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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

Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia:a randomized controlled study

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Journal of Geriatric Cardiology 2024年第8期21卷 791-798页

作者： Jing SHI Ming-Lu Xu Mei-Jiao HE Wan-Lan BO Hai-Yu ZHANG Dang-hui SuN Ding-Yu WANG Xiao-Yu WANG Qun SHAO Yu-Jiao PAN Yu ZHANG Chen-guang DAI Jing-Ying WANG Lin-Wei ZHANG guang-Zhong LIu Yue LI for the GPROT Study Group Department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbinChina Department of Gastroenterology the Fourth Affiliated HospitalHarbin Medical UniversityHarbinChina Department of Cardiology Harbin Medical University Cancer HospitalHarbinChina Department of Cardiology Shenzhen People’s HospitalShenzhenChina National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical UniversityHarbinChina NHC Key Laboratory of Cell Transplantation Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang ProvinceHeilongjiang Province Clinical Medical Research Center for Hypertensionthe First Affiliated HospitalHarbin Medical UniversityHarbinChina Institute of Metabolic Disease Heilongjiang Academy of Medical ScienceHarbinChina 不详

BACKGROuND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin *** acetate(Gefarnate)is an anti-ulcer *** was reported that geraniol might participate in lipid metabolism through a variety of *** aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual *** In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,*** baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were *** After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant *** The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual *** suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

关键词： nat alone Lipid

A model reduction approach for discrete-time linear time-variant systems with delayed inputs

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Science China(Information Sciences) 2024年第4期67卷 197-217页

作者： Ai-Guo Wu guang-Ren DuAN Yu WANG Jie ZHANG School of Mechanical Engineering and Automation Harbin Institute of Technology(Shenzhen) HIT Wuhu Robot Technology Research Institute Center for Control Science and Technology Southern University of Science and Technology

A model reduction approach is presented for discrete-time linear time-variant input-delayed systems. According to this proposed approach, a dynamical variable is constructed by taking advantage of the current state and historical information of input. It is revealed that the behavior of this dynamical variable is governed by a discrete-time linear delay-free system. It is worth noting that the presented variable transformation does not require the system matrix to be invertible. Based on the reduced delay-free models,stabilizing control laws can be easily obtained for the original delayed system. For the case with a single input delay, the constructed variable is an exact prediction for the future state, and thus the stabilizing control law could be designed by replacing the future state with its prediction. Finally, three discrete-time periodic systems with delayed input are employed to illustrate how to utilize the presented model reduction approaches.

关键词： reduction approach predictor-based feedback time-varying systems delayed input periodic system

Impact wear properties of dissimilar joints between bainitic frogs and pearlite rails

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Journal of Iron and Steel Research International 2024年第1期31卷 275-287页

作者： Pin-yong Zeng Chun-guang Zuo Xiao-yu Zhang Wei Li Tribology Research Institute Southwest Jiaotong UniversityChengdu610031SichuanChina

The impact wear behavior and damage mechanism of dissimilar welded joints between u26Mn frog and u75 V rail before and after normalizing treatment were studied by cyclic impact *** experiment indicated that the impact wear volume of the joints increased with the increasing number of impact *** main wear mechanisms include pitting wear,mild fatigue wear,delamination wear,and fatigue wear,and plastic deformation was the primary impact wear *** them,fatigue wear had the greatest influence on wear volume,while other wear mechanisms had limited *** impact wear resistance of the base material was better than that of the heat-affected *** treatment was beneficial to improving the impact wear resistance of welded joints owing to its effect to promote pearlite recovery,grain refinement,and uniform distribution of *** martensite generated in the rail welded joints aggravated the impact wear damage to the materials,which should be avoided.

关键词： Dissimilar welded joint Impact wear Bainitic steel Damage mechanism Wear rate

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基于混合元的变刚度层合板静力学分析

工程力学 2024年第3期41卷 19-25页

作者：杨立洲卿光辉中国民航大学航空工程学院天津300300

针对变刚度层合结构,大多采用板壳理论或常规的位移有限元法分析其力学行为。相较位移元,非协调广义部分混合元同时引入位移和应力边界条件,提高了应力结果精度,且边界应力更符合真实情况。扩展了纯弹性体的非协调广义部分混合元理论,... 详细信息

针对变刚度层合结构,大多采用板壳理论或常规的位移有限元法分析其力学行为。相较位移元,非协调广义部分混合元同时引入位移和应力边界条件,提高了应力结果精度,且边界应力更符合真实情况。扩展了纯弹性体的非协调广义部分混合元理论,提出适用于变刚度层合结构修正的非协调广义部分混合元模型。与ABAQuS计算结果对比证明,即使在网格较稀疏的情况下,该文方法也具有较好的适用性,且数值结果精确度高。通过算例分析了纤维铺设角度的变化对变刚度层合板平面内位移场的影响,可为变刚度结构的设计提供一定的思路。

关键词：变刚度结构层合板非协调广义混合元有限元法静力学分析

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Tough Hydrogen Bonding Crosslinked Poly (3-fluorothiophene) Network via Electrosynthesis for High-performance Electrochromic Supercapacitors

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Chinese Journal of Polymer Science 2024年第11期 1749-1757页

作者： Chun-hui Du Yu-Hua Xu hui Li Zhi-Xin Wu Han-Jun Yang Xi-Mei Liu Bao-Yang Lu guang-Ming Nie Ge Zhang Jiangxi Key Lab of Flexible Electronics Flexible Electronics Innovation InstituteJiangxi Science & Technology Normal University Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science MOEState Key Laboratory Base of Eco-chemical EngineeringCollege of Chemistry and Molecular EngineeringQingdao University of Science and Technology

As a type of bi-functional device,electrochromic supercapacitors （EC-SCs） have attracted extensive attention in diverse applications such as flexible ***,despite recent encouraging progress,rational design and development of high-performance EC-SC materials with desirable stability remain challenging for practical ***,we propose a fluorination strategy to develop high-performance EC-SC materials with tough hydrogen bonding cross-linked intermolecular polymer network by one-step electrosynthesis of *** electrosynthesized free-standing poly（3-fluorothiophene）(PFT) films simultaneously achieve high electrochromic performance （optical contrast 42%at 560 nm with reversible color changes between purple and blue）,and good capacitance property (290 F·g-1,1 A·g-1),as well as outstanding cyclic stability （uction after 20000 cycles）.We further demonstrate the fabrication of PFT-based flexible electrochromic supercapacitor devices （FESDs）,and the resultant devices can be used to visually monitor the energy storage state in real-time and maintain outstanding stability under mechanical distortion like *** a tough fluorination hydrogen bonding cross-linking strategy may provide a new design concept for high-performance EC-SC materials and reliable FESDs toward practical applications.

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Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging

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Protein & Cell 2024年第8期15卷 612-632页

作者： Qinchao Hu Bin Zhang Yaobin Jing Shuai Ma Lei Hu jingyi Li Yandong Zheng Zijuan Xin Jianmin Peng Si Wang Bin Cheng Jing Qu Weiqi zhang guang-hui Liu Songlin Wang State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou 510060China Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Laboratory of Oral Health and Beijing Stomatological HospitalCapital Medical UniversityBeijing 100050China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China university of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuan Wu HospitalCapital Medical UniversityBeijing 100053China Intemational Center for Aging and Cancer Hainan Medical UniversityHaikou 571199China Aging Biomarker Consortium Beijing 100101China

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory ***,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still ***,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were *** cells were identified as the most affected cell types by aging in the *** analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal *** decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation *** work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.

关键词： single-nucleus RNA-sequencing primate gingiva aging YAP

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

Serum activin A as a prognostic biomarker for community acquired pneumonia

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World Journal of Clinical Cases 2024年第22期12卷 5016-5023页

作者： Yu-Ting Wang Yan Liu guang-hui Zhou Kan Liu Yan Fen hui Ding Pulmonary and Critical Care Medicine Yixing People’s Hospital of Jiangsu UniversityYixing 214200Jiangsu ProvinceChina

BACKGROuND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)*** To evaluate the association between serum activin A levels and prognosis in CAP *** A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition,and 48 healthy individuals as the control group were enrolled in this *** concentrations of activin A were measured using enzymelinked *** interaction between activin A levels and etiologies of CAP was *** on the severity of CAP,110 patients(65.48%)were categorized into group-I,42(25%)cases were grouped into group-II,and 16(9.52%)cases were categorized into *** Serum activin A levels were higher in patients with CAP than controls,but independent of ***,the scores of Pneumonia Severity Index(PSI)and CuRB-65 positively correlated with the increasing levels of serum activin A,and were at their highest peak in individuals in group-III(P1).Combining activin A with CuRB-65 or PSI was more effective in improving predictive property(P1).According to Cox proportional regression analysis,after adjusting clinical parameters,we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients(P1).CONCLuSION Higher level of serum activin A was associated with poor prognosis of *** A can be used as a more valuable biomarker of prognosis in CAP patients.

关键词： Community-acquired pneumonia Activin A Etiology Prognosis Etiology