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Di-and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair

Science China(Life sciences) 2024年第6期67卷 1089-1105页

作者： Runfa Chen Meng-Jie Zhao Yu-Min Li Ao-Hui Liu Ru-Xin Wang Yu-Chao Mei Xuefeng Chen Hai-Ning Du Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismHubei Clinical Research Center of Emergency and ResuscitationEmergency Center of Zhongnan HospitalWuhan UniversityWuhan 430072China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismWuhan UniversityWuhan 430072China

Histone H3 Lys36(H3K36)methylation and its associated modifiers are crucial for DNA double-strand break(DSB)repair,but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is ***,we unveil the distinct roles of H3K36 dimethylation(H3K36me2)and H3K36 trimethylation(H3K36me3)in DSB repair via non-homologous end joining(NHEJ)or homologous recombination(HR).Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency.y Ku70 and Rfa1 bind H3K36me2-or H3K36me3-modified peptides and chromatin,*** these interactions impairs y Ku70 and Rfa1 recruitment to damaged H3K36me2-or H3K36me3-rich loci,increasing DNA damage sensitivity and decreasing repair ***,H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit y Ku70 or Rfa1 under DSB ***,human KU70 and RPA1,the homologs of y Ku70 and Rfa1,exclusively associate with H3K36me2 and H3K36me3 in a conserved *** findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways,highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

关键词： histone H3K36 methylation Ku70 RPA non-homologous end joining homologous recombination

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Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli

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Biomedical and Environmental sciences 2024年第2期37卷 228-232页

作者： YE Qiao HUO Jia Nan LUO Yuan MEI Zhu Song FANG Long Mei GUO Bing Qian WANG Guang Yun Laboratory of clinical medicine Air Force Medical CenterAir Force Medical UniversityBeijing 100142China

As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis *** this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibition of so... 详细信息

关键词： hypoxic Sodium observing

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Variations, effectiveness and its associated factors of a nationwide web-based hypertension management training project in China: insights from a government-led campaign for 1.2 million lay health workers

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Journal of Geriatric Cardiology 2024年第7期21卷 733-750页

作者： Wei WANG Hai-Bo ZHANG Jia-Min LIU Yan LI Na TIAN Lei YAN Jin-Xiao SONG Mei-Li LI Yue PENG Jing LI National Primary Health Care Hypertension Management Office National Clinical Research Center for Cardiovascular DiseasesNHC Key Laboratory of Clinical Research for Cardiovascular MedicationsFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES To evaluate the effectiveness of a large-scale,web-based,in-service hypertension management training project among lay health workers(LHWs)at primary care health(PHC)settings in China,and to examine the factors contributing to the of *** METHODS We used data from a web-based national hypertension management training project implemented in 2018,it was designed to facilitate LHWs to learn,understand,and apply the relevant knowledge and skills in hypertension management through providing training courses by use of the web-based platform with unified *** LHWs were required to parti-cipate in the exams before and after training to acquire scores for the use of evaluating their performance of hypertension man-agement *** first used descriptive analysis to present the variations of effectiveness in hypertension management knowledge among LHWs by important ***,we used multilevel logistic regression to examine the individual regional factors contributing to the variations and quantify the magnitude of how these factors affected training *** RESULTS There were 1,208,610 LHWs who completed training and were ***,the scores of LHWs in-creased significantly from 62.87±21.14 out of 100 in the pre-test to 88.30±11.31 in the post-test by 25.43(95%confidence interval[CI]:25.40-25.47).Training contents involved in antihypertensive medication showed the lowest score(54.36)in the pre-test and soared the most after training,up to 84.22 by 54.94%.Individual factors associated with disparities in the knowledge of hyperten-sion management decreased substantially after training,which included sex,age,education,practice type,professional level,and hierarchy of working *** variations were shown at the provincial level,with the majority of them being ex-by factors at the regional *** CONCLUSIONS Accessible web-based training modality,government efforts,accompanie

关键词： hypertension workers nationwide

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Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 51-64页

作者： Mingming XU Zhaoliang LIU Wenhua HU Ying HAN Zhen WU Sufeng CHEN Peng XIA Jing DU Xumin ZHANG Piliang HAO Jun XIA Shuang YANG center for clinical Mass Spectrometry College of Pharmaceutical SciencesSoochow UniversitySuzhou215123China School of Life Science and Technology ShanghaiTech UniversityShanghai201210China State Key Laboratory of Genetic Engineering Department of BiochemistrySchool of Life SciencesFudan UniversityShanghai200438China Department of clinical Laboratory center Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou310014China

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival ***,no methods have been derived that can reliably identify early precursors of development into ***,it is urgent to discover early molecular changes during pancreatic *** aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further ***,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient *** profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific *** results indicated the potential role for tumor-specific glycosylation as disease *** also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

关键词： Pancreatic cancer Glycosylation Biomarker Glycoproteomics Mass spectrometry

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Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo Department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

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Meiotic nuclear divisions 1 suppresses the proliferation and invasion of pancreatic cancer cells via regulating H2A.X variant histone

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BIOCELL 2024年第1期48卷 111-122页

作者： DONGQIN WANG YAN SHI ZHIQIANG WANG JING ZHANG LUYAO WANG HONGYU MA SHUHUA SHI XIAOFU LIAN HUA HUANG XIAOJING WANG CHAOQUN LIAN Anhui Province Key Laboratory of clinical and Preclinical Research in Respiratory Disease Molecular Diagnosis CenterThe Department of Pulmonary Critical Care MedicineFirst Affiliated Hospital of Bengbu Medical CollegeBengbu233030China Department of Genetics School of Life SciencesBengbu Medical CollegeBengbu233000China Department of clinical Medicine Bengbu Medical CollegeBengbu233030China Research center of clinical Laboratory Science Bengbu Medical CollegeBengbu233030China

Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality ***,prevention and effective treatment are urgent issues that need to be ***:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival ***,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of *** small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell ***:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell *** healing and Transwell assays revealed that MND1 knockdown reduced cell migration and *** cytometry revealed that inhibiting MND1 hindered the cell ***,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of ***,MND1 had a positive effect on H2AFX expression in PC *** MND1 expression suggests the low overall survival rate of individuals diagnosed with ***:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.

关键词： Pancreatic carcinoma MND1 H2AFX Cell cycle

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Saponin Ⅰ from Shuitianqi(Rhizoma Schizocapasae Plantagineae) inhibits metastasis by negatively regulating the transforming growth factor-β1/Smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model

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Journal of Traditional Chinese Medicine 2024年第4期44卷 642-651页

作者： LYU Meixian ZHOU Huan ZHI Limin ZHOU Jinling GAN Rizhi QIN Yanping HE Nengting ZUO Qiqi LI Hao DONG Min LIANG Gang Pharmaceutical College Guangxi Medical University Department of pharmacy Affiliated Tumor Hospital of Guangxi Medical University Drug clinical trial Facility office the People's Hospital of Guangxi Zhuang Autonomous Region College of pharmacy Guangxi University of Chinese Medicine Department of pharmacy the Second Affiliated Hospital of Guangxi Medical University Department of pharmacy People's Hospital of Guangxi Hezhou Department of pharmacy Guangzhou Women and Children's Medical Center Liuzhou Hospital Department of pharmacy First Affiliated Hospital of Gannan Medical University

OBJECTIVE: To examine the influence of Saponin Ⅰ from Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPH Ⅰ) on hepatocellular carcinoma(HCC) metastasis,and to elucidate the underlying ***: The intrahepatic metastasis Bagg's Albino/c(BALB/c) mouse model was established with human hepatocellular carcinomas(HepG2) cells, then treated with normal saline(once per day), cisplatin(2 mg/kg, once every 2 d), and SSPH Ⅰ(25, 50, and 75 mg/kg, once per day). Then, we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology ***: Based on our analysis, SSPH Ⅰ significantly alleviated hepatocyte necrosis and tumor cells ***, SSPH Ⅰ suppressed extracellular matrix(ECM) degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2), MMP-9, CD31, CD34,and vascular endothelial growth factor(VEGF) ***, SSPH Ⅰ repressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β 1)/Smad7 axis and epithelial-mesenchymal transition(EMT), as evidenced by the scarce TGF-β1, Ncadherin, and Vimentin expressions, and elevated Smad7 and E-cadherin ***: The SSPH Ⅰ-mediated negative regulation of the TGF-β 1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

关键词： Saponin I from Shuitianqi (Rhizoma Schizocapasae Plantagineae) Smad7 protein carcinoma, hepatocellular epithelial-mesenchymal transition transforming growth factor beta1

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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi LUAN Yang YANG Ying LUAN Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China School of Laboratory Medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China center for Translational Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Henan Key Laboratory of Precision clinical pharmacy Zhengzhou UniversityZhengzhou450052China Henan Engineering Research center for Application&Translation of Precision clinical pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality ***,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for ***-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and ***,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to *** review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in ***,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating ***,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer:A systematic review and meta-analysis

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Chinese Medical Journal 2024年第8期137卷 949-958页

作者： Zhengtong Lv Liuqi Song Miao Wang Huimin Hou Haodong Li Xuan Wang Jianye Wang Jianlong Wang Ming Liu Department of Urology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Graduate School of Peking Union Medical College and Chinese Academy of Medical sciences Beijing 100730China Peking University Fifth School of clinical Medicine Beijing 100730China Peking University China-Japan Friendship School of clinical Medicine Beijing 100029China

Background:Lymph node staging of prostate cancer(PCa)is important for planning and monitoring of treatment.^(18)F-prostate specific membrane antigen positron emission tomography/computerized tomography(^(18)F-PSMA PET/CT)has several advantages over^(68)Ga-PSMA PET/CT,but its diagnostic value requires further *** meta-analysis focused on establishing the diagnostic utility of^(18)F-PSMA PET/CT for lymph node staging in medium/high-risk ***:We searched the EMBASE,PubMed,Cochrane library,and Web of Science databases from inception to October 1,*** cancer,^(18)F,lymph node,PSMA,and PET/CT were used as search terms and the language was limited to *** additionally performed a manual search using the reference lists of key *** and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included ***,specificity,the positive and negative likelihood ratio(PLR and NLR),diagnostic odds ratio(DOR),area under the curve(AUC),and 95%confidence interval(CI)were used to evaluate the diagnostic value of^(18)F-PSMA PET/*** 17 software was employed for calculation and statistical ***:A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this *** the patient level,the results of each consolidated summary were as follows:sensitivity of 0.57(95%CI 0.39-0.73),specificity of 0.95(95%CI 0.92-0.97),PLR of 11.2(95%CI 6.6-19.0),NLR of 0.46(95%CI 0.31-0.68),DOR of 25(95%CI 11-54),and AUC of 0.94(95%CI 0.92-0.96).At the lesion level,the results of each consolidated summary were as follows:sensitivity of 0.40(95%CI 0.21-0.62),specificity of 0.99(95%CI 0.95-1.00),PLR of 40.0(95%CI 9.1-176.3),NLR of 0.61(95%CI 0.42-0.87),DOR of 66(95%CI 14-311),and AUC of 0.86(95%CI 0.83-0.89).Conclusions:^(18)F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk *** diag

关键词： ^(18)F-PSMA PET/CT Diagnostic test Lymph node Meta-analysis Prostate cancer

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Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

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Current Medical Science 2024年第1期44卷 102-109页

作者： Tian-ci LIU Mo-han ZHENG Xing-yue ZENG Rui KANG Ayibaota Bahabayi Bulidierxin Tuerhanbayi Song-song LU Chen LIU Department of clinical Laboratory Peking University People's HospitalBeijing 100044China School of Basic Medical sciences Peking University Health Science CenterBeijing 100191China

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their *** Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy *** cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also *** correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further *** The TFR/TFH ratio increased significantly in NSCLC *** CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage ***-1^(+)ICOS+TFH cells showed a downward trend with increasing *** IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy ***,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar *** numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage *** Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

关键词： non-small cell lung cancer follicular helper T cells follicular regulatory T cells progression

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