Xiaodong Wang - Dalian Institute of Chemical Physics
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Dalian Institute of Chemical Physics
Publications Authored By Xiaodong Wang
Medicinal chemistry efforts yielded a highly potent, selective, and metabolically stable drug candidate, compound 56 (RIPA-56). Biochemical studies and molecular docking revealed that RIP1 is the direct target of this new series of type III kinase inhibitors. In the SIRS mice disease model, 56 efficiently reduced tumor necrosis factor alpha (TNFα)-induced mortality and multiorgan damage. Compared to known RIP1 inhibitors, 56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies.
The triketones as obtained can be used as feedstocks in the production of conducting or semi-conducting polymers. By the solvent-free intramolecular aldol condensation over solid base catalysts, these triketones were selectively converted to diketones which can be used as the intermediates in synthesis of useful chemicals or polymers. As another application, the triketones and diketones can also be utilized as precursors for the synthesis of jet fuel range branched cycloalkanes which have low freezing points (224-250 K) and high densities (~0.81 g mL-1).
Here we exploited this property to sequence and catalog more than 10 million mutations in the protein-coding regions of 2,735 mutant lines of tetraploid and hexaploid wheat. We detected, on average, 2,705 and 5,351 mutations per tetraploid and hexaploid line, respectively, which resulted in 35-40 mutations per kb in each population. With these mutation densities, we identified an average of 23-24 missense and truncation alleles per gene, with at least one truncation or deleterious missense mutation in more than 90% of the captured wheat genes per population. This public collection of mutant seed stocks and sequence data enables rapid identification of mutations in the different copies of the wheat genes, which can be combined to uncover previously hidden variation. Polyploidy is a central phenomenon in plant evolution, and many crop species have undergone recent genome duplication events. Therefore, the general strategy and methods developed herein can benefit other polyploid crops.
The uniformity, size, and density of Ga nanodroplets can be tuned by the incident angles of ion beam. The ion beam current also plays a critical role in the self-ordering of Ga nanodroplets, and it is found that the droplets exhibit a similar droplet size but higher density and better uniformity with increasing the ion beam current. In addition, more complex arrangements of nanodroplets are achieved via in situ patterning and ion-beam-directed migration of Ga atoms. Particularly, compared to the destructive formation of nanodroplets through direct ion beam bombardment, the controllable assembly of nanodroplets on intact surfaces can be used as templates for fabrication of ordered semiconductor nanostructures by droplet epitaxy.
Nine patients in arm A and 15 patients in arm B received a median of 6 cycles of chemotherapy, and a median of 11 cycles (arm A) and 9 cycles (arm B) of duligotuzumab. Dose-limiting toxicities occurred in 3 patients in arm A and 1 patient in arm B. Grade ≥ 3 treatment-related adverse events (graded according to graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]) in ≥ 3 patients were neutropenia (5 patients), hypokalemia (4 patients), dehydration (3 patients), anemia (3 patients), and diarrhea (3 patients) in arm A, and neutropenia (8 patients), anemia (5 patients), febrile neutropenia (4 patients), leukopenia (3 patients), thrombocytopenia (3 patients), and hypomagnesemia (3 patients) in arm B. The chemotherapy dose was reduced in 19 of 24 patients. Sixteen patients (67%) demonstrated objective responses regardless of human papillomavirus status or neuregulin 1 (NRG1) mRNA expression (arm A: 2 confirmed complete responses and 4 confirmed partial responses; arm B: 2 confirmed complete responses and 8 confirmed partial responses).
Duligotuzumab in combination with cisplatin/5-fluorouracil or carboplatin/paclitaxel demonstrated encouraging activity in patients with recurrent/metastatic squamous cell cancer of the head and neck; an association with increased frequency and severity of select adverse events relative to historical data was suggestive of the potentiation of chemotherapy-related adverse events. Cancer 2016;122:3803-3811. © 2016 American Cancer Society.
In the hydroformylation of olefins, single-atom Rh catalysts supported on ZnO nanowires demonstrate similar efficiency (TON≈40000) compared to that of homogeneous Wilkinson's catalyst (TON≈19000). HAADF-STEM and infrared CO chemisorption experiments identified isolated Rh atoms on the support. XPS and XANES spectra indicate that the electronic state of Rh is almost metallic. The catalysts are about one or two orders of magnitude more active than most reported heterogeneous catalysts and can be reused four times without an obvious decline in activity.
sp. tritici, we identified a conserved rust protein that interacts with wheat NPR1 and named it PNPi (for Puccinia NPR1 interactor). PNPi interacts with the NPR1/NIM1-like domain of NPR1 via its C-terminal DPBB_1 domain. Using bimolecular fluorescence complementation assays, we detected the interaction between PNPi and wheat NPR1 in the nucleus of Nicotiana benthamiana protoplasts. A yeast three-hybrid assay showed that PNPi interaction with NPR1 competes with the interaction between wheat NPR1 and TGA2.2. In barley transgenic lines overexpressing PNPi, we observed reduced induction of multiple PR genes in the region adjacent to Pseudomonas syringae pv. tomato DC3000 infection. Based on these results, we hypothesize that PNPi has a role in manipulating wheat defense response via its interactions with NPR1.
The present work solves the tag SNP selection problem by efficiently balancing the computational complexity and accuracy, and improves the coverage in genomic diversity in a cost-effective manner. The employed algorithm makes use of mutual information to explore the multi-locus association between SNPs and can handle different data types and conditions. Experiments with benchmark HapMap data sets show comparable or better performance against the state-of-the-art algorithms. In particular, as a novel application, the genome-wide SNP tagging is performed in the 1000 Genomes Project data sets, and produced a well-annotated database of tagging variants that capture the common genotype diversity in 2,504 samples from 26 human populations. Compared to conventional methods, the algorithm requires as input only the genotype (or haplotype) sequences, can scale up to genome-wide analyses, and produces accurate solutions with more information-rich output, providing an improved platform for researchers towards the subsequent association studies.
The most active macrocycles had an EC50 below 40 nM in a cell-based MerTK phosphor-protein ELISA assay. The X-ray structure of macrocyclic analogue 3 complexed with MerTK was also resolved and demonstrated macrocycles binding in the ATP binding pocket of the MerTK protein as anticipated. In addition, the lead compound 16 (UNC3133) had a 1.6 h half-life and 16% oral bioavailability in a mouse PK study.
We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo, without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).
In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections.
, quercetin for positive and negative ion detection and 9-aminoacridine for negative ion detection), and metabolite identification, a total of 1091 metabolites including 1032 lipids and 59 other metabolites were routinely detected and successfully localized. Of these compounds, 250 and 217 were only detected in either the cancerous or the non-cancerous regions respectively, although we cannot rule out the presence of these metabolites at concentrations below the detection limit. In addition, 152 of the other 624 metabolites showed differential distributions (p<0.05, t-test) between the two regions of the tissues. Further studies on a larger number of clinical specimens will need to be carried out to confirm this large number of apparently cancer-related metabolites. The successful determination of the spatial locations and abundances of these endogenous biomolecules indicated significant metabolism abnormalities - e.g., increased energy charge and under-expression of neutral acyl glycerides, in the prostate cancer samples. To our knowledge, this work has resulted in MALDI-MS imaging of the largest group of metabolites in prostate cancer thus far and demonstrated the importance of using complementary matrices for comprehensive metabolomic imaging by MALDI-MS. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
An enzyme-linked immunosorbent assay (ELISA) in 384-well format was employed to evaluate the inhibitory activity of macrocycles in a cell-based assay assessing tyrosine phosphorylation of MerTK. Through structure-activity relationship (SAR) studies, analogue 11 [UNC2541; (S)-7-amino-N-(4-fluorobenzyl)-8-oxo-2,9,16-triaza-1(2,4)-pyrimidinacyclohexadecaphane-1-carboxamide] was identified as a potent and MerTK-specific inhibitor that exhibits sub-micromolar inhibitory activity in the cell-based ELISA. In addition, an X-ray structure of MerTK protein in complex with 11 was resolved to show that these macrocycles bind in the MerTK ATP pocket.
Over the Pd-modified magnesium- aluminium hydrotalcite (Pd-MgAl-HT) catalyst, a high total carbon yield (73.0 %) of C12 oxygenates can be achieved under mild conditions. In the second bed, the C12 oxygenates generated in the first bed were hydrogenated to dodecanol over a Ru/C catalyst or hydrodeoxygenated to 2,4,8-trimethylnonane over a Cu/SiO2 catalyst. The as-obtained dodecanol can be used as feedstock in the production of sodium dodecylsulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS), which are widely used as surfactants or detergents. The asobtained 2,4,8-trimethylnonane can be blended into conventional jet fuel without hydroisomerization.
Except for ND6 and 8 tRNAs, all other genes are encoded on the heavy strand. The base composition of the 13 mitochondrial protein-coding genes in the third position was relatively low (9.7%). The complete mitogenome may provide important date set for the study of genetic mechanism of S. hasta.
Giving rats either EE alone or IR alone increased placental levels of HIF-1α, REDD1, glucose transporter-1 (GLUT1), and phosphoglycerate kinase-1 (PGK1), and decreased placental mTOR and lactic dehydrogenase A (LDHA) expression compared with the control rats. Subjecting EE-treated rats to IR did not further alter placental levels of REDD1 or mTOR, while it did elevate placental HIF-1α, GLUT1, and PGK1 expression, and decline LDHA expression. By contrast, mRNA levels did not differ significantly among the four groups for any of the proteins analyzed.
This study manifested that placental HIF-1α and its downstream glucose metabolism effectors can effectively react to hypoxia in EE-induced cholestasis rats. However, hypoxia-induced REDD1 and mTOR alternation, which responds efficiently in normal placentas, was impaired in EE-induced cholestasis placentas.
HAI consisted of infusions of oxaliplatin 40 mg/m(2) for 2 hours, followed by 5-fluorouracil 800 mg/m(2) for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. (©) RSNA, 2016.
First, an initial result is rapidly recovered using a coarse discretization mesh. Then, the reconstructed fluorophore area in the initial result is selected as a feasible region to guide the reconstruction using a fine discretization mesh. Simulation experiments on a digital mouse and small animal experiment in vivo are performed to validate the proposed strategy. It demonstrates that the presented strategy provides a good distribution of fluorophore with limited projections of fluorescence measurements. Hence, it is suitable for reconstruction of limited-projection FMT.
This study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed.
All ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p < 0.05). Arterial oxygen saturation and pre-delivery arterial oxygen tension during oxygen inhalation were significantly lower in group II (p < 0.05). Pulmonary arterial blood pressure (PABP) in both groups were high while ejection fractions (EF) were significantly lower in group II (p < 0.05). The incidence of pre-delivery heart failure in group II was substantially higher than in survivors (100 vs.14.3%, p < 0.05). Fetal complications were exceptionally high: preterm delivery (88%), small for gestational age (83%), fetal mortality (27%) and neonatal mortality (25%).
In west China,the perinatal outcome of pregnant women with ES is poor, especially when complicated with high pulmonary arterial hypertension (PAH). Pregnancy remains strongly contraindicated in ES. Effective contraception is essential, and the option of terminating pregnancy in the first trimester should be presented to pregnant women with ES.
Expectant management was carried out with early diagnosis of heterotopic cesarean scar pregnancy (HCSP), and selective fetal reduction of cesarean scar pregnancy (CSP) was performed by ultrasound-guided intrathoracic injection of potassium chloride (KCl) at 16 + 4 weeks of gestation due to aggravation of CSP. Preservation of the intrauterine pregnancy was successful and a healthy baby was delivered by cesarean section at 37 + 6 weeks of gestation.
Heterotopic cesarean scar pregnancy is an extremely rare form of heterotopic pregnancy. Patients should be appropriately counseled regarding the different treatment options available. An ultrasound-guided injection of potassium chloride may constitute a safe, minimally invasive and reliable way to terminate the heterotopic gestation and preserve the intrauterine pregnancy. Intensive management should be performed during the ongoing pregnancy and cesarean section.
Western blot analysis was adopted to measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to study cell proliferation, invasion and migration activity, and the apoptosis rate was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor tissues but high in lung adenocarcinoma tissues, and it was reversely proportional to the differentiation degree. Following transfection with SATB1-siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition, the proliferation, invasion and migration abilities of cells decreased significantly while the apoptosis rate increased significantly (P<0.01). In conclusion SATB1 is closely associated with the pathogenesis and development of lung adenocarcinoma.
5% (375/2422, 95% CI 14.0-16.9%). Between 2009 and 2014, the HIV prevalence of MSM remained high, with HIV-positivity rates of 15.0%, 15.1%, 16.3%, 13.9%, 17.8% and 14.0% each year respectively (χ(2) for trend = 0.008, P = 0.931). However, the majority (89.8%) of participants had had anal sex in the six months prior to the interview, and the percentage always using condoms during anal sex increased over the study period (36.7% in 2009, 39.8% in 2010, 36.9% in 2011, 46.2% in 2012, 65.1% in 2013, 49.0% in 2014; Chi-square for trend = 49.883, P < 0.001). HIV prevalence among MSM in Chengdu city has remained high. Given the continuing high levels of unprotected anal intercourse and high HIV prevalence among MSM, more effective intervention strategies are required to increase the coverage of MSM by risk-reduction interventions and to promote HIV testing among this population.
Maternal serum or placental CRH/UCN levels in the control rats were relatively consistent during 14-21DG. Serum CRH was reduced in the EE-treated rats compared with the control rats at 21DG. Regarding serum UCN, we observed a decrease at 17DG as well as an increase at 21DG in the EE-treated rats compared with the controls. Moreover, we observed a noticeable reduction of placental CRH/UCN expression at 17 or 19DG in the EE-treated rats compared with the control rats. The serum bile acids levels exhibited an inverse correlation with placental CRH/UCN expression. EE-induced cholestasis rats might serve as a good model to further investigate the pathological mechanism underlying CRH/UCN dysregulation in ICP.
The reprogramming procedure comprised reverse transcription‑polymerase chain reaction and immunofluorescence staining; furthermore, electrophysiological profiling demonstrated the characteristics of the induced‑resembled neurons. The present study obtained a novel type of human irNC from human melanoma, which secreted BDNF continuously, providing a model for neuron‑like cells. Thus, irNCs offer promise in investigating various neural diseases by using neural‑like cells derived directly from the patient of interest.
Inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups.
The inflammatory mediators (CRP, IL-6, TNF-α) were lower in the FTS group than in the traditional group (P < 0.05) on postoperative day (POD) 1, POD 4, and POD 6, and the immunological indicators (IgG, IgA, C3, C4) of the FTS group were superior to those of the traditional group (P < 0.05) on POD 4 and POD 6. The time to first aerofluxus, defecation, oral intake, and ambulation after surgery was shorter in the FTS group than in the traditional group (P < 0.05); however, the duration of postoperative hospitalization did not differ significantly between the two groups (P > 0.05). The total complications were significantly lower in the FTS group than in the traditional group (P < 0.05).
The FTS program can decrease inflammation, maintain immune homeostasis, and improve rehabilitation effects in colorectal surgery patients.
Scanning electron microscopy revealed the excellent biocompatibility of bio-derived bone with bone marrow-derived MSCs and OBs differentiated from MSCs. Western blot analysis revealed that many cytokines, which play key roles in HSPC regulation, were comprehensively secreted, while ELISA revealed that extracellular matrix molecules were also highly expressed. Hoechst 33342/propidium iodide ﬂuorescence staining proved that our system could be used to supply a long-term culture of HSPCs. Flow cytometric analysis and qPCR of p21 expression demonstrated that our system significantly promoted the self-renewal and ex vivo expansion of HSPCs. Colony-forming unit (CFU) and long-term culture-initiating cell (LTC-IC) assays confirmed that our system has the ability for both the expansion of CD34+ hematopoietic stem cells (HPCs) and the maintenance of a primitive cell subpopulation of HSCs. The severe-combined immunodeficient mouse repopulating cell assay revealed the promoting effects of our system on the expansion of long-term primitive transplantable HSCs. In conclusion, our system may be a more comprehensive and balanced system which not only promotes the self-renewal and ex vivo expansion of HSPCs, but also maintains primitive HPCs with superior phenotypic and functional attributes.
0-136.3 mm). Lipiodol retention pattern was assessed by CBCT at the endpoint of cTACE compared by fluoroscopy. Depending on the pattern of tumor covered by lipiodol three classes were defined: complete (more than 90 %, no peripheral defects), moderate (50-90 %, some with or without peripheral defects), and poor (less than 50 %). Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on follow-up contrast enhanced (CE) computed tomography (CT) or magnetic resonance imaging (MRI) obtained 4-6 weeks post-cTACE. Correlations between lipiodol retention patterns on CBCT and fluoroscopy as well as tumor response were assessed using multivariate logistic regression.
Of 51 hepatic tumors, 40 (78.4 %) had complete response (CR); 8 (15.7 %) had partial response (PR); 1 (2.0 %) had stable disease (SD); and 2 (3.9 %) had progressive disease (PD). The degree of lipiodol retention scored excellent, moderate, and poor, in fluoroscopic images vs CBCT images were 23 (45.1 %) vs 39 (76.5 %), 19 (37.3 %) vs 11 (21.6 %), and 9 (17.6 %) vs 1 (2.0 %), respectively. Lipiodol retention assessment with CBCT (Az = 0.75) is more accurate than fluoroscopy (Az = 0.54) in predicting target tumor response. Other than lipiodol retention pattern assessed with CBCT (p = 0.01), tumor size (p = 0.04) is an independent predictors of CR.
CBCT is more accurate than fluoroscopy in classification of lipiodol retention pattern in HCC tumors at the time of cTACE. CBCT could be used as a reliable intra precedural monitoring modality of cTACE.
In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment.
qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI. The mimic technique was used to further confirm the regulatory effect of miR-34a on the potential target genes. RESULTS The expression level of miR-34a decreased immediately after SCI and persisted for 21 days after SCI. The expression level of miR-34c began decreasing at day 1 after SCI and persisted until day 14. The expression level of miR-34b did not undergo significant change after SCI. The results of double immunofluorescence and in-situ hybridization suggested that miR-34a was highly expressed in spinal cord neurons. Based on our bioinformatics analysis, we postulated that miR-34a might participate in post-SCI cell apoptosis by regulating the target gene Notch1, and likely participated in the inflammatory response and glial scar formation by regulating the candidate genes Csf1r and PDGFRa, respectively. The expression levels of the candidate genes Csf1r and PDGFRa were consistent with Notch1 after SCI. The mimic technique further confirmed the regulatory effect of miR-34a on the aforementioned target genes. CONCLUSIONS We postulate that miR-34a and miR-34c might participate in multiple aspects of cytobiological activities following SCI. MiR-34a in particular may participate in cell apoptosis, inflammatory response, and glial scar formation by regulating the target gene Notch1 and candidate target genes Csf1r and PDGFRa respectively.
Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database. GBM cell lines (A172, SF188, U251) were treated in vitro with increasing doses of UNC2025 (50-400nM). Cell count and viability were determined by trypan blue exclusion. Cell cycle profiles and induction of apoptosis were assessed by flow cytometric analysis after BrdU or Po-Pro-1/propidium iodide staining, respectively. Polyploidy was detected by propidium iodide staining and metaphase spread. Cellular senescence was determined by β-galactosidase staining and senescence-associated secretory cytokine analysis.
Decreased overall survival significantly correlated with high levels of GAS6 expression in GBM, highlighting the importance of TAM kinase signaling in GBM tumorigenesis and/or therapy resistance and providing strong rationale for targeting these pathways in the clinic. All three GBM cell lines exhibited dose dependent reductions in cell number and colony formation (>90% at 200nM) after treatment with UNC2025. Cell cycle analysis demonstrated accumulation of cells in the G2/M phase and development of polyploidy. After extended exposure, 60-80% of cells underwent apoptosis. The majority of surviving cells (65-95%) were senescent and did not recover after drug removal. Thus, UNC2025 mediates anti-tumor activity in GBM by multiple mechanisms.
The findings described here provide further evidence of oncogenic roles for MERTK in GBM, demonstrate the importance of kinase activity for MERTK tumorigenicity and validate UNC2025, a novel MERTK inhibitor, as a potential therapeutic agent for treatment of GBM.
We present here an in-house front-end system design that generates the 1053 nm seed laser for the ps/ns beam directly from the 800 nm femtosecond laser, which enables the three beams to have intrinsic synchronization. The results show that a seed laser of 140 μJ energy and 1053 nm central wavelength with 34 nm spectral width (FWHM) is generated and the shot-to-shot timing jitter (peak-to-valley) between the fs and the ps beam is less than 1.32 ps.
After administered systemically in mice in vivo, all conjugates induced prolonged increase in pro-inflammatory cytokines and antigen-specific IgG levels in serum compared with free compounds. Results from molecular dynamics (MD) simulations further confirmed the conclusion and provided the details of interaction to explain the phenomenon of experiment. In conclusion, we discovered that TLR-7 could be activated via some conjugates of weak ligand and weak antigen, which could be safer adjuvant candidates for vaccines in the future.
On account of different polarities of endogenous metabolites, this method was established to overcome the boundedness of a single chromatographic approach. As a result, 18 potential metabolites for diagnosing BC were identified. A nonparametric Mann-Whitney U test, heat map, and the receiver operating characteristic (ROC) were exploited to analyze the data with the purpose of evaluating the predictive power of the 18 biomarkers. Significant differences (P<0.05) were disclosed in terms of the levels of the 18 potential biomarkers between BC patients and healthy controls (HC). Among the 18 biomarkers, three up-regulated metabolites, LysoPC (18:1), LysoPC (22:6) and MG (0:0/14:0/0:0) displayed the area under the curve (AUC) values of 0.920, 0.920 and 0.929, respectively, indicating the high accuracy of this method to predict BC. In this study, an integrated metabonomics analysis in human saliva for identifying potential biomarkers to diagnose and stage BC was successfully eastablished, which was non-invasive, reliable, low-cost, and simple. The HILIC was demonstrated to be essential for a comprehensive saliva metabonomics profiling as well as RPLC separation. This saliva metabonomics technique may provide new insight into the discovery and identification of diagnostic biomarkers for BC.
11). Morphological and 26S rDNA sequence analyses indicated that strain S4 belonged to Eupenicillium, while strain S7 was an unclassified Trichocomaceae. Further investigation showed that both strains were endowed with the ability to resist Al; strain S4 accumulated such a substantial amount of Al that its growth was limited to a larger extent than strain S7. The lower amounts of Al adsorbed in the mycelium and the much larger amounts of Al retained in the medium, in addition to the color change of the culture solution, implied that these two strains may resist Al by preventing Al from entering the cell and by chelating Al by secreting unique metabolites outside of the cell.
Here, we performed comparative microRNA profiling between in vivo-fertilized (IVO group) and in vitro-fertilized (IVF group) mouse embryos at Embryonic Day 3.5 (E3.5) and E7.5. Our dynamic analyses showed that the dysregulated microRNAs were mainly associated with the regulation of genes involved in carcinogenesis, genetic information processing, glucose metabolism, cytoskeleton organization, and neurogenesis. Further analysis showed that miR-199a-5p was consistently downregulated in IVF embryos compared with their IVO counterparts. Through gain- and loss-of-function experiments, we demonstrated that IVF-induced downregulation of miR-199a-5p results in a higher glycolytic rate and lower developmental potential of IVF blastocysts, including cell lineage misallocation and lower fetal survival post implantation. Therefore, preventing downregulation of miR-199a-5p may become an effective strategy for improving the development of IVF peri-implantation embryos in the future.
The BioCreative Interactive task (IAT) is a track designed for exploring user-system interactions, promoting development of useful TM tools, and providing a communication channel between the biocuration and the TM communities. In BioCreative V, the IAT track followed a format similar to previous interactive tracks, where the utility and usability of TM tools, as well as the generation of use cases, have been the focal points. The proposed curation tasks are user-centric and formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators participated. Two levels of user participation were offered to broaden curator involvement and obtain more feedback on usability aspects. The full level participation involved training on the system, curation of a set of documents with and without TM assistance, tracking of time-on-task, and completion of a user survey. The partial level participation was designed to focus on usability aspects of the interface and not the performance per se In this case, biocurators navigated the system by performing pre-designed tasks and then were asked whether they were able to achieve the task and the level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested.Database URL: http://www.biocreative.org.
We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.
UNC2025 potently inhibited pro-survival signaling, induced apoptosis and reduced proliferation and colony formation in MerTK-expressing ALL and AML cell lines and patient samples. Approximately 30% of primary leukemia patient samples (78 of 261 total) were sensitive to UNC2025. Sensitive samples were most prevalent in the AML, T-ALL, and minimally differentiated (M0) AML subsets. UNC2025 inhibited MerTK in bone marrow leukemia cells and had significant therapeutic effects in xenograft models, with dose-dependent decreases in tumor burden and consistent two-fold increases in median survival, irrespective of starting disease burden. In a patient-derived AML xenograft model, treatment with UNC2025 induced disease regression. Additionally, UNC2025 increased sensitivity to methotrexate in vivo, suggesting that addition of MerTK-targeted therapy to current cytotoxic regimens may be particularly effective and/or allow for chemotherapy dose reduction.
The broad spectrum activity mediated by UNC2025 in leukemia patient samples and xenograft models, alone or in combination with cytotoxic chemotherapy, support continued development of MerTK inhibitors for treatment of leukemia.
Here, our study demonstrates that paeoniflorin can induce the production of regulatory dendritic cells from human peripheral blood monocyte-derived immature dendritic cells in the absence or presence of lipopolysaccharide (LPS) but not from mature dendritic cells, thereby demonstrating the potential of paeoniflorin as a specific immunosuppressive drug with fewer complications and side effects. These regulatory dendritic cells treated with paeoniflorin exhibited high CD11b/c and low CD80, CD86 and CD40 expression levels as well as enhanced abilities to capture antigen and promote the proliferation of CD4(+)CD25(+) T cells and reduced abilities to migrate and promote the proliferation of CD4(+) T cells, which is associated with the upregulation of endogenous transforming growth factor (TGF)-β-mediated indoleamine 2,3-dioxygenase (IDO) expression. Collectively, paeoniflorin could program immature dendritic cells (imDCs) and imDCs stimulated with LPS toward a regulatory DC fate by upregulating the endogenous TGF-β-mediated IDO expression level, thereby demonstrating its potential as a specific immunosuppressive drug.
Also, effects of the two lake conditions on photosynthetic efficiency of phytoplankton are still poorly understood. This study will evaluate the effect of these two conditions on photosynthetic efficiency and APA. Sediments used in the indoor experiments were collected from Zhushan Bay in Lake Taihu. Turbulence was generated by rotors to simulate the strong wind-induced disturbance in Lake Taihu. Results of the experiments showed that TN and TP in the stable and episodically turbulent conditions were not significantly different, with TN ranging from 1.34 to 1.90 mg/L and TP from 0.08 to 0.18 mg/L. Whereas, the soluble reactive phosphorus in the episodically turbulent condition was significantly higher than in the stable condition. Episodic turbulence could enhance P cycling by resuspending sediment-associated P, which alleviated algal P limitation. In stable conditions, P deficiency induced the production of high APA, which enhanced the availability of P. Although episodic turbulence could also cause increased algal biomass, photosynthetic efficiency of the algae was also affected not only by the nutrients but also by many other factors, especially light availability. Our results suggest that episodic turbulence is an important driver of biogeochemical cycling in large shallow hypertrophic lake ecosystem.
Here, we aimed to enhance the biallelic mutation rate with reduced mosaicism by optimization of the concentration and injection time of the Cas9/sgRNA mixture in porcine parthenotes. The results showed that the efficient biallelic mutation (93%) and low mosaicism (33%) could be achieved in porcine parthenotes by cytoplasmic injection of Cas9 mRNA/sgRNA (125/12.5 ng/μl) after 8 h of parthenogenetical activation. Thus, our study provides an effective strategy for increasing the biallelic mutation rate and population homogeneity of genetically modified parthenotes, which will strengthen the role of parthenotes in uncovering early embryonic development and assessing the mutation efficiency due to the simplicity and adaptability of CRISPR/Cas9.
In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5months. Afterward, mice were treated with metformin (50mg/kg or 200mg/kg) for 15days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dose-dependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis.
We analyzed the digit ratio and foreskin condition in 176 cases (range 0-6years). The boys were divided into four groups according to their ages: group 1, neonates (below 28days, n=13); group 2, infants (1-12months, n=45); group 3, toddlers (1-2years old, n=42); group 4, preschool children (3-6years old, n=76). We measured the lengths of the second and fourth digits of the left and right hands. The foreskin status was classified into 4 types. Type I (phimosis), type II (partial phimosis), type III (adhesion of prepuce), type IV (normal).
The phimosis rate was 92.3%, 82.2%, 45.2%, and 38.7% in group 1 to group 4. In contrast, the proportion of normal foreskin increased from 0% in neonates to 13.2% in preschool children. The percentage of higher level of foreskin development shows a downward trend with the increase of digits ratio, and as the age grows, the percentage of normal foreskin cases also increases.
These results suggest that a higher R2D:4D (right hand 2D:4D) is a risk factor for phimosis in the early human development. Age is also a significant influence factor of foreskin conditions. Additional research is required to identify pathophysiologic mechanisms and to determine clinical significance.
PSA transcripts were detected in 57% of abiraterone acetate-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS.
PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 1-9. ©2016 AACR.
Herein, we investigate the effects of traditional Chinese DCHJ on DCregs differentiation and a mouse model of skin transplantation. The current study demonstrates that DCHJ can induce dendritic cells to differentiate into DCregs, which are represented by high CD11b and low CD86 and HLA-DR expression as well as the secretion of IL-10 and TGF-β. In addition, DCHJ inhibited DC migration and T cell proliferation, which correlated with increased IDO expression. Furthermore, DCHJ significantly prolonged skin graft survival time in a mouse model of skin transplantation without any liver or kidney toxicity. The traditional Chinese formula DCHJ has the potential to be a potent immunosuppressive agent with high efficiency and nontoxicity.
05). The right coronary artery was the most involved (70.6%) in CAE compared with left circumflex (52.9%) and left anterior descending (41.2%). Coronary artery aneurysm coexisted with coronary artery disease (CAD) more frequently than CAE (P = .002), and the modified Gensini score of CAA was also higher than that of CAE (P < .001). The average maximum diameter was smaller, and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was lower in CAA than CAE in all 3 coronary arteries (P < .001). Multivariate analysis showed that hyperlipidemia (P = .02), smoking (P = .04), and family history of CAD (P = .02) were the independent variables most strongly associated with CAA, but not CAE. This study suggests that there are significant differences in coronary angiographic characteristics and CV risk factors between CAA and CAE.
A total of 22 children with iliac bone destruction were enrolled in this retrospective analysis from two children's hospitals during July 2007 to April 2015. Clinical features, imaging, and histopathological findings were analysed. The mode of iliac bone destruction, lesion structure, and the relationship between the range of soft tissue mass and cortical destruction were determined based on imaging data. The data were analysed using descriptive methods. Of the iliac bone destruction cases, eight cases were neuroblastoma iliac bone metastasis, seven cases were bone eosinophilic granuloma, two cases were Ewing's sarcoma, two cases were osteomyelitis, one case was bone cyst, one case was bone fibrous dysplasia, and one case was non-Hodgkin's lymphoma. Iliac bone destruction varies widely in children. Metastatic neuroblastoma and eosinophilic granuloma are the most commonly involved childhood tumours.
GRHL3 expression status was evaluated by immunohistochemical analysis. Survival analysis using the Kaplan-Meier method and multivariate analysis were conducted to adjust the effect of GRHL3 expression as a potential independent prognostic factor. In the enrolled 967 patients, GRHL3 expression was detected in 398 (41.16 %) patients under immunohistochemical analysis. The 5-year survival rate in patients with GRHL3 expression was significantly lower than that in those without GRHL3 expression (37.8 vs 52.8 %, P < 0.001). Multivariate analysis identified GRHL3 expression as an independent predictor of poor survival. The sensitivity and specificity of GRHL3 for the diagnosis of germinal center B cell (GCB)/non-GCB was 89.2 % (182/204) and 82.1 % (174/212), respectively. GRHL3 expression may be useful as a prognostic factor and for the diagnosis GCB/non-GCB of diffuse large B cell lymphoma.
S‑SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills‑and valleys'' growth pattern; R‑SMCs displayed increased proliferation rates, growing as mono‑ or multi‑layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet‑derived growth factor (PDGF)‑BB with or without the gap junction blocker 18α‑glycyrrhetinic acid. Stent‑induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R‑ and S‑SMCs. Cx40 was the most abundant Cx in S‑SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R‑SMCs. Notably, PDGF‑BB converted S‑SMCs to R‑SMCs, with increased Cx43 expression, while 18α‑glycyrrhetinic acid inhibited the PDGF‑BB‑induced phenotypic alterations in S‑SMCs. Additionally, restenosis was confirmed in pigs 1‑month subsequent to stent placement. R‑SMCs were the major cell population isolated from stent‑induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention.
After four rounds of bio-panning, seven unique clones were positive by phage ELISA. Among them, C27 and C22, which demonstrated the highest affinity to ZnT8, were expressed in Escherichia coli Top10F' and then purified by affinity chromatography. C27 and C22 specifically bound ZnT8 N/C fusion protein and ZnT8 C terminal dimer with one Arg325Trp mutation. The specificity to human islet cells of these scFvs were further confirmed by immunohistochemistry. In conclusion, we have successfully constructed a T1D phage display antibody library and identified two ZnT8-specific scFv clones, C27 and C22. These ZnT8-specific scFvs are potential agents in immunodiagnostic and immunotherapy of T1D.
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.
In total, 13,205 differential expressed genes were detected, of which 6111 genes were significantly down-regulated, while 7094 genes were significantly up-regulated in the young inflorescences of APL01 compared with PL01. The expression levels of a vast number of genes involved in protein biosynthesis were altered in response to the early flowering and apetalous character. Based on the putative rapeseed flowering genes, an early flowering network, mainly comprised of vernalization and photoperiod pathways, was built. Additionally, 36 putative upstream genes possibly governing the apetalous character of line APL01 were identified, and six genes potentially regulating petal origination were obtained by combining with three petal-related quantitative trait loci. These findings will facilitate understanding of the molecular mechanisms underlying floral transition and petal initiation in B. napus.
The RsICE1 gene was expressed constitutively with higher transcriptional levels in the roots and stems of radish seedlings. The NaCl, cold, and ABA treatments could significantly upregulate RsICE1 expression levels, but dehydration stress had a weak effect on its expression. Ectopic expression of the RsICE1 gene in rice conferred enhanced tolerance to low-temperature stress grounded on a higher survival rate, higher accumulation of soluble sugars and free proline content, a decline in electrolyte leakage and MDA levels, and higher chlorophyll levels relative to control plants. OsDREBL and OsTPP1, downstream cold-regulated genes, were remarkably upregulated at transcription levels in rice overexpressing RsICE1 under low-temperature stress, which indicated that RsICE1 was involved in CBF/DREB1 cold-regulated signal networks. Overall, the above data showed that RsICE1 played an active role in improving rice cold tolerance, most likely resulting from the upregulation of OsDREBL and OsTPP1 expression levels by interacting with the RsICE1 gene under low-temperature stress.
6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years.
Experimental results showed a correlative relationship among those operation states (N pulses/Nth-order HML/"giant pulses" of N bound solitons) at different pump power levels. The birefringence induced by the erbium-doped fiber inside the laser cavity played a vital role in the transitions of those operation states.
Most of the related anatomical structures could be clearly observed under the endoscope. The shortest distances from the highest point of arcuate eminence to the foramen spinosum, the greater superficial petrosal nerve hiatus, the intersection of the greater superficial petrosal nerve and mandibular nerve, and the outside edge of the trigeminal impression are 22.90 ± 2.34, 14.05 ± 2.09, 24.94 ± 1.98, 23.49 ± 2.38 mm. The area of routine milled Kawase rhombus is 3.04 ± 0.47 cm, which would increase 0.66 cm on average after the maximum drilling of the petrous apex.
The intradural subtemporal keyhole Kawase approach can provide an ideal exposure to the petroclival and ventrolateral brainstem regions via the endoscope with less damaging of the normal structures. It can be used to treat the lesions located in those areas through the natural gap combined with the drilling of petrous apex bone.
coli BL 21 (DE3) and IL-23p19 protein expression was induced by IPTG and identified with SDS-PAGE analysis and Western blotting. After purified by Ni(+) affinity column chromatography, the IL-23p19 protein was used as the antigen to immunize New Zealand rabbit to prepare the antiserum. The polyclonal antibody against the mouse IL-23p19 was isolated from antiserum by affinity chromatography. Antibody titer was detected by ELISA. Antibody specificity was evaluated by Western blotting.
The pET-16b-IL-23p19 recombinant plasmid was successfully constructed and the IL-23p19 protein was effectively expressed in E. coli BL 21 (DE3). The antibody was successfully prepared by immunizing New Zealand rabbit with the IL-23p19 protein four times. ELISA showed that the titer of the anti-mouse IL-23p19 polyclonal antibody was about 1:256,000. Western blotting confirmed that anti-mouse IL-23p19 polyclonal antibody could specifically recognize the IL-23p19 protein.
We have successfully prepared the anti-IL-23p19 polyclonal antibody with the high titer and specificity.
Hepatic arterial embolization episodes within 30days from biopsy were identified via radiology PACS. Electronic medical record review was performed for indication of embolization and postembolization clinical course.
The incidence of postbiopsy bleeding requiring embolization was 0.5% (12/2335 biopsies). In those with bleeding, 1/12 (8%) had no hepatic arterial findings at angiography. Angiographic hepatic arterial findings resolved after embolization in 11/11 patients (100% technical success). Bleeding ceased after embolization in 10/12 patients (83% clinical success). Complications were seen in 2/12 (17%) patients: cholecystitis and hepatic infarct, respectively. Delayed presentation of bleeding (defined as >24h postbiopsy) occurred in 5/12 (42%) patients; the longest latency was 12days.
The overall incidence of bleeding requiring embolization in our population was 0.5%. This complication rate compares favorably to the 0-4.2% (median: 0.29%) rate quoted in the available, heterogeneous, literature on this topic. Delayed presentation occurred in almost half of patients. Arterial embolization carries excellent technical and clinical success rates.
Meanwhile, luciferase reporter assay proved that the PKM2 is the target of miR-122, and we reported that the glucose metabolism is significantly up-regulated in Huh7/R cells. Importantly, overexpression of miR-122 in Huh7/R cells reversed the doxorubicin-resistance through the inhibition of PKM2, inducing the apoptosis in doxorubicin-resistant cancer cells. Thus, this study revealed that the dysregulated glucose metabolism contributes to doxorubicin resistance, and the inhibition of glycolysis induced by miR-122 might be a promising therapeutic strategy to overcome doxorubicin resistance in hepatocellular carcinoma.
This finding suggests that there is an interaction between AR signaling activity and docetaxel sensitivity. Here we demonstrate that the prostate cancer cell lines LNCaP and LAPC4 display markedly different sensitivity to docetaxel with AR activation, and RNA-seq analysis of these cell lines identified KDM5D (lysine-specific demethylase 5D) encoded on the Y chromosome as a potential mediator of this sensitivity. Knocking down KDM5D expression in LNCaP leads to docetaxel resistance in the presence of dihydrotestosterone. KDM5D physically interacts with AR in the nucleus, and regulates its transcriptional activity by demethylating H3K4me3 active transcriptional marks. Attenuating KDM5D expression dysregulates AR signaling, resulting in docetaxel insensitivity. KDM5D deletion was also observed in the LNCaP-derived CRPC cell line 104R2, which displayed docetaxel insensitivity with AR activation, unlike parental LNCaP. Dataset analysis from the Oncomine database revealed significantly decreased KDM5D expression in CRPC and poorer prognosis with low KDM5D expression. Taking these data together, this work indicates that KDM5D modulates the AR axis and that this is associated with altered docetaxel sensitivity.
Here we aimed to evaluate whether SSEP can consistently and objectively assess transmission of deep sensory pathways, and to examine the effects of umbilical cord mesenchymal stem cell (UCMSC) transplantation on SSEP and NPP as assessed by the pain rating index (PRI) in a patient with a 2-year history of complete cervical SCI. We demonstrate that SSEP can directly reflect physiological function of myelinated large fibers in deep sensory pathway transmission (NPP is also transmitted by the same pathway). One year after UCMSC transplantation, the SSEP parameter, PRI, and clinical presentations of NPP significantly improved.
Spinal cord, neuropathic pain, somatosensory evoked potential, umbilical cord mesenchymal stem cells.
Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NFκB pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NFκB pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9's potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NFκB pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NFκB pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies.
Content of the study would include social demographic characteristics, number of sexual partners, sexual behaviors, and the symptoms assessment on depression and anxiety.χ(2)-test,t-test and non-conditional Multiple logistic Regression methods were used to examine the risky sexual behaviors with multiple sexual partners among the participants engaged in this project.
Mean age of the 501 participants was (30.24±7.70) years old. In the past 6 months, 17.4% (87/501) of them had engaged in unprotected sexual behavior with two or more sexual partners. Factors at risk would include: being married (OR=1.93, 95%CI: 0.77-4.84), divorced or widowed (OR=3.94, 95%CI: 1.66-9.36), having primary male sexual partners (OR=5.04, 95%CI: 1.08-23.54) and casual or commercial male sexual partners (OR=2.54, 95%CI: 1.34-4.80) in the past 6 months, drinking alcohol (OR=3.00, 95%CI: 1.37-6.62) or Rush (alkyl nitrite) (OR=3.53, 95%CI: 1.72-7.23) during sexual acts, sharing their HIV-infection status to their partly primary male sexual partners (OR=1.84, 95%CI:0.78-4.33) or not (OR=2.68, 95% CI: 1.25-5.73), and having high sexual sensation seeking scores (OR=1.09, 95%CI: 1.03-1.15).
Unprotected sexual behaviors with multiple sexual partners among HIV-positive MSM played an important role in expediting the HIV transmission. Development of intervention programs to minimize the risk sexual behaviors and setting up efficient medical and biological measures in controlling the HIV transmission were in urgent need.
Patients received a screw-retained splinted fixed permanent restoration in one edentulous region 6-8 weeks after surgery. Follow-up took place at 6 and 12 months after loading. Marginal bone level alteration, implant survival and clinical findings were assessed using descriptive statistics. The data were analysed on a patient level, implying that the mean overall implants by patient was used as the statistical unit. The data from the three centres were pooled in the statistical analyses.
A total of 107 implants were inserted in 45 patients. Twelve months after loading, the implant survival rate was 100%, with a mean (± std) marginal bone gain of 0.08 ± 0.411 mm and healthy soft tissue status.
Early loading of splinted OsseoSpeed(™) TX implants was an effective and safe treatment for partial edentulism of the posterior mandible. CLINICAL TRIAL REGISTRATION NUMBER ON CLINICALTRIALS.GOV: NCT01346683.
Furthermore, it overcomes the structural instability problem of Sr2Be2B2O7, which is confirmed by the obtainment of large single crystals and phonon dispersion calculations. These attributes make it very attractive for next-generation deep-UV NLO materials. The substitution of Be for Al and Li in beryllium borates provides a new opportunity to design beryllium-free deep-UV NLO materials with good performance.
83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer.
The as-prepared IrFe bimetallic nanomaterials were served as catalysts for the selective hydrogenation of 3-nitrostyrene to 3-aminostyrene, and it is found that the catalytic performance was related to the morphology and composition of these nanomaterials. Ir1Fe4 was subsequently identified to be a highly active and exceedingly selective catalyst with good stability and recyclability for the hydrogenation of 3-nitrostyrene, underscoring a remarkable "synergistic effect" of the two metals appearing as the form of Ir nanoparticles loaded on Fe2O3 flakes. For Ir nanoparticles, they act as an active species for the hydrogenation; for Fe2O3 flakes, they favor the preferential adsorption of nitro groups, which account for the better chemoselectivity to objective product.
However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications.
We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.
napus, however, no studies have focused on the six agronomic traits (seed number per silique, silique length, silique breadth, silique thickness, seed density and silique volume) simultaneously, and the genetic determinism of such complex traits have not been fully elucidated.
In this study, the six silique traits were evaluated using 348 lines of a doubled haploid population, the KN population. The results showed that 2, 4, 1, 1 and 2 QTLs explaining > 10 % of phenotypic variation were obtained for silique length, silique breadth, silique thickness, seed number per silique and silique volume, respectively. Notably, three major effect QTLs (cqSB-C6-1, cqSB-C6-2 and cqSV-C6-3) were identified in at least three environments, and 17 unique QTLs controlling at least two traits were obtained. A high-density consensus map containing 1225 markers was constructed for QTL comparison by combining the KN map with other five published maps. The comparative results revealed that 14, 13 and 11 QTLs for silique breadth, silique thickness and silique volume might be the potential new QTLs because few QTLs for these traits were reported in B. napus. In addition, potential new QTLs for silique length (11), seed number per silique (6) and seed density (5) were also identified. Twenty-five candidate genes underlying 27 QTLs for silique related traits were obtained.
This study constructed QTL analysis in B. napus, and obtained 60 consensus QTLs for six silique related traits. The potential new QTLs will enhance our understanding of the genetic control of silique traits, and the stable QTLs provided the targets for improving seed yield in future. These findings provided comprehensive insights into the genetic network affecting silique traits at QTL level in B. napus.
Here, we describe MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells. In murine orthotopic xenograft models, once-daily oral therapy prolonged survival 2- to 3-fold over that of vehicle-treated controls. Additionally, MRX-2843 retained activity against quizartinib-resistant FLT3-ITD-mutant proteins with clinically relevant alterations at the D835 or F691 loci and prolonged survival in xenograft models of quizartinib-resistant AML. Together, these observations validate MRX-2843 as a translational agent and support its clinical development for the treatment of AML.
Moreover, E-rGO showed a high electric conductivity close to that of H-rGO after ultrasonic treatment for 12 h, which indicated that ED had the desired reducibility. The present approach could help to broaden the application field of graphene nanosheets and provide a new opportunity for developing high performance graphene/polymer-matrix composites.
TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.
One hundred and three DDH patients treated in The Soochow University Children's Hospital between 2006 and 2012 were assessed; patients with known causes of neuron muscular and abnormal hip joint origin were excluded. Fifty-four suitable patients, demonstrating 71 dysplasia hips with complete clinical record and adequate X-ray films, were enrolled in this study. Patients were divided into group A (conservative interventions failed, followed by salvage peri-acetabular osteotomy) and group B (conservative treatment only); a total of 16 quantitative parameters were measured on each pelvic X-ray film.
Among 71 hip joints measured, 29 hips of group A underwent salvage peri-acetabular osteotomy (40.8 %,) showed higher X2, Y, h, and Smith c/b (Vh) (p < 0.05). The age, c, HT, b, A2 in the group A salvage operation were statistically significantly different compared to group B patients (without salvage operations) (p < 0.05).
Pre-operative pelvic X-ray film assessment of acetabulum lateralization markers (X2, c, HT, c/b ratio) and the superior migration measurements (Y, h, h/b ratio) are potentially valuable radiographic indicators for determining which DDH patients will require peri-acetabular osteotomy.
The expression of SLCO2B1 was examined in prostatectomy samples, and the impact of SLCO2B1 expression level on DHEAS (dehydroepiandrosterone sulfate) uptake was evaluated in cell lines.
The association between exonic SNP rs12422149 and TTP in patients treated with ADT was confirmed in univariable (P = .019) and multivariable analyses (adjusted hazard ratio, 1.31; 95% CI, 1.00 to 1.72 for GG v AA/AG; P = .049). Because OS had not been previously evaluated, we examined the association in the combined initial and validation cohorts (N = 1,094). The intronic SNP rs1077858 was associated with OS in both univariable (P = .009; Bonferroni's method adjusted P = .027) and multivariable analyses (adjusted hazard ratio, 1.35; 95% CI, 1.07 to 1.71 for GG v AA/AG; P = .012). SLCO2B1 expression in normal prostate tissue and in 22RV1 cells carrying the major allele of SNP rs1077858 was significantly lower than in cells carrying the risk allele. We show in vitro that SLCO2B1 expression levels correlated with DHEAS uptake by PC cells.
The association of SNP rs1077858 with OS may be a result of differential SLCO2B1 expression and the consequent increased uptake of DHEAS and subsequent resistance to ADT, which, in turn, may contribute to decreased OS.
We examined the effects of a novel adenine type of TLR7 agonists on both innate and adaptive immune activation in vitro and in vivo. We established the local and distant tumor‑bearing mice derived from murine mammary carcinoma cell line (4T1) to model metastatic disease. Our data demonstrated that SZU101 was able to stimulate innate immune cells to release cytokines at the very high level compared with LPS at the same or lower concentration. Locally intratumoral SZU101 injection can elicit a systemic antitumor effect on murine breast tumor model. SZU101 affected the frequency of intratumoral immune cell infiltration, including the percentage of CD4+ and CD8+ increase, and the ratio of Tregs decrease. Our data reveal that the antitumor effect of SZU101 is associated with multiple mechanisms, inducing tumor‑specific immune response, activation of innate immune cells and modulation of the tumor microenvironment.
Over-expression of miR-125a increased the chemo-resistance to gemcitabine in SW1990 cells, while down-regulation of miR-125a in SW1990GZ cells increased chemo-sensitivity to gemcitabine. By using bioinformatics analysis tool (Targetscan), the 3' untranslated region (3'UTR) of A20 gene was found to be a target of miR-125a. Luciferase reporter assay further confirmed that A20 3'UTR is a direct target of miR-125a. Over-expression of A20 in SW1990 cells increased chemo-sensitivity to gemcitabine, while knockdown of A20 in SW1990 cells promoted the chemo-resistance to gemcitabine. Finally, the expression level of miR-125a in pancreatic cancer tissues from chemo-sensitive patients was significantly lower than that from chemo-resistant patients, and was inversely correlated with the A20 mRNA levels. In conclusion, our results suggest that miR-125a promotes chemo-resistance to gemcitabine in pancreatic cells through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.
In this work, we report a sub-nano Rh/TiO2 catalyst that can completely convert CO at 223 K. This catalyst exhibits at least three orders of magnitude higher turnover frequency (TOF) than the best Rh-based catalysts and comparable to the well-known Au/TiO2 for CO oxidation. The specific size range of 0.4-0.8 nm Rh clusters is critical to the facile activation of O2 over the Rh-TiO2 interface in a form of Rh-O-O-Ti (superoxide). This superoxide is ready to react with the CO adsorbed on TiO2 sites at cryogenic temperatures.
This plasmonic structure paves the way to nanoscale UV-optical lasers and sensors.
Totally, 18 and 208 QTLs for SY and SYRTs were observed, respectively, and then these QTLs were integrated into 144 consensus QTLs using a meta-analysis. Three major QTLs for SY were observed, including cqSY-C6-2 and cqSY-C6-3 that were expressed stably in winter cultivation area for 3 years and cqSY-A2-2 only expressed in spring rapeseed area. Trait-by-trait meta-analysis revealed that the 144 consensus QTLs were integrated into 72 pleiotropic unique QTLs. Among them, all the unique QTLs affected SY, except for uq.A6-1, including uq.A2-3, uq.C1-2, uq.C1-3, uq.C6-1, uq.C6-5, and uq.C6-6 could also affect more than two SYRTs. According to the constructed high-density consensus map and QTL comparison from literatures, 36 QTLs from five populations were co-localized with QTLs identified in this study. In addition, 13 orthologous genes were observed, including five each gene for SY and thousand seed weight, and one gene each for biomass yield, branch height, and plant height. The genomic information of these QTLs will be valuable in hybrid cultivar breeding and in analyzing QTL expression in different environments.
Using a new bioorthogonal ligation method (TQ ligation), we reveal that the direct cellular target of KA is heat shock protein 90 (HSP90). Further studies demonstrate that KA covalently binds to a previously uncharacterized cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its cochaperone CDC37, which leads to inhibition of RIP3-dependent necroptosis and promotion of apoptosis in multiple cancer cell lines. Collectively, our findings demonstrate that KA is an effective HSP90 inhibitor that has potential anti-necroptosis and anti-inflammation applications.
Results implied that the main composes of EPS, including polysaccharide (PS) and protein (PN), decreased from 5.92±0.13 and 23.55±0.76 mg/g SS to 4.11±0.09 and 9.55±0.68 mg/g SS after the addition of different doses of Zn (II). 3D-EEM showed that the intensities of PN-like substances and humic-like substances were obviously decreased during the sorption process. According to synchronous fluorescence spectra, the quenching mechanism between PN-like substances and Zn (II) was mainly caused by a static quenching process. Additionally, 2D-COS indicated that PN-like substances were more susceptible to Zn (II) binding than humic-like substances. It was also found that the main functional groups for complexation of Zn (II) and EPS were OH groups, N-H groups and C=O stretching vibration. The findings of this study are significant to reveal the fate of heavy metal during its sorption process onto aerobic granular sludge through EPS binding, and provide useful information on the interaction between EPS and heavy metal.
The project has evolved from its original remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research.
In this study, we found that Salvianolic acid B (Sal B) treatment significantly inhibited liver fibrosis in CCl4-treated rats, HSC-T6 cells and rat primary HSCs, resulting in the suppression of type I collagen and alpha-smooth muscle actin. Also, Sal B suppressed HSC activation and cell proliferation in vitro. Interestingly, Sal B treatment induced the inactivation of Wnt/β-catenin pathway, with an increase in P-β-catenin and Wnt inhibitory factor 1 (WIF1). We demonstrated that the anti-fibrotic effects caused by Sal B were, at least in part, via WIF1. Moreover, our study revealed that miR-17-5p was reduced in vivo and in vitro after Sal B treatment. As confirmed by luciferase activity assays, WIF1 was a direct target of miR-17-5p. Notably, the suppression of HSCs induced by Sal B was almost inhibited by miR-17-5p mimics. Collectively, we demonstrated that miR-17-5p activates Wnt/β-catenin pathway to result in HSC activation through inhibiting WIF1 expression.
Such work has shown the importance of adaptation in calibrating face perception based on prior visual exposure. In the present study, we showed for the first time that emotion-laden sounds, like laughter, adapt the visual perception of emotional faces, that is, subjects more frequently perceived faces as sad after listening to a happy sound. Furthermore, via electroencephalography recordings and event-related potential analysis, we showed that there was a neural correlate underlying the perceptual bias: There was an attenuated response occurring at ∼ 400 ms to happy test faces and a quickened response to sad test faces, after exposure to a happy sound. Our results provide the first direct evidence for a behavioral cross-modal adaptation effect on the perception of facial emotion, and its neural correlate.
2 and 6704.2, showed significantly differential distributions at the p < 0.05 (t-test) level between the cancerous and the noncancerous regions of the tissue. Among these 17 species, the distributions of apolipoprotein C-I, S100-A6, and S100-A8 were verified by immunohistological staining. In summary, this study resulted in the imaging of the largest group of proteins in prostate cancer tissues by MALDI-MS reported thus far, and is the first to show a correlation between S100 proteins and prostate cancer in a MS imaging study. The successful imaging of the three proteins only found in the cancerous tissues, as well as those showing differential expressions demonstrated the potential of MCAEF-MALDI/MS for the in situ detection of potential cancer biomarkers. Copyright © 2015 John Wiley & Sons, Ltd.
To solve the nonconvex L1-2 minimization problem, an iterative method based on the difference of convex algorithm (DCA) is presented. In each DCA iteration, the update of solution involves an L1 minimization subproblem, which is solved by the alternating direction method of multipliers with an adaptive penalty. We investigated the performance of the proposed method with both simulated data and in vivo experimental data. The results demonstrate that the DCA for L1-2 minimization outperforms the representative algorithms for L1, L2, L1/2, and L0 when the system matrix is highly coherent.
The electromagnetic properties of ordered SnO2 foams were also investigated by a network analyzer. The results reveal that the microwave absorption properties of SnO2 foams were dependent on their configuration. The microwave absorption capabilities of SnO2 foams were increased by increasing the size of pores in the foam configuration. Furthermore, the electromagnetic wave absorption was also correlated with the pore contents in SnO2 foams. The large and high amounts pores can bring about more interfacial polarization and corresponding relaxation. Thus, the perfect ordered honeycomb-like SnO2 foams obtained in the existence of large amounts of 322 nm polystyrene spheres showed the outstanding electromagnetic wave absorption properties. The minimal reflection loss (RL) is -37.6 dB at 17.1 GHz, and RL less than -10 dB reaches 5.6 GHz (12.4-18.0 GHz) with thin thickness of 2.0 mm. The bandwidth (<-10 dB, 90% microwave dissipation) can be monitored in the frequency regime of 4.0-18.0 GHz with absorber thickness of 2.0-5.0 mm. The results indicate that these ordered honeycomb SnO2 foams show the superiorities of wide-band, high-efficiency absorption, multiple reflection and scatting, high antioxidation, lightweight, and thin thickness.
To optimize the selection, a minimum connected dominating set (CDS) strategy is adopted. However, existing approaches focus on minimizing the size of the CDS, neglecting an important factor: the weight of links. In this paper, we propose a distributed maximizing the probability of information diffusion (DMPID) algorithm in the cyber-physical integrated network. Unlike previous approaches that only consider the size of CDS selection, DMPID also considers the information spread probability that depends on the weight of links. To weaken the effects of excessively-weighted links, we also present an optimization strategy that can properly balance the two factors. The results of extensive simulation show that DMPID can nearly double the information diffusion probability, while keeping a reasonable size of selection with low overhead in different distributed networks.
The data were collected by computer assisted survey, including social demography, the coverage of HIV related follow-up intervention and ART, related knowledge level, sexual behaviors in the last 6 months, as well as notification to sexual partners and family. We analyzed the influence factors for initiating ART by Multiple Unconditioned Logistic Regression.
Among 501 HIV-positive MSM, the ratio of CD4 counting and HIV viral load testing were 90.8% (455) and 19.4% (97), respectively. The percentage of the latest CD4 counting not more than 350 per µl was 33.0% (150/455). The coverage of initiated ART among the participants who met the qualification was 56.0% (84/150). The multivariable Logistic regression analysis showed that the possibility of not on ART among participants who were migrants increased to 5.21(2.33-11.66) times of the local residents and the possibility among participants who were diagnosed STD in the last year increased to 2.70(1.12-6.55) times of those who were not infected STD, the possibility of not on ART among participants who had sex with male occasional or commercial partner in the last 6 months increased to 2.16(1.03-4.50) times of those who hadn't, and the possibility among participants who had anal sex with condom use in the past 6 months increased to 2.68(1.10-6.50) times of those who couldn't insist using condom.
There were low coverage of series of HIV/AIDS related intervention services among HIV-positive MSM in Chengdu, Chongqi and Guangzhou. Migrants, had sex with male occasional or commercial partner, had anal sex with condom use in the past 6 months, not infected STD in the last year may be the independent risk factors for HIV-positive MSM to not initiating ART.
2 cases had follicular hyperplasia, 1 case had a few ooze after taking out the plastic type. All cases had endogenous foreign bodies, taking the shape of the bronchial tree or a funicular. Block shape and sites were as follows: right main bronchus 2 cases, superior lobe of right lung 1 case, right middle bronchial 1 case, left main bronchus 2 cases, 1 case with left lower lobe, right main bronchus and left lower lobe bronchus 1 case. The breath sounds of the affected side become more enhanced after operation, with the alliviation of dyspnea. All cases recovered after ICU treatment. The pathologic examination were all type I plastic bronchitis.
Removement of the endogenous foreign body via rigid bronchoscopy is the effective method in the treatment of plastic bronchitis. Plastic bronchitis is a rapid-developing critical, urgent disease.In order to reduce the mortality, early diagnosis and timely surgery are necessary.
Furthermore, the relevant measurements about the optic canal were recorded.
Through the supraorbital keyhole, the endoscope was introduced into the extradural space, and the following structures could be exposed and identified: the sphenoid ridge, the anterior clinoid process, the roof of the optic canal and the falciform ligament. The roof and lateral wall of the optic canal were removed using a drill under the endoscope, and more sufficient decompression could be achieved by further incising the falciform ligament and optic sheath. After measurement, the distance from the zygomatic process of the frontal bone to the optic canal was 59.32 ± 2.27 mm, the distance from the upper midpoint of the posterior foramen of the optic canal to the internal carotid artery was 3.80 ± 0.93 mm.
According to the cadaveric study, it is feasible to perform the endoscopic decompression of optic nerve with a clear view through the supraorbital keyhole extradural approach. Our study may provide a minimally invasive and safe option for the optic nerve decompression.
Customized ensemble multiwavelet method for aero-engine rotor condition identification, using measured vibration data, is developed in this paper. First, customized multiwavelet basis function with strong adaptivity is constructed via symmetric multiwavelet lifting scheme. Then vibration signal is processed by customized ensemble multiwavelet transform. Next, normalized information entropy of multiwavelet decomposition coefficients is computed to directly reflect and evaluate the condition. The proposed approach is first applied to fault detection of an experimental aero-engine rotor. Finally, the proposed approach is used in an engineering application, where it successfully identified the crack fault of a demountable disk-drum aero-engine rotor. The results show that the proposed method possesses excellent performance in fault detection of aero-engine rotor. Moreover, the robustness of the multiwavelet method against noise is also tested and verified by simulation and field experiments.
It plays important roles in chronic inflammation and autoimmune diseases. However, little is known about relationship between IL-21 and LDH. This study was aimed to determine the association between IL-21 levels and pain scores in LDH patients compared to healthy controls.We enrolled 34 LDH patients and 20 healthy controls in this study. The LDH patients underwent surgery. Pain intensity was recorded using visual analogue scale (VAS) scores preoperatively. Serum IL-21 and IL-17 levels in the peripheral blood were determined using enzyme-linked immunosorbent assay. Disc tissue was examined using western blot and quantitative reverse-transcription polymerase chain reaction to determine IL-21, IL-17, and cyclooxygenase (COX)-2 expression, and using immunohistochemistry to assess IL-21 expression.LDH patients exhibited significantly higher levels of serum IL-21 and IL-17 than healthy controls. Moreover, higher expression of IL-21, IL-17, and COX-2 was found in the protein and mRNA levels in disc tissues from LDH patients than in normal disc tissues. Different parameters like VAS pain scores, IL-17, and COX-2 were positively correlated with the IL-21 levels. Enhanced production of IL-21 in disc tissues of LDH patients was also confirmed using immunohistochemical analyses.We concluded that inflammation was responsible for the pain associated with LDH, and that increased IL-21 expression may be associated with the pathogenesis of LDH.
Surface roughness was measured using a profilometer. After veneer sintering, the flexural strength σ was measured with biaxial flexure test and the reliability of strength was analyzed with Weibull distribution. Failure modes and fractographic patterns were analyzed by optical stereo and scanning electron microscopy (SEM).
For LDG, no significant difference was found for the flexural strength values among groups (F=0.406, P=0.750). No significant difference was found in Weibull modulus among groups(the confidence bounds overlapped with each other). SEM and optical stereo observation results showed that all the bilayered LDG specimens failed cohesively. For zirconia, Mean flexural strength values were (541 ± 75), (533 ± 73), (529 ± 78) and (640 ± 95) MPa for groups A, B, C and D, respectively, and group D demonstrated a significantly higher flexural strength compared to the other three groups(P<0.05). No significant difference were found among groups(the confidence bounds overlapped with each other). Specimens in all groups failed mainly adhesively, while those in group D presented lower percentage of adhesive failure.
Core ceramic surface treatment has no influence on the failure behaviors of LDG based bilayered structures. Sandblasting can increase the flexural strength of bilayered zirconia structures by reducing the incidence of delamination.
Besides, phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was evidenced to govern this stem cell recruitment in CML pathogenesis. Overall, our observations defined a novel critical role for TGF-β1 induced PI3K/Akt/NF-κB signaling pathway in the recruitment of the malignant cells in CML by releasing s-KitL and s-ICAM-1 and this was through a distinct PI3K/Akt/NF-κB signaling pathway.
A high-density genetic linkage map was constructed based on 2,755 bins involving 11,458 SNPs and 57 simple sequence repeats, and was used to identify loci associated with petalous degree (PDgr). The linkage map covered 2,027.53 cM, with an average marker interval of 0.72 cM. The AH map had good collinearity with the B. napus reference genome, indicating its high quality and accuracy. After phenotypic analyses across five different experiments, a total of 19 identified quantitative trait loci (QTLs) distributed across chromosomes A3, A5, A6, A9 and C8 were obtained, and these QTLs were further integrated into nine consensus QTLs by a meta-analysis. Interestingly, the major QTL qPD.C8-2 was consistently detected in all five experiments, and qPD.A9-2 and qPD.C8-3 were stably expressed in four experiments. Comparative mapping between the AH map and the B. napus reference genome suggested that there were 328 genes underlying the confidence intervals of the three steady QTLs. Based on the Gene Ontology assignments of 52 genes to the regulation of floral development in published studies, 146 genes were considered as potential candidate genes for PDgr. The current study carried out a QTL analysis for PDgr using a high-density SNP map in B. napus, providing novel targets for improving seed yield. These results advanced our understanding of the genetic control of PDgr regulation in B. napus.