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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 Naqiong 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 specific.The 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 BP.The association between RNAm-SNPs,gene expression,and BP were examined.Results A total of 355 RNAm-SNPs related to m6A,m1A,m5C,m7G,and A-to-I modification were associated with BP.The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway.The BP GWAS signals were significantly enriched with m6A-SNPs,highlighting the potential functional relevance of m6A in physiological processes influencing BP.Notably,m6A-SNPs in CYP11B1,PDE3B,HDAC7,ACE,SLC4A7,PDE1A,FRK,MTHFR,NPPA,CACNA1D,and HDAC9 were identified.Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected.RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection(AD)cases and controls.In 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 cells.Conclusion The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs,gene expression,and BP.The 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

Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo wu Yu Kang Xiang Luo Shaoxing Dai yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

New power system development path mechanism design

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Global Energy Interconnection 2023年第2期6卷 166-174页

作者： Xiangyu Chen Guang Tian Yan Huang Yang Yang Jialin Li yuxi wu Yuanying Chi State Grid Hebei Electric Power Co. Ltd.ShijiazhuangHebei 050022P.R.China Energy Development Research Institute China Southern Power GridGuangzhou 510623P.R.China Economic and Technical Research Institute of State Grid Hebei Electric Power Co.Ltd. ShijiazhuangHebei 050022P.R.China School of Economics and Management North China Electric Power UniversityBeijing 102206P.R.China School of Economics and Management Beijing University of TechnologyBeijing 100124P.R.China

Carrying out green energy transformation,implementing clean energy power replacement and supply,and developing a new power system are some primary driving forces needed to fulfill China’s carbon-peak and carbon-neutral strategic goals.The construction of new power systems in China’s provinces and cities is developing rapidly,and the lack of a typical model promotes the application.The new power system path design should be based on the actual development of the power grid in different regions,energy use characteristics,and other actual needs to carry out the differentiated path design.In this context,this study analyzes the characteristics of the new domestic power system based on the policy background of the new domestic power system,constructs a new model for power system development stage identification,and proposes the overall design of the new power system development path from the power supply,transmission and distribution,and load sides.It also uses the Hebei South Network as an example to explore the development stage of the Hebei South Grid based on actual development needs.Finally,this study designs a novel power system development path for the entire supply and demand chain for the Hebei South Grid to propose ideas for constructing a new power system in China and to help green energy transformation.

关键词： New power system Energy transformation Path design

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies

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Cancer Communications 2024年第3期44卷 408-432页

作者： Lu Tang Huan Zhang Fen Zhou Qiuzhe Wei Mengyi Du Jianghua wu Chenggong Li Wenjing Luo Jie Zhou Xindi Wang Zhaozhao Chen Yinqiang Zhang Zhongpei Huang Zhuolin wu yuxi Wen Huiwen Jiang Danying Liao Haiming Kou Wei Xiong Heng Mei Yu Hu Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Clinical Medical Center of Cell Therapy For Neoplastic Disease WuhanHubeiP.R.China Key Laboratory of Biological Targeted Therapy the Ministry of EducationWuhanHubeiP.R.China Department of Thoracic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Pediatrics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Key Laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China

Background:Chimeric antigen receptor T(CAR-T)therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignan-cies,but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood.This study aims to explore the molecular deter-minants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy.Methods:The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing.The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells.In addition,the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models.Results:The CRISPR/Cas9-based knockout screening showed that the enrich-ment of autophagy-related genes(ATG3,BECN1,and RB1CC1)provided protec-tion of cancer cells from CD19 CAR-T cell-mediated cytotoxicity.These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy.Notably,higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer respon-siveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy.Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell ther-apy.Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma.Moreover,our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via th

关键词： CAR-T resistance Autophagy Immune evasion Apoptosis Chemotaxis

First-principles Study on the Ductility Effect of Zirconium and Its Distinct Behavior from Boron to Restrain Hydrogen-induced Embrittlement in Ni-Ni3Al Alloys

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Journal of Materials Science & Technology 2008年第2期24卷 165-171页

作者： yuxi wu Yuanming WANG Shenyang National Laboratory for Materials Science Institute of Metal Research Chinese Academy of Sciences Shenyang 110016 China Anhui University of Technology Graduate School of AHUT Maanshan 243002 China

By studying a cluster model containing Ni region （phase）, NiaAI region （phase） and Ni/Ni3Al region （interface） with a first-principles method, the occupation behavior and the ductility effect of zirconium in a Ni-Ni3Al system were investigated. It is found that zirconium has a stronger segregation tendency to Ni region than to Ni3Al region. The bond order analyses based on Rice-Wang model and the maximum theoretical shear stress model, however, show that zirconium has different degrees of ductility effect in these three regions, which originates from its different ability to increase the Griffith work of interracial cleavage 2γint and to decrease the maximum theoretical shear stress τmax. In addition, it is revealed in this paper that the distinct behavior of zirconium from boron to restrain hydrogen-induced embrittlement can be attributed to their different influences on the crystalline and electronic structures in Ni-Ni3Al alloys.

关键词： Interface Occupation behavior Embrittlement Ductility

Cu_(1)-B dual-active sites catalysts for the efficient dehydrogenative coupling and CO_(2)electroreduction

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Nano Research 2023年第4期16卷 4582-4588页

作者： Konglin wu Zhaobin Fang Cheng Peng Yining Zhang Binbin Jiang Yanshang Kang Zhiming Chen Mingfu Ye yuxi wu Xianwen Wei Shoujie Liu Sha Li Jian Zhang Key Laboratory of Metallurgical Emission Reduction&Resources Recycling of Ministry of Education Anhui University of TechnologyMaanshan 243002China Anhui Laboratory of Clean Catalytic Engineering School of Chemical and Environmental EngineeringAnhui Polytechnic UniversityWuhu 241000China Institute of Clean Energy and Advanced Nanocatalysis(iClean) School of Chemistry and Chemical EngineeringAnhui University of TechnologyMaanshan 243002China Chemistry and Chemical Engineering Guangdong Laboratory Shantou 515063China Institute of Molecular Plus Tianjin UniversityTianjin 300072China School of Chemistry and Chemical Engineering Anqing Normal UniversityAnqing 246001China Jiangxi Province Engineering Research Center of Ecological Chemical Industry Jiujiang UniversityJiujiang 332005China College of Chemistry and Materials Engineering Wenzhou UniversityWenzhou 325035China

Dual-active sites(DASs)catalysts have positive potential applications in broad fields because of their specific active sites and synergistic catalytic effects.Therefore,the controllable synthesis and finely regulating the activity of such catalysts has become a hot research area for now.In this work,we developed a pyrolysis-etching-hydrogen activation strategy to prepare the DASs catalysts involving single-atom Cu and B on N-doped porous carbon material(Cu_(1)-B/NPC).Numerous systematic characterization and density functional theoretical(DFT)calculation results showed that the Cu and B existed as Cu-N4 porphyrinlike unit and B-N_(3)unit in the obtained catalyst.DFT calculations further revealed that single-atom Cu and B sites were linked by bridging N atoms to form the Cu_(1)-B-N6 dual-sites.The Cu_(1)-B/NPC catalyst was more effective than the single-active site catalysts with B-N_(3)sites in NPC(B/NPC)and Cu-N4 porphyrin-like sites in NPC(Cu_(1)/NPC),respectively,for the dehydrogenative coupling of dimethylphenylsilane(DiMPSH)with various alcohols,performing the great activity(>99%)and selectivity(>99%).The catalytic performances of the Cu_(1)-B/NPC catalyst remained nearly unchanged after five cycles,also indicating its outstanding recyclability.DFT calculations showed that the Cu_(1)-B-N6 dual-sites exhibited the lowest energy profile on the potential energy surface than that of sole B-N_(3)and Cu-N4 porphyrin-like sites.Furthermore,the rate-limiting step of dehydrogenation of DiMPSH on Cu_(1)-B-N6 dual-sites also showed a much lower activation energy than the other two single sites.Benefitting from the superiority of the Cu_(1)-B-N6 dual-sites,the Cu_(1)-B/NPC catalyst can also be used for CO_(2)electroreduction to produce syngas.Thus,DASs catalysts are promising to achieve multifunctional catalytic properties and have aroused positive attention in the field of catalysis.

关键词： dual-active sites single-atom catalysis porous carbon dehydrogenative coupling

认同与互动:主流媒体新闻海报的传播效果影响因素与框架分析

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传媒观察 2024年第1期 28-38页

作者：吴晔刘禹希北京师范大学新闻传播学院北京100875

新闻海报日渐成为我国主流媒体在社交平台上向受众传递新闻信息的重要载体。本研究立足于计算图像传播视角,采用视觉框架理论和计算机视觉技术,以人民日报2022年全年新闻海报微博数据为样本(1111条),考察了新闻海报外延层次和风格层次... 详细信息

新闻海报日渐成为我国主流媒体在社交平台上向受众传递新闻信息的重要载体。本研究立足于计算图像传播视角,采用视觉框架理论和计算机视觉技术,以人民日报2022年全年新闻海报微博数据为样本(1111条),考察了新闻海报外延层次和风格层次视觉框架的分布特征及其对于传播效果的影响。外延层次框架包括新闻主题、人物呈现和标题句式三个变量;风格层次框架包括图文组合情况、主要色调和信息量三个变量;传播效果聚焦于认同效果和互动效果两个维度。结果表明,外延层次和风格层次框架整体上对认同效果和互动效果产生显著影响。具体而言,政治外交和灾难事故等主题的新闻海报更容易获得认同和引发互动;包含多种媒介形式的新闻海报有助于更广泛传播;感叹句式标题、包含人物元素、暖色调等因素对提高新闻海报传播效果有积极作用。本研究不仅深化了对新闻海报在计算图像传播背景下的传播机制的理解,也为媒体从业者提供了实践指导,指出了计算图像传播在新闻传播实践中的应用价值和前景。

关键词：新闻海报传播效果视觉框架理论计算机视觉新浪微博

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中国全科医学 2024年第24期27卷 2954-2960,2968页

作者：祁海燕王捷罗玉玺武云新疆医科大学第一附属医院全科医学科新疆维吾尔自治区乌鲁木齐市830011 新疆医科大学第一附属医院临床药学科新疆维吾尔自治区乌鲁木齐市830011 新疆医科大学第一临床医学院新疆维吾尔自治区乌鲁木齐市830011

背景近年来众多研究表明高尿酸血症(HUA)是某些疾病的影响因素,然而HUA是否为慢性肺源性心脏病(CPHD)的影响因素仍需进一步研究。目的探讨HUA与CPHD的相关性,旨在为CPHD患者血尿酸(SUA)水平的管理提供理论依据。方法纳入2019—2023年新... 详细信息

背景近年来众多研究表明高尿酸血症(HUA)是某些疾病的影响因素,然而HUA是否为慢性肺源性心脏病(CPHD)的影响因素仍需进一步研究。目的探讨HUA与CPHD的相关性,旨在为CPHD患者血尿酸(SUA)水平的管理提供理论依据。方法纳入2019—2023年新疆医科大学第一附属医院收治的1171例慢性阻塞性肺疾病(COPD)患者为研究对象,根据其是否患有CPHD分为CPHD组(470例)和COPD组(701例)。收集患者一般资料和实验室检查及超声心动图检查结果。采用LASSO回归法对变量进行筛选,采用倾向性评分匹配法(PSM)排除混杂因素影响。采用多因素Logistic回归分析探究COPD患者合并CPHD的影响因素。结果CPHD组女性、汉族、吸烟、饮酒、特发性肺纤维化、慢性支气管炎、支气管哮喘比例、淋巴细胞百分比、左心室舒张末期内径、左心室收缩末期内径、心输出量、左心室射血分数低于COPD组,心功能3~4级、HUA、肺栓塞、先天性心脏病比例、红细胞计数、中性粒细胞百分比、SUA、血尿素氮、D-二聚体、N末端-B型利钠肽前体、右心房内径、右心室内径、左心房内径、右心室流出道内径、肺动脉内径高于COPD组,差异有统计学意义(P381.29μmol/L)患者患有CPHD的风险增加1.421倍。结论HUA是CPHD疾病发生、发展的影响因素,积极控制SUA水平有助于预防CPHD的发生、发展。

关键词：肺心病高尿酸血症肺疾病,慢性阻塞性病例对照研究最小绝对收缩和选择算法倾向性评分

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从生态翻译学看散文英译中主体间性的实现——以《雨前》英译本比较研究为例

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现代英语 2024年第1期 102-104页

作者：吴羽希天津财经大学天津300222

相比硕果累累的邻近文体诗歌和小说,散文英译任重道远。何其芳的《雨前》文言溢美、意境融彻,通过对自然画卷的细腻描摹,赋予了生灵万物与人类同等的主体位,无形之中渗透出作者人与自然和谐共生的生态观。文章拟以张梦井和杜耀文译文、R... 详细信息

相比硕果累累的邻近文体诗歌和小说,散文英译任重道远。何其芳的《雨前》文言溢美、意境融彻,通过对自然画卷的细腻描摹,赋予了生灵万物与人类同等的主体位,无形之中渗透出作者人与自然和谐共生的生态观。文章拟以张梦井和杜耀文译文、Robert Neather译文以及张培基译文为研究对象,从生态翻译学角度展开比较研究,探讨译者在散文英译中如何实现多元主体和谐统一的主体间性,从而使译文达到理想的审美境界。

关键词：生态翻译学主体间性何其芳雨前