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Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants

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Chronic Diseases and Translational Medicine 2024年第2期10卷 118-129页

作者： Huan Zhang Yuxi Chen Peng xu Dan Liu Naq.ong Wu Laiyuan Wang Xingbo Mo Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Department of EpidemiologySchool of Public HealthMedical College of Soochow UniversitySuzhouJiangsuChina Cardiometabolic Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Cardiovascular Epidemiology&Department of Epidemiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina MOE Key Laboratory of Geriatric Diseases and Immunology School of Public HealthCenter for Genetic Epidemiology and GenomicsMedical College of Soochow UniversitySuzhouJiangsuChina

Background Genome-wide association studies(GWAS)have identified more than a thousand loci for blood pressure(BP).Functional genes in these loci are cell-type *** aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms(RNAm-SNPs).Methods Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium,we identified associations between RNAm-SNPs and *** association between RNAm-SNPs,gene expression,and BP were *** A total of 355 RNAm-SNPs related to m6A,m1A,m5C,m7G,and A-to-I modification were associated with *** related genes were enriched in the pancreatic secretion pathway and renin secretion *** BP GWAS signals were significantly enriched with m6A-SNPs,highlighting the potential functional relevance of m6A in physiological processes influencing ***,m6A-SNPs in CYP11B1,PDE3B,HDAC7,ACE,SLC4A7,PDE1A,FRK,MTHFR,NPPA,CACNA1D,and HDAC9 were *** methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were ***-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection(AD)cases and *** scRNA-seq.study,we identified ARID5A,HLA-DPB1,HLA-DRA,IRF1,LINC01091,MCL1,MLF1,MLXIPL,NAA16,NADK,RERG,SRM,and USP53 as differential expression genes for AD in aortic *** The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs,gene expression,and *** identified BP-associated genes in aortic cells were associated with AD.

关键词： aortic dissection blood pressure genome-wide association study RNA modification single-cell

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Specific Heat and Interface Energy of Nanostructured ZrAlNiCuCo Alloy

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Journal of Materials Science & Technology 1997年第4期13卷 284-288页

作者： Jiang, q.Sui, ZX Li, JC xu, XY Dept. of Materials Science and Engineering Jilin University of Technology Changchun 130025 China

The specific heat of the nanostructured crystals, the glass, the liq.id and the crystals for a ZrAlNiCuCo alloy has been measured by using the differential scanning calorimeter. The specific heat value and its temperature coefficient of the nanostructured crystals are larger than that of the relaxed glass and of the crystals. Through measuring crystallization enthalpies and specific heat of the alloy in different states, the enthalpy differences among the crystals, the liq.id and the nanostructured crystals are calculated and the interface energies of nanostructured crystals are estimated. The stability and the grain size limit of the nanostructured crystals are discussed.

关键词： Nanostructured materials

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青藏高原及其周边二叠纪综合地层、生物群以及古地理和古气候演化

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中国科学：地球科学 2024年第4期54卷 1125-1170页

作者：沈树忠张以春袁东勋徐海鹏琚琦张华郑全锋罗茂侯章帅南京大学地球科学与工程学院内生金属矿床成矿机制研究国家重点实验室关键地球物质循环前沿科学中心南京210023 中国科学院南京地质古生物研究所现代古生物学和地层学国家重点实验室南京210008 中国科学院大学南京学院南京210049 中国矿业大学资源与地球科学学院徐州221116

二叠纪是青藏高原各块体演化的关键时段,发生了一系列重大地质和生物事件,当时横跨南北半球统一的泛大陆演化到了鼎盛阶段,阻断了全球东西向的赤道暖流的同时,在泛大陆的东侧形成了一个半封闭的、具有重要历史意义的特提斯洋暖池,是古-... 详细信息

二叠纪是青藏高原各块体演化的关键时段,发生了一系列重大地质和生物事件,当时横跨南北半球统一的泛大陆演化到了鼎盛阶段,阻断了全球东西向的赤道暖流的同时,在泛大陆的东侧形成了一个半封闭的、具有重要历史意义的特提斯洋暖池,是古-中生代之交生物与环境演变的引擎.青藏高原二叠纪地层分布广泛、化石丰富,从南到北由于跨越不同的纬度带体现出不同的特点.雅鲁藏布江以南的喜马拉雅特提斯带当时位于冈瓦纳大陆印度板块北缘,整个二叠纪沉积含有典型的冈瓦纳冷水型生物群;雅鲁藏布江缝合带内的灰岩外来体时代集中在瓜德鲁普世(Guadalupian,中二叠世)中、晚期至早三叠世,古生物地理与喜马拉雅特提斯带有显著差异,最有可能为新特提斯洋中的海山型沉积.基墨里(Cimmerian)微地块群在乌拉尔世(Cisuralian,早二叠世)早期阿瑟尔期-萨克马尔期(Asselian-Sakmarian)全部位于冈瓦纳大陆北缘,均发育冰海相沉积及冈瓦纳型冷水生物群.乌拉尔世中期(约290~280Ma)基墨里微地块群由于印度板块北缘Panjal Traps等大火成岩省岩浆活动与冈瓦纳大陆裂解,并以不同的速度向北漂移.可以分为两个条带,由南羌塘、保山和Sibuma地块组成的北基墨里微地块群漂移速度较快,在亚丁斯克期(Artinskian)就已经出现大量碳酸盐岩沉积和暖水生物群,因此,它们最先从冈瓦纳大陆裂解并进入低纬度暖水区域;而由拉萨、腾冲和Irrawaddy地块组成的南基墨里微地块群,漂移速度相对较慢,在空谷(Kungurian)晚期才开始出现大规模碳酸盐岩沉积,并延续至乐平世(Lopingian,晚二叠世),瓜德鲁普世和乐平世地层中含暖水生物为主的动物群,因此,这些地块至少在空谷晚期已经从冈瓦纳大陆北缘分离,裂解时间稍晚于北基墨里微地块群;这种沉积和古生物地理的时空演变差异性表明乌拉尔世的裂解事件造成了中特提斯洋和新特提斯洋的开启和形成.更北的北羌塘地块由于整个二叠纪地层中均含有典型的暖水生物群,与华南地区、思茅地块和印支地块等可以比较,属于古特提斯洋北部的块体.因此,二叠纪中、晚期特提斯域形成了古、中、新特提斯多岛洋共存的局面,是当时构造活动最活跃的地区和全球生物多样性的中心.此外,青藏高原多个块体在二叠纪位于南半球中高纬度地区,完整记录了晚古生代大冰期、亚丁斯克期全球变暖和二叠纪末快速变暖等重大古气候事件,对于阐明板块运动和全球气候演变对生物群时空分布的影响具有举足轻重的作用.

关键词：二叠纪特提斯洋青藏高原生物群古地理

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Packing Densities and Glass Forming Ability of Alloys

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Journal of Materials Science & Technology 1996年第4期12卷 299-302页

作者： Jiang, q.xu, XY Niu, HJ Lu, XX Dept. of Materials Science and Engineering Jilin University of Technology Changchun 130025 China

The random closed packing fraction of hard balls of three different sizes were measured by use of the Archimedes method. This packing fraction increases as the kind of balls with different sizes increases. The packing fraction is related to the mixing entropy of an ideal solution in respect to the holes among the hard balls. The composition zone of La-Al-Ni amorphous alloy made by cooling the alloy melt with a cooling rate of 90 Ks(-1) is located at same zone of the largest values of packing fraction and mixing entropy of hard balls in the ternary system, where the proportion of atom sizes of La, Al and Ni is similar to that of hard balls. The packing fraction and the mixing entropy are q.alitatively considered as one of the criteria of the glass forming ability of alloys.

关键词： Amorphous materials

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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang xu Zhu Zeq.n Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q.3.13 locus,acted as a transcription factor playing critical roles in *** subseq.ent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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DEFORMATION　AND　FRACTURE　MECHANISMS　OF　TWO－PHASE　TiAl－BASED　ALLOYS　WITH　FULLY　LAMELLAR　MICROSTRUCTURE

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Acta Metallurgica Sinica(English Letters) 1995年第Z1期8卷 359-368页

作者： Y. G .Zhang, C. q. Chen (Beijing University of Aeronautics and Astronautics, Beijing 100083, China)q. xu (Beijing Laboratory of Electron Microscopy, Chinese Academy of Sciences. Beijing,China)M. C. Chaturvedi (The University of Manitoba, Winnipeg, Manito Beijing Univ of Aeronautics and Astronautics Beijing China

A two-phase TiAl-based alloy with fully lamellar structure has been deformed al room temperature and the deformed microstructures have been examined in dtails by optical microscopy(OM), scanning electron microscopy(SEM) and transmission electron microscopy(TEM) . Deformation mechanisms in the γ-TiAl phase has been defined and the role of grain boundaries in the deformation and fracture has been assessed Some of the mechanisms of interactions between twinning or gliding dislocations and three types of γ γ domain boundaries or γ α_2 interface in a lamellar grain have been identified and resistance of the various domain boundaries or the interface to the propagation of twinning has been evaluated

关键词： TiAl Deformation mechanism Lamellae Twinning

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INFLUENCE OF TEMPERATURE AND PRESSURE ON THE KINETICS OF Mg-6mol%LaNi PREPARED BY HYDRIDING COMBUSTION SYNTHESIS

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Acta Metallurgica Sinica(English Letters) 2006年第2期19卷 124-132页

作者： q. Li K.C. Chou K.D. xu L.J. Jiang J.Y. Zhang X.G. Lu School of Materials Science and Engineering Shanghai University Shanghai 200072 China Department of Physical Chemistry University of Science and Technology Beijing Beijing 100083 China General Research Institute for Nonferrous Metals Beijing 100088 China

A new model to study the hydriding/dehydriding （H/D） kinetic mechanism has been applied in the two-phase （α-β） region of the Mg-6mol%LaNi composite at temperature and pressure ranging from 523 to 623K and 0.256 to 0.992MPa H2. respectively. The coincidence of the theoretical calculation with the experimental data indicates that the rate-limiting step is hydrogen diffusion in the β phase for hydriding process and the diffusion of hydrogen in the α solid solution for hydrogen desorption with activation energies 89500 and 87900J/mol H2 for HID processes, respectively, which were much smaller than those of MgH2 and can be attributed to the La and Ni additions.

关键词： powder metallurgy hydrogen storage materials kinetics

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Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

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Chinese Journal of Cancer 2011年第6期30卷 415-425页

作者： Callinice D. Capo-chichi Kathy q. Cai Jennifer Smedberg Parvin Ganjei-Azar Andrew K. Godwin Xiang-Xi xu Sylvester Comprehensive Cancer Center University of Kansas Medical Center Kansas City KS 66160 USA. Department of Medicine University of Kansas Medical Center Kansas City KS 66160 USA. Ovarian Cancer Program Fox Chase Cancer Center Philadelphia PA 19111 USA Department of Pathology University of Kansas Medical Center Kansas City KS 66160 USA. Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City KS 66160 USA. Department of Obstetrics and Gynecology University of Miami School of Medicine Miami FL 33136 USA

Through advances in technology,the genetic basis of cancer has been investigated at the genomic level,and many fundamental q.estions have begun to be *** several key unresolved q.estions in cancer biology,the molecular basis for the link between nuclear deformation and malignancy has not been *** hallmark of human cancer is aneuploidy;however,the causes and conseq.ences of aneuploidy are unanswered and are hotly contested *** found that nuclear lamina proteins lamin A/C are absent in a significant fraction(38%) of human breast cancer *** in lamin A/C-positive breast cancer,lamin A/C expression is heterogeneous or aberrant(such as non-nuclear distribution) in the population of tumor cells,as determined by immunohistology and immunofluorescence *** most breast cancer cell lines,a significant fraction of the lamin A/C-negative population was *** determine the conseq.ences of the loss of lamin A/C,we suppressed their expression by shRNA in noncancerous primary breast epithelial ***-regulation of lamin A/C in breast epithelial cells led to morphological deformation,resembling that of cancer cells,as observed by immunofluorescence *** lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ *** conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.

关键词：核纤层蛋白乳腺癌蛋白表达损失核被膜乳腺上皮细胞非整倍体整性

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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiq.ang xu q.lian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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Ground-state mass of ^(22)Al and test of state-of-the-art ab initio calculations

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Chinese Physics C 2024年第3期48卷 72-78页

作者：孙铭泽于越王新鹏王猛李健国张玉虎 K.Blaum 陈祖毅陈瑞九邓涵宇付超义葛文文黄文嘉焦红扬李红蕙李宏福罗胤芳廖挺 YuALitvinov 司敏帅鹏史金阳王茜邢元明徐星徐瑚珊许甫荣袁琪 T.Yamaguchi 颜鑫亮杨建成原有进周小红周旭张敏曾奇 CAS Key Laboratory of High Precision Nuclear Spectroscopy Institute of Modern PhysicsChinese Academy of SciencesLanzhou 730000China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China Max-Planck-Institut für Kernphysik Saupfercheckweg 169117 HeidelbergGermany GSI Helmholtzzentrum für Schwerionenforschung Planckstraße 164291 DarmstadtGermany Advanced Energy Science and Technology Guangdong Laboratory Huizhou516007China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China Department of Physics Saitama UniversitySaitama 338-8570Japan School of Nuclear Science and Engineering East China University of TechnologyNanchang 330013China

The ground-state mass excess of the T_(z)=−2 drip-line nucleus ^(22)Al is measured for the first time as 18103(10)keV using the newly-developed Bρ-defined isochronous mass spectrometry method at the cooler storage ring in *** new mass excess value allowed us to determine the excitation energies of the two low-lying 1+states in ^(22)Al with significantly reduced uncertainties of 51 *** compared to the analogue states in its mirror nucleus ^(22)F,the mirror energy differences of the two 1^(+)states in the ^(22)Al-^(22)F mirror pair are determined to be−625(51)keV and−330(51)*** excitation energies and mirror energy differences are used to test the state-of-the-art ab initio valence-space in-medium similarity renormalization group calculations with four sets of interactions derived from the chiral effective field *** mechanism leading to the large mirror energy differences is investigated and attributed to the occupation of theπs_(1/2) orbital.

关键词： nuclear mass Bρ-defined IMS mirror energy difference ab initio VS-IMSRG calculations chiral interactions

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