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| 1 | Methylated and thiolated arsenic species for environmental and health research——A review on synthesis and characterization显示文摘Hundreds of millions of people around the world are exposed to elevated concentrations of inorganic and organic arsenic compounds, increasing the risk of a wide range of health effects. Studies of the environmental fate and human health effects of arsenic require authentic arsenic compounds. We summarize here the synthesis and characterization of more than a dozen methylated and thiolated arsenic compounds that are not commercially available. We discuss the methods of synthesis for the following14 trivalent(Ⅲ) and pentavalent() arsenic compounds: monomethylarsonous acid(MMA~Ⅲ), dicysteinylmethyldithioarsenite(MMA~Ⅲ(Cys)_2), monomethylarsonic acid(MMA~Ⅴ),monomethylmonothioarsonic acid(MMMTAⅤ) or monothio-MMA~Ⅴ, monomethyldithioarsonic acid(MMDTA~Ⅴ) or dithio-MMA~Ⅴ, monomethyltrithioarsonate(MMTTA~Ⅴ) or trithio-MMA~Ⅴ,dimethylarsinous acid(DMA~Ⅲ), dimethylarsino-glutathione(DMA~Ⅲ(SG)), dimethylarsinic acid(DMA~Ⅴ), dimethylmonothioarsinic acid(DMMTA~Ⅴ) or monothio-DMAⅤ, dimethyldithioarsinic acid(DMDTA~Ⅴ) or dithio-DMA~Ⅴ, trimethylarsine oxide(TMAO~Ⅴ), arsenobetaine(AsB), and an arsenicin-A model compound. We have reviewed and compared the available methods,synthesized the arsenic compounds in our laboratories, and provided characterization information. On the basis of reaction yield, ease of synthesis and purification of product, safety considerations, and our experience, we recommend a method for the synthesis of each of these arsenic compounds. | William R.Cullen Qingqing Liu Xiufen Lu Anthony McKnight-Whitford Hanyong Peng Aleksandra Popowich Xiaowen Yan Qi Zhang Michael Fricke Hongsui Sun X.Chris Le | 2016 | Journal of Environmental Sciences2016,28,11: | 12 |
| 2 | Biomimetic Corrugated Silicon Nanocone Arrays for Self-Cleaning Antireflection Coatings显示文摘Corrugated silicon nanocone(SiNC)arrays have been fabricated on a silicon wafer by two polystyrene-sphere-monolayer-masked etching steps in order to create high-performance antireflective coatings.The reflectance was reduced from above 35%to less than 0.7%in the range 400-1050 nm,and it remained below 0.5%at incidence angles up to 70°at 632.8 nm for both s-and p-polarized light.The fluorinated corrugated SiNC array surface exhibits superhydrophobic properties with a water contact angle of 164°. | Yandong Wang Nan Lu Hongbo Xu Gang Shi Miaojun Xu Xiaowen Lin Haibo Li Wentao Wang Dianpeng Qi Yanqing Lu Lifeng Chi | 2010 | Nano Research2010,3,7: | 8 |
| 3 | Genome evolution trend of common carp (Cyprinus carpio L.) as revealed by the analysis of microsatellite loci in a gynogentic family显示文摘Genome evolution arises from two main ways of duplication and reduction. Fish specific genome duplication (FSGD) may have occurred before the radiation of the teleosts. Common carp (Cyprinus carpio L.) has been considered to be a tetraploid species, because of its chromosome numbers (2n=100) and its high DNA content. Using 69 microsatellite primer pairs, the variations were studied to better understand the genome evolution (genome duplication and diploidization) of common carp from a gynogenetic family. About 48% of primer pairs were estimated to amplify duplicates based on the number of PCR amplification per individual. Segregation patterns in the family suggested a partially duplicated genome structure and disomic inheritance. This indicates that the common carp is tetraploid and polyploidy occurred by allotetraploidy. Two primer pairs (HLJ021 and HLJ332) were estimated to amplify reduction based on the number of PCR amplification per individual. One allele in HLJ002 locus and HLJ332 locus was clearly lost in the gynogenetic family and the same as in six wild populations. Segregation patterns in the family suggested a partially diplodization genome structure. A hypothesis transition (dynamic) and equilibrium (static) were proposed to explain the common carp genome evolution between genome duplication and diploidization. | Yah Zhang Liqun Liang Peng Jiang Dayu Li Cuiyun Lu Xiaowen Sun | 2008 | Journal of Genetics and Genomics2008,35,2: | 7 |
| 4 | Generalized multipath planning model for ride-sharing systems显示文摘 | Jamal YOUSAF JuanziLI Lu CHEN Jie TANG Xiaowen DAI | 2014 | Frontiers of Computer Science2014,8,1: | 5 |
| 5 | Niacin alters the ruminal microbial composition of cattle under high-concentrate condition显示文摘To understand the effects of niacin on the ruminal microbial ecology of cattle under high-concentrate diet condition, Illumina MiSeq sequencing technology was used. Three cattle with rumen cannula were used in a 3 x 3 Latin-square design trial. Three diets were fed to these cattle during 3 periods for 3 days, respectively: high-forage diet(HF; forage-to-concentrate ratio = 80:20), high-concentrate diet(HC;forage-to-concentrate ratio=20:80), and HC supplemented with 800 mg/kg niacin(HCN). Ruminal pH was measured before feeding and every 2 h after initiating feeding. Ruminal fluid was sampled at the end of each period for microbial DNA extraction. Overall, our findings revealed that subacute ruminal acidosis(SARA) was induced and the a-diversity of ruminal bacterial community decreased in the cattle of HC group. Adding niacin in HC could relieve the symptoms of SARA in the cattle but the ruminal pH value and the Shannon index of ruminal bacterial community of HCN group were still lower than those of HF group. Whatever the diet was, the ruminal bacterial community of cattle was dominated by Bacteroidetes,Firmicutes and Proteobacteria. High-concentrate diet significantly increased the abundance of Prevotella,and decreased the abundance of Paraprevotella, Sporobacter, Ruminococcus and Treponema than HF.Compared with HC, HCN had a trend to decrease the percentage of Prevotella, and to increase the abundance of Succiniclasticum, Acetivibrio and Treponema. Increasing concentrate ratio could decrease ruminal pH value, and change the ruminal microbial composition. Adding niacin in HC could increase the ruminal pH value, alter the ruminal microbial composition. | Dan Luo Yufei Gao Youyou Lu Mingren Qu Xiaowen Xiong Lanjiao Xu Xianghui Zhao Ke Pan Kehui Ouyang | 2017 | Animal Nutrition2017,,2: | 4 |
| 6 | LncDACH1 promotes mitochondrial oxidative stress of cardiomyocytes by interacting with sirtuin3 and aggravates diabetic cardiomyopathy显示文摘Diabetic cardiomyopathy(DCM)is a common complication in diabetic patients.The molecular mechanisms of DCM remain to be fully elucidated.The intronic long noncoding RNA of DACH1(lnc DACH1)has been demonstrated to be closely associated with heart failure and cardiac regeneration.In this study,we investigated the role of lnc DACH1 in DCM and the underlying molecular mechanisms.The expression of lnc DACH1 was increased in DCM hearts and in high glucose-treated cardiomyocytes.Knockout of lnc DACH1 reduced mitochondrial oxidative stress,cell apoptosis,cardiac fibrosis and hypertrophy,and improved cardiac function in DCM mice.Overexpression of lnc DACH1 exacerbated mitochondria-derived reactive oxygen species(ROS)level and apoptosis,decreased activity of manganese superoxide dismutase(Mn-SOD);while silencing of lnc DACH1 attenuated ROS production,mitochondrial dysfunction,cell apoptosis,and increased the activity of Mn-SOD in cardiomyocytes treated with high glucose.Lnc DACH1 directly bound to sirtuin3(SIRT3)and facilitated its degradation by ubiquitination,therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse hearts.In addition,SIRT3 silencing abrogated the protective effects of lnc DACH1 deficiency in cardiomyocytes.In summary,lnc DACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse hearts.Inhibition of lnc DACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy. | Qi Zhang Danyang Li Xue Dong Xiaowen Zhang Junwu Liu Lili Peng Bo Meng Qi Hua Xinyu Pei Lu Zhao Xiaoxi Hu Yang Zhang Zhenwei Pan Yanjie Lu Baofeng Yang | 2022 | Science China(Life Sciences)2022,65,6: | 4 |
| 7 | Severity of early allograft dysfunction following donation after circulatory death liver transplantation:a multicentre study显示文摘Background:Early allograft dysfunction(EAD)is associated with decreased graft and patient survival rates.This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death(DCD)liver transplantation(LT).Furthermore,the influence of operative time on EAD incidence was also evaluated.Methods:In this retrospective,multicentre cohort study,nomograms were established based on a single-centre training cohort(n=321)and validated in a 3-center validation cohort(n=501).Results:The incidence rate of EAD was 46.4%(149/321)in the training cohort and 40.5%(203/501)in the validation cohort.Of the 149 EAD patients in the training cohort,77 patients with either elevated alanine aminotransferase(ALT)or aspartate aminotransferase(AST)were classified as having EAD type A,and the rest of the EAD patients were classified as having EAD type B.Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A(P=0.043 and 0.044,respectively).We further developed a nomogram to predict EAD(graft weight,cold ischemia time,donor age,model for end-stage liver disease(MELD)score)and another nomogram to predict EAD type B(graft weight,cold ischemia time,MELD score).The nomograms for the prediction of EAD and EAD type B had good discrimination[concordance index(C-index)=0.712(0.666-0.758),0.707(0.641-0.773)]and calibration[Hosmer-Lemeshow(HL)P=0.384,P=0.425]in the validation cohort.An increased operative time(>6 h)was associated with increased EAD and EAD type B incidence in the high-risk group(P=0.005,P=0.020,respectively).Conclusions:EAD type B was associated with decreased graft and patient survival rates.The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients. | Kun Wang Di Lu Yuhui Liu Wangyao Li Li Zhuang Zhenyu Ma Qinfen Xie Binhua Pan Yichao Wu Junli Chen Lidan Lin Xiaowen Feng Qiang Wei Xuyong Wei Haiyang Xie Zhengxin Wang Shusen Zheng Xiao Xu | 2021 | Hepatobiliary Surgery and Nutrition2021,10,1: | 4 |
| 8 | A consensus linkage map of common carp (Cyprinus carpio L.) to compare the distribution and variation of QTLs associated with growth traits显示文摘The ability to detect and identify quantitative trait loci (QTLs) in a single population is often limited. Analyzing multiple populations in QTL analysis improves the power of detecting QTLs and provides a better understanding of their functional allelic variation and distribution. In this study, a consensus map of the common carp was constructed, based on four populations, to compare the distribution and variation of QTLs. The consensus map spans 2371.6 cM across the 42 linkage groups and comprises 257 microsatellites and 421 SNPs, with a mean marker interval of 3.7 cM/marker. Sixty-seven QTLs affecting four growth traits from the four populations were mapped to the consensus map. Only one QTL was common to three populations, and nine QTLs were detected in two populations. However, no QTL was common to all four populations. The results of the QTL comparison suggest that the QTLs are responsible for the phenotypic variability observed for these traits in a broad array of common carp germplasms. The study also reveals the different genetic performances between major and minor genes in different populations. | ZHENG XianHu KUANG YouYi LV WeiHua CAO DingChen ZHANG XiaoFeng LI Chao LU CuiYun SUN XiaoWen | 2013 | Science China(Life Sciences)2013,56,4: | 4 |
| 9 | Schisandrol A protects AGEs-induced neuronal cells death by allosterically targeting ATP6V0d1 subunit of V-ATPase显示文摘Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products(AGEs)-induced neuronal cell apoptosis;however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A(SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase(V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification.Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial-lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy. | Xiaoqing Zhou Shaoyang Zhao Tingting Liu Lu Yao Meimei Zhao Xiaoming Ye Xiaowen Zhang Qiang Guo Pengfei Tu Kewu Zeng | 2022 | Acta Pharmaceutica Sinica B2022,12,10: | 3 |
| 10 | Comparative tribological properties of magnesium hexasilicate and serpentine powder as lubricating oil additives under High temperature显示文摘 | Xiaowen Qi Ling Lu Zhining Jia Yulin Yang Huiran Liu | 2011 | Tribology International2011,,: | 3 |
| 11 | Rational design of palladium single-atoms and clusters supported on silicoaluminophosphate-31 by a photochemical route for chemoselective hydrodeoxygenation of vanillin显示文摘Chemoselective hydrodeoxygenation of vanillin is of great importance in converting biomass into high value-added chemicals.Herein,we describe a facile photochemical route to access palladium single atoms and clusters supported on silicoaluminophosphate-31(SAPO-31)as a highly active,chemoselective,and reusable catalyst for hydrodeoxygenation of vanillin.Characterizations by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy,extended X-ray absorption fine structure measurement,and CO-absorbed diffuse reflectance infrared Fourier transform spectroscopy reveal the atomically dispersed palladium single atoms and clusters are loosely bonded and randomly dispersed,without forming strong palladium-palladium metallic bonding,over the SAPO-31 support.This catalyst,with a full metal availability to the reactants,exhibits exceptional catalytic activity(TOF:3,000 h^(−1),Yield:>99%)in the hydrodeoxygenation of vanillin toward 2-methoxy-4-methylphenol(MMP)under mild conditions(1 atm,80°C,30 min),along with excellent stability,scalability(up to 100-fold),and wide substrate scope.The superior catalytic performance can be attributed to the synergistic effect of the positively charged palladium single atoms and fully exposed clusters,as well as the strong metal-support interactions.This work may offer a new avenue for the design and synthesis of fully exposed metal catalysts with targeted functionalities. | Xiaowen Lu Chunmu Guo Mingyang Zhang Leipeng Leng J.Hugh Horton Wei Wu Zhijun Li | 2021 | Nano Research2021,14,11: | 3 |
| 12 | Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy显示文摘Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells(ECs) initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment.Radiotherapy(RT) is a vital tumor treatment modality. Currently, more than 60% of patients with malignant tumors receive RT at certain points during their treatment. Hypoxia induced by abnormal microvessels can hamper the cytotoxic effect of ionizing radiation, particularly, stereotactic body radiotherapy(SBRT). Anti-angiogenesis(AA) agents are known to reduce and renormalize microvessels in tumors, and hence alleviate hypoxia. The combination of AA agents with SBRT may have a synergistic role in inhibiting the growth of tumors. On the contrary, large doses of irradiation may affect tumor microvessels itself. In this review, we aim to clarify the relationship between SBRT and microvessel formation in tumors. In addition, we provide a retrospective analysis of the combination therapy involving SBRT and AA agents in preclinical and clinical practice to define its role in antitumor treatment. | Xiaowen Sun Lei Deng You Lu | 2018 | Chinese Journal of Cancer Research2018,30,1: | 3 |
| 13 | Dynamic Clustering of Coordinated Multi-point Transmission Based on Friends Algorithm显示文摘Coordinated multi-point(Co MP) transmission has been regarded as a fascinating technology for4 G wireless communication systems. In this paper, the Co MP dynamic clustering problem is studied, a Friends algorithm(F-A) is proposed based on the procedure of making friends in human society, and then a dynamic clustering scheme is proposed based on F-A. The mutual interference among cells of the network is considerate in this algorithm, which can be obtained by CSI feedback.Compared to Traversal search(T-S) algorithm, the proposed algorithm has lower computational complexity, and the performance is almost equal. Simulation results show the proposed scheme is effective for dynamic clustering. | HENG Wei LIANG Tian MENG Chao LI Shihuan LU Xiaowen | 2015 | Chinese Journal of Electronics2015,24,2: | 2 |
| 14 | Photoreduction of CO_(2) in the presence of CH_(4) over g-C_(3)N_(4) modified with TiO_(2) nanoparticles at room temperature显示文摘CO_(2)reduction under simulated sunlight over photocatalysts has become an attractive researcher area recently.In this work,carbon nitride compounds modified by TiO_(2)nanoparticles(TNPs)have been used for the photoreduction of CO_(2)in the presence of CH_(4)at room temperature.Briefly,a series of noble-metal-free TNP-graphitic-carbon nitride(g-C_(3)N_(4),also abbreviated CN)photocatalysts with different TNPs loadings and calcination temperatures have been synthesized by a wet-chemical method.The characterization results of XRD,FTIR,SEM,TEM,BET,XPS,CO_(2)Adsorption,UV-vis,and PL demonstrate that the BET surface area and CO_(2)adsorption capacity have been improved after the calcination.Besides,the g-C_(3)N_(4)has been successfully coupled with the TNPs and a heterojunction has formed at their interface.These characters contribute to increase the photocatalytic activity of TNPs-CN toward reducing CO_(2)in the presence of CH_(4),and its'performance is better than bare g-C_(3)N_(4),Titania(P_(25))-CN,MgO-CN,or Cu_(2)O-CN.Orthogonal experiments are then carried out to investigate the sensitivity factors and optimum conditions.The sensitivity results show that the reaction pressure makes little difference on the photocatalysis results,which verifies the photoinduced CO_(2)-CH_(4)reaction has a tiny change in gas volume.In addition,under the optimum conditions,the turnover frequency(TOF)of CO after 4 h reaction can reach 9.98μmol g-cat.^(-1)h^(-1),and traces of ethane and ethylene have been detected during the reactions.In addition,surface acetate and carbonaceous deposit are found on the(20)TNPs-CN/450 surface after continuous 24 h irradiation under the optimum conditions,which resulting in the inactivation of the catalyst.Finally,possible reaction mechanisms have been proposed based on the results. | Ming Chen Jiachen Wu Chongchong Lu Xiao Luo Yangqiang Huang Bo Jin Hongxia Gao Xiaowen Zhang Morris Argyle Zhiwu Liang | 2021 | Green Energy & Environment2021,6,6: | 2 |
| 15 | KH型剪切调控蛋白:星形胶质细胞炎性细胞因子生成检测点显示文摘中枢神经系统(CNS)慢性炎性反应是许多神经退行性疾病和自身免疫性疾病的主要病理特点之一。作为免疫活性细胞,星形胶质细胞(Ast)在CNS炎性反应过程中发挥了重要作用。它可表达许多细胞因子,如肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)等,这些细胞因子可直接或通过募集免疫细胞等途径间接促进炎性反应。检测点的存在可保证这些细胞因子的生成受到严密控制。细胞因子mRNA3’-非翻译区的腺苷酸/尿苷酸富含元件(ARE)由于可调节mRNA稳定性和翻译效率而扮演着主要检测点的角色。KH型剪切调控蛋白(KSRP)是一种RNA结合蛋白,可通过与ARE结合降低mRNA的稳定性。本研究检测了KSRP对Ast细胞因子表达和旁分泌表型的影响。笔者发现了一个包括TNF-α和L-1β在内的炎性介质网络。与同窝出生的对照小鼠相比,KSRP-/-小鼠Ast上述炎性介质的表达在RNA水平增高了2~4倍。而这种KSRP-/-小鼠Ast激活后产生的TNF-α和IL-1β甚至能达到对照组的15倍以上。离体情况下,KSRP-/-Ast条件性培养液有趋化作用且能诱导神经元死亡。令人惊讶的是,笔者发现仅通过特定途径激活Ast后才能观察到部分mRNA半衰期延长。荧光素酶报告系统研究显示KSRP可在转录水平和转录后水平调节细胞因子基因的表达。本研究提示KSRP在促炎介质的调控方面发挥重要作用,因此在CNS炎性和自身免疫性疾病中有广泛意义。 | XUELIN LI WEI-JYE LIN CHING-YI CHEN YING SI XIAOWEN ZHANG LIANG LU ESTHER SUSWAM LEI ZHENG PETER H. KING | 2012 | 神经损伤与功能重建2012,7,6: | 1 |
| 16 | Shape-controlled synthesis o{ TiO2 hollow structures and their application in lithium batteries 显示文摘 | Wang Yong Su Xiaowen and Lu Shan | 2012 | Journal of Materials Chemistry2012,22,5: | 1 |
| 17 | Evolutionary relationship of three mitten crabs(Eriocheir sp)revealed by mitogenome and 5S ribosomal DNA analysis显示文摘To reveal the evolutionary relationship of three mitten crabs(Eriocheir sinensis,E.hepuensis,and E.japonica),complete mitogenomes and nuclear 5S rDNA sequences were analyzed.Sequencing revealed that the mitogenomes analyzed shared conserved organization of the coding and non-coding regions but genetic variation was identified.Among the three mitten crabs distinct tandem repeats were identified in the mitochondrial D-loop region.The 5S gene(5S rDNA)sequence was highly conserved across the three species,whereas non-transcribed spacer(NTS)region exhibit high levels of variation including insertions,deletions and point mutations.Cluster analysis suggested that the three mitten crabs had their own independent 5S rDNA sequence variation and evolutionary pattern.Both mitogenome and 5S rDNA sequence analysis revealed significant genetic variation across the mitten crabs species.Phylogenetic analysis using mitogenome and 5S rDNA sequences demonstrated that E.japonica was relatively more distant from E.sinensis and E.hepuensis.This study extended our previous knowledge and confirmed that the three mitten crabs are likely to be genetically differentiated species.In addition,our study also provided insights into the conservation of pure natural resources of E.sinensis,an important aquaculture species. | Xiaowen Chen Jun Wang Lei Huang Wucheng Yue Jixing Zou Chunhong Yuan Guoqing Lu Chenghui Wang | 2017 | Aquaculture and Fisheries2017,2,6: | 1 |
| 18 | Spatial, Temporal and Genetic Dynamics Characteristics of Influenza B Viruses in China, 1973–2018显示文摘Annual influenza B virus epidemics and outbreaks cause severe influenza diseases in humans and pose a threat to public health. China is an important epidemic area of influenza B viruses. However, the spatial, temporal transmission pathways and the demography history of influenza B viruses in China remain unknown. We collected the haemagglutinin gene sequences sampled of influenza B virus in China between 1973 and 2018. A Bayesian Markov chain Monte Carlo phylogeographic discrete approach was used to infer the spatial and temporal phylodynamics of influenza B virus. The Bayesian phylogeographic analysis of influenza B viruses showed that the North subtropical and South subtropical zones are the origins of the Victoria and Yamagata lineage viruses, respectively. Furthermore, the South temperate and North subtropical zones acted as transition nodes in the Victoria lineage virus dispersion network and that the North subtropical and Mid subtropical zones acted as transition nodes in the Yamagata lineage virus dispersion network. Our findings contribute to the knowledge regarding the spatial and temporal patterns of influenza B virus outbreaks in China. | Xiaowen Li Karen Kie Yan Chan Bo Xu Ming Lu Bing Xu | 2020 | Virologica Sinica2020,35,1: | 1 |
| 19 | Analysis of Clinicopathologic Features and Prognostic Factors in Hepatoid Adenocarcinoma of the Stomach显示文摘 | Xiaowen Liu Yufan Cheng Weiqi Sheng Hongfen Lu Xiaoli Xu Yu Xu Ziwen Long Huiyan Zhu Yanong Wang | 2010 | The American Journal of Surgical Pathology2010,,10: | 1 |
| 20 | Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice显示文摘We here report a genome-editing strategy to correct spinal muscular atrophy(SMA).Rather than directly targeting the pathogenic exonic mutations,our strategy employed Cas9 and guide-sg RNA for the targeted disruption of intronic splicing-regulatory elements.We disrupted intronic splicing silencers(ISSs,including ISS-N1 and ISS+100)of survival motor neuron(SMN)2,a key modifier gene of SMA,to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs.Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration.Furthermore,co-injection of Cas9 mRNA from Streptococcus pyogenes(SpCas9)or Cas9 from Staphylococcus aureus(SaCas9)alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56%and 100%of severe SMA transgenic mice(Smn-/-,SMN2tg/-).The median survival of the resulting mice was extended to>400 days.Collectively,our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. | Jin-Jing Li Xiang Lin Cheng Tang Ying-Qian Lu Xinde Hu Erwei Zuo He Li Wenqin Ying Yidi Sun Lu-Lu Lai Hai-Zhu Chen Xin-Xin Guo Qi-Jie Zhang Shuang Wu Changyang Zhou Xiaowen Shen Qifang Wang Min-Ting Lin Li-Xiang Ma Ning Wang Adrian R.Krainer Linyu Shi Hui Yang Wan-Jin Chen | 2020 | National Science Review2020,7,1: | 1 |