检索结果-南通市图书馆

Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment

在线全文

学校读者我要写书评

暂无评论

Cellular & Molecular Immunology 2024年第1期21卷 47-59页

作者： Yu Zheng Haihui Jiang Naixue Yang Shaoping Shen Daosheng Huang Lemei Jia Jing Ling Longchen Xu Mingxiao Li Kefu Yu Xiaohui Ren Yong Cui xun Lan Song Lin Xin Lin Institute for Immunology and School of Medicine Tsinghua UniversityBeijing100084China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityChina.National Clinical Research Center for Neurological DiseasesCenter of Brain TumorBeijing Institute for Brain Disorders and Beijing Key Laboratory of Brain TumorBeijing100070China Department of Neurosurgery Peking University Third HospitalPeking UniversityBeijing100191China Tsinghua-Peking Center for Life Sciences Beijing100084China

A highly immunosuppressive tumor microenvironment(TME)and the presence of the blood‒brain barrier are the two major obstacles to eliciting an effective immune response in patients with high-grade glioma(HGG).Here,we tried to enhance the local innate immune response in relapsed HGG by intracranially injecting poly(I:C)to establish a robust antitumor immune response in this registered clinical trial(NCT03392545).During the follow-up,12/27(44.4%)patients who achieved tumor control concomitant with survival benefit were regarded as responders in our study.We found that the T-cell receptor(TCR)repertoire in the TME was reshaped after poly(I:C)treatment.Based on the RNA-seq analysis of tumor samples,the expression of annexin A1(ANXA1)was significantly upregulated in the tumor cells of nonresponders,which was further validated at the protein level.In vitro and in vivo experiments showed that ANXA1 could induce the production of M2-like macrophages and microglia via its surface receptor formyl peptide receptor 1(FPR1)to establish a Treg cell-driven immunosuppressive TME and suppress the antitumor immune response facilitated by poly(I:C).The ANXA1/FPR1 signaling axis can inhibit the innate immune response of glioma patients by promoting an anti-inflammatory and Treg-driven TME.Moreover,ANXA1 could serve as a reliable predictor of response to poly(I:C),with a notable predictive accuracy rate of 92.3%.In light of these notable findings,this study unveils a new perspective of immunotherapy for gliomas.

关键词： glioma ANXA1 TLR3 poly(I:C) immunotherapy

G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang Ting Chen xun Lu Xiaobing lan Ziqiang Chen Shaoyong Lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Stem Cells 2024年第2期16卷 114-125页

作者： Hong-Yan Long Zu-Ping Qian Qin lan Yong-Jie Xu Jing-Jing Da Fu-xun Yu Yan Zha Graduate School Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Laboratory Medicine Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Department of Nephrology Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Key Laboratory of Diagnosis and Treatment of Pulmonary Immune Diseases National Health CommissionGuizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

关键词： Kidney Organoids Human pluripotent stem cell Development Vascular system Disease modeling

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang lan Yang Yangsen Ou Rui Hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie Yu Zhang Chunting He Cheng Ma Tao Gong Ling Zhang Zhirong Zhang xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

Genome-wide evolution analysis reveals low CpG contents of fast-evolving genes and identifies antiviral microRNAs

在线全文

学校读者我要写书评

暂无评论

Journal of Genetics and Genomics 2020年第1期47卷 49-60页

作者： Wenhong Zu Hang Zhang xun Lan Xu Tan MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology School of Pharmaceutical SciencesTsinghua UniversityBeijing100084China Beijing Advanced Innovation Center for Structural Biology.Beijing Frontier Research Center for Biological Structures Tsinghua UniversityBeijing100084China Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing100084China Center for Infectious Disease Research Tsinghua UniversityBeijing100084China Tsinghua-Peking Center for Life Sciences Beijing100084China

Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes;thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.

关键词： Host-virus interaction Positive selection CpG dinucleotide Noncoding RNA MicroRNA

基于SMOTE和Inception-CNN的种植和组培金线莲鉴别

在线全文

学校读者我要写书评

暂无评论

光谱学与光谱分析 2024年第1期44卷 158-163页

作者：蓝艳王武许文柴琴琴李玉榕张勋福州大学电气工程与自动化学院福建福州350108 福建中医药大学药学院福建福州350122

金线莲是一种珍贵中药材,其治疗、保健作用十分显著。金线莲培育方式主要有种植、组培等,不同培育方式的金线莲,在性状上仅表现出细微差异,但药用、市场价值差异显著,培育方式鉴别能有效保证药用疗效、维护良好市场秩序,然而由于不同品... 详细信息

金线莲是一种珍贵中药材,其治疗、保健作用十分显著。金线莲培育方式主要有种植、组培等,不同培育方式的金线莲,在性状上仅表现出细微差异,但药用、市场价值差异显著,培育方式鉴别能有效保证药用疗效、维护良好市场秩序,然而由于不同品系、产地、培育时间等复合差异的影响,增加了培育方式鉴别难度与复杂度。提出一种基于改进1D-Inception-CNN模型的金线莲培育方式鉴别方法。采用近红外光谱仪采集种植、组培金线莲的光谱,首先使用合成少数类过采样技术(SMOTE)进行过采样以解决种植品、组培品样本比例不平衡问题,其次构建基于改进Inception结构的一维卷积神经网络对来自不同品系、产地、培育时间的金线莲进行种植品、组培品鉴别,最后采用贝叶斯优化方法对构建的卷积神经网络模型超参数进行优化;最终五折交叉验证平均鉴别准确率、精确率、召回率、综合评价指标高达97.95%、 96.16%、 100%、 98.02%。研究表明,实验提出的鉴别模型为快速鉴别金线莲种植品、组培品提供一种有效方法。

关键词：金线莲少数类过采样技术 Inception模块一维卷积神经网络贝叶斯优化

舞蹈类“非遗”与地方高校专业教育的耦合模式研究——以肇庆地区为例

在线全文

学校读者我要写书评

暂无评论

肇庆学院学报 2024年第1期45卷 37-41页

作者：兰寻肇庆学院音乐学院广东肇庆526061

为深入学习贯彻习近平总书记关于弘扬中华优秀传统文化重要思想,落实教育部对高等艺术人才培养的目标与要求。以肇庆地区舞蹈类非遗为抓手,以本地高校的专业教育和文化传承双重职能为契机,深入探讨其结构功能,分析其耦合关系,探索具有... 详细信息

为深入学习贯彻习近平总书记关于弘扬中华优秀传统文化重要思想,落实教育部对高等艺术人才培养的目标与要求。以肇庆地区舞蹈类非遗为抓手,以本地高校的专业教育和文化传承双重职能为契机,深入探讨其结构功能,分析其耦合关系,探索具有地域性、科学性和可持续发展性的耦合模式,旨在为各地舞蹈专业教育与非遗工作的可持续发展提供可行性依据,共同促进深刻变革,发挥领域间的有效耦合效应,激活其发展潜力。

关键词：舞蹈类非遗肇庆地方高校舞蹈专业耦合模式

Novel technologies in cfDNA analysis and potential utility in clinic

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Cancer Research 2021年第6期33卷 708-718页

作者： Jie Li Mengyue Xu Junya Peng Jingqiao Wang Yupei Zhao Wenming Wu xun Lan Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing 100084China Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China Department of Medical Research Peking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China Tsinghua-Peking Joint Center for Life Sciences Tsinghua UniversityBeijing 100084China Department of State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China

The profiling of plasma cell-free DNA(cfDNA)is becoming a valuable tool rapidly for tumor diagnosis,monitoring and prognosis.Diverse plasma cfDNA technologies have been in routine or emerging use,including analyses of mutations,copy number alterations,gene fusions and DNA methylation.Recently,new technologies in cfDNA analysis have been developed in laboratories,and potentially reflect the status of epigenetic modification,the immune microenvironment and the microbiome in tumor tissues.In this review,the authors discuss the principles,methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.

关键词： cfDNA liquid biopsy cancer diagnosis recurrence monitoring therapy response

在线全文

学校读者我要写书评

暂无评论

尿素/过硫酸钠纸基微流体燃料电池产电特性

工程热物理学报 2024年第2期45卷 525-534页

作者：陈曦叶丁丁朱恂杨扬兰巧陈蓉廖强重庆大学低品位能源利用技术及系统教育部重点实验室重庆400030 重庆大学能源与动力工程学院工程热物理研究所重庆400030

本文提出一种尿素/过硫酸钠完全被动式纸基微流体燃料电池,通过方波电流法将非贵金属镍催化剂电沉积到碳纸上制备阳极,阴极无需催化剂负载,电池成本大大降低。在不同结构及燃料、氧化剂、电解液浓度下测试了电池性能,结果表明,双层纸结... 详细信息

本文提出一种尿素/过硫酸钠完全被动式纸基微流体燃料电池,通过方波电流法将非贵金属镍催化剂电沉积到碳纸上制备阳极,阴极无需催化剂负载,电池成本大大降低。在不同结构及燃料、氧化剂、电解液浓度下测试了电池性能,结果表明,双层纸结构能大幅提高反应物流速,强化反应物传质,提高性能;电池在电极间距为6 mm、燃料浓度为0.3 mol·L^(-1)、氧化剂和电解液浓度均为1.0 mol·L^(-1)时,峰值功率密度和极限电流密度分别为5.9 m W·cm^(-2)和23.5 m A·cm^(-2),且运行稳定性较好。

关键词：尿素/过硫酸钠纸基微流体燃料电池性能稳定性