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Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Chinese Medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang Department of physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China Department of physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life Sciences Westlake UniversityHangzhouZhejiang 310024China key Laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to *** study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic ***:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type *** metabolomics was carried out to examine the alterations of metabolites in nucleotide *** efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in ***-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver ***:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated *** nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of ***,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver ***:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver *** repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

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Effect of methylimidazolium-based ionic liquids on vapor–liquid equilibrium behavior of tert-butyl alcohol + water azeotropic mixture at 101.3 kPa

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Chinese Journal of Chemical Engineering 2016年第3期24卷 365-372页

作者： Zhigang Zhang Qiang Zhang Tao Zhang Qinqin Zhang Wenxiu Li liaoning provincial key Laboratory of Chemical Separation Technology Shenyang University of Chemical Technology

Three ionic liquids(ILs),1-ethyl-3-methylimidazolium bromine([EMIM]Br),1-butyl-3-methylimidazolium bromine([BMIM]Br),and 1-hexyl-3-methylimidazolium bromine([HMIM]Br),were used as the solvent for separation of {tert-butyl alcohol(TBA)+ water} ***–liquid equilibrium(VLE)data for {TBA + water + IL}ternary systems were measured at 101.3 k *** results indicate that all the three ILs produce an obvious effect on the VLE behavior of {TBA + water} system and eliminate the azeotropy in the whole concentration range.[EMIM]Br is the best solvent for the separation of {TBA + water} system by extractive distillation among the three *** experimental VLE data for the ternary systems are correlated with the NRTL model equation with good *** are given with activity coefficients of water and TBA,and the experimental VLE-temperature data for {TBA or water + IL} binary systems.

关键词： Azeotrope Ionic liquids Vapor-liquid equilibrium Relative volatility NRTL model

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Ribonucleotide reductase subunit M1 blocks glucose catabolism via phosphorylation of pyruvate kinase M2 in human esophageal squamous cell cancer

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Genes & Diseases 2024年第3期11卷 69-71页

作者： Jian Yang Lingxiao Wang Hui Sun Zhenxiang Zhao Yanchuan Ma Zhen Hu Liqin Zhai Yonggang Wang Translational Medicine Research Center Shanxi Medical UniversityTaiyuanShanxi030001China Department of Cell Biology and Genetics Shanxi Medical UniversityTaiyuanShanxi 030001China key Laboratory of Cellular physiology of the Ministry of Education Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Colorectal Surgery The Fifth Clinical Medical College of Shanxi Medical UniversityTaiyuanShanxi 030012China Science&Technology Information and Strategy Research Center of Shanxi TaiyuanShanxi 030006China Department of Pathology Shanxi Provincial People's HospitalTaiyuanShanxi 030012China Department of Anatomy College of Basic MedicineShanxi Medical UniversityTaiyuanShanxi 030001China

Esophageal squamous cell cancer(EScC)is one of the malignant tumors with high morbidity and mortality all over the world.^(1) In recent years,combined chemotherapy has gradually been the effective treatment method for EscC ***,it is imperative to explore potential therapeutic targets for the treatment of *** previously reported a high-frequency amplification of pyrimidine metabolic pathway-related genes in EsCC tissues.

关键词： squamous esophageal cancer

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Bimetallic CoNi single atoms supported on three-dimensionally ordered mesoporous chromia: highly active catalysts for n-hexane combustion

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Green Energy & Environment 2024年第7期9卷 1122-1137页

作者： Xiuqing Hao Yuxi Liu Jiguang Deng Lin Jing Jia Wang Wenbo Pei Hongxing Dai Beijing key Laboratory for Green Catalysis and Separation Key Laboratory of Beijing on Regional Air Pollution Control Key Laboratory of Advanced Functional Materials Education Ministry of China Laboratory of Catalysis Chemistry and Nanoscience Department of Chemical Engineering Faculty of Environment and Life Beijing University of Technology

Developing the alternative supported noble metal catalysts with low cost,high catalytic efficiency,and good resistance toward carbon dioxide and water vapor is critically demanded for the oxidative removal of volatile organic compounds （VOCs）.In this work,we prepared the mesoporous chromia-supported bimetallic Co and Ni single-atom （Co1Ni1/meso-Cr2O3） and bimetallic Co and Ni nanoparticle (CoNPNiNP/mesoCr2O3) catalysts adopting the one-pot polyvinyl pyrrolidone （PVP）-and polyvinyl alcohol （PVA）-protecting approaches,*** results indicate that the Co1Ni1/meso-Cr2O3catalyst exhibited the best catalytic activity for n-hexane (C6H14) combustion (T50%and T90%were 239 and 263℃ at a space velocity of 40,000 mL g-1h-1;apparent activation energy and specific reaction rate at 260℃ were 54.7 kJ mol-1and 4.3×10-7mol g-1cats-1,respectively),which was associated with its higher (Cr5++Cr6+) amount,large n-hexane adsorption capacity,and good lattice oxygen mobility that could enhance the deep oxidation of n-hexane,in which Ni1was beneficial for the enhancements in surface lattice oxygen mobility and low-temperature reducibility,while Co1preferred to generate higher contents of the high-valence states of chromium and surface oxygen species as well as adsorption and activation of n-hexane.n-Hexane combustion takes place via the Mars van Krevelen（MvK） mechanism,and its reaction pathways are as follows:n-hexane→olefins or 3-hexyl hydroperoxide→3-hexanone,2-hexanone or 2,5-dimethyltetrahydrofuran→2-methyloxirane or 2-ethyl-oxetane→acrylic acid→COx→CO2and H2O.

关键词： Three-dimensional ordered mesoporous chromium oxide Supported bimetallic single-atom catalyst Cobalt−nickel single atoms n -Hexane combustion Catalytic reaction mechanism

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Leaching behavior and microstructure of phosphorus in converter slag

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Journal of Iron and Steel Research International 2024年第7期31卷 1646-1660页

作者： Chao-gang Zhou Jin-yue Li Qing-gong Chen Yin-ye Yang Wei Gong Li-qun Ai Shu-huan Wang Bei-yue Ma College of Metallurgy and Energy North China University of Science and TechnologyTangshan 063210HebeiChina key Laboratory for Ferrous Metallurgy and Resources Utilization of Ministry of Education Wuhan University of Science and TechnologyWuhan 430081HubeiChina College of Materials Science and Engineering Guizhou Minzu UniversityGuiyang 550025GuizhouChina School of Materials and Architectural Engineering Guizhou Normal UniversityGuiyang 550025GuizhouChina School of Metallurgy Northeastern UniversityShenyang 110819LiaoningChina

Converter slag is a by-product of the steelmaking process and contains a large amount of Ca,Fe,P and other *** the phosphorus in the converter slag can be effectively extracted,the resulting phosphorus can be used as a phosphate *** in converter slag is mainly enriched in 2CaO·SiO_(2)-3CaO·P_(2)O_(5)(C_(2)S-C_(3)P)solid solution and is easily dissolved in ***,acid leaching method was used to dissolve the solid solution to extract phosphorus in converter slag,so as to realize the recycling of phosphorus resources in converter *** leaching behavior of three actual converter slags from different steel mills in acid leaching solutions composed of citric acid,sodium hydroxide,hydrochloric acid and deionized water was studied by X-ray diffraction,scanning electron microscopy combined with energy dispersive spectrometry,Fourier transform infrared spectroscopy and Raman spectroscopy to reveal the change in object image structure as well as SiO_(4) and PO_(4) tetrahedron before and after acid *** results show that only a small amount of phosphorus in converter slag with too low basicity is enriched in C_(2)S-C_(3)P solid solution,resulting in poor leaching *** the converter slag has a high basicity,the removal effect of phosphorus is 70.64%-81.88%.In addition,when the basicity of converter slag is roughly the same,the dephosphorization effect of slag with high FeO content is relatively *** acid leaching will cause depolymerization behavior of SiO_(4) and PO_(4) tetrahedron,so that the mole fraction of Q0(Si)(asymmetric stretching vibration of Si-O bond in SiO_(4) tetrahedron with bridge oxygen number of 0)and NBO/Si(non-bridging oxygen in silicate tetrahedra)will ***-containing solids can be obtained from the solution after acid leaching through static precipitation,and the solids have the potential to make phosphate fertilizers.

关键词： Dephosphorization converter slag Acid leaching Phosphorus Solid solution Slag structure

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Circulating biomarker-and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy

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Chinese Medical Journal 2024年第1期137卷 73-81页

作者： Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang Department of Cardiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Cardiology Institute of Vascular MedicinePeking University Third HospitalBeijing 100191China Department of Cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Beijing key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100083China Department of physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100083China key Laboratory of Molecular Cardiovascular Science Ministry of EducationBeijing 100191China

Background:Dilated cardiomyopathy(DCM)has a high mortality rate and is the most common indication for heart *** study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation(ACM/HTx)risk in DCM ***:The present study is a retrospective cohort *** demographic,clinical,blood test,and cardiac magnetic resonance imaging(CMRI)data of DCM patients in the tertiary center(Fuwai Hospital)were *** primary endpoint was ACM/*** least absolute shrinkage and selection operator(LASSO)Cox regression model was applied for variable *** Cox regression was used to develop a *** concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curve,and decision curve analysis(DCA)were used to evaluate the performance of the ***:A total of 218 patients were included in the present *** were randomly divided into a training cohort and a validation *** nomogram was established based on eight variables,including mid-wall late gadolinium enhancement,systolic blood pressure,diastolic blood pressure,left ventricular ejection fraction,left ventricular end-diastolic diameter,left ventricular end-diastolic volume index,free triiodothyronine,and N-terminal pro-B type natriuretic *** AUCs regarding 1-year,3-year,and 5-year ACM/HTx events were 0.859,0.831,and 0.840 in the training cohort and 0.770,0.789,and 0.819 in the validation cohort,*** calibration curve and DCA showed good accuracy and clinical utility of the ***:We established and validated a circulating biomarker-and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients,which might help risk stratification and decision-making in clinical practice.

关键词： Cardiomyopathy,dilated Heart transplantation Mortality Nomograms Least absolute shrinkage and selection operator Decision curve analysis

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Discovering deaminases using AlphaFold2:a strategy to search for tool proteins for gene editing

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Signal Transduction and Targeted Therapy 2024年第3期9卷 822-824页

作者： Yongye Huang Jianxin Jiang Min Wu key Laboratory of Bioresource Research and Development of liaoning Province College of Life and Health SciencesNortheastern UniversityShenyang 110169China Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China Wenzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University WenzhouZhejiang 325000China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China The Joint Research Center Affiliated Xiangshan Hospital of Wenzhou Medical UniversityNingboChina

A recent study by Huang et *** in Cell reported the application of AlphaFold2 to forecast the structures of deaminase proteins and cluster them based on structural similarity,creating a truncated Sdd that can be used as a cytosine base editor(CBE)to be integrated into a single adeno-associated virus(AAV)1 This ground-breaking study aided by the artificial intelligence system would largely broaden the utility of tool proteins for gene editing.

关键词： CBE Alpha editor

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Pd Pt VO_(x)/CeO_(2)-ZrO_(2):Highly efficient catalysts with good sulfur dioxide-poisoning reversibility for the oxidative removal of ethylbenzene

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Journal of Environmental Sciences 2024年第4期138卷 153-166页

作者： Jia Wang Yuxi Liu Jiguang Deng Lin Jing Xiuqing Hao Xing Zhang Xiaohui Yu Hongxing Dai Beijing key Laboratory for Green Catalysis and Separation Key Laboratory of Beijing on Regional Air Pollution ControlKey Laboratory of Advanced Functional MaterialsEducation Ministry of ChinaLaboratory of Catalysis Chemistry and NanoscienceDepartment of Chemical EngineeringFaculty of Environment and LifeBeijing University of TechnologyBeijing 100124China

The PdPtVO_(x)/CeO_(2)-ZrO_(2)(PdPtVO_(x)/CZO)catalysts were obtained by using different approaches,and their physical and chemical properties were determined by various *** activities of these materials in the presence of H_(2)O or SO_(2)were evaluated for the oxidation of ethylbenzene(EB).The PdPtVO_(x)/CZO sample exhibited high catalytic activity,good hydrothermal stability,and reversible sulfur dioxide-poisoning performance,over which the specific reaction rate at 160℃,turnover frequency at 160℃(TOF_(Pd or Pt)),and apparent activation energy were 72.6 mmol/(g_(Pt)·sec)or 124.2 mmol/(g_(Pd)·sec),14.2 sec^(-1)(TOF_(Pt))or 13.1 sec^(-1)(TOF_(Pd)),and 58 k J/mol,*** large EB adsorption capacity,good reducibility,and strong acidity contributed to the good catalytic performance of PdPtVO_(x)/*** activity of PdPtVO_(x)/CZO decreased when 50 ppm SO_(2)or(1.0 vol.%H_(2)O+50 ppm SO_(2))was added to the feedstock,but was gradually restored to its initial level after the SO_(2)was cut *** good reversible sulfur dioxide-resistant performance of PdPtVO_(x)/CZO was associated with the facts:(i)the introduction of SO_(2)leads to an increase in surface acidity;(ii)V can adsorb and activate SO_(2),thus accelerating formation of the SO_(x)^(2-)(x=3 or 4)species at the V and CZO sites,weakening the adsorption of sulfur species at the PdPt active sites,and hence protecting the PdPt active sites to be not poisoned by SO_(2).EB oxidation over PdPtVO_(x)/CZO might take place via the route of EB→styrene→phenyl methyl ketone→benzaldehyde→benzoic acid→maleic anhydride→CO_(2)and H_(2)O.

关键词： Ceria-zirconia Supported palladium-platinum-vanadium catalyst Volatile organic compound Ethylbenzene oxidation Sulfur dioxide resistance

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LSD1调控颗粒细胞自噬并抑制Wt1参与FSH调节的有腔卵泡形成

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Science Bulletin 2024年第8期69卷 1122-1136页

作者：朱子健何美娜张拓赵庭秦韶刚高萌王文基郑文影陈子琦刘龙萍郝明周波张华王建斌王凤超夏国良王超 State key Laboratory of Farm Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China College of Basic Medicine Guizhou Medical UniversityGuiyang 550025China Guizhou provincial key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases Department of PhysiologyCollege of Basic MedicineGuizhou Medical UniversityGuiyang 550025China School of Life Sciences Taizhou UniversityTaizhou 318000China School of Life Sciences Tsinghua UniversityBeijing 100084China Transgenic Animal Center National Institute of Biological SciencesBeijing 102206China key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China College of Life ScienceNingxia UniversityYinchuan 750021China

In a growing follicle,the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical *** apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development,the underlying mechanisms require substantial *** to our study,along with FSH-induced antral follicles(AFs)formation,both lysine-specific demethylase 1(LSD1)protein levels and autophagy increased simultaneously in granulosa cells(GCs)in a time-dependent manner,we therefore evaluated the importance of LSD upon facilitating the formation of AFs correlated to autophagy in *** knockout of Lsdl in GCs resulted in significantly decreased AF number and subfertility in females,accompanied by marked suppression of the autophagy in *** the one hand,depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog(WT1),at both the protein and mRNA ***1 prevented the expression of FSH receptor(Fshr)in GCs and thus reduced the responsiveness of the secondary follicles to FSH *** the other hand,depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in *** finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase ***,the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.

关键词： LSD1 Autophagy H3K4me2 WT1 Follicle formation Follicle stimulating hormone

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State key Laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina Department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina Department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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