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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing chen zhang Shuai Ma Weiqi zhang daoyuan Huang Bin zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu Yang Yu Jing Qu Si Wang Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research Center Peking UniversityThird HospitalBeijing 100191China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian ***,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal *** study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

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Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： daoyuan Huang Qian Zhao Kuan Yang Jinghui Lei Ying Jing Hongyu Li chen zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing Qu Weiqi zhang Si Wang Guang-Hui Liu Advanced Innovation Centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational MedicineCenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing100101China CAS Key Laboratory of Genomic and Precision Medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China National Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to *** investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC ***,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang cheng Weiqi zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

考虑奖惩分配机制的畜禽粪污第三方治理演化博弈分析——基于“无过错责任原则”

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中国农业资源与区划 2024年第1期45卷 223-237页

作者：张浩胡子坤庄道元淮北师范大学经济与管理学院安徽淮北235000

[目的]为了有效推动我国畜禽养殖粪污治理,促进农业的可持续发展。[方法]文章基于组织行为视角,采用演化博弈的方法,构建畜禽粪污治理中养殖企业、第三方治理公司和地方政府的三方演化博弈模型,依据“无过错责任原则”,对养殖企业与第... 详细信息

[目的]为了有效推动我国畜禽养殖粪污治理,促进农业的可持续发展。[方法]文章基于组织行为视角,采用演化博弈的方法,构建畜禽粪污治理中养殖企业、第三方治理公司和地方政府的三方演化博弈模型,依据“无过错责任原则”,对养殖企业与第三方治理公司的责任进行界定,并引入奖惩分配机制,通过求解三方复制动态方程均衡点,对各主体的渐进式稳定条件进行了分析,运用MATLAB软件仿真了相关参数对系统稳定性的影响。[结果]奖惩力度、奖惩分配系数以及声誉收益的提高均对养殖企业和第三方治理公司的行为产生正向影响,且养殖企业较第三方治理公司表现出更强的收益敏感性,上级政府的政策支持和行政问责力度的增大以及地方政府监管成本的降低均可以有效避免地方政府监管缺位现象的发生。[结论]建议落实养殖企业和第三方治理公司的主体责任,设置合理的奖惩力度和分配系数。

关键词：奖惩分配机制畜禽粪污第三方治理演化博弈无过错责任原则

要素替代弹性、有偏技术进步和劳动收入份额上升

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财贸经济 2024年第1期45卷 141-157页

作者：尹恒张道远李辉中国人民大学国家发展与战略研究院 100872 中国人民大学财政金融学院 100872

资本一劳动替代弹性是理解劳动收入份额演变的关键。本文在一个整合生产端和需求端的结构估计框架内同时纳入中性和有偏技术进步,使用全国税收调查数据估计微观替代弹性,然后加总得到宏观替代弹性,并在此基础上考察金融危机以来劳动收... 详细信息

资本一劳动替代弹性是理解劳动收入份额演变的关键。本文在一个整合生产端和需求端的结构估计框架内同时纳入中性和有偏技术进步,使用全国税收调查数据估计微观替代弹性,然后加总得到宏观替代弹性,并在此基础上考察金融危机以来劳动收入份额上升的驱动力。研究结果如下,(1)2007-2016年微观替代弹性平均为2.877,且制造业要高于服务业。考虑需求价格弹性和资本密集度等其他企业异质性后,中国全行业加总替代弹性为2.540,表明中国资本和劳动要素总体呈现替代关系。(2)给定替代弹性估计,2007年后劳动收入份额上升并非由要素相对价格变化驱动,劳动市场垄断及劳动调整成本等剩余未解释因素的影响也较小。真正动因在于有偏技术进步,它可以解释这一时期劳动收入份额变化的187%,且有偏技术进步对制造业劳动收入份额上升的促进作用明显高于服务业。本文描述了金融危机以来中国资本一劳动替代弹性演变的整体图景,并据此识别出近年来劳动收入份额上升的核心动力,可以为新时期推动中国经济高质量发展的公共政策提供重要的决策依据。

关键词：替代弹性劳动收入份额有偏技术进步结构估计要素相对价格

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基于群组决策的寒区隧道冻害风险评价研究

铁道工程学报 2024年第3期41卷 91-99页

作者：张亚琴王道远袁金秀张业权赵斌崔光耀章浩天孙梁河北交通职业技术学院石家庄050091 河北省季冻区公路服役安全与预警技术创新中心石家庄050091 中铁十九局集团第三工程有限公司沈阳110136 北方工业大学北京100144 河北省交通规划设计研究院有限公司石家庄050299

研究目的:为客观有效评估隧道冻害程度,基于群组决策和三角模糊数法构建寒区隧道冻害风险评价模型。首先,采用更有利于专家表达的三角模糊数建立判断矩阵,利用相容度指标确定专家判断水平,从而赋予相应权重;其次,综合考虑引起寒区隧道... 详细信息

研究目的:为客观有效评估隧道冻害程度,基于群组决策和三角模糊数法构建寒区隧道冻害风险评价模型。首先,采用更有利于专家表达的三角模糊数建立判断矩阵,利用相容度指标确定专家判断水平,从而赋予相应权重;其次,综合考虑引起寒区隧道冻害的温度、水文、围岩条件和工程措施等因素,形成二级评价指标,通过三角模糊数群组决策模型确定各指标权重;再次,将二级评价指标分为10个定量指标和6个定性指标,定量指标按梯形分布建立隶属度函数,定性指标由专家按百分制打分,再按梯形分布函数确定各等级隶属度;最后,通过模糊综合评价方法计算确定隧道冻害等级,并提供相应的预防措施。研究结论:(1)选取温度、水文、围岩条件和工程措施4个一级指标、16个二级指标,设置4个冻害等级,构建了基于三角模糊数的群组决策寒区隧道冻害风险综合评价体系;(2)本文提出的冻害风险评价模型应用于杀虎口隧道,风险等级评价结果与隧道实际冻害一致,验证了模型的合理性;(3)本文模型更加客观全面,可为隧道冻害风险提供安全预警和防控建议。

关键词：寒区隧道三角模糊数群组决策冻害风险综合评价

Implications for rock instability precursors and principal stress direction from rock acoustic experiments

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International Journal of Mining Science and Technology 2021年第5期31卷 789-798页

作者： Longjun Dong Yongchao chen daoyuan Sun Yihan zhang School of Resources and Safety Engineering Central South UniversityChangsha 410083China

The characteristics of rock instability precursors and the principal stress direction are very crucial for the prevention of geological *** study investigated the qualitative relationship between rock instability precursors and principal stress direction through wave velocity in rock acoustic emission(AE)*** show that the wave velocity variation exhibits obvious anisotropic characteristics in 0%–20%and 60%–90%of peak strength due to the differences of stress-induced microcrack *** amplitude of wave velocity variation is related to the azimuth and position of wave propagation path,which indicates that the principal stress direction can be identified by the anisotropic characteristics of wave velocity ***,the experiments also demonstrate that the AE event rate and wave velocity show quiet and stable variations in the elastic stage of rock samples,while they present a trend of active and unstable variations in the plastic *** implies that both the AE event rate and wave velocity are effective monitoring parameters for rock *** anisotropic characteristics of the wave velocity variation and AE event rate are beneficial complements for identifying the rock instability precursors and determining the principal stress direction,which provides a new analysis method for stability monitoring in practical rock engineering.

关键词： Precursor characteristics Wave velocity Acoustic emission Anisotropic Principal stress direction

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露天原料场堆取料机共轨布置方案探讨

港口装卸 2024年第3期 68-70页

作者：张道远北京首钢国际工程技术有限公司北京市100043 北京市冶金三维仿真设计工程技术研究中心

针对某露天原料场进行封闭改造后出现的储存能力不足、部分堆取料机超负荷工作等问题,提出一种原料场改造方案,在原料场新增一台堆料机,并与现有取料机共轨布置,给出了设备设施改造、工艺流程优化、共轨堆取料机智能化改造技术要点。项... 详细信息

针对某露天原料场进行封闭改造后出现的储存能力不足、部分堆取料机超负荷工作等问题,提出一种原料场改造方案,在原料场新增一台堆料机,并与现有取料机共轨布置,给出了设备设施改造、工艺流程优化、共轨堆取料机智能化改造技术要点。项目投产后运转良好,达到了原料场性能升级的预期目标。

关键词：堆取料机共轨布置智能化改造原料场

Desiccation tolerance in bryophytes： the rehydration proteomes of Bryum argenteum provide insights into the resuscitation mechanism

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Journal of Arid Land 2018年第1期10卷 152-167页

作者： GAO Bei zhang daoyuan LI Xiaoshuang YANG Honglan LIANG Yuqing chen Moxian zhang yuanming zhang Jianhua Andrew WOOD Key Laboratory of Biogeography and Bioresource in Arid Land Xinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China School of Life Sciences and State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongHong KongChina Department of Biology Faculty of ScienceHong Kong Baptist UniversityHong KongChina Department of Plant Biology Southern Illinois University-CarbondaleCarbondaleIL 62901-6509USA

Bryum argenteum Hedw. is a desiccation tolerant bryophyte and belongs to one of the most important components of the biological soil crusts （BSCs） found in the deserts of Central Asia. Limited information is available on rehydration-responsive proteins in desiccation tolerant plants. As a complement to our previous research analyzing the rehydration transcriptome, we present a parallel quantitative proteomic effort to study rehydration-responsive proteins. Bryophyte gametophores were desiccated （Dry） and rehydrated for 2 h （R2） and 24 h （R24）. Proteins from Dry, R2 and R24 gametophores were labeled by isobaric tags for relative and absolute quantitation （iTRAQ） to determine the relative abundance of rehydration-responsive proteins. A total of 5503 non-redundant protein sequences were identified and 4772 （86.7%） protein sequences were annotated using Gene Ontology （GO） terms and Pfam classifications. Upon rehydration 239 proteins were elevated and 461 proteins were reduced as compared to the desiccated protein sample. Differentially up-regulated proteins were classified into a number of categories including reactive oxygen species scavenging enzymes, detoxifying enzymes, Late Embryogenesis Abundant （LEA） proteins, heat shock proteins, proteasome components and proteases, and photosynthesis and translation related proteins. Furthermore, the results of the correlation between transcriptome and proteome revealed the discordant changes in the expression between protein and mRNA.

关键词： desiccation tolerance B*Tum Physcomitrellapatens proteome iTRAQ rehydration