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Unraveling the nexus between cellular senescence and malignant transformation:a paradigm shift in cancer research

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Cancer Biology & Medicine 2024年第7期21卷 541-546页

作者： Xiaoyu Song Xiyan Liu Qiqiang Guo Hongde Xu Liu Cao The College of Basic Medical Science Health Sciences InstituteChina Medical UniversityShenyang 110122China key laboratory of cell Biology of ministry of Public health Key Laboratory of Medical Cell Biology of Ministry of EducationKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors of Ministry of EducationLiaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and PreventionChina Medical UniversityShenyang 110122China

cellular senescence, a natural process wherein cells cease division and undergo irreversible growth arrest, has long captivated the curiosity of scientists because of its many implications in aging and disease. Recent research has shed light on the nexus between cellular senescence and malignant transformation, thus leading to a paradigm shift in understanding cancer development and progression.

关键词： malignant cancer transformation

TIP60 acetylation of Bub1 regulates centromeric H2AT120 phosphorylation for faithful chromosome segregation

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Science China(Life Sciences) 2024年第9期67卷 1957-1969页

作者： Mengjie Sun Biying Yang Guangwei Xin Yao Wang Jia Luo Qing Jiang Chuanmao Zhang The Academy for cell and Life health Faculty of Life Science and TechnologyKunming University of Science and TechnologyKunming 650500China The key laboratory of cell Proliferation and Differentiation of the ministry of Education College of Life SciencesPeking UniversityBeijing 100871China

Proper function of the centromeres ensures correct attachment of kinetochores to spindle microtubules and faithful chromosome segregation in *** in the integrity and function of centromeres can result in chromosome missegregation and genomic ***1 is essential for the mitotic centromere dynamics,yet the underlying molecular mechanisms remain largely ***,we demonstrate that TIP60 acetylates Bub1 at K424 and K431 on kinetochores in early *** acetylation increases the kinase activity of Bub1 to phosphorylate centromeric histone H2A at T120(H2Ap T120),which recruits Aurora B and Shugoshin 1(Sgo1)to regulate centromere integrity,protect centromeric cohesion,and ensure the subsequent faithful chromosome *** of the nonacetylated Bub1 mutant reduces its kinase activity,decreases the level of H2Ap T120,and disrupts the recruitment of centromere proteins and chromosome congression,leading to genomic instability of daughter *** cells exit mitosis,HDAC1-regulated deacetylation of Bub1 decreases H2Ap T120 levels and thereby promotes the departure of centromeric CPC and Sgo1,ensuring timely centromeres ***,our results reveal a molecular mechanism by which the acetylation and deacetylation cycle of Bub1 modulates the phosphorylation of H2A at T120 for recruitment of Aurora B and Sgo1 to the centromeres,ensuring faithful chromosome segregation during mitosis.

关键词： acetylation Bub1 TIP60 H2ApT120 chromosome segregation

Polyaspers A and B,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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Chinese Journal of Chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang Hubei key laboratory of Natural Medicinal Chemistry and Resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Institute of Organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei key laboratory of Wudang Local Chinese Medicine Research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

Current status and challenges of pig-to-human organ xenotransplantation

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Science China(Life Sciences) 2024年第4期67卷 829-831页

作者： Minghui Fang Yong-Guang Yang Zheng Hu key laboratory of Organ Regeneration&transplantation of ministry of Education and National-Local Joint Engineering Laboratory of Animal Models for Human DiseasesThe First Hospital of Jilin UniversityChangchun 130061China

Organ shortage is a global *** collected by the Global Observatory on Donation and transplantation reveals that over 150,000 solid organ transplants are conducted globally each year,a 52%increase from 2010(http://***/... 详细信息

关键词： globally global shortage

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li key laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou Regenerative Medicine and health Guang Dong laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

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Science China(Life Sciences) 2024年第9期67卷 2033-2035页

作者： Meihan Gong Ye Yuan Zhongye Dai Xuejiao Lv Jiacheng Su Dawei Huo Lin Niu Xu Chen Xudong Wu State key laboratory of Experimental Hematology The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsKey Laboratory of Immune Microenvironment and Disease(Ministry of Education)Department of Cell BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Bone Marrow transplantation Center the First Affiliated HospitalZhejiang University School of MedicineLiangzhu LaboratoryInstitute of HematologyZhejiang UniversityHangzhou 311113China

Dear Editor,Polycomb group proteins,conserved epigenetic transcriptional repressors,are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al.,2017).The polycomb repressive complex 2(PRC2)catalyzes H3 lysine-27 trimethylation(H3K27me3)to establish a delicate balance with H3K4me3,forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

关键词： valent thereby subsequent

Reduced clinical severity during 2022 Shanghai Spring epidemic of SARS-CoV-2 omicron BA.2 variant infection——an integrated account of virus pathogenicity and vaccination effectiveness

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National Science Review 2024年第4期11卷 24-27页

作者： Xingyue Wu Yao Chen Kangli Cao Yao Shen Xueling Wu Yilin Yang Zhongshu Kuang Qingrun Li Zhenzhen Lu Yichen Jia Mian Shao Guorong Gu Xiangwei Wang Ye Yao Ying Wang Shaodie Chen Zhigao Yu Wei Wei Longfei Ding Lulu Lan Tianwen Gu Xiangyu Long Jian Sun Lingyu Xing Jiayuan Shen Yi Han Yue Luo Sucheng Mu Mengna Lin Xiaoyan Zhang Rong Zeng Jianqing Xu Guoping Zhao Lihong Huang Zhenju Song Department of Emergency Medicine Clinical Center for Bio-Therapy Department of Biostatistics and Department of UrologyShanghai Key Laboratory of Lung Inflammation and Injury Zhongshan Hospital Fudan University Department of Respiratory and Critical Care Medicine Shanghai Pudong Hospital Fudan University Department of Pulmonology Renji Hospital Shanghai Jiao Tong University School of Medicine key laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai Public health Clinical Center Fudan University Department of Biostatistics School of Public Health Key Laboratory of Public Health Safety of Ministry of Education and Shanghai Institute of Infectious Disease and Biosecurity School of Public Health Fudan University Shanghai Institute of Immunology Department of Immunology and Microbiology Shanghai Institute of Virology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationSchool of Medicine Shanghai Jiao Tong University State key laboratory of Genetic Engineering Fudan Microbiome CenterSchool of Life Sciences Fudan University Bio-Med Big Data Center Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

The emergence of SARS-Co V-2 variant of concern omicron BA.2 led to high infection incidence rates as well as reduced severity of COVID-19 during the Shanghai Spring epidemic of 2022 [1]. We assessed the role of viral pathogenicity and the effectiveness of inactivated vaccines in a retrospective observational study including 10 258 confirmed COVID-19cases identified between April and June of 2022, from four COVID-19 designated hospitals located in two areas of Shanghai, namely the West Bund and the East Bund, where the populations’ demographic characteristics varied significantly (Table S1, Fig. S1).

关键词： REPLICATION

Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo Stem cell Biology and Therapy laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma Stemness

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 712-728页

作者： Xiaoxuan Zhong Xiang Wei Yan Xu Xuehai Zhu Bo Huo Xian Guo Gaoke Feng Zihao Zhang Xin Feng Zemin Fang Yuxuan Luo Xin Yi Ding-Sheng Jiang Division of Cardiovascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China key laboratory of Organ transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart ***,we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum-and PDGF-BB-induced vascular smooth muscle cells(VSMCs),and in tissues of carotid artery injury-induced neointimal ***2 overexpression in VSMCs(Smyd2-vTg)facilitates,but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in *** sequencing revealed that SMYD2 knockdown represses the expression of serum response factor(SRF)target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC ***3 directly interacts with and deacetylates SRF,which enhances SRF transcriptional activity in ***,SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its ***966,a specific inhibitor of HDAC3,not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs,but also inhibits carotid artery injury-induced neointima formation in ***3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent *** results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

关键词： Neointimaformation Histonemethylation Histoneacetylation SRFacetylation SMYD2 HDAC3 LLY-507 RGFP966