High Thermal Dissipation of Normally off p-GaN Gate AlGaN/GaN HEMTs on 6-Inch N-Doped Low-Resistivity SiC Substrate.

Efficient heat removal through the substrate is required in high-power operation of AlGaN/GaN high-electron-mobility transistors (HEMTs). Thus, a SiC substrate was used due to its popularity. This article reports the electrical characteristics of normally off p-GaN gate AlGaN/GaN high-electron-mobility transistors (HEMTs) on a low-resistivity SiC substrate compared with the traditional Si substrate. The p-GaN HEMTs on the SiC substrate possess several advantages, including electrical characteristics and good qualities of epitaxial crystals, especially on temperature performance. Additionally, the price of the low-resistivity SiC substrate is three times lower than the ordinary SiC substrate.

Pan-cancer analysis of CXCR4 carcinogenesis in human tumors.

BACKGROUND: C-X-C chemokine receptor 4 (CXCR4) is a specific receptor of stromal cell-derived factor-1, also known as CXCL12. The interaction between CXCL12 and its receptor CXCR4 can activate various signaling pathways, including gene expression, cell proliferation, migration, tumorigenesis, angiogenesis, etc. Although there is evidence to support the association between CXCR4 and some cancers, there is no pan-cancer analysis. To fill this gap, we analyzed the role of CXCR4 in cancer-based on The Cancer Genome Atlas (TCGA). METHODS: We used TCGA, Genotype-Tissue Expression (GTEx) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to analyze the expression, variation and phosphorylation of CXCR4 in different cancers. At the same time, we also carried out Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) enrichment analysis. RESULTS: We found that CXCR4 expression was significantly increased in bladder urothelial carcinoma (BLCA) and other cancers, and CXCR4 expression in BLCA, cervical squamous cell carcinoma (CESC) and other cancers was related to tumor stage. CXCR4 expression was positively correlated with tumor-associated fibroblasts in BLCA, breast adenocarcinoma (BRCA), CESC and other cancers. GO analysis showed that CXCR4-related genes were mainly enriched in biological processes (BPs) and cellular components (CCs). KEGG analysis showed that CXCR4 was mainly involved in "chemokine signaling pathway", "natural killer cell-mediated cytotoxicity", and "JAK-STAT signaling pathway". CONCLUSIONS: The expression of CXCR4 in different cancers has different effects on the prognosis of patients and the infiltration of immune cells.

[Prevalence of pediatric asthma in the rural areas of China: a Meta analysis].

OBJECTIVE: To systematically review the prevalence of pediatric asthma in the rural areas of China, and to provide data for the prevention and treatment of pediatric asthma. METHODS: PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang Database, and Embase were searched for cross-sectional studies on the prevalence of pediatric asthma in the rural areas of China published up to August 31, 2019. Two researchers independently conducted preliminary screening and data extraction. Stata 14.0 and R software were used to perform a Meta analysis of prevalence rate. Subgroup analysis was also performed. RESULTS: A total of 24 articles were reviewed, with a sample size of 212 814 children, among whom there were 3 254 children with asthma, with an overall prevalence rate of 2.02% (95%CI: 1.67%-2.36%). Boys had a significantly higher prevalence rate than girls (3.64% vs 2.03%, P<0.001). The annual prevalence rate increased from 1.21% in 1990-1999 to 3.36% in 2011-2015. The prevalence rate of pediatric asthma was 3.15% in South China, which was higher than that in East China (2.31%), Southwest China (2.15%), North China (1.19%), and Central China (1.12%). Preschool children had the highest prevalence rate of 2.63%, followed by infants and young children (2.48%) and school-age children (1.41%). CONCLUSIONS: The prevalence rate of pediatric asthma is relatively low but tends to increase in the rural areas of China. Boys have a higher prevalence rate of asthma than girls, and the prevalence rate is higher in South China. Preschool children have the highest prevalence rate.

Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats.

AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis. METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs. RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization. CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.

Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats.

AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved. METHODS: Sophocarpine was injected intraperitoneally in two distinct rat hepatic fibrosis models induced either by dimethylnitrosamine or bile duct ligation. Masson's trichrome staining, Sirius red staining and hepatic hydroxyproline level were used for collagen determination. Primary hepatic stellate cells (HSCs) were isolated and treated with different concentrations of sophocarpine. Real-time reverse transcription-polymerase chain reaction was used to detect the mRNA levels of fibrotic markers and cytokines. The expression of pathway proteins was measured by Western blot. The Cell Counting Kit-8 test was used to detect the proliferation rate of activated HSCs treated with a gradient concentration of sophocarpine. RESULTS: Sophocarpine decreased serum levels of aminotransferases and total bilirubin in rats under chronic insult. Moreover, administration of sophocarpine suppressed extracellular matrix deposition and prevented the development of hepatic fibrosis. Furthermore, sophocarpine inhibited the expression of α-smooth muscle actin (SMA), interleukin (IL)-6, transforming growth factor-ß1 (TGF-ß1), Toll-like receptor 4 (TLR4), and extracellular-related kinase (ERK) in rats. Sophocarpine also down-regulated the mRNA expression of α-SMA, collagen I, collagen III, TGF-ß1, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1, and decreased protein levels of TLR4, p-ERK, p-JNK, p-P38 and p-IKK in vitro after Lipopolysaccharide induction. In addition, sophocarpine inhibited the proliferation of HSCs accompanied by a decrease in the expression of Cyclin D1. The protein level of proliferating cell nuclear antigen was decreased in activated HSCs following a gradient concentration of sophocarpine. CONCLUSION: Sophocarpine can alleviate liver fibrosis mainly by inhibiting the TLR4 pathway. Sophocarpine may be a potential chemotherapeutic agent for chronic liver diseases.

Suppression of CB1 cannabinoid receptor by lentivirus mediated small interfering RNA ameliorates hepatic fibrosis in rats.

It is recognized that endogenous cannabinoids, which signal through CB1 receptors in hepatic stellate cells (HSCs), exert a profibrotic effect on chronic liver diseases. In this study, we suppressed CB1 expression by lentivirus mediated small interfering RNA (CB1-RNAi-LV) and investigated its effect on hepatic fibrosis in vitro and in vivo. Our results demonstrated that CB1-RNAi-LV significantly inhibited CB1 expression, and suppressed proliferation and extracellular matrix production in HSCs. Furthermore, CB1-RNAi-LV ameliorated dimethylnitrosamine induced hepatic fibrosis markedly, which was associated with the decreased expression of mesenchymal cell markers smooth muscle α-actin, vimentin and snail, and the increased expression of epithelial cell marker E-cadherin. The mechanism lies on the blockage of Smad signaling transduction induced by transforming growth factor ß1 and its receptor TGF-ß RII. Our study firstly provides the evidence that CB1-RNAi-LV might ameliorate hepatic fibrosis through the reversal of epithelial-to-mesenchymal transition (EMT), while the CB1 antagonists AM251 had no effect on epithelial-mesenchymal transitions of HSCs. This suggests that CB1 is implicated in hepatic fibrosis and selective suppression of CB1 by small interfering RNA may present a powerful tool for hepatic fibrosis treatment.

Sophocarpine alleviates non-alcoholic steatohepatitis in rats.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is one entity in the spectrum of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to explore the prevention and therapeutic effect of sophocarpine on experimental rat NASH. METHODS: Sophocarpine with the dosage of 20 mg/kg/day was injected into NASH rats. At the end of 12 weeks, all rats were killed to detect the degree of fatty degeneration, inflammation and fibrosis. RESULTS: Sophocarpine intervention (in the pro-treated and treated groups) resulted in a significant decrease of liver weight, liver index, serum transaminase and serum lipids. Messenger RNA expressions of leptin, interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, procollagen-I and α-smooth muscle actin (SMA) and deposition of IL-6, TNF-α and TGF-ß1 in liver decreased, whereas the messenger RNA expression of adiponectin increased significantly compared with that in the model group. Moreover, histological improvement was also observed in the sophocarpine intervention group. In addition, there was no significant difference in any detected indicator between the pro-treated and treated group. CONCLUSIONS: Sophocarpine could decrease the level of serum transaminase, improve lipid metabolism, reduce synthesis of inflammatory cytokines TNF-α, TGF-ß1 and IL-6, activate protective adipocytokine adiponectin, and might be selected as a promising agent for the clinical prevention and therapy of NASH.

RNA interference targeting the platelet-derived growth factor receptor beta subunit ameliorates experimental hepatic fibrosis in rats.

BACKGROUND/AIMS: Platelet-derived growth factor (PDGF) is the strongest stimulator of the proliferation of hepatic stellate cells (HSCs). PDGF receptor beta subunit (PDGFR-beta) is acquired on HSCs proliferation induced by PDGF. In this study, we aim to investigate the effect of PDGFR-beta small interference RNA (siRNA) on experimental hepatic fibrosis. METHODS: We constructed a PDGFR-beta siRNA expression plasmid and investigated its effect on the activation of HSCs. Bromodeoxyuridine incorporation was performed to investigate the effect of PDGFR-beta siRNA on HSCs proliferation. A hydrodynamics-based transfection method was used to deliver PDGFR-beta siRNA to rats with hepatic fibrosis. The distribution of transgenes in the liver was observed by immunofluorescence. The antifibrogenic effect of PDGFR-beta siRNA was investigated pathologically. RESULTS: Platelet-derived growth factor receptor-beta subunit siRNA could significantly downregulate PDGFR-beta expression, suppress HSCs activation, block the mitogen-activated protein kinase signalling pathway and inhibit HSCs proliferation in vitro. PDGFR-beta siRNA expression plasmid could be delivered into activated HSCs by the hydrodynamics-based transfection method, and remarkably improve the liver function of the rat model induced by dimethylnitrosamine and bile duct ligation. Furthermore, the progression of fibrosis in the liver was significantly suppressed by PDGFR-beta siRNA in both animal models. CONCLUSIONS: Platelet-derived growth factor receptor-beta subunit siRNA may be presented as an effective antifibrogenic gene therapeutic method for hepatic fibrosis.

The restorative effect of taurine on experimental nonalcoholic steatohepatitis.

Our objective was to explore the restorative effect of taurine on experimental nonalcoholic steatohepatitis (NASH). Thirty-six SD rats were randomly divided into three groups, 12 in each group: the normal group was fed standard rat diet; the model group and the treatment group were both fed a high-fat rat diet for 12 weeks, and the rats in the treatment group were simultaneously injected with taurine subcutaneously for 8 weeks. Hepatic histological change was observed; TNF-alpha and TGF-beta(1) protein expression was identified by immunohistochemistry; mRNA expression of TNF-alpha, TGF-beta(1), type I procollagen, and adiponectin was measured by RT-PCR; body weight, weight gain, liver weight, and liver index were measured; and biochemical parameters monitored included serum transaminases, serum lipids, fasting plasma glucose, and hepatic level of oxidative stress. Rats in the model group showed a significant increase in liver weight, liver index, serum transaminase activities, serum triglyceride, fasting plasma glucose, and oxidative stress; the mRNA expression of TNF-alpha, TGF-beta(1), and type I procollagen increased, whereas the expression of adiponectin decreased significantly, compared with that in the normal group. The typical hepatic lesions of NASH were observed histologically in the model group. Taurine treatment resulted in a significant decrease in liver weight, liver index, serum transaminase activities, serum triglyceride, fasting plasma glucose, and oxidative stress; the mRNA expression of TNF-alpha, TGF-beta(1), and type I procollagen decreased, but the expression of adiponectin increased significantly, compared with that in the model group. Histological improvement was observed in the treatment group. In conclusion, taurine could inhibit lipid peroxidation, improve lipid and glucose metabolism, decrease synthesis of TNF-alpha and TGF-beta(1), promote synthesis of adiponectin, and have a restorative effect on experimental NASH.

[Effect of qingfei oral liquid on protein expression of transforming growth factor-beta1 and platelet derived growth factor-BB of adenovirus type 3I, 7b induced human embryonic lung fibroblast cells].

OBJECTIVE: To explore the effect of qingfei oral liquid (QOL) contained serum on protein expression of transforming growth factor-beta1 (TGF-beta1) and platelet derived growth factor-BB (PDGF-BB) of adenovirus type 3I, 7b induced human embryonic lung fibroblast cells. METHODS: The cells were divided into 5 groups, the normal cells group (NCG), the virus control group (VCG), the blank serum group (BSG), the ribavirin group (RVG) and the QOL contained serum group (QSG). All the cells except those in the NCG were challenged by adenovirus type 3I, 7b and treated with correspondent medicine. The contents of TGF-beta1 and PDGF-BB in the supernatant of cell culture were monitored by ELISA and compared among groups. RESULTS: Contents of TGF-beta1 and PDGF-BB in VCG were significantly higher, while those in QSG were significantly lower than those in VCG (P < 0.01). CONCLUSION: Adenovirus infection can increase the protein expression of TGF-beta1 and PDGF-BB of human embryonic lung fibroblast cells. QOL can decrease the protein expression of these cytokines, which maybe one of the mechanisms of its antiviral effect.

[Inhibition of proliferation of hepatic stellate cells by taurine is mediated via regulating cell cycle proteins].

OBJECTIVE: To explore the possible mechanism(s) of taurine-inhibiting the proliferation of hepatic stellate cells (HSC), this study investigated the effect of taurine on the HSC cell cycle and its regulatory protein expression. METHODS: Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry. Cell cycle regulatory protein Cyclin D1 and P21waf1 expression were determined by immunocytochemistry and image-analysis system, and real-time quantitative PCR. RESULTS: HSC proliferation was markedly inhibited when HSC were treated with taurine at concentrations of 5, 10, 20, 30, 40 and 50 mmol/L for 48 hours, and the inhibition rates were 6.7%, 14.4%, 23.3%, 32.2%, 36.7% and 45.6% respectively (P < 0.05-0.01). In the flow cytometry analysis, it was found that taurine could block HSC in the G0/G1 phase from entering the S phase, resulting in more cells in the G0/G1 phase and fewer in the S phase. The percentage of the cells in the G0/G1 phase and the S phase at the dosage of 40 mmol/L were 68.2%+/-1.4% and 26.2+/-1.3% respectively, which was significantly different in comparison to the controls (56.2%+/-1.7% and 38.5%+/-0.8% respectively, P < 0.01). HSC expressed cyclin D1 and P21waf1. Taurine inhibited cyclin D1 expression and induced P21waf1 expression. The cyclin D1 protein and mRNA in the HSC treated with 40 mmol/L taurine were significantly reduced compared with the controls [protein (optical density value): 0.13+/-0.02 versus 0.18+/-0.02, P < 0.01; mRNA: 5776.7+/-3345.0 versus 18,400.6+/-1374.8 copies/10(6) GAPDH, P < 0.01]; and the P21waf1 protein and mRNA were markedly increased compared with the controls [protein (optical density value): 0.19+/-0.02 versus 0.14+/-0.01, P < 0.01; mRNA: 44,866.7+/-3910.7 versus 16,933.3+/-960.9 copies/10(6) GAPDH, P less than 0.05]. CONCLUSIONS: Cyclin D1 and P21waf1 were cell cycle regulatory proteins in HSC, and taurine can inhibit the HSC cyclin D1 expression and stimulate P21waf1 expression, facilitate arresting cells in G0/G1 phase, and suppress cell proliferation.