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38篇 您的检索式:作者名="Ting Xi Liu"
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1Precise nanomedicine for intelligent therapy of cancer显示文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.Huabing Chen Zhanjun Gu Hongwei An Chunying Chen Jie Chen Ran Cui Siqin Chen Weihai Chen Xuesi Chen Xiaoyuan Chen Zhuo Chen Baoquan Ding Qian Dong Qin Fan Ting Fu Dayong Hou Qiao Jiang Hengte Ke Xiqun Jiang Gang Liu Suping Li Tianyu Li Zhuang Liu Guangjun Nie Muhammad Ovais Daiwen Pang Nasha Qiu Youqing Shen Huayu Tian Chao Wang Hao Wang Ziqi Wang Huaping Xu Jiang-Fei Xu Xiangliang Yang Shuang Zhu Xianchuang Zheng Xianzheng Zhang Yanbing Zhao Weihong Tan Xi Zhang Yuliang Zhao 2018Science China Chemistry2018,61,12:19
2Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma显示文摘Esophageal squamous cell carcinoma(ESCC)is a poor-prognosis cancer type with limited understanding of its molecular etiology.Using 508 ESCC genomes,we identified five novel significantly mutated genes and uncovered mutational signature clusters associated with metastasis and patients’outcomes.Several functional assays implicated that NFE2L2 may act as a tumor suppressor in ESCC and that mutations in NFE2L2 probably impaired its tumor-suppressive function,or even conferred oncogenic activities.Additionally,we found that the NFE2L2 mutations were significantly associated with worse prognosis of ESCC.We also identified potential noncoding driver mutations including hotspot mutations in the promoter region of SLC35E2 that were correlated with worse survival.Approximately 5.9%and 15.2%of patients had high tumor mutation burden or actionable mutations,respectively,and may benefit from immunotherapy or targeted therapies.We found clinically relevant coding and noncoding genomic alterations and revealed three major subtypes that robustly predicted patients’outcomes.Collectively,we report the largest dataset of genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment.Yongping Cui Hongyan Chen Ruibin Xi Heyang Cui Yahui Zhao Enwei Xu Ting Yan Xiaomei Lu Furong Huang Pengzhou Kong Yang Li Xiaolin Zhu Jiawei Wang Wenjie Zhu Jie Wang Yanchun Ma Yong Zhou Shiping Guo Ling Zhang Yiqian Liu Bin Wang Yanfeng Xi Ruifang Sun Xiao Yu Yuanfang Zhai Fang Wang Jian Yang Bin Yang Caixia Cheng Jing Liu Bin Song Hongyi Li Yi Wang Yingchun Zhang Xiaolong Cheng Qimin Zhan Yanhong Li Zhihua Liu-Show 2020Cell Research2020,30,10:19
3Plasma metabolomic and lipidomic alterations associated with COVID-19显示文摘The pandemic of the coronavirus disease 2019(COVID-19)has become a global public health crisis.The symptoms of COVID-19 range from mild to severe,but the physiological changes associated with COVID-19 are barely understood.In this study,we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms.We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients,indicating that the development of COVID-19 affected their whole-body metabolism.In particular,malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction,respectively.It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms.And,more importantly,guanosine monophosphate(GMP),which is mediated not only by GMP synthase but also by CD39 and CD73,is significantly changed between healthy subjects and patients with COVID-19,as well as between the mild and fatal cases.In addition,dyslipidemia was observed in patients with COVID-19.Overall,the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19.This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets,as well as an important resource for further studies of the pathogenesis of COVID-19.Di Wu Ting Shu Xiaobo Yang Jian-Xin Song Mingliang Zhang Chengye Yao Wen Liu Muhan Huang Yuan Yu Qingyu Yang Tingju Zhu Jiqian Xu Jingfang Mu Yaxin Wang Hong Wang Tang Tang Yujie Ren Yongran Wu Shu-Hai Lin Yang Qiu Ding-Yu Zhang You Shang Xi Zhou 2020National Science Review2020,7,7:9
4WGDI:A user-friendly toolkit for evolutionary analyses of whole-genome duplications and ancestral karyotypes显示文摘Evidence of whole-genome duplications(WGDs)and subsequent karyotype changes has been detected in most major lineages of living organisms on Earth.To clarify the complex resulting multi-layered patterns of gene collinearity in genome analyses,there is a need for convenient and accurate toolkits.To meet this need,we developed WGDI(Whole-Genome Duplication Integrated analysis),a Python-based command-line tool that facilitates comprehensive analysis of recursive polyploidization events and cross-species genome alignments.WGDI supports three main workflows(polyploid inference,hierarchical inference of genomic homology,and ancestral chromosome karyotyping)that can improve the detection of WGD and characterization of WGD-related events based on high-quality chromosome-level genomes.Significantly,it can extract complete synteny blocks and facilitate reconstruction of detailed karyotype evolution.This toolkit is freely available at GitHub(https://github.com/SunPengChuan/wgdi).As an example of its application,WGDI convincingly clarified karyotype evolution in Aquilegia coerulea and Vitis vinifera following WGDs and rejected the hypothesis that Aquilegia contributed as a parental lineage to the allopolyploid origin of core dicots.Pengchuan Sun Beibei Jiao Yongzhi Yang Lanxing Shan Ting Li Xiaonan Li Zhenxiang Xi Xiyin Wang Jianquan Liu 2022Molecular Plant2022,15,12:5
5Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders显示文摘Dear Editor,Autism spectrum disorders(ASD)are complex neurodevelopmental disorders characteristic of core behavioral traits like restricted,repetitive behaviors and deficiency in social interactions.1 The prevalence of ASD has rapidly increased worldwide,rising from 1/149 in 2000,1/68 in 2012,and to?1/40 in 2016 of children at the age of 3-17 in the United States.2 ASD prevalence was found to be associated with socioeconomic status(SES)as overpresented in high-income households,3 and to be significantly enriched in certain regions,e.g.,reaching up to 4.88%in Florida.2 In the last decades,advances in genetic studies have led to unprecedented understanding of the genetic factors that were associated with<50%of human ASD.Zijian Hao Qionghui Wu Zhengwei Li Yali Li Qiu Li Xi Lai Huan Liu Menghuan Zhang Ting Yang Jie Chen Yaping Tang Jingkun Miao Huatai Xu Tingyu Li Ronggui Hu 2019Cell Research2019,29,10:5
6Small ubiquitin-related modifier paralogs are indispensable but functionally redundant during early development of zebrafish显示文摘到许多蛋白质的小 ubiquitin 相关的修饰词(相扑) 变化形式调整多样的细胞的过程,包括抄写,房间周期规定和染色体正直的维护。在 vivo 调查相扑 paralogs 的生物功能,我们在 zebrafish 的早开发使他们失去活性。当作为 Ubc9 缺乏的,为所有三相扑 paralogs 缺乏的 zebrafish 胚胎显示了严重缺点时,单个相扑 paralog 的损失与正常开发兼容。相扑缺乏的胚胎能被一个单个人或 zebrafish 相扑救。当关键时结构的基本离氨酸残余和 N 终端相扑的未组织的段是批评的为在 vivo 营救, SUMO2 的一致 K11 sumoylation 地点是非必需的,在这个潜在的地点上暗示那链形成为正常开发是非本质的。所有三相扑的 Inactivation 触发了 p53 依赖的 apoptosis, p53 的进一步的 inactivation 恢复了正常 zebrafish 开发。有趣地,我们也证明 p53 的主导的否定截断的形式,螖 1 13p53,显著地弄钝相扑在 vivo 的导致弄空的 p53 活动。一起拿,我们的结果建议相扑 paralogs 不可缺少,却冗余,在 zebrafish 的早发展。Hao Yuan Jun Zhou Min Deng Xi Liu Morgane Le Bras Hugues de The Sai Juan Chen Zhu Chen Ting Xi Liu Jun Zhu 2010Cell Research2010,20,2:4
7Chinese expert consensus on the management of chimeric antigen receptor T cell therapy-associated coagulopathy显示文摘Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted.Attention should be paid to the safety of CAR-T therapy.The main adverse effects of CAR-T therapy are cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS).[4]Heng Mei Fangping Chen Yue Han Ming Hou He Huang Xiaojun Huang Yuhua Li Aibin Liang Qifa Liu Ting Niu Jun Peng Wenbin Qian Yongping Song Jianxiang Wang Ying Wang Depei Wu Kailin Xu Linhua Yang Renchi Yang Lei Zhang Liansheng Zhang Xi Zhang Xiaohui Zhang Weili Zhao Weidong Han Yu Hu 2022Chinese Medical Journal2022,,14:4
82022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma显示文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.Ping Li Yang Liu Yun Liang Jian Bo Sujun Gao Yongxian Hu Yu Hu He Huang Xiaojun Huang Hongmei Jing Xiaoyan Ke Jianyong Li Yuhua Li Qifa Liu Peihua Lu Heng Mei Ting Niu Yongping Song Yuqin Song Liping Su Sanfang Tu Jianxiang Wang Depei Wu Zhao Wang Kailin Xu Zhitao Ying Qingming Yang Yajing Zhang Fengxia Shi Bin Zhang Huilai Zhang Xi Zhang Mingfeng Zhao Weili Zhao Xiangyu Zhao Liang Huang Jun Zhu Wenbin Qian Weidong Han Aibin Liang 2023Cancer Biology & Medicine2023,20,2:3
9Short-lived AIM2 Inflammasome Activation Relates to Chronic MCMV Infection in BALB/c Mice显示文摘Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(MCMV)infection in BALB/c and C57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV.BALB/c and C57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.Contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of MCMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of MCMV infection.Yuan-yuan LU Xing-lou LIU Yuan HUANG Yi LIAO Ting XI Ya-nan ZHANG Lin-lin ZHANG Sai-nan SHU Feng FANG 2019Current Medical Science2019,39,6:3
10A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis显示文摘Rui Liu Chunni Zhang Zhibin Hu Gou Li Cheng Wang Cuihua Yang Dingzhi Huang Xi Chen Haiyang Zhang Rui Zhuang Ting Deng Hua Liu Jingjing Yin Sufen Wang Ke Zen Yi Ba Chen-Yu Zhang 2010European Journal of Cancer2010,,5:3
11CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression显示文摘Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders.Trefoil factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood.Here,we found that the upregulated TFF3 in CRC predicted a worse overall survival rate.TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis.CD147,a membrane protein,was identified as a binding partner for TFF3.Via binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and invasion.PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC progression.Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression.The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor.Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice.Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.Hong-Yong Cui Shi-Jie Wang Fei Song Xu Cheng Gang Nan Yu Zhao Mei-Rui Qian Xi Chen Jia-Yue Li Fen-Ling Liu Yu-Meng Zhu Ruo-Fei Tian Bin Wang Bin Wu Yang Zhang Xiu-Xuan Sun Ting Guo Xiang-Min Yang Hai Zhang Ling Li Jing Xu Hui-Jie Bian Jian-Li Jiang Zhi-Nan Chen 2021Signal Transduction and Targeted Therapy2021,6,8:3
12Association between PTCH1 gene polymorphisms and chronic obstructive pulmonary disease susceptibility in a Chinese Han population:a case-control study显示文摘Background:Chronic obstructive pulmonary disease(COPD)is a leading cause of morbidity and mortality worldwide.Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1,a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function.The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.Methods:We performed a case-control study including 296 patients with COPD and 300 healthy individuals.Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants.Odds ratios(ORs)and 95%confidence intervals(95%CIs)were estimated using logistic regression analysis after adjustment for age,gender,and smoking.Results:In total,28 single-nucleotide polymorphisms were identified in patients with COPD.Among them,'A'allele of rs28491365(OR:1.388,95%CI:1.055-1.827,P=0.018),and'G'alleles of rs10512248(OR:1.299,95%CI:1.021-1.653,P=0.033)and rs28705285(OR:1.359,95%CI:1.024-1.803,P=0.033;respectively)were significantly associated with an increased COPD risk.Genetic model analysis revealed that the'T/T'genotype of rs34695652 was associated with a decreased COPD risk under the recessive model(OR:0.490,95%CI:0.270-0.880,P=0.010),whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age,gender,and smoking status(OR:6.364,95%CI:1.220-33.292,P=0.028).Conclusions:The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.Xi Kang Ting Guo Lyu Liu Shui-Zi Ding Cheng Lei Hong Luo 2020Chinese Medical Journal2020,,17:3
13Association of assisted reproductive technology, germline de novo mutations and congenital heart defects in a prospective birth cohort study显示文摘Emerging evidence suggests that children conceived through assisted reproductive technology(ART)have a higher risk of congenital heart defects(CHDs)even when there is no family history.De novo mutation(DNM)is a well-known cause of sporadic congenital diseases;however,whether ART procedures increase the number of germline DNM(gDNM)has not yet been well studied.Here,we performed whole-genome sequencing of 1137 individuals from 160 families conceived through ART and 205 families conceived spontaneously.Children conceived via ART carried 4.59 more gDNMs than children conceived spontaneously,including 332 paternal and 1.26 maternal DNMs,after correcting for parental age at conception,cigarette smoking,alcohol drinking,and exercise behaviors.Paternal DNMs in offspring conceived via ART are characterized by C>T substitutions at CpG sites,which potentially affect protein-coding genes and are significantly associated with the increased risk of CHD.In addition,the accumulation of non-coding functional mutations was independently associated with CHD and 87.9% of the mutations were originated from the father.Among ART offspring,infertility of the father was associated with elevated paternal DNMs;usage of both recombinant and urinary follicle-stimulating hormone and high-dosage human chorionic gonadotropin trigger was associated with an increase of maternal DNMs.In sum,the increased gDNMs in offspring conceived by ART were primarily originated from fathers,indicating that ART itself may not be a major reason for the accumulation of gDNMs.Our findings emphasize the importance of evaluating the germline status of the fathers in families with the use of ART.Cheng Wang Hong Lv Xiufeng Ling Hong Li Feiyang Diao Juncheng Dai Jiangbo Du Ting Chen Qi Xi Yang Zhao Kun Zhou Bo Xu Xiumei Han Xiaoyu Liu Meijuan Peng Congcong Chen Shiyao Tao Lei Huang Cong Liu Mingyang Wen Yangqian Jiang Tao Jiang Chuncheng Lu Wei Wu Di Wu Minjian Chen Yuan Lin Xuejiang Guo Ran Huo Jiayin Liu Hongxia Ma Guangfu Jin Yankai Xia Jiahao Sha Hongbing Shen Zhibin Hu 2021Cell Research2021,31,8:2
14Maternal Murine Cytomegalovirus Infection during Pregnancy Up-regulates the Gene Expression of Toll-like Receptor 2 and 4 in Placenta显示文摘Yi LIAO Ya-nan ZHANG Xing-lou LIU Yuan-yuan LU Lin-lin ZHANG Ting XI Sai-nan SHU Feng FANG 2018Current Medical Science2018,38,4:2
152021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy显示文摘Immune thrombocytopenia(ITP)is an acquired disease characterized by isolated thrombocytopenia,which is one of the most common causes of thrombocytopenia during pregnancy.Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications.Therefore,we established this consensus statement on the diagnosis and management of ITP during pregnancy(detailed information is available in the Supplementary File,http://links.lww.com7CM9/A978).Zhang Xiaohui Chen Fangping Chen Xiequn Cheng Yunfeng Fang Meiyun Feng Jianming Fu Haixia Gao Hong Han Yue He Aili Hou Ming Hu Yu Huang Ruibin Huang Wenrong Jing Zhicheng Kong Peiyan Liang Aibin Liang Meiying Liu Daihong Liu Junling Liu Lin Liu Xiaowei Ma Liangming Mei Heng Ni Heyu Niu Ting Peng Jun Qiao Jianlin Ren Jinhai Song Yongping Tang Liang V Tong Tong Wang Shaoyuan Wang Xin Wang Zhao Wei Hui Wu Depei Wu Guangsheng Xu Caigang Xu Xue Xu Yajing Yang Linhua Yang Renchi Yang Tonghua Yin Chenghong Yu Li Zhang Guangsen Zhang Lei Zhang Liansheng Zhang Xi Zhao Weili Zhao Yongqiang Zhou Daobin Zhou Hu Zhou Zeping Zhu Tienan Wang Jianliu Huang Xiaojun 2022Chinese Medical Journal2022,,8:2
16Electrochemical sensor based on a poly (para-aminobenzoic acid) film modified glassy carbon electrode for the determination of melamine in milk显示文摘Ya Ting Liu Jian Deng Xi Lin Xiao 2011Electrochimica Acta2011,,56:1
17A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis显示文摘Rui Liu Chunni Zhang Zhibin Hu Gou Li Cheng Wang Cuihua Yang Dingzhi Huang Xi Chen Haiyang Zhang Rui Zhuang Ting Deng Hua Liu Jingjing Yin Sufen Wang Ke Zen Yi Ba Chen-Yu Zhang 2010European Journal of Cancer2010,,5:1
18Autophagy suppresses tumorigenesis of hepatitis B virus‐associated hepatocellular carcinoma through degradation of microRNA‐224显示文摘Sheng‐Hui Lan Shan‐Ying Wu Roberto Zuchini Xi‐Zhang Lin Ih‐Jen Su Ting‐Fen Tsai Yen‐Ju Lin Cheng‐Tao Wu Hsiao‐Sheng Liu 2014Hepatology2014,,2:1
19Peak radial and circumferential strain measured by velocity vector imaging is a novel index for detecting vulnerable plaques in a rabbit model of atherosclerosis显示文摘Lei Zhang Yan Liu Peng Fei Zhang Yu Xia Zhao Xiao Ping Ji Xiao Ting Lu Wen Qiang Chen Chun Xi Liu Cheng Zhang Yun Zhang 2010Atherosclerosis2010,,1:1
20DOCK2 regulates antifungal immunity by regulating RAC GTPase activity显示文摘Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.Xiaojian Ma Xi Tan Bingbing Yu Wanwei Sun Heping Wang Huijun Hu Yanyun Du Ruirui He Ru Gao Qianwen Peng Zhihui Cui Ting Pan Xiong Feng Junhan Wang Chengqi Xu Bin Zhu Wei Liu Chenhui Wang 2022Cellular & Molecular Immunology2022,19,5:1
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