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| 1 | Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome显示文摘Hutchinson-Gilford 早衰症候群(HGPS ) 和沃纳症候群(WS ) 是二最好描绘的人的 progeroid 症候群。HGPS 被一个点变化在 lamin A (LMNA ) 基因引起,导致截断的蛋白质 productprogerin 的生产。WS 被变化在 WRN 基因引起,编码 loss-of-function RecQ DNA helicase。这里,由基因编辑,我们创造了 isogenic 人的胚胎的干细胞(转换字符) 与异质接合(G608G/+) 或同型结合(G608G/G608G ) LMNA 变化和 biallelic WRN 大美人为为 HGPS 和 WS 致病建模,分别地。当转换字符和 endothelial 房间(EC ) 没介绍早熟的老朽的任何特征时, HGPS 间充质、 WS 间充质的干细胞(MSC ) 与不同动力学显示出联系老化的显型。当 HGPS-MSCs 展出了迟了发作的尖锐早衰 characterisitcs 时, WS-MSCs 有早发作的温和早衰显型。一起拿,我们的学习比较并且形成对照不同病理 underpinning 二早衰混乱,并且提供可靠干细胞为病理学、生理的老化识别新治疗学的策略的基于的模型。 | Zeming Wu Weiqi Zhang Moshi Song Wei Wang Gang Wei Wei Li Jinghui Lei Yu Huang Yanmei Sang Piu Chan Chang Chen Jing Qu Keiichiro Suzuki Juan Carlos Izpisua Belmonte Guang-Hui Liu | 2018 | Protein & Cell2018，9，4： | 15 |
| 2 | Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding显示文摘 | Jiping Yang Jingyi Li Keiichiro Suzuki Xiaomeng Liu Jun Wu Weiqi Zhang Ruotong Ren Weizhou Zhang Piu Chan Juan Carlos Izpisua Belmonte Jing Qu Fuchou Tang Guang-Hui Liu | 2017 | Cell Research2017，27，9： | 12 |
| 3 | Single-cell transcriptomic atlas of primate cardiopulmonary aging显示文摘Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019(COVID-19).Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed.Here,we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung,heart and artery,the top tissues targeted by SARS-CoV-2.Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging.With age,expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2(ACE2)was increased in the pulmonary alveolar epithelial barrier,cardiomyocytes,and vascular endothelial cells.We found that interleukin 7(IL7)accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner.Furthermore,treatment with vitamin C blocked IL7-induced ACE2 expression.Altogether,our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2,suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly. | Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu | 2021 | Cell Research2021，31，4： | 10 |
| 4 | Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration显示文摘Accumulating evidence indicates an association between the circadian clock and the aging process.However,it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes.Here,we identified a transcription factor-independent role of CLOCK,a core component of the molecular circadian clock machinery,in counteracting human mesenchymal stem cell(hMSC)decay.CLOCK expression was decreased during hMSC aging.In addition,CLOCK deficiency accelerated hMSC senescence,whereas the overexpression of CLOCK,even as a transcriptionally inactive form,rejuvenated physiologically and pathologically aged hMSCs.Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1,thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences.Finally,gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice.These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin,promoting tissue regeneration,and mitigating aging-associated chronic diseases. | Chuqian Liang Zunpeng Liu Moshi Song Wei Li Zeming Wu Zehua Wang Qiaoran Wang Si Wang Kaowen Yan Liang Sun Tomoaki Hishida Yanning Cai Juan Carlos lzpisua Belmonte Pedro Guillen Piu Chan Qi Zhou Weiqi Zhang Jing Qu Guang-Hui Liu | 2021 | Cell Research2021，31，2： | 8 |
| 5 | Single-nucleus transcriptomic landscape of primate hippocampal aging显示文摘The hippocampus plays a crucial role in learning and memory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases.Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing.Here,we reported a variety of new aging-associated phenotypic changes of the primate hippocampus.These include,in particular,increased DNA damage and heterochromatin erosion with time,alongside loss of proteostasis and elevated inflammation.To understand their cellular and molecular causes,we established the first single-nucleus transcriptomic atlas of primate hippocampal aging.Among the 12 identified cell types,neural transiently amplifying progenitor cell(TAPC)and microglia were most affected by aging.In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory;additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte,as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis.This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases. | Hui Zhang Jiaming Li Jie Ren Shuhui Sun Shuai Ma Weiqi Zhang Yang Yu Yusheng Cai Kaowen Yan Wei Li Baoyang Hu Piu Chan Guo-Guang Zhao Juan Carlos Izpisua Belmonte Qi Zhou Jing Qu Si Wang Guang-Hui Liu | 2021 | Protein & Cell2021，12，9： | 5 |
| 6 | A single-cell transcriptomic atlas of primate pancreatic islet aging显示文摘Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes.Endocrine cells age heterogeneously,complicating the efforts to unravel the molecular drivers underlying endocrine aging.To overcome these obstacles,we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys.Despite sex differences and increased transcriptional variations,agedβ-cells showed increased unfolded protein response(UPR)along with the accumulation of protein aggregates.We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways,comprising adaptive UPR during pancreatic aging.Notably,we found aging-relatedβ-cell-specific upregulation of HSP90 B1,an endoplasmic reticulum-located chaperone,impeded high glucose-induced insulin secretion.Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis,suggesting an avenue to delayingβ-cell aging and preventing aging-related diabetes. | Jingyi Li Yuxuan Zheng Pengze Yan Moshi Song Si Wang Liang Sun Zunpeng Liu Shuai Ma Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Weiqi Zhang Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | National Science Review2021，8，2： | 3 |
| 7 | Long-term evaluation of biliary reconstruction after partial resection of segments IV and V in iatrogenic injuries显示文摘 | Miguel ángel Mercado M.D. Carlos Chan M.D. Héctor Orozco M.D. José M. Villalta M.D. Alexandra Barajas-Olivas M.D. Javier Era?a M.D. Ismael Domínguez M.D | 2006 | Journal of Gastrointestinal Surgery2006，，1： | 3 |
| 8 | A systematic review and meta-analysis of gastric cancer treatment in patients with positive peritoneal cytology显示文摘 | Carlos Suhady Cabalag Steven Tuck Foo Chan Yui Kaneko Cuong Phu Duong | 2015 | Gastric Cancer2015，，1： | 2 |
| 9 | New Era of Liver Transplantation for Hepatitis B: A 17-Year Single-Center Experience显示文摘 | Dean M. Anselmo Rafik M. Ghobrial Lee Chan Jung Michael Weaver Carlos Cao Sammy Saab Greg Kunder Pauline W. Chen Douglas G. Farmer Hasan Yersiz Angeles Baquerizo Sunil Geevarghese Steven H. Han Leonard Goldstein Curtis D. Holt Jeffrey A. Gornbein Ronald W | 2002 | Annals of Surgery2002，，5： | 1 |
| 10 | Tuberculous Meningitis: Diagnosis and Treatment Overview显示文摘 | Grace E. Marx Edward D. Chan Carlo Garzelli | 2011 | Tuberculosis Research and Treatment2011，，： | 1 |
| 11 | Aortic Arch Advancement for Aortic Coarctation and Hypoplastic Aortic Arch in Neonates and Infants显示文摘 | Carlos M. Mery Francisco A. Guzmán-Pruneda Kathleen E. Carberry Carmen H. Watrin Grant R. McChesney Joyce G. Chan Iki Adachi Jeffrey S. Heinle E. Dean McKenzie Charles D. Fraser | 2014 | The Annals of Thoracic Surgery2014，，： | 1 |
| 12 | Surgical management of extrahepatic portal hypertension and variceal bleeding显示文摘 | Hector Orozco M.D. Takeshi Takahashi M.D. Miguel Agel Mercado M.D. Eduardo Prado M.D. Carlos Chan M.D | 1994 | World Journal of Surgery1994，，2： | 1 |
| 13 | FOXO3-engineered human mesenchymal progenitor cells efficiently promote cardiac repair after myocardial infarction显示文摘Dear Editor,Myocardial infarction(MI)is the irreversible cardiomyocyte death resulting from prolonged oxygen deprivation due to obstructed blood supply(ischemia),leading to contractile dysfunction and cardiac remodeling.In recent decades,stem cell transplantation has been extensively investigated for the repair of injured heart in animal studies and clinical trials(Kanelidis et al.,2017;Gyongyosi et al.,2018). | Jinghui Lei Si Wang Wang Kang Qun Chu Zunpeng Liu Liang Sun Yun Ji Concepcion Rodriguez Esteban Yan Yao Juan Carlos Izpisua Belmonte Piu Chan Guang-Hui Liu Weiqi Zhang Moshi Song Jing Qu | 2021 | Protein & Cell2021，12，2： | 1 |
| 14 | New Era of Liver Transplantation for Hepatitis B: A 17-Year Single-Center Experience显示文摘 | Dean M. Anselmo Rafik M. Ghobrial Lee Chan Jung Michael Weaver Carlos Cao Sammy Saab Greg Kunder Pauline W. Chen Douglas G. Farmer Hasan Yersiz Angeles Baquerizo Sunil Geevarghese Steven H. Han Leonard Goldstein Curtis D. Holt Jeffrey A. Gornbein Ronald W | 2002 | Annals of Surgery2002，，5： | 1 |
| 15 | Significance of Troponin Elevation After Severe Traumatic Brain Injury显示文摘 | Ali Salim Pantelis Hadjizacharia Carlos Brown Kenji Inaba Pedro G. R. Teixeira Linda Chan Peter Rhee Demetrios Demetriades | 2008 | The Journal of Trauma: Injury, Infection, and Critical Care2008，，1： | 1 |
| 16 | Recommendations for the nomenclature of IgG4‐related disease and its individual organ system manifestations显示文摘 | John H. Stone Arezou Khosroshahi Vikram Deshpande John K. C. Chan J. Godfrey Heathcote Rob Aalberse Atsushi Azumi Donald B. Bloch William R. Brugge Mollie N. Carruthers Wah Cheuk Lynn Cornell Carlos Fernandez‐Del Castillo Judith A. Ferry David Forcione Gü | 2012 | Arthritis & Rheumatism2012，，10： | 1 |
| 17 | Intrahepatic Repair of Bile Duct Injuries. A Comparative Study显示文摘 | Miguel ángel Mercado Carlos Chan Noel Salgado-Nesme Federico López-Rosales | 2008 | Journal of Gastrointestinal Surgery2008，，2： | 1 |
| 18 | Recommendations for the nomenclature of IgG4‐related disease and its individual organ system manifestations显示文摘 | John H. Stone Arezou Khosroshahi Vikram Deshpande John K. C. Chan J. Godfrey Heathcote Rob Aalberse Atsushi Azumi Donald B. Bloch William R. Brugge Mollie N. Carruthers Wah Cheuk Lynn Cornell Carlos Fernandez‐Del Castillo Judith A. Ferry David Forcione Gü | 2012 | Arthritis & Rheumatism2012，，10： | 1 |
| 19 | Recommendations for the nomenclature of IgG4‐related disease and its individual organ system manifestations显示文摘 | John H. Stone Arezou Khosroshahi Vikram Deshpande John K. C. Chan J. Godfrey Heathcote Rob Aalberse Atsushi Azumi Donald B. Bloch William R. Brugge Mollie N. Carruthers Wah Cheuk Lynn Cornell Carlos Fernandez‐Del Castillo Judith A. Ferry David Forcione Gü | 2012 | Arthritis & Rheumatism2012，，10： | 1 |
| 20 | New Era of Liver Transplantation for Hepatitis B: A 17-Year Single-Center Experience显示文摘 | Dean M. Anselmo Rafik M. Ghobrial Lee Chan Jung Michael Weaver Carlos Cao Sammy Saab Greg Kunder Pauline W. Chen Douglas G. Farmer Hasan Yersiz Angeles Baquerizo Sunil Geevarghese Steven H. Han Leonard Goldstein Curtis D. Holt Jeffrey A. Gornbein Ronald W | 2002 | Annals of Surgery2002，，5： | 1 |
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