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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

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

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

Laparoscopy combined with hysteroscopy in the treatment of Robert’s uterus accompanied by adenomyosis:A case report

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World Journal of Clinical Cases 2024年第25期12卷 5769-5774页

作者： Jie Dong Jia-Jian Wang jing-ying Fei Li-Fang Wu ying-ying Chen Department of Gynecology Huzhou Maternity&Child Health Care HospitalHuzhou 313000Zhejiang ProvinceChina Department of Ultrasound Huzhou Maternity&Child Health Care HospitalHuzhou 313000Zhejiang ProvinceChina

BACKGROUND Gynaecologists should be aware of a rare obstructive Mullerian duct abnormality like Robert’s uterus and perform further surgery when *** SUMMARY We report a 41-year-old mother of two children with Robert’s uterus who was examined and treated by laparoscopy and *** the existing cases reported in the literature,this patient had a late onset of Robert’s uterus *** to right tubal ectopic pregnancy 3 years previously,the patient was treated with right salpingectomy and left tubal ligation but suffered aggravated left lower abdominal *** was examined and treated by laparoscopy and hysteroscopy,and is completely asymptomatic at 5-year *** The typical obstructive Mullerian abnormality requires further *** laparoscopy and hysteroscopy is an effective,minimally invasive technique with better recovery outcomes than traditional transabdominal procedures.

关键词： Laparoscopy Hysteroscopy Robert’s uterus Mullerian duct abnormality Case report

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宁夏地区新生儿杜氏肌营养不良症筛查

中国当代儿科杂志 2024年第3期26卷 258-261页

作者：井淼王悦景晓莹毛新梅北京大学第一医院宁夏妇女儿童医院/宁夏回族自治区妇幼保健院遗传代谢性疾病科宁夏银川750002

目的初步评估宁夏地区男性新生儿人群中杜氏肌营养不良症(Duchennemusculardystrophy,DMD)发病率,建立新生儿DMD筛查的临界值以区分新生儿正常人群和患病人群。方法采用免疫荧光分析法对10000例男性新生儿足跟干血斑滤纸片中的肌酸激酶... 详细信息

目的初步评估宁夏地区男性新生儿人群中杜氏肌营养不良症(Duchennemusculardystrophy,DMD)发病率,建立新生儿DMD筛查的临界值以区分新生儿正常人群和患病人群。方法采用免疫荧光分析法对10000例男性新生儿足跟干血斑滤纸片中的肌酸激酶同工酶浓度进行检测,筛查出高于正常临界值的新生儿,召回进行血清肌酸激酶浓度测定,异常者通过基因检测以明确DMD诊断。结果共筛查10000例男性新生儿,其中2例新生儿经基因检测确诊为DMD,初步估算宁夏地区男性新生儿DMD发病率为1/5000;宁夏地区新生儿肌酸激酶同工酶浓度临界值为468.57ng/mL。结论在宁夏地区进行新生儿DMD筛查是可行的,通过对DMD患儿的早期筛查、早期诊断和早期治疗,可以改善患儿生活质量,为家庭再生育赢得更短的决策时间。

关键词：杜氏肌营养不良症筛查发病率肌酸激酶同工酶临界值新生儿

基于DIC技术的钢筋混凝土梁剪切裂缝自动提取与量化方法

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工程力学 2024年第S01期41卷 187-196页

作者：杨子涵舒江鹏杨静滢李俊白勇浙江大学建筑工程学院浙江杭州310058

针对钢筋混凝土梁实验中剪切斜裂缝的自动化定位、全域范围内各方向宽度量化及扩展追踪问题,该文提出一种基于数字图像相关技术(DIC)的裂缝自动提取与宽度量化的计算方法。由DIC计算得出的水平、竖直、剪切应变场来计算试件表面的主拉... 详细信息

针对钢筋混凝土梁实验中剪切斜裂缝的自动化定位、全域范围内各方向宽度量化及扩展追踪问题,该文提出一种基于数字图像相关技术(DIC)的裂缝自动提取与宽度量化的计算方法。由DIC计算得出的水平、竖直、剪切应变场来计算试件表面的主拉伸应变场,并将试件表面主应变大于某一阈值的部分视为开裂。对开裂部分进行形态学操作,提取出裂缝骨架线。在骨架线两侧定义裂缝运动参考点,根据参考点的运动来计算裂缝的发展规律。该计算方法实现了混凝土梁加载过程中任意方向上裂缝自动化检测及高精度量化,并且能够处理试件局部旋转的问题,充分了利用DIC测量技术的潜力。通过实验室内四组钢筋混凝土梁剪切实验验证该方法的有效性与精度。结果表明:该方法能够在多加载阶段实时追踪全域范围内各方向的裂缝开展并量化。

关键词：钢筋混凝土梁剪切裂缝数字图像相关实时追踪量化主应变场

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油品检定仪器精度提升及标准化方法探索

纯碱工业 2024年第4期 32-34页

作者：周莉荆莹山东柏森化工技术检测有限责任公司山东东营257000

设备润滑油的品质直接影响机械的运转性能与寿命,因此准确检定其关键指标至关重要。本文系统探讨了提升检定仪器精度、实现行业标准化的解决方案。通过优化粘度计、水分仪等核心部件设计,改进信号处理与自动标定环节,仪器线性度和重复... 详细信息

设备润滑油的品质直接影响机械的运转性能与寿命,因此准确检定其关键指标至关重要。本文系统探讨了提升检定仪器精度、实现行业标准化的解决方案。通过优化粘度计、水分仪等核心部件设计,改进信号处理与自动标定环节,仪器线性度和重复性得到显著提升。在检定方法上,针对新型合成润滑油的特性,构建了基于多元回归的标准曲线修正模型,形成一套规范化操作规程。数据处理中,采用小波变换与局部加权回归散点平滑相结合的融合算法,抑制了噪声与异常值影响。多个典型矿物油与合成油检定案例表明,改进方案能使仪器精度提高,为后续推广应用和行业标准制定奠定了基础。

关键词：润滑油检定精度提升标准曲线修正模型小波变换标准化

1-磷酸鞘氨醇受体3对脂多糖处理大鼠肾小管上皮细胞凋亡的影响

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现代实用医学 2024年第2期36卷 166-169页

作者：吴晋应静宁波大学附属第一医院宁波315010

目的探讨1-磷酸鞘氨醇受体3(S1PR3)对脂多糖(LPS)处理大鼠肾小管上皮细胞凋亡的影响。方法将培养好的大鼠肾小管细胞(NRK-52E)分为对照组、LPS组、S1PR3激动剂+LPS组。对照组不做处理;LPS组予LPS(20μg/ml)刺激12h后做离心收集待检;S1PR... 详细信息

目的探讨1-磷酸鞘氨醇受体3(S1PR3)对脂多糖(LPS)处理大鼠肾小管上皮细胞凋亡的影响。方法将培养好的大鼠肾小管细胞(NRK-52E)分为对照组、LPS组、S1PR3激动剂+LPS组。对照组不做处理;LPS组予LPS(20μg/ml)刺激12h后做离心收集待检;S1PR3激动剂+LPS组先用S1PR3激动剂KRX-725预处理2 h后再予LPS(20μg/ml)刺激12 h后做离心收集待检。流式细胞术检测各组细胞凋亡率、钙离子表达及caspase-3表达的差异,ELISA试剂盒检测Calpain 1、Calpain 2的表达差异,Western Blot检测各组细胞中S1PR3的表达差异。结果LPS处理后脓毒症NRK-52E细胞模型成功建立,相比于对照组,LPS组和S1PR3激动剂+LPS组的细胞凋亡率、S1PR3表达、钙离子浓度、Calpain 1与Calpain2的表达、caspase-3表达均显著增加(均P<0.05);与LPS组相比,S1PR3激动剂+LPS组的细胞凋亡率、钙离子浓度、Calpain 1与Calpain2的表达、caspase-3表达均显著增加(均P<0.05),S1PR3表达显著增加(P<0.05)。结论S1PR3的激活能够增加肾小管上皮细胞内的钙离子浓度,从而激活caspase-3细胞凋亡信号通路,导致脓毒症肾小管上皮细胞凋亡增加。

关键词：脓毒症 1-磷酸鞘氨醇受体3 肾小管上皮细胞凋亡

利用野生种Solanum boliviense创制马铃薯抗寒种质

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作物学报 2024年第6期50卷 1384-1393页

作者：刘园园董建科应静文梅文祥程刚郭晶晶焦文标宋波涛华中农业大学园艺林学学院/农业农村部马铃薯生物学与生物技术重点实验室/果蔬园艺作物种质创新与利用全国重点实验室湖北武汉430070 鄂州市农产品质量安全检验检测所湖北鄂州436099 华中农业大学信息学院湖北武汉430070

马铃薯栽培种不耐低温霜冻,低温直接影响植株和块茎的生长和发育,进而影响马铃薯的产量。马铃薯野生种抗性资源丰富,***等野生种存在丰富的低温霜冻抗性,它们是改良马铃薯栽培种的重要资源。本研究在对野生种***不同株系进行抗寒性鉴定... 详细信息

马铃薯栽培种不耐低温霜冻,低温直接影响植株和块茎的生长和发育,进而影响马铃薯的产量。马铃薯野生种抗性资源丰富,***等野生种存在丰富的低温霜冻抗性,它们是改良马铃薯栽培种的重要资源。本研究在对野生种***不同株系进行抗寒性鉴定的基础上,筛选得到综合性状优良的株系BLV29-2(***)并与二倍体栽培种ED25进行杂交和回交,获得了抗寒性较强的种间杂种材料;再利用秋水仙素处理部分抗寒性明显改良的种间杂种株系,对这些加倍株系进行抗寒性和农艺性状鉴定,结果表明所有加倍材料在株高、花粉粒直径和单个薯重等方面均有显著增加,大部分材料加倍前后抗寒性无显著变化,但较栽培种对照显著提升。将加倍株系T-FT073-4-7与优良四倍体栽培种华薯13号进行杂交,杂交后代自然霜冻评级结果出现抗感分离,47%材料的抗寒性偏向母本T-FT073-4-7,显著高于父本栽培种,进一步结合田间农艺性状筛选出了部分综合性状优良且抗寒性显著改良的育种材料。本研究已成功将二倍体野生种***的优良抗寒性导入四倍体栽培种中,改良了现有栽培种对低温敏感的不足,为抗寒遗传育种材料的选育和进一步改良奠定了重要基础。

关键词：马铃薯抗寒农艺性状染色体加倍遗传改良

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