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326篇 您的检索式:作者名="Wang Lixia"
    题名 作者 年代 出处 被引量
1Heavy metal pollution of soils and vegetables in the midstream and downstream of the Xiangjiang River, Hunan Province显示文摘219 农业土壤和 48 件蔬菜样品的一个总数在湖南省 Xiangjiang 河(Hengyang 长沙节) 从中流并且下游地被收集。累积特征。WANG Lixia GUO Zhaohui XIAO Xiyuan CHEN Tongbin LIAO Xiaoyong SONG Jie WU Bin 2008Journal of Geographical Sciences2008,18,3:56
2Regional assessment of cadmium pollution in agricultural lands and the potential health risk related to intensive mining activities: A case study in Chenzhou City, China显示文摘The purpose of this study was to assess the extent of cadmium (Cd) contamination in agricultural soil and its potential risk for people. Soils, rice, and vegetables from Chenzhou City, Southern China were sampled and analyzed. In the surface soils, the 95% confidence interval for the mean concentration of Cd varied between 2.72 and 4.83 mg/kg (P < 0.05) in the survey, with a geometric mean concentration of 1.45 mg/kg. Based on the GIS map, two hot spot areas of Cd in agricultural soils with high Cd concentrations were identified to be located around the Shizhuyuan, Jinshiling, and Yaogangxian mines, and the Baoshan and Huangshaping mines, in the center of the city. About 60% of the total investigated area, where the agricultural soil Cd concentration is above 1 mg/kg, is distributed in a central belt across the region. The critical distances, at which the soil Cd concentration were increased by the mining activities, from the mines of the soils were 23 km for the Baoshan mine, 46 km for the Huangshaping mine, and 63 km for the Shizhuyuan mine, respectively. These are distances calculated from models. The Cd concentrations in rice samples ranged from 0.01 to 4.43 mg/kg and the mean dietary Cd intake from rice for an adult was 191 μg/d. Results of risk indexes showed that soil Cd concentrations possessed risks to local residents whose intake of Cd from rice and vegetables grown in soils in the vicinity of the mine was 596 μg/d.ZHAI Limei LIAO Xiaoyong CHEN Tongbin YAN Xiulan XIE Hua WU Bin WANG Lixia 2008Journal of Environmental Sciences2008,20,6:35
3SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2显示文摘Huize Pan Di Guan Xiaomeng Liu Jingyi Li Lixia Wang Jun Wu Junzhi Zhou Weizhou Zhang Ruotong Ren Weiqi Zhang Ying Li Jiping Yang Ying Hao Tingting Yuan Guohong Yuan Hu Wang Zhenyu Ju Zhiyong Mao Jian Li Jing Qu FuchouTang Guang-Hui Liu 2016Cell Research2016,26,2:32
4Hydrogen sulfide induced by nitric oxide mediates ethylene-induced stomatal closure of Arabidopsis thaliana显示文摘Pharmacological, laser scanning confocal microscopic (LSCM), real-time PCR and spectrophotographic approaches are used to study the roles of hydrogen sulfide (H2S) and nitric oxide (NO) in signaling transduction of stomatal movement response to ethylene in Arabidopsis thaliana. In the present study, inhibitors of H2S synthesis were found to block ethylene-induced stomatal closure of Arabidopsis. Treatment with ethylene induced H2S generation and increased L-/D-cysteine desulfhydrase (pyridoxal-phosphate-dependent enzyme) activity in leaves. Quantitative PCR analysis showed AtL-CDes and AtD-CDes transcripts were induced by ethylene. It is suggested that ethylene-induced H2S levels and L-/D-cysteine desulfhydrase activity decreased when NO was compromised. The data clearly show that ethylene was able to induce H2S generation and stomatal closure in Atnoa1 plants, but failed in the Atnia1,nia2 mutant. Inhibitors of H2S synthesis had no effect on ethylene-induced NO accumulation and nitrate reductase (NR) activity in guard cells or leaves of Arabidopsis, whereas ethylene was able to induce NO synthesis. Therefore, we conclude that H2S and NO are involved in the signal transduction pathway of ethylene-induced stomatal closure. In Arabidopsis, H2S may represent a novel downstream indicator of NO during ethylene-induced stomatal movement.LIU Jing HOU LiXia LIU GuoHua LIU Xin WANG XueChen 2011Chinese Science Bulletin2011,56,33:23
5Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis显示文摘Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the precise mechanism of how autophagy links to cell death remains to be fully understood.Beclin 1 is a dual regulator for both autophagy and apoptosis.In this study we found that Beclin 1 was a substrate of caspase-3 with two cleavage sites at positions 124 and 149,respectively.Furthermore,the autophagosome formation occurred,followed by the appearance of morphological hallmarks of apoptosis after staurosporine treatment.The cleavage products of Beclin 1 reduced autophagy and promoted apoptosis in HeLa cells and the cells in which Beclin 1 was stably knocked down by specific shRNA.In addition,the cleavage of Beclin 1 resulted in abrogating the interaction between Bcl-2 with Beclin 1,which could be blocked by z-VAD-fmk.Thus,our results suggest that the cleavage of Beclin 1 by caspase-3 may contribute to inactivate autophagy leading towards augmented apoptosis.Yushan Zhu Lixia Zhao Lei Liu Ping Gao Weili Tian Xiaohui Wang Haijing Jin Haidong Xu Quan Chen 2010Protein & Cell2010,1,5:17
6Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing显示文摘单个房间的定序是为描出的一个强大的工具为个性化的癌症管理的同种细胞的关系和识别关键司机基因。这里,我们执行了结肠癌的一个盒子的单个房间的定序的分析。人口遗传分析在肿瘤房间人口识别了二独立克隆。主要肿瘤克隆作为早 oncogenic 事件怀有 APC 和 TP53 变化,而次要的克隆包含了优势的 CDC27 和 PABPC1 变化。在这二克隆的次要的克隆支持的 APC 和 TP53 变化的缺席从二细胞的起源被导出。体的变化等位基因频率系列的检查另外 21 个整个织物的定序 exome 的盒子在结肠癌揭示了同种细胞的起源的异质。下次,我们识别了在单个房间的水平显示出变化的高频率,但是在人口水平展出了低流行的变异的基因 SLC12A5。变异的 SLC12A5 的功能的描述在结肠癌揭示了它的潜在的 oncogenic 效果。我们的学习在单个房间的水平支持提供第一条 exome 宽的证据那结肠癌能具有 biclonal 起源,并且建议在一个队的低流行的变化可以也在单个水平起重要 protumorigenic 作用。Chang Yu Jun Yu Xlaotlan Yao Wllham KK Wu Youyong Lu Senwel Tang Xiangchun Li Li Bao Xiaoxing Li Yong Hou Renhua Wu Min Jian Ruoyan Chen Fan Zhang Lixia Xu Fan Fan Jun He Qiaoyi Liang Hongyi Wang Xueda Hu Minghui He Xiang Zhang Hancheng Zheng Qibin Li Hanjie Wu Yan Chen Xu Yang Shida Zhu Xun Xu Huanming Yang Jian Wang Xiuqing Zhang Joseph JY Sung Yingrui Li Jun Wang 2014Cell Research2014,,6:16
7Application of entropy production theory to hydro-turbine hydraulic analysis显示文摘The understanding of hydraulic behavior in the hydro turbine requires the detailed study of fluid flow in the turbine. Previous methods of analyzing the numerical simulation results on the fluid machinery are short of intuitiveness on energy dissipation.In this paper, the energy dissipation was analyzed based on the entropy production theory. 3-D steady flow simulations and entropy production calculations of the reduced hydro turbine were carried out. The results indicated that the entropy production theory was suitable for evaluating the performance of the hydro turbine. The energy dissipation in the guide vanes area weighted nearly 25% of the whole flow passage, and mainly happened at the head and tail areas of the vanes. However, more than half the energy dissipation occurred in the runner, mostly at the leading edge of runner blade and the trailing edge of run-ner blade. Meanwhile, close to 20% of the energy dissipation occurred in the elbow. And it can be concluded that the method of entropy production analysis has the advantages of determining the quantity of energy dissipation and where the dissipation happens.GONG RuZhi WANG HongJie CHEN LiXia LI DeYou ZHANG HaoChun WEI XianZhu 2013Science China(Technological Sciences)2013,56,7:15
8Hydrogen Sulfide Regulates Ethylene-induced Stomatal Closure in Arabidopsis thaliana显示文摘Hydrogen sulfide (H2S) is a newly-discovered signaling molecule in plants and has caused increasing attention in recent years, but its function in stomatal movement is unclear. In plants, H2S is synthesized via cysteine degradation catalyzed by D-/L-cysteine desulfhydrase (D-/L-CDes). AtD-/L-CDes::GUS transgenic Arabidopsis thaliana (L.) Heynh. plants were generated and used to investigate gene expression patterns, and results showed that AtD-/L-CDes can be expressed in guard cells. We also determined the subcellular localization of AtD-/L-CDes using transgenic plants of AtD-/L-CDes::GFP, and the results showed that AtD-CDes and AtL-CDes are located in the chloroplast and in the cytoplasm, respectively. The transcript levels of AtD-CDes and AtL-CDes were affected by the chemicals that cause stomatal closure. Among these factors, ACC, a precursor of ethylene, has the most significant effect, which indicates that the H2S generated from D-/L-CDes may play an important role in ethylene-induced stomatal closure. Meanwhile, H2S synthetic inhibitors significantly inhibited ethylene-induced stomatal closure in Arabidopsis. Ethylene treatment caused an increase of H2S production and of AtD-/L-CDes activity in Arabidopsis leaves. AtD-/L-CDes over-expressing plants exhibited enhanced induction of stomatal closure compared to the wild-type after ethylene treatment; however, the effect was not observed in the Atd-cdes and Atl-cdes mutants. In conclusion, our results suggest that the D-/L-CDes-generated H2S is involved in the regulation of ethylene-induced stomatal closure in Arabidopsis thaliana.Zhihui Hou Lanxiang Wang Jing Liu Lixia Hou Xin Liu 2013Journal of Integrative Plant Biology2013,55,3:13
9Cerebral small vessel disease or intracranial large vessel atherosclerosis may carry different risk for future strokes显示文摘Background The effect of cerebral small vessel disease(CSVD)and intracranial arterial stenosis(ICAS)on stroke outcomes remains unclear.Methods Data of 1045 patients with minor stroke or transient ischaemic attack(TIA)were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events(CHANCE)trial.We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale(mRS)scores using ordinal logistic regression models.Results Among the 1045 patients,CSVD was present in 830 cases(79.4%)and ICAS in 460(44.0%).Patients with>1 ICAS segment showed the highest risk of new strokes(HR 2.03,95%CI 1.15 to 3.56,p=0.01).No association between CSVD and the occurrence of new strokes was found.The presence of severe CSVD(common OR(cOR)2.01,95%CI 1.40 to 2.89,p<0.001)and>1 ICAS segment(cOR 2.15,95%CI 1.57 to 2.93,p<0.001)was associated with higher mRS scores.Severe CSVD(HR 10.70,95%CI 1.16 to 99.04,p=0.04),but not ICAS,was associated with a higher risk of bleeding events.Six-point modified CSVD score improved the predictive power for bleeding events and disability.Interpretation CSVD is associated with more disability and bleeding events,and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months.CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Huimin Chen Yuesong Pan Lixia Zong Jing Jing Xia Meng Yuyuan Xu Hongyi Yan Xingquan Zhao Liping Liu Hao Li S Claiborne Johnston Yongjun Wang Yilong Wang 2020Stroke & Vascular Neurology2020,5,2:13
10Paleoclimate Modeling in China: A Review显示文摘This paper provides a review of paleoclimate modeling activities in China. Rather than attempt to cover all topics, we have chosen a few climatic intervals and events judged to be particularly informative to the international community. In historical climate simulations, changes in solar radiation and volcanic activity explain most parts of reconstructions over the last millennium prior to the industrial era, while atmospheric greenhouse gas concentrations play the most important role in the20 th century warming over China. There is a considerable model–data mismatch in the annual and boreal winter temperature change over China during the mid-Holocene [6000 years before present(ka BP)], while coupled models with an interactive ocean generally perform better than atmospheric models. For the Last Glacial Maximum(21 ka BP), climate models successfully reproduce the surface cooling trend over China but fail to reproduce its magnitude, with a better performance for coupled models. At that time, reconstructed vegetation and western Pacific sea surface temperatures could have significantly affected the East Asian climate, and environmental conditions on the Qinghai–Tibetan Plateau were most likely very different to the present day. During the late Marine Isotope Stage 3(30–40 ka BP), orbital forcing and Northern Hemisphere glaciation, as well as vegetation change in China, were likely responsible for East Asian climate change. On the tectonic scale,the Qinghai–Tibetan Plateau uplift, the Tethys Sea retreat, and the South China Sea expansion played important roles in the formation of the East Asian monsoon-dominant environment pattern during the late Cenozoic.JIANG Dabang YU Ge ZHAO Ping CHEN Xing LIU Jian LIU Xiaodong WANG Shaowu ZHANG Zhongshi YU Yongqiang LI Yuefeng JIN Liya XU Ying JU Lixia ZHOU Tianjun YAN Xiaodong 2015Advances in Atmospheric Sciences2015,32,2:12
11Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders:executive summary and 2019 update of the management of high-risk population显示文摘Aim Cerebrovascular disease is the leading cause of death and disability in China,causing a huge burden among patients and their families.Hence,stroke prevention is critical,especially in the high-risk population.Here,we present the evidence-based guideline suitable for the Chinese population.Methods Literature search of PubMed and Cochrane library(from January 1964 to June 2019)was done.After thorough discussion among the writing group members,recommendations were listed and summarised.This guideline was reviewed and discussed by the fellow writing committees of the Chinese Stroke Association’s Stroke.Results This evidence-based guideline was written in three parts:controlling the risk factors of stroke,utilisation of antiplatelet agents and assessing the risks of first-ever stroke.All recommendations were listed along with the recommending classes and levels of evidence.Conclusions This guideline provides recommendations for primary prevention of cerebrovascular disease among high-risk population in China.Controlling related risk factors,appropriately using antiplatelet agents,assessing the risk of developing first-ever stroke should help reduce the rate of cerebrovascular disease in China.Yilong Wang Shangrong Han Haiqiang Qin Huaguang Zheng Bin Jiang Yong Cao Yuan Gao Ling Guan Qian Jia Yong Jiang Yuming Jiao Shuya Li Yapeng Li Zixiao Li Wei Liu Xiaojuan Ru Dongling Sun Haixin Sun Penglian Wang Tingting Wang Lixia Zong Lei Guo Xuewei Xie Yuming Xu Yuyuan Xu Xiaomeng Yang Yingying Yang Mengyuan Zhou Wenzhi Wang Chinese Stroke Association Stroke Council Guideline Writing Committee 2020Stroke & Vascular Neurology2020,5,3:11
12CRISPR/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 2017Protein & Cell2017,8,5:10
13Construction of an integrated map and location of a bruchid resistance gene in mung bean显示文摘Bruchid beetle(Callosobruchus chinensis) poses a serious threat to the production and storage of mung bean(Vigna radiata). Mapping bruchid resistance(Br) will provide an important basis for cloning the responsible gene(s) and elucidating its functional mechanism, and will also facilitate marker-assisted selection in mung bean breeding. Here, we report the construction of the genetic linkage groups of mung bean and mapping of the Br1 locus using an RIL population derived from a cross between Berken, a bruchid-susceptible line, and ACC41, a bruchid-resistant line. A total of 560 markers were mapped onto 11 linkage groups,with 38.0% of the markers showing distorted segregation. The lengths of the linkage groups ranged from 45.2 to 117.0 c M with a total coverage of 732.9 c M and an average interval of1.3 c M between loci. Br1 was located on LG9 between BM202(0.7 c M) and Vr2-627(1.7 c M).Based on 270 shared SSR markers, most of the linkage groups were assigned to specific chromosomes. These results should further accelerate the genetic study of this crop.Lixia Wang Chuanshu Wu Min Zhong Dan Zhao Li Mei Honglin Chen Suhua Wang Chunji Liu Xuzhen Cheng 2016The Crop Journal2016,4,5:9
14Salmeterol attenuates the inflammatory response in asthma and decreases the pro-inflammatory cytokine secretion of dendritic cells显示文摘Salmeterol 是长行动的 β激活 adenylate cyclase 的 2 收缩筋,引起长持续的 bronchodilation 并且被用于许多年到控制气喘。然而,很少信息都不关于 salmeterol 的 immunoregulatory 效果是可得到的。我们发现 salmeterol 减少在表示了肿瘤坏死 factor-alpha, interleukin-1 和 interleukin-6 的质问变应原的老鼠的一个模型的支持 inflammatory cytokines 的生产。树枝状的房间(DC ) 是介绍抗原的房间并且在航线充当哨兵。我们发现了那 salmeterol (10 −5 mol/l ) 减少了 lipopolysaccharide 引起的发炎(0.1 µ g/ml ) 在激活的鼠科的骨头导出髓的 DC。而且,西方的污点证明这保护的效果被禁止通过原子 factor-kappa B 发信号部分调停(NF-κ B ) ,激活 mitogen 的蛋白质 kinase (MAPK ) 小径和津贴的戏剧性地减少的层次。我们建议 salmeterol 由 modulating DC 调整导致变应原的气喘的发炎。在结论,我们提供 DC 是为对气喘的 salmeterol 的行动负责的目标免疫者房间的证据。Zhenli Hu Ruohua Chen Zhijian Cai Lei Yu Yang Fei Lixia Weng Jinghan Wang Xiahui Ge Tianyi Zhu Jianli Wang Chong Bai 2012Cellular & Molecular Immunology2012,9,3:8
15Synthesis of graphene on a Ni film by radio-frequency plasma-enhanced chemical vapor deposition显示文摘Large-area single-or multilayer graphene of high quality is synthesized on Ni films by radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD) at a relatively low temperature (650℃).In the deposition process,a trace amount of CH4 gas (2-8 sccm (sccm denotes standard cubic centimeter per minute at STP)) is introduced into the PECVD chamber and only a short deposition time (30-60 s) is used.Single-or multilayer graphene is obtained because carbon atoms from the discharging CH4 diffuse into the Ni film and then segregate out at its surface.The layer number of the obtained graphene increases when the deposition time or CH4 gas flow rate is increased.This investigation shows that PECVD is a simple,low-cost,and effective technique to synthesize large-area single-or multilayer graphene,which has potential for application as electronic devices.QI JunLei ZHANG LiXia CAO Jian ZHENG WeiTao WANG Xin FENG JiCai 2012Chinese Science Bulletin2012,57,23:8
16Spatio-temporal differentiation of landscape ecological niche in western ecological frangible region: A case study of Yan'an region in northwestern China显示文摘In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpful for comprehensively appraising landscape spatial patterns and ecological functions, also, presents a new method for analyzing landscape features from multidimensional aspects. The practice process is demonstrated by taking Yan’an region in northwestern China as a case. Firstly, the indices system including spatial attribute and functional attribute is established for assessing landscape ecological niche. Additionally, two-dimensional figures are drawn for comparing the spatio-temporal features of landscape ecological niche in 1987 and 2000 among the 13 administrative counties. The results show that from 1987 to 2000, towards Yan’an region, spatial attribute value of landscape ecological niche changes from 1.000 to 1.178 with an obvious increment, and functional attribute value changes from 0.989 to 1.069 with a little increment, both of which enhance the regional landscape ecological niche. Towards each county, spatial attribute value of landscape ecological niche increases to different extent while functional attribute value changes dissimilarly with an increment or a decrement.REN Zhiyuan WANG Lixia 2007Journal of Geographical Sciences2007,17,4:8
17NH3-SCR performance and the resistance to SO2 for Nb doped vanadium based catalyst at low temperatures显示文摘Niobium oxide as the promoter was doped in the V/WTi catalyst for the selective catalytic reduction(SCR)of NO.The results showed that the addition of Nb_2O_5could improve the SCR activity at low temperatures and the 6 wt.%additive was an appropriate dosage.The enhanced reaction activity of adsorbed ammonia species and the improved dispersion of vanadium oxide might be the reasons for the elevation of SCR activity at low temperatures.The resistances to SO_2of 3V6Nb/WTi catalyst at different temperatures were investigated.FTIR spectrum and TG-FTIR result indicated that the deposition of ammonium sulfate species was the main deactivation reason at low temperatures,which still exhibited the reactivity with NO above 200°C on the catalyst surface.There was a synergistic effect among NH_3,H_2O and SO_2that NH_3and H_2O both accelerated the catalyst deactivation in the presence of SO_2at 175°C.The thermal treatment at 400°C could regenerate the deactivated catalyst and get SCR activity recovered.The particle and monolith catalysts both kept stable NO_xconversion at 225°C with high concentration of H_2O and SO_2during the long time tests.Lin Zhu Zhaoping Zhong Jianming Xue Yueyang Xu Chunhua Wang Lixia Wang 2018Journal of Environmental Sciences2018,30,3:8
18Epidermal growth factor improves intestinal morphology by stimulating proliferation and differentiation of enterocytes and mTOR signaling pathway in weaning piglets显示文摘Epidermal growth factor(EGF) has been shown to improve piglet intestinal morphology and epithelial recovery. In an attempt to further understand the mechanisms behind these improvements, this study tested the hypothesis that dietary EGF may affect intestinal morphology by stimulating the proliferation and differentiation of enterocytes in weaning piglets. In piglets receiving200 μg kg^-1 EGF, crypt depth and villus height increased(P<0.05). Adding 400 μg kg^-1 EGF increased villus height-to-crypt depth ratio(P<0.05), but reduced crypt depth(P<0.05). Dietary supplementation with 200 μg kg^-1 EGF significantly increased the number of Ki67-positive cells(P<0.01) and tended to increase the mRNA level of proliferating cell nuclear antigen(P<0.10).However, this supplementation decreased the expression level of intestinal fatty acid-binding protein(P<0.05). Piglets fed with400 μg kg^-1 EGF had an increased mRNA level of intestinal alkaline phosphatase(P<0.05). The phosphorylation of m TOR(mammalian target of rapamycin) was observed in the 200 μg kg^-1 EGF group. These results suggest that dietary supplementation with a low level of EGF improved piglet intestinal morphology through stimulating the proliferation and differentiation of enterocytes, and the mTOR signaling pathway may partly be involved in this process.Lixia Wang Fan Zhu Huansheng Yang Jianzhong Li Yali Li Xueqin Ding Xia Xiong Fengjie Ji Hanlin Zhou Yulong Yin 2020Science China(Life Sciences)2020,63,2:7
19Conversion between polarization states based on a metasurface显示文摘Transmission of an anisotropic metasurface is analyzed in a polar base relying on the Jones calculus, and polarization conversion from the spatial uniform polarization to the spatial nonuniform polarization is explored.Simple and compact polarization converters based on rectangular holes or cross holes etched in silver film are designed, and polarization conversions from the linear and circular polarization to the radial and azimuthal polarization are realized. Numerical simulations of three designed polarization converters consisting of rectangular holes equivalent to polarizers and quarter-and half-wave plates, exhibit the perfect polarization conversion.The experiment results consistent with the simulations verify theoretic predictions. This study is helpful for designing metasurface polarization converters and expanding the application of a metasurface in polarization manipulations.SHUYUN TENG QI ZHANG HAN WANG LIXIA LIU HAORAN LV 2019Photonics Research2019,7,3:7
20Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction显示文摘Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature aging.However,the pathogenesis of CS remains unclear due to the limitations of current disease models.Here,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 system.CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage stress.Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6.We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS pathologies.Moreover,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS.Collectively,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao 2020Protein & Cell2020,11,1:7
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