Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechani...Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC.Methods:HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status.Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A(SDHA)expression and M2 macrophage infiltration.SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments,including co-culturing,flow cytometry,and enzyme-linked immunosorbent assay.Western blotting assay,functional assays,and subcutaneous tumor model mice were used to elucidate the molecular mechanisms underlying succinate-mediated HCC cell-macrophage interactions in the TME.Results:Higher infiltration of M2 macrophages correlated with worse prognosis in HCC patients.SDHA was downregulated in HCC tumor tissues and showed a negative correlation with M2 macrophage infiltration.SDHA knockdown promoted M2 macrophage polarization,whereas SDHA overexpression reversed this effect.Mechanistically,SDHA deficiency in HCC cells induced succinate accumulation,which promoted M2 macrophage polarization by activating the G protein-coupled receptor 91(GPR91)/signal transducer and activator of transcription 3(STAT3)pathway.Concurrently,succinate stimulation enhanced mitochondrial oxidative phosphorylation in M2 macrophages,thereby promoting HCC progression.Serum succinate levels were elevated in HCC patients.The receiver operating characteristic curve analysis indicated that serum succinate is a promising diagnostic marker for HCC(area under the curve=0.815).Conclusion:SDHA deficiency leads to succinate accumulation,which promotes M2 macrophage polarization through the GPR91/STAT3 pathway,thereby facilitating HCC progression.Based on these findings,serum succinate could be a promising diagnostic biomarker for HCC.展开更多
在研究船舶动力定位系统的过程中,研制一款便携式人机界面——单手柄操作板,主要介绍其硬件电路板现场处理模块的软件及硬件的设计实现过程。采用AT91SAM9G45嵌入式微处理器作为硬件电路的核心,根据单手柄操作板的人机交互操作需求和系...在研究船舶动力定位系统的过程中,研制一款便携式人机界面——单手柄操作板,主要介绍其硬件电路板现场处理模块的软件及硬件的设计实现过程。采用AT91SAM9G45嵌入式微处理器作为硬件电路的核心,根据单手柄操作板的人机交互操作需求和系统通信需求扩展多种功能接口电路。为便于应用程序的二次开发,引入Windows CE 6.0嵌入式操作系统,开发各种接口驱动程序。研制的单手柄操作板具有JoyStick操纵杆、按钮、指示灯和旋转编码开关旋钮等操作接口,支持液晶显示屏图形化显示,其功能、性能和重量均能满足便携式、移动操作的要求。展开更多
基金supported by the Central Government-Guided Local Science and Technology Development Fund Project(Science and Technology Innovation Base Project)(Grant No.236Z7749G)Hebei Provincial Precision Medicine Innovation and Development Joint Fund Incubation Project(Grant No.H2025206547)Hebei Provincial Basic Research Special Youth Science Fund Project(Grant No.H2025206274).
文摘Background:Hepatocellular carcinoma(HCC)is an aggressive and lethal malignancy.Metabolic reprogramming dynamically remodels the tumor microenvironment(TME)and drives HCC progression.This study investigated the mechanism through which metabolic reprogramming remodels the TME in HCC.Methods:HCC patient transcriptome data were subjected to bioinformatics analysis to identify differentially expressed genes and immune infiltration status.Immunohistochemical analysis was performed to determine the correlation between succinate dehydrogenase complex subunit A(SDHA)expression and M2 macrophage infiltration.SDHA-knockdown or SDHA-overexpressing HCC cells were used for in vitro experiments,including co-culturing,flow cytometry,and enzyme-linked immunosorbent assay.Western blotting assay,functional assays,and subcutaneous tumor model mice were used to elucidate the molecular mechanisms underlying succinate-mediated HCC cell-macrophage interactions in the TME.Results:Higher infiltration of M2 macrophages correlated with worse prognosis in HCC patients.SDHA was downregulated in HCC tumor tissues and showed a negative correlation with M2 macrophage infiltration.SDHA knockdown promoted M2 macrophage polarization,whereas SDHA overexpression reversed this effect.Mechanistically,SDHA deficiency in HCC cells induced succinate accumulation,which promoted M2 macrophage polarization by activating the G protein-coupled receptor 91(GPR91)/signal transducer and activator of transcription 3(STAT3)pathway.Concurrently,succinate stimulation enhanced mitochondrial oxidative phosphorylation in M2 macrophages,thereby promoting HCC progression.Serum succinate levels were elevated in HCC patients.The receiver operating characteristic curve analysis indicated that serum succinate is a promising diagnostic marker for HCC(area under the curve=0.815).Conclusion:SDHA deficiency leads to succinate accumulation,which promotes M2 macrophage polarization through the GPR91/STAT3 pathway,thereby facilitating HCC progression.Based on these findings,serum succinate could be a promising diagnostic biomarker for HCC.
文摘在研究船舶动力定位系统的过程中,研制一款便携式人机界面——单手柄操作板,主要介绍其硬件电路板现场处理模块的软件及硬件的设计实现过程。采用AT91SAM9G45嵌入式微处理器作为硬件电路的核心,根据单手柄操作板的人机交互操作需求和系统通信需求扩展多种功能接口电路。为便于应用程序的二次开发,引入Windows CE 6.0嵌入式操作系统,开发各种接口驱动程序。研制的单手柄操作板具有JoyStick操纵杆、按钮、指示灯和旋转编码开关旋钮等操作接口,支持液晶显示屏图形化显示,其功能、性能和重量均能满足便携式、移动操作的要求。
