BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To ...BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To investigate the expression and function of UCP1 in gastric cancer(GC).METHODS UCP1 protein expression in 211 GC tissues was examined using immunohisto-chemistry.Bisulfite sequencing PCR(BSP)was used to detect the methylation status of the UCP1 promoter in GC cell lines and tissues.The relationship between UCP1 expression and clinicopathological parameters was analyzed.CCK8,scratch,transwell,and flow cytometry assays were carried out to analyze the proliferation,migration,invasion,and apoptosis of GC cell lines after knockdown or overexpression of UCP1 in vitro.A nude mouse tumor xenograft model was used to investigate the function of UCP1 in vivo.RNA sequencing,Kyoto Ency-clopedia of Genes and Genomes analysis,and Rap1 pull-down assays were performed to identify the pathway associated with UCP1.RESULTS Loss of UCP1 was significantly associated with gender,poor differentiation,and advanced TNM stage of GC.Hypermethylation of UCP1 was confirmed in GC cells and tumor tissues by BSP.Overexpression of UCP1 suppressed GC cell proliferation,migration,and invasion,and it promoted apoptosis in vitro.UCP1 overexpression also suppressed GC tumor growth in vivo.Moreover,overexpression of UCP1 in GC cells resulted in a significant decrease in active Rap1 protein levels,whereas downregulation of UCP1 markedly enhanced Rap1 activity.CONCLUSION UCP1 downregulation in GC through promoter hypermethylation is related to the progression of GC,indicating that UCP1 plays a role as a tumor suppressor in GC.It regulates Rap1 signaling and may be a potential therapeutic target in GC.展开更多
为更好地描述砂土力学行为的围压相关性,首先,分析总结了砂土基本力学特性随围压的变化规律:随围压的降低,砂土基本力学性质表现出更为强烈的围压依赖性,临界状态应力比由常量变为随围压敏感的变量,剪胀也由随围压平缓变化转变为急剧增...为更好地描述砂土力学行为的围压相关性,首先,分析总结了砂土基本力学特性随围压的变化规律:随围压的降低,砂土基本力学性质表现出更为强烈的围压依赖性,临界状态应力比由常量变为随围压敏感的变量,剪胀也由随围压平缓变化转变为急剧增加。随后,在黏土和砂土的统一硬化模型(unified hardening model for cloy and sand,CSUH模型)的理论框架下,引入了咬合应力参数以描述临界状态的强度特征;提出了非耦合塑性体应变的概念,从微观层面解释了低围压下强剪胀的机制,在分析围压对压剪耦合影响规律的基础上,构造了非耦合塑性体应变的表达式,继而建立了一个可细化描述围压效应的砂土统一硬化(unified hardening,UH)模型。相较于CSUH模型,考虑围压效应的UH模型仅增加了两个参数,且参数易于确定。最后,通过与试验数据、CSUH模型预测结果对比,验证了所建立模型的合理性及适用性。展开更多
基金Supported by the Nanjing Health Science and Technology Development Fund,No.YKK24223.
文摘BACKGROUND Uncoupling protein 1(UCP1)plays a pivotal role in modulating energy expen-diture and maintaining metabolic homeostasis within brown and beige adipo-cytes.It has also been implicated in tumorigenesis.AIM To investigate the expression and function of UCP1 in gastric cancer(GC).METHODS UCP1 protein expression in 211 GC tissues was examined using immunohisto-chemistry.Bisulfite sequencing PCR(BSP)was used to detect the methylation status of the UCP1 promoter in GC cell lines and tissues.The relationship between UCP1 expression and clinicopathological parameters was analyzed.CCK8,scratch,transwell,and flow cytometry assays were carried out to analyze the proliferation,migration,invasion,and apoptosis of GC cell lines after knockdown or overexpression of UCP1 in vitro.A nude mouse tumor xenograft model was used to investigate the function of UCP1 in vivo.RNA sequencing,Kyoto Ency-clopedia of Genes and Genomes analysis,and Rap1 pull-down assays were performed to identify the pathway associated with UCP1.RESULTS Loss of UCP1 was significantly associated with gender,poor differentiation,and advanced TNM stage of GC.Hypermethylation of UCP1 was confirmed in GC cells and tumor tissues by BSP.Overexpression of UCP1 suppressed GC cell proliferation,migration,and invasion,and it promoted apoptosis in vitro.UCP1 overexpression also suppressed GC tumor growth in vivo.Moreover,overexpression of UCP1 in GC cells resulted in a significant decrease in active Rap1 protein levels,whereas downregulation of UCP1 markedly enhanced Rap1 activity.CONCLUSION UCP1 downregulation in GC through promoter hypermethylation is related to the progression of GC,indicating that UCP1 plays a role as a tumor suppressor in GC.It regulates Rap1 signaling and may be a potential therapeutic target in GC.
文摘为更好地描述砂土力学行为的围压相关性,首先,分析总结了砂土基本力学特性随围压的变化规律:随围压的降低,砂土基本力学性质表现出更为强烈的围压依赖性,临界状态应力比由常量变为随围压敏感的变量,剪胀也由随围压平缓变化转变为急剧增加。随后,在黏土和砂土的统一硬化模型(unified hardening model for cloy and sand,CSUH模型)的理论框架下,引入了咬合应力参数以描述临界状态的强度特征;提出了非耦合塑性体应变的概念,从微观层面解释了低围压下强剪胀的机制,在分析围压对压剪耦合影响规律的基础上,构造了非耦合塑性体应变的表达式,继而建立了一个可细化描述围压效应的砂土统一硬化(unified hardening,UH)模型。相较于CSUH模型,考虑围压效应的UH模型仅增加了两个参数,且参数易于确定。最后,通过与试验数据、CSUH模型预测结果对比,验证了所建立模型的合理性及适用性。
