Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
Filtering capacitor with compact configuration and a wide range of operating voltage has been attracting increasing attention for the smooth conversion of the electric signal in modern circuits.Lossless integration of...Filtering capacitor with compact configuration and a wide range of operating voltage has been attracting increasing attention for the smooth conversion of the electric signal in modern circuits.Lossless integration of capacitor units can be regarded as one of the efficient ways to achieve a wider voltage range,which has not yet been fully conquered due to the lack of rational designs of the electrode structure and integration technology.This study presents an alternatingly stacked assemble technology to conveniently fabricate compact aqueous hybrid integrated filtering capacitors on a large scale,in which a unit consists of rGO/MXene composite film as a negative electrode and PEDOT:PSS based film as a positive electrode.Benefiting from the synergistic effect of rGO and MXene components,and morphological characteristics of PEDOT:PSS,the capacitor unit exhibits outstanding AC line filtering with a large areal specific energy density of 1,015 μF V^(2)cm^(-2)(0.28 μW h cm^(-2)) at 120 Hz.After rational integration,the assembled capacitors present compact/lightweight configuration and lossless frequency response,as reflected by almost constant resistor-capacitor time constant of 0.2 ms and dissipation factor of 15% at120 Hz,identical to those of the single capacitor unit.Apart from standing alone steadily on a flower,a small volume(only 8.1 cm^(3)) of the integrated capacitor with 70 units connected in series achieves hundred-volts alternating current line filtering,which is superior to most reported filtering capacitors with sandwich configuration.This study provides insight into the fabrication and application of compact/ultralight filtering capacitors with lossless frequency response,and a wide range of operating voltage.展开更多
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
基金supported by the NSFC(21805072,22075019,22035005)the National Key R&D Program of China(2017YFB1104300)。
文摘Filtering capacitor with compact configuration and a wide range of operating voltage has been attracting increasing attention for the smooth conversion of the electric signal in modern circuits.Lossless integration of capacitor units can be regarded as one of the efficient ways to achieve a wider voltage range,which has not yet been fully conquered due to the lack of rational designs of the electrode structure and integration technology.This study presents an alternatingly stacked assemble technology to conveniently fabricate compact aqueous hybrid integrated filtering capacitors on a large scale,in which a unit consists of rGO/MXene composite film as a negative electrode and PEDOT:PSS based film as a positive electrode.Benefiting from the synergistic effect of rGO and MXene components,and morphological characteristics of PEDOT:PSS,the capacitor unit exhibits outstanding AC line filtering with a large areal specific energy density of 1,015 μF V^(2)cm^(-2)(0.28 μW h cm^(-2)) at 120 Hz.After rational integration,the assembled capacitors present compact/lightweight configuration and lossless frequency response,as reflected by almost constant resistor-capacitor time constant of 0.2 ms and dissipation factor of 15% at120 Hz,identical to those of the single capacitor unit.Apart from standing alone steadily on a flower,a small volume(only 8.1 cm^(3)) of the integrated capacitor with 70 units connected in series achieves hundred-volts alternating current line filtering,which is superior to most reported filtering capacitors with sandwich configuration.This study provides insight into the fabrication and application of compact/ultralight filtering capacitors with lossless frequency response,and a wide range of operating voltage.
