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
BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to hum...BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.展开更多
Objective:To investigate the correlation of BI-RADS grading with cancer cell proliferation and invasion.Methods: A total of 138 patients who were diagnosed with breast cancer in our hospital between August 2015 and Oc...Objective:To investigate the correlation of BI-RADS grading with cancer cell proliferation and invasion.Methods: A total of 138 patients who were diagnosed with breast cancer in our hospital between August 2015 and October 2017 were divided into 2 cases at stage Ⅲ, 51 cases at stage Ⅳ and 85 cases at stage Ⅴ after the BI-RADS grading was reviewed. Differences in the expression of proliferation-related genes and invasion-related genes were compared among the three groups of patients.Results: Expressions of pro-proliferation genes MTA2, mTOR, PKM2, Notch1 and FSCN1 mRNA in lesion tissue of patients at stage Ⅴ and Ⅳ were higher than those of patients at stage Ⅲ whereas expressions of anti-proliferation genes BRCA1 and PTEN mRNA were lower than those of patients at stage Ⅲ;expressions of pro-invasion genes Gab2 and NUAK1 mRNA were higher than those of patients at stage Ⅲ whereas expressions of anti-invasion genes EBP50, EDN3, FBXW7 and NDRG1 mRNA were lower than those of patients at stage Ⅲ. With the increase of BI-RADS grades, the expression levels of pro-proliferation genes and pro-invasion genes further increased while the expression levels of anti-proliferation and anti-invasion genes further decreased in the lesion tissue.Conclusions: BI-RADS grading of patients with breast cancer is positively correlated with the proliferation and invasion activity of cancer cells.展开更多
Before and after heat treatment,0Cr15Ni5Cu3MoN stainless steel(SS)samples were immersed in sulfate-reducing bacteria(SRB)environment to study the effect of heat treatment on the antimicrobial properties of Cu-containi...Before and after heat treatment,0Cr15Ni5Cu3MoN stainless steel(SS)samples were immersed in sulfate-reducing bacteria(SRB)environment to study the effect of heat treatment on the antimicrobial properties of Cu-containing stainless steel.The effect of heat treatment on the corrosion resistance and antibacterial ability of 0Cr15Ni5Cu3MoN SS was studied by scanning electron microscopy,transmission electron microscopy,laser scanning confocal microscopy,and electrochemistry.The results show that 0Cr15Cu3 SS has better antibacterial properties with fewer bacteria adsorbed on the surface after heat treatment,and its corrosion resistance is significantly improved.Interestingly,on the 7th day of immersion,the corrosion resistance of the heat-treated stainless steel was lower than that of the rolled stainless steel.This was due to the fact that the rolled samples were protected by biofilm at this time,while the surface bacteria on the heat-treated samples died,resulting in the exposure of the substrate surface and thus reducing the corrosion resistance of the heat-treated samples.Thus,because of the strong bactericidal properties of the heat-treated Cu-containing stainless steel,the corrosion resistance of the samples suddenly decreases in the middle stage of corrosion,and this discovery provides a new view to study the corrosion process of Cu-containing stainless steel in the SRB environment.展开更多
Fully dense aluminum nitride(AIN) ceramics were synthesized by self-propagating high-temperature synthesis(SHS) method using AIN powder as raw material with Y_2 O_3 additive. The sintering behavior was studied at diff...Fully dense aluminum nitride(AIN) ceramics were synthesized by self-propagating high-temperature synthesis(SHS) method using AIN powder as raw material with Y_2 O_3 additive. The sintering behavior was studied at different sintering temperatures and additive contents. The change of phase compositions, secondary phase distributions and grain morphologies during sintering process were investigated. It is shown that fully dense ceramics using AIN powder prepared by SHS method can be obtained when the sintering temperature is above 1830 ℃. Both Y_2 O_3 content and sintering temperature have an important influence on the formation of Y-Al-O phase and grain shape. When Y_2 O_3 content is identified, the grain morphology converts from polyhedron into sphere-like shape with the rise of sintering temperature. At a certain sintering temperature,the grain size decreases with the increase in Y_2 O_3 content. The influencing mechanisms of different YAl-O secondary phases and sintering temperatures on the grain size and morphology were also discussed based on the experimental results.展开更多
Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired immunity.The molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been elusive.Here,we found tha...Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired immunity.The molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been elusive.Here,we found that IL-37 transgenic(IL-37tg)mice were highly susceptible to colitis-associated colorectal cancer(CAC)and suffered from dramatically increased tumor burdens in colon.Nevertheless,IL-37 is dispensable for intestinal mutagenesis,and CRC cell proliferation,apoptosis,and migration.Notably,IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models.CD8^(+)T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice,enabling tumor evasion of immune surveillance.The dysfunction led by IL-37 antagonizes IL-18–induced proliferation and effector function of CD8+T cells,which was dependent on SIGIRR(single immunoglobulin interleukin-1 receptor-related protein).Finally,we observed that IL-37 levels were significantly increased in CRC patients,and positively correlated with serum CRC biomarker CEA levels,but negatively correlated with the CD8+T cell infiltration in CRC patients.Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancerimmunity cycle as therapeutic targets in CRC.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.
文摘BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.
文摘Objective:To investigate the correlation of BI-RADS grading with cancer cell proliferation and invasion.Methods: A total of 138 patients who were diagnosed with breast cancer in our hospital between August 2015 and October 2017 were divided into 2 cases at stage Ⅲ, 51 cases at stage Ⅳ and 85 cases at stage Ⅴ after the BI-RADS grading was reviewed. Differences in the expression of proliferation-related genes and invasion-related genes were compared among the three groups of patients.Results: Expressions of pro-proliferation genes MTA2, mTOR, PKM2, Notch1 and FSCN1 mRNA in lesion tissue of patients at stage Ⅴ and Ⅳ were higher than those of patients at stage Ⅲ whereas expressions of anti-proliferation genes BRCA1 and PTEN mRNA were lower than those of patients at stage Ⅲ;expressions of pro-invasion genes Gab2 and NUAK1 mRNA were higher than those of patients at stage Ⅲ whereas expressions of anti-invasion genes EBP50, EDN3, FBXW7 and NDRG1 mRNA were lower than those of patients at stage Ⅲ. With the increase of BI-RADS grades, the expression levels of pro-proliferation genes and pro-invasion genes further increased while the expression levels of anti-proliferation and anti-invasion genes further decreased in the lesion tissue.Conclusions: BI-RADS grading of patients with breast cancer is positively correlated with the proliferation and invasion activity of cancer cells.
基金supported by the National Natural Science Foundation of China(52074149,52204346)the Key Project of Liaoning Science and Technology Education Department(LJKZ0287,2020LNZD07)+1 种基金and the State Key Laboratory of Marine Equipment Made of Metal Material and Application(Grant No.HGSKL-USTLN-2021-07)the University of Science and Technology Liaoning Graduate Science Innovation Project(LKDYC202230).
文摘Before and after heat treatment,0Cr15Ni5Cu3MoN stainless steel(SS)samples were immersed in sulfate-reducing bacteria(SRB)environment to study the effect of heat treatment on the antimicrobial properties of Cu-containing stainless steel.The effect of heat treatment on the corrosion resistance and antibacterial ability of 0Cr15Ni5Cu3MoN SS was studied by scanning electron microscopy,transmission electron microscopy,laser scanning confocal microscopy,and electrochemistry.The results show that 0Cr15Cu3 SS has better antibacterial properties with fewer bacteria adsorbed on the surface after heat treatment,and its corrosion resistance is significantly improved.Interestingly,on the 7th day of immersion,the corrosion resistance of the heat-treated stainless steel was lower than that of the rolled stainless steel.This was due to the fact that the rolled samples were protected by biofilm at this time,while the surface bacteria on the heat-treated samples died,resulting in the exposure of the substrate surface and thus reducing the corrosion resistance of the heat-treated samples.Thus,because of the strong bactericidal properties of the heat-treated Cu-containing stainless steel,the corrosion resistance of the samples suddenly decreases in the middle stage of corrosion,and this discovery provides a new view to study the corrosion process of Cu-containing stainless steel in the SRB environment.
基金financially supported by the International Cooperation Project of Zhejiang Province (No. 2012C24007)
文摘Fully dense aluminum nitride(AIN) ceramics were synthesized by self-propagating high-temperature synthesis(SHS) method using AIN powder as raw material with Y_2 O_3 additive. The sintering behavior was studied at different sintering temperatures and additive contents. The change of phase compositions, secondary phase distributions and grain morphologies during sintering process were investigated. It is shown that fully dense ceramics using AIN powder prepared by SHS method can be obtained when the sintering temperature is above 1830 ℃. Both Y_2 O_3 content and sintering temperature have an important influence on the formation of Y-Al-O phase and grain shape. When Y_2 O_3 content is identified, the grain morphology converts from polyhedron into sphere-like shape with the rise of sintering temperature. At a certain sintering temperature,the grain size decreases with the increase in Y_2 O_3 content. The influencing mechanisms of different YAl-O secondary phases and sintering temperatures on the grain size and morphology were also discussed based on the experimental results.
基金This work was supported by the National Natural Science Foundation of China(81472650,81602763,81573050,82003358,81673061,81703132,31872739,31271483)the Key Research and Development Program of Sichuan Province[2020YFS0271]+5 种基金Project funded by China Postdoctoral Science Foundation(2016M592673,2018M631087,and 2017T100700)the Sichuan Provincial Outstanding Youth Fund(2015JQ0025)the Postdoctoral Fund for West China Hospital(2019HXBH075)the Fundamental Research Funds for the Central Universities(2019SCU12041,the Postdoctoral Foundation of Sichuan University)the National Science and Technology Major Project(2018ZX09733001-001-006 and 2019ZX09201003-003)the Sichuan Science and Technology Program(2021YJ0420).
文摘Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired immunity.The molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been elusive.Here,we found that IL-37 transgenic(IL-37tg)mice were highly susceptible to colitis-associated colorectal cancer(CAC)and suffered from dramatically increased tumor burdens in colon.Nevertheless,IL-37 is dispensable for intestinal mutagenesis,and CRC cell proliferation,apoptosis,and migration.Notably,IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models.CD8^(+)T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice,enabling tumor evasion of immune surveillance.The dysfunction led by IL-37 antagonizes IL-18–induced proliferation and effector function of CD8+T cells,which was dependent on SIGIRR(single immunoglobulin interleukin-1 receptor-related protein).Finally,we observed that IL-37 levels were significantly increased in CRC patients,and positively correlated with serum CRC biomarker CEA levels,but negatively correlated with the CD8+T cell infiltration in CRC patients.Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancerimmunity cycle as therapeutic targets in CRC.
