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Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis

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Journal of Molecular Cell Biology 2020年第1期12卷 71-83页

作者： Jing-Yi li Yi-Feng liu Hai-Yan Xu jun-yu Zhang Ping-Ping Lv Miao-E liu Yan-yun Ying Ye-Qing Qian Kun li cheng li yun Huang Gu-Feng Xu Guo-lian Ding yu-Chan Mao chen-Ming Xu Xin-Mei liu jian-zhong Sheng Dan Zhang He-Feng Huang Key Laboratory of Reproductive Genetics(Ministry of Education)and Department of Reproductive Endocrinology Women's HospitalZhejiang University School of MedicineHangzhou 310006China International Peace Maternal and Child Health Hospital Shanghai Jiao Tong UniversityShanghai 200030China Department of Pathology&Pathophysiology Zhejiang University School of MedicineHangzhou 310000China

Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic ***,its roles in spermatogenesis and testicular aging were not *** we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency *** this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature ***-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate *** truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature ***,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive *** present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.

关键词： testicular aging spermatogenesis BNC1 TAF7L gene mutation

Investigations of the dielectronic recombination of phosphorus-like tin at CSRm

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Chinese Physics B 2018年第6期27卷 268-273页

作者： Xin Xu Shu-Xing Wang zhong-Kui Huang Wei-qiang Wen Han-Bing Wang Tian-Heng Xu Xiao-Ya Chuai li-jun Dou Wei-Qing Xu Chong-Yang chen Chuan-Ying li jian-Guo Wang Ying-Long Shi chen-zhong Dong li-jun Mao Da-yu Yin Jie li jian-cheng Yang you-Jin yuan Xin-Wen Ma and lin-Fan Zhu Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics University of Science and Technology of China Hefei 230026 China Synergetic Innovation Center of Quantum Information and Quantum Physics University of Science and Technology of China Hefei 230026 China Institute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 China School of Physical Sciences University of the Chinese Academy of Sciences Beijing 100049 China Shanghai EBIT Laboratory Institute of Modern Physics and Key Laboratory of Nuclear Physics and Ion-beam Application （MOE） Fudan University Shanghai 200433 China National Synchrotron Radiation Laboratory University of Science and Technology of China Hefei 230026 China 7 The Key Laboratory of Computational Physics Institute of Applied Physics and Computational Mathematics Beijing 100088 China 8Institute for Fundamental Physics Tianshui Normal University Tianshui 741000 China 9 Key Laboratory of Atomic and Molecular Physics and Functional Materials of Gansu Province College of Physics and Electronic Engineering Northwest Normal University Lanzhou 730070 China

The electron–ion recombination for phosphorus-like^（112） Sn^（35＋）has been measured at the main cooler storage ring of the Heavy Ion Research Facility in Lanzhou, China, employing an electron–ion merged-beams technique. The absolute total recombination rate coefficients for electron–ion collision energies from 0 e V–14 e V are presented. Theoretical calculations of recombination rate coefficients were performed using the Flexible Atomic Code to compare with the experimental results. The contributions of dielectronic recombination and trielectronic recombination on the experimental rate coefficients have been identified with the help of the theoretical calculation. The present results show that the trielectronic recombination has a substantial contribution to the measured electron–ion recombination spectrum of^（112）Sn^（35＋）. Although a reasonable agreement is found between the experimental and theoretical results the precise calculation of the electron–ion recombination rate coefficients for M-shell ions is still challengeable for the current theory.

关键词： dielectronic recombination trielectronic recombination storage ring electron cooling

On the radial velocity calibrations in the LAMOST medium-resolution spectroscopic survey of nebulae

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Research in Astronomy and Astrophysics 2021年第3期21卷 1-14页

作者： Juan-Juan Ren Hong Wu Chao-jian Wu Wei Zhang jian-jun chen Chih-Hao Hsia Fan Yang Chao liu jian-Rong Shi yu-zhong Wu Hui Zhu Bin li zhong-Rui Bai Hao Tian Yong-Hui Hou CAS Key Laboratory of Space Astronomy and Technology National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyTaipaMacaoChina University of Chinese Academy of Sciences Beijing 100049China Purple Mountain Observatory Chinese Academy of SciencesNanjing 210008China University of Science and Technology of China Hefei 230026China Nanjing Institute of Astronomical Optics&Technology National Astronomical ObservatoriesChinese Academy of SciencesNanjing 210042China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China

Accurate radial velocity determinations of optical emission lines(i.e.,[NⅡ]λλ6548,6584,Hαand[SⅡ]λλ6717,6731)are very important for investigating the kinematic and dynamic properties of *** second stage survey program of Large sky Area Multi-Object fiber Spectroscopic Telescope(LAMOST)has started a sub-survey of nebulae(MRS-N)which will spectroscopically observe the optical emission lines of a large sample of nebulae near the Galactic *** now,15 MRS-N plates have been observed from September 2017 to june *** on fitting the sky emission lines in the red band spectra of MRS-N,we investigate the precision of wavelength calibration and find there are systematic deviations of radial velocities(RVs)from~0.2 to 4 km s^(-1) for different *** for the plates obtained in March 2018,the systematic deviations of RVs can be as large as~4 km s^(-1),which then go down to~0.2-0.5 kms^(-1) at the end of 2018 and January *** RV calibration function is proposed for these MRS-N plates,which can simultaneously and successfully calibrate the systematic deviations and improve the precision of RVs.

关键词： ISM:general ISM:kinematics and dynamics technique:spectroscopic technique:radial velocities

Towards the full realization of the RIBLL2 beam line at the HIRFL-CSR complex

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Science Bulletin 2018年第2期63卷 78-80页

作者： Bao-Hua Sun jian-Wei Zhao Xue-Heng Zhang li-Na Sheng Zhi-yu Sun Isao Tanihata Satoru Terashima Yong Zheng li-Hua Zhu li-Min Duan liu-Chun He Rong-jiang Hu Guang-Shuai li Wen-jian lin Wei-Ping lin Chuan-Ye liu zhong liu chen-Gui Lu Xin-Wen Ma li-jun Mao Yi Tian Feng Wang Meng Wang Shi-Tao Wang Jia-Wen Xia Xiao-Dong Xu Hu-Shan Xu Zhi-Guo Xu jian-cheng Yang Da-yu Yin you-Jin yuan Wen-Long Zhan yu-Hu Zhang Xiao-Hong Zhou School of Physics and Nuclear Energy Engineering Beihang University Beijing 100191 China International Research Center for Nuclei and Particles in the Cosmos Beijing 100191 China Institute of Modern Physics Chinese Academy of Sciences Lanzhou 730000 China

More than 99%of the mass in the visible universe—the material that makes up ourselves,our planet,stars—is in the atomic *** the matter has existed for billions of years,only over the past few decades have we had the tools and the knowledge necessary to get a basic understanding of the structure and dynamic of *** physicists around the world have made tremendous strides by initiating a broad range of key

关键词： HIRFL-CSR 横梁建筑群排队原子核物理学家试验性世界

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection:a randomized trial

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3009-3018页

作者： jun liu Dan-Dan li Wei Dong yu-Qi liu Yang Wu Da-Xuan Tang Fu-Chun Zhang Meng Qiu Qi Hua Jing-yu He jun li Bai Du Ting-Hai Du lin-lin Niu Xue-jun jiang Bo Cui jiang-Bin chen Yang-Gan Wang Hai-Rong Wang Qin yu Jing He Yi-lin Mao Xiao-Fang Bin yue Deng yu-Dan Tian Qing-Hua Han Da-Jin liu li-Qin Duan Ming-jun Zhao Cui-Ying Zhang Hai-Ying Dai Ze-Hua li Ying Xiao you-Zhi Hu Xiao-yu Huang Kun Xing Xin jiang Chao-Feng liu Jing An Feng-Chun li Tao Tao Jin-Fa jiang Ying Yang Yao-Rong Dong Lei Zhang Guang Fu Ying li Shu-Wei Huang li-Ping Dou Lan-jun Sun Ying-qiang Zhao Jie li yun Xia jun liu Fan liu Wen-Jin He Ying li jian-Cong Tan Yang lin Ya-Bin Zhou jian-Fei Yang Guo-Qing Ma Hui-jun chen He-Ping liu Zong-Wu liu jian-Xiong liu Xiao-Jia Luo Xiao-Hong Bin Ya-Nan yu Hai-Xia Dang Bing li Fei Teng Wang-Min Qiao Xiao-Long Zhu Bing-Wei chen Qi-Guang chen Chun-Ti Shen Yong-Yan Wang yun-Dai chen zhong Wang Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijingChina Department of Cardiology Chinese PLA General HospitalBeijingChina Department of Cardiology Dongfang Hospital Affiliated to Beijing University of Chinese MedicineBeijingChina Department of Geratology Peking University Third HospitalBeijingChina Department of Cardiology Xuan Wu HospitalCapital Medical UniversityBeijingChina Department of Cardiology Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina Department of Cardiology First Affiliated Hospital of Henan University of Chinese MedicineZhengzhouHenanChina Department of Cardiology Wuhan University Renmin HospitalWuhanHubeiChina Department of Cardiology Wuhan University Zhongnan HospitalWuhanHubeiChina Affiliated zhongshan Hospital of Dalian University DalianLiaoningChina Department of Cardiology Second Affiliated Hospital to Hunan University of Chinese MedicineChangshaHunanChina Department of Cardiology First Affiliated Hospital to Changchun University of Chinese MedicineChangchunJilinChina Department of Cardiology First Affiliated Hospital to Shanxi Medical UniversityTaiyuanShanxiChina Department of Cardiology Affiliated Hospital of Shanxi University of Chinese MedicineXianyangShanxiChina Department of Cardiology Changsha Central HospitalChangshaHunanChina Department of Cardiology Hubei Provincial Hospital of Traditional Chinese MedicineWuhanHubeiChina Department of Cardiology Shanxi Provincial People's HospitalXi'anShanxiChina Department of Cardiology Shanxi Province Hospital of Traditional Chinese MedicineXi'anShanxiChina Department of Cardiology Xi'an City Hospital of Traditional Chinese MedicineXi'anShanxiChina Department of Cardiology Shanghai Tongji HospitalShanghaiChina Department of Cardiology Shanghai Municipal Hospital of Traditional Chinese MedicineShanghaiChina Department of Cardiology The First Hospital of ChangshaChangshaHunanChina Department of Cardiology Xinhua Hospi

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart ***,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and *** performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by ***,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol *** assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear *** study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target

关键词： angina injection sketch

Research on in-situ condition preserved coring and testing systems

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Petroleum Science 2021年第6期18卷 1840-1859页

作者： He-Ping Xie Tao liu Ming-zhong Gao ling chen Hong-Wei Zhou Yang Ju Feng Gao Xiao-Bo Peng Xiong-jun li Rui-Dong Peng Ya-Nan Gao Cong li Zhi-qiang He Ming-Qing Yang Zhi-yu Zhao Guangdong Provincial Key Laboratory of Deep Earth Sciences and Geothermal Energy Exploitation and Utilization Institute of Deep Earth Sciences and Green EnergyCollege of Civil and Transportation EngineeringShenzhen UniversityShenzhen518060GuangdongChina Shenzhen Key Laboratory of Deep Underground Engineering Sciences and Green Energy Shenzhen UniversityShenzhen518060GuangdongChina MOE Key Laboratory of Deep Earth Science and Engineering College of Water Resource and HydropowerSichuan UniversityChengdu 610065SichuanChina School of Mechanical Engineering Sichuan UniversityChengdu610065SichuanChina Institute of New Energy and Low-Carbon Technology Sichuan UniversityChengdu610065SichuanChina State Key Laboratory of Coal Resources and Safe Mining China University of Mining and Technology(Beijing)Beijing100083China Frontier Science Research Center for Fluidized Mining of Deep Underground Resources China University of Mining and TechnologyXuzhou221116JiangsuChina

As shallow resources are increasingly depleted,the mechanics'theory and testing technology of deep insitu rock has become *** coring technologies obtain rock samples without retaining the in-situ environmental conditions,leading to distortion of the measured ***,a coring and testing systems retaining in-situ geological conditions is presented:the coring system that obtains in-situ rock samples,and the transfer and testing system that stores and analyzes the rocks under a reconstructed *** ICP-Coring system mainly consists of the pressure controller,active insulated core reactor and insulation layer and sealing *** ultimate bearing strength of 100 MPa for pressurepreservation,temperature control accuracy of 0.97%for temperature-retained are ***_(4)and CO permeability of the optimized sealing film are as low as 3.85 and 0.33 ppm/*** average tensile elongation of the film is 152.4%and the light transmittance is reduced to 0%.Additionally,the pressure and steady-state temperature accuracy for reconstructing the in-situ environment of transfer and storage system up to 1%and±0.2 is *** error recorded of the noncontact sensor ring made of lowdensity polymer is less than 6%than that of the contact *** system can provide technical support for the deep in-situ rock mechanics research,improving deep resource acquisition capabilities and further clarifying deep-earth processes.

关键词： Deep mining In-situ environmental conditions In-situ condition preserved coring and testing In-situ transfer Deep-earth processes ICP-Coring In-situ condition-preserved coring

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

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Chinese Journal of Cancer 2016年第12期35卷 713-724页

作者： Qing-Qing Cai li-Yang Hu Qi-Rong Geng Jie chen Zhen-Hai Lu Hui-Lan Rao Qing liu Wen-Qi jiang Hui-qiang Huang Tong-yu lin zhong-jun Xia State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuang-zhou 510060GuangdongP.R.China. Department of Medical Oncology Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuang-zhou 510060GuangdongP.R.China. Department of Hematology Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Guangdong Province Key Laboratory of Arrhythmia and Elec-trophysiology Guangzhou 510120GuangdongP.R.China. Department of Radiotherapy Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhou 510120GuangdongP.R.China. Department of Colorectal Carci-noma Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Cancer Preven-tion Research Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China.

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse ***: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P 46 months, 25(4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3?year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R?CHOP group(P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much beneit in terms of preventing CNS relapse. Bone involvement [hazard ratio(HR) = 4.21, 95% conidence interval(CI) 1.38–12.77], renal involvement(HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase(ALP) >110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) 35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent p

关键词： Diffuse large B?cell lymphoma Central nervous system relapse Risk factor Rituximab Intrathecal chemotherapy prophylaxis

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients

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Signal Transduction and Targeted Therapy 2022年第1期7卷 228-242页

作者： Jin-Lan Zhang yu-Huan li Lu-Lu Wang Hong-Qi liu Shuai-Yao Lu Yong liu Ke li Bin liu Su-yun li Feng-Min Shao Kun Wang Ning Sheng Rui li Jin-Jin Cui Pei-Chun Sun Chun-Xia Ma Bo Zhu Zhe Wang yuan-Hao Wan Shi-Shan yu Yongsheng Che Chao-Yang Wang chen Wang qiangqian Zhang li-Min Zhao Xiao-zhong Peng Zhenshun cheng jun-Biao Chang jian-Dong jiang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Institute of Medical Biology Chinese Academy of Medical Science and Peking Union Medical CollegeKunming 650031 YunnanChina Genuine Biotech.Inc. Pingdingshan 467000 HenanChina Department of Respiratory Medicine Zhongnan Hospital of Wuhan UniversityWuhan Research Center for Infectious Diseases and CancerWuhan 430071 HubeiChina The First Affiliated Hospital of Henan University of Chinese Medicine Zhengzhou 450000 HenanChina Department of Internal Medicine Henan Provincial Peoples HospitalZhengzhou 450003 HenanChina Henan Key Laboratory of Organic Functional Molecule and Drug Innovation School of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007 HenanChina National Clinical Research Center for Respiratory Diseases Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100005China School of Chemistry Zhengzhou UniversityZhengzhou 450001 HenanChina

Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 *** monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 *** administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest *** gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)***,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.

关键词： patients inhibited concentrated

Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts

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Bioactive Materials 2023年第10期28卷 206-226页

作者： yun jiang ling-ling Zhang Fan Zhang Wei Bi Peng Zhang Xiu-jian yu Sen-Le Rao Shi-Hui Wang qiang li chen Ding Ying Jin zhong-Min liu Huang-Tian Yang Translational Medical Center for Stem Cell Therapy&Institute for Heart Failure and Regenerative Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai200092China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of Sciences(CAS)CASShanghai200031PR China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development School of Life SciencesInstitute of Biomedical SciencesHuman Phenome InstituteZhongshan HospitalFudan UniversityShanghai200433China Institute for Stem Cell and Regeneration CASBeijing100101PR China

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

关键词： Induced human pluripotent stem cells Cardiac lineage cells Extracellular matrix patch Cardiomyocyte regeneration Infarcted heart repair