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生命的化学 2024年第5期44卷 928-932页

作者：王晓静赵福昌刘招舰苏擘岳学田王向东山东大学基础医学院细胞生物学系济南250012 山东大学公共卫生学院济南250012

为全面提升医学研究生细胞生物学课程的铸魂育人功能,本文从设置课程教学的素质目标、思政元素融入课程教学内容和教学方法改革等角度,探索了习近平新时代中国特色社会主义思想在医学研究生教学中的实施方案,旨在建立完善全员、全程、... 详细信息

为全面提升医学研究生细胞生物学课程的铸魂育人功能,本文从设置课程教学的素质目标、思政元素融入课程教学内容和教学方法改革等角度,探索了习近平新时代中国特色社会主义思想在医学研究生教学中的实施方案,旨在建立完善全员、全程、全方位的育人体系和培养符合新时代要求的高层次医学人才。

关键词：习近平新时代中国特色社会主义思想细胞生物学医学研究生教学方法

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ZHX2 deficiency promotes liver regeneration by enhancing mitochondrial oxidative phosphorylation

ZHX2 deficiency promotes liver regeneration by enhancing mit...

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第十四届全国免疫学学术大会

作者： Yankun Zhang xuetian yue Chunhong Ma School of Basic Medical Sciences Shandong University

The liver has an exceptional capacity for regeneration which is crucial for maintaining liver *** metabolism and cell division are hallmarks of liver regeneration(LR),we investigated the role of Zinc-finger and homeboxes 2(ZHX2),a transcription factor critical for regulating liver postnatal gene expression,cell proliferation and hepatic lipid hemostasis,in *** results show that hepatocyte-specific Zhx2 knockout(Zhx2-KO) enhances LR after 2/3 partial hepatectomy and carbon tetrachloride(CCI4) exposure in *** of ZHX2 results in increased mitochondrial oxidative phosphorylation(OXPHOS) and higher production of ATP in hepatocytes,suppling energy for hepatocyte ***2 repressed mitochondrial OXPHOS through two ***,ZHX2 binds to the promoters of a subset of electron transport chain(ETC) genes for ***,ZHX2 reduces stability of peroxisome proliferator-activated receptor-γ coactlvator-1 a(PGC-1α) to decrease mitochondrial mass and *** of PGC-1α or ETC abolishes the enhanced LR caused by Zhx2 *** study highlights a novel and important mechanism underlying mitochondrial regulation during LR.

关键词： Liver regeneration ZHX2 PGC-1α Mitochondria Oxidative phosphorylation

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EC330, a small-molecule compound, is a potential novel inhibitor of LIF signaling

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Journal of Molecular Cell Biology 2020年第6期12卷 477-480页

作者： xuetian yue Fangnan Wu Jianming Wang Kaitlin Kim Bindu Santhamma Kalarickal VDileep Kam YJZhang Suryavathi Viswanadhapalli Ratna KVadlamudi Gulzar Ahmed Zhaohui Feng Klaus Nickisch Wenwei Hu Rutgers Cancer Institute of New Jersey Rutgers UniversityNew BrunswickNJ 08903USA Evestra Inc.San AntonioTX 78245USA Laboratory for Structural Bioinformatics Center for Biosystems Dynamics ResearchRIKENYokohama 230-0045Japan Department of Obstertrics and Gynecology University of Texas Health San AntonioSan AntonioTX 78229USA

Dear Editor,LIF,a multi-functional cytokine,is frequently overexpressed in many human cancers,including breast,colorectal,and pancreatic cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Pascual-Garcia et al.,2019;Shi et al.,2019;Wang et al.,2019).LIF overexpression is frequently associated with poor prognosis in human cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014).LIF functions through binding to LIF receptor complex composed of LIF receptor(LIF-R)and glycoprotein gp130(Taga and Kishimoto,1997;Heinrich et al.,2003;Watanabe et al.,2006).LIF overexpression induces activation of several oncogenic signaling pathways in a cell/tissue type-specific manner,including STAT3,PI3K/AKT,and mTOR,which in turn promotes proliferation,metastasis,and therapeutic resistance of cancer cells(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Shi et al.,2019).Recent studies have suggested that LIF is a potential important target for cancer therapy,especially for cancers with LIF *** neutralization antibodies(LIF neu Abs)have been reported to block LIF signaling and largely abolish the promoting effect of LIF on cancer progression(Li et al.,2014;yue et al.,2016;Shi et al.,2019).

关键词： PI3K/AKT STAT3 metastasis

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ZHX2 reverses MDR1-associated multidrug resistance by interfering with NF-YA in liver tumor cells

ZHX2 reverses MDR1-associated multidrug resistance by interf...

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第十届全国免疫学学术大会

作者： Hongxin Ma xuetian yue Lifen Gao Xiaohong Liang Chunhong Ma Department of Immunology Shandong University School of Medicine

Background:We reported the tumor suppressor function of Zinc-fingers and homeoboxes 2(ZHX2)in hepatocellular carcinoma(HCC).Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple ***,the mechanisms involve in this process remain ***:Here,we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1)expression resulting in increased sensitivity to chemotherapeutic ***:Cisplatin(CDDP)and Adriamycin(ADM)were involved in this *** viability and apoptosis were *** mircroscope and flow cytometry were used to estimate drug efflux in ADM treated *** effect of ZHX2 in CDDP mediated suppression on tumor growth was further verified in tumor *** blot,RT-PCR and luciferase reporter assays were included to assay the regulation of ZHX2 on expression of multidrug resistance protein 1(MDR1).Ch IP and EMSA were used to measure the binding of ZHX2 with MDR1 ***:Increased ZHX2 levels correlated with reduced MDR1 expression and enhanced cytotoxicity of CDDP and ADM in HCC ***,elevated ZHX2 significantly reduced ADM efflux and greatly increased CDDP-mediated suppression of liver tumor growth in ***,immunohistochemical staining demonstrated the inverse correlation of ZHX2 and MDR1 expression in HCC *** report assay showed that ZHX2 repressed MDR1promoter activity,while knockdown of NF-YA or mutating the NF-Y binding site eliminated ZHX2-mediated repression of MDR1 ***-IP and Ch IP assay further suggested that ZHX2 interacted with NF-YA and reduced NF-Y binding to the MDR1 ***:Taken together,we clarify that ZHX2 represses NF-Y-mediated activation of MDR1 transcription and enhances the effects of chemotherapeutics in HCC cells.

关键词： ZHX2 MDR1 HCC multidrug resistance

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Zinc Fingers and Homeoboxes 2(ZHX2) Regulates the Expression of DNA Methyltransferase 3B(DNMT3B) in Hepatocellular Carcinoma

Zinc Fingers and Homeoboxes 2(ZHX2) Regulates the Expression...

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第十届全国免疫学学术大会

作者： Ying He xuetian yue Hongxin Ma Zhenyu Zhang Chunhong Ma Institute of Basic Medical Sciences Qilu Hospital Shandong University Institute of Immunology Shandong University School of Medicine

Background:Aberrant DNA methylation were associated with many kinds of human tumors,including hepatocellular carcinoma(HCC).ZHX2 functioned as a transcriptional repressor and inhibited cell proliferation in *** early Ch IP-on-chip and microarray results showed ZHX2 might bind to the promoter of DNMT3B and regulate its m RNA ***:This study aimed to study the effect of ZHX2 on DNMT3B expression in HCC and elucidate the ***:Immunohistochemistry was performed to analyze the expression of ZHX2 and DNMT3B in tissue microarrays containing 44 HCC tumors and their matched adjacent non-tumor *** correlation of ZHX2 and DNMT3B expression level was studied in HCC cell ***,we cloned the DNMT3B promoter region(-1226bp to+206bp),and explored the mechanism by Ch IP-PCR analysis and luciferase reporter ***:It was showed nuclear staining of DNMT3B mainly in both HCC tissues and matched adjacent non-tumor tissues,and stronger staining intensity in HCC ***2 also showed high nuclear expression in non-tumor tissues,but mostly lost its nuclear location ability in HCC *** analysis suggested the nuclear expression level of ZHX2 was negatively related to that of *** was also confirmed that ZHX2 could downregulated DNMT3B expression in ZHX2 overexpression and knockdown HCC cell models by western blot and *** IP-PCR confirmed that ZHX2 could bind to DNMT3B promoter *** we cloned DNMT3B promoter sequence and verified that ZHX2 could repress DNMT3B promoter activity with a 38.5%reduction based on the dual luciferase reporter ***:In HCC tissue,there is a negative correlation between the expression of ZHX2 and *** in HCC cell lines ZHX2 represses the protein and m RNA expression of ***2 inhibits the transcription of DNMT3B by binding to its promoter region,suggesting that ZHX2 should be developed into DNMT3B inhibitor as peptide drug for cancer treatment.

关键词： HCC DNMT3B ZHX2 ChIP

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Role of ZHX2 in regulating human lipoprotein lipase

Role of ZHX2 in regulating human lipoprotein lipase

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2012全国临床微生物与感染免疫学术研讨会

作者： Ma Hongxin,Liang Xiaohong,Gao Lifen,yue xuetian,Zhang Zhenyu,Liu Peng,Guo Min,Yan Wenjiang, Ma Chunhong~* Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China

Background & Aims Dyslipidemia is a major risk factor for many chronic diseases such as cardiovascular and cerebrovascular diseases,chronic liver disease,diabetes mellitus,*** report identified zinc-fingers and homeoboxes 2(ZHX2),one member of ZHX family,as a potential regulator of lipoprotein *** has been well recognized that ZHX2 works as a transcriptional repressor by interaction with *** lipase (LPL),one of the key enzymes in plasma lipid metabolism,can be regulated by ***,we hypothesized that ZHX2 might regulate lipoprotein metabolism by transcriptional repression on LPL ***,we investigate the role and mechanisms in which ZHX2 regulated LPL. Methods To confirm the effect of ZHX2 on LPL,ZHX2 overexpressing plasmid and specific siRNA were transfected into different hepatoma cell *** blot(WB) and RT-PCR were used to analyze the expression of *** reporter assays were introduced to observe the influence of ZHX2 on serial truncated and mutational human LPL *** immunoprecipitation(ChIP) assays were involved to identify the binding inteaction between ZHX2 and LPL promoter. Results Overexpression of ZHX2 significantly repressed the expression of LPL in CHO and HepG2 cell,while ZHX2 knockdown increased LPL expression in SMMC7721 and QSG7701 cell *** reporter assays proved that ZHX2 suppressed the activity of LPL promoter in a dose-dependent manner,suggesting that ZHX2 inhibits the transcription of *** lucierase reporter assay with serial truncated LPL promoters identified the region from -96 to -38 of LPL promoter as critical region responsible for ZHX2 *** of ChIP assays presented that ZHX2 could bind to this region of LPL promoter. Conclusions For the first time,we demonstrated that ZHX2 suppresse the expression of LPL by binding its promoter *** findings may give new light on lipoprotein regulation and provide a new target for dyslipid

关键词： ZHX2 dyslipidemia LPL NF-YA

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TIPE1 is down-regulated in human hepatocellular cancer and inhibits cell proliferation

TIPE1 is down-regulated in human hepatocellular cancer and i...

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2012全国临床微生物与感染免疫学术研讨会

作者： Zhang Zhenyu,Liang Xiaohong,Gao Lifen,Ma Hongxin,Liu Xiao,Pan Yingfang,yue xuetian,Yan Wenjiang,Sun Wensheng,Ma Chunhong~* Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China

TIPEl(TNFAIP8L1) is a member of tumor necrosis factor alpha-induced protein 8 family(TIPE),which contains four members,TIPE,TIPE1,TIPE2 and *** is the first identified member and is considered to be connected with apoptosis and carcinogenesis,while TIPE2 is considered as a negative regulator of innate immunity and cellular immunity,but little is known about *** only research about TIPEl by Professor Junying Yuan proved that knockdown of TIPEl inhibits necroptosis and apoptosis in L929 cells,besides this,there is no research about TIPEl and human ***,we for the first time,reported the expression and role of TIPEl in *** analysis of TIPEl in 100 hepatocellular cancer samples and their corresponding noncancerous tissues identified the decreased expression of TIPEl inHCC tissues compared with their corre-

关键词： TIPE1 HCC Cell growth

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Transcriptional up-regulation of FOXP3 by AP-1/HBx:a novel mechanism for tumour growth in hepatocellular carcinoma

Transcriptional up-regulation of FOXP3 by AP-1/HBx:a novel m...

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2012全国临床微生物与感染免疫学术研讨会

作者： Zhang Xiaoning,Gao Lifen,yue xuetian,Zhang Feng,Liu Peng,Pan Yingfang,Zhang Zhenyu,Liu Xiao, Gai Xiaoxiao,Liang Xiaohong,Ma Chunhong~* Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China

Backgroud & Aims Transcription factor forkhead box protein 3(FOXP3) has been identified in different cancer cells where it plays contradict *** strongly suggests the urgency to study the expression pattern and function of FOXP3 in different types of ***,we aim to explore the expression and biological functions of FOXP3 in hepatocellular carcinoma(HCC) and to uncover the role of HBx in regulating FOXP3 expression. Methods FOXP3 expression in malignant hepatocytes was detected by immunohistochemical ***-mediated transcriptional regulation of FOXP3 was studied by cotransfection and luciferase reporter *** biological function of FOXP3 in vitro was analyzed by CCK-8,colony formation assay and cell cycle analysis. Results Augmented FOXP3 expression is detected in liver cells from cancer *** FOXP3 staining in malignant hepatocytes from patients with HBV infection was significantly stronger than that from non-HBV infection (P=0.0268).In accordance,HBx enhance FOXP3 expression by up-regulating FOXP3 promoter activity in HCC cell *** AP-1 binding site at -465 bp to -445 bp of FOXP3 promoter is responsible for HBx-induced FOXP3 transcriptional *** vitro assays show that enhanced expression of FOXP3 significantly promotes HCC cell growth and colony formation *** down of FOXP3 dampen the HBx-mediated acceleration of cell growth in HepG2. Conclusion Our data provides the first molecular mechanism describing the HBx-mediated transcriptional upregulation of FOXP3 which might play important role in the development of HBV related HCC by promoting the growth and proliferation of liver cancer cells.

关键词： Forkhead box protein 3 HBV X protein AP-1 Transcription Regulation Hepatocellular carcinoma

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Novel tumor suppressor gene ZHX2 enhances cisplatin sensitivity in hepato-cellular carcinoma cells

Novel tumor suppressor gene ZHX2 enhances cisplatin sensitiv...

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2012全国临床微生物与感染免疫学术研讨会

作者： yue xuetian,Liang Xiaohong,Ma Hongxin,Guo Min,Liu Peng,Zhao Di,Zhang Zhenyu,Liu Xiao,Gai Xiaoxiao,Pan Yingfang,Gao Lifen Ma Chunhong~* Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China

Zinc-fingers and homeoboxes 2(ZHX2) repress transcription of several genes associated with liver cancer,including a-fetoprotein(AFP),glypican 3 and ***,little is known about the role of ZHX2 indevelopment of hepatocellular carcinoma(HCC).We recently identified the tumor suppressor role of ZHX2 in *** of ZHX2 was significantly decreased in clinical hepatocellular carcinoma(HCC) tissues which correlated with reduced overall survival time of patients,high levels of tumor microvascularization,and hepatocyte *** analysis demonstrated that ZHX2 inhibits HCC cell proliferation,by preventing expression of cyclins A and E,and reduces growth of xenograft tumors in *** data indicated that loss of nuclear ZHX2 might be an early step in the development of HCC(Gastroenterology 2012). In this report,we examined the effect of a combination treatment using ZHX2 gene transfer and chemotherapeutic drug cisplatin(CDDP) on HCC and explored the underlying *** demonstrated that the combination of ZHX2 gene transfer and CDDP induced enhanced growth inhibition and increased apoptosis in HCC cell lines. Consistently,ZHX2 plus CDDP led to augmented cytochrome c release,more cleaved caspase-9 and ***, combination of ZHX2 with CDDP suppressed the growth of HepG2.2.15 xenograft in nude mice with more efficiency than ZHX2 gene transfer or CDDP *** findings suggest that the combination of ZHX2 gene transfer and cisplatin might represent a promising strategy for treating HCC.

关键词： ZHX2 tumor suppressor gene,CDDP combination chemotherapy HCC

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Identification of Milankovitch Cycles and Calculation of Net Primary Productivity of Paleo-peatlands using Geophysical Logs of Coal Seams

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Acta Geologica Sinica(English Edition) 2022年第6期96卷 1830-1841页

作者： SHAO Longyi WEN He GAO Xiangyu Baruch SPIRO WANG xuetian YAN Zhiming David J.LARGE College of Geoscience and Surveying Engineering China University of Mining and Technology(Beijing)Beijing 100083China Department of Earth Sciences Natural History MuseumLondon SW75BDUK Institute of Architectural Engineering Weifang UniversityWeifangShandong 261061China Faculty of Engineering University of NottinghamNottingham NG72RDUK

Individual coal seams formed in paleo-peatlands represent sustained periods of terrestrial carbon accumulation and a key environmental indicator attributed to this record is the rate of carbon *** the rate of carbon accumulation requires a measure of time contained within the *** study aimed to determine this rate via the identification of Milankovitch orbital cycles in the *** geophysical log is an ideal paleoclimate proxy and has been widely used in the study of sedimentary records using spectral *** analyses of geophysical log from thick coal seams can be used to identify the Milankovitch cycles and to calculate the period of the coal *** considering the carbon loss during coalification,the long-term average carbon accumulation rate and net primary productivity(NPP)of paleo-peatlands in coal seams can be *** review paper presents the procedures of analysis,assessment of results and interpretation of geophysical logs in determining the NPP of paleo-peatlands.

关键词： paleo-peatlands Milankovitch cycle carbon accumulation rate net primary productivity(NPP) coal seam

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