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| 1 | Prevalence and evolution of drug resistance HIV-1 variants in Henan, China显示文摘To understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug nave AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug nave patients. The prevalence rate of drug resistant HIV strains were 13. 9%, 45.4% and 62.7% in drug nave patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT+DDI+NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continu- ation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible. | Jing Yun LI Han Ping LI Lin LI Hong LI Zhe WANG Kun YANG Zuo Yi BAO Dao Min ZHUANG Si Yang LIU Yong Jian LIU Hui XING Yi Ming SHAO | 2005 | Cell Research2005，15，11： | 34 |
| 2 | Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999-2017显示文摘Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics,management and outcomes of young breast cancer patients over time.Methods: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and1999-2015 were identified in the Fudan University Shanghai Cancer Center(FUSCC) and the population-based Surveillance, Epidemiology, and End Results(SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.Results: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ(DCIS)(from 8.8% to 16.9%;P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort(from 35.3% to 41.9%;P=0.008), whereas it decreased in SEER cohort(from 42.4% to 33.0%;P<0.0001). The percentage of estrogen receptor(ER)-positive cancers was consistently increased in both the invasive ductal carcinoma(IDC) and DCIS patients in the two cohorts. Breastconserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.Conclusions: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial deescalation in surgical therapies in young breast cancer patients. | Rong Guo Jing Si Jingyan Xue Yonghui Su Miao Mo Benlong Yang Qi Zhang Weiru Chi Yayun Chi Jiong Wu | 2019 | Chinese Journal of Cancer Research2019，31，4： | 24 |
| 3 | Discovery of Late Cretaceous foraminifera in the Songliao Basin: Evidence from SK-1 and implications for identifying seawater incursions显示文摘The Songliao Basin is the largest oil-bearing basin in China.In the absence of sufficient evidence,the possibility of seawater incursion(s) into the Songliao Basin remains controversial.Recently,we discovered relatively abundant foraminifera fossils from units 1 and 2 of the Nenjiang Formation of borehole SK-1.Benthic foraminifera (Gavlinella sp.,Anomalinoides sp.,Pullenia sp.,Haplophragmoides sp.,Karrorulina hokkaidoana,Clavulinoides sp.),as well as planktonic foraminifera (Archaeoglobigerina blowi,Archaeoglobigerina cretacea and Hedbergella flandrini),were identified.These fossils were widely distributed in the marine Cretaceous.According to the global distribution of the above-mentioned planktonic foraminifera,the age of these fossil bearing strata appears to be Late Coniacian to Santonian.More importantly,these foraminifera provide direct evidence for marine water incursions into the Songliao Basin during deposition of the Lower Nenjiang Formation. | XI DangPeng WAN XiaoQiao FENG ZhiQiang LI Shun FENG ZiHui JIA JianZhong JING Xia SI WeiMin | 2011 | Chinese Science Bulletin2011，56，3： | 21 |
| 4 | ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer显示文摘 | Shunrong Ji Yi Qin Si Shi Xiangyuan Liu Hongli HU Hu Zhou Jing Gao Bo Zhang Wenyan Xu Jiang Liu Dingkong Liang Liang Liu Chen Liu Jiang Long Haijun Zhou Paul J Chiao Jin Xu Quanxing Ni Daming Gao Xianjun Yu | 2015 | Cell Research2015，25，5： | 19 |
| 5 | Relationship between serum homocysteine levels and long-term outcomes in patients with ST-segment elevation myocardial infarction显示文摘Background:The mortality of cardiovascular disease is constantly rising,and novel biomarkers help us predict residual risk.This study aimed to evaluate the predictive value of serum homocysteine (HCY) levels on prognosis in patients with ST-segment elevation myocardial infarction (STEMI).Methods:The 419 consecutive patients with STEMI,treated at one medical center,from March 2010 to December 2015 were retrospectively investigated.Peripheral blood samples were obtained within 24 h of admission and HCY concentrations were measured using an enzymatic cycling assay.The patients were divided into high HCY level (H-HCY) and low HCY level (L-HCY) groups.Short- and long-term outcomes were compared,as were age-based subgroups (patients aged 60 years and younger vs.those older than 60 years).Statistical analyses were mainly conducted by Student t-test,Chi-squared test,logistic regression,and Cox proportional-hazards regression.Results:The H-HCY group had more males (84.6% vs.75.4%,P=0.018),and a lower prevalence of diabetes (20.2% vs.35.5%,P<0.001),compared with the L-HCY group.During hospitalization,there were seven mortalities in the L-HCY group and 10 in the H-HCY group (3.3% vs.4.8%,P= 0.440).During the median follow-up period of 35.8 (26.9–46.1) months,33 (16.2%) patients in the L-HCY group and 48 (24.2%) in the H-HCY group experienced major adverse cardiovascular and cerebrovascular events (MACCE)(P=0.120).History of hypertension (hazard ratio [HR]:1.881,95% confidence interval [CI]:1.178–3.005,P=0.008) and higher Killip class (HR:1.923,95% CI:1.419–2.607,P<0.001),but not HCY levels (HR:1.007,95% CI:0.987–1.027,P=0.507),were significantly associated with long-term outcomes.However,the subgroup analysis indicated that in older patients,HCY levels were significantly associated with long-term outcomes (HR:1.036,95% CI:1.011–1.062,P=0.005).Conclusion:Serum HCY levels did not independently predict in-hospital or long-term outcomes in patients with STEMI;however,among elderly patients with STEMI,this study revealed a risk profile for late outcomes that incorporated HCY level. | Jin Si Xue-Wen Li Yang Wang Ying-Hua Zhang Qing-Qing Wu Lei-Min Zhang Xue-Bing Zuo Jing Gao Jing Li | 2019 | Chinese Medical Journal2019，，9： | 15 |
| 6 | Expressions of ICAM-1 and its mRNA in sera and tissues of patients with hepatocellular carcinoma显示文摘INTRODUCTIONThe increased expression of ICAM-1 on a widerange of cells and in the sera of patients withmalignancies, chronic liver diseases andinflammation diseases has been described since thelate 1980s[1-22]. Recently rapid progress in studieson expression of ICAM-1 in patients withhepatocellular carcinoma ( HCC ) have beenachieved, including clinical and experimentalresearches[23-31]. | Jing Xu1 Ming Hui Mei1 Si En Zeng2 Qing Fen Shi3 Yong Ming Liu4 Li Ling Qin3 1Department of Hepatobiliary Surgery2Department of Pathology3Institute of Hepatobiliary Surgery4Department of Biochemistry, Guilin 541001, Guangxi Province, China | 2001 | World Journal of Gastroenterology2001，7，1： | 14 |
| 7 | Low-dose quercetin positively regulates mouse healthspan显示文摘Dear Editor,Aging is the leading risk factor for many chronic diseases,accounting for almost 60%of all deaths worldwide.How to achieve healthy aging,alleviate aging-related diseases,and extend healthspan has become a main topic of biomedical research(He et al.,2019).Geroprotective compounds,such as metformin and rapamycin,have been shown to improve both healthspan and lifespan in mice(Martin-Montalvo et al.,2013;Bitto et al.,2016),whereas nicotinamide partially improves healthspan in mice(Mitchell et al.,2018). | Lingling Geng Zunpeng Liu Si Wang Shuhui Sun Shuai Ma Xiaoqian Liu Piu Chan Liang Sun Moshi Song Weiqi Zhang Guang-Hui Liu Jing Qu | 2019 | Protein & Cell2019，10，10： | 12 |
| 8 | Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs显示文摘干皮病 pigmentosum (XP ) 是联系 XP 的基因的变化引起的一组基因混乱,导致 DNA 修理的缺陷。XP 病人经常展出神经病学的退化,而是内在的机制是未知的,部分地由于合适的疾病模型的缺乏。这里,我们产生了包括 XPA, XPB, XPC, XPG,和 XPV 在五不同 XP 基因怀有变化的病人特定的导致的 pluripotent 干细胞(iPSCs ) 。这些 iPSCs 进一步被区分到神经房间,并且他们到 DNA 损坏应力的危险性被调查。在神经干细胞(NSC ) 或神经原的 XPA 的变化导致了严重 DNA 损坏修理缺点,并且有变异的 XPA 的这些神经房间对 DNA 导致损坏的 apoptosis 过分敏感。因此, XP 变异的神经房间代表珍贵工具在 XP 病人澄清神经病学的畸形的分子的机制。 | Lina Fu Xiuling Xu Ruotong Ren Jun Wu Weiqi Zhang Jiping Yang Xiaoqing Ren Si Wang Yang Zhao Liang Sun Yang Yu Zhaoxia Wang Ze Yang Yun Yuan Jie Qiao Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu | 2016 | Protein & Cell2016，7，3： | 11 |
| 9 | Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing显示文摘Many human genetic diseases,including Hutchinson-Gilford progeria syndrome(HGPS),are caused by single point mutations.HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene.Base editors(BEs)composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions.Here,we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA(gRNA)targeting the LMNA gene via microinjection into monkey zygotes.Five out of six newborn monkeys carried the mutation specifically at the target site.HGPS monkeys expressed the toxic form of lamin A,progerin,and recapitulated the typical HGPS phenotypes including growth retardation,bone alterations,and vascular abnormalities.Thus,this monkey model genetically and clinically mimics HGPS in humans,demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates. | Fang Wang Weiqi Zhang Qiaoyan Yang Yu Kang Yanling Fan Jingkuan Wei Zunpeng Liu Shaoxing Dai Hao Li Zifan Li Lizhu Xu Chu Chu Jing Qu Chenyang Si Weizhi Ji Guang-Hui Liu Chengzu Long Yuyu Niu | 2020 | Protein & Cell2020，11，11： | 11 |
| 10 | 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 |
| 11 | CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs显示文摘 | Lixia Wang Fei Yi Lina Fu Jiping Yang Si Wang Zhaoxia Wang Keiichiro Suzuki Liang Sun Xiuling Xu Yang Yu Jie Qiao Juan Carlos Izpisua Belmonte Ze Yang Yun Yuan Jing Qu Guang-Hui Liu | 2017 | Protein & Cell2017，8，5： | 10 |
| 12 | SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer显示文摘SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging. | Shijia Bi Zunpeng Liu Zeming Wu Zehua Wang Xiaoqian Liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2020 | Protein & Cell2020，11，7： | 10 |
| 13 | A human circulating immune cell landscape in aging and COVID-19显示文摘Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly. | Yingfeng Zheng Xiuxing Liu Wenqing Le Lihui Xie He Li Wen Wen Si Wang Shuai Ma Zhaohao Huang Jinguo Ye Wen Shi Yanxia Ye Zunpeng Liu Moshi Song Weiqi Zhang Jing-Dong J.Han Juan Carlos lzpisua Belmonte Chuanle Xiao Jing Qu Hongyang Wang Guang-Hui Liu Wenru Su | 2020 | Protein & Cell2020，11，10： | 10 |
| 14 | Green light-emitting diodes based on hybrid perovskite films with mixed cesium and methylammonium cations显示文摘我们报导高质量的 C 0.4 麻省 0.6 PbBr 3 有在进 perovskite 晶体的 C + 的介绍之上的将近完整的表面范围和好排放性质的薄电影。C 0.4 麻省 0.6 PbBr 3 薄电影在轻射出的二极管作为放射性的层被使用。~ 的最大的外部量效率 2.0% 为这些绿射出的设备被完成。 | Junjie Si Yang Liu Nana Wang Meng Xu Jing Li Haiping He Jianpu Wang Yizheng Jin | 2017 | Nano Research2017，10，4： | 9 |
| 15 | Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation显示文摘The clinical application of doxorubicin(DOX) in cancer chemotherapy is limited by its lifethreatening cardiotoxic effects. Chrysophanol(CHR), an anthraquinone compound isolated from the rhizome of Rheum palmatum L., is considered to play a broad role in a variety of biological processes.However, the effects of CHR’s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9 C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide(3 AB)and ABT888. Ectopic expression of PARP1 effectively blocked this CHR’s cardioprotection against DOX-induced cardiomyocyte injury in H9 C2 cells. Furthermore, pre-administration with both CHR and 3 AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague–Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy. | Jing Lu Jingyan Li Yuehuai Hu Zhen Guo Duanping Sun Panxia Wang Kaiteng Guo Dayue Darrel Duan Si Gao Jianmin Jiang Junjian Wang Peiqing Liu | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 8 |
| 16 | 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 |
| 17 | Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China显示文摘Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes. | MA Yan ZHU Dong Shan CHEN Ren Bo SHI Nan Nan LIU Si Hong FAN Yi Pin WU Gui Hui YANG Pu Ye BAI Jiang Feng CHEN Hong CHEN Li Ying FENG Qiao GUO Tuan Mao HOU Yong HU Gui Fen HU Xiao Mei HU Yun Hong HUANG Jin HUANG Qiu Hua HUANG Shao Zhen JI Liang JIN Hai Hao LEI Xiao LI Chun Yan LI Min Qing LI Qun Tang LI Xian Yong LIU Hong De LIU Jin Ping LIU Zhang MA Yu Ting MAO Ya MO Liu Fen NA Hui WANG Jing Wei SONG Fang Li SUN Sheng WANG Dong Ting WANG Ming Xuan WANG Xiao Yan WANG Yin Zhen WANG Yu Dong WU Wei WU Lan Ping XIAO Yan Hua XIE Hai Jun XU Hong Ming XU Shou Fang XUE Rui Xia YANG Chun YANG Kai Jun YUAN Sheng Li ZHANG Gong Qi ZHANG Jin Bo ZHANG Lin Song ZHAO Shu Sen ZHAO Wan Ying ZHENG Kai ZHOU Ying Chun ZHU Jun Teng ZHU Tian Qing ZHANG Hua Min WANG Yan Ping WANG Yong Yan 无 | 2020 | Biomedical and Environmental Sciences2020，33，12： | 8 |
| 18 | Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells显示文摘Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation.However,the underlying cellular and molecular mechanisms remain unidentified.Here,we generated non-integrative induced pluripotent stem cells(iPSCs)from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation(c.3226C>T,p.R1076C).Vascular smooth muscle cells(VSMCs)differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes,including activation of the NOTCH and NF-kB signaling pathway,cytoskeleton disorganization,and excessive cell proliferation.In comparison,these abnormalities were not observed in vascular endothelial cells(VECs)derived from the patients iPSCs.Importantly,the abnormal upregulation of NF-kB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor,providing a potential therapeutic strategy for CADASIL.Overall,using this iPSCbased disease model,our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease. | Chen Ling Zunpeng Liu Moshi Song Weiqi Zhang Si Wang Xiaoqian Liu Shuai Ma Shuhui Sun Lina Fu Qun Chu Juan Carlos Izpisua Belmonte Zhaoxia Wang Jing Qu Yun Yuan Guang-Hui Liu | 2019 | Protein & Cell2019，10，4： | 7 |
| 19 | Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency显示文摘Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease(KBD) and in an established T-2 toxin-and selenium(Se) deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD. | YANG Hao Jie ZHANG Ying WANG Zhi Lun XUE Sen Hai LI Si Yuan ZHOU Xiao Rong ZHANG Meng FANG Qian WANG Wen Jun CHEN Chen DENG Xiang Hua CHEN Jing Hong | 2017 | Biomedical and Environmental Sciences2017，30，5： | 7 |
| 20 | Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis显示文摘RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis. | Xing Zhang Zunpeng Liu Xiaoqian Liu Si Wang Yiyuan Zhang Xiaojuan He Shuhui Sun Shuai Ma Ng Shyh-Chang Feng Liu Qiang Wang Xiaoqun Wang Lin Liu Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2019 | Protein & Cell2019，10，9： | 7 |
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