest University, Xi'an, Shaanxi 710069, China.

Limited-projection fluorescence molecular tomography (FMT) has short data acquisition time that allows fast resolving of the three-dimensional visualization of fluorophore within small animal in vivo. However, limited-projection FMT reconstruction suffers from severe ill-posedness because only limited projections are used for reconstruction. To alleviate the ill-posedness, a feasible region extraction strategy based on a double mesh is presented for limited-projection FMT.Read More

First, an initial result is rapidly recovered using a coarse discretization mesh. Then, the reconstructed fluorophore area in the initial result is selected as a feasible region to guide the reconstruction using a fine discretization mesh. Simulation experiments on a digital mouse and small animal experiment in vivo are performed to validate the proposed strategy. It demonstrates that the presented strategy provides a good distribution of fluorophore with limited projections of fluorescence measurements. Hence, it is suitable for reconstruction of limited-projection FMT.

2016Nov
BMC Pregnancy Childbirth
BMC Pregnancy Childbirth 2016 Nov 16;16(1):356. Epub 2016 Nov 16.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, 3rd section, South Renmin Road, Chengdu, 610041, China.

Eisenmenger's syndrome (ES) consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level. The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity and mortality in patients with ES. This study is to assess maternal and fetal outcomes in patients with ES.Read More


This study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed.
All ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p < 0.05). Arterial oxygen saturation and pre-delivery arterial oxygen tension during oxygen inhalation were significantly lower in group II (p < 0.05). Pulmonary arterial blood pressure (PABP) in both groups were high while ejection fractions (EF) were significantly lower in group II (p < 0.05). The incidence of pre-delivery heart failure in group II was substantially higher than in survivors (100 vs.14.3%, p < 0.05). Fetal complications were exceptionally high: preterm delivery (88%), small for gestational age (83%), fetal mortality (27%) and neonatal mortality (25%).
In west China,the perinatal outcome of pregnant women with ES is poor, especially when complicated with high pulmonary arterial hypertension (PAH). Pregnancy remains strongly contraindicated in ES. Effective contraception is essential, and the option of terminating pregnancy in the first trimester should be presented to pregnant women with ES.

2016Nov
BMC Pregnancy Childbirth
BMC Pregnancy Childbirth 2016 Nov 29;16(1):380. Epub 2016 Nov 29.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Heterotopic cesarean scar pregnancy is a cesarean scar pregnancy combined with an intrauterine pregnancy that predisposes a woman to life-threatening complications such as uterine rupture and massive bleeding. Preservation of the intrauterine pregnancy in heterotopic cesarean scar pregnancy is a great challenge.
We report a case of a 33-year-old woman with heterotopic cesarean scar pregnancy after IVF-embryo transfer (ET).Read More

Expectant management was carried out with early diagnosis of heterotopic cesarean scar pregnancy (HCSP), and selective fetal reduction of cesarean scar pregnancy (CSP) was performed by ultrasound-guided intrathoracic injection of potassium chloride (KCl) at 16 + 4 weeks of gestation due to aggravation of CSP. Preservation of the intrauterine pregnancy was successful and a healthy baby was delivered by cesarean section at 37 + 6 weeks of gestation.
Heterotopic cesarean scar pregnancy is an extremely rare form of heterotopic pregnancy. Patients should be appropriately counseled regarding the different treatment options available. An ultrasound-guided injection of potassium chloride may constitute a safe, minimally invasive and reliable way to terminate the heterotopic gestation and preserve the intrauterine pregnancy. Intensive management should be performed during the ongoing pregnancy and cesarean section.

2016Nov
Oncol Lett
Oncol Lett 2016 Nov 22;12(5):3818-3824. Epub 2016 Sep 22.
Department of Thoracic Surgery, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121000, P.R. China.

The present study aimed to explore the clinical characteristics of special adenine-thymine-rich sequence-binding protein 1 (SATB1) in lung adenocarcinoma and its role in the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cell line A549. The expression of SATB1 was first studied in tumor tissues of lung adenocarcinoma and adjacent non-tumor tissues. The siRNA green fluorescent protein expression vector of SATB1 was constructed and transfected into the lung adenocarcinoma cell line A549, then a fluorescence microscope was used to study the transfection efficiency.Read More

Western blot analysis was adopted to measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to study cell proliferation, invasion and migration activity, and the apoptosis rate was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor tissues but high in lung adenocarcinoma tissues, and it was reversely proportional to the differentiation degree. Following transfection with SATB1-siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition, the proliferation, invasion and migration abilities of cells decreased significantly while the apoptosis rate increased significantly (P<0.01). In conclusion SATB1 is closely associated with the pathogenesis and development of lung adenocarcinoma.

2016Oct
Int J STD AIDS
Int J STD AIDS 2016 Oct 24;27(12):1057-1062. Epub 2015 Sep 24.
Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, China

To describe the trends of the HIV epidemic among men who have sex with men (MSM) in Chengdu city, China, consecutive cross-sectional surveys were conducted by the Chengdu Center for Disease Control and Prevention. These surveys were carried out between 2009 and 2014 according to the protocol of the national HIV Sentinel Surveillance System. For the 2422 MSM who participated in the survey, the overall HIV prevalence was 15.Read More

5% (375/2422, 95% CI 14.0-16.9%). Between 2009 and 2014, the HIV prevalence of MSM remained high, with HIV-positivity rates of 15.0%, 15.1%, 16.3%, 13.9%, 17.8% and 14.0% each year respectively (χ(2) for trend = 0.008, P = 0.931). However, the majority (89.8%) of participants had had anal sex in the six months prior to the interview, and the percentage always using condoms during anal sex increased over the study period (36.7% in 2009, 39.8% in 2010, 36.9% in 2011, 46.2% in 2012, 65.1% in 2013, 49.0% in 2014; Chi-square for trend = 49.883, P < 0.001). HIV prevalence among MSM in Chengdu city has remained high. Given the continuing high levels of unprotected anal intercourse and high HIV prevalence among MSM, more effective intervention strategies are required to increase the coverage of MSM by risk-reduction interventions and to promote HIV testing among this population.

2016Oct
Reprod. Toxicol.
Reprod Toxicol 2016 Oct 1;65:179-186. Epub 2016 Aug 1.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China. Electronic address:

Intrahepatic cholestasis of pregnancy(ICP) is complicated by acute placental-fetal hypoxia. Corticotropin-releasing hormone(CRH) and urocortin(UCN) are vasodilatory regulators of blood flow in the placenta. An ethinylestradiol(EE)-induced cholestasis rat model was reproduced and serum/placental CRH/UCN were detected during 14-21days of gestation(DG).Read More

Maternal serum or placental CRH/UCN levels in the control rats were relatively consistent during 14-21DG. Serum CRH was reduced in the EE-treated rats compared with the control rats at 21DG. Regarding serum UCN, we observed a decrease at 17DG as well as an increase at 21DG in the EE-treated rats compared with the controls. Moreover, we observed a noticeable reduction of placental CRH/UCN expression at 17 or 19DG in the EE-treated rats compared with the control rats. The serum bile acids levels exhibited an inverse correlation with placental CRH/UCN expression. EE-induced cholestasis rats might serve as a good model to further investigate the pathological mechanism underlying CRH/UCN dysregulation in ICP.

2016Oct
Mol Med Rep
Mol Med Rep 2016 Oct 8;14(4):3134-44. Epub 2016 Aug 8.
Department of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, P.R. China.

Induced-resembled neuronal cells (irNCs) are generated by reprogramming human melanoma cells through the introduction of key transcription factors, providing novel concepts in the treatment of malignant tumor cells and making it possible to supply neural cells for laboratory use. In the present study, irNCs were derived from A375 cells by inducing the 'forced' overexpression of specific genes, including achaete‑scute homolog 1 (Ascl1), neuronal differentiation factor 1 (Neurod1), myelin transcription factor 1 (Myt1), brain protein 2 (Brn2, also termed POU3F2) and human brain‑derived neurotrophic factor (h‑BDNF). irNCs induced from A375 cells express multiple neuronal markers and fire action potentials, exhibiting properties similar to those of motor neurons.Read More

The reprogramming procedure comprised reverse transcription‑polymerase chain reaction and immunofluorescence staining; furthermore, electrophysiological profiling demonstrated the characteristics of the induced‑resembled neurons. The present study obtained a novel type of human irNC from human melanoma, which secreted BDNF continuously, providing a model for neuron‑like cells. Thus, irNCs offer promise in investigating various neural diseases by using neural‑like cells derived directly from the patient of interest.

2016Oct
Int J Colorectal Dis
Int J Colorectal Dis 2016 Oct 12;31(10):1675-82. Epub 2016 Aug 12.
West China School of Nursing, Sichuan University, Chengdu, 610041, China.

The objective of this study is to explore the effects of the fast-track surgery (FTS) program on inflammation and immunity in patients undergoing colorectal surgery.
From August 2014 to March 2015, a prospective and randomized controlled trial of 230 patients who underwent colorectal surgery was performed. The patients were randomly assigned to an FTS group (116 patients) or a traditional group (114 patients).Read More

Inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups.
The inflammatory mediators (CRP, IL-6, TNF-α) were lower in the FTS group than in the traditional group (P < 0.05) on postoperative day (POD) 1, POD 4, and POD 6, and the immunological indicators (IgG, IgA, C3, C4) of the FTS group were superior to those of the traditional group (P < 0.05) on POD 4 and POD 6. The time to first aerofluxus, defecation, oral intake, and ambulation after surgery was shorter in the FTS group than in the traditional group (P < 0.05); however, the duration of postoperative hospitalization did not differ significantly between the two groups (P > 0.05). The total complications were significantly lower in the FTS group than in the traditional group (P < 0.05).
The FTS program can decrease inflammation, maintain immune homeostasis, and improve rehabilitation effects in colorectal surgery patients.

2016Oct
Int. J. Mol. Med.
Int J Mol Med 2016 Oct 19;38(4):1141-51. Epub 2016 Aug 19.
Department of Hematology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.

Recent studies have indicated that the hematopoietic stem/progenitor cell (HSPC) niche, consisting of two major crucial components, namely osteoblasts (OBs) and mesenchymal stromal cells (MSCs), is responsible for the fate of HSPCs. Thus, closely mimicking the HSPC niche ex vivo may be an efficient strategy with which to develop new culture strategies to specifically regulate the balance between HSPC self-renewal and proliferation. The aim of this study was to establish a novel HSPC three-dimensional culture system by co-culturing bone marrow-derived MSCs and OBs differentiated from MSCs without any cytokines as feeder cells and applying bio-derived bone from human femoral metaphyseal portion as the scaffold.Read More

Scanning electron microscopy revealed the excellent biocompatibility of bio-derived bone with bone marrow-derived MSCs and OBs differentiated from MSCs. Western blot analysis revealed that many cytokines, which play key roles in HSPC regulation, were comprehensively secreted, while ELISA revealed that extracellular matrix molecules were also highly expressed. Hoechst 33342/propidium iodide fluorescence staining proved that our system could be used to supply a long-term culture of HSPCs. Flow cytometric analysis and qPCR of p21 expression demonstrated that our system significantly promoted the self-renewal and ex vivo expansion of HSPCs. Colony-forming unit (CFU) and long-term culture-initiating cell (LTC-IC) assays confirmed that our system has the ability for both the expansion of CD34+ hematopoietic stem cells (HPCs) and the maintenance of a primitive cell subpopulation of HSCs. The severe-combined immunodeficient mouse repopulating cell assay revealed the promoting effects of our system on the expansion of long-term primitive transplantable HSCs. In conclusion, our system may be a more comprehensive and balanced system which not only promotes the self-renewal and ex vivo expansion of HSPCs, but also maintains primitive HPCs with superior phenotypic and functional attributes.

2016Oct
Cancer Imaging
Cancer Imaging 2016 Oct 3;16(1):32. Epub 2016 Oct 3.
Department of Interventional Radiology, Peking University Cancer Hospital & Institute, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, 100142, China.

To investigate accuracy of intraprocedural cone beam computed tomography (CBCT) compared to fluoroscopy for detection of lipiodol retention pattern during conventional transarterial chemoembolization (cTACE) of hepatocellular carcinoma (HCC) and its correlation with short-term response.
Between September 2013 and July 2014, 29 patients with HCC underwent chemoembolization of 51 tumors (mean diameter 28.1 mm, range 10.Read More

0-136.3 mm). Lipiodol retention pattern was assessed by CBCT at the endpoint of cTACE compared by fluoroscopy. Depending on the pattern of tumor covered by lipiodol three classes were defined: complete (more than 90 %, no peripheral defects), moderate (50-90 %, some with or without peripheral defects), and poor (less than 50 %). Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on follow-up contrast enhanced (CE) computed tomography (CT) or magnetic resonance imaging (MRI) obtained 4-6 weeks post-cTACE. Correlations between lipiodol retention patterns on CBCT and fluoroscopy as well as tumor response were assessed using multivariate logistic regression.
Of 51 hepatic tumors, 40 (78.4 %) had complete response (CR); 8 (15.7 %) had partial response (PR); 1 (2.0 %) had stable disease (SD); and 2 (3.9 %) had progressive disease (PD). The degree of lipiodol retention scored excellent, moderate, and poor, in fluoroscopic images vs CBCT images were 23 (45.1 %) vs 39 (76.5 %), 19 (37.3 %) vs 11 (21.6 %), and 9 (17.6 %) vs 1 (2.0 %), respectively. Lipiodol retention assessment with CBCT (Az = 0.75) is more accurate than fluoroscopy (Az = 0.54) in predicting target tumor response. Other than lipiodol retention pattern assessed with CBCT (p = 0.01), tumor size (p = 0.04) is an independent predictors of CR.
CBCT is more accurate than fluoroscopy in classification of lipiodol retention pattern in HCC tumors at the time of cTACE. CBCT could be used as a reliable intra precedural monitoring modality of cTACE.

2016Oct
Front Immunol
Front Immunol 2016 4;7:403. Epub 2016 Oct 4.
BGI-Shenzhen, Shenzhen, China; China National Genebank-Shenzhen, BGI-Shenzhen, Shenzhen, China; Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance.Read More

In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment.

2016Oct
Med. Sci. Monit.
Med Sci Monit 2016 Oct 25;22:3981-3993. Epub 2016 Oct 25.
Department of Histology and Embryology, Medical College, Nantong University, Nantong, Jiangsu, China (mainland).

BACKGROUND Results from DNA microarray experiments have shown that the expression of miR-34s undergoes significant changes following spinal cord injury (SCI). The present study was designed to detect changes in the expression of miR-34s and its target genes during the acute and sub-acute stages of SCI. MATERIAL AND METHODS Luxol fast blue (LFB) staining for myelin was used to observe the differences in the general morphology of the spinal cord after SCI in a contusion model in rats.Read More

qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI. The mimic technique was used to further confirm the regulatory effect of miR-34a on the potential target genes. RESULTS The expression level of miR-34a decreased immediately after SCI and persisted for 21 days after SCI. The expression level of miR-34c began decreasing at day 1 after SCI and persisted until day 14. The expression level of miR-34b did not undergo significant change after SCI. The results of double immunofluorescence and in-situ hybridization suggested that miR-34a was highly expressed in spinal cord neurons. Based on our bioinformatics analysis, we postulated that miR-34a might participate in post-SCI cell apoptosis by regulating the target gene Notch1, and likely participated in the inflammatory response and glial scar formation by regulating the candidate genes Csf1r and PDGFRa, respectively. The expression levels of the candidate genes Csf1r and PDGFRa were consistent with Notch1 after SCI. The mimic technique further confirmed the regulatory effect of miR-34a on the aforementioned target genes. CONCLUSIONS We postulate that miR-34a and miR-34c might participate in multiple aspects of cytobiological activities following SCI. MiR-34a in particular may participate in cell apoptosis, inflammatory response, and glial scar formation by regulating the target gene Notch1 and candidate target genes Csf1r and PDGFRa respectively.

2016Oct
PLoS ONE
PLoS One 2016 26;11(10):e0165107. Epub 2016 Oct 26.
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA, 30322, United States of America.

MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines.Read More


Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database. GBM cell lines (A172, SF188, U251) were treated in vitro with increasing doses of UNC2025 (50-400nM). Cell count and viability were determined by trypan blue exclusion. Cell cycle profiles and induction of apoptosis were assessed by flow cytometric analysis after BrdU or Po-Pro-1/propidium iodide staining, respectively. Polyploidy was detected by propidium iodide staining and metaphase spread. Cellular senescence was determined by β-galactosidase staining and senescence-associated secretory cytokine analysis.
Decreased overall survival significantly correlated with high levels of GAS6 expression in GBM, highlighting the importance of TAM kinase signaling in GBM tumorigenesis and/or therapy resistance and providing strong rationale for targeting these pathways in the clinic. All three GBM cell lines exhibited dose dependent reductions in cell number and colony formation (>90% at 200nM) after treatment with UNC2025. Cell cycle analysis demonstrated accumulation of cells in the G2/M phase and development of polyploidy. After extended exposure, 60-80% of cells underwent apoptosis. The majority of surviving cells (65-95%) were senescent and did not recover after drug removal. Thus, UNC2025 mediates anti-tumor activity in GBM by multiple mechanisms.
The findings described here provide further evidence of oncogenic roles for MERTK in GBM, demonstrate the importance of kinase activity for MERTK tumorigenicity and validate UNC2025, a novel MERTK inhibitor, as a potential therapeutic agent for treatment of GBM.

Xingguang-III is a large hybrid optical parametric amplification/chirped pulse amplification laser that outputs synchronized femtosecond, picosecond, and nanosecond beams with three different wavelengths, i.e., 800, 1053, and 527 nm, respectively.Read More

We present here an in-house front-end system design that generates the 1053 nm seed laser for the ps/ns beam directly from the 800 nm femtosecond laser, which enables the three beams to have intrinsic synchronization. The results show that a seed laser of 140 μJ energy and 1053 nm central wavelength with 34 nm spectral width (FWHM) is generated and the shot-to-shot timing jitter (peak-to-valley) between the fs and the ps beam is less than 1.32 ps.

2016Sep
Eur J Med Chem
Eur J Med Chem 2016 Sep 30;120:111-20. Epub 2016 Apr 30.
Shenzhen University Cancer Research Center, Shenzhen 518060, China. Electronic address:

To study the structure-activity relationship (SAR) of Toll-like receptor 7 (TLR-7) agonists based on 8-oxoadenines, a novel subset of C9-substituted 8-hydroxy-2-(2-methoxyethoxy)-adenines and their antigen conjugates were synthesized. In vitro, the ability of cytokines (IL-12p70 and IFN-γ) induction of ligands with alkyl acid at C9-position were very weak compared with benzoic acid counter parts. Unexpectedly, its antigen conjugates that conjugated with proteins or peptides with weak immunogenicity, showed enhanced activity of cytokines induction.Read More

After administered systemically in mice in vivo, all conjugates induced prolonged increase in pro-inflammatory cytokines and antigen-specific IgG levels in serum compared with free compounds. Results from molecular dynamics (MD) simulations further confirmed the conclusion and provided the details of interaction to explain the phenomenon of experiment. In conclusion, we discovered that TLR-7 could be activated via some conjugates of weak ligand and weak antigen, which could be safer adjuvant candidates for vaccines in the future.

2016Sep
Talanta
Talanta 2016 Sep 7;158:351-60. Epub 2016 May 7.
Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu 610064, China. Electronic address:

Breast cancer (BC) is not only the most frequently diagnosed cancer, but also the leading cause of cancer death among women worldwide. This study aimed to screen the potential salivary biomarkers for breast cancer diagnosis, staging, and biomarker discovery. For the first time, a UPLC-MS based method along with multivariate data analysis, was proposed for the global saliva metabonomics analysis and diagnosis of BC, which used both hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) separations and operated in both positive (ESI+) and negative (ESI-) ionization modes.Read More

On account of different polarities of endogenous metabolites, this method was established to overcome the boundedness of a single chromatographic approach. As a result, 18 potential metabolites for diagnosing BC were identified. A nonparametric Mann-Whitney U test, heat map, and the receiver operating characteristic (ROC) were exploited to analyze the data with the purpose of evaluating the predictive power of the 18 biomarkers. Significant differences (P<0.05) were disclosed in terms of the levels of the 18 potential biomarkers between BC patients and healthy controls (HC). Among the 18 biomarkers, three up-regulated metabolites, LysoPC (18:1), LysoPC (22:6) and MG (0:0/14:0/0:0) displayed the area under the curve (AUC) values of 0.920, 0.920 and 0.929, respectively, indicating the high accuracy of this method to predict BC. In this study, an integrated metabonomics analysis in human saliva for identifying potential biomarkers to diagnose and stage BC was successfully eastablished, which was non-invasive, reliable, low-cost, and simple. The HILIC was demonstrated to be essential for a comprehensive saliva metabonomics profiling as well as RPLC separation. This saliva metabonomics technique may provide new insight into the discovery and identification of diagnostic biomarkers for BC.

2016Sep
Indian J. Microbiol.
Indian J Microbiol 2016 Sep 30;56(3):344-52. Epub 2016 Apr 30.
Department of Hydrosciences, State Key Laboratory of Pollution Control and Resources Reuse, Nanjing University, Nanjing, China.

Acidic red soil from a forest in Jiangxi Province was selected to isolate aluminum (Al)-resistant microbes, from which eight fungi were isolated. Two strains (S4 and S7) were found to be extremely tolerant to Al concentrations of up to 550 mmol L(-1) and could grow at low pH levels (3.20-3.Read More

11). Morphological and 26S rDNA sequence analyses indicated that strain S4 belonged to Eupenicillium, while strain S7 was an unclassified Trichocomaceae. Further investigation showed that both strains were endowed with the ability to resist Al; strain S4 accumulated such a substantial amount of Al that its growth was limited to a larger extent than strain S7. The lower amounts of Al adsorbed in the mycelium and the much larger amounts of Al retained in the medium, in addition to the color change of the culture solution, implied that these two strains may resist Al by preventing Al from entering the cell and by chelating Al by secreting unique metabolites outside of the cell.

2016Sep
Biol. Reprod.
Biol Reprod 2016 Sep 3;95(3):54. Epub 2016 Aug 3.
National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China

Although in vitro fertilization (IVF), one of the most effective and successful assisted reproductive technologies, is widely used for treating infertility and in animal breeding, increasing evidence indicates that IVF offspring are linked to various short- or long-term consequences. Erroneous epigenetic modifications induced by IVF are suspected of contributing to these consequences. Among these epigenetic modifications, microRNAs may affect embryo implantation and early postimplantation development.Read More

Here, we performed comparative microRNA profiling between in vivo-fertilized (IVO group) and in vitro-fertilized (IVF group) mouse embryos at Embryonic Day 3.5 (E3.5) and E7.5. Our dynamic analyses showed that the dysregulated microRNAs were mainly associated with the regulation of genes involved in carcinogenesis, genetic information processing, glucose metabolism, cytoskeleton organization, and neurogenesis. Further analysis showed that miR-199a-5p was consistently downregulated in IVF embryos compared with their IVO counterparts. Through gain- and loss-of-function experiments, we demonstrated that IVF-induced downregulation of miR-199a-5p results in a higher glycolytic rate and lower developmental potential of IVF blastocysts, including cell lineage misallocation and lower fetal survival post implantation. Therefore, preventing downregulation of miR-199a-5p may become an effective strategy for improving the development of IVF peri-implantation embryos in the future.

2016Sep
Chem. Commun. (Camb.)
Chem Commun (Camb) 2016 Sep 22;52(74):11092-5. Epub 2016 Aug 22.
Department of Polymer Science and Engineering, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China.

Polyhedral oligomeric silsesquioxanes (POSSs) were adsorbed on methylaluminoxane-activated silica for the immobilization of fluorinated bis(phenoxyimine)Ti complexes (FI catalyst). These POSSs have been characterized as horizontal spacers isolating the active sites and hindering the chain overlap in polymerization. The heterogeneous catalyst exhibits considerable activity in the synthesis of weakly entangled polyethylene.Read More

2016Sep
Sci Rep
Sci Rep 2016 Sep 1;6:32379. Epub 2016 Sep 1.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Jet fuel range branched cycloalkanes with high density (0.82 g mL(-1)) and low freezing point (217-219 K) was first prepared by the solvent-free intramolecular aldol condensation of the trione from the hydrolysis of the alkylation product of mesityl oxide and 2-methylfuran (or the one-pot reaction of mesityl oxide, 2-methylfuran and water), followed by hydrodeoxygenation (HDO).Read More

Fully automated text mining (TM) systems promote efficient literature searching, retrieval, and review but are not sufficient to produce ready-to-consume curated documents. These systems are not meant to replace biocurators, but instead to assist them in one or more literature curation steps. To do so, the user interface is an important aspect that needs to be considered for tool adoption.Read More

The BioCreative Interactive task (IAT) is a track designed for exploring user-system interactions, promoting development of useful TM tools, and providing a communication channel between the biocuration and the TM communities. In BioCreative V, the IAT track followed a format similar to previous interactive tracks, where the utility and usability of TM tools, as well as the generation of use cases, have been the focal points. The proposed curation tasks are user-centric and formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators participated. Two levels of user participation were offered to broaden curator involvement and obtain more feedback on usability aspects. The full level participation involved training on the system, curation of a set of documents with and without TM assistance, tracking of time-on-task, and completion of a user survey. The partial level participation was designed to focus on usability aspects of the interface and not the performance per se In this case, biocurators navigated the system by performing pre-designed tasks and then were asked whether they were able to achieve the task and the level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested.Database URL: http://www.biocreative.org.

2016Sep
Sci Rep
Sci Rep 2016 Sep 12;6:33226. Epub 2016 Sep 12.
Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University, Shanghai, 200001, China.

To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015.Read More

We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

MerTK tyrosine kinase is ectopically expressed in 30-50% of acute lymphoblastic leukemias (ALL) and over 80% of acute myeloid leukemias (AML) and is a potential therapeutic target. Here, we evaluated the utility of UNC2025, a MerTK tyrosine kinase inhibitor, for treatment of acute leukemia.
Pre-clinical in vitro and in vivo assays using cell lines and primary leukemia patient samples were utilized to evaluate anti-leukemic effect of UNC2025.Read More


UNC2025 potently inhibited pro-survival signaling, induced apoptosis and reduced proliferation and colony formation in MerTK-expressing ALL and AML cell lines and patient samples. Approximately 30% of primary leukemia patient samples (78 of 261 total) were sensitive to UNC2025. Sensitive samples were most prevalent in the AML, T-ALL, and minimally differentiated (M0) AML subsets. UNC2025 inhibited MerTK in bone marrow leukemia cells and had significant therapeutic effects in xenograft models, with dose-dependent decreases in tumor burden and consistent two-fold increases in median survival, irrespective of starting disease burden. In a patient-derived AML xenograft model, treatment with UNC2025 induced disease regression. Additionally, UNC2025 increased sensitivity to methotrexate in vivo, suggesting that addition of MerTK-targeted therapy to current cytotoxic regimens may be particularly effective and/or allow for chemotherapy dose reduction.
The broad spectrum activity mediated by UNC2025 in leukemia patient samples and xenograft models, alone or in combination with cytotoxic chemotherapy, support continued development of MerTK inhibitors for treatment of leukemia.

2016Aug
Immunol. Res.
Immunol Res 2016 Aug;64(4):988-1000
Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.

Regulatory dendritic cells are a potential therapeutic tool for assessing a variety of immune overreaction diseases. Paeoniflorin, a bioactive glucoside extracted from the Chinese herb white paeony root, has been shown to be effective at inhibiting the maturation and immunostimulatory function of murine bone marrow-derived dendritic cells. However, whether paeoniflorin can program conventional dendritic cells toward regulatory dendritic cells and the underlying mechanism remain unknown.Read More

Here, our study demonstrates that paeoniflorin can induce the production of regulatory dendritic cells from human peripheral blood monocyte-derived immature dendritic cells in the absence or presence of lipopolysaccharide (LPS) but not from mature dendritic cells, thereby demonstrating the potential of paeoniflorin as a specific immunosuppressive drug with fewer complications and side effects. These regulatory dendritic cells treated with paeoniflorin exhibited high CD11b/c and low CD80, CD86 and CD40 expression levels as well as enhanced abilities to capture antigen and promote the proliferation of CD4(+)CD25(+) T cells and reduced abilities to migrate and promote the proliferation of CD4(+) T cells, which is associated with the upregulation of endogenous transforming growth factor (TGF)-β-mediated indoleamine 2,3-dioxygenase (IDO) expression. Collectively, paeoniflorin could program immature dendritic cells (imDCs) and imDCs stimulated with LPS toward a regulatory DC fate by upregulating the endogenous TGF-β-mediated IDO expression level, thereby demonstrating its potential as a specific immunosuppressive drug.

2016Aug
Environ Sci Pollut Res Int
Environ Sci Pollut Res Int 2016 Aug 6;23(16):16183-93. Epub 2016 May 6.
Fishery Machinery and Instrument Research Institute, Chinese Academy of Fisheries Sciences, Shanghai, 200092, China.

Sediments play important roles, as nutrient reservoir, especially in shallow lake ecosystem. The water column of large shallow lakes is often stable but also disturbed by turbulence causing resuspension of sediments. While considerable research has been carried out to investigate the influence of sediment resuspension on nutrient release, fewer studies have been done to understand the contribution of alkaline phosphatase activity (APA) in water as a response to the two conditions (turbulence and stability).Read More

Also, effects of the two lake conditions on photosynthetic efficiency of phytoplankton are still poorly understood. This study will evaluate the effect of these two conditions on photosynthetic efficiency and APA. Sediments used in the indoor experiments were collected from Zhushan Bay in Lake Taihu. Turbulence was generated by rotors to simulate the strong wind-induced disturbance in Lake Taihu. Results of the experiments showed that TN and TP in the stable and episodically turbulent conditions were not significantly different, with TN ranging from 1.34 to 1.90 mg/L and TP from 0.08 to 0.18 mg/L. Whereas, the soluble reactive phosphorus in the episodically turbulent condition was significantly higher than in the stable condition. Episodic turbulence could enhance P cycling by resuspending sediment-associated P, which alleviated algal P limitation. In stable conditions, P deficiency induced the production of high APA, which enhanced the availability of P. Although episodic turbulence could also cause increased algal biomass, photosynthetic efficiency of the algae was also affected not only by the nutrients but also by many other factors, especially light availability. Our results suggest that episodic turbulence is an important driver of biogeochemical cycling in large shallow hypertrophic lake ecosystem.

2016Aug
Biochem. Biophys. Res. Commun.
Biochem Biophys Res Commun 2016 Aug 21;476(4):225-9. Epub 2016 May 21.
National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, No. 2 Yuan Ming Yuan Xi Lu, Haidian District, Beijing 100193, PR China. Electronic address:

The parthenotes represent ideal models mimicking the embryonic development and characterizing the function of maternal genomes as well as an alternative source of pluripotent cell lines. Besides, parthenogenetically activated (PA) embryos serve as a rapid assay system to maximize the efficiency of generating genetically modified pig CRISPR/Cas9 system, an efficient and multiplex gene editing tool, has been utilized to modify the genome of porcine parthenotes. However, lower biallelic mutation rate and high mosaicism frequency were observed.Read More

Here, we aimed to enhance the biallelic mutation rate with reduced mosaicism by optimization of the concentration and injection time of the Cas9/sgRNA mixture in porcine parthenotes. The results showed that the efficient biallelic mutation (93%) and low mosaicism (33%) could be achieved in porcine parthenotes by cytoplasmic injection of Cas9 mRNA/sgRNA (125/12.5 ng/μl) after 8 h of parthenogenetical activation. Thus, our study provides an effective strategy for increasing the biallelic mutation rate and population homogeneity of genetically modified parthenotes, which will strengthen the role of parthenotes in uncovering early embryonic development and assessing the mutation efficiency due to the simplicity and adaptability of CRISPR/Cas9.

2016Aug
J. Endocrinol.
J Endocrinol 2016 Aug 10;230(2):227-37. Epub 2016 Jun 10.
Department of Biochemistry and Molecular BiologyThird Military Medical University, Chongqing, China

In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying these effects are still incompletely understood. Emerging evidence suggest metformin as leptin sensitizer to mediate the weight-loss effect in the brain.Read More

In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5months. Afterward, mice were treated with metformin (50mg/kg or 200mg/kg) for 15days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dose-dependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis.

2016Aug
Early Hum. Dev.
Early Hum Dev 2016 Aug 4;99:21-5. Epub 2016 Jul 4.
The second Affiliated Hospital of XinJiang Medical University, XinJiang, China. Electronic address:

Many researchers have adopted 2D:4D (second to fourth finger length ratio) as a noninvasive retrospective biomarker for prenatal androgen exposure in recent years. It is thought to be related to diverse traits including behavioral phenotypes, disease susceptibility, and development of urogenital system.
To examine the relationship between 2D:4D and early foreskin development.Read More


We analyzed the digit ratio and foreskin condition in 176 cases (range 0-6years). The boys were divided into four groups according to their ages: group 1, neonates (below 28days, n=13); group 2, infants (1-12months, n=45); group 3, toddlers (1-2years old, n=42); group 4, preschool children (3-6years old, n=76). We measured the lengths of the second and fourth digits of the left and right hands. The foreskin status was classified into 4 types. Type I (phimosis), type II (partial phimosis), type III (adhesion of prepuce), type IV (normal).
The phimosis rate was 92.3%, 82.2%, 45.2%, and 38.7% in group 1 to group 4. In contrast, the proportion of normal foreskin increased from 0% in neonates to 13.2% in preschool children. The percentage of higher level of foreskin development shows a downward trend with the increase of digits ratio, and as the age grows, the percentage of normal foreskin cases also increases.
These results suggest that a higher R2D:4D (right hand 2D:4D) is a risk factor for phimosis in the early human development. Age is also a significant influence factor of foreskin conditions. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance.

We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients.
RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses.Read More


PSA transcripts were detected in 57% of abiraterone acetate-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS.
PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 1-9. ©2016 AACR.

2016Aug
Evid Based Complement Alternat Med
Evid Based Complement Alternat Med 2016 25;2016:9179470. Epub 2016 Jul 25.
Department of Genetics, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.

Recently, regulatory dendritic cells (DCregs), a newly described dendritic cell subset with potent immunomodulatory function, have attracted increased attention for their utility in treating immune response-related diseases, such as graft-versus-host disease, hypersensitivity, and autoimmune diseases. Danchaiheji (DCHJ) is a traditional Chinese formula that has been used for many years in the clinic. However, whether DCHJ can program dendritic cells towards a regulatory phenotype and the underlying mechanism behind this process remain unknown.Read More

Herein, we investigate the effects of traditional Chinese DCHJ on DCregs differentiation and a mouse model of skin transplantation. The current study demonstrates that DCHJ can induce dendritic cells to differentiate into DCregs, which are represented by high CD11b and low CD86 and HLA-DR expression as well as the secretion of IL-10 and TGF-β. In addition, DCHJ inhibited DC migration and T cell proliferation, which correlated with increased IDO expression. Furthermore, DCHJ significantly prolonged skin graft survival time in a mouse model of skin transplantation without any liver or kidney toxicity. The traditional Chinese formula DCHJ has the potential to be a potent immunosuppressive agent with high efficiency and nontoxicity.

2016Aug
Angiology
Angiology 2016 Aug 27. Epub 2016 Aug 27.
Department of Cardiovascular, Tongji University School of Medicine, Shanghai East Hospital, Shanghai, China

The differences in angiographic characteristics and cardiovascular (CV) risk factors between coronary artery aneurysm (CAA) and coronary artery ectasia (CAE) have not been compared systematically. Of 10 876 patients undergoing coronary angiography, patients with CAA (n = 85) and CAE (n = 51) were screened. The prevalence of CAA was greater than that of CAE (P < .Read More

05). The right coronary artery was the most involved (70.6%) in CAE compared with left circumflex (52.9%) and left anterior descending (41.2%). Coronary artery aneurysm coexisted with coronary artery disease (CAD) more frequently than CAE (P = .002), and the modified Gensini score of CAA was also higher than that of CAE (P < .001). The average maximum diameter was smaller, and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was lower in CAA than CAE in all 3 coronary arteries (P < .001). Multivariate analysis showed that hyperlipidemia (P = .02), smoking (P = .04), and family history of CAD (P = .02) were the independent variables most strongly associated with CAA, but not CAE. This study suggests that there are significant differences in coronary angiographic characteristics and CV risk factors between CAA and CAE.

2016Aug
Biomed Res Int
Biomed Res Int 2016 8;2016:2131859. Epub 2016 Aug 8.
Department of Orthopedics Surgery, Children's Hospital of SooChow University, Suzhou 215003, China.

Iliac bone destruction in children is uncommon and presents various imaging features. Correct diagnosis based on clinical and imaging features is difficult. This research aimed to retrospectively explore the clinical features, imaging, and histopathological diagnosis of children with iliac bone destruction.Read More

A total of 22 children with iliac bone destruction were enrolled in this retrospective analysis from two children's hospitals during July 2007 to April 2015. Clinical features, imaging, and histopathological findings were analysed. The mode of iliac bone destruction, lesion structure, and the relationship between the range of soft tissue mass and cortical destruction were determined based on imaging data. The data were analysed using descriptive methods. Of the iliac bone destruction cases, eight cases were neuroblastoma iliac bone metastasis, seven cases were bone eosinophilic granuloma, two cases were Ewing's sarcoma, two cases were osteomyelitis, one case was bone cyst, one case was bone fibrous dysplasia, and one case was non-Hodgkin's lymphoma. Iliac bone destruction varies widely in children. Metastatic neuroblastoma and eosinophilic granuloma are the most commonly involved childhood tumours.

2016Jul
Tumour Biol.
Tumour Biol 2016 Jul 22;37(7):9657-61. Epub 2016 Jan 22.
Department of Thoracic Surgery, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.

In the present study, we assessed the GRHL3 expression in 967 patients with diffuse large B cell lymphomas to identify the potential prognostic value and the development of specific therapeutic strategies. All patients enrolled were from a previous study by Hao Zhang et al. (BMC Cancer 14:333, 2014).Read More

GRHL3 expression status was evaluated by immunohistochemical analysis. Survival analysis using the Kaplan-Meier method and multivariate analysis were conducted to adjust the effect of GRHL3 expression as a potential independent prognostic factor. In the enrolled 967 patients, GRHL3 expression was detected in 398 (41.16 %) patients under immunohistochemical analysis. The 5-year survival rate in patients with GRHL3 expression was significantly lower than that in those without GRHL3 expression (37.8 vs 52.8 %, P < 0.001). Multivariate analysis identified GRHL3 expression as an independent predictor of poor survival. The sensitivity and specificity of GRHL3 for the diagnosis of germinal center B cell (GCB)/non-GCB was 89.2 % (182/204) and 82.1 % (174/212), respectively. GRHL3 expression may be useful as a prognostic factor and for the diagnosis GCB/non-GCB of diffuse large B cell lymphoma.

2016Jul
Mol Med Rep
Mol Med Rep 2016 Jul 13;14(1):41-8. Epub 2016 May 13.
Department of Cardiology, East Hospital at Tongji University, Shanghai 200120, P.R. China.

The current study aimed to investigate the relevance of the gap junction protein connexin Cx43 in coronary artery smooth muscle cell (SMC) heterogeneity and coronary artery restenosis. SMCs were isolated from the coronary artery of 3‑month‑old pigs using enzymatic digestion. Two distinct SMC populations were isolated: Rhomboid (R) and spindle‑shaped (S) cells.Read More

S‑SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills‑and valleys'' growth pattern; R‑SMCs displayed increased proliferation rates, growing as mono‑ or multi‑layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet‑derived growth factor (PDGF)‑BB with or without the gap junction blocker 18α‑glycyrrhetinic acid. Stent‑induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R‑ and S‑SMCs. Cx40 was the most abundant Cx in S‑SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R‑SMCs. Notably, PDGF‑BB converted S‑SMCs to R‑SMCs, with increased Cx43 expression, while 18α‑glycyrrhetinic acid inhibited the PDGF‑BB‑induced phenotypic alterations in S‑SMCs. Additionally, restenosis was confirmed in pigs 1‑month subsequent to stent placement. R‑SMCs were the major cell population isolated from stent‑induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention.

2016Jul
Sci China Life Sci
Sci China Life Sci 2016 Jul 7;59(7):686-93. Epub 2016 Jun 7.
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Zinc transporter 8 (ZnT8) is a major autoantigen and a predictive marker in type 1 diabetes (T1D). To investigate ZnT8-specific antibodies, a phage display library from T1D was constructed and single-chain antibodies against ZnT8 were screened and identified. Human T1D single-chain variable fragment (scFv) phage display library consists of approximately 1×10(8) clones.Read More

After four rounds of bio-panning, seven unique clones were positive by phage ELISA. Among them, C27 and C22, which demonstrated the highest affinity to ZnT8, were expressed in Escherichia coli Top10F' and then purified by affinity chromatography. C27 and C22 specifically bound ZnT8 N/C fusion protein and ZnT8 C terminal dimer with one Arg325Trp mutation. The specificity to human islet cells of these scFvs were further confirmed by immunohistochemistry. In conclusion, we have successfully constructed a T1D phage display antibody library and identified two ZnT8-specific scFv clones, C27 and C22. These ZnT8-specific scFvs are potential agents in immunodiagnostic and immunotherapy of T1D.

2016Jul
Mol. Cell
Mol Cell 2016 Jul;63(2):229-39
National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China. Electronic address:

In response to apoptotic stimuli, mitochondria in mammalian cells release cytochrome c and other apoptogenic proteins, leading to the subsequent activation of caspases and apoptotic cell death. This process is promoted by the pro-apoptotic members of the Bcl-2 family of proteins, such as Bim and Bax, which, respectively, initiate and execute cytochrome c release from the mitochondria. Here we report the discovery of a small molecule that efficiently blocks Bim-induced apoptosis after Bax is activated on the mitochondria.Read More

The cellular target of this small molecule was identified to be the succinate dehydrogenase subunit B (SDHB) protein of complex II of the mitochondrial electron transfer chain (ETC). The molecule protects the integrity of the ETC and allows treated cells to continue to proliferate after apoptosis induction. Moreover, this molecule blocked dopaminergic neuron death and reversed Parkinson-like behavior in a rat model of Parkinson's disease.

2016Jul
Sci Rep
Sci Rep 2016 Jul 27;6:30576. Epub 2016 Jul 27.
State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.

Floral transition and petal onset, as two main aspects of flower development, are crucial to rapeseed evolutionary success and yield formation. Currently, very little is known regarding the genetic architecture that regulates flowering time and petal morphogenesis in Brassica napus. In the present study, a genome-wide transcriptomic analysis was performed with an absolutely apetalous and early flowering line, APL01, and a normally petalled line, PL01, using high-throughput RNA sequencing.Read More

In total, 13,205 differential expressed genes were detected, of which 6111 genes were significantly down-regulated, while 7094 genes were significantly up-regulated in the young inflorescences of APL01 compared with PL01. The expression levels of a vast number of genes involved in protein biosynthesis were altered in response to the early flowering and apetalous character. Based on the putative rapeseed flowering genes, an early flowering network, mainly comprised of vernalization and photoperiod pathways, was built. Additionally, 36 putative upstream genes possibly governing the apetalous character of line APL01 were identified, and six genes potentially regulating petal origination were obtained by combining with three petal-related quantitative trait loci. These findings will facilitate understanding of the molecular mechanisms underlying floral transition and petal initiation in B. napus.

2016Jul
Protoplasma
Protoplasma 2016 Jul 29. Epub 2016 Jul 29.
Daqing Branch of Heilongjiang Academy of Agricultural Sciences, 163319, Daqing, China.

The ICE1 transcription factor plays a critical role in plant cold tolerance via triggering CBF/DREB1 cold-regulated signal networks. In this work, a novel MYC-type ICE1-like gene, RsICE1, was isolated from radish (Raphanus sativus L.), and its function in cold tolerance was characterized in rice.Read More

The RsICE1 gene was expressed constitutively with higher transcriptional levels in the roots and stems of radish seedlings. The NaCl, cold, and ABA treatments could significantly upregulate RsICE1 expression levels, but dehydration stress had a weak effect on its expression. Ectopic expression of the RsICE1 gene in rice conferred enhanced tolerance to low-temperature stress grounded on a higher survival rate, higher accumulation of soluble sugars and free proline content, a decline in electrolyte leakage and MDA levels, and higher chlorophyll levels relative to control plants. OsDREBL and OsTPP1, downstream cold-regulated genes, were remarkably upregulated at transcription levels in rice overexpressing RsICE1 under low-temperature stress, which indicated that RsICE1 was involved in CBF/DREB1 cold-regulated signal networks. Overall, the above data showed that RsICE1 played an active role in improving rice cold tolerance, most likely resulting from the upregulation of OsDREBL and OsTPP1 expression levels by interacting with the RsICE1 gene under low-temperature stress.

2016Jun
Sci Rep
Sci Rep 2016 Jun 22;6:28414. Epub 2016 Jun 22.
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.Read More

6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years.

Bound states of two solitons are among the typical forms of bound states and can be observed in various operation states of mode-locked fiber lasers. We experimentally investigated bound solitons (BSs) in a passively mode-locked erbium-doped fiber laser based on a semiconductor saturable absorber mirror, whose operation states can be switched among multiple pulses, passively harmonic mode-locking, and "giant pulses" by simply adjusting the in-line polarization controller with the pump power fixed. Up to four pulses, fourth-order harmonic mode-locking (HML), and a "giant pulse" with four BSs were obtained with increasing pump power.Read More

Experimental results showed a correlative relationship among those operation states (N pulses/Nth-order HML/"giant pulses" of N bound solitons) at different pump power levels. The birefringence induced by the erbium-doped fiber inside the laser cavity played a vital role in the transitions of those operation states.

2016May
J Craniofac Surg
J Craniofac Surg 2016 May;27(3):e240-4
*Department of Neurosurgery, Clinical Medical College of Yangzhou University, Yangzhou†Department of Neurosurgery, People's Hospital Affiliated to Jiangsu University, Zhenjiang, China.

To study the endoscope anatomy of the petroclival and ventrolateral brainstem regions via the intradural subtemporal keyhole Kawase approach and discuss the feasibility and indications of this approach to the regions.
Craniotomy procedures performed via the intradural subtemporal keyhole Kawase approach were simulated on 16 sides of 8 adult cadaveric heads fixed by formalin, and the related anatomical structures were observed through the 0-degree endoscope or alternatively 30-degree one. Measurements of the shortest distances from the highest point of arcuate eminence to the 4 anatomic marks and the lengths of the Kawase rhombus were recorded, and the 2 kinds of milled ranges of petrous apex were compared.Read More


Most of the related anatomical structures could be clearly observed under the endoscope. The shortest distances from the highest point of arcuate eminence to the foramen spinosum, the greater superficial petrosal nerve hiatus, the intersection of the greater superficial petrosal nerve and mandibular nerve, and the outside edge of the trigeminal impression are 22.90 ± 2.34, 14.05 ± 2.09, 24.94 ± 1.98, 23.49 ± 2.38 mm. The area of routine milled Kawase rhombus is 3.04 ± 0.47 cm, which would increase 0.66 cm on average after the maximum drilling of the petrous apex.
The intradural subtemporal keyhole Kawase approach can provide an ideal exposure to the petroclival and ventrolateral brainstem regions via the endoscope with less damaging of the normal structures. It can be used to treat the lesions located in those areas through the natural gap combined with the drilling of petrous apex bone.

2016May
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016 May;32(5):688-92
Laboratory of Molecular Immunology, School of life sciences, Zhengzhou University, Zhengzhou 450000, China. *Corresponding authors, E-mail:

To prepare the polyclonal antibody against mouse interleukine-23 p19 (IL-23p19).
The murine full-length IL-23p19 gene was subcloned into pET16 expression vector to construct the recombinant plasmid pET-16b-IL-23p19. The plasmid was transformed into E.Read More

coli BL 21 (DE3) and IL-23p19 protein expression was induced by IPTG and identified with SDS-PAGE analysis and Western blotting. After purified by Ni(+) affinity column chromatography, the IL-23p19 protein was used as the antigen to immunize New Zealand rabbit to prepare the antiserum. The polyclonal antibody against the mouse IL-23p19 was isolated from antiserum by affinity chromatography. Antibody titer was detected by ELISA. Antibody specificity was evaluated by Western blotting.
The pET-16b-IL-23p19 recombinant plasmid was successfully constructed and the IL-23p19 protein was effectively expressed in E. coli BL 21 (DE3). The antibody was successfully prepared by immunizing New Zealand rabbit with the IL-23p19 protein four times. ELISA showed that the titer of the anti-mouse IL-23p19 polyclonal antibody was about 1:256,000. Western blotting confirmed that anti-mouse IL-23p19 polyclonal antibody could specifically recognize the IL-23p19 protein.
We have successfully prepared the anti-IL-23p19 polyclonal antibody with the high titer and specificity.

2016May
Clin Imaging
Clin Imaging 2016 May-Jun;40(3):535-40. Epub 2015 Nov 14.
Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

To report incidence of acute versus delayed presentations of bleeding requiring embolization after focal liver biopsy, in correlation with angiographic findings and treatment success rates. The available literature will be reviewed as well.
Health Insurance Portability and Accountability Act-compliant institutional review board approved retrospective review of 2180 consecutive patients undergoing 2335 targeted liver biopsies at a tertiary-care cancer center.Read More

Hepatic arterial embolization episodes within 30days from biopsy were identified via radiology PACS. Electronic medical record review was performed for indication of embolization and postembolization clinical course.
The incidence of postbiopsy bleeding requiring embolization was 0.5% (12/2335 biopsies). In those with bleeding, 1/12 (8%) had no hepatic arterial findings at angiography. Angiographic hepatic arterial findings resolved after embolization in 11/11 patients (100% technical success). Bleeding ceased after embolization in 10/12 patients (83% clinical success). Complications were seen in 2/12 (17%) patients: cholecystitis and hepatic infarct, respectively. Delayed presentation of bleeding (defined as >24h postbiopsy) occurred in 5/12 (42%) patients; the longest latency was 12days.
The overall incidence of bleeding requiring embolization in our population was 0.5%. This complication rate compares favorably to the 0-4.2% (median: 0.29%) rate quoted in the available, heterogeneous, literature on this topic. Delayed presentation occurred in almost half of patients. Arterial embolization carries excellent technical and clinical success rates.

2016May
PLoS ONE
PLoS One 2016 3;11(5):e0152090. Epub 2016 May 3.
Department of Infectious Disease, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs in the treatment of hepatoma. However, acquired drug resistance is one of the major challenges for the chemotherapy. In this study, a down-regulation of miR-122 was observed in doxorubicin-resistant Huh7 (Huh7/R) cells compared with its parental Huh7 cells, suggesting miR-122 is associated with the chemoresistance.Read More

Meanwhile, luciferase reporter assay proved that the PKM2 is the target of miR-122, and we reported that the glucose metabolism is significantly up-regulated in Huh7/R cells. Importantly, overexpression of miR-122 in Huh7/R cells reversed the doxorubicin-resistance through the inhibition of PKM2, inducing the apoptosis in doxorubicin-resistant cancer cells. Thus, this study revealed that the dysregulated glucose metabolism contributes to doxorubicin resistance, and the inhibition of glycolysis induced by miR-122 might be a promising therapeutic strategy to overcome doxorubicin resistance in hepatocellular carcinoma.

2016May
Proc. Natl. Acad. Sci. U.S.A.
Proc Natl Acad Sci U S A 2016 May 16;113(22):6259-64. Epub 2016 May 16.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215; Harvard Medical School, Boston, MA 02215

The androgen receptor (AR) plays an essential role in prostate cancer, and suppression of its signaling with androgen deprivation therapy (ADT) has been the mainstay of treatment for metastatic hormone-sensitive prostate cancer for more than 70 y. Chemotherapy has been reserved for metastatic castration-resistant prostate cancer (mCRPC). The Eastern Cooperative Oncology Group-led trial E3805: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) showed that the addition of docetaxel to ADT prolonged overall survival compared with ADT alone in patients with metastatic hormone-sensitive prostate cancer.Read More

This finding suggests that there is an interaction between AR signaling activity and docetaxel sensitivity. Here we demonstrate that the prostate cancer cell lines LNCaP and LAPC4 display markedly different sensitivity to docetaxel with AR activation, and RNA-seq analysis of these cell lines identified KDM5D (lysine-specific demethylase 5D) encoded on the Y chromosome as a potential mediator of this sensitivity. Knocking down KDM5D expression in LNCaP leads to docetaxel resistance in the presence of dihydrotestosterone. KDM5D physically interacts with AR in the nucleus, and regulates its transcriptional activity by demethylating H3K4me3 active transcriptional marks. Attenuating KDM5D expression dysregulates AR signaling, resulting in docetaxel insensitivity. KDM5D deletion was also observed in the LNCaP-derived CRPC cell line 104R2, which displayed docetaxel insensitivity with AR activation, unlike parental LNCaP. Dataset analysis from the Oncomine database revealed significantly decreased KDM5D expression in CRPC and poorer prognosis with low KDM5D expression. Taking these data together, this work indicates that KDM5D modulates the AR axis and that this is associated with altered docetaxel sensitivity.

2016May
Pain Physician
Pain Physician 2016 May;19(4):E659-66
Department of Cell Therapy, the General Hospital of Chinese People's Armed Police Forces, Beijing.

Spinal cord injury (SCI) causes a high incidence of motor and sensory dysfunctions accompanied with neuropathic pain. No effective treatment is available. Both somatosensory evoked potential (SSEP) and neuropathic pain (NPP) are transmitted via myelinated large diameter fibers of deep sensory pathways.Read More

Here we aimed to evaluate whether SSEP can consistently and objectively assess transmission of deep sensory pathways, and to examine the effects of umbilical cord mesenchymal stem cell (UCMSC) transplantation on SSEP and NPP as assessed by the pain rating index (PRI) in a patient with a 2-year history of complete cervical SCI. We demonstrate that SSEP can directly reflect physiological function of myelinated large fibers in deep sensory pathway transmission (NPP is also transmitted by the same pathway). One year after UCMSC transplantation, the SSEP parameter, PRI, and clinical presentations of NPP significantly improved.
Spinal cord, neuropathic pain, somatosensory evoked potential, umbilical cord mesenchymal stem cells.

2016Apr
PLoS Comput. Biol.
PLoS Comput Biol 2016 Apr 14;12(4):e1004820. Epub 2016 Apr 14.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.

Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NFκB) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members' biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete.Read More

Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NFκB pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NFκB pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9's potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NFκB pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NFκB pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies.

2016Apr
Zhonghua Liu Xing Bing Xue Za Zhi
Zhonghua Liu Xing Bing Xue Za Zhi 2016 Apr;37(4):517-21
Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei 230032, China.

This study aimed to investigate the status of multiple sexual partners and unprotected sexual behaviors and related influencing factors among HIV-positive men who have sex with men (MSM).
HIV-positive men having sex with men aged 18 years or older, living in Chengdu, Chongqing or Guangzhou were recruited by using the " snowballing" sampling method. Participants completed the questionnaire on computers, after filling in the Informed Consent Form.Read More

Content of the study would include social demographic characteristics, number of sexual partners, sexual behaviors, and the symptoms assessment on depression and anxiety.χ(2)-test,t-test and non-conditional Multiple logistic Regression methods were used to examine the risky sexual behaviors with multiple sexual partners among the participants engaged in this project.
Mean age of the 501 participants was (30.24±7.70) years old. In the past 6 months, 17.4% (87/501) of them had engaged in unprotected sexual behavior with two or more sexual partners. Factors at risk would include: being married (OR=1.93, 95%CI: 0.77-4.84), divorced or widowed (OR=3.94, 95%CI: 1.66-9.36), having primary male sexual partners (OR=5.04, 95%CI: 1.08-23.54) and casual or commercial male sexual partners (OR=2.54, 95%CI: 1.34-4.80) in the past 6 months, drinking alcohol (OR=3.00, 95%CI: 1.37-6.62) or Rush (alkyl nitrite) (OR=3.53, 95%CI: 1.72-7.23) during sexual acts, sharing their HIV-infection status to their partly primary male sexual partners (OR=1.84, 95%CI:0.78-4.33) or not (OR=2.68, 95% CI: 1.25-5.73), and having high sexual sensation seeking scores (OR=1.09, 95%CI: 1.03-1.15).
Unprotected sexual behaviors with multiple sexual partners among HIV-positive MSM played an important role in expediting the HIV transmission. Development of intervention programs to minimize the risk sexual behaviors and setting up efficient medical and biological measures in controlling the HIV transmission were in urgent need.

2016Mar
J. Clin. Periodontol.
J Clin Periodontol 2016 Mar 1;43(3):298-304. Epub 2016 Mar 1.
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.

To evaluate the 12-months clinical and radiological outcomes with the OsseoSpeed(™) TX implant using an early loading protocol in patients with missing teeth in the posterior mandible.
Forty-five subjects, with Kennedy class I or II edentulism in the mandible, were enrolled at three centres in China. Two or three implants were placed in one edentulous region using a one-stage procedure.Read More

Patients received a screw-retained splinted fixed permanent restoration in one edentulous region 6-8 weeks after surgery. Follow-up took place at 6 and 12 months after loading. Marginal bone level alteration, implant survival and clinical findings were assessed using descriptive statistics. The data were analysed on a patient level, implying that the mean overall implants by patient was used as the statistical unit. The data from the three centres were pooled in the statistical analyses.
A total of 107 implants were inserted in 45 patients. Twelve months after loading, the implant survival rate was 100%, with a mean (± std) marginal bone gain of 0.08 ± 0.411 mm and healthy soft tissue status.
Early loading of splinted OsseoSpeed(™) TX implants was an effective and safe treatment for partial edentulism of the posterior mandible. CLINICAL TRIAL REGISTRATION NUMBER ON CLINICALTRIALS.GOV: NCT01346683.

2016Mar
J. Am. Chem. Soc.
J Am Chem Soc 2016 Mar 25;138(9):2961-4. Epub 2016 Feb 25.
State Key Laboratory of Structural Chemistry, and Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences , Fuzhou, Fujian 350002, China.

A beryllium-free deep-ultraviolet (deep-UV) nonlinear optical (NLO) material K3Ba3Li2Al4B6O20F is developed mainly by the element substitution of Be for Al and Li from Sr2Be2B2O7 that was considered as one of the most promising deep-UV NLO materials. K3Ba3Li2Al4B6O20F preserves the structural merits of Sr2Be2B2O7 and thus exhibits no layering growth tendency and possesses the optical properties required for deep-UV NLO applications, including deep-UV transparency, phase-matchability, and sufficiently large second-harmonic generation (1.5 × KH2PO4).Read More

Furthermore, it overcomes the structural instability problem of Sr2Be2B2O7, which is confirmed by the obtainment of large single crystals and phonon dispersion calculations. These attributes make it very attractive for next-generation deep-UV NLO materials. The substitution of Be for Al and Li in beryllium borates provides a new opportunity to design beryllium-free deep-UV NLO materials with good performance.

2016Mar
Oncotarget
Oncotarget 2016 Mar;7(12):14831-40
Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou City, Jiangsu Province of P. R. China, 225001.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.Read More

83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer.

2016Mar
Langmuir
Langmuir 2016 Mar 9;32(11):2771-9. Epub 2016 Mar 9.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , 457 Zhongshan Road, Dalian 116023, P.R. China.

By a reverse microemulsion method, a series of IrFe bimetallic nanomaterials of variable morphologies and compositions is synthesized and characterized by (57)Fe Mössbauer spectroscopy, XRD, XPS, and TEM. The structure evolution, such as IrFe alloy nanoparticles to Ir nanoparticles on Fe2O3 flakes, can be simply tuned by changing the molar ratio of Ir to Fe precursors. In terms of Fe, the relative content of IrFe alloy decreased with the increase of Fe species doped, while that of Fe2O3 flakes increased until reached 100%.Read More

The as-prepared IrFe bimetallic nanomaterials were served as catalysts for the selective hydrogenation of 3-nitrostyrene to 3-aminostyrene, and it is found that the catalytic performance was related to the morphology and composition of these nanomaterials. Ir1Fe4 was subsequently identified to be a highly active and exceedingly selective catalyst with good stability and recyclability for the hydrogenation of 3-nitrostyrene, underscoring a remarkable "synergistic effect" of the two metals appearing as the form of Ir nanoparticles loaded on Fe2O3 flakes. For Ir nanoparticles, they act as an active species for the hydrogenation; for Fe2O3 flakes, they favor the preferential adsorption of nitro groups, which account for the better chemoselectivity to objective product.

2016Mar
Proc. Natl. Acad. Sci. U.S.A.
Proc Natl Acad Sci U S A 2016 Mar 7;113(12):3197-202. Epub 2016 Mar 7.
National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, People's Republic of China;

Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns.Read More

However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications.

2016Mar
Nat Commun
Nat Commun 2016 Mar 15;7:10982. Epub 2016 Mar 15.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours.Read More

We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.

2016Mar
BMC Plant Biol.
BMC Plant Biol 2016 Mar 22;16:71. Epub 2016 Mar 22.
Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

Yield of rapeseed is determined by three components: silique number, seed number per silique and thousand seed weight. Seed number per silique and thousand seed weight are influenced by silique length, seed density, silique breadth, silique thickness and silique volume. Some QTLs for silique traits have been reported in B.Read More

napus, however, no studies have focused on the six agronomic traits (seed number per silique, silique length, silique breadth, silique thickness, seed density and silique volume) simultaneously, and the genetic determinism of such complex traits have not been fully elucidated.
In this study, the six silique traits were evaluated using 348 lines of a doubled haploid population, the KN population. The results showed that 2, 4, 1, 1 and 2 QTLs explaining > 10 % of phenotypic variation were obtained for silique length, silique breadth, silique thickness, seed number per silique and silique volume, respectively. Notably, three major effect QTLs (cqSB-C6-1, cqSB-C6-2 and cqSV-C6-3) were identified in at least three environments, and 17 unique QTLs controlling at least two traits were obtained. A high-density consensus map containing 1225 markers was constructed for QTL comparison by combining the KN map with other five published maps. The comparative results revealed that 14, 13 and 11 QTLs for silique breadth, silique thickness and silique volume might be the potential new QTLs because few QTLs for these traits were reported in B. napus. In addition, potential new QTLs for silique length (11), seed number per silique (6) and seed density (5) were also identified. Twenty-five candidate genes underlying 27 QTLs for silique related traits were obtained.
This study constructed QTL analysis in B. napus, and obtained 60 consensus QTLs for six silique related traits. The potential new QTLs will enhance our understanding of the genetic control of silique traits, and the stable QTLs provided the targets for improving seed yield in future. These findings provided comprehensive insights into the genetic network affecting silique traits at QTL level in B. napus.

2016Mar
JCI Insight
JCI Insight 2016 Mar;1(3):e85630
Aflac Cancer Center of Children's Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, Georgia, USA. ; Winship Cancer Institute, Emory University, Atlanta, GA, USA.

FMS-like tyrosine kinase 3-targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist for the treatment of FLT3-independent AML, demonstrating the need for novel therapies that reduce toxicity and improve survival. MERTK receptor tyrosine kinase is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis.Read More

Here, we describe MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells. In murine orthotopic xenograft models, once-daily oral therapy prolonged survival 2- to 3-fold over that of vehicle-treated controls. Additionally, MRX-2843 retained activity against quizartinib-resistant FLT3-ITD-mutant proteins with clinically relevant alterations at the D835 or F691 loci and prolonged survival in xenograft models of quizartinib-resistant AML. Together, these observations validate MRX-2843 as a translational agent and support its clinical development for the treatment of AML.

We report a simple and facile method of reducing and modifying graphene oxide (GO) simultaneously using ethylene diamine (ED). The ED-modified and reduced GO (denoted as E-rGO) as well as the GO reduced by hydrazine hydrate (denoted as H-rGO) were characterized by Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), Raman spectra, Thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). It was found that as-prepared E-rGO exhibited good dispersibility in water and water-borne polyurethane (denoted as WPU) matrix and improve greatly the mechanical properties of WPU matrix.Read More

Moreover, E-rGO showed a high electric conductivity close to that of H-rGO after ultrasonic treatment for 12 h, which indicated that ED had the desired reducibility. The present approach could help to broaden the application field of graphene nanosheets and provide a new opportunity for developing high performance graphene/polymer-matrix composites.

2016Feb
Anticancer Drugs
Anticancer Drugs 2016 Feb;27(2):118-26
aKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional Therapy bDepartment of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, China.

Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer.Read More

TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.

2016Feb
Int Orthop
Int Orthop 2016 Feb 28;40(2):341-5. Epub 2015 Nov 28.
Department of Orthopaedics, Children's Hospital of Soochow University, Suzhou Industrial Park, No.92 Zhongnan Street, Suzhou, Jiangsu Province, People's Republic of China.

Open surgery, nonsurgical positioning device and casting are mainstay treatments of developmental dysplasia of the hip (DDH). The optimal indicators for surgical interventions remain unclear. In this study, we aim to establish empirical, sensitive radiographic indicators for peri-acetabular osteotomy intervention in developmental dysplasia in Chinese children.Read More


One hundred and three DDH patients treated in The Soochow University Children's Hospital between 2006 and 2012 were assessed; patients with known causes of neuron muscular and abnormal hip joint origin were excluded. Fifty-four suitable patients, demonstrating 71 dysplasia hips with complete clinical record and adequate X-ray films, were enrolled in this study. Patients were divided into group A (conservative interventions failed, followed by salvage peri-acetabular osteotomy) and group B (conservative treatment only); a total of 16 quantitative parameters were measured on each pelvic X-ray film.
Among 71 hip joints measured, 29 hips of group A underwent salvage peri-acetabular osteotomy (40.8 %,) showed higher X2, Y, h, and Smith c/b (Vh) (p < 0.05). The age, c, HT, b, A2 in the group A salvage operation were statistically significantly different compared to group B patients (without salvage operations) (p < 0.05).
Pre-operative pelvic X-ray film assessment of acetabulum lateralization markers (X2, c, HT, c/b ratio) and the superior migration measurements (Y, h, h/b ratio) are potentially valuable radiographic indicators for determining which DDH patients will require peri-acetabular osteotomy.

To validate the association of three previously demonstrated SLCO2B1 germline variants with time to progression (TTP) in patients receiving androgen-deprivation therapy (ADT), and to evaluate if the SLCO2B1 genetic variants impacted overall survival (OS) for prostate cancer (PC).
Three single nucleotide polymorphisms (SNPs), exonic SNP rs12422149 and intronic SNPs rs1789693 and rs1077858, were genotyped in an independent validation cohort of 616 patients with PC who were treated with ADT at the Dana-Farber Cancer Institute from 1996 to 2013. Multivariable Cox proportional hazards regression adjusting for known prognostic factors estimated the association of these genetic variants with TTP and OS in patients receiving ADT.Read More

The expression of SLCO2B1 was examined in prostatectomy samples, and the impact of SLCO2B1 expression level on DHEAS (dehydroepiandrosterone sulfate) uptake was evaluated in cell lines.
The association between exonic SNP rs12422149 and TTP in patients treated with ADT was confirmed in univariable (P = .019) and multivariable analyses (adjusted hazard ratio, 1.31; 95% CI, 1.00 to 1.72 for GG v AA/AG; P = .049). Because OS had not been previously evaluated, we examined the association in the combined initial and validation cohorts (N = 1,094). The intronic SNP rs1077858 was associated with OS in both univariable (P = .009; Bonferroni's method adjusted P = .027) and multivariable analyses (adjusted hazard ratio, 1.35; 95% CI, 1.07 to 1.71 for GG v AA/AG; P = .012). SLCO2B1 expression in normal prostate tissue and in 22RV1 cells carrying the major allele of SNP rs1077858 was significantly lower than in cells carrying the risk allele. We show in vitro that SLCO2B1 expression levels correlated with DHEAS uptake by PC cells.
The association of SNP rs1077858 with OS may be a result of differential SLCO2B1 expression and the consequent increased uptake of DHEAS and subsequent resistance to ADT, which, in turn, may contribute to decreased OS.

2016Feb
Oncol. Rep.
Oncol Rep 2016 Feb 18;35(2):793-800. Epub 2015 Nov 18.
Cancer Research Center, National‑Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.

Immunotherapy is emerging as a powerful and active tumor-specific approach against cancer via triggering the immune system. Toll-like receptors (TLRs) are fundamental elements of the immune system, which facilitate our understanding of the innate and adaptive immune pathways. TLR agonists used as single agents can effectively eradicate tumors due to their potent stimulation of innate and adaptive immunity.Read More

We examined the effects of a novel adenine type of TLR7 agonists on both innate and adaptive immune activation in vitro and in vivo. We established the local and distant tumor‑bearing mice derived from murine mammary carcinoma cell line (4T1) to model metastatic disease. Our data demonstrated that SZU101 was able to stimulate innate immune cells to release cytokines at the very high level compared with LPS at the same or lower concentration. Locally intratumoral SZU101 injection can elicit a systemic antitumor effect on murine breast tumor model. SZU101 affected the frequency of intratumoral immune cell infiltration, including the percentage of CD4+ and CD8+ increase, and the ratio of Tregs decrease. Our data reveal that the antitumor effect of SZU101 is associated with multiple mechanisms, inducing tumor‑specific immune response, activation of innate immune cells and modulation of the tumor microenvironment.

2016Feb
Acta Biochim. Biophys. Sin. (Shanghai)
Acta Biochim Biophys Sin (Shanghai) 2016 Feb 11;48(2):202-8. Epub 2016 Jan 11.
Department of Hepatobiliary and Pancreatic Surgery, the Northern Jiangsu People's Hospital, Clinic Medical College of Yangzhou University, Yangzhou 225001, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly human malignant diseases and the sixth leading cause of cancer-related deaths in China. Gemcitabine is the only first-line chemotherapeutic agent used for the palliative treatment of patients with PDAC, but chemo-resistance limits their efficacy. Here, we showed that miR-125a was up-regulated in chemo-resistant SW1990GZ cells when compared with SW1990 cells.Read More

Over-expression of miR-125a increased the chemo-resistance to gemcitabine in SW1990 cells, while down-regulation of miR-125a in SW1990GZ cells increased chemo-sensitivity to gemcitabine. By using bioinformatics analysis tool (Targetscan), the 3' untranslated region (3'UTR) of A20 gene was found to be a target of miR-125a. Luciferase reporter assay further confirmed that A20 3'UTR is a direct target of miR-125a. Over-expression of A20 in SW1990 cells increased chemo-sensitivity to gemcitabine, while knockdown of A20 in SW1990 cells promoted the chemo-resistance to gemcitabine. Finally, the expression level of miR-125a in pancreatic cancer tissues from chemo-sensitive patients was significantly lower than that from chemo-resistant patients, and was inversely correlated with the A20 mRNA levels. In conclusion, our results suggest that miR-125a promotes chemo-resistance to gemcitabine in pancreatic cells through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.

2016Feb
Angew. Chem. Int. Ed. Engl.
Angew Chem Int Ed Engl 2016 Feb 21;55(8):2820-4. Epub 2016 Jan 21.
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

The discovery that gold catalysts could be active for CO oxidation at cryogenic temperatures has ignited much excitement in nanocatalysis. Whether the alternative Pt group metal (PGM) catalysts can exhibit such high performance is an interesting research issue. So far, no PGM catalyst shows activity for CO oxidation at cryogenic temperatures.Read More

In this work, we report a sub-nano Rh/TiO2 catalyst that can completely convert CO at 223 K. This catalyst exhibits at least three orders of magnitude higher turnover frequency (TOF) than the best Rh-based catalysts and comparable to the well-known Au/TiO2 for CO oxidation. The specific size range of 0.4-0.8 nm Rh clusters is critical to the facile activation of O2 over the Rh-TiO2 interface in a form of Rh-O-O-Ti (superoxide). This superoxide is ready to react with the CO adsorbed on TiO2 sites at cryogenic temperatures.

2016Feb
Nanoscale
Nanoscale 2016 Feb;8(7):4030-6
Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing, 100124, P.R. China. and Beijing Key Lab of Microstructure and Property of Advanced Material, Beijing University of Technology, Beijing, 100124, P.R. China.

We present the surface plasmon polariton (SPP)-enhanced ultraviolet (UV) emission of an Au@SiO2/ZnO hybrid nanostructure. We achieved approximately 20- and 8-fold enhancements of the UV-emitting intensities from Au-SPP coupled nanometre- and micrometre-scaled ZnO wires through an optimized 5 nm-thick SiO2 spacer compared to that obtained from bare ZnO on a Si substrate without SPP coupling. Cathodoluminescence measurements and simulations demonstrated that the plasmonic hybrid nanostructure enables the strong localization of the SPP field, resulting in significantly enhanced UV emission.Read More

This plasmonic structure paves the way to nanoscale UV-optical lasers and sensors.

2016Feb
Front Plant Sci
Front Plant Sci 2016 28;7:17. Epub 2016 Jan 28.
Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyWuhan, China; Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal UniversityHuanggang, China.

Seed yield (SY) is the most important trait in rapeseed, is determined by multiple seed yield-related traits (SYRTs) and is also easily subject to environmental influence. Many quantitative trait loci (QTLs) for SY and SYRTs have been reported in Brassica napus; however, no studies have focused on seven agronomic traits simultaneously affecting SY. Genome-wide QTL analysis for SY and seven SYRTs in eight environments was conducted in a doubled haploid population containing 348 lines.Read More

Totally, 18 and 208 QTLs for SY and SYRTs were observed, respectively, and then these QTLs were integrated into 144 consensus QTLs using a meta-analysis. Three major QTLs for SY were observed, including cqSY-C6-2 and cqSY-C6-3 that were expressed stably in winter cultivation area for 3 years and cqSY-A2-2 only expressed in spring rapeseed area. Trait-by-trait meta-analysis revealed that the 144 consensus QTLs were integrated into 72 pleiotropic unique QTLs. Among them, all the unique QTLs affected SY, except for uq.A6-1, including uq.A2-3, uq.C1-2, uq.C1-3, uq.C6-1, uq.C6-5, and uq.C6-6 could also affect more than two SYRTs. According to the constructed high-density consensus map and QTL comparison from literatures, 36 QTLs from five populations were co-localized with QTLs identified in this study. In addition, 13 orthologous genes were observed, including five each gene for SY and thousand seed weight, and one gene each for biomass yield, branch height, and plant height. The genomic information of these QTLs will be valuable in hybrid cultivar breeding and in analyzing QTL expression in different environments.

2016Feb
Cell Chem Biol
Cell Chem Biol 2016 Feb 28;23(2):257-66. Epub 2016 Jan 28.
National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China; Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China. Electronic address:

RIP3-dependent necroptosis has recently garnered significant interest because of the unique signaling mechanisms and pathologic functions involved in this process. Accordingly, a number of chemical screens have identified several effective small-molecule inhibitors that specifically block necroptosis. Here, we report the discovery that kongensin A (KA), a natural product isolated from Croton kongensis, is a potent inhibitor of necroptosis and an inducer of apoptosis.Read More

Using a new bioorthogonal ligation method (TQ ligation), we reveal that the direct cellular target of KA is heat shock protein 90 (HSP90). Further studies demonstrate that KA covalently binds to a previously uncharacterized cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its cochaperone CDC37, which leads to inhibition of RIP3-dependent necroptosis and promotion of apoptosis in multiple cancer cell lines. Collectively, our findings demonstrate that KA is an effective HSP90 inhibitor that has potential anti-necroptosis and anti-inflammation applications.

2016Jan
J. Hazard. Mater.
J Hazard Mater 2016 Jan 10;301:407-15. Epub 2015 Sep 10.
Key Laboratory of Chemical Sensing & Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, PR China.

The aim of this study was to evaluate the interaction between extracellular polymeric substances (EPS) and Zn (II) during the sorption process of Zn (II) onto aerobic granular sludge. Batch results showed that the adsorption rate of Zn (II) onto aerobic granular sludge was better fitted with pseudo-second order kinetics model, and the adsorption isotherm data agreed well with Freundlich equation. Extracellular polymeric substances (EPS) for Zn (II) binding during sorption process was investigated by using a combination of three-dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence spectra, two-dimensional correlation spectroscopy (2D-COS) and Fourier transform infrared spectroscopy (FTIR).Read More

Results implied that the main composes of EPS, including polysaccharide (PS) and protein (PN), decreased from 5.92±0.13 and 23.55±0.76 mg/g SS to 4.11±0.09 and 9.55±0.68 mg/g SS after the addition of different doses of Zn (II). 3D-EEM showed that the intensities of PN-like substances and humic-like substances were obviously decreased during the sorption process. According to synchronous fluorescence spectra, the quenching mechanism between PN-like substances and Zn (II) was mainly caused by a static quenching process. Additionally, 2D-COS indicated that PN-like substances were more susceptible to Zn (II) binding than humic-like substances. It was also found that the main functional groups for complexation of Zn (II) and EPS were OH groups, N-H groups and C=O stretching vibration. The findings of this study are significant to reveal the fate of heavy metal during its sorption process onto aerobic granular sludge through EPS binding, and provide useful information on the interaction between EPS and heavy metal.

2016Jan
Nucleic Acids Res.
Nucleic Acids Res 2016 Jan 17;44(D1):D774-80. Epub 2015 Nov 17.
Informatics and Bio-computing Platform, Ontario Institute for Cancer Research, Toronto, ON M5G0A3, Canada Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.

WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes.Read More

The project has evolved from its original remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research.

2016Jan
Oncotarget
Oncotarget 2016 Jan;7(1):81-93
Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Aberrant Wnt/β-catenin pathway contributes to the development of liver fibrosis. MicroRNAs (MiRNAs) are found to act as regulators of the activation of hepatic stellate cell (HSC) in liver fibrosis. However, whether miRNAs activate Wnt/β-catenin pathway in activated HSCs during liver fibrosis is largely unknown.Read More

In this study, we found that Salvianolic acid B (Sal B) treatment significantly inhibited liver fibrosis in CCl4-treated rats, HSC-T6 cells and rat primary HSCs, resulting in the suppression of type I… collagen and alpha-smooth muscle actin. Also, Sal B suppressed HSC activation and cell proliferation in vitro. Interestingly, Sal B treatment induced the inactivation of Wnt/β-catenin pathway, with an increase in P-β-catenin and Wnt inhibitory factor 1 (WIF1). We demonstrated that the anti-fibrotic effects caused by Sal B were, at least in part, via WIF1. Moreover, our study revealed that miR-17-5p was reduced in vivo and in vitro after Sal B treatment. As confirmed by luciferase activity assays, WIF1 was a direct target of miR-17-5p. Notably, the suppression of HSCs induced by Sal B was almost inhibited by miR-17-5p mimics. Collectively, we demonstrated that miR-17-5p activates Wnt/β-catenin pathway to result in HSC activation through inhibiting WIF1 expression.

2016Jan
Cereb. Cortex
Cereb Cortex 2016 Jan 4. Epub 2016 Jan 4.
Division of Psychology, School of Humanities and Social Sciences, Nanyang Technological University, Singapore 637332, Singapore.

Adaptation is fundamental in sensory processing and has been studied extensively within the same sensory modality. However, little is known about adaptation across sensory modalities, especially in the context of high-level processing, such as the perception of emotion. Previous studies have shown that prolonged exposure to a face exhibiting one emotion, such as happiness, leads to contrastive biases in the perception of subsequently presented faces toward the opposite emotion, such as sadness.Read More

Such work has shown the importance of adaptation in calibrating face perception based on prior visual exposure. In the present study, we showed for the first time that emotion-laden sounds, like laughter, adapt the visual perception of emotional faces, that is, subjects more frequently perceived faces as sad after listening to a happy sound. Furthermore, via electroencephalography recordings and event-related potential analysis, we showed that there was a neural correlate underlying the perceptual bias: There was an attenuated response occurring at ∼ 400 ms to happy test faces and a quickened response to sad test faces, after exposure to a happy sound. Our results provide the first direct evidence for a behavioral cross-modal adaptation effect on the perception of facial emotion, and its neural correlate.

2016Jan
J Mass Spectrom
J Mass Spectrom 2016 Jan;51(1):86-95
University of Victoria-Genome British Columbia Proteomics Centre, #3101-4464 Markham St., Vancouver Island Technology Park, Victoria, BC, V8Z 7X8, Canada.

In this work, we combined a newly developed matrix coating technique - matrix coating assisted by an electric field (MCAEF) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to enhance the imaging of peptides and proteins in tissue specimens of human prostate cancer. MCAEF increased the signal-to-noise ratios of the detected proteins by a factor of 2 to 5, and 232 signals were detected within the m/z 3500-37500 mass range on a time-of-flight mass spectrometer and with the sinapinic acid MALDI matrix. Among these species, three proteins (S100-A9, S100-A10, and S100-A12) were only observed in the cancerous cell region and 14 proteins, including a fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2, a fragment of cAMP-regulated phosphoprotein 19, 3 apolipoproteins (C-I, A-I, and A-II), 2 S100 proteins (A6 and A8), β-microseminoprotein, tumor protein D52, α-1-acid glycoprotein 1, heat shock protein β-1, prostate-specific antigen, and 2 unidentified large peptides at m/z 5002.Read More

2 and 6704.2, showed significantly differential distributions at the p < 0.05 (t-test) level between the cancerous and the noncancerous regions of the tissue. Among these 17 species, the distributions of apolipoprotein C-I, S100-A6, and S100-A8 were verified by immunohistological staining. In summary, this study resulted in the imaging of the largest group of proteins in prostate cancer tissues by MALDI-MS reported thus far, and is the first to show a correlation between S100 proteins and prostate cancer in a MS imaging study. The successful imaging of the three proteins only found in the cancerous tissues, as well as those showing differential expressions demonstrated the potential of MCAEF-MALDI/MS for the in situ detection of potential cancer biomarkers. Copyright © 2015 John Wiley & Sons, Ltd.

2016Jan
Biomed Res Int
Biomed Res Int 2016 6;2016:5065217. Epub 2016 Dec 6.
School of Information Sciences and Technology, Northwest University, Xi'an, Shaanxi 710027, China.

Sparse reconstruction inspired by compressed sensing has attracted considerable attention in fluorescence molecular tomography (FMT). However, the columns of system matrix used for FMT reconstruction tend to be highly coherent, which means L1 minimization may not produce the sparsest solution. In this paper, we propose a novel reconstruction method by minimization of the difference of L1 and L2 norms.Read More

To solve the nonconvex L1-2 minimization problem, an iterative method based on the difference of convex algorithm (DCA) is presented. In each DCA iteration, the update of solution involves an L1 minimization subproblem, which is solved by the alternating direction method of multipliers with an adaptive penalty. We investigated the performance of the proposed method with both simulated data and in vivo experimental data. The results demonstrate that the DCA for L1-2 minimization outperforms the representative algorithms for L1, L2, L1/2, and L0 when the system matrix is highly coherent.

2015Dec
ACS Appl Mater Interfaces
ACS Appl Mater Interfaces 2015 Dec 17;7(47):26217-25. Epub 2015 Nov 17.
School of Materials Science and Engineering, Zhengzhou University , Zhengzhou 450001, China.

Ordered honeycomb-like SnO2 foams were successfully synthesized by means of a template method. The honeycomb SnO2 foams were analyzed by X-ray diffraction (XRD), thermogravimetric and differential scanning calorimetry (TG-DSC), laser Raman spectra, scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR). It can be found that the SnO2 foam configurations were determined by the size of polystyrene templates.Read More

The electromagnetic properties of ordered SnO2 foams were also investigated by a network analyzer. The results reveal that the microwave absorption properties of SnO2 foams were dependent on their configuration. The microwave absorption capabilities of SnO2 foams were increased by increasing the size of pores in the foam configuration. Furthermore, the electromagnetic wave absorption was also correlated with the pore contents in SnO2 foams. The large and high amounts pores can bring about more interfacial polarization and corresponding relaxation. Thus, the perfect ordered honeycomb-like SnO2 foams obtained in the existence of large amounts of 322 nm polystyrene spheres showed the outstanding electromagnetic wave absorption properties. The minimal reflection loss (RL) is -37.6 dB at 17.1 GHz, and RL less than -10 dB reaches 5.6 GHz (12.4-18.0 GHz) with thin thickness of 2.0 mm. The bandwidth (<-10 dB, 90% microwave dissipation) can be monitored in the frequency regime of 4.0-18.0 GHz with absorber thickness of 2.0-5.0 mm. The results indicate that these ordered honeycomb SnO2 foams show the superiorities of wide-band, high-efficiency absorption, multiple reflection and scatting, high antioxidation, lightweight, and thin thickness.

2015Nov
Sensors (Basel)
Sensors (Basel) 2015 Nov 11;15(11):28513-30. Epub 2015 Nov 11.
School of Computer, National University of Defense Technology, Changsha 410073, China.

Nowadays, our living environment has been embedded with smart objects, such as smart sensors, smart watches and smart phones. They make cyberspace and physical space integrated by their abundant abilities of sensing, communication and computation, forming a cyber-physical integrated network. In order to maximize information diffusion in such a network, a group of objects are selected as the forwarding points.Read More

To optimize the selection, a minimum connected dominating set (CDS) strategy is adopted. However, existing approaches focus on minimizing the size of the CDS, neglecting an important factor: the weight of links. In this paper, we propose a distributed maximizing the probability of information diffusion (DMPID) algorithm in the cyber-physical integrated network. Unlike previous approaches that only consider the size of CDS selection, DMPID also considers the information spread probability that depends on the weight of links. To weaken the effects of excessively-weighted links, we also present an optimization strategy that can properly balance the two factors. The results of extensive simulation show that DMPID can nearly double the information diffusion probability, while keeping a reasonable size of selection with low overhead in different distributed networks.

To understand the coverage of HIV related intervention and antiviral treatment among HIV-positive men who have sex with men (MSM) and to examine factors of initiating antiretroviral treatment.
A total of 501 HIV-positive MSM were recruited by "snowballing" sampling in Chengdu (160), Chongqing (168) and Guangzhou (173) from January to June, 2013. Participants who were older than18 years, had sex with men, HIV-infected, were living in these 3 cities when survey was conducted were eligible for subjects of this survey.Read More

The data were collected by computer assisted survey, including social demography, the coverage of HIV related follow-up intervention and ART, related knowledge level, sexual behaviors in the last 6 months, as well as notification to sexual partners and family. We analyzed the influence factors for initiating ART by Multiple Unconditioned Logistic Regression.
Among 501 HIV-positive MSM, the ratio of CD4 counting and HIV viral load testing were 90.8% (455) and 19.4% (97), respectively. The percentage of the latest CD4 counting not more than 350 per µl was 33.0% (150/455). The coverage of initiated ART among the participants who met the qualification was 56.0% (84/150). The multivariable Logistic regression analysis showed that the possibility of not on ART among participants who were migrants increased to 5.21(2.33-11.66) times of the local residents and the possibility among participants who were diagnosed STD in the last year increased to 2.70(1.12-6.55) times of those who were not infected STD, the possibility of not on ART among participants who had sex with male occasional or commercial partner in the last 6 months increased to 2.16(1.03-4.50) times of those who hadn't, and the possibility among participants who had anal sex with condom use in the past 6 months increased to 2.68(1.10-6.50) times of those who couldn't insist using condom.
There were low coverage of series of HIV/AIDS related intervention services among HIV-positive MSM in Chengdu, Chongqi and Guangzhou. Migrants, had sex with male occasional or commercial partner, had anal sex with condom use in the past 6 months, not infected STD in the last year may be the independent risk factors for HIV-positive MSM to not initiating ART.

2015Nov
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2015 Nov;50(11):944-7
Department of Otorhinolaryngology, Children's Hospital of Hebei Province, Shijiazhuang 050031, China.

To explore the role of rigid bronchoscope in the diagnosis and treatment of plastic bronchitis.
Various clinical parameters, the key points of operation and postoperative recovery were analyzed in 8 patients with plastic bronchitis treated in Department and ICU using retrospective analysis.
All cases demonstrated bronchial lumen stenosis, mucous membrance coarse, congestion, edema in the affected side.Read More

2 cases had follicular hyperplasia, 1 case had a few ooze after taking out the plastic type. All cases had endogenous foreign bodies, taking the shape of the bronchial tree or a funicular. Block shape and sites were as follows: right main bronchus 2 cases, superior lobe of right lung 1 case, right middle bronchial 1 case, left main bronchus 2 cases, 1 case with left lower lobe, right main bronchus and left lower lobe bronchus 1 case. The breath sounds of the affected side become more enhanced after operation, with the alliviation of dyspnea. All cases recovered after ICU treatment. The pathologic examination were all type I plastic bronchitis.
Removement of the endogenous foreign body via rigid bronchoscopy is the effective method in the treatment of plastic bronchitis. Plastic bronchitis is a rapid-developing critical, urgent disease.In order to reduce the mortality, early diagnosis and timely surgery are necessary.

2015Nov
Turk Neurosurg
Turk Neurosurg 2015 Nov 13. Epub 2015 Nov 13.
The Second Affiliated Hospital of Soochow University.

Many approaches for optic nerve decompression have their own advantages and disadvantages. The aim of this study was to perform endoscopic decompression of optic nerve through the supraorbital keyhole and evaluate its feasibility.
Ten adult cadaveric heads were studied using 4-mm, 0- and 30-degree rigid endoscopes to perform the optic nerve decompression through the supraorbital keyhole extradural approach.Read More

Furthermore, the relevant measurements about the optic canal were recorded.
Through the supraorbital keyhole, the endoscope was introduced into the extradural space, and the following structures could be exposed and identified: the sphenoid ridge, the anterior clinoid process, the roof of the optic canal and the falciform ligament. The roof and lateral wall of the optic canal were removed using a drill under the endoscope, and more sufficient decompression could be achieved by further incising the falciform ligament and optic sheath. After measurement, the distance from the zygomatic process of the frontal bone to the optic canal was 59.32 ± 2.27 mm, the distance from the upper midpoint of the posterior foramen of the optic canal to the internal carotid artery was 3.80 ± 0.93 mm.
According to the cadaveric study, it is feasible to perform the endoscopic decompression of optic nerve with a clear view through the supraorbital keyhole extradural approach. Our study may provide a minimally invasive and safe option for the optic nerve decompression.

2015Oct
Sensors (Basel)
Sensors (Basel) 2015 Oct 23;15(10):26997-7020. Epub 2015 Oct 23.
Technology Center, CNPC Logging CO., LTD, Xi'an 710077, China.

The demountable disk-drum aero-engine rotor is an important piece of equipment that greatly impacts the safe operation of aircraft. However, assembly looseness or crack fault has led to several unscheduled breakdowns and serious accidents. Thus, condition monitoring and fault diagnosis technique are required for identifying abnormal conditions.Read More

Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments.

2015Oct
Iran J Allergy Asthma Immunol
Iran J Allergy Asthma Immunol 2015 Oct;14(5):509-18
Department of Orthopedics, The Third Affiliated Hospital of Nantong University, Nantong, People's Republic of China.

Inflammation is an important reaction underlying lumbar disc herniation (LDH). Th17 cells play a critical role in immune activation. Interleukin (IL)-21 controls the functional activity of effector T-helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation.Read More

It plays important roles in chronic inflammation and autoimmune diseases. However, little is known about relationship between IL-21 and LDH. This study was aimed to determine the association between IL-21 levels and pain scores in LDH patients compared to healthy controls.We enrolled 34 LDH patients and 20 healthy controls in this study. The LDH patients underwent surgery. Pain intensity was recorded using visual analogue scale (VAS) scores preoperatively. Serum IL-21 and IL-17 levels in the peripheral blood were determined using enzyme-linked immunosorbent assay. Disc tissue was examined using western blot and quantitative reverse-transcription polymerase chain reaction to determine IL-21, IL-17, and cyclooxygenase (COX)-2 expression, and using immunohistochemistry to assess IL-21 expression.LDH patients exhibited significantly higher levels of serum IL-21 and IL-17 than healthy controls. Moreover, higher expression of IL-21, IL-17, and COX-2 was found in the protein and mRNA levels in disc tissues from LDH patients than in normal disc tissues. Different parameters like VAS pain scores, IL-17, and COX-2 were positively correlated with the IL-21 levels. Enhanced production of IL-21 in disc tissues of LDH patients was also confirmed using immunohistochemical analyses.We concluded that inflammation was responsible for the pain associated with LDH, and that increased IL-21 expression may be associated with the pathogenesis of LDH.

2015Aug
Zhonghua Kou Qiang Yi Xue Za Zhi
Zhonghua Kou Qiang Yi Xue Za Zhi 2015 Aug;50(8):474-7
Email:

To evaluate the effect of core ceramic surface treatment on the failure behaviors of two bilayered all- ceramic structures.
Lithium disilicate glass-ceramic (LDG, IPS e.max Press) and Zirconia(Cercon) specimens were divided into 4 groups(n=12) according to the following surface treatment methods: ground successively to 1 000(group A), 600(group B) and 320(group C) grit silicon carbide(SiC) papers and sandblasted with 110 µm aluminum oxide particle(group D, as control).Read More

Surface roughness was measured using a profilometer. After veneer sintering, the flexural strength σ was measured with biaxial flexure test and the reliability of strength was analyzed with Weibull distribution. Failure modes and fractographic patterns were analyzed by optical stereo and scanning electron microscopy (SEM).
For LDG, no significant difference was found for the flexural strength values among groups (F=0.406, P=0.750). No significant difference was found in Weibull modulus among groups(the confidence bounds overlapped with each other). SEM and optical stereo observation results showed that all the bilayered LDG specimens failed cohesively. For zirconia, Mean flexural strength values were (541 ± 75), (533 ± 73), (529 ± 78) and (640 ± 95) MPa for groups A, B, C and D, respectively, and group D demonstrated a significantly higher flexural strength compared to the other three groups(P<0.05). No significant difference were found among groups(the confidence bounds overlapped with each other). Specimens in all groups failed mainly adhesively, while those in group D presented lower percentage of adhesive failure.
Core ceramic surface treatment has no influence on the failure behaviors of LDG based bilayered structures. Sandblasting can increase the flexural strength of bilayered zirconia structures by reducing the incidence of delamination.

2015Jan
Int J Clin Exp Pathol
Int J Clin Exp Pathol 2015 1;8(10):12595-607. Epub 2015 Oct 1.
Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.

Chronic myeloid leukemia (CML) can be contextualized as a disease of unregulated self-renewal of stem cells which exist in a quiescent state and are instructed to differentiate and mobilize to circulation under pathologic circumstances leading to tumor invasion and metastasis. Here we found that matrix metalloproteinase-9 (MMP-9), induced by TGF-β1, upregulated s-KitL and s-ICAM-1, permitting the transfer of c-kit(+) hematopoietic stem cells (HSCs) from the quiescent to proliferative niche in CML. Further study showed that this MMP-9 production was raised by CML specific BCR/ABL(+) oncogene mediated TGF-β1.Read More

Besides, phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was evidenced to govern this stem cell recruitment in CML pathogenesis. Overall, our observations defined a novel critical role for TGF-β1 induced PI3K/Akt/NF-κB signaling pathway in the recruitment of the malignant cells in CML by releasing s-KitL and s-ICAM-1 and this was through a distinct PI3K/Akt/NF-κB signaling pathway.

2015Jan
Front Plant Sci
Front Plant Sci 2015 23;6:1164. Epub 2015 Dec 23.
Key Laboratory of Cotton and Rapeseed, Ministry of Agriculture, Institute of Industrial Crops, Jiangsu Academy of Agricultural SciencesNanjing, China; Jiangsu Collaborative Innovation Center for Modern Crop ProductionNanjing, China.

The apetalous genotype is a morphological ideotype for increasing seed yield and should be of considerable agricultural use; however, only a few studies have focused on the genetic control of this trait in Brassica napus. In the present study, a recombinant inbred line, the AH population, containing 189 individuals was derived from a cross between an apetalous line 'APL01' and a normally petalled variety 'Holly'. The Brassica 60 K Infinium BeadChip Array harboring 52,157 single nucleotide polymorphism (SNP) markers was used to genotype the AH individuals.Read More

A high-density genetic linkage map was constructed based on 2,755 bins involving 11,458 SNPs and 57 simple sequence repeats, and was used to identify loci associated with petalous degree (PDgr). The linkage map covered 2,027.53 cM, with an average marker interval of 0.72 cM. The AH map had good collinearity with the B. napus reference genome, indicating its high quality and accuracy. After phenotypic analyses across five different experiments, a total of 19 identified quantitative trait loci (QTLs) distributed across chromosomes A3, A5, A6, A9 and C8 were obtained, and these QTLs were further integrated into nine consensus QTLs by a meta-analysis. Interestingly, the major QTL qPD.C8-2 was consistently detected in all five experiments, and qPD.A9-2 and qPD.C8-3 were stably expressed in four experiments. Comparative mapping between the AH map and the B. napus reference genome suggested that there were 328 genes underlying the confidence intervals of the three steady QTLs. Based on the Gene Ontology assignments of 52 genes to the regulation of floral development in published studies, 146 genes were considered as potential candidate genes for PDgr. The current study carried out a QTL analysis for PDgr using a high-density SNP map in B. napus, providing novel targets for improving seed yield. These results advanced our understanding of the genetic control of PDgr regulation in B. napus.