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Background The gene polymorphism of interleukin-6 (IL-6) has been shown to be implicated in tuberculosis susceptibility in many studies, but with conflicting results. This study aimed to provide more accurate estimation of the relationship between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis. Method A literature search was performed in PubMed, EMBASE, and other databases. Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated. Statistical analyses were performed by using STATA 12.0. Results Twelve publications with 2635 cases and 3049 controls were included. The pooled analysis demonstrated significant evidence of association between IL-6 (-174G/C) and low risk of tuberculosis in dominant model (CC+GC vs GG: OR =0.693, 95% CI 0.581-0.826, p

The identification of aberrant microRNA (miRNA) expression during chemical-induced hepatic dysfunction will lead to a better understanding of the substantial role of miRNAs in liver diseases. 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to hepatic abnormalities in occupationally exposed populations. To explore whether aberrant miRNA expression is involved in liver abnormalities mediated by 1,2-DCE exposure, we examined alterations in miRNA expression patterns in the livers of NIH Swiss mice after dynamic inhalation exposure to 350 or 700 mg m-3 1,2-DCE for 28 days. Using a microarray chip, we discovered that only mmumiR-451a was significantly upregulated in the liver tissue of mice exposed to 700 mg m-3 1,2-DCE; this finding was validated by quantitative real-time polymerase chain reaction. In vitro study revealed that it was metabolite 2-chloroacetic acid, not 1,2-DCE that resulted in the upregulation of mmu-miR-451a in the mouse AML12 cell line. Furthermore, our data showed that the upregulation of mmu-miR-451a induced by 2-chloroacetic acid could suppress the expression of glycerol kinase and lead to the inhibition of glycerol gluconeogenesis in mouse liver tissue and AML12 cells. These observations provide evidence that hepatic mmu-miR-451a responds to 1,2-DCE exposure and might induce glucose metabolism disorders by suppressing the glycerol gluconeogenesis process.

// Hao Wang 1, * , Shujin Guo 2, * , Chun Wan 1, * , Ting Yang 1 , Ni Zeng 1 , Yanqiu Wu 1 , Lei Chen 1 , Yongchun Shen 1 and Fuqiang Wen 1 1 Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Chengdu 610041, China 2 Internal Medicine of Sichuan Provincial People's Hospital and Sichuan Academy of Medical Science, Chengdu 610072, China * These authors contributed equally to this work Correspondence to: Yongchun Shen, email: shen_yongchun@126.com Fuqiang Wen, email: wenfuqiang.scu@gmail.com Keywords: sepsis, mortality, polymorphism, meta-analysis Received: June 28, 2017 Accepted: August 27, 2017 Published: September 13, 2017 ABSTRACT Background: The -308G/A polymorphism in the gene encoding tumor necrosis factor-α (TNF-α) has been implicated in sepsis risk in many studies but with variable results. This study aimed to comprehensively assess the evidence of association between this polymorphism and risk of sepsis and sepsis-related mortality. Materials and Methods: PubMed, EMBASE and other databases were searched to identify relevant studies, and data were analyzed using Review Manager 5.0 and STATA 12.0. Results: Data from 34 publications involving 12,284 subjects were meta-analyzed. Combined analysis revealed an association between TNF-α -308G/A gene polymorphism and risk of sepsis (AA+GA vs. GG, OR 1.35, 95% CI 1.10–1.67, P = 0.005). This association was observed in the Caucasian subgroup (OR 1.50, 95% CI 1.13–2.00, P = 0.006), but not in the Asian subgroup. Across the entire study population, the polymorphism was also significantly related to septic shock risk (OR 1.52, 95% CI 1.18–1.95, P = 0.001) but not to sepsis-related mortality (OR 0.99, 95% CI 0.71–1.40, P = 0.97). Conclusions: This meta-analysis suggests that the -308G/A gene polymorphism in the TNF-α gene may contribute to risk of sepsis and septic shock, but not risk of mortality.

// Shaqiu Zhang 1,2,6,* , Tamer al-Maghout 2,6,* , Rosi Bissinger 2,6 , Ni Zeng 2,3,6 , Lisann Pelzl 2,6 , Madhuri S. Salker 2,4,6 , Anchun Cheng 1,** , Yogesh Singh 2,5,6,** and Florian Lang 2,6** 1 Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, P.R. China 2 Department of Internal Medicine III, Tubingen University, Gmelinstraβe, Tubingen, Germany 3 Department of Cleft Lip and Palate Surgery, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China 4 Institute of Women’s Health, Tubingen University, Calwerstraβe, Tubingen, Germany 5 Institute of Medical Genetics and Applied Genomics, Tubingen University, Calwerstraβe, Tubingen, Germany 6 Institute of Physiology I, Tubingen University, Gmelinstraβe, Tubingen, Germany * Equal contributions thus sharing first authorship ** Equal contributions thus sharing last authorship Correspondence to: Anchun Cheng, email: // Yogesh Singh, email: // Florian Lang, email: // Keywords : Murine CD4 + T cells, human leukaemic T cell lymphoblasts, EGCG, SOCE, miR-15b, Immunology and Microbiology Section, Immune response, Immunity Received : January 10, 2017 Accepted : July 26, 2017 Published : August 08,2017 Abstract CD4 + T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4 + T cells triggers cytosolic Ca 2+ release with subsequent store operated Ca 2+ entry (SOCE), which is accomplished by the pore forming Ca 2+ release activated Ca 2+ (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2). Green tea polyphenol epigallocatechin-3-gallate (EGCG) acts as a potent anti-inflammatory and anti-oxidant agent for various types of cells including immune cells. However, how post-transcriptional gene regulators such as miRNAs are involved in the regulation of Ca 2+ influx into murine CD4 + T cells and human Jurkat T cells through EGCG is not defined. EGCG treatment of murine CD4 + T cells significantly down-regulated the expression of STIM2 and Orai1 both at mRNA and protein levels. Furthermore, EGCG significantly decreased SOCE in both murine and human T cells. EGCG treatment increased miRNA-15b (miR-15b) abundance in both murine and human T cells. Bioinformatics analysis reveals that miR-15b, which has a STIM2 binding site, is involved in the down-regulation of SOCE. Overexpression of miR-15b significantly decreased the mRNA and protein expression of STIM2 and Orai1 in murine T cells. Treatment of Jurkat T cells with 10 µM EGCG further decreased mTOR and PTEN protein levels. EGCG decreased mitochondrial membrane potential (MMP) in both human and murine T cells. In conclusion, the observations suggest that EGCG inhibits the Ca 2+ entry into murine and human T cells, an effect accomplished at least in part by up-regulation of miR-15b.

Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin. We verified that high fat diet lipid accumulation is also capable of inducing Wnt/β-catenin. Caloric restriction inhibits hepatosteatosis, reduces Wnt/β-catenin activation and blocks the expansion of TICs leading to complete inhibition of tumorigenesis without affecting the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) loss regulated protein kinase B (AKT) activation. Pharmacological inhibition or loss of the Wnt/β-catenin signal represses TIC growth in vitro, and decreases the accumulation of TICs in vivo. In human liver cancers, ontology analysis of gene set enrichment analysis (GSEA)-defined Wnt signature genes indicates that Wnt signaling is significantly induced in tumor samples compared with healthy livers. Indeed, Wnt signature genes predict 90% of tumors in a cohort of 558 patient samples. Selective depletion of macrophages leads to reduction of Wnt and suppresses tumor development, suggesting infiltrating macrophages as a key source for steatosis-induced Wnt expression. These data established Wnt/β-catenin as a novel signal produced by infiltrating macrophages induced by steatosis that promotes growth of tumor progenitor cells, underlying the increased risk of liver tumor development in obese individuals.

Herein, we report a new approach to fabricate polyvinyl alcohol (PVA) based hydrophilic monoliths by alcoholysis of porous emulsion-templated polyvinyl acetate (PVAc). The precursory PVAc-based monolith is obtained by polymerization of a W/O high internal phase emulsion (HIPE) containing vinyl acetate as the external phase while water as the internal phase. As an alcoholysis-stable tri-functional commonomer, triallyl isocyanurate is chosen as the crosslinking agent to prevent possible collapse of the polymeric skeleton and the consequent losses in mechanical properties during the alcoholysis step. By alcoholysis of the resulting PVAc-based monolith, the PVA-based monoliths are successful prepared as confirmed by FTIR analysis. BET analysis and SEM observation confirm the formation of open-cell and highly interconnected porous structures of PVA-based monoliths with surface areas of around 16 m2/g. Stemming from the intrinsic hydrophilicity of hydroxyl and morphology, PVA-based monoliths exhibit great enhancement in hydrophilicity with a much lower water contact angles than that of PVAc-based monoliths.

In situ gelling delivery systems for the ocular administration of drugs has been a major focus of research over the past two decades, improving the treatment of diseases of the anterior segment of the eye by simple, safe, and reproducible drug administration. This drug delivery strategy results in high ocular bioavailability by avoiding rapid precorneal clearance resulting from nasolacrimal drainage and eye blinking. However, the development of such unconventional forms requires many parameters to be mastered, such as gelation time, viscoelastic behavior, mucoadhesion, and sustained release. In this review, we describe and assess the in vitro and in vivo methods available for in situ gelling ophthalmic delivery systems, highlighting the advantages of existing methods and, in some cases, the need for more relevant assays.

Excessive exposure to 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to liver dysfunction. To fully explore the mechanism of 1,2-DCE-induced hepatic abnormalities, 30 male National Institutes of Health (NIH) Swiss mice were exposed to 0, 350, or 700mg/m3 of 1,2-DCE, via inhalation, 6h/day for 28days. Increased liver/body weight ratios, as well as serum AST and serum ALT activity were observed in the 350 and 700mg/m3 1,2-DCE exposure group mice, compared with the control group mice. In addition, decreased body weights were observed in mice exposed to 700mg/m3 1,2-DCE, compared with control mice. Exposure to 350 and 700mg/m3 1,2-DCE also led to significant accumulation of hepatic glycogen, free fatty acids (FFA) and triglycerides, elevation of blood triglyceride and FFA levels, and decreases in blood glucose levels. Results from microarray analysis indicated that the decreases in glucose-6-phosphatase catalytic subunit (G6PC) and liver glycogen phosphorylase (PYGL) expression, mediated by the activation of AKT serine/threonine kinase 1 (Akt1), might be responsible for the hepatic glycogen accumulation and steatosis. Further in vitro study demonstrated that 2-chloroacetic acid (1,2-DCE metabolite), rather than 1,2-DCE, up-regulated Akt1 phosphorylation and suppressed G6PC and PYGL expression, resulting in hepatocellular glycogen accumulation. These results suggest that hepatic glucose and lipid homeostasis are impaired by 1,2-DCE exposure via down-regulation of PYGL and G6PC expression, which may be primarily mediated by the 2-chloroacetic acid-activated Akt1 pathway.

Many players regulating the CD4+ T cell-mediated inflammatory response have already been identified. However, the critical nodes that constitute the regulatory and signalling networks underlying CD4 T cell responses are still missing. Using a correlation network-guided strategy based on time-series transcriptome data of human CD4+CD25- effector T cells (Teffs), here we identified VIMP (VCP-interacting membrane protein), one of the 25 genes encoding selenocysteine in humans, as a gene regulating the effector functions of human CD4 T cells. Knocking-down VIMP in Teffs enhanced their proliferation and expression of several cytokines, including IL-2 and CSF2. We identified VIMP as an endogenous inhibitor of cytokine production in Teffs via both, the E2F5 transcription regulatory pathway and the Ca2+/NFATC2 signalling pathway. Our work not only indicates that VIMP might be a promising therapeutic target for various diseases involving CD4 T cells, but also shows that our network-guided approach might be generally applicable to different types of cells and can significantly aid in predicting new functions of the genes of interest.One-sentence summaryUsing a network-guided approach, we identified that Selenoprotein S (SELS or VIMP) negatively regulates cytokine expression of human CD4+ effector T cells via the E2F5 and calcium Ca2+/NFATC2 pathways.

Surface defect detection is an indispensable step in the production process. Recent researches based on deep learning have paid primarily attention to improving accuracy. However, it is difficult to apply in real situation, because of huge number of parameters and the strict hardware requirements. In this paper, a lightweight fully convolutional neural network, named LFCSDD, is proposed. The parameters of our model are 11x fewer than baselines at least, and obtain the accuracy of 99.72% and 98.74% on benchmark defect datasets, DAGM 2007 and KolektorSDD, respectively, outperforming all the baselines. In addition, our model can process the images with different sizes, which is verified on the RSDDs with the accuracy of 97.00%.

Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme into the tricarboxylic acid (TCA) cycle. Here we show that PARK7/DJ-1, a key familial Parkinson’s disease (PD) gene, is a pacemaker controlling PDH activity in CD4 regulatory T cells (Tregs). DJ-1 bound to PDH-E1 beta (PDHB), inhibiting the phosphorylation of PDH-E1 alpha (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Dj-1 depletion impaired Treg proliferation and cellularity maintenance in older mice, increasing the severity during the remission phase of experimental autoimmune encephalomyelitis (EAE). The compromised proliferation and differentiation of Tregs in Dj-1 knockout mice were caused via regulating PDH activity. These findings provide novel insight into the already complicated regulatory machinery of the PDH complex and demonstrate that the DJ-1-PDHB axis represents a potent target to maintain Treg homeostasis, which is dysregulated in many complex diseases.

Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson's disease gene) is a pacemaker regulating PDH activity in CD4

In this study, we evaluated the function and regulation of the long non-coding RNA (lncRNA) FAM83H-AS1 in triple-negative breast cancer (TNBC). Our data show that the FAM83H-AS1 levels are increased in human TNBC cells and tissues. Proliferation, migration, and invasion of TNBC cells are decreased by FAM83H-AS1 suppression, but increased by FAM83H-AS1 overexpression. Bioinformatics analysis revealed that miR-136-5p is a potential target of FAM83H-AS1. MiR-136-5p expression is decreased in TNBC tissues, and its overexpression suppresses TNBC cell proliferation, migration, and invasion. MiR-136-5p suppression reverses the FAM83H-AS1 silencing-mediated inhibition of TNBC cell proliferation, migration, and invasion, suggesting that FAM83H-AS1 exerts its oncogenic effect by inhibiting miR-136-5p. Our data identify metadherin (MTDH) as the target gene of miR-136-5p, and demonstrate that the MTDH expression is increased in human TNBC tissues, which induces proliferation, migration, and invasion of TNBC cells. Importantly, our in vivo data show that FAM83H-AS1 also promotes tumor growth in TNBC mouse xenografts. Together, our results demonstrate that FAM83H-AS1 functions as an oncogenic lncRNA that regulates miR-136-5p and MTDH expression during TNBC progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC.

BACKGROUND: Despite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC). METHODS: Using in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts. RESULTS: The MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8(+) T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC. CONCLUSION: We identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes. FUNDING: This work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.

Angiopoietin like 4 (ANGPTL4) is a secreted glycoprotein involved in lipid metabolism, vascular permeability, angiogenesis and inflammatory signaling. Although it has been implicated in experimental acute lung injury, its role in acute respiratory distress syndrome (ARDS) remains unknown. This study aims at identifying ANGPTL4 as a new clinical biomarker for ARDS. ARDS patients were enrolled following Berlin definition, and control subjects without a diagnosis of any pulmonary disorders were recruited. Serum and bronchoalveolar lavage fluid (BALF) levels of ANGPTL4, IL-6, IL-8 and TNF-α were measured with Human Magnetic Luminex Assay. Albumin levels were evaluated using ELISA and the ratio of BALF albumin to serum albumin (BA/SA) was calculated as the positive indicator of pulmonary permeability. Fifty consecutive patients and 25 control subjects were included (median APACHE II score of 22, PaO2/FiO2 ratio 136). Both serum and BALF levels of ANGPTL4 in ARDS patients were significantly higher than those in control subjects (706±97 vs. 84±7 ng/mL, p

Background: Hysteroscopic procedures were widely applied but the clinical effects of antibiotic prophylaxis for these operations were not specifically addressed. In current study, we aimed to investigate the role of prophylactic antibiotics in hysteroscopic procedures by meta-analysis. Methods: We conducted literature retrieval in electronic databases, including MEDLINE, EMBASE, and Cochrane Central, to identify relevant randomized controlled trials (RCTs) investigating the clinical effects of antibiotic prophylaxis for hysteroscopic procedures. The postoperative infection rate was selected for pooled estimation. The I2 index statistic was used to assess heterogeneity. Publication bias was evaluated using funnel plots and Egger test. Sensitivity analysis based on different subcategories was conducted to examine the stability of the main results. Results: Four RCTs including 2221 patients were identified for the final quantitative analysis. Pooled estimation indicated no significant difference in infection rate between the antibiotic prophylaxis group and control group (test for OR: Z = 0.50, P = .616; 95% CI: 0.987–1.008). Sensitivity analysis based on surgical procedure, antibiotic application, follow-up time and administration time revealed similar results. Conclusion: Based on current objective evidence, we conclude that antibiotic prophylaxis exhibits no clinical benefit for hysteroscopic procedures. Therefore, it is not recommended. Meanwhile, more high-quality RCTs are needed to support our conclusion.

Sorafenib is the most widely used first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but such treatment provides only limited survival benefits that might be related to the immune status of distinct tumor microenvironments. A fundamental understanding of the distribution and phenotypes of T lymphocytes in tumors will undoubtedly lead to the development of novel immunotherapeutic strategies that could possibly enhance the efficacy of sorafenib treatments. Flow cytometry, immunohistochemistry and immunofluorescence analyses were performed to detect the infiltration and distribution of various leukocyte populations, and the expression of different immune checkpoint molecules in fresh HCC tumor tissues. Correlations among indicating genes were calculated in 365 patients with HCC from The Cancer Genome Atlas (TCGA) data set, and the cumulative overall survival time was calculated using the Kaplan–Meier method. Moreover, role of adenosinergic pathway on sorafenib anti-tumor efficacy was investigated using both subcutaneous and orthotopic transplantation tumor model in immune competent C57BL/6 mice. We revealed that levels of CD3+ and CD8+ T cells were significantly downregulated in HCC tumor tissue, so were the infiltration of CD169+ cells (a Mφ subpopulation with T cell activation capacities) and their contact with CD8+ cells in tumor milieus. Moreover, levels of PD-1 and CD39 expression were significantly upregulated in human HCC-infiltrating CD4+ and CD8+ T cells, and CD39+CD8+ T cells exhibited a CD69+PD-1+perforinlowIFNγlow “exhausted” phenotype. Levels of both CD39+ T cells infiltration and adenosine receptor ADORA2B expression in tumor tissues were negatively correlated with overall survival of patients with HCC. Accordingly, mice treated with sorafenib in combination with adenosine A2B receptor blockage reagents exhibited significantly reduced tumor progression compared with control groups. These results suggest that adenosinergic pathway might represent an applicable target for sorafenib-combined-therapies in human HCC.

Osteoinduction refers to de novo bone formation induced by biomaterials in places where physiologically no bone tissue is formed. Biomaterials with osteoinductive capacities have been shown to fill bone defects of critical sizes with ubiquitous new bone formation. Therefore, osteoinduction has been regarded as an important characteristic for biomaterials aiming at bone regeneration. In our study, we tested osteoinductive capacities of different calcium phosphate bioceramic particles, calcium phosphate scaffolds, and porous poly(trimethylene carbonate)(PTMC)-calcium phosphate composite scaffolds in a sheep model. Biphasic calcium phosphate (BCP) particles of 45-150 μm and 150-500 μm, microporous β-tricalcium phosphate (β-TCP) particles of 45-150 μm, non-microporous β-TCP particles of 45-150 μm and 150-500 μm, and porous β-TCP scaffolds were implanted in sheep long dorsal muscle for three and nine months. Likewise, porous composite scaffolds, in which BCP particles, microporous β-TCP particles and β-TCP particles, all of 45-150 μm, had been incorporated into PTMC matrices, were implanted in sheep long dorsal muscle for three and nine months. Porous PTMC scaffolds were implanted as controls. Abundant new bone formation was induced by BCP particles of both size ranges, the β-TCP scaffold was also able to induce new bone formation at both three and nine months follow up, while no new bone formation was induced by the other biomaterials. Implantation of the abovementioned biomaterials led to uneventful degradation of the PTMC matrices and the incorporated calcium phosphate particles, and provoked no obvious tissue reaction. Future studies are needed to determine the optimal composition of composite biomaterials based on PTMC and calcium phosphate to produce osteoinductive composites.

Epidemiological and experimental data have implicated the role of di(2-ethylhexyl) phthalate (DEHP) and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in the pathogenesis of metabolic syndrome, including the impairment of hepatic glucose metabolism. To elucidate the underlying mechanism by which DEHP or MEHP perturbs hepatic glucose homeostasis, we compared the effect of DEHP (0–200 μM) and MEHP (0–200 μM) on glucose metabolism in HepG2 cells. In this study, we found that MEHP can induce more severe impairments in glucose homeostasis than DEHP can; these include increased hepatic gluconeogenesis via receptor substrate-1/protein kinase B/fork-head box protein O1 (IRS-1/AKT/FOXO1)-mediated phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6PC) up-regulation, as well as decreased hepatic glycogen synthesis via glucokinase (GCK) inhibition and IRS-1/AKT/glycogen synthase kinase-3β (GSK-3β)-mediated glycogen synthase (GYS) inactivation. Additionally, our results demonstrated that retinol binding protein 4 (RBP4), an insulin resistance-inducing factor, plays a critical role in the MEHP-induced disorder of glucose homeostasis and the dysfunction of insulin signaling transduction, whereas the deletion of RBP4 by the clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR/Cas9) significantly reversed these toxic effects. Although these should be interpreted with caution in view of limited in vivo evidence, the present study provides the first in vitro evidence for potential involvements of RBP4 in disturbance of glucose homeostasis in the MEHP-treated HepG2 cells.

Background/Aims: Tumor cell proliferation is modified by 1,25-Dihydroxy-Vitamin D3 (1,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions and lactate, which is in part accomplished by Na+/H+ exchangers, such as NHE1 and monocarboxylate transporters, such as MCT4. An effect of 1,25(OH)2D3 on those transport processes has, however, never been reported. As cytosolic pH impacts on apoptosis, the study further explored the effect of 1,25(OH)2D3 on apoptosis and on the apoptosis regulating kinase AKT, transcription factor Forkhead box O-3 (FOXO3A) and B-cell lymphoma protein BCL-2. Methods: In human endometrial adenocarcinoma (Ishikawa) cells, cytosolic pH (pHi) was determined utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, NHE1 and MCT4 transcript levels using qRT-PCR, NHE1, MCT4, total & phospho AKT, total & phospho-FOXO3A and BCL-2 protein abundance by Western blotting, lactate concentration in the supernatant utilizing a colorimetric enzyme assay and cell death quantification using CytoTox 96®, Annexin V and Propidium Iodide staining. Results: A 24 hours treatment with 1,25(OH)2D3 (100 nM) significantly increased cytosolic pH (pHi), significantly decreased Na+/H+ exchanger activity, NHE1 and MCT4 transcript levels as well as protein abundance and significantly increased lactate concentration in the supernatant. Treatment of Ishikawa cells with 1,25(OH)2D3 (100 nM) further triggered apoptosis, an effect paralleled by decreased phosphorylation of AKT and FOXO3A as well as decreased abundance of BCL-2. Conclusions: In Ishikawa cells 1,25(OH)2D3 is a powerful stimulator of glycolysis, an effect presumably due to cytosolic alkalinization. Despite stimulation of glycolysis, 1,25(OH)2D3 stimulates slightly but significantly suicidal cell death, an effect presumably in part due to decreased activation of AKT with decreased inhibition of pro-apoptotic transcription factor FOXO3A and downregulation of the anti-apoptotic protein BCL-2.

Background/Aims: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients’ epithelium and stroma is significantly lower. Methods: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. Results: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. Conclusion: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

Background: LEFTY2, a suppressor of cell proliferation, tumor growth, regulator of stemness and embryonic differentiation, is a negative regulator of cancer cell reprogramming. Malignant transformation may lead to migration requiring loss of adhesion and gain of migratory activity. Signaling involved in the orchestration of migration, proliferation and spreading of cells include focal adhesion kinase (FAK) and adhesion molecule E-cadherin. Aims: The present study explored whether LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover, the study explored the involvement of microRNA-200a (miR-200a), which is known to regulate cellular adhesion by targeting E-Cadherin. Methods: FAK activity was estimated from FAK phosphorylation quantified by Western blotting, migration utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining, respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy. Results: LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67 expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked by FAK inhibitor PF 573228 (50 µM). Addition of LEFTY2 in the presence of PF-573228 did not result in a further significant decline of migration. Conclusion: In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration.

The characteristics of AlGaN-based deep ultraviolet light-emitting diodes (UV LEDs) with quaternary AlInGaN streamlined quantum barriers (QBs) are investigated in this paper. The simulated results show that the light output power and the internal quantum efficiency (IQE) of deep UV LEDs with AlInGaN streamlined QBs have been improved obviously, and the efficiency droop effect has been significantly alleviated. After in-depth study, it is shown that quaternary AlInGaN streamlined QBs is designed to reduce the polarization charge density between quantum wells (QWs) and QBs, and relieve band bending. In addition, the streamline barrier can reduce the kinetic energy of injected carriers, and improve the probability of the carriers being bounced back to the quantum wells, so as to enhance the capture of carriers in the quantum wells. As a result, the recombination rate of electron and hole in the QWs is enhanced, the light output power and the IQE are improved, and the efficiency droop effect is alleviated.

Myeloid cells, including monocytes/macrophages (Mo/Mϕ), neutrophils, and dendritic cells, can mediate divergent immune responses according to different pathological conditions. In cancer, myeloid cells play important roles in disease progression and therapy, suggesting that appraising the overall and exact intratumoral myeloid response may provide valuable information that may help to predict cancer prognosis and tailor more precise therapies. In this study, we screened biomarkers that cover major myeloid subtypes in human tumors, then constructed and validated a simple prognostic signature, called Myeloid Response Score (MRS), based on a dataset from a multi-center cohort of 1,177 HCC patients. Using multiplex immunofluorescence staining, we observed a shift of predominant myeloid population from CD169+, CD169−CD11b−CD14+, and CD169−CD11b−CD163+ Mo/Mϕs in MRSlow HCC to neutrophils and CD11b+CD169− Mo/Mϕs in MRShigh tumor. Transcriptomic and flow cytometric analyses showed that MRShigh HCC exhibited patterns of CD8+ T cell exhaustion including impaired cytotoxicity and increased PD-1 expression, suggesting highly suppressive immune microenvironment. The “climb trajectory” of MRSs between HCC tumors were depicted using the TCGA dataset, and was linked to CD8+ T cell dysfunction and poorer survival of patients. Moreover, MRS-based nomograms were highly discriminative, accurate, and useful in predicting HCC prognosis and we provide additional evidence that MRS may associate with the efficacies of post-recurrence sorafenib and transcatheter arterial chemoembolization (TACE) treatments. Together, we constructed and validated a new myeloid signature with valuable immunological and clinical potential.

Semantic maps are powerful tools for analyzing cross-language variations with implications between semantic functions to construct the relevant conceptual space. However, as existing semantic maps cannot illustrate the imbalance of implications between functions, a further discussion of inferring implications is highly demanded. The problem of inferring implications and the imbalance of implications between functions above is similar to the well-known problem of generating all significant association rules between items purchased by customers, and the Apriori algorithm offers an effective solution to relieve such issue. Here, alternative schematic diagrams based on the Apriori algorithm are employed to supplement semantic maps, which is justified by reproducing the same results as Cysouw obtained on person marking using his datasets. Furthermore, in our study, an implication in number from singular to plural is observed in person marking. We have solved the issue of imbalance and obtained credible implication rules between primitives in groups. We can mine practicable directed implication rules and reveal rules hard to notice before, such as active primitives between groups.

Staphylococcus aureus (S.aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. So developing an efficacious vaccine against S.aureus is urgently required. In the present study, we selected five conserved antigens, which were all well-characterized virulence factor of S. aureus by using a reverse vaccine strategy and developed a recombinant five-antigen S. aureus vaccine (rFSAV). Including the secreted factors α-hemolysin (Hla), staphylococcal enterotoxin B (SEB), and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC). rFSAV provided consistent protection in S. Aureus lethal sepsis, pneumonia and fracture fixation mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S.aureus strains. Meanwhile, rFSAV immunized mice with an optimal immunization procedure (days 0, 3, and 7) were able to induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus. Moreover, the importance of specific antibodies in protection was demonstrated by passive transfer experiments. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection. Funding Statement: This work was supported by the National Natural Science Foundation of China [grant number 81172892 and 31370932] and the key project of innovative drug development [grant number 2015ZX09101033 and 2016ZX09J16102-002]. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: All animal care and use protocols in this study were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal experiments in this study were approved by the Animal Ethical and Experimental Committee of the Third Military Medical University (Chongqing, Permit No. 2011- 04) in accordance with their rules and regulations.

International audience; Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen.

Staphylococcus aureus (S.aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. Developing an efficacious vaccine against S.aureus is urgently required. In the present study, we selected five conserved antigens, including the secreted factors &alpha, hemolysin (Hla), staphylococcal enterotoxin B (SEB) and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC). They were all well-characterized virulence factor of S. aureus and developed a recombinant five-antigen S. aureus vaccine (rFSAV), rFSAV provided consistent protection in S. aureus lethal sepsis and pneumonia mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S. aureus strains. Meanwhile, rFSAV immunized mice were able to induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus. Moreover, the importance of specific antibodies in protection was demonstrated by antibody function tests in vitro and in vivo. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection.

To investigate the ageing status for male population aged or over 20 years old in urban communities, clarifying their distribution characteristics and rules, and to provide reference for aging research. Methods: A total of 1 120 men aged or over 20 years old in Nanchang were obtained by stratified sampling, and the aging scale was measured in 9 groups. The distribution characteristics of aging scores were analyzed by normality test, variance analysis, and linear correlation. Results: The total score of aging and the scores of physiological, psychological, and physiological dimensions were 54.01±9.24, 32.33±7.54, 14.66±1.64, and 7.02±1.16, respectively. The scores were positively correlated with age. The total score curve of aging was significantly increased in the 25-30 and 30-40, 65-70 and 70-75 years old groups. The physiological dimension curve was similar to the total score curve. The psychological dimension curve was more pronounced at 55-60 and 60-65 years old groups. The social dimension curve raised slowly and smoothly at all ages. Conclusion: The total score and the scores for all dimensions of male physiological-psycho-sociological increase with age; and changes near the age group of 55-60 and 60-65 are obvious, providing reference for the understanding of male aging.目的：探讨城市社区20岁及以上男性人群衰老状态，阐明其分布特点及规律，为衰老评价及老龄化研究提供参考。方法：通过分层抽样获取1 120名南昌市20岁及以上男性，分9个年龄组进行衰老量表测量；运用正态性检验、方差分析、线性相关等统计学方法分析男性衰老分值的分布特点。结果：男性衰老量表总分为54.01±9.24，生理维度为(32.33±7.54)分，心理维度为(14.66±1.64)分、社会维度为(7.02±1.16)分，衰老分值与年龄呈正相关，在25~30岁至30~40岁和65~70岁至70~75岁表现出比较明显的曲线上升。不同年龄段各维度得分不同，且各维度得分与年龄均呈正相关。生理维度曲线变化与衰老总分曲线类似，心理在55~60岁至60~65岁组的上升曲线相对明显，社会维度的曲线各年龄段处于缓慢平稳上升。结论：男性衰老量表的实证研究表明男性在生理、心理、社会维度衰老分值及总分随年龄增加而上升，且在55~60岁至60~65岁表现出较明显的变化，为评估男性衰老状态提供了参考。.

Previous studies assessing secondhand smoke (SHS) and risk of mental health problems have yielded inconsistent results. We performed a meta-analysis to statistically assess the association between SHS exposure, depressive symptoms and psychological distress among adults. A systematically search of Pubmed (1946–2015) and EMBASE (1976–2015) was conducted and supplemented by bibliographies of all retrieved articles to find additional relevant citations. Odds ratios (OR) and associated 95 % confidence interval (CI) of each eligible study were extracted and pooled in our meta-analysis. A total of 11 studies comprising 86,739 participants met the inclusion criteria. A random-effect model was used in meta-analysis since considerable heterogeneity was expected. Our results indicate that SHS exposure was significantly associated with depressive symptoms (OR 1.60, 95 % CI 1.35–1.90) and psychological distress (OR 1.32, 95 % CI 1.11–1.56). Exposure to SHS among non-smoker is associated with depressive symptoms and psychological distress, emphasizing the significance of reducing SHS exposure at a population level.

Morin, a flavonoid isolated from Morus alba L. (Moraceae), possesses anti-inflammatory, antiangiogenic among other biological activities. This study investigated its effect on type II collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms in view of synovial angiogenesis. Morin administered po attenuated arthritic progression as indicated by reduction of arthritis scores and paw swelling. It also markedly reduced serum levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but increased the level of anti-inflammatory cytokine interleukin-10, and ameliorated histopathological changes of joints. Morin markedly inhibited expression of CD31, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor in synovial membrane tissues, and decreased serum levels of VEGF in CIA rats. In vitro, morin markedly inhibited VEGF-induced migration and tube formation in human umbilical vein endothelial cells. These results indicate that morin had antirheumatoid potential, and its mechanism might be associated with inhibition of synovial angiogenesis.

A new mercury(II) complex containing dmit ligand and biquaternary ammonium cation, DPyE[Hg(dmit)2] (1) (DPyE2+ = N,N’-ethylidenedipyridinium, dmit = 1,3-dithiol-2-thione-4,5-dithiolate), was synthesized and fully characterized by elemental analysis, IR, 1H-NMR, UV–Vis, TG, single crystal X-ray diffraction, and powder X-ray diffraction. Moreover, the electrochemical properties and conductivities of complex 1 were studied by cyclic voltammetry and four-probe AC technique, respectively. Complex 1 crystallizes in the monoclinic space group P 21/n with a = 8.1815(2) A, b = 12.8701(5) A, c = 23.2681(7) A, β = 90.922(3)°, Z = 4, V = 2449.75(14) A3, Dc = 2.114 g·cm–3. The crystal structure shows that the dihedral angle of two dmit ligands of [Hg(dmit)2]2– anion is closed to vertical, which results in the formation of a distorted HgS4 tetrahedral geometry. The S···S short contacts assemble [Hg(dmit)2]2– anions into 1D, 2D, and 3D supramolecular network. The DPyE2+ cations are located in the caves, providing additi...

Background: Nonsyndromic orofacial clefts (NSOCs) are the most common craniofacial birth defects with complex etiology in which multiple genes and environmental exposures are involved. Bone morphogenetic protein 7 (BMP7), as a member of the transforming growth factor-beta (TGF-beta) superfamily, has been shown to play crucial roles in palate and other orofacial ectodermal appendages development in animal models. Material and Methods: This study was designed to investigate the possible associations between BMP7 gene and the NSOCs (221 case-parent trios) in Western Han Chinese. Five tagSNPs at BMP7, rs12438, rs6099486, rs6127973, rs230188 and rs6025469 were picked and tried to cover the entire gene. In order to identify the contribution of BMP7 gene to the etiology of NSOCs, we performed several statistical analysis from different aspects including transmission disequilibrium test (TDT), pairwise linkage disequilibrium (LD), parent-of-origin effect and Chi-squared/Fisher’s exact tests. Results: Rs6127973 G allele and G/G homozygotes were over-transmitted for both NSOCs ( P =0.005 and P =0.011, respectively) and NSCL/P ( P =0.0061 and P =0.011, respectively), rs6127973 G allele was also paternally over- transmitted for both NSOCs ( P =0.0061) and NSCL/P ( P =0.011). Conclusions: This study suggested that rs6127973 may be a risk factor of being NSOCs and confirmed the role of BMP7 gene in orofacial deformity from Western Han Chinese, which will also supply scientific evidence for future research and genetic counseling.

Background The gene polymorphism of interleukin-6 (IL-6) has been shown to be implicated in tuberculosis susceptibility in many studies, but with conflicting results. This study aimed to provide more accurate estimation of the relationship between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis Method A literature search was performed in PubMed, EMBASE, and other databases. Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated. Statistical analyses were performed by using STATA 12.0. Results Twelve publications with 2635 cases and 3049 controls were included. The pooled analysis demonstrated significant evidence of association between IL-6 (−174G/C) and low risk of tuberculosis in dominant model (CC+GC vs GG: OR =0.693, 95% CI 0.581–0.826, p

Background The ability of interleukins (ILs) to differentiate tuberculous pleural effusion from other types of effusion is controversial. The aim of our study was to summarize the evidence for its use of ruling out or in tuberculous pleural effusion. Methods Two investigators independently searched PubMed, EMBASE, Web of Knowledge, CNKI, WANFANG, and WEIPU databases to identify studies assessing diagnostic role of ILs for tuberculous pleural effusion published up to January, 2017. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The pooled diagnostic sensitivity and specificity of ILs were calculated by using Review Manager 5.3. Area under the summary receiver operating characteristic curve (AUC) was used to summarize the overall diagnostic performance of individual markers. Results Thirty-eight studies met our inclusion criteria. Pooled sensitivity, specificity and AUC for chosen ILs were as follows: IL-2, 0.67,0.76 and 0.86; IL-6, 0.86, 0.84 and 0.90; IL-12, 0.78, 0.83 and 0.86; IL-12p40, 0.82,0.65 and 0.76; IL-18, 0.87, 0.92 and 0.95; IL-27, 0.93, 0.95 and 0.95; and IL-33, 0.84, 0.80 and 0.88. Conclusions Some of these ILs may assist in diagnosing tuberculous pleural effusion, though no single IL is likely to show adequate sensitivity or specificity on its own. Further studies on a large scale with better study design should be performed to assess the diagnostic potential of ILs. Electronic supplementary material The online version of this article (10.1186/s12890-017-0530-3) contains supplementary material, which is available to authorized users.

To build a social aging scale for healthy people, and get the accuracy and feasibility of the scale to judge the aging of healthy people on the basis of the empirical research. Methods: Stratified random sampling was conducted according to the nine different age groups, and the age-related social function information was collected for healthy people by using the scale, which was made in our own plant; the distribution of the score, the correlations between the score and age or telomere length were analyzed by statistical software. Results: A total of 2 297 subjects were collected for the analysis. The ratio of male to female was 0.8:1. Social function of aging score was in the range of 3.00-12.90; aging score of personal ability was in the range of 1.00-4.45; aging score of social participation was in the range of 1.00-4.52; and aging score of organizational communication was in the range of 1.00-5.00. The correlation coefficient of aging scores with age was 0.696 (P0.001). The result of telomere length showed that the relative telomere length was 1.056±0.261. The telomere length in different groups were significantly different (F=35.803, P0.001). The telomere length was negatively correlated with aging (r=-0.964, P0.001) and social function of aging (r=-0.857, P0.001), respectively. Conclusion: The scores of age-related social function, personal ability, social participation, and organizational communication are increased with age. The telomere length is negatively correlated to aging score. The scale is applicable to measure social function of aging, which can provide reference for evaluation of the comprehensive of aging.目的：以自制社会功能性衰老量表为根据，在现场人群实证基础上探析该量表判断健康人衰老的可行性和实用性。方法：按9个年龄组分层随机抽样，运用自制量表获取反映研究对象社会功能衰老的现况资料；统计分析个体社会功能衰老得分分布情况及其与年龄、端粒长度的相关性。结果：现场调查人数共2 297，男女比0.8:1；社会功能性衰老总分为3.00~12.90分，个人能力、社会参与、组织交往得分分别为1.00~4.45，1.00~4.52，1.00~5.00分；年龄与衰老分值的相关性较高(r=0.696，P0.001)；调查对象相对端粒长度为1.056±0.261，不同年龄间相对端粒长度差异具有统计学意义(F=35.803，P0.001)；端粒长度与年龄呈负相关(r=-0.964，P0.001)，与社会功能性衰老得分呈负相关(r=–0.857，P0.001)。结论：社会功能衰老总分及各维度得分随年龄增大而升高，并与端粒长度呈负相关；量表适用于社会功能性衰老测评，为衰老综合性评估提供参考。.

Buccal administration route is a promising way for a large number of drugs exhibiting a low oral bioavailability. The present work describes the formulation and evaluation of a mucoadhesive and thermosensitive in situ gelling delivery system based on poloxamer 407, poloxamer 188 and xanthan gum for buccal drug delivery. First, the mucoadhesion properties were evaluated using a tensile test. The effect of xanthan gum on the mucoadhesion force was demonstrated. Then, to assess the buccal residence time which reflects the mucoadhesion properties, the validation of a fluorescence probe for in vivo optical imaging experiment was conducted. Methyl-Cyanine 5 derivative (Me-Cy5) was used to label the hydrogels, dissolution tests and permeation studies through buccal epithelium cells showed that Me-Cy5 release from hydrogels was mainly due to an erosion mechanism and presented a limited penetration across epithelium cells. These results suggest that, Me-Cy5 is a suitable marker for thermosensitive in situ gelling delivery systems as the probe mostly stays entrapped in the hydrogel and do not cross the epithelial barrier. Buccal residence performance of the hydrogel was evaluated for the first time by non-invasive optical imaging after administration to mice. This technique is an interesting alternative compared to visual observations and sacrifice involved experiments, which could also be exploited to various administration routes.

With the progress of science and technology, robot technology has a rapid development and penetrated into the social production of all aspects. To achieve the natural communication between men and machine that voice interaction is the future of human- computer interaction mainstream. While network language constitutes an important part of people's daily life in the information age, some negative phenomena also arise—the abuse of the Internet violence language. In this paper, through the introduction of speech recognition and synthesis technology, the NAO robot is developed and embedded in the open artificial intelligence platform of IFLYTEK, which is based on the vocabulary of high frequency Internet violence and the corresponding quiz database is established at the same time. When people talk with the NAO containing the Internet violence language, the robot will prompt immediately and persuades them to use civilized language, which will standardize the network language environment, and further promote the construction of socialist spiritual civilization.

The thyroid hormone responsive spot 14 (THRSP) gene is a de novo lipogenesis-related gene that plays a significant role in the initiation and development of nonalcoholic fatty liver disease (NAFLD). Several previous studies had shown that endogenous and environmental factors could regulate the expression of THRSP. The role of microRNAs (miRNAs), however, in controlling THRSP expression has not been investigated. In this study, we first constructed the hepatic steatosis cell model by using a mixture of free fatty acids (FFAs; oleate/palmitate, 2:1 ratio) to treat and demonstrate the promotive role of THRSP in lipid accumulation in hepatic cells. By analyzing the photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) database and performing a luciferase reporter assay, we confirmed that microRNA-451a specifically binds to mouse and human THRSP 3'UTR and inhibits its activity. Overexpression of miR-451a efficiently reduced THRSP mRNA and protein expression as well as triglyceride (TG) accumulation in cultured hepatic cells (AML12 and HepG2). Moreover, overexpression of miR-451a significantly decreases TG accumulation in the livers of mice injected with an miR-451a agomir. All these results demonstrated that miR-451a might participate in the FFA-induced hepatic steatosis by regulating the expression of the THRSP gene which represents a new potential target for NAFLD therapy.

With the advancement of science and technology, robot technology has penetrated in all aspects of social production and has rapid development. At the same time, voice technology has become a comprehensive human intelligence in various fields of technology and the mainstream is to realize the human-computer interaction between men while machine natural communication is the mainstream of human-computer. Based on the teaching of campus life and moral education, this paper introduces the speech recognition and synthesis technology and embeds the open artificial intelligence platform of IFLYTEK to NAO robot with voice interchange as the core and designs the program of the voice dialogue database between college instructor and student, which achieves the robot and students intelligent interaction function, promoting the cause of higher education and making further breakthrough in the education industry.

Receptor for advanced glycation end products (RAGE) is implicated in inflammatory responses in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), but its role in pulmonary edema formation remains unclear, especially in infection-related ARDS mainly caused by pneumonia or sepsis. In this study, we investigated the role of RAGE in alveolar fluid regulation by using RAGE gene knockout (RAGE) mice in a murine ALI model induced by lipopolysaccharide (LPS), and by comparing soluble RAGE (sRAGE) levels in serum and bronchial alveolar lavage fluid between ARDS patients and control subjects. We found that RAGE knockout significantly improved alveolar fluid clearance and reduced pulmonary vascular albumin leakage upon LPS challenge. Furthermore, LPS-induced substantial decrease in lung expression of sodium-potassium ATPase (Na,K-ATPase), epithelial sodium channel, and zonula occluden-1 (ZO-1) were fully or partially restored by the deletion of RAGE. In addition to this, LPS-induced lung leukocyte infiltration and inflammatory cytokine and chemokine release were all attenuated in RAGE mice as compared to wide-type mice. In infection-related ARDS patients, both serum and bronchial alveolar lavage fluid levels of the sRAGE were much higher than those in control subjects, and they were positively correlated with pulmonary vascular permeability and levels of interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-2. Taken together, we provided the first direct evidence for the essential role of RAGE in regulating lung fluid balance in infection-related ARDS/ALI. The underlying mechanisms may involve the downregulation of both ion-channel and tight junction proteins mediated by RAGE signaling in bacterial endotoxin-induced lung injury.

Gene knockdown and knockout using RNAi and CRISPR/Cas9 allow for efficient evaluation of gene function, but it is unclear how the choice of technology can influence the results. To compare the phenotypes obtained using siRNA and CRISPR/Cas9 technologies, aldehyde dehydrogenase 2 (ALDH2) was selected as an example. In this study, we constructed one HepG2 cell line with a homozygous mutation in the fifth exon of ALDH2 (ALDH2-KO1 cell) using the eukaryotic CRISPR/Cas9 expression system followed by the limited dilution method and one HepG2 cell line with different mutations in the ALDH2 gene (ALDH2-KO2 cell) using the lentivirus CRISPR/Cas9 system. Additionally, one ALDH2-knockdown (KD) HepG2 cell line was created using siRNA. The reproducibility of these methods was further verified in the HEK293FT cell line. We found that the mRNA expression level of ALDH2 was significantly decreased and the protein expression level of ALDH2 was completely abolished in the ALDH2-KO cell lines, but not in ALDH2-KD cells. Furthermore, the functional activity of ALDH2 was also markedly disrupted in the two ALDH2-KO cell lines compared with ALDH2-KD and wild-type cells. The lack of ALDH2 expression mediated by CRIPSR/Cas9 resulted in a more dramatic increase in the cellular susceptibility to chemical-induced reactive oxygen species generation, cytotoxicity, apoptosis, and inflammation, especially at low concentrations compared with ALDH2-KD and WT cells. Therefore, we consider the gene knockout cell line created by CRISPR/Cas9 to be a more useful tool for identifying the function of a gene.