为提高热轧态0Cr21A16合金板材的组织均匀性和塑性,以改善其高温性能及冷加工特性,分析研究了不同温度的热处理试验及组织性能。采用光学显微镜、X射线衍射仪、Gleeble高温热拉伸实验、扫描电镜和纳米压痕仪等研究了热处理前后0Cr21Al6...为提高热轧态0Cr21A16合金板材的组织均匀性和塑性,以改善其高温性能及冷加工特性,分析研究了不同温度的热处理试验及组织性能。采用光学显微镜、X射线衍射仪、Gleeble高温热拉伸实验、扫描电镜和纳米压痕仪等研究了热处理前后0Cr21Al6合金板材的显微组织和力学性能。结果表明,通过热处理的方式改善0Cr21Al6合金板材的组织均匀性,在960℃保温6 min 40 s后快速冷却,晶粒平均尺寸为42μm,整体的晶粒尺寸相对于940、980、1000、1020℃热处理后较为均匀、细小,硬度和塑性达到最佳匹配,断裂韧度KIC在960℃处理下达到最佳,拥有最佳的综合性能,可有效避免生产过程中材料的脆性断裂问题。另外Gleeble实验显示1000℃以上的热处理温度不再适合于热加工。展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid drople...Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.展开更多
Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding...Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.展开更多
Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and s...Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.展开更多
Objective Overweight and obesity prevalence has increased in low-income countries.This study systematically reviewed the obesity trend,disparities,and prevention and control efforts in Nepal.Methods We searched PubMed...Objective Overweight and obesity prevalence has increased in low-income countries.This study systematically reviewed the obesity trend,disparities,and prevention and control efforts in Nepal.Methods We searched PubMed and Google Scholar for articles and reports published between January 1,2004 and December 31,2022.Additional information on National policies and programs related to obesity prevention was retrieved from governmental websites and consultation with relevant experts.Overweight and obesity were defined using the World Health Organization body mass index cut points.Thirty-two studies and reports were included.Results Overall,overweight and obesity rates increased in all groups in Nepal although nationally representative data remained limited.The combined overweight and obesity(OW/OB)and obesity rates in women aged 15-49 years increased from 8.5%to 22.2%and from 0.9%to 5.1%between 2006 and 2016,respectively.OW/OB and obesity rates in men were 17.1%and 2.5%based on data from the 2016 Demographic and Health Survey.OW/OB rate in under-five children increased from 0.6%to 2.8%between 2006 and 2016.Obesity rates for school-age(5-9 years)boys and girls in 2016 were 2.4%and 2.8%,respectively,and were 1.1%and 1.4%for male and female adolescents aged 10-19 years,respectively.OW/OB prevalence was much higher among women,residents in urban areas and central provinces,and in higher socioeconomic status groups.Projected prevalence of OW/OB and obesity for 2030 in adults aged 15-49 was 44.7%and 8.3%,respectively,while it was 2.2%for OW/OB in preschool children.Policies and direct interventions that specifically focused on obesity prevention and control are limited.Conclusions OW/OB prevalence in Nepal has increased during the past 1.8 decades,disproportionately affecting population groups.Existing interventions mostly focused on undernutrition with some indirect implications for obesity prevention.In the future,Nepal needs to develop population-based programs for obesity prevention.展开更多
文摘为提高热轧态0Cr21A16合金板材的组织均匀性和塑性,以改善其高温性能及冷加工特性,分析研究了不同温度的热处理试验及组织性能。采用光学显微镜、X射线衍射仪、Gleeble高温热拉伸实验、扫描电镜和纳米压痕仪等研究了热处理前后0Cr21Al6合金板材的显微组织和力学性能。结果表明,通过热处理的方式改善0Cr21Al6合金板材的组织均匀性,在960℃保温6 min 40 s后快速冷却,晶粒平均尺寸为42μm,整体的晶粒尺寸相对于940、980、1000、1020℃热处理后较为均匀、细小,硬度和塑性达到最佳匹配,断裂韧度KIC在960℃处理下达到最佳,拥有最佳的综合性能,可有效避免生产过程中材料的脆性断裂问题。另外Gleeble实验显示1000℃以上的热处理温度不再适合于热加工。
基金Discipline Key Special ProjectGrant/Award Number:XKZDQY202001+7 种基金Henan Provincial Key R&D and Promotion Special ProjectGrant/Award Number:212102310033Henan Provincial Medical Science and Technology Tackling ProgramGrant/Award Number:LHGJ20220557Key R&D Program of ChinaGrant/Award Number:2020YFC2006100,2020YFC2009000 and 2020YFC2009006National Natural Science Foundation of ChinaGrant/Award Number:31471330 and 81870408。
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.
基金supported by Zhengzhou Major Collaborative Innovation Project(No.18XTZX12003)Key Projects of Discipline Construction in Zhengzhou University(No.XKZDJC202001)+1 种基金National Key Research and Development Program in China(No.2020YFC2006100)Medical Service Capacity Improvement Project of Henan Province in China(Grant Number Yu Wei Medicine[2017]No.66).
文摘Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.
基金supported by the Major Research Program of the National Natural Science Foundation of China(Subproject No.81991503)the Youth Research Program of the National Natural Science Foundation of China(No.82201069)+1 种基金the Innovative Talent Promotion Plan of Shaanxi Province-Research Fund for Young Star of Science and Technology(No.2021KJXX-24,No.2022KJXX-100)Basic and Applied Basic Research Fund of Guangdong Province(No.2023A1515012126).
文摘Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.
基金This study was funded by the research grants from the Key Research and Development Program of Shaanxi Province of China(2022SF-125 and 2021ZDLSF02-14).
文摘Objective Overweight and obesity prevalence has increased in low-income countries.This study systematically reviewed the obesity trend,disparities,and prevention and control efforts in Nepal.Methods We searched PubMed and Google Scholar for articles and reports published between January 1,2004 and December 31,2022.Additional information on National policies and programs related to obesity prevention was retrieved from governmental websites and consultation with relevant experts.Overweight and obesity were defined using the World Health Organization body mass index cut points.Thirty-two studies and reports were included.Results Overall,overweight and obesity rates increased in all groups in Nepal although nationally representative data remained limited.The combined overweight and obesity(OW/OB)and obesity rates in women aged 15-49 years increased from 8.5%to 22.2%and from 0.9%to 5.1%between 2006 and 2016,respectively.OW/OB and obesity rates in men were 17.1%and 2.5%based on data from the 2016 Demographic and Health Survey.OW/OB rate in under-five children increased from 0.6%to 2.8%between 2006 and 2016.Obesity rates for school-age(5-9 years)boys and girls in 2016 were 2.4%and 2.8%,respectively,and were 1.1%and 1.4%for male and female adolescents aged 10-19 years,respectively.OW/OB prevalence was much higher among women,residents in urban areas and central provinces,and in higher socioeconomic status groups.Projected prevalence of OW/OB and obesity for 2030 in adults aged 15-49 was 44.7%and 8.3%,respectively,while it was 2.2%for OW/OB in preschool children.Policies and direct interventions that specifically focused on obesity prevention and control are limited.Conclusions OW/OB prevalence in Nepal has increased during the past 1.8 decades,disproportionately affecting population groups.Existing interventions mostly focused on undernutrition with some indirect implications for obesity prevention.In the future,Nepal needs to develop population-based programs for obesity prevention.
