Hui Jiang - Southeast University

Hui Jiang
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Name
Hui Jiang
Affiliation
Southeast University
Country
China

Publications Authored By Hui Jiang

2017Apr
Biosens Bioelectron
Biosens Bioelectron 2017 Apr 28;90:436-442. Epub 2016 Sep 28.
School of Food Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225127, PR China. Electronic address:

This paper reports the a novel and simple mast cell-based electrochemical method for detecting of bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs), which can be utilized to preliminarily evaluate the toxicity of food-borne pathogenic bacteria. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide hydrogel were immobilized on a gold electrode, while mast cells as recognition elements were cultured in a 3D cell culture system. Electrochemical impedance spectroscopy (EIS) was utilized to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC12-HSL).Read More

The results indicated that cellular activities such as cell viability, apoptosis, intracellular calcium, and degranulation were markedly influenced by the AHLs. Importantly, the exposure of 3OC12-HSL to mast cells induced a marked decrease in the electrochemical impedance signal in a dose-dependent manner. The detection limit for 3OC12-HSL was 0.034μM with a linear range of 0.1-1μM. These results were confirmed via conventional cell assay and transmission electron microscope (TEM) analysis. Altogether, the proposed method appears to be an innovative and effective approach to the quantitative measurement of Gram-negative bacterial quorum signaling molecules; to this effect, it also may serve as a primary evaluation of the cytotoxicity of food-borne pathogens.

2017Mar
Biosens Bioelectron
Biosens Bioelectron 2017 Mar 27;89(Pt 1):422-429. Epub 2016 Apr 27.
State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, No. 2 Sipailou, Nanjing 210096, China. Electronic address:

A self-assembly composite of graphene-pyrroloquinoline quinone (PQQ) was fabricated and modified on glassy carbon electrode (GCE) for sensitive detection of nicotinamide adenine dinucleotide (NADH). Chitosan (CTS) was applied to disperse graphene to form a stable robust film on GCE. A synergistic effect between PQQ and graphene was observed during the electrocatalytic oxidation of NADH, with about 260mV reduction in the oxidation potential and 2.Read More

5-fold increase in the oxidation current compared with those on the bare GCE. The electrochemical sensors based on the modified electrodes allowed the detection of NADH with a good linear dependence from 0.32 to 220µM with a high sensitivity of 0.421µAµM(-1)cm(-2) and a low detection limit of 0.16µM (S/N=3). It could also eliminate the interference of electroactive substances like ascorbic acid (AA), uric acid, and dopamine and its derivatives. The outstanding performances of graphene-PQQ/CTS composite capable of improving the electrical conductivity and accelerating the electron transport suggested its promising applications for design of different graphene based composites used in electrochemical sensing and energy fields.

2017Jan
J. Natl. Cancer Inst.
J Natl Cancer Inst 2017 Jan 5;109(1). Epub 2016 Oct 5.
Department of Pathology (SS, RM, SMD, XC, AMC), Michigan Center for Translational Pathology (SS, RM, FYF, SMD, XC, AMC), Department of Radiation Oncology (JRE, FYF), Comprehensive Cancer Center (FYF), Department of Surgery, Section of Thoracic Surgery (GC, DGB), Department of Biostatistics (HJ, AMC), and Howard Hughes Medical Institute (AMC), University of Michigan, Ann Arbor, MI

Precision therapy for lung cancer will require comprehensive genomic testing to identify actionable targets as well as ascertain disease prognosis. RNA-seq is a robust platform that meets these requirements, but microarray-derived prognostic signatures are not optimal for RNA-seq data. Thus, we undertook the first prognostic analysis of lung adenocarcinoma RNA-seq data and generated a prognostic signature.Read More


Lung adenocarcinoma RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) were divided chronologically into training (n = 255) and validation (n = 157) cohorts. In the training cohort, prognostic association was assessed by univariate Cox analysis. A prognostic signature was built with stepwise multivariable Cox analysis. Outcomes by risk group, stage, and mutation status were analyzed with Kaplan-Meier and multivariable Cox analyses. All the statistical tests were two-sided.
In the training cohort, 96 genes had prognostic association with P values of less than or equal to 1.00x10(-4), including five long noncoding RNAs (lncRNAs). Stepwise regression generated a four-gene signature, including one lncRNA. Signature high-risk cases had worse overall survival (OS) in the TCGA validation cohort (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 2.00 to 14.62) and a University of Michigan institutional cohort (n = 67; HR = 2.05, 95% CI = 1.18 to 4.55), and worse metastasis-free survival in the TCGA validation cohort (HR = 3.05, 95% CI = 2.31 to 13.37). The four-gene prognostic signature also statistically significantly stratified overall survival in important clinical subsets, including stage I (HR = 2.78, 95% CI = 1.91 to 11.13), EGFR wild-type (HR = 3.01, 95% CI = 1.73 to 14.98), and EGFR mutant (HR = 8.99, 95% CI = 62.23 to 141.44). The four-gene prognostic signature also stood out on top when compared with other prognostic signatures.
Here, we present the first RNA-seq prognostic signature for lung adenocarcinoma that can provide a powerful prognostic tool for precision oncology as part of an integrated RNA-seq clinical sequencing program.

2017Jan
J. Neurochem.
J Neurochem 2017 Jan 20;140(2):307-319. Epub 2016 Dec 20.
Brain Research Institute, Qilu Hospital of Shandong University, Jinan, Shandong, China.

The over-expression of regulator of calcineurin 1 isoform 1 (RCAN1.1) has been implicated in mitochondrial dysfunctions of Alzheimer's disease; however, the mechanism linking RCAN1.1 over-expression and the mitochondrial dysfunctions remains unknown.Read More

In this study, we use human neuroblastoma SH-SY5Y cells stably expressing RCAN1.1S and rat primary neurons infected with RCAN1.1S expression lentivirus to study the association of RCAN1 with mitochondrial functions. Our study here showed that the over-expression of RCAN1.1S remarkably up-regulates the expression of adenine nucleotide translocator (ANT1) by stabilizing ANT1 mRNA. The increased ANT1 level leads to accelerated ATP-ADP exchange rate, more Ca(2+) -induced mitochondrial permeability transition pore opening, increased cytochrome c release, and eventually cell apoptosis. Furthermore, knockdown of ANT1 expression brings these mitochondria perturbations caused by RCAN1.1S back to normal. The effect of RCAN1.1S on ANT1 was independent of its inhibition on calcineurin. This study elucidated a novel function of RCAN1 in mitochondria and provides a molecular basis for the RCAN1.1S over-expression-induced mitochondrial dysfunctions and neuronal apoptosis.

2017Jan
Neuroreport
Neuroreport 2017 Jan;28(1):23-27
School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression.Read More

According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

2017Jan
Adv. Mater. Weinheim
Adv Mater 2017 Jan 4. Epub 2017 Jan 4.
School of Materials Science and Engineering, Nanyang Technological University, 639798, Singapore.

Focusing on the bottleneck of molecularly engineered organic semiconductors, a breakthrough is made to tune the electronic properties of organic semiconductors from p-type to n-type by using fluorinated metal phthalocyanines as examples. The experimentally observed p-type to n-type transition characteristics of single-crystal field-effect devices result from a combination of extrinsic and intrinsic properties of materials with different fluoridation substitution.Read More

2016Dec
Clin. Biochem.
Clin Biochem 2016 Dec 27;49(18):1354-1360. Epub 2016 Apr 27.
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Optimal conditions for blood collection for circulating tumor DNA (ctDNA) are still being developed. Although both Streck and EDTA tubes are commonly used, their ability to stabilize ctDNA as a function of time and temperature post-collection has not been thoroughly studied. Additionally, the potential utility of CellSave tubes (commonly used for circulating tumor cell) for ctDNA measurements has not been studied.Read More


Blood was collected into Streck, EDTA, and CellSave tubes from ten patients with metastatic breast cancer enrolled in the MI-ONCOSEQ tumor sequencing program at the University of Michigan and kept either on ice or at room temperature until plasma isolation. Plasma was processed after 2, 6, and 48h post-collection. We used droplet digital PCR (ddPCR) to quantify plasma ctDNA and wild-type DNA for six patients who had tumor tissue mutations represented in commercially available ddPCR assays.
ctDNA abundance was similar and stable for up to 6h in all tube types, and there was no effect of storage temperature on the yield for Streck and EDTA tubes. After 48h, however, one out of four patients with detectable ctDNA showed a ~50% decline in ctDNA in the EDTA tube, and three out of six patients showed a 2-3-fold increase in wild-type DNA in the EDTA tube.
Streck, EDTA, and CellSave tubes showed similar performance in preserving ctDNA for up to 6h before plasma isolation. Streck and CellSave tubes more consistently stabilized ctDNA and wild-type DNA at 48h than EDTA tubes.

2016Dec
Fundam Clin Pharmacol
Fundam Clin Pharmacol 2016 Dec 14;30(6):511-516. Epub 2016 Jul 14.
Department of Anaesthesiology, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, China.

Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction, and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings.Read More

Our previous studies indicated that propofol attenuated high glucose-induced endothelial apoptosis, dysfunction, and inflammation via inhibiting reactive oxygen species (ROS) accumulation. However, the mechanisms by which propofol reduces high glucose-induced endothelial ROS accumulation are still obscure. In this study, we examined how propofol attenuates high glucose-induced endothelial ROS accumulation. Compared with 5 mm glucose treatment, 15 mm glucose upregulated the expression of pin-1, phosphatase A2 (PP2A), p66(shc) and mitochondrial p66(shc) expression, increased p66(shc) -Ser(36) phosphorylation, and O2·- accumulation. More importantly, although propofol had no effect on 15 mm glucose-induced p66(shc) -Ser(36) phosphorylation and pin-1 expression, propofol could downregulated PP2A expression and p66(shc) expression in whole-cell and mitochondrion, resulting in the reduction of O2·- accumulation. Moreover, we demonstrated that the antioxidative effect of propofol was similar to that of calyculin A, an inhibitor of PP2A. In contrast, FTY720, an activator of PP2A, antagonized the effect of propofol. Our data indicated that the antioxidative effect of propofol was achieved by downregulating PP2A expression, resulting in the inhibition of p66(shc) -Ser(36) dephosphorylation and mitochondrial p66(shc) expression.

2016Dec
J Ethnopharmacol
J Ethnopharmacol 2016 Dec 4;193:140-149. Epub 2016 Aug 4.
College of Pharmacy, Anhui university of Chinese Medicine, 103 Meishan Road, Hefei, China.

Chronic glomerulonephritis (CGN) is a primary glomerular disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine for treatment of CGN, but the comprehensive molecular mechanism underlying this therapeutic effect is not clear to date. The aim of this study was to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats.Read More


For gene expression analysis, four samples of glomerular tissue from rats in the Qi Teng Xiao Zhuo granule group and four samples each from the adriamycin treated and control groups were hybridized with Agilent Rat 4×44K whole genome microarrays. KEGG and Gene Ontology (GO) analyses and LIMMA, String and Cytoscape software were used to analyze the functional microarray data and screen differentially expressed genes. Hub genes were identified using Pathway Studio software. Real-time PCR was performed to verify the selected genes.
Microarray gene expression analysis showed that Pnoc, Cacfd1, Fos, Igll1, Lcn2, and Syk were among the most downregulated genes in the Qi Teng Xiao Zhuo granule group compared with the adriamycin treated group, whereas Cyp2c7, Hsd3b6, Acsm5, and Ugt2b15 were significantly upregulated. Functional analysis demonstrated that metabolism of xenobiotics by cytochrome P450, the B cell receptor signaling pathway, and cytokine-cytokine receptor interaction pathways were significantly downregulated in the Qi Teng Xiao Zhuo granule group and that GO terms related to positive regulation of immune response, immune response-activating signal transduction, cell differentiation, cell cycle, proliferation, and adhesion were significantly affected. Fos and Syk were considered to be potential hub genes.
In the adriamycin-induced CGN rat model, comprehensive molecular mechanisms were involved with complex gene expression alterations containing many altered pathways and GO terms. However, how Qi Teng Xiao Zhuo granules regulate these events warrants further investigation.

Premature ejaculation (PE) is one of the most prevalent yet under-reported sexual disorders. Differing sociocultural norms across the Asia-Pacific region provide unique challenges in PE management.
This web-based study collected data from 5,038 men and women across 11 countries in the Asia-Pacific region.Read More

Respondents were recruited from an existing database.
The initiators and barriers for PE discussions and for seeking professional management following self-treatment, as well as their choices and expectations of healthcare professionals (HCPs).
More than two-thirds of respondents have discussed PE with their partners, and men are more likely to initiate the discussion. Top drivers were for both partners to attain sexual satisfaction and greater fulfillment in the relationship. Emotional insecurity was the top barrier for men as they did not want to feel hurt or inadequate. Before consulting an HCP, more than two-thirds of men self-treated their PE for at least 20 months. The primary reason for stopping self-treatment and seeking medical management was a lack of improvement in sexual satisfaction. The ideal attributes that men seek in their HCP included trust and being knowledgeable about PE management.
Attitudes and barriers to PE and its treatment in the Asia-Pacific region are poorly understood. Many men are reluctant to seek professional advice and therefore resort to self-treatment for extended periods. HCPs can play a key role to empower PE sufferers and partners to understand the prevalence, medical relevance, treatability, and negative impacts of PE on sexual and overall relationships. Greater awareness of the diverse cultural and social norms, education of both partners and HCPs, and the involvement of HCPs through a patient-centric approach are all pivotal in managing PE optimally across the Asia-Pacific region.

Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal. We prepared liver-specific mice deficient in the serine palmitoyltransferase long chain base subunit 2 gene using an albumin-cyclization recombination approach and found that the deficient mice have severe jaundice.Read More

Moreover, the deficiency impairs hepatocyte polarity, attenuates liver regeneration after hepatectomy, and promotes tumorigenesis. Importantly, we show that the deficiency significantly reduces sphingomyelin but not other sphingolipids in hepatocyte plasma membrane; greatly reduces cadherin, the major protein in adherens junctions, on the membrane; and greatly induces cadherin phosphorylation, an indication of its degradation. The deficiency affects cellular distribution of β-catenin, the central component of the canonical Wnt pathway. Furthermore, such a defect can be partially corrected by sphingomyelin supplementation in vivo and in vitro.
The plasma membrane sphingomyelin level is one of the key factors in regulating hepatocyte polarity and tumorigenesis. (Hepatology 2016;64:2089-2102).

2016Dec
Redox Biol
Redox Biol 2016 Dec 17;10:1-11. Epub 2016 Sep 17.
Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address:

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown.Read More

Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund's adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia.

2016Dec
Small
Small 2016 Dec 27;12(45):6255-6265. Epub 2016 Sep 27.
State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab), School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.

Cancer treatment has a far greater chance of success if the neoplasm is diagnosed before the onset of metastasis to vital organs. Hence, cancer early diagnosis is extremely important and remains a major challenge in modern therapeutics. In this contribution, facile and new method for rapid multimodal tumor bioimaging is reported by using biosynthesized iron complexes and gold nanoclusters via simple introduction of AuCl4(-) and Fe(2+) ions.Read More

The observations demonstrate that the biosynthesized Au nanoclusters may act as fluorescent and computed tomography probes for cancer bioimaging while the iron complexes behave as effective contrast agent for magnetic resonance imaging. The biosynthesized iron complexes and gold nanoclusters are found biocompatible in vitro (MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay) and in vivo for all the vital organs of circulatory and excretory system. These observations raise the possibility that the biosynthesized probes may find applications in future clinical diagnosis for deep seated early neoplasms by multimodal imaging.

2016Dec
J. Ind. Microbiol. Biotechnol.
J Ind Microbiol Biotechnol 2016 Dec 18;43(12):1693-1703. Epub 2016 Oct 18.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.

FK506 (tacrolimus), which is produced by many Streptomyces strains, is clinically used as an immunosuppressive agent and for treatment of inflammatory skin diseases. Here, we identified that the FK506 biosynthetic gene cluster in an industrial FK506-producing strain Streptomyces tsukubaensis L19 is organized as eight transcription units. Two pathway-specific regulators, FkbN and Tcs7, involved in FK506 biosynthesis from S.Read More

tsukubaensis L19 were characterized in vivo and in vitro. FkbN activates the transcription of six transcription units in FK506 biosynthetic gene cluster, and Tcs7 activates the transcription of fkbN. In addition, the DNA-binding specificity of FkbN was determined. Finally, a high FK506-producing strain was constructed by overexpression of both fkbN and tcs7 in S. tsukubaensis L19, which improved FK506 production by 89 % compared to the parental strain.

2016Dec
Biotechnol. Lett.
Biotechnol Lett 2016 Dec 6;38(12):2015-2021. Epub 2016 Sep 6.
College of Life Sciences, Zhejiang University, 866 Yuhangtang Rd, Hangzhou, 310058, Zhejiang, China.

Synthetic biology has been applied to direct improvement of valuable metabolite productions. Tacrolimus (FK506), a clinically used immunosuppressive agent isolated from many Streptomyces, is produced by fermentation in industry. Here we chose FK506 as an example to review recent progress in improving FK506 production, including enhancing transcription levels of biosynthetic genes, accelerating post-translational modification levels of biosynthetic enzymes, increasing activities of rate limiting enzymes, and rational supplement of limited precursors.Read More

FK506 production was increased from 25 % to sevenfold by these synthetic biology approaches.

Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Read More

Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL Analysis of intracellular calcium ([Ca(2+)]i) dynamics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from this individual (TECRLHom-hiPSCs), his heterozygous but clinically asymptomatic father (TECRLHet-hiPSCs), and a healthy individual (CTRL-hiPSCs) from the same Sudanese family, revealed smaller [Ca(2+)]i transient amplitudes as well as elevated diastolic [Ca(2+)]i in TECRLHom-hiPSC-CMs compared with CTRL-hiPSC-CMs. The [Ca(2+)]i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine-induced [Ca(2+)]i transients. In addition, the decay phase of the [Ca(2+)]i transient was slower in TECRLHom-hiPSC-CMs due to decreased SERCA and NCX activities. Furthermore, TECRLHom-hiPSC-CMs showed prolonged action potentials (APs) compared with CTRL-hiPSC-CMs. TECRL knockdown in control human embryonic stem cell-derived CMs (hESC-CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLHom-hiPSC-CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT Patient-specific hiPSC-CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.

2016Dec
Am J Speech Lang Pathol
Am J Speech Lang Pathol 2016 Dec 9:1-12. Epub 2016 Dec 9.
Texas Tech University Health Sciences Center, Lubbock.

This study was designed to provide recommended amounts of treatment to achieve the optimal amount of language gain for children with language impairment.
The authors retrospectively analyzed treatment outcomes for 233 children for delivered dose, intensity, and cumulative intensity of therapy. The steps of the analytical process they applied to arrive at algorithms for recommended amounts of treatment were (1) multilevel modeling to predict children's language gains from the 3 intensity parameters and (2) extraction of regression weights to create a recommended amount of treatment.Read More


Optimal outcomes can be identified using an equation specifying Ŷ = desired points of change (e.g., 0.6 SD units), V = child's baseline language skills, D = average number of minutes spent targeting language in a session, F = total number of sessions conducted across the year, and D × F = product of planned dose and frequency (cumulative intensity). Input of the values for Ŷ and V provides recommended amount of treatment.
This study constitutes the first effort to provide empirical guidance on intensity of treatment for children with language impairment. The use of algorithm-driven dosage recommendations may be more effective than clinician judgment and trial and error, although these correlational results must be confirmed with experimental methods.

2016Dec
Sci Rep
Sci Rep 2016 Dec 12;6:38936. Epub 2016 Dec 12.
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, P. R. China.

Pancreatic cancer is a devastating disease with poor prognosis. The association between vitamin A, retinol and carotenoid intake and the risk of pancreatic cancer occurrence remains controversial, and therefore it is necessary to make a meta-analysis to clarify the association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk. In the present study, PubMed and EMBASE databases were used to identify qualified studies.Read More

The association between dietary vitamin A, retinol and carotenoids was estimated by pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). It was found that there was an inverse correlation between vitamin A, beta-carotene and lycopene intake and the risk of pancreatic cancer (for vitamin A, pooled OR = 0.85, 95%CI = 0.74-0.97, P = 0.015; for beta-carotene, pooled OR = 0.78, 95%CI = 0.66-0.92, P = 0.003; for lycopene, pooled OR = 0.84, 95%CI = 0.73-0.97, P = 0.020), which was more prominent in case-control study subgroup. In conclusion, dietary vitamin A, beta-carotene and lycopene might inversely correlate with pancreatic cancer.

2016Dec
Onco Targets Ther
Onco Targets Ther 2016 11;9:6953-6963. Epub 2016 Nov 11.
Department of Hematology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor. This study aimed to explore the effect of portulacerebroside A (PCA) on the adhesion, migration, and invasion in human leukemia HL60 cells and U937 cells and clarify the possible mechanisms involved, which could provide potential strategies for the treatment of AML. By methyl thiazolyl tetrazolium analysis, it was found that PCA (1-10 μM) suppressed the cell viability in a time- and dose-dependent manner.Read More

A total of 1, 2, and 5 μM of PCA dramatically inhibited the adhesion, migration, and invasion of HL60 cells and U937 cells in a dose-dependent manner. Phosphorylation level of JNK and P38 protein level was measured by Western blot. After the real-time quantification polymerase chain reaction and Western blot detection of the total RNA and protein, messenger RNA, and protein expression levels of Ras homologous C (RhoC), metastasis-associated gene 1 (MTA1) and matrix metalloproteinase-2/9 (MMP-2/9) were decreased significantly in a dose-dependent manner. The phosphorylation level of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38) was decreased dramatically in HL60 cells and U937 cells after PCA treatment. In conclusion, PCA significantly inhibits the adhesion, migration, and invasion of HL60 cells and U937 cells by suppressing the p38/JNK pathway and regulating the expressions of related genes.

2016Dec
Int J Environ Res Public Health
Int J Environ Res Public Health 2016 Dec 11;13(12). Epub 2016 Dec 11.
Department of Social Medicine and Health Management, School of Public Health, Central South University, Changsha 410078, China.

Background: Environmental tobacco smoke (ETS) exposure is associated with an increased risk of many diseases. Many countries have ratified a national smoking ban in public places, but studies on factors related to smoking issues in public places post-ban are lacking. Aim: To identify facilitators and barriers that influenced smokers' compliance with smoking bans in public places.Read More

Methods: Using PubMed, MEDLINE, and the Web of Science database, we conducted a systematic search of English articles published before June 2015 on factors of smokers' compliance with the smoking bans in public places. Results: A total of 390 references were identified, among which seventeen articles (twelve quantitative studies, two qualitative studies, three mixed-method studies) were included in this review. These studies focused on four types of public places including recreational venues (n = 7), hospital (n = 5), school (n = 4), and workplace (n = 1). Factors at the  individual-, interpersonal-, and organizational-level were identified: at the individual level, nicotine dependence, insufficiency of tobacco-related knowledge, and the negative attitudes towards smoking bans were the most commonly identified barriers; at the interpersonal level, the smoking behaviors of people around, close relatives, and friends' approval were the main barriers; and at the organizational level, the main barriers were inefficient implementation of the bans and the inconvenience of the designative smoking areas. Conclusions: This synthesis of the literature provided evidence of the identified barriers and facilitators of smokers' compliance with the smoking bans. It will be beneficial for the policy-maker to consider interventions on multiple levels of factors to overcome the barriers and enhance smokers' compliance with the smoking bans in public places.

2016Dec
Anal Bioanal Chem
Anal Bioanal Chem 2016 Dec 27. Epub 2016 Dec 27.
School of Environment and Chemical Engineering, North China Electric Power University, Beijing, 102206, China.

The sensitive and selective determination of fluoride ions is particularly significant in environmental protection, food safety, and health care products. In this work, a highly selective turn-on fluorescent probe for fluoride ions has been synthesized by simply functionalizing fluorescent isophthalaldehyde with silicone-oxygen bonding. The selectivity of the probe is based on the specific reactivity of the silyl group toward fluoride ions in aqueous solution.Read More

The nucleophilic substitution reaction of fluoride ions triggers the cleavage of the Si-O bond to release a strongly fluorescent product, which can be used for the determination of fluoride ions by fluorescence intensity enhancement. The probe molecules are specifically responsive and highly selective for the fluoride anion over other relevant anions and cations. This fluorescent probe also shows high photostability and exhibits good sensitivity for fluoride ions, and the limit of detection is as low as 67 ppb. We have demonstrated its application for on-site sensitive determination of fluoride ions for environmental monitoring and protection.

2016Dec
Inflammation
Inflammation 2016 Dec 27. Epub 2016 Dec 27.
Cardiology Department of Chinese PLA General Hospital, 28# Fuxing Road, Haidian District, Beijing, China.

Immune suppression plays critical roles in the development of chronic osteomyelitis, and the mechanisms underlying the development of immune suppression in chronic osteomyelitis have attracted much attention. LAG-3 is an important suppressor of T cell activation, but the role of LAG-3 in the immune regulation of chronic osteomyelitis is currently unknown. We sought to demonstrate if LAG-3 plays crucial roles in chronic osteomyelitis progression and has effects on immune suppression and exhausting of T cells, and what is the mechanism underlying LAG-3 deregulation in chronic osteomyelitis.Read More

We examined the expression of LAG-3 in the T cells of peripheral blood of 50 healthy controls and 50 patients with chronic osteomyelitis by flow cytometry. Clinical data were analyzed to determine the correlation between inflammation index and LAG-3 expression. Moreover, we isolated the CD4(+) T cells from healthy controls and chronic osteomyelitis patients to compare cell proliferation and IFN-γ production. Chromatin immunoprecipitation assays were utilized to analyze the epigenetic modification on LAG-3 expression in T cells. We found that LAG-3 was significantly increased in the T cells of peripheral blood from chronic osteomyelitis patients. Subsequently, clinical data analysis suggested that the higher expression of LAG-3 was associated with severer inflammation situation. Consistently, LAG-3(+)CD4(+) T cells exhibited impaired cell proliferation and IFN-γ secretion. Deregulation of histone methylation mediated the increase of LAG-3(+) T cells during chronic osteomyelitis. Taken together, our study demonstrates the increase of LAG-3(+) T cells and its immune regulatory roles in chronic osteomyelitis progression, suggesting new mechanisms and potential therapeutic targets for chronic osteomyelitis.

2016Dec
Antimicrob. Agents Chemother.
Antimicrob Agents Chemother 2016 Dec 28. Epub 2016 Dec 28.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China

We report here a new type of plasmid that carries the mcr-1 gene, the pMCR-1-P3 plasmid, harbored in an Escherichia coli strain isolated from a pig farm in China. pMCR-1-P3 belongs to the IncY incompatibility group, and is a phage-like plasmid that contains a large portion of phage-related sequences. The backbone of this plasmid is different from other mcr-1-carrying plasmids reported previously.Read More

2016Nov
Gene
Gene 2016 Nov 7;593(1):131-42. Epub 2016 Aug 7.
College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, China. Electronic address:

Long non-coding RNAs (LncRNAs) are an important class of widespread molecules involved in diverse biological functions, which are exceptionally expressed in numerous types of diseases. Currently, limited study on LncRNA in rheumatoid arthritis (RA) is available. In this study, we aimed to identify the specifically expressed LncRNA that are relevant to adjuvant-induced arthritis (AA) in rats, and to explore the possible molecular mechanisms of RA pathogenesis.Read More


To identify LncRNAs specifically expressed in rheumatoid arthritis, the expression of LncRNAs in synoviums of rats from the model group (n=3) was compared with that in the control group (n=3) using Arraystar Rat LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR).
Up to 260 LncRNAs were found to be differentially expressed (≥1.5-fold-change) in the synoviums between AA model and the normal rats (170 up-regulated and 90 down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs, XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected to analyze the relationship between LncRNAs and RA via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the AA rats.
These results revealed that clusters of LncRNAs were uniquely expressed in AA rats compared with controls, which manifests that these differentially expressed LncRNAs in AA rats might play a vital role in RA development. Up-regulation or down-regulation of the six LncRNAs might contribute to the molecular mechanism underlying RA. To sum up, our study provides potential targets for treatment of RA and novel profound understanding of the pathogenesis of RA.

2016Nov
Int. Immunopharmacol.
Int Immunopharmacol 2016 Nov 16;40:300-309. Epub 2016 Sep 16.
Department of Clinical Laboratory, PLA General Hospital, 100853 Beijing, People's Republic of China. Electronic address:

Hypobaric hypoxia, frequently encountered at high altitude, may lead to lung and cerebrum injury. Our study aimed to investigate whether puerarin could exert ameliorative effects on rats exposed to hypobaric hypoxia via regulation of aquaporin (AQP) and NF-κB signaling pathway in lung and cerebrum.
40 Sprague Dawley rats were divided into four groups (normal control group, hypobaric hypoxia group, puerarin group and dexamethasone group).Read More

Wet/dry ratio, blood gas, pathological changes of lung and cerebrum and spatial memory were observed in each group. Inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were determined with ELISA and expression of AQP1, AQP4, NF-κB signaling pathway in lung and cerebrum with western blot RESULTS: Puerarin showed significant preventative effects on tissue injury and behavioral changes, as evidenced by histopathological findings and Morris water maze. In addition, levels of inflammatory cytokines in BALF decreased in the two preventative groups compared with those of hypobaric hypoxia group. AQP in lung and cerebrum increased under the condition of hypobaric hypoxia while was down regulated in both two preventative groups. NF-κB and IκB was also inhibited by puerarin.
Our study suggested that lung and cerebrum injury, increased inflammatory cytokines in BALF and increased AQP1, AQP4 and NF-κB signaling pathway occurred under the condition of hypobaric hypoxia. Moreover, puerarin could prevent lung and cerebrum injury of rats exposed to hypobaric hypoxia via down-regulation of inflammatory cytokines, AQP1 and AQP4 expression and NF-κB signaling pathway.

2016Nov
Oncotarget
Oncotarget 2016 Nov;7(48):78726-78735
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underlying pathways require to be elucidated.Read More

In this study, we detected a positive association between MFHAS1 expression in TAMs and human colorectal cancer (CRC) TNM stage. Supernatant of CT26 murine CRC cells induced MFHAS1 expression in RAW264.7 murine macrophages. Additionally, CT26 supernatant induced the M2 marker CD206 and activated the pro-M2 STAT6 and KLF4 signaling in control but not MFHAS1-silenced RAW264.7 macrophages. Moreover, supernatant of control, but not MFHAS1-silenced macrophages promoted CT26 cell proliferation, migration and epithelial-mesenchymal transition. Compared with control macrophages, MFHAS1-silenced macrophages showed significantly reduced protumoral effects in vivo. Together, these results suggested that CRC cells induce M2 polarization of TAMs through MFHAS1 induction and subsequent STAT6 and KLF4 activation to promote CRC progress. Finally, similar to CT26 supernatant stimulation, peroxisome proliferator-activated receptor-γ (PPARγ) activation by rosiglitazone induced M2 polarization of RAW264.7 macrophages through MFHAS1-dependent pathway. Our results highlight the role of MFHAS1 as a regulator of macrophages polarization and CRC progress.

2016Nov
Acta Pharmacol. Sin.
Acta Pharmacol Sin 2016 Nov 29;37(11):1481-1489. Epub 2016 Aug 29.
Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

LS-007 is a CDK inhibitor, which exhibits potent antitumor activity against chronic lymphocytic leukemia and ovarian cancer cells. In this study, we further evaluated the antitumor activity of LS-007 alone and in combination with a Bcl-2 inhibitor ABT-199 in acute leukemia (AL) cells.
Cell viability was detected using resazurin assay, and cell apoptosis was examined using Annexin V/PI double staining and flow cytometry.Read More

The inhibition of LS-007 on kinases was evaluated with the mobility shift assay or ELISA. The expression of relevant signaling molecules was assessed using Western blotting and RT-PCR. Primary lymphocytes from patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were separated using Ficoll-Paque PLUS.
LS-007 inhibited the proliferation of 6 AL cell lines with IC50 values of 100-200 nmol/L, and decreased the survival of ALL and AML patient-derived lymphocytes with mean LD50 value of 67 and 102 nmol/L, respectively. In kinase assays in vitro, LS-007 was more selective for the CDK family, inhibiting CDK2, CDK9, CDK1 and CDK4 at low nanomolar concentrations. In HL-60 and CCRF-CEM cells, LS-007 (0.1-0.4 μmol/L) dose-dependently induced cell apoptosis predominantly through CDK9 inhibition-related dephosphorylation at the ser2 residue of RNA pol II and the corresponding depletion of anti-apoptotic proteins, especially Mcl-1 and XIAP. LS-007 (0.2 and 0.4 μmol/L) also induced cell apoptosis in the patient-derived lymphocytes. In HL-60, CCRF-CEM and Molt-4 cells, combined application of LS-007 with ABT-199 (1 or 2 μmol/L) markedly increased cell apoptosis with a maximal decrease in the XIAP levels as compared with either drug used alone.
CDK inhibitor LS-007 potently inhibits the established human AL cell lines and primary AL blasts, and it also shows remarkable synergy with Bcl-2 inhibitor ABT-199.

2016Nov
Am J Transl Res
Am J Transl Res 2016 15;8(10):4472-4477. Epub 2016 Oct 15.
Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University 305 Zhongshan East Road, Nanjing, Jiangsu, China.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. In this study, we examined if the hydrogen could inhibit inflammation in a mouse model of collagen-induced arthritis (CIA) via oxidative stress on RA-FLSs. Moreover, to identify the mechanisms of action, we evaluated the effect of hydrogen on RA-FLSs development and the expression of pro-inflammatory cytokines and signaling pathways.Read More

Based on our result, H2 enriched medium can increase super oxide dismutase (SOD) level following H2O2 treatment and decrease 8-hydroxy-2'-deoxyguanosine (8-OHdG) level. Since H2O2 treatment activates MAPK, NF-κB and TGF-β1 in cells, our study suggested that H2 could inhibit H2O2 activated MAPK and NF-κB activation as well as TGF-β1 expression in treated cells. Taken together, our data suggested that H2 can directly neutralize OH and ONOO(-) to reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by H2O2 in RA-FLSs. H2 can provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.

2016Nov
Sci Rep
Sci Rep 2016 Nov 10;6:36786. Epub 2016 Nov 10.
Casali Center of Applied Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.

We present an all-additive manufacturing method that is performed at mild conditions, for the formation of organic single crystals at specific locations, without any photolithography prefabrication process. The method is composed of two steps; inkjet printing of a confinement frame, composed of a water soluble electrolyte. Then, an organic semiconductor solution is printed within the confinement to form a nucleus at a specific location, followed by additional printing, which led to the growth of a single crystal.Read More

The specific geometry of the confinement enables control of the specific locations of the single crystals, while separating the nucleation and crystal growth processes. By this method, we printed single crystals of perylene, which are suitable for the formation of OFETs. Moreover, since this method is based on a simple and controllable wet deposition process, it enables formation of arrays of single crystals at specific locations, which is a prerequisite for mass production of active organic elements on flexible substrates.

2016Nov
Sci Rep
Sci Rep 2016 Nov 14;6:36987. Epub 2016 Nov 14.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, PR China.

Due to the high toxicity of bacterial lipopolysaccharide (LPS), resulting in sepsis and septic shock, two major causes of death worldwide, significant effort is directed toward the development of specific trace-level LPS detection systems. Here, we report sensitive, user-friendly, high-throughput LPS detection in a 96-well microplate using a transcriptional biosensor system, based on 293/hTLR4A-MD2-CD14 cells that are transformed by a red fluorescent protein (mCherry) gene under the transcriptional control of an NF-κB response element. The recognition of LPS activates the biosensor cell, TLR4, and the co-receptor-induced NF-κB signaling pathway, which results in the expression of mCherry fluorescent protein.Read More

The novel cell-based biosensor detects LPS with specificity at low concentration. The cell-based biosensor was evaluated by testing LPS isolated from 14 bacteria. Of the tested bacteria, 13 isolated Enterobacteraceous LPSs with hexa-acylated structures were found to increase red fluorescence and one penta-acylated LPS from Pseudomonadaceae appeared less potent. The proposed biosensor has potential for use in the LPS detection in foodstuff and biological products, as well as bacteria identification, assisting the control of foodborne diseases.

2016Nov
Biomed. Chromatogr.
Biomed Chromatogr 2016 Nov 17. Epub 2016 Nov 17.
Department of Pharmacy, The first affiliated hospital of Anhui university of Chinese medicine, 117 Meishan Road, Hefei, China.

The aim of this study was to explore the changes in the urine metabolic spectrum in rats with the early stage of liver fibrosis using gas chromatography-time of flight/mass spectrometry (GC-TOF/MS), try to search for potential biomarkers and elucidate the probably metabonomic pathogenesis. The early stage of liver fibrosis was established with a single subcutaneously injection carbon tetrachloride (CCl4 ) twice each week for 4 weeks continuously. At the end of the experiment, GC-TOF/MS technology with multivariate statistical approaches such as principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to analyze the changes in the metabolic spectrum trajectory and identify potential biomarkers.Read More

The results showed that twelve potential biomarkers in the model group such as succinic acid, threonine, lactose and so on were selected, which indicate that the metabonomic pathogenesis of the early stage of liver fibrosis may be related to disorders of energy metabolism, amino acid metabolism, fatty acid metabolism.

Blocking hepatic very low density lipoprotein (VLDL) secretion via genetic or pharmacologic inhibition of microsomal triglyceride (TG) transfer protein (Mttp) causes hepatic steatosis, yet the risks for developing hepatic fibrosis are poorly understood. Here we report that liver-specific Mttp knockout mice (Mttp-LKO) exhibit both steatosis and fibrosis, which is exacerbated by a high trans fat, fructose diet. When crossed into germline Liver fatty acid binding protein null mice (Mttp-LKO, L-Fabp (-/-) , ie DKO mice) hepatic steatosis was greatly diminished and fibrosis prevented, on both low and high fat diets.Read More

The mechanisms underlying protection include reduced long chain fatty acid (FA) uptake, shifts in FA distribution (lipidomic profiling) and metabolic turnover, specifically decreased hepatic 18:2 FA and TG species and a shift in 18:2 FA utilization for oxidation versus incorporation into newly synthesized TG. DKO mice were protected against fasting induced hepatic steatosis (a model of enhanced exogenous FA delivery), yet developed steatosis upon induction of hepatic de novo lipogenesis with fructose feeding. Mttp-LKO mice, on either the L-Fabp null or Apobec1 null background (ie apolipoprotein B100 only) exhibited only subtle increases in endoplasmic reticulum stress, suggesting that an altered unfolded protein response is unlikely to account for the attenuated phenotype in DKO mice. Acute, antisense-mediated L-Fabp knockdown in Mttp-LKO mice also reduced FA uptake, increased oxidation versus incorporation of 18:2 species with complete reversal of hepatic steatosis, but increased hepatic injury and worsened fibrosis.
Perturbing exogenous hepatic FA utilization modulates both hepatic steatosis and fibrosis in the setting of hepatic Mttp deletion, adding new insight into the pathophysiological mechanisms and consequences of defective VLDL secretion. This article is protected by copyright. All rights reserved.

2016Nov
Mar Drugs
Mar Drugs 2016 Nov 18;14(11). Epub 2016 Nov 18.
College of Science, National University of Defense Technology, Changsha 410073, Hunan, China.

μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds.Read More

To assess the contributions of individual disulfide bonds of GIIIA to the blockade of NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala. The inhibitory potency of the analogues against NaV1.4 was assayed by whole cell patch-clamp on rNaV1.4, heterologously expressed in HEK293 cells. The corresponding IC50 values were 0.069 ± 0.005 μM for GIIIA, 2.1 ± 0.3 μM for GIIIA-1, 3.3 ± 0.2 μM for GIIIA-2, and 15.8 ± 0.8 μM for GIIIA-3 (-1, -2 and -3 represent the removal of disulfide bridges Cys3-Cys15, Cys4-Cys20 and Cys10-Cys21, respectively). Other analogues were not active enough for IC50 measurement. Our results indicate that all three disulfide bonds of GIIIA are required to produce effective inhibition of NaV1.4, and the removal of any one significantly lowers its sodium channel binding affinity. Cys10-Cys21 is the most important for the NaV1.4 potency.

Adenovirus is a leading cause of respiratory infection in children. Salivirus/klassevirus was first identified as an etiologic agent of gastroenteritis and was never reported in respiratory infection cases. The case being discussed here caught our attention because, although it is a common respiratory infection, it was fatal, while similar cases were mild.Read More

In order to find potential causes in the fatal case, we describe the clinical diagnosis and treatment, the sequencing analysis of the salivirus/klassevirus, and the co-infectious adenovirus. Metagenomics sequencing was conducted on the samples from a nasopharyngeal swab of the children with adenovirus infection. Sequences were assembled using IDBA-ud (1.1.1); phylogenetic analysis was performed using MEGA 5.2. RT-PCR and quantitative PCR were performed to verify the existence of the virus in the samples. A nearly full genome of this new virus strain was obtained with 7633 nt encoding a polyprotein of 2331 aa. Meanwhile, it was detected specifically in the nasopharyngeal swab by RT-PCR. Further, homology analysis indicated that the virus has a closer relationship with Salivirus A strain in Shanghai (GU245894). Our study reports the first case of Human salivirus/klassevirus in respiratory specimens of a child with fatal adenovirus infection in Shenzhen, China. The finding and investigation of the virus will provide more useful information for the clinical diagnosis of unexplained lethal infection and expand our knowledge of the new family, salivirus/klassevirus in picornavirus.

2016Oct
J. Immunol.
J Immunol 2016 Oct 26;197(7):2880-90. Epub 2016 Aug 26.
State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China; and

Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages.Read More

This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3). Using a genetic inactivation approach together with pharmacological perturbations in mouse cells, we show that PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages, via metabolically supporting the engulfment and removal of virus-infected cells. Furthermore, the antiviral function of PFKFB3, as well as some contribution of its action from the hematopoietic compartment, was confirmed in a mouse model of respiratory syncytial virus infection. Therefore, different from the long-standing perception of glycolysis as a proviral pathway, our findings establish an antiviral, immunometabolic aspect of glycolysis that may have therapeutic implications.

2016Oct
Biochem. Biophys. Res. Commun.
Biochem Biophys Res Commun 2016 Oct 30;479(4):683-689. Epub 2016 Sep 30.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address:

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases and hepatocellular carcinoma (HCC). Golgi protein 73 (GP73), a resident Golgi membrane protein, is a novel serum biomarker for the diagnosis of liver diseases and HCC. Although previous studies have demonstrated that HCV upregulates GP73 expression and GP73 promotes HCV secretion through its interaction with apolipoprotein E (ApoE), the exact mechanism underlying GP73 regulates HCV secretion remains unclear.Read More

In this study, we demonstrated that GP73 mediates the interaction of ApoE with HCV NS5A protein to promote HCV secretion. We revealed that GP73 is colocalized with HCV replication complex in infected-Huh7.5.1 cells. Further studies demonstrated that GP73 interacted with both NS5A and ApoE proteins. Furthermore, knockdown of GP73 significantly reduced the binding of NS5A with ApoE, and the production of virus particles in culture supernatant. Taken together, our studies revealed that GP73 promotes HCV secretion by directly mediating the interaction of ApoE with HCV replication complex through binding with HCV NS5A.

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands.Read More

We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

2016Oct
Sci Rep
Sci Rep 2016 Oct 20;6:35475. Epub 2016 Oct 20.
Laboratory of Molecular Pharmacology, IMM, Peking University, Beijing, 100871, China.

Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear.Read More

In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K(+) channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.

2016Oct
BMC Bioinformatics
BMC Bioinformatics 2016 Oct 6;17(Suppl 13):336. Epub 2016 Oct 6.
Department of Biology, Indiana State University, Terre Haute, IN, 47809, USA.

MicroRNAs (miRNA) are short nucleotides that interact with their target genes through 3' untranslated regions (UTRs). The Cancer Genome Atlas (TCGA) harbors an increasing amount of cancer genome data for both tumor and normal samples. However, there are few visualization tools focusing on concurrently displaying important relationships and attributes between miRNAs and mRNAs of both cancer tumor and normal samples.Read More

Moreover, a deep investigation of miRNA-mRNA target and biological relationships across multiple cancer types by integrating web-based analysis has not been thoroughly conducted.
We developed an interactive visualization tool called MMiRNA-Viewer that can concurrently present the co-relationships of expression between miRNA-mRNA pairs of both tumor and normal samples into a single graph. The input file of MMiRNA-Viewer contains the expression information including fold changes between normal and tumor samples for mRNAs and miRNAs, the correlation between mRNA and miRNA, and the predicted target relationship by a number of databases. Users can also load their own input data into MMiRNA-Viewer and visualize and compare detailed information about cancer-related gene expression changes, and also changes in the expression of transcription-regulating miRNAs. To validate the MMiRNA-Viewer, eight types of TCGA cancer datasets with both normal and control samples were selected in this study and three filter steps were applied subsequently. We performed Gene Ontology (GO) analysis for genes available in final selected 238 pairs and also for genes in the top 5 % (95 percentile) for each of eight cancer types to report a significant number of genes involved in various biological functions and pathways. We also calculated various centrality measurement matrices for the largest connected component(s) in each of eight cancers and reported top genes and miRNAs with high centrality measurements.
With its user-friendly interface, dynamic visualization and advanced queries, we also believe MMiRNA-Viewer offers an intuitive approach for visualizing and elucidating co-relationships between miRNAs and mRNAs of both tumor and normal samples. We suggest that miRNA and mRNA pairs with opposite fold changes of their expression and with inverted correlation values between tumor and normal samples might be most relevant for explaining the decoupling of mRNAs and their targeting miRNAs in tumor samples for certain cancer types.

2016Oct
Biomed Res Int
Biomed Res Int 2016 29;2016:4967275. Epub 2016 Sep 29.
Department of Cardiovascular Surgery, General Hospital of Shenyang Military, Shenyang, China.

Objective. To investigate the effects of diabetes mellitus (DM) in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Method.Read More

A total of 728 patients with DM and 1380 patients without DM who underwent OPCAB treatment from March 2012 to April 2015 were reviewed. The effects of DM on intraoperative variables and postoperative complications were determined using propensity score analysis. Results. Two well-matched subgroups were selected using propensity score analysis (DM = 728, no-DM = 728) to compare the perioperative outcome. The duration of the ICU stay, in hours (55.2 ± 53.0 versus 49.29 ± 51.30, P < 0.05), postoperative new-onset atrial fibrillation (20.9% versus 14.97%, P < 0.05), and postoperative infection (9.2% versus 4.67%, P < 0.05) were greater in DM patients, as indicated by univariate analysis. Conclusion. OPCAB was found to be effective in DM patients, but postoperative infection and postoperative new-onset atrial fibrillation were found to be more likely to occur in DM patients than in other patients. DM was found to be a powerful risk factor for postoperative infection and postoperative new-onset atrial fibrillation.

2016Oct
Tumour Biol.
Tumour Biol 2016 Oct;37(10):14331
Department of Pathology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
2016Sep
Biosens Bioelectron
Biosens Bioelectron 2016 Sep 11;83:126-33. Epub 2016 Apr 11.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Synergetic Innovation Center of Food Safety, Jiangnan University, Wuxi, Jiangsu 214122, PR China. Electronic address:

In this study a novel cell-to-cell electrochemical microfluidic chip was developed for qualitative and quantitative analysis of food allergen. Microfluidic cell culture, food allergen-induced cell morphological changes, and cell metabolism measurements were performed simultaneously using the aforementioned device. RBL-2H3 mast cells and ANA-1 macrophages have been used within a cell co-culture model to observe their allergic response when they are introduced to the antigen stimulus.Read More

Two cell cultivation microfluidic channels are located in the microfluidic chip, which is fabricated with four groups of gold electrodes, with an additional "capillary". In order to detect the allergic response, the cells were stimulated with dinitrophenylated bovine serum albumin (DNP-BSA) without anti-DNP IgE incubation. When exocytosis occurs, the cell-secreted inflammatory cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cell impedance changes were detected using cell-based electrochemical assay. Results indicate that the real-time cell allergic response are accurately monitored by this electrochemical microfluidic chip, which provides a general example of rapidly prototyped low-cost biosensor technology for applications in both food allergen detection and investigation.

2016Sep
Gene
Gene 2016 Sep 21;589(1):72-80. Epub 2016 May 21.
College of Pharmacy, Anhui university of Chinese medicine, 103 Meishan Road, Hefei, China. Electronic address:

Chronic glomerulonephritis (CGN) is the most common form of the glomerular disease with unclear molecular mechanisms, which related to immune-mediated inflammatory diseases. The aim of this study was to characterize differentially expressed genes in the normal and adriamycin-induced CGN rats by microarray analysis, and to determine the potential molecular mechanisms of CGN pathogenesis.
For the gene expression analysis, fresh glomerular tissues from both normal and adriamycin treated rats (n=4, respectively) were collected.Read More

Total RNA was extracted and subjected to Agilent Rat 4×44 K whole genome microarray. KEGG, Gene Ontology (GO) analyze, LIMMA, String and Cytoscape software were applied to screen and analyze differentially regulated genes. In addition, the Real-time polymerase chain reaction (RT-PCR) was performed to verify the selected genes.
2334 differentially regulated genes were identified including 1294 up-regulated genes and 1040 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 27 genes may be key controlled genes in the pathogenesis of CGN, including 14 up-regulated genes (Fos, Myc, Kng1, Rac2, Pik3r1, Egr1, Icam1, Syk, Anxa1, Lgals3, Ptprc, Runx1, Itgb7, Ccl6) and 13 down-regulated genes (Aldh2, Dpyd, Mthfd1, Gldc, Ppar-α, Igf1, Pomc, Oas1a, Gsr, Acox1, Cyp1a1, Ugt2b15, Hsd3b6), which primarily contribute to biological processes such as, cell cycle, cell proliferation, inflammatory response, immune response, metabolic process, and so on. Fos and Syk were considered as potent hub genes.
Global gene expression profile analysis showed that the molecular mechanism of CGN pathogenesis may be related to the promotion of cell cycle and mitosis, dysregulation of cytokine secretion and disordered inflammatory response as well as abnormal metabolism.

2016Sep
Toxicon
Toxicon 2016 Sep 13;120:175-84. Epub 2016 Aug 13.
State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address:

The actual health risk from exposure to combined mycotoxins is unknown, and few studies have focused on changes to cellular biological systems (e.g., metabolomics) caused by combined mycotoxic effects.Read More

To evaluate the combined mycotoxic effects of deoxynivalenol (DON) and zearalenone (ZEN) on the level of cellular biological systems, gas chromatographic, time-of-flight mass spectroscopy (GC-TOF/MS) of the complete murine macrophage ANA-1 cell metabolome was implemented in this study. Using optimized chromatography and mass spectrometry parameters, the metabolites detected by GC-TOF/MS were identified and processed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection on latent-structures discriminant analysis (OPLS-DA). The metabolite sets were screened for further pathway analysis under rules of t-test (P) value < 0.05, VIP value > 1, and similarity value > 500. The mainly interfered metabolism pathways were categorized into two dominant types: amino acid metabolism and glycometabolism. Four metabolites, palmitic acid, 1-monopalmitin, ribose-5-phosphate and 2-deoxy-D-galactose, occur only under combined "DON + ZEN" treatment, indicating abnormal metabolism in ANA-1 cells. The metabolic state of ANA-1 cells under induction by combined "DON + ZEN" illustrates that DON may inhibit the estrogenic effects of ZEN. Thus, the combined effect of "DON + ZEN" may exacerbate toxicity in the pentose phosphate pathway, while palmitic acid metabolism is likely a new pathway effected by the combination, "DON + ZEN."

2016Sep
Protein Pept. Lett.
Protein Pept Lett 2016 ;23(11):1032-1037
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.

Many polyketides show biological activities and have thus been applied in clinics, as food additives, and in agriculture. Type II thioesterases (TEIIs) play an important role in polyketide biosynthesis. Most TEIIs belong to α/β-hydrolase family and usually contain a catalytic triad Ser-His-Asp.Read More

In polyketide biosynthesis, TEIIs can play an editing role by removal of aberrant non-extendable acyl units in elongation steps, a starter unit selection role by removal of unfavored starter acyl units in initiation steps, and a releasing role by removal of final product in termination steps. Complementation of TEIIs has been observed and applied.

2016Sep
PLoS ONE
PLoS One 2016;11(9):e0161928. Epub 2016 Sep 23.
BGI Education Center, University of Chinese Academy of Science, Shenzhen 518083, China.

With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma.Read More

However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses.
In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%.
Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome.

2016Sep
Tumour Biol.
Tumour Biol 2016 Sep 20;37(9):12397-12402. Epub 2016 Jun 20.
Department of Pathology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.

Prostate cancer is the commonest male malignancy in the Western world, but its morbidity is much lower in China. The principal aim of this study was to evaluate the frequency of TMPRSS2:ERG fusion in Chinese prostate cancer patients using immunohistochemistry and reverse transcription polymerase chain (RT-PCR). In addition, we compared the ERG protein expression with TMPRSS2:ERG fusion gene.Read More

The relationship between ERG expression and clinicopathologic features was also examined. Samples from patients who underwent radical prostatectomies in Changhai Hospital (Shanghai, China) were collected and stored in ethically approved tissue banks. One hundred seventy-four prostate cancer tissue samples and 10 normal tissues were marked on standard hematoxylin-eosin (HE) sections, punched out of the paraffin blocks and inserted into a recipient block using tissue arrayer instruments. Immunohistochemistry and RT-PCR were employed to detect TMPRSS2:ERG fusion gene. ERG was highly expressed in the nuclei of endothelial cells of vessels and weak cytoplasmic staining was occasionally observed. ERG positive staining was present in 14.9 % (26/174) of the tumor samples in microarray. All benign prostate samples were found to be negative. RT-PCR results revealed that 11.1 % (15/135) were TMPRSS2:ERG fusion positive. Altogether, there was a good agreement of ERG immunostaining with the presence of TMPRSS2:ERG. However, no correlation was observed between ERG expression and age, Gleason score, stage, surgical margin, and seminal vesicle involvement in Chinese patients. In the present study, we identified a high correlation between ERG expression and ERG TMPRSS2:ERG, with 100 % sensitivity and 88.9 % specificity. The expression level of ERG was unrelated to the age, Gleason score, stage, surgical margin, and seminal vesicle involvement. Therefore, the association between ERG expression and prostate cancer based on Chinese population should be further investigated in the future.

2016Aug
Inflammation
Inflammation 2016 Aug;39(4):1434-40
School of Life Sciences, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, People's Republic of China.

Asthma is a chronic inflammatory airway disease. It was prevalently perceived that Th2 cells played the crucial role in asthma pathogenesis, which has been identified as the important target for anti-asthma therapy. The soluble IL-4 receptor (sIL-4R), which is the decoy receptor for Th2 cytokine IL-4, has been reported to be effective in treating asthma in phase I/II clinical trail.Read More

To develop more efficacious anti-asthma agent, we attempt to test whether the Helicobacter pylori neutrophil-activating protein (HP-NAP), a novel TLR2 agonist, would enhance the efficacy of sIL-4R in anti-asthma therapy. In our work, we constructed a pcDNA3.1-sIL-4R-NAP plasmid, named PSN, encoding fusion protein of murine sIL-4R and HP-NAP. PSN significantly inhibited airway inflammation, decreased the serum OVA-specific IgE levels and remodeled the Th1/Th2 balance. Notably, PSN is more effective on anti-asthma therapy comparing with plasmid only expressing sIL-4R.

Continued use of trastuzumab in PTEN-deficient HER2+ breast cancer induces the epithelial-to-mesenchymal transition (EMT), transforms HER2+ to triple negative breast cancer, and expands breast cancer stem cells (BCSCs). Using cancer cell lines with two distinct states, epithelial and mesenchymal, we identified novel targets during EMT in PTEN-deficient trastuzumab-resistant breast cancer. Differential gene expression and distinct responses to a small molecule in BT474 (HER2+ trastuzumab-sensitive) and the PTEN-deficient trastuzumab-resistant derivative (BT474-PTEN-LTT) provided the selection tools to identify targets during EMT.Read More

siRNA knockdown and small molecule inhibition confirmed MEOX1 as one of the critical molecular targets to regulate both BCSCs and mesenchymal-like cell proliferation. MEOX1 was associated with poor survival, lymph node metastasis, and stage of breast cancer patients. These findings suggest that MEOX1 is a clinically relevant novel target in BCSCs and mesenchymal-like cancer cells in PTEN-deficient trastuzumab resistant breast cancer and may serve as target for future drug development.

2016Aug
Proc. Natl. Acad. Sci. U.S.A.
Proc Natl Acad Sci U S A 2016 Aug 15;113(31):8861-6. Epub 2016 Jul 15.
Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305;

Many important crops are members of the Poaceae family, which develop root systems characterized by a high degree of root initiation from the belowground basal nodes of the shoot, termed the crown. Although this postembryonic shoot-borne root system represents the major conduit for water uptake, little is known about the effect of water availability on its development. Here we demonstrate that in the model C4 grass Setaria viridis, the crown locally senses water availability and suppresses postemergence crown root growth under a water deficit.Read More

This response was observed in field and growth room environments and in all grass species tested. Luminescence-based imaging of root systems grown in soil-like media revealed a shift in root growth from crown-derived to primary root-derived branches, suggesting that primary root-dominated architecture can be induced in S. viridis under certain stress conditions. Crown roots of Zea mays and Setaria italica, domesticated relatives of teosinte and S. viridis, respectively, show reduced sensitivity to water deficit, suggesting that this response might have been influenced by human selection. Enhanced water status of maize mutants lacking crown roots suggests that under a water deficit, stronger suppression of crown roots actually may benefit crop productivity.

2016Aug
Oncotarget
Oncotarget 2016 Aug;7(35):57379-57390
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China.

Pancreatic cancer (PC) is one of the most common causes of cancer-related death. The underlying mechanism of PC is not completely understood at present. Studies in recent years have demonstrated that long non-coding RNAs (lncRNAs) have multiple biological functions in cell growth, differentiation and proliferation.Read More

Notably, expressions of some lncRNAs undergo significant changes in the initiation and progression of cancers. In addition, lncRNAs are reported to be involved in various steps of PC development and have a potential value in the diagnosis, treatment and prognostic prediction of PC. In this review, we highlight recent evidence related to the molecular mechanism of lncRNAs in growth, survival, invasion, metastasis, angiogenesis and apoptosis of PC cells, and discuss the potential clinical application of lncRNAs to the diagnosis, treatment and prognostic prediction of PC.

2016Aug
Anal. Chim. Acta
Anal Chim Acta 2016 Aug 1;933:66-74. Epub 2016 Jun 1.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address:

A high-sensitive nonenzymatic hydrogen peroxide (H2O2) biosensor based on cuprous iodide and graphene (CuI/Gr) composites has been explored for the detection of H2O2 released by living cells and monitoring the oxidative stress of cells under excellular stimulation. The biosensor properties were evaluated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), amperometric i-t curve, and the redox-competition mode of scanning electrochemical microscopy (SECM). Our observations demonstrate that the CuI/Gr nanocomposites modified glassy carbon electrode (GCE) exhibits excellent catalytic activity for H2O2 with relatively low detection limit and a wide linear range from 0.Read More

5 μM to 3 mM. Moreover, the redox-competition mode of SECM imaging study further illustrates the improved electrochemical catalytic capability for H2O2 reduction with CuI/Gr nanocomposites deposited on graphite electrode. Hence, the as-prepared nonenzymatic H2O2 biosensor could be used to detect H2O2 release from different kinds of living cells under stimulation while eliminating the interference of ascorbic acid.

2016Aug
Sci Rep
Sci Rep 2016 Aug 8;6:31270. Epub 2016 Aug 8.
State Key Laboratory of Food Science and Technology, School of Food Science of Jiangnan University, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Wuxi, Jiangsu, 214122, China.

During an exposure, humans and animals are most often exposed to a mixture rather than individual mycotoxins. In this study, a Human Embryonic Kidney 293 cell (HEK-293) fluorescence sensor was developed to detect and evaluate mycotoxins, deoxynivalenol (DON) and zearalenone (ZEN) compounds, produced by Fusarium culmorum that are common food contaminants. TRE-copGFP (green fluorescent protein) and ERE-TagRFP (red fluorescent protein) plasmids were constructed and cotransfected into HEK-293 cells through a highly efficient, lipid-mediated, DNA-transfection procedure.Read More

Results show that fluorescence intensity was proportional to DON and ZEN concentrations, ranging from 2 to 40 ng/mL and 10 to 100 ng/mL respectively, with a detection limit of 0.75 ng/mL and 3.2 ng/mL respectively. The EC50 of DON and ZEN are 30.13 ng/mL and 76.63 ng/mL respectively. Additionally, ZEN may have a synergistic effect on enhancing AP-1 activity of the toxicity pathway of DON. These data indicate the high sensitivity and effectiveness of our biosensor system in the evaluation of the combined toxicity of ZEN, DON and their derivatives. In addition, this approach is suitable for an early warning method for the detection of ZEN and DON family mycotoxins contamination without higher-priced, conventional analytical chemistry methods.

2016Aug
J Biomol Screen
J Biomol Screen 2016 Aug 23. Epub 2016 Aug 23.
Department of Hematology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

In the present study, we sought to define genes associated with immune thrombocytopenia (ITP). Microarray analysis revealed that of 1002 genes associated with ITP, 309 genes had downregulated expression and 693 genes had upregulated expression in patients with ITP. Gene set enrichment analysis revealed that 11 pathways were positively correlated to ITP, such as type I diabetes mellitus, intestinal immune network for IgA production, and oxidative phosphorylation.Read More

The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased. In conclusion, the gene expression profile of patients with ITP has established a foundation to study the gene mechanism of ITP progression.

2016Aug
J. Int. Med. Res.
J Int Med Res 2016 Aug 25. Epub 2016 Aug 25.
Department of Urology, Xiang Ya Hospital, Central South University, Changsha, China

To investigate the impact of urethral catheterization on uroflow by comparing urodynamic parameters of free uroflowmetry versus pressure-flow study in adult patients with benign prostatic hyperplasia, female stress incontinence, lumbosacral spinal injury or spina bifida.
Each patient was required to perform pressure-flow study immediately following free uroflowmetry. Maximum flow rate (Qmax), average flow rate (Qave), voided volume (VV), Tmax (time to Qmax) and post-voiding residual urine (PVR) were compared between the two tests.Read More


Out of 120 patients, transurethral catheterization significantly impacted uroflow. In male patients with benign prostatic hyperplasia (n = 50), Qmax, Qave and Tmax were significantly different between free uroflow and pressure-flow study. In patients with female stress incontinence (n = 30), there were no statistically significant between-test differences in VV and Tmax, but Qmax, Qave and PVR were significantly different. In patients with spinal injury or spina bifida (n = 40), Qmax, Qave and VV were significantly different between free uroflow and pressure-flow study.
Urethral catheterization adversely impacts uroflow in patients with benign prostatic hyperplasia, female stress incontinence, spinal injury or spina bifida. Free uroflowmetry should be performed before pressure-flow study.

2016Aug
Oncoimmunology
Oncoimmunology 2016 Aug 11;5(8):e1207841. Epub 2016 Jul 11.
Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University , Luzhou, Sichuan, P.R. China.

The B7 gene family has crucial roles in the regulation of adaptive cellular immunity. In cancer, deregulation of co-inhibitory B7 molecules is associated with reduced antitumor immunity and cancer immune evasion. FDA approval of cancer immunotherapy antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)-both ligands of the B7 family-demonstrate the impact of these checkpoint regulators in cancer.Read More

Using data from cBioPortal, we performed comprehensive molecular profiling of the 10 currently known B7 family proteins in 105 different cancers. B7 family members were amplified in breast cancer: with B7 mRNA levels upregulated in a cohort of 1,098 patients with all types of breast cancer and in 82 patients with triple-negative breast cancer. Promoter methylation analysis indicated an epigenetic basis for deregulation of certain B7 family genes in breast cancer. Moreover, patients with B7-H6 genomic alterations had significantly worse overall survival, and certain clinical attributes were associated with B7-H6 expression, which indicates that B7-H6 may be a potential target for breast cancer immunotherapy. Finally, using network analysis (based on data from cBioportal), we identified BTLA, MARCH8, PLSCR1 and SMAD3 as potentially involved in T cell signaling under regulation of B7 family proteins.

2016Jul
Biosens Bioelectron
Biosens Bioelectron 2016 Jul 8;81:349-57. Epub 2016 Mar 8.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address:

In this study, a sensitive and simple electrochemical murine macrophage (Ana-1) cell sensor has been developed for early detection of lipopolysaccharides (LPS) to evaluate the toxicity of pathogenic bacteria. Magnetic glassy carbon electrode (MGCE), which possesses excellent reproducibility and regeneration qualities, was modified with a nanocomposite to improve electrochemical signals and enhance the sensitivity. The synthesized magnetic nanoparticles (MNPs) were internalized into murine macrophages, which completed the immobilization of macrophages onto the modified electrode for evaluating the cytotoxicity of LPS by electrochemical impedance spectroscopy (EIS).Read More

The MNPs facilitated reusability of the proposed sensor by allowing removal of the magnetic core from the electrode. Our results indicated that LPS caused a marked decrease in electrochemical impedance in a dose-dependent manner in range of 1-5μg/mL. By SEM, we found that microvilli on the plasma membrane became scarce and the membrane became smooth on cells incubated with LPS, which lessens the absorption of cells to reduce the impedance. And biological assay indicated that EIS patterns were correlated with the calcium concentration in cells, and suggested that [Ca(2+)]i production increased in cells incubated with LPS and its mobilization altered electrochemical signals. Compared with conventional methods, this electrochemical test is inexpensive, highly sensitive, and has a quick response, and thus provides a new avenue for evaluating the cytotoxicity of pathogens.

2016Jul
Lancet Infect Dis
Lancet Infect Dis 2016 Jul 17;16(7):e108-18. Epub 2016 May 17.
Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China; School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China. Electronic address:

Avian influenza A H5N1 viruses have caused many, typically severe, human infections since the first human case was reported in 1997. However, no comprehensive epidemiological analysis of global human cases of H5N1 from 1997 to 2015 exists. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the outbreaks since November, 2014, which have the highest number of cases ever reported worldwide in a similar period.Read More

Data on individual patients were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May, 1997, and April, 2015. The number of affected countries rose between 2003 and 2008, with expansion from east and southeast Asia, then to west Asia and Africa. Most cases (67·2%) occurred from December to March, and the overall case-fatality risk was 483 (53·5%) of 903 cases which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November, 2014, compared with the cases beforehand, there were no significant differences in the fatality risk, history of exposure to poultry, history of patient contact, and time from onset to hospital admission in the recent cases.

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy.Read More

We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

2016Jul
Biomater Sci
Biomater Sci 2016 Jul 27;4(7):1085-91. Epub 2016 May 27.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease which is difficult to cure. When Alzheimer's disease occurs, the level of zinc ions in the brain changes, and the relevant amount of zinc ions continue decreasing in the cerebrospinal fluid and plasma of Alzheimer's patients with disease exacerbation. In view of these considerations, we have explored a new strategy for the in vivo rapid fluorescence imaging of Alzheimer's disease through target bio-labeling of zinc oxide nanoclusters which were biosynthesized in vivo in the Alzheimer's brain via intravenous injection of zinc gluconate solution.Read More

By using three-month-old and six-month-old Alzheimer's model mice as models, our observations demonstrate that biocompatible zinc ions could pass through the blood-brain barrier of the Alzheimer's disease mice and generate fluorescent zinc oxide nanoclusters (ZnO NCs) through biosynthesis, and then the bio-synthesized ZnO NCs could readily accumulate in situ on the hippocampus specific region for the in vivo fluorescent labeling of the affected sites. This study provides a new way for the rapid diagnosis of Alzheimer's disease and may have promising prospects in the effective diagnosis of Alzheimer's disease.

2016Jul
Europace
Europace 2016 Jul 7. Epub 2016 Jul 7.
Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan, Shandong Province 250014, China

The meta-analysis was aimed to search for candidate blood markers whose pre-ablation level was associated with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA).
A systematic literature search of PubMed, EMBASE, Springer Link, Web of Science, Wiley-Cochrane library, and supplemented with Google scholar search engine was performed. Thirty-six studies covering 11 blood markers were qualified for this meta-analysis.Read More

Compared with the nonrecurrence group, the recurrence group had increased pre-ablation level of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), C-reactive protein, low density lipoprotein (LDL), and tissue inhibitor of metal loproteinase-2 (TIMP-2) [standardized mean difference (95% confidence interval): 0.37 (0.13-0.61), 0.77 (0.40-1.14), 1.25 (0.64-1.87), 0.37 (0.21-0.52), 0.35 (0.10-0.60), 0.24 (0.07-0.42), 0.17 (0.00-0.34), respectively], while no statistical difference of pre-ablation level of white blood cell, total cholesterol, triglyceride, and transforming growth factor-β1 was found. Subgroup analysis demonstrated that ANP was associated with AF recurrence in participants who had no concomitant structural heart diseases (SHD); however, not in participants who had SHD, C-reactive protein was associated with AF recurrence in Asian studies, whereas not in European studies.
Increased pre-ablation level of ANP, BNP, NT-pro-BNP, IL-6, C-reactive protein, LDL, and TIMP-2 was associated with greater risk of AF recurrence after RFCA.

2016Jul
Evid Based Complement Alternat Med
Evid Based Complement Alternat Med 2016 15;2016:2018704. Epub 2016 Jun 15.
Department of Pharmacy, Yijishan Hospital, Wannan Medical College, Wuhu 241000, China.

1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is a bioactive compound isolated from Securidaca inappendiculata Hassk. and validated with antiproliferative activities on a panel of cancer cell lines. This study was designed to investigate its growth inhibitory effects on multidrug resistance (MDR) non-small cell lung carcinoma (NSCLC) cell line A549/Taxol and explore the possible linkage between modulation of MAPKs and the bioactivities.Read More

Its growth inhibitory potency on the cells was estimated by MTT assay, and flow cytometric analysis was employed to investigate its potential cell cycle arrest and proapoptosis effects. Expressions of hallmark proteins were assessed by Western-Blot method. The results showed A549/Taxol cells were sensitive to XAN. XAN inhibited the proliferation of A549/Taxol cells in the time and concentration dependent manners. It acted as a potent inducer of apoptosis and cell cycle arrest in the cells. Western-Blot investigation validated the proapoptosis and cell cycle arrest activities of XAN and the potential of MDR reversion. Upregulation of p38 by XAN, which accounted for the cell cycle arrest at G2 phase, and the downregulation of ERK associated with the proapoptosis activity were also revealed. Further analysis found p53 may be the central role mediated the bioactivities of MAPKs in A549/Taxol cells. Based on these evidences, a conclusion has been deduced that XAN could be a potential agent for MDR NSCLC therapy targeting specifically MAPKs.

The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method.
A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA.Read More

Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated.
33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively.
Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.

2016Jul

Major depressive disorders (MDD) is a common mental disorder with high prevalence, frequent relapse and associated with heavy disease burden. Heritability, environment and their interaction play important roles in the development of MDD. MDD patients usually display a wide variation in clinical symptoms and signs, while the diagnosis of MDD is relatively subjective.Read More

The treatment response varies substantially between different subtypes of MDD patients and only half respond adequately to the first antidepressant. This study aims to define subtypes of MDD, develop multi-dimension diagnostic test and combined predictors for improving the diagnostic accuracy and promoting personalized intervention in MDD patients.
This is a multi-center, multi-stage and prospective study. The first stage of this study is a case-control study, aims to explore the risk factors for developing MDD and then define the subtypes of MDD using 1200 MDD patients and 1200 healthy controls with a set of questionnaire. The second stage is a diagnostic test, aims to indentify and replicate the potential indicators to assist MDD diagnosis using 600 MDD patients and 300 healthy controls from the first stage with a set of questionnaire, neuropsychological assessment and a series of biomarkers. The third stage is a 96-week longitudinal study, including 8-week acute period treatment and 88-week stable period treatment, aims to identify overall predictors of treatment effectiveness on MDD at week 8 post treatment and to explore the predictors on MDD prognosis in the following 2 years using 600 MDD patients from the first stage with a set of questionnaire, neuropsychological assessment and a series of biomarkers. The primary outcome measure is the change of the total score of 17-Item Hamilton Rating Scale for Depression.
This study will provide strong and suitable evidence for enhancing the accuracy of MDD diagnosis and promoting personalized treatment for MDD patients in clinical practice.
ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.

2016Jul
Evid Based Complement Alternat Med
Evid Based Complement Alternat Med 2016 30;2016:9634750. Epub 2016 Jun 30.
School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied.Read More

In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved.

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
Influenza Other Respir Viruses
Influenza Other Respir Viruses 2016 Jul 28. Epub 2016 Jul 28.
China-US Collaborative Program on Emerging and Re-Emerging Infection Disease, Center for Global Health, Centers for Disease Control and Prevention, Beijing, China.

Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China.
We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes.Read More

Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza.
During the study period, 15 354 children aged <15 years with signs and symptoms of SARI were enrolled at hospital admission. severe acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. P<.05). Only 16% (1116/7145) of enrolled patients had received seasonal trivalent influenza vaccination within 12 months of hospital admission. Non-vaccinated influenza cases were more likely than vaccinated influenza cases to have pneumonia (31/133, 23% vs 37/256, 15%, P<.05). severe acute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, P<.05).
Influenza A (H3N2) virus infection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children.

2016Jun
J. Int. Med. Res.
J Int Med Res 2016 Jun 14;44(3):613-9. Epub 2016 Mar 14.
Department of Urology, Xiang Ya Hospital, Central South University, Changsha, China

To compare the clinical effectiveness of three-dimensional (3D) and two-dimensional (2D) laparoscopic imaging systems for radical cystectomy (RC) with pelvic lymph node dissection.
This was a retrospective analysis of data collected from all patients who underwent RC with pelvic lymph node dissection between January 2013 and May 2014, performed by a single surgeon in our clinic. Demographic characteristics and operative data from the procedure were collected and compared.Read More


Data were available from 42 patients (mean age 63 ± 6.7 years) of whom 18 were operated on using a 3D imaging laparoscope (Group 3D) and 24 were operated on using a conventional 2D laparoscope (Group 2D). There were no statistically significant differences in patient characteristics between the two groups (P > 0.05). There was no difference between groups in the mean (±SD) number of lymph nodes retrieved from each patient (13.2 ± 4.6 and 12.5 ± 4.3, for the 3D and 2D groups respectively), or in blood loss. PLND duration and total operative time were statistically significantly lower in Group 3D than in group 2D. There were no statistically significant between-group differences in postoperative hospital stay or total cost of the procedures. Serious postoperative complications occurred in one patient (5.6%) in group 3D, and four patients (16.7%) in group 2D (P = 0.075).
With the assistance of 3D stereoscopic imaging, surgeons may be able to reduce both the duration of lymph node dissection and overall operative time during laparoscopic RC with pelvic lymph node dissection, without increasing postoperative hospital stay or total cost.

2016Jun
Oncol. Rep.
Oncol Rep 2016 Jun 29;35(6):3541-7. Epub 2016 Mar 29.
Department of ENT, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, P.R. China.

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts.Read More

Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood.Read More


Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed.
29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence.
Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors. Prostate 76:845-853, 2016. © 2016 Wiley Periodicals, Inc.

Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory-confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions.Read More

Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity.

2016Jun
Neurol Genet
Neurol Genet 2016 Jun 12;2(3):e78. Epub 2016 May 12.
Department of Neuroscience (I.M., K.A.M.), Scripps Research Institute, Jupiter, FL; Shenzhen Key Laboratory of Neurogenomics (M.F., J.Z.), BGI-Shenzhen (M.F., C.G., J.Z., H.J.), Shenzhen, China; Department of Pediatric Metabolism (R.K.Ö., D.Y.Y., A.D.), Institute of Child Health; Department of Pediatric Neurology (D. Yalnızoğlu), Faculty of Medicine, Hacettepe University, Ankara, Turkey; Department of Pediatric Neurology (D. Yüksel), Dr. Sami Ulus Maternity and Children's Research and Training Hospital, Ministry of Health, Ankara, Turkey; Sanford Children's Health Research Center (A.Y., A.M., S.C.B., P.L.C.), Sioux Falls, SD; Department of Child Health (S.P.-L., M.C.K.), University of Arizona College of Medicine, Phoenix, AZ; Movement Disorders Center and Neurogenetics Research Program (S.P.-L., M.C.K.), Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ; and Program in Neuroscience (M.C.K.), Arizona State University, Tempe, AZ.
2016Jun
Sci Rep
Sci Rep 2016 Jun 27;6:28510. Epub 2016 Jun 27.
Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore.

Excited state dynamics in two strong organic electron acceptor systems, TCNQ and F4TCNQ single crystals, was studied. After absorption of a single photon, dianions are formed in both crystals on ultrashort timescale: TCNQ τ < 50 fs, F4TCNQ τ = 4 ps. By use of transient absorption spectroscopy, we demonstrate that the dianion formation in F4TCNQ is mediated by the radical anion precursor which is described by a two-step model.Read More

Our measurements show the phenomenon that in this quinoid acceptor crystals in the absence of additional donor molecule, it is possible to resolve the two step formation of a doubly charged anion upon absorption of a single low energy photon (2.6 eV).

Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of the >100 variants associated with T2D and related traits in genome-wide association studies (GWAS), >90% occur in non-coding regions, suggesting a strong regulatory component to T2D risk. Here to understand how T2D status, metabolic traits and genetic variation influence gene expression, we analyse skeletal muscle biopsies from 271 well-phenotyped Finnish participants with glucose tolerance ranging from normal to newly diagnosed T2D.Read More

We perform high-depth strand-specific mRNA-sequencing and dense genotyping. Computational integration of these data with epigenome data, including ATAC-seq on skeletal muscle, and transcriptome data across diverse tissues reveals that the tissue-specific genetic regulatory architecture of skeletal muscle is highly enriched in muscle stretch/super enhancers, including some that overlap T2D GWAS variants. In one such example, T2D risk alleles residing in a muscle stretch/super enhancer are linked to increased expression and alternative splicing of muscle-specific isoforms of ANK1.

2016Jun
Prep. Biochem. Biotechnol.
Prep Biochem Biotechnol 2016 Jun 1:1-5. Epub 2016 Jun 1.
a Research Center of Biological Information , College of Science, National University of Defense Technology , Changsha , China.

In the present study, we used Escherichia coli to produce recombinant Hainantoxin-III (rHNTX-III), a 33-amino acid peptic toxin from the tarantula spider Haplopelma hainanum. The toxin has three pairs of disulfide bonds. A pET-HS-HNTX-III vector was constructed and transformed into the E.Read More

coli strain SHuffle(TM). rHNTX-III was expressed using auto-induction medium. After using a Ni-NTA column, the expressed fusion protein was digested using SUMO protease (ULP1) to remove the HIS-SUMO tag, and then RP-HPLC and ultrafiltration were used for further purification. Then the rHNTX-III was identified by MALDI-TOF/TOF mass spectrometry. The purified rHNTX-III was further analyzed using a whole-cell patch-clamp assay. It was shown that the rHNTX-III was able to block currents generated by human Nav1.7 (hNav1.7) at an IC50 of 225 nM and also have high selectivity for different voltage-gated sodium channels. Therefore, it has very similar activity to the natural one.

2016May
Cancer Lett.
Cancer Lett 2016 May 2;375(1):39-46. Epub 2016 Mar 2.
Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. Electronic address:

The purpose of this study is to report the first nationwide protocol (Wuhan Protocol) developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma. In this study, we reported the final analysis, which includes 153 hepatoblastoma patients in 13 hospitals from January 2006 to December 2013. The 6-year overall survival and event-free survival rates were 83.Read More

3 ± 3.1% and 71.0 ± 3.7%, respectively, in this cohort. The univariate analysis revealed that female (P = 0.027), under 5 years of age (P = 0.039), complete surgical resection (P = 0.000), no metastases (P = 0.000), and delayed surgery following neoadjuvant chemotherapy (P = 0.000) had better prognosis. In multivariate analysis, male, 5 years of age or above, stage PRETEXT III or IV, and incomplete surgical resection were among the some adverse factors contributing to poor prognosis. The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries. However, the protocol remains to be further optimized in standardizing surgical resection (including liver transplantation), refining risk stratification and risk-based chemotherapy.

2016May
J Fluoresc
J Fluoresc 2016 May 15;26(3):977-85. Epub 2016 Mar 15.
School of Resource and Environmental Science, Anqing Normal University, Anqing, 246133, People's Republic of China.

An acrylic monomer bearing xanthene group, N-oxethyl acrylate-N'-rhodamine B hydrazide (ARBHE) was synthesized from N-hydroxyl ethyl-N'-rhodamine hydrazide (RBHE) and acryloyl chloride (Ac) in the presence of triethylamine in dry dichloromethane (CH2Cl2) at room temperature. The synthesized ARBHE was identified by FTIR, (1)H NMR spectra and elementary analysis. Copolymer poly(AM-ARBHE) of ARBHE and AM was synthesized with thermal initiator by free radical precipitation polymerization and it was characterized by the method of FTIR and (1)H NMR.Read More

Its molecular weights (Mη) was 7.03 × 10(3) g mol(-1) and the content of rhodamine units in the polymer chains was 1.44 % in mole fraction. The ability of the poly(AM-ARBHE) to detect different metal cations (Ag(+), Ba(2+), Cd(2+) Co(2+), Cr(3+), Cu(2+), Co(2+) K(+), La(3+), Mg(2+), Na(+), Ni(2+), Pb(2+), Fe(2+), Fe(3+), Hg(2+) and Zn(2+)) in water was investigated. Upon addition of Cr(3+), Fe(3+) or Hg(2+) ions to the aqueous solution, visual color change and fluorescence enhancement were observed. Moreover, other metal ions did not induce obvious changes to the fluorescence spectra except to Fe(2+). The detection limit of poly(AM-ARBHE) was less than 1 × 10(-11) M. The results suggest that this copolymer may offer potential as a polymeric sensor for Cr(3+), Fe(3+) and Hg(2+) ions in water.

2016May
Oncotarget
Oncotarget 2016 May;7(18):25208-23
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs.Read More

RNA-sequencing and pathway analysis identified the c-Myc transcriptional program as one of the top distinguishing features. c-Myc protein levels were highly correlative with AML disease latency in mice. Functionally, overexpression of c-Myc resulted in a more aggressive proliferation rate in MLL-FP cell lines. While all MLL-FP transformed cells displayed sensitivity to BET inhibitors, high c-Myc expressing cells showed greater resistance to Brd4 inhibition. The Myc target Lin28B was also differentially expressed in MLL-FP cell lines in agreement with c-Myc expression. Examination of Lin28B miRNAs targets revealed that let-7g was significantly increased in leukemic cells associated with the longest disease latency and forced let-7g expression induced differentiation of leukemic blasts. Thus, differential regulation of the c-Myc/Lin28/let-7g program by different MLL-FPs is functionally related to disease latency and BET inhibitor resistance in MLL leukemias.

2016May
Anal. Chem.
Anal Chem 2016 May 14;88(9):4766-71. Epub 2016 Apr 14.
State Key Laboratory of Bioelectronics and School of Biological Science and Medical Engineering, Southeast University , Nanjing, Jiangsu 210096, P. R. China.

The photoluminescence (PL) of nonthiolate ligand capped Au nanoclusters (NCs) is usually quenched by thiols due to the tight adsorption of thiols to the Au surface and formation of larger non-PL species. However, we here report an unexpected PL enhancement of cytidine stabilized Au (AuCyt) NCs triggered by thiols, such as reduced glutathione (GSH) at sub-μM level, while such phenomena have not been observed for Au NCs capped with similar adenosine/cytidine nucleotides. The mass spectroscopic results indicate that this enhancement may be caused by the formation of smaller, but highly fluorescent, Au species etched by thiols.Read More

This enables the sensitive detection of GSH from 20 nM to 3 μM, with an ultralow detection limit of 2.0 nM. Moreover, the glutathione reductase (GR) activity can be determined by the initial rate of GSH production, i.e., the maximum PL increasing rate, with a linear range of 0.34-17.0 U/L (1 U means reduction of 1.0 μmol of oxidized glutathione per min at pH 7.6 at 25 °C) and a limit of detection of 0.34 U/L. This method allows the accurate assays of GR in clinical serum samples as well as the rapid screening of GR inhibitors, indicating its promising biomedical applications.

2016May
Nutr Metab (Lond)
Nutr Metab (Lond) 2016 17;13:36. Epub 2016 May 17.
Department of Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Ave, Box 5, Brooklyn, NY 11203 USA.

Serum preβ1-high density lipoprotein (preβ1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum preβ1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. However, there are still debatable questions for its quantification and coronary artery disease (CAD) relevance.Read More


We isolated the preβ1-HDL using a new native polyacrylamide gel electrophoresis (PAGE) system and lipid pre-staining serum. We established a two-demensional gel electrophoresis system.
We measured the preβ1-HDL in Tangier disease patients and subjects with cholesterol ester transfer protein (CETP) mutation. The preβ1-HDL is clearly separated from lipid-free apoA-I monomer and cannot be converted into other HDL particles under lecithin-cholesterol acyltransferase (LCAT) inhibition. This preβ1-HDL is a spheroidal particle with the highest apoA-1/cholesterol ratio and highest density (≥1.21 g/ml), as compared with all other HDLs. Importantly, we found that serum from subjects with Tangier disease or with cholesterol ester transfer protein (CETP) mutation have no detectible preβ1-HDL particles. We recruited a total of 102 subjects underwent diagnostic coronary angiography and measured their preβ1-HDL levels. Among them, 56 had no stenosis of coronary artery and 46 were diagnosed as CAD, which was predefined as the presence of a luminal diameter stenosis ≥50 % in at least 1 major coronary artery territory. We found that preβ1-HDL is independently and negatively associated with the severity of the coronary artery stenosis (Gensini score).
We established a novel and simple method for human serum preβ1-HDL quantification. We found that human lower preβ1-HDL is an independent predictor for severer coronary artery stenosis.

2016May
J Comput Graph Stat
J Comput Graph Stat 2016;25(1):301-320. Epub 2016 Mar 9.
Department of Statistics and Health Research and Policy, Stanford University, Stanford, CA 94305.

Optional Pólya tree (OPT) is a flexible nonparametric Bayesian prior for density estimation. Despite its merits, the computation for OPT inference is challenging. In this paper we present time complexity analysis for OPT inference and propose two algorithmic improvements.Read More

The first improvement, named limited-lookahead optional Pólya tree (LL-OPT), aims at accelerating the computation for OPT inference. The second improvement modifies the output of OPT or LL-OPT and produces a continuous piecewise linear density estimate. We demonstrate the performance of these two improvements using simulated and real date examples.

2016May
Nan Fang Yi Ke Da Xue Xue Bao
Nan Fang Yi Ke Da Xue Xue Bao 2016 May;36(5):649-54
School of Life Sciences, Zhengzhou University, Zhengzhou 450000, China.E-mail:

To detect the expression of protein 4.1 family members in mouse melanoma cell lines and evaluate their effect on cell proliferation.
PCR and Western blot were used to detected to the expression of protein 4.Read More

1 family members (4.1R, 4.1B, 4.1G, and 4.1N) at the mRNA and protein levels in B16 and B16-F10 cell lines. The expression plasmid vector pEGFP-N1-EPB41L3 carrying 4.1B gene sequence amplified from genomic RNA of mouse embryo fibroblasts was constructed and transiently transfected into mouse melanoma cells. The change in cell proliferation was assessed using MTT assay.
The mRNA and protein expressions of all the protein 4.1 family members, with the exception of 4.1B, were detected in both B16 and B16-F10 cells. Transfection of cells with the eukaryotic expression vector pEGFP-N1-EPB41L3 markedly inhibited cell proliferation as compared with the non-transfected cells.
The eukaryotic expression vector carrying EPB41L3 sequence is capable of inhibiting the proliferation of mouse melanoma B16 and B16-F10 cells.

2016Apr
J. Cell Biol.
J Cell Biol 2016 Apr 4;213(1):49-63. Epub 2016 Apr 4.
National Institute of Biological Sciences, Beijing 102206, China

Mitochondria-associated degradation (MAD) mediated by the Cdc48 complex and proteasome degrades ubiquitinated mitochondrial outer-membrane proteins. MAD is critical for mitochondrial proteostasis, but it remains poorly characterized. We identified several mitochondrial Cdc48 substrates and developed a genetic screen assay to uncover regulators of the Cdc48-dependent MAD pathway.Read More

Surprisingly, we identified Doa1, a substrate-processing factor of Cdc48 that inhibits the degradation of some Cdc48 substrates, as a critical mediator of the turnover of mitochondrial Cdc48 substrates. Deletion ofDOA1causes the accumulation and mislocalization of substrates on mitochondria. Profiling of Cdc48 cofactors shows that Doa1 and Cdc48(-Ufd1-Npl4)form a functional complex mediating MAD. Biochemically, Doa1 interacts with ubiquitinated substrates and facilitates substrate recruitment to the Cdc48(-Ufd1-Npl4)complex. Functionally, Doa1 is critical for cell survival under mitochondrial oxidative stress, but not ER stress, conditions. Collectively, our results demonstrate the essential role of the Doa1-Cdc48(-Ufd1-Npl4)complex in mitochondrial proteostasis and suggest that Doa1 plays dual roles on the Cdc48 complex.

2016Apr

Phosphopantetheinyl transferases (PPTases) play essential roles in both primary metabolisms and secondary metabolisms via post-translational modification of acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs). In this study, an industrial FK506 producing strain Streptomyces tsukubaensis L19, together with Streptomyces avermitilis, was identified to contain the highest number (five) of discrete PPTases known among any species thus far examined. Characterization of the five PPTases in S.Read More

tsukubaensis L19 unveiled that stw ACP, an ACP in a type II PKS, was phosphopantetheinylated by three PPTases FKPPT1, FKPPT3, and FKACPS; sts FAS ACP, the ACP in fatty acid synthase (FAS), was phosphopantetheinylated by three PPTases FKPPT2, FKPPT3, and FKACPS; TcsA-ACP, an ACP involved in FK506 biosynthesis, was phosphopantetheinylated by two PPTases FKPPT3 and FKACPS; FkbP-PCP, an PCP involved in FK506 biosynthesis, was phosphopantetheinylated by all of these five PPTases FKPPT1-4 and FKACPS. Our results here indicate that the functions of these PPTases complement each other for ACPs/PCPs substrates, suggesting a complicate phosphopantetheinylation network in S. tsukubaensis L19. Engineering of these PPTases in S. tsukubaensis L19 resulted in a mutant strain that can improve FK506 production.

2016Apr
Sci Rep
Sci Rep 2016 Apr 7;6:24105. Epub 2016 Apr 7.
School of Materials Science and Engineering, Nanyang Technological University, 639798 Singapore.

Due to the two dimensional confinement of electrons in a monolayer of 2D materials, the properties of monolayer can be controlled by electrical field formed on the monolayer surface. F4TCNQ was evaporated on MoS2 and WS2 monolayer forming dipoles between strong acceptor, F4TCNQ, and monolayers of MoS2 or WS2. The strong acceptor attracts electrons (charge transfer) and decreases the number of the ionized excitons.Read More

Free excitons undergo radiative recombination in both MoS2 and WS2. Moreover, the photoluminescence enhancement is stronger in WS2 where the exciton-phonon coupling is weaker. The theoretical model indicates that the surface dipole controls the radiative exciton recombination and enhances photoluminescence radiation. Deposition of F4TCNQ on the 2D monolayers enables a convenient control of the radiative exciton recombination and leads to the applications of these materials in lasers or LEDs.

2016Apr
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016 Apr;32(4):457-61
First Hospital Affiliated to Anhui university of TCM, Grade 3 Laboratory of Traditional Chinese Medicine Preparation, State Administration of TCM, Modern Chinese Medicine Department of Internal Medicine Application Foundation Research and Development Laboratory, Hefei 230031, China.

To observe the effects of Xinfeng capsule (XFC) treatment on the expressions of Bcl-2, Bax and caspase-3 in the synovium tissues of the adjuvant-induced arthritis (AA) rats and explore the possible mechanisms.
Spague-Dawley (SD) rats were randomly divided into normal group, model group, XFC (1.5, 3.Read More

0, 6.0 g/kg) groups and 40 mg/kg tripterygium glycosides tablet (TGT) group, with 10 rats in each group. Arthritis rat was induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant (FCA) in the left paw. XFC at different doses and TGT, diluted in water, were administrated via gavage, once a day from the 19th day to the 48th day after AA induction. The normal and model rats were orally administered the same volume of saline solution. Then, ankle-joint samples were taken to examine the degree of AA by HE staining. Bcl-2, Bax and caspase-3 mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Meanwhile, the protein expression levels of Bcl-2, Bax and caspase-3 were detected by immunohistochemistry and Western blotting.
Compared with the model group, XFC treatment improved histopathological changes, such as synovial hyperplaisia, pannus formation, and so on. Furthermore, XFC (3.0 and 6.0 g/kg) groups not only obviously attenuated mRNA and protein expressions of Bcl-2, but also obviously up-regulated the expressions of Bax and caspase-3 both at protein and mRNA levels.
XFC has a protective effect on AA rats, which might be partly associated with its regulatory role in decreasing the expression of Bcl-2 and promoting the expressions of Bax and caspase-3.

2016Apr
World J. Gastroenterol.
World J Gastroenterol 2016 Apr;22(13):3693-700
Hui Jiang, Na Ta, Xiao-Yi Huang, Ming-Hua Zhang, Jing-Jing Xu, Jian-Ming Zheng, Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Perivascular epithelioid cell tumor (PEComa) of the pancreas is an unusual tumor deriving from mesenchyma. This paper described a case of pancreatic PEComa, which was initially suspected as neuroendocrine carcinoma by biopsy, and therefore surgical treatment was recommended due to undetermined diagnosis. Examination of the surgical specimen under a microscope showed that the tumor cell's morphology was epithelioid or spindle-shaped, and ranged in a nested pattern.Read More

Additionally, these cells had a large extent of acidophilic cytoplasm, no mitotic figures, and expressed HMB-45, melan-p, and smooth muscle actin immunohistochemically. Pathological examination indicated that PEComa originated from the pancreas, but symptoms related to tuberous sclerosis were absent. Since PEComa is extremely rare in the pancreas, it is likely to be ignored in differential diagnosis. In conclusion, our article highlighted the clinicopathological features of PEComa, and we conducted a literature review focusing on PEComa so as to deepen the understanding of this tumor type.

To investigate the inhibitory effect of Panax notoginseng saponins (PNS) on liver fibrosis and explore the underlying mechanisms.
Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. The effect of PNS on CCl4-induced liver fibrosis was studied with histochemical and biochemical analysis.Read More

Transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and collagen I mRNA expression were determined by reverse transcripwhile, the protein expression levels of α-SMA, collagen I, phosphorylation-Janus activated kinase signal transducer (p-Jak2)/Jak2, and phosphorylation-activator of transcription (p-Stat)3/Stat3 were determined by immunohistochemistry and/or immunoblotting.
PNS treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase and aspartate aminotransferase. Histopathological results indicated that PNS alleviated liver damage and reduced the formation of fibrous septa. Moreover, PNS significantly decreased liver hydroxyproline and significantly attenuated expressions of collagen I, α-SMA, TGF-β1, p-Jak2 / Jak2, and p-Stat3/Stat3 in the rat liver fibrosis model and HSCs.
PNS can relieve liver fibrosis by modulating Jak2/Stat3 signaling transduction pathway, which may be one of its mechanisms to suppress hepatic fibrosis.

2016Mar
Org. Lett.
Org Lett 2016 Mar 15;18(5):972-5. Epub 2016 Feb 15.
Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.

A palladium-catalyzed arylation of aryl sulfenate anions generated from aryl 2-(trimethylsilyl)ethyl sulfoxides and CsF has been developed. This protocol is effective for the synthesis of diaryl sulfoxides and heteroaryl aryl sulfoxides under mild conditions employing aryl bromides. Various functional groups, including those with acidic protons, are well tolerated.Read More

2016Mar
PLoS ONE
PLoS One 2016 9;11(3):e0150713. Epub 2016 Mar 9.
Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China.

After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents.
We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia.Read More

For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012.
Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients.
There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.

2016Mar
Onco Targets Ther
Onco Targets Ther 2016 23;9:885-94. Epub 2016 Feb 23.
Department of Urology, First Affiliated Hospital of Dalian Medical University, Beijing, People's Republic of China.

Growing evidence suggests that arsenic trioxide (As2O3) induces apoptosis and inhibits tumor cell growth in prostate cancer (PCa), although details of the mechanism are still inconclusive. We investigated the antitumor effect of As2O3 in human PCa cell lines LNCaP and PC3 and the underlying mechanisms by focusing on the Wnt signaling pathway.
The effect of As2O3 on the viability and apoptosis of PCa cells was investigated by cholecystokinin-8 and flow cytometry.Read More

The expression of the related proteins in the Wnt signaling pathway and the downstream target genes of the Wnt signaling pathway was examined by Western blot and quantitative real-time PCR assay. The methylation status of the SFRP1 gene promoter was assessed by bisulfite sequencing.
As2O3 inhibited the viability of PCa cells and induced apoptosis of PCa cells in a dose-dependent manner. The protein level of phosphoglycogen synthase kinase-3β was upregulated, whereas the protein level of β-catenin and the mRNA levels of c-MYC, MMP-7, and COX-2 were downregulated in a dose-dependent manner in PCa cells treated with As2O3. In addition, As2O3 upregulated the protein and mRNA levels of secreted frizzled related protein-1, and increased the demethylation of the SFRP1 gene promoter.
Our results suggest that As2O3 may inhibit cell viability and induce apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in both androgen-dependent and -independent human PCa.

2016Mar
Autoimmune Dis
Autoimmune Dis 2016 18;2016:5690935. Epub 2016 Feb 18.
College of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei 230038, China.

We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers.Read More

Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism.

2016Mar
J. Orthop. Res.
J Orthop Res 2016 Mar 21. Epub 2016 Mar 21.
Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, PR China.

There have been several sustained-release materials containing anti-tuberculosis drug to enhance concentration in foci of spinal tuberculosis but what map by which composite drug delivery system is released is not known. Isoniazid (INH) lactic-co-glycolic acid (PLGA) and INH hydroxyapatite (HA) microspheres were prepared respectively. The rabbits were modeled by tuberculosis strains and sustained-release microspheres were incubated in the foci.Read More

INH concentrations in the HA group were higher than those of INH and PLGA groups at L3, L4, and L5 vertebra 2 d after the drugs were embedded (P < 0.05). INH concentrations in the HA group were higher than those of INH and PLGA groups in L3 vertebra 4 d after the drugs were embedded (P < 0.05). INH concentrations in the PLGA group were higher than those of INH and HA groups in L5 vertebra; INH concentrations of the HA group were higher than those of INH and PLGA groups in L4 vertebra 6 d after the drugs were embedded (P < 0.05). These microspheres can enhance INH concentration in the foci. Furthermore, HA microspheres elicit osteogenic effects. HA is better than PLGA in terms of infiltration, but PLGA is better than HA in terms of distribution. This article is protected by copyright. All rights reserved.

2016Feb
Kidney Blood Press. Res.
Kidney Blood Press Res 2016 14;41(1):70-7. Epub 2016 Feb 14.
Cardiovascular Disease Research Institute, The Third People's Hospital of Chengdu, The Second Affiliated Chengdu Clinical College of Chongqing Medical University, Chengdu, Sichuan, China.

Both kidney dysfunction and cognitive impairment are common problems in hypertensive patients. However, few studies have explored the association between these conditions in hypertensive patients aged 80 or over. The current study was undertaken to determine the impact of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) on cognitive impairment among an 80-year-old population with untreated hypertension in China.Read More


A total of 395 hypertensive patients aged 80 or over were assessed for the presence of cognitive impairment according to the 30-item Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score below 24 on MMSE. eGFR was evaluated using the Chinese Modification of Diet in Renal Disease equation. CKD was defined according to categorical approach, which is based on "YES" (eGFR below 60 ml/min) or "NO" (eGFR above 60 ml/min).
The mean (SD) age was 83.0 ± 2.6 years for the sample, of whom 69.8% were female. There were 59 (14.9%) and 280 (71.1%) prevalent cases of CKD and cognitive impairment, respectively. CKD patients were older, had higher scores on Activity of Daily Living (ADL), and lower score on MMSE. After controlling for potential confounding, multiple logistic regressions demonstrated that both CKD and eGFR were associated with cognitive impairment in hypertensive patients aged 80 or over.
Our study found that both CKD and eGFR were associated with cognitive impairment among hypertensive patients aged 80 or over in China. Therefore, targeted screening for cognitive impairment should be considered in these patients with CKD.

2016Feb
PLoS ONE
PLoS One 2016 17;11(2):e0148506. Epub 2016 Feb 17.
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong Special Administrative Region, China.

In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity.Read More


We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4-4.1), compared to a mean of 3.3 days (95% CrI: 2.9-3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47-1.97).
We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration.

To study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.
TM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.Read More


CFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.
The CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

In order to achieve the rapid monitoring of process state of solid state fermentation (SSF), this study attempted to qualitative identification of process state of SSF of feed protein by use of Fourier transform near infrared (FT-NIR) spectroscopy analysis technique. Even more specifically, the FT-NIR spectroscopy combined with Adaboost-SRDA-NN integrated learning algorithm as an ideal analysis tool was used to accurately and rapidly monitor chemical and physical changes in SSF of feed protein without the need for chemical analysis. Firstly, the raw spectra of all the 140 fermentation samples obtained were collected by use of Fourier transform near infrared spectrometer (Antaris II), and the raw spectra obtained were preprocessed by use of standard normal variate transformation (SNV) spectral preprocessing algorithm.Read More

Thereafter, the characteristic information of the preprocessed spectra was extracted by use of spectral regression discriminant analysis (SRDA). Finally, nearest neighbors (NN) algorithm as a basic classifier was selected and building state recognition model to identify different fermentation samples in the validation set. Experimental results showed as follows: the SRDA-NN model revealed its superior performance by compared with other two different NN models, which were developed by use of the feature information form principal component analysis (PCA) and linear discriminant analysis (LDA), and the correct recognition rate of SRDA-NN model achieved 94.28% in the validation set. In this work, in order to further improve the recognition accuracy of the final model, Adaboost-SRDA-NN ensemble learning algorithm was proposed by integrated the Adaboost and SRDA-NN methods, and the presented algorithm was used to construct the online monitoring model of process state of SSF of feed protein. Experimental results showed as follows: the prediction performance of SRDA-NN model has been further enhanced by use of Adaboost lifting algorithm, and the correct recognition rate of the Adaboost-SRDA-NN model achieved 100% in the validation set. The overall results demonstrate that SRDA algorithm can effectively achieve the spectral feature information extraction to the spectral dimension reduction in model calibration process of qualitative analysis of NIR spectroscopy. In addition, the Adaboost lifting algorithm can improve the classification accuracy of the final model. The results obtained in this work can provide research foundation for developing online monitoring instruments for the monitoring of SSF process.