BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。展开更多
Objective:To observe the therapeutic effect of high-flux hemodialysis on patients with end-stage renal disease,and to evaluate cardiac function and interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(T...Objective:To observe the therapeutic effect of high-flux hemodialysis on patients with end-stage renal disease,and to evaluate cardiac function and interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(TNF).-αeffects such as cytokine levels.Methods:Eighty patients with end-stage renal disease who underwent hemodialysis in the Department of Nephrology,Wuyi Hospital of Jiangmen City from June 2016 to June 2018 were enrolled.According to their dialysis methods,they were divided into high-flux dialysis group(40 cases).Low-throughput dialysis group(40 cases).The differences of cardiac function,renal function and IL-6,IL-8 and TNF-αlevels between the two groups before and after dialysis were observed.Results:After treatment,LAD,RAD and LVEF in both groups were lower than those before treatment,and LVEF in high throughput dialysis group was lower than that in low throughput dialysis group(t=9.191,6.559,P<0.01).After treatment,SBP,DBP,24hSBP SD and 24hDBP SD in both groups were lower than those before treatment,and those in high throughput dialysis group were lower than those in low flux dialysis group(t=6.217,10.611,12.082,6.564,P<0.01).There was no difference in cytokine levels between the two groups before treatment.After treatment,I of the two groups of patients was not different from that of the two groups.The levels of IL 6 and TNF-αin high throughput dialysis group were lower than those before treatment,and the levels of IL 6 and GFRαin high throughput dialysis group were lower than those in low flux dialysis group(t=14.245、4.595、6.458,P<0.01).After treatment,BUN,SCr and GFR in high throughput dialysis group were higher than those before treatment,and those in high throughput dialysis group were lower than those in low flux dialysis group(t=7.805,12.819,P<0.01).Conclusion:High-flux hemodialysis has a better therapeutic effect on patients with end-stage renal disease,which can significantly improve the heart function of patients and reduce the levels of IL-6 and other cytokines.It has good application value.展开更多
Wearable biopotential sensing devices are essential to long-term and real-time monitoring of human health.Non-contact,capacitive sensing electrodes prevent potential skin iritations,and are thus beneficial for long-te...Wearable biopotential sensing devices are essential to long-term and real-time monitoring of human health.Non-contact,capacitive sensing electrodes prevent potential skin iritations,and are thus beneficial for long-term monitoring.Existing capacitive electrodes are either connected to a separate control circuit via external wires or have limited sensing capacitances,which leads to low signal qualities.This study demonstrates a stretchable capacitive sensing device with integrated electrodes and control electronics,with enhanced signal qualities.The electrodes and the control electronics are fabricated on a common fabric substrate for breathability and strain-limiting protection.The stretchable electrodes are based on an island-bridge design with a stretchability as high as-100%,and an area ratio as high as-80%.By using a dielectric calcium copper titanate(CCTO)composite as the adhesive layer,the electrode capacitance can be increased,yielding an enhanced signal-to-noise ratio(SNR)in the acquired biopotentials.This device offers a convenient and comfortable approach for long-term non-contact monitoring of biopotential signals.展开更多
基金the National Natural Science Foundation of China,No.82070869 and 82270914.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。
基金Science and technology planning project of Jiangmen city, Guangdong province (2016-100-8)
文摘Objective:To observe the therapeutic effect of high-flux hemodialysis on patients with end-stage renal disease,and to evaluate cardiac function and interleukin-6(IL-6),interleukin-8(IL-8)and tumor necrosis factor-α(TNF).-αeffects such as cytokine levels.Methods:Eighty patients with end-stage renal disease who underwent hemodialysis in the Department of Nephrology,Wuyi Hospital of Jiangmen City from June 2016 to June 2018 were enrolled.According to their dialysis methods,they were divided into high-flux dialysis group(40 cases).Low-throughput dialysis group(40 cases).The differences of cardiac function,renal function and IL-6,IL-8 and TNF-αlevels between the two groups before and after dialysis were observed.Results:After treatment,LAD,RAD and LVEF in both groups were lower than those before treatment,and LVEF in high throughput dialysis group was lower than that in low throughput dialysis group(t=9.191,6.559,P<0.01).After treatment,SBP,DBP,24hSBP SD and 24hDBP SD in both groups were lower than those before treatment,and those in high throughput dialysis group were lower than those in low flux dialysis group(t=6.217,10.611,12.082,6.564,P<0.01).There was no difference in cytokine levels between the two groups before treatment.After treatment,I of the two groups of patients was not different from that of the two groups.The levels of IL 6 and TNF-αin high throughput dialysis group were lower than those before treatment,and the levels of IL 6 and GFRαin high throughput dialysis group were lower than those in low flux dialysis group(t=14.245、4.595、6.458,P<0.01).After treatment,BUN,SCr and GFR in high throughput dialysis group were higher than those before treatment,and those in high throughput dialysis group were lower than those in low flux dialysis group(t=7.805,12.819,P<0.01).Conclusion:High-flux hemodialysis has a better therapeutic effect on patients with end-stage renal disease,which can significantly improve the heart function of patients and reduce the levels of IL-6 and other cytokines.It has good application value.
基金research sponsored by Air Force Research Laboratory under agreement number FA8650-18-2-5402.
文摘Wearable biopotential sensing devices are essential to long-term and real-time monitoring of human health.Non-contact,capacitive sensing electrodes prevent potential skin iritations,and are thus beneficial for long-term monitoring.Existing capacitive electrodes are either connected to a separate control circuit via external wires or have limited sensing capacitances,which leads to low signal qualities.This study demonstrates a stretchable capacitive sensing device with integrated electrodes and control electronics,with enhanced signal qualities.The electrodes and the control electronics are fabricated on a common fabric substrate for breathability and strain-limiting protection.The stretchable electrodes are based on an island-bridge design with a stretchability as high as-100%,and an area ratio as high as-80%.By using a dielectric calcium copper titanate(CCTO)composite as the adhesive layer,the electrode capacitance can be increased,yielding an enhanced signal-to-noise ratio(SNR)in the acquired biopotentials.This device offers a convenient and comfortable approach for long-term non-contact monitoring of biopotential signals.
