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| 1 | Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis显示文摘Complement is known to play a role in alcoholic fatty liver disease (AFLD), but the underlying mechanisms are poorly understood, thereby constraining the development of a rational approach for therapeutic intervention in the complement system. C3 deficiency has been shown to impart protective effects against ethanol-induced hepatic steatosis and inflammation. Here we demonstrate a protection effect in wild-type mice by treatment with CR2-Crry, a specific inhibitor of C3 activation. The expression of glycine transfer (t) RNA-derived fragments (Gly-tRFs) is upregulated in ethanol-fed mice and inhibition of Gly-tRFs in vivo decreases chronic ethanol feeding-induced hepatosteatosis without affecting inflammation. The expression of Gly-tRF was downregulated in C3-deficient or CR2-Crry-treated mice, but not in C5-deficient mice;Gly-tRF expression was restored by the C3 activation products C3a or Asp (C3a-des-Arg) via the regulation of CYP2E1. Transcriptome profiling of hepatic tissues showed that Gly-tRF inhibitors upregulate the expression of sirtuin1 (Sirt1) and subsequently affect downstream lipogenesis and β-oxidation pathways. Mechanistically, Gly-tRF interacts with AGO3 to downregulate Sirt1 expression via sequence complementarity in the 3′ UTR. Notably, the expression levels of C3d, CYP2E1 and Gly-tRF are upregulated, whereas Sirt1 is decreased in AFLD patients compared to healthy controls. Collectively, our findings suggest that C3 activation products contribute to hepatosteatosis by regulating the expression of Gly-tRF. Complement inhibition at the C3 activation step and treatment with Gly-tRF inhibitors may be potential and precise therapeutic approaches for AFLD. | Fudi Zhong Zhigao Hu Keqing Jiang Biao Lei Zhan Wu Guandou Yuan Hongliang Luo Chunqiang Dong Bo Tang Chaowen Zheng Shuai Yang Yonglian Zeng Zhenya Guo Shuiping Yu Huizhao Su Guo Zhang Xiaoqiang Qiu Stephen Tomlinson Songqing He | 2019 | Cell Research2019,29,7: | 14 |
| 2 | How Work Organization Affects the Prevalence of WMSDs: A Case-control Study显示文摘Objective In this study, we aimed at exploring the association between work-related musculoskeletal disorders(WMSDs) and work organization based on a case-control study. Methods A total of 1938 workers who claimed to suffer from WMSDs were selected from Beijing, Henan, Hubei, and the Guangdong province. The control group consisted of 2009 workers employed in similar industries without severe disease or musculoskeletal discomforts. We used a modified version of the questionnaire developed by the NMQ and the DMQ to investigate individual and work-related factors. Results A total of 13 variables(P<0.1) were selected by the chi-square test and finally, 7 variables entered into the equation, with 6 variables reaching statistical significance(P<0.05). The odds ratios(OR) of ‘work changing with season' and ‘sufficient rest time' did not reach 1(0.749 and 0.441, respectively). In addition, ‘sufficient rest time' seemed to be the stronger protective factor according to its higher standardized coefficient. And ‘repetitive work every minute', ‘constantly repetitive work'(every day), ‘shortage of site personnel', and ‘often switching shifts with others' seemed to be the risk factors. Conclusion Work organization may have comprehensive effects on the occurrence of WMSDs. This pattern of associations suggests that further investigation into the mechanism of how work organization affects the prevalence of WMSDs is required. | LIU Lu CHEN Song Gen TANG Shi Chuan WANG Sheng HE Li Hua GUO Ze Hua LI Jing Yun YU Shan Fa WANG Zhong Xu | 2015 | Biomedical and Environmental Sciences2015,28,9: | 11 |
| 3 | DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia显示文摘目的: DanHong 开注射(DHI ) 决定相对氨基酸内容和新陈代谢的小径怎么与变化在处理以后与服的局部缺血在老鼠调整药理学显型。 | Zhi-li GUO Yan ZHU Xiao-tao SU Jun LIU Qian-xu YANG Jing-yi NAN Bu-chang ZHAO Ying-ying ZHANG Ya-nan YU Bing LI Hong-bin XIAO Zhong WANG | 2015 | Acta Pharmacologica Sinica2015,36,6: | 10 |
| 4 | Bartonella Species Detected in the Plateau Pikas(Ochotona curzoiae) from Qinghai Plateau in China显示文摘Bartonella 种类能感染许多哺乳动物的主人并且在人引起许多疾病,但是在那里有不是在 Ochotonidae 的 Bartonella 感染的报告。这是第一研究在 Qinghai 高原在高原一种短耳野兔检测 Bartonella,提供为对在这个区域的人的 Bartonella 感染的风险评价的基线数据。我们与 18.99% 的积极的率在 Qinghai 的 Binggou 和 Maixiu 区域从 79 只一种短耳野兔获得了 15 Bartonella 紧张。基于基因定序的 Bartonella 柠檬酸盐 synthase (gltA ) 的种系发生的分析,大多数紧张是仔细与 B 有关。taylorii (3/15 ) 和 B。grahamii (12/15 ) 。后者是在人的病原的紧张。我们的结果建议相应预防和控制策略应该在 Qinghai 省被考虑。 | RAO Hua Xiang YU Juan GUO Peng MA Yong Cheng LIU Qi Yong JIAO Ming MA Zhong Wen GE Hua WANG Chun Xiang SONG Xiu Ping SHI Yan LI Dong Mei | 2015 | Biomedical and Environmental Sciences2015,28,9: | 8 |
| 5 | Syntheses and characterization of anti-thrombotic and anti-oxidative Gastrodin-modified polyurethane for vascular tissue engineering显示文摘Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels(<6 mm inner diameter).Here,polyurethane(PU)elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated.The films had inter-connected pores with porosities equal to or greater than 86%and pore sizes ranging from 250 to 400μm.Incorporation of Gastrodin into PU films resulted in desirable mechanical properties,hydrophilicity,swelling ratios and degradation rates without collapse.The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability.The Gastrodin/PU had better anti-coagulation response(less observable BSA,fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood).Red blood cell compatibility,measured by hemolysis,was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups.Notably,Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs,correlated with decreasing pro-inflammatory cytokines TNF-αand IL-1β in RAW 264.7 cells.Upon implantation in a subcutaneous pocket,PU was encapsulated by an obvious fibrous capsule,concurrent with a large amount of inflammatory cell infiltration,while Gastrodin/PU induced a thinner fibrous capsule,especially 2Gastrodin/PU.Further,enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment,as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo.These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration,thus providing new insight into the development of clinically effective vascular grafts. | Meng Zheng Jiazhi Guo Qing Li Jian Yang Yi Han Hongcai Yang Mali Yu Lianmei Zhong Di Lu Limei Li Lin Sun | 2021 | Bioactive Materials2021,6,2: | 7 |
| 6 | Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis显示文摘Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal medicine.However,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.Aims The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.MEDLINE,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were searched.The included outcomes were dependency,motor function,depression and swallowing function.Subgroup analysis was performed,and publication bias was assessed using funnel plots.Summary of review 58 studies and 6339 patients were included in the meta-analysis.Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone.Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.Conclusions Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone.However,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias.So,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined. | Linda LD Zhong Ya Zheng Alexander Y Lau Norman Wong Liang Yao Xingyao Wu Tengteng Shao Zhenxing Lu Huijuan Li Chun Sum Yuen Jianwen Guo Suzanne Lo Janita Chau Kam Wa Chan Bacon Fung Leung Ng Zhaoxiang Bian Edwin Chau-leung Yu | 2022 | Stroke & Vascular Neurology2022,7,1: | 7 |
| 7 | Pristimerin protects against inflammation and metabolic disorder in mice through inhibition of NLRP3 inflammasome activation显示文摘Excessive activation of NLRP3 inflammasome is associated with the pathogenesis of inflammatory diseases.Pristimerin(Pri)is a quinonoid triterpene derived from traditional Chinese medical herb Celastraceae and Hippocrateaceae.Pri has shown antifungal,antibacterial,antioxidant,and anticancer activities.In this study we investigated whether NLRP3 inflammasome was associated with the anti-inflammatory activity of Pri.We showed that Pri(0.1−0.4μM)dose-dependently blocked caspase-1 activation and IL-1βmaturation in LPS-primed mouse bone-marrow-derived macrophages(BMDMs).Pri specifically inhibited NLRP3 inflammasome activation,had no visible effects on NLRC4 and AIM2 inflammasome activation.Furthermore,we demonstrated that Pri blocked the assembly of the NLRP3 inflammasome via disturbing the interaction between NEK7 and NLRP3;theα,β-unsaturated carbonyl moiety of Pri was essential for NLRP3 inflammasome inactivation.In LPS-induced systemic inflammation mouse model and MSU-induced mouse peritonitis model,preinjection of Pri(500μg/kg,ip)produced remarkable therapeutic effects via inhibition of NLRP3 inflammasome in vivo.In HFD-induced diabetic mouse model,administration of Pri(100μg·kg^(−1)·d^(−1),ip,for 6 weeks)reversed HFD-induced metabolic disorders via suppression of NLRP3 inflammasome activation.Taken together,our results demonstrate that Pri acts as a NLRP3 inhibitor,suggesting that Pri might be useful for the treatment of NLRP3-associated diseases. | Qun Zhao Yun Bi Jian Guo Ying-xiang Liu Jing Zhong Long-rui Pan Yan Tan Xian-jun Yu | 2021 | Acta Pharmacologica Sinica2021,42,6: | 6 |
| 8 | Adaptive optics based on machine learning: a review显示文摘Adaptive optics techniques have been developed over the past half century and routinely used in large ground-based telescopes for more than 30 years.Although this technique has already been used in various applications,the basic setup and methods have not changed over the past 40 years.In recent years,with the rapid development of artificial in-telligence,adaptive optics will be boosted dramatically.In this paper,the recent advances on almost all aspects of adapt-ive optics based on machine learning are summarized.The state-of-the-art performance of intelligent adaptive optics are reviewed.The potential advantages and deficiencies of intelligent adaptive optics are also discussed. | Youming Guo Libo Zhong Lei Min Jiaying Wang Yu Wu Kele Chen Kai Wei Changhui Rao | 2022 | Opto-Electronic Advances2022,5,7: | 6 |
| 9 | Role of corticotrophin releasing hormone in cerebral infarction-related gastrointestinal barrier dysfunction显示文摘 | Ye-cheng Liu Zhi-wei Qi Shi-gong Guo Zhong Wang Xuc-zhong Yu Sui Ma | 2011 | World Journal of Emergency Medicine2011,2,1: | 6 |
| 10 | Selective extraction and separation of Fe,Mn oxides and organic materials in river surficial sediments显示文摘In order to investigate the adsorption mechanism of trace metals to surficial sediments (SSs), a selective extraction procedure was improved in the present work. The selective extraction procedure has been proved to selectively remove and separate Fe, Mn oxides and organic materials (OMs) in the non-residual fraction from the SSs collected in Songhua River, China. After screening different kinds of conventional extractants of Fe and Mn oxides and OMs used for separation of heavy metals in the soils and sediments, NH2OH·HCl (0.1 mol/L) + HNO3 (0.1 mol/L), (NH4)2C2O4 (0.2 mol/L) + H2C2O4 (pH 3.0), and 30% of H2O2 were respectively applied to selectively extract Mn oxides, Fe/Mn oxides and OMs. After the extraction treatments, the target components were removed with extraction efficiencies between 86.09%—93.36% for the hydroxylamine hydrochloride treatment, 80.63%—101.09% for the oxalate solution extraction, and 94.76%—102.83% for the hydrogen peroxide digestion, respectively. The results indicate that this selective extraction technology was effective for the extraction and separation of Fe, Mn oxides and OMs in the SSs, and important for further mechanism study of trace metal adsorption onto SSs. | LI Feng-mei WANG Xiao-li LI Yu GUO Shu-hai ZHONG Ai-ping | 2006 | Journal of Environmental Sciences2006,18,6: | 6 |
| 11 | Alterations of brain local functional connectivity in amnestic mild cognitive impairment显示文摘Background:Resting-state functional magnetic resonance imaging studies using a regional homogeneity(ReHo)method have reported that amnestic mild cognitive impairment(aMCI)was associated with abnormalities in local functional connectivity.However,their results were not conclusive.Methods:Seed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI.Results:We identified 10 studies with 11 datasets suitable for inclusion,including 378 patients with aMCI and 435 healthy controls.This meta-analysis identified significant ReHo alterations in patients with aMCI relative to healthy controls,mainly within the default mode network(DMN)(bilateral posterior cingulate cortex[PCC],right angular gyrus,bilateral middle temporal gyri,and left parahippocampal gyrus/hippocampus),executive control network(right superior parietal lobule and dorsolateral prefrontal cortex),visual network(right lingual gyrus and left middle occipital gyrus),and sensorimotor network(right paracentral lobule/supplementary motor area,right postcentral gyrus and left posterior insula).Significant heterogeneity of ReHo alterations in the bilateral PCC,left parahippocampal gyrus/hippocampus,and right superior parietal lobule/angular gyrus was observed.Exploratory meta-regression analyses indicated that general cognitive function,gender distribution,age,and education level partially contributed to this heterogeneity.Conclusions:This study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN,executive control network,visual network,and sensorimotor network.These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks.These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI.Confounding factors merit much attention and warrant future investigations. | Dan Zheng Wei Xia Zhong Quan Yi Pan Wen Zhao Jian Guo Zhong Hai Cun Shi Hua Liang Li Zhen Yu Dai Ping Lei Pan | 2018 | Translational Neurodegeneration2018,7,1: | 5 |
| 12 | Nosocomial Infection Surveillance in a Tuberculosis Specialized Hospital in China显示文摘Nosocomial infections(NIs) are a critical issue affecting the quality of healthcare. In this study, we performed a retrospective study to explore the incidence rates, mortality rates, and microbial spectrum of NIs in Beijing Chest Hospital, a tuberculosis(TB) specialized hospital in China. Our data demonstrate that the overall incidence rate of inpatients with NIs slightly decreased from 2012 to 2016, which may be associated with the implementation of hand hygiene measures, while the mortality rates associated with NI did not significantly change. In addition, the species distribution of NIs was quite different from that presented in previous reports, and Klebsiella pneumoniae was the most frequently isolated microorganism. | XIE Zhong Yao HUANG Guo Fang GAO Hui CHI Yu Qing WANG Yan Xia PANG Yu WANG Jing Ping | 2017 | Biomedical and Environmental Sciences2017,30,9: | 5 |
| 13 | MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer显示文摘 | Hongxia Deng Yanan Guo Haojun Song Bingxiu Xiao Weiliang Sun Zhong Liu Xiuchong Yu Tian Xia Long Cui Junming Guo | 2013 | Gene2013,,: | 5 |
| 14 | Outgassing analysis of molecular glass photoresists under EUV irradiation显示文摘A device was designed and assembled to analyze the outgassing of molecular glass(MG)photoresists under extreme ultraviolet(EUV)exposure.The outgassing of the photoresists with different components and different concentrations of tert-butoxycarbonyl(t-Boc),photo-generated acid(PAG),and acid quencher was systematically investigated.Based on experiments,some solutions for reducing the outgassing of MG photoresists were proposed. | CHEN Li XU Jian YUAN Hua YANG Shu Min WANG Lian Sheng WU Yan Qing ZHAO Jun CHEN Ming LIU Hai Gang LI Sha Yu TAI Ren Zhong WANG Shuang Qing YANG Guo Qiang | 2014 | Science China Chemistry2014,57,12: | 4 |
| 15 | Evaluation and treatment of altered mental status patients in the emergency department:Life in the fast lane显示文摘BACKGROUND:Altered mental status(AMS) is a very common emergency case,but the exact etiology of many AMS patients is unknown.Patients often manifest vague symptoms,thus,AMS diagnosis and treatment are highly challenging for emergency physicians.The aim of this study is to provide a framework for the assessment of AMS patients.This assessment should allow providers to better understand the etiology of mental status changes and therefore improve diagnostic skills and management.METHODS:This is a prospective cohort observational study.We recruited all adult patients with undifferentiated AMS at a single center tertiary care academic emergency department over 24months(June 2009 to June 2011).Demographic characteristics,clinical manifestations,assessment approaches,causative factors,emergency treatments and outcomes were collected prospectively.RESULTS:In 1934 patients with AMS recruited,accounting for 0.93%of all emergency department(ED) patients,1 026(53.1%) were male,and 908(46.9%) female.Their average age was 51.95±15.71 years.Etiologic factors were neurological(n=641;35.0%),pharmacological and toxicological(n=421;23.0%),systemic and organic(n=266;14.5%),infectious(n=167;9.1%),endocrine/metabolic(n=145;7.9%),psychiatric(n=71;3.9%),traumatic(n=38;2.1%),and gynecologic and obstetric(n=35;1.9%).Total mortality rate was 8.1%(n=156).The death rate was higher in elderly patients(≥60) than in younger patients(10.8%vs.6.9%,P=0.003).CONCLUSIONS:Patients with AMS pose a challenge for ED physicians.The most frequently encountered diagnostic categories causing AMS were primary CNS disorders,intoxication,organ system dysfunction,and endocrine/metabolic diseases.AMS has a high fatality rate in the ED.AMS is an important warning signal for ED patients because of its potentially fatal and reversible effects.Prompt evaluation and treatment are essential to decreasing morbidity and mortality associated with AMS. | Hai-yu Xiao Yu-xuan Wang Teng-da Xu Hua-dong Zhu Shu-bin Guo Zhong Wang Xue-zhong Yu | 2012 | World Journal of Emergency Medicine2012,3,4: | 4 |
| 16 | Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications显示文摘 | Xing Liu Fen-Fen Yu Yi-Min Zhong Xin-Xing Guo Zhen Mao | 2015 | Chinese Medical Journal2015,,18: | 4 |
| 17 | Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies显示文摘Neutralizing monoclonal antibodies(nAbs)to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represent promising candidates for clinical intervention against coronavirus disease 2019(COVID-19).We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain(RBD)of the viral spike(S)protein and the receptor angiotensin converting enzyme 2(ACE2).However,the structural basis for their potent neutralizing activity remains unclear.Here,we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2.The bivalent binding of the full-length IgG is found to associate with more RBDs in the“up”conformation than the monovalent binding of Fab,perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein.Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities.This work provides a structural basis for further understanding the mechanism of nAbs,especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit. | Renhong Yan Ruoke Wang Bin Ju Jinfang Yu Yuanyuan Zhang Nan Liu Jia Wang Qi Zhang Peng Chen Bing Zhou Yaning Li Yaping Shen Shuyuan Zhang Long Tian Yingying Guo Lu Xia Xinyue Zhong Lin Cheng Xiangyang Ge Juanjuan Zhao Hong-Wei Wang Xinquan Wang Zheng Zhang Linqi Zhang Qiang Zhou | 2021 | Cell Research2021,31,5: | 4 |
| 18 | A titanium dioxide nanorod array as a high-affinity nano-bio interface of a microfluidic device for efficient capture of circulating tumor cells显示文摘处理临床的问题的 Nanomaterials 表演答应机会(例如传播肿瘤房间的不够的俘获;CTC ) 经由为生物房间的高表面 area-to-volume 比率和高亲密关系。然而,怎么与高特性遗体为有效 CTC 俘获在一台 microfluidic 设备作为一个 nano 简历接口使用这些 nanomaterials 挑战。在现在的工作,我们首先发现那钛二氧化物(能方便地在底层的多重类型上被准备的 TiO 2) nanorod 数组为肿瘤房间有高亲密关系。然后, TiO 2 nanorod 数组在有经由热水的反应的六角形地有图案的 Si micropillars 的 microchannel 的表面上是垂直地成年的,层次地形成 micro-nano 3D 的一种新类型结构化的 microfluidic 设备。当这 3D 的一个敏感 nano 简历接口层次地组织了 microfluidic 设备,垂直地成年的 TiO 2 nanorod 数组被使用,哪个显示出 CTC 俘获的高效率(76.7% 潩獮 ? 畯 ? 牰灯獯摥栠杩 ? 数晲牯慭据 ? 潍 ? ??? 猯'T  ̄楢獯湥潳獲挠湡搠瑥捥 ?? 卐? 潣据湥牴瑡潩吗?? | Jichuan Qiu Kun Zhao Linlin Li Xin Yu Weibo Guo Shu Wang Xiaodi Zhang Caofeng Pan Zhong Lin Wang Hong Liu | 2017 | Nano Research2017,10,3: | 3 |
| 19 | Genomic landscapes of Chinese sporadic autism spectrum disordersrevealed by whole-genome sequencing显示文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment. | Jinyu Wu Ping Yu Xin Jin Xiu Xu Jinchen Li Zhongshan Li Mingbang Wang Tao Wang Xueli Wu Yi Jiang Wanshi Cai Junpu Mei Qingjie Min Qiong Xu Bingrui Zhou Hui Guo Ping Wang Wenhao Zhou Zhengmao Hu Yingrui Li Tao Cai Yi Wang Kun Xia Yong-Hui Jiang Zhong Sheng Sun | 2018 | Journal of Genetics and Genomics2018,45,10: | 3 |
| 20 | Structural basis of ALMT1-mediated aluminum resistance in Arabidopsis显示文摘The plant aluminum(Al)-activated malate transporter ALMT1 mediates the efflux of malate to chelate the Al in acidic soils and underlies the plant Al resistance.Here we present cryo-electron microscopy(cryo-EM)structures of Arabidopsis thaliana ALMT1(AtALMT1)in the apo,malate-bound,and Al-bound states at neutral and/or acidic pH at up to 3.0Åresolution.The AtALMT1 dimer assembles an anion channel and each subunit contains six transmembrane helices(TMs)and six cytosolicα-helices.Two pairs of Arg residues are located in the center of the channel pore and contribute to malate recognition.Al binds at the extracellular side of AtALMT1 and induces conformational changes of the TM1-2 loop and the TM5-6 loop,resulting in the opening of the extracellular gate.These structures,along with electrophysiological measurements,molecular dynamic simulations,and mutagenesis study in Arabidopsis,elucidate the structural basis for Al-activated malate transport by ALMT1. | Jiangqin Wang Xiafei Yu Zhong Jie Ding Xiaokang Zhang Yanping Luo Ximing Xu Yuan Xie Xiaoxiao Li Tian Yuan Shao Jian Zheng Wei Yang Jiangtao Guo | 2022 | Cell Research2022,32,1: | 3 |