Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal ...Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal medicine for the treatment of liver diseases.In the current study,we aim to systemically evaluate the therapeutic effects of saikosaponin A(SSa)and saikosaponin D(SSd),the major bioactive monomers in RB,against NAFLD and to investigate the underlying mechanisms.Our results demonstrated that both SSa and SSd improved diet-induced NAFLD.Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes,like Lipe and Lipg.SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1 a expression.Bioinformatic analysis further predicted the implication of master transcription factors,including peroxisome proliferator-activated receptor alpha(PPARα),in the protective effects of SSa and SSd.These results were further confirmed in vitro in mouse primary hepatocytes.In summary,our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins(SSs),and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.展开更多
Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and proces...Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and process factors during interval operations and can accumulate over multiple intervals.The aim is to enhance the robustness of high-speed rail station arrival and departure track utilization schemes.Design/methodologylapproach-To achieve this objective,the paper simulates actual train operations,incorporating the fluctuations in interval operation times into the utilization of arrival and departure tracks at the station.The Monte Carlo simulation method is adopted to solve this problem.This approach transforms a nonlinear model,which includes constraints from probability distribution functions and is difficult to solve directly,into a linear programming model that is easier to handle.The method then linearly weights two objectives to optimize the solution.Findings-Through the application of Monte Carlo simulation,the study successfully converts the complex nonlinear model with probability distribution function constraints into a manageable linear programming model.By continuously adjusting the weighting coefficients of the linear objectives,the method is able to optimize the Pareto solution.Notably,this approach does not require extensive scene data to obtain a satisfactory Pareto solution set.Originality/value-The paper contributes to the field by introducing a novel method for optimizing high-speed rail station arrival and departure track utilization in the presence of fluctuations in interval operation times.The use of Monte Carlo simulation to transform the problem into a tractable linear programming model represents a significant advancement.Furthermore,the method's ability to produce satisfactory Pareto solutions without relying on extensive data sets adds to its practical value and applicability in real-world scenarios.展开更多
Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoh...Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.展开更多
目的:对罗德岛大学嗓音依从性评估量表(the university of Rhode Island change assessment of voice,URICA-Voice)英文版进行汉化,并对中文版量表进行信度和效度检验。方法:对URICA-Voice英文量表进行直译、文化调试、专家咨询、预调...目的:对罗德岛大学嗓音依从性评估量表(the university of Rhode Island change assessment of voice,URICA-Voice)英文版进行汉化,并对中文版量表进行信度和效度检验。方法:对URICA-Voice英文量表进行直译、文化调试、专家咨询、预调查、回译等汉化过程后形成中文版URICA-Voice量表。采用便利抽样选取2022年2月-2022年5月在中山大学孙逸仙纪念医院、河南中医药大学第一附属医院、佛山市第一人民医院、广东省中医院言语治疗中心的嗓音治疗患者为调查对象并发放该量表问卷,回收后进行信效度检验。通过克朗巴赫ɑ(Cronbachɑ)系数评价量表信度;采用临界比值法和题总Pearson相关系数进行项目分析;运用条目水平的内容效度(item-level content validity index,I-CVI)、量表水平的内容效度(scale-level content validity index,S-CVI)和验证性因子分析进行量表效度检验。结果:共收回247份有效问卷。(1)项目分析:32个条目的高低分组临界比均>3.00,差异均有统计学意义(P<0.01);所有条目与总分的Pearson相关均达到显著(P<0.01)。(2)效度分析:量表的I-CVI=1.00,S-CVI/Ave=1.00;χ^(2)/df=2.30,RMSEA=0.07。除条目9和23外,其余各条目标准化因子载荷系数均>0.50,量表4个维度的AVE均>0.50,组合信度均>0.70,各维度与其他维度的相关系数均小于该维度的AVE平方根。(3)信度分析:量表总体Cronbachɑ系数=0.94,量表4个维度的Cronbachɑ系数分别为0.88、0.92、0.94、0.88。结论:URICA-Voice中文版量表具有良好的信度和效度,可作为国内嗓音训练依从性评估的特异性测量工具。展开更多
The high-voltage battery has now become a goal in order to meet the demands for high energy density.However,the severe side reactions between Li metal and carbonate-based electrolytes in this system result in unstable...The high-voltage battery has now become a goal in order to meet the demands for high energy density.However,the severe side reactions between Li metal and carbonate-based electrolytes in this system result in unstable interphase,leading to non-uniform Li-ion flux and thus aggravating the dendrite growth of Li.The protect interphase,traditional solid electrolyte interface(SEI),is a loose solid layer consisted of many components,which generally does not possess the function of preventing the lithium budding.Herein,based on polysulfide solubility in ester,we proposed a strategy to eliminate the dendrite by constructing a unique SEI in which the dynamic polysulfides were in situ formed and encapsuled.For this purpose,a 2-fluorophenylsulfur pentafluoride(2-FSPF)was employed as an additive in carbonate-based electrolyte that can be decomposed electrochemically during battery operation to form such a polysulfide-rich interphase.These polysulfides with certain fluidity can adhere to dynamically the budding tip of Li metal,as a so-called tip-inhibitor,when the local current density of the tip rising,thus to hinder Li^(+)diffusion toward the tip,resulting in inhibiting the further growth of Li dendrites and leveling the Li deposition.At the current density of 1 mA cm^(-2),the average Coulombic efficiency of Li//Cu cells is as high as 98.39%during 600 cycles,and the stable cycling of Li//Li symmetric cell reaches 3500 h.Furthermore,due to the high anodic stability,the Li//high-voltage LiCoO_(2)(LCO)full cells and Li–O_(2)battery achieve excellent cycle performance with lean electrolyte.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81773997 and 81073148 to Rong SunNo.82004029 to Runping Liu+3 种基金No.82004045 to Xiaojiaoyang Li)Beijing University of Chinese Medicine(No.2020-JYB-ZDGG-038 to Runping Liu,China)supported by grants from Beijing Nova Program of Science&Technology(Nos.Z201100006820025 and Z191100001119088,China)supported by research fund‘Traditional Chinese medicine pharmacology and toxicology expert(No.ts201511107)’from the Taishan Scholar Project of Shandong Province(China)。
文摘Nonalcoholic fatty liver disease(NAFLD)has become one of the most prominent causes of chronic liver diseases and malignancies.However,few therapy has been approved.Radix Bupleuri(RB)is the most frequently used herbal medicine for the treatment of liver diseases.In the current study,we aim to systemically evaluate the therapeutic effects of saikosaponin A(SSa)and saikosaponin D(SSd),the major bioactive monomers in RB,against NAFLD and to investigate the underlying mechanisms.Our results demonstrated that both SSa and SSd improved diet-induced NAFLD.Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes,like Lipe and Lipg.SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1 a expression.Bioinformatic analysis further predicted the implication of master transcription factors,including peroxisome proliferator-activated receptor alpha(PPARα),in the protective effects of SSa and SSd.These results were further confirmed in vitro in mouse primary hepatocytes.In summary,our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins(SSs),and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.
文摘Purpose-The purpose of this paper is to eliminate the fluctuations in train arrival and departure times caused by skewed distributions in interval operation times.These fluctuations arise from random origin and process factors during interval operations and can accumulate over multiple intervals.The aim is to enhance the robustness of high-speed rail station arrival and departure track utilization schemes.Design/methodologylapproach-To achieve this objective,the paper simulates actual train operations,incorporating the fluctuations in interval operation times into the utilization of arrival and departure tracks at the station.The Monte Carlo simulation method is adopted to solve this problem.This approach transforms a nonlinear model,which includes constraints from probability distribution functions and is difficult to solve directly,into a linear programming model that is easier to handle.The method then linearly weights two objectives to optimize the solution.Findings-Through the application of Monte Carlo simulation,the study successfully converts the complex nonlinear model with probability distribution function constraints into a manageable linear programming model.By continuously adjusting the weighting coefficients of the linear objectives,the method is able to optimize the Pareto solution.Notably,this approach does not require extensive scene data to obtain a satisfactory Pareto solution set.Originality/value-The paper contributes to the field by introducing a novel method for optimizing high-speed rail station arrival and departure track utilization in the presence of fluctuations in interval operation times.The use of Monte Carlo simulation to transform the problem into a tractable linear programming model represents a significant advancement.Furthermore,the method's ability to produce satisfactory Pareto solutions without relying on extensive data sets adds to its practical value and applicability in real-world scenarios.
基金supported by projects of the National Natural Science Foundation of China(61425025)the Beijing Municipal Science and Technology Project(Z151100000915070 and Z171100000117008)。
基金supported by the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(Grant No.2022YFC3502104,China)supports from VA Merit Award 5 I01 BX005730+2 种基金National Institutes of Health Grant R01 R01DK-057543 to Huiping Zhou(USA)National High-Level Talents Special Support Program to Xiaojiaoyang Li(China)Fundamental Research Funds for the Central Universities(Grant No.2023-JYBJBZD-046 to Xiaojiaoyang Li,China)。
文摘Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.
文摘目的:对罗德岛大学嗓音依从性评估量表(the university of Rhode Island change assessment of voice,URICA-Voice)英文版进行汉化,并对中文版量表进行信度和效度检验。方法:对URICA-Voice英文量表进行直译、文化调试、专家咨询、预调查、回译等汉化过程后形成中文版URICA-Voice量表。采用便利抽样选取2022年2月-2022年5月在中山大学孙逸仙纪念医院、河南中医药大学第一附属医院、佛山市第一人民医院、广东省中医院言语治疗中心的嗓音治疗患者为调查对象并发放该量表问卷,回收后进行信效度检验。通过克朗巴赫ɑ(Cronbachɑ)系数评价量表信度;采用临界比值法和题总Pearson相关系数进行项目分析;运用条目水平的内容效度(item-level content validity index,I-CVI)、量表水平的内容效度(scale-level content validity index,S-CVI)和验证性因子分析进行量表效度检验。结果:共收回247份有效问卷。(1)项目分析:32个条目的高低分组临界比均>3.00,差异均有统计学意义(P<0.01);所有条目与总分的Pearson相关均达到显著(P<0.01)。(2)效度分析:量表的I-CVI=1.00,S-CVI/Ave=1.00;χ^(2)/df=2.30,RMSEA=0.07。除条目9和23外,其余各条目标准化因子载荷系数均>0.50,量表4个维度的AVE均>0.50,组合信度均>0.70,各维度与其他维度的相关系数均小于该维度的AVE平方根。(3)信度分析:量表总体Cronbachɑ系数=0.94,量表4个维度的Cronbachɑ系数分别为0.88、0.92、0.94、0.88。结论:URICA-Voice中文版量表具有良好的信度和效度,可作为国内嗓音训练依从性评估的特异性测量工具。
基金financial support from the NSFC projects(U1805254,21773192,22072117,and 22179112)
文摘The high-voltage battery has now become a goal in order to meet the demands for high energy density.However,the severe side reactions between Li metal and carbonate-based electrolytes in this system result in unstable interphase,leading to non-uniform Li-ion flux and thus aggravating the dendrite growth of Li.The protect interphase,traditional solid electrolyte interface(SEI),is a loose solid layer consisted of many components,which generally does not possess the function of preventing the lithium budding.Herein,based on polysulfide solubility in ester,we proposed a strategy to eliminate the dendrite by constructing a unique SEI in which the dynamic polysulfides were in situ formed and encapsuled.For this purpose,a 2-fluorophenylsulfur pentafluoride(2-FSPF)was employed as an additive in carbonate-based electrolyte that can be decomposed electrochemically during battery operation to form such a polysulfide-rich interphase.These polysulfides with certain fluidity can adhere to dynamically the budding tip of Li metal,as a so-called tip-inhibitor,when the local current density of the tip rising,thus to hinder Li^(+)diffusion toward the tip,resulting in inhibiting the further growth of Li dendrites and leveling the Li deposition.At the current density of 1 mA cm^(-2),the average Coulombic efficiency of Li//Cu cells is as high as 98.39%during 600 cycles,and the stable cycling of Li//Li symmetric cell reaches 3500 h.Furthermore,due to the high anodic stability,the Li//high-voltage LiCoO_(2)(LCO)full cells and Li–O_(2)battery achieve excellent cycle performance with lean electrolyte.
