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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan qiyong Gong Zhongwei Gu Hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT2. colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Laboratory and Semi-Field Evaluation on S-Methoprene Formulations Against Anopheles sinensis(Diptera:Culicidae)—Yuxi City,Yunnan Province,China

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China CDC weekly 2024年第6期6卷 105-108页

作者： Wenbo Hu Yijin Chen Ying Liang Tianyun Su qiyong Liu Xuewen Li Xiaobo Liu School of Public Health Cheeloo College of MedicineShandong UniversityJinan CityShandong ProvinceChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases WHO Collaborating Centre for Vector Surveillance and ManagementDepartment of Vector Biology and ControlNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina EcoZone International Riverside CityCAUSA Department of Environment and Health School of Public HealthCheeloo College of MedicineShandong UniversityJinan CityShandong ProvinceChina Department of Vector Control School of Public HealthShandong UniversityJi’nan CityShandong ProvinceChina Xinjiang Key Laboratory of Vector-borne Infectious Diseases Urumqi CityXinjiang830002

Summary What is already known about this topic?Anopheles sinensis(***)is the predominant malaria vector in *** impact of S-methoprene on the emergence process of mosquito larvae suggests its potential as a control met... 详细信息

关键词： sinensis China. predominant

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Roles of concentration-dependent Cu doping behaviors on the thermoelectric properties of n-type Mg_(3)Sb_(1.5)Bi_(0.5)

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Journal of Materiomics 2024年第1期10卷 154-162页

作者： Xinxin Yang Heng Ni Xiaotong Yu Biao Cao Juanjuan Xing qiyong Chen Lili Xi Jiandang Liu Jiye Zhang Kai Guo Jing-Tai Zhao School of Materials Science and Engineering Shanghai University99 Shangda RoadShanghai200444China Materials Genome Institute Shanghai University99 Shangda RoadShanghai200444China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefeiAnhui230026China School of Physics and Materials Science Guangzhou UniversityGuangzhou510006China Research Center for Advanced Information Materials(CAIM) Huangpu Research&Graduate School of Guangzhou UniversitySino-Singapore Guangzhou Knowledge CityHuangpu DistrictGuangzhou510555China Key Lab of Si-based Information Materials&Devices and Integrated Circuits Design Department of Education of Guangdong ProvinceChina School of Materials Science and Engineering Guilin University of Electronic TechnologyGuilin541004China Guangxi Key Laboratory of Information Materials Guilin University of Electronic TechnologyGuilin541004China

Large Seebeck coefficients induced by high degeneracy of conduction band minimum,and low intrinsic lattice thermal conductivity originated from large lattice vibrational anharmonicity render Mg_(3)Sb_(2.as a promising n-type thermoelectric ***,we demonstrated unique concentration-dependent occupation behaviors of Cu in Mg_(3.4)Sb_(1.5)Bi_(0.49)Te_(0.01)matrix,evidenced by structural characterization and transport property *** is found that Cu atoms prefer to enter the interstitial lattice sites in Mg_(3)Sb_(2.host with low doping level(Mg_(3.4)Sb_(1.5)Bi_(0.49)Te_(0.01)+x%Cu,x2.3×10^(4)S/m at 300 K,increasing by 300%compared with that of the pristine *** figure of merit zT values in the whole measured temperature range are significantly improved by the synergetic improvement of power factor and reduction of thermal *** average zT∼1.07 from 32. K to 773 K has been achieved for the Mg_(3.4)Sb_(1.5)Bi_(0.49)Te_(0.01)+0.3%Cu sample,which is about 30%higher than that of the Mg_(3.4)Sb_(1.5)Bi_(0.49)Te_(0.01) sample.

关键词： Mg_(3)Sb_(2. Cu doping Concentration-dependent occupation Thermoelectric properties Average zT

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Relationships Between Meteorological Factors and Mongolian Gerbils and Its Flea Burdens—Xilingol League,Inner Mongolia Autonomous Region,China,2.12.2.2.

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China CDC weekly 2024年第23期6卷 547-552,I0012-I0018页

作者： Ke Li Zhenxu Wang Xiaohui Wei Haoqiang Ji Meng Shang Nan Chang Zihao Wang Chenran Guo Lei Xu Ning Zhao qiyong Liu National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina School of Public Health Nanjing Medical UniversityNanjing CityJiangsu ProvinceChina Cheeloo College of Medicine Shandong UniversitySchool of Public HealthJinan CityShandong ProvinceChina Vanke School of Public Health Tsinghua UniversityBeijingChina

Introduction:Plague is a significant global infectious disease,its spread is linked to host and flea *** conditions can impact flea populations and host densities,hence influencing plague *** the connection between meteorological factors,flea populations,and rodent densities in Inner Mongolia’s natural plague foci can aid in predicting and managing plague ***:Monthly data on flea index,rodent density,meteorological factors,and normalized difference vegetation index(NDVI)were collected for the study *** additive modeling(GAM)was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent *** equation modeling(SEM)was employed to investigate the relationships among meteorological factors,NDVI,flea index,and rodent ***:GAM analysis revealed that temperature,precipitation,relative humidity,and NDVI had significant linear,non-linear,and time-lagged impacts on the density of Mongolian gerbils and the flea *** analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils,or indirectly impact NDVI,subsequently influencing gerbil density and the flea ***:Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil *** study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system,offering valuable insights for predicting and managing plague outbreaks.

关键词： meteorological offering humidity

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A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie Yang Jie Li Qiao Kong Siming Zhou Hongbao Sun Lili Pan qiyong Gong Ping Feng Haoxing Wu Department of Radiology and Huaxi MR Research Center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of Nuclear Medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China Clinical Trial Center and National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang Jie Zhoua qiyong Gong Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT2.),mouse breast cancer(4T1)and human breast cancer(MDA-MB-2.1)*** cytotoxicity against CT2. MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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萧萐父先生的学术贡献与精神遗产——纪念萧萐父先生诞辰100周年

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中国哲学史 2024年第3期 42-50页

作者：郭齐勇武汉大学中国传统文化研究中心

萧萐父先生是我国现当代中国哲学史家、人文学者、诗人哲学家。他对中国哲学史教材编写、方法论探索、王夫之哲学、道家风骨说、佛教证悟论、明清启蒙说、近现代蜀学等领域都有研究与创获。他的代表作《中国哲学史方法论各议》《中国哲... 详细信息

萧萐父先生是我国现当代中国哲学史家、人文学者、诗人哲学家。他对中国哲学史教材编写、方法论探索、王夫之哲学、道家风骨说、佛教证悟论、明清启蒙说、近现代蜀学等领域都有研究与创获。他的代表作《中国哲学史方法论各议》《中国哲学启蒙的坎珂道路》《吹沙集》(三卷)等论文、著作的学思创造,是2.世纪后半叶中国哲学史现代转型的重要成果。萧萐先生的启蒙观的要旨,是从中国文化传统中寻找自己的现代性的根芽,强调本土文化中孕育了现代性。他主张的是中国式的启蒙,是中华文化主体的彰显,而不是全盘西化与全盘式的反传统,驳斥了中国自身不能产生现代性因素的西方偏见,这就超越了西方中心主义,也就蕴含了“启蒙反思”。

关键词：萧萐父早期启蒙说中国式现代化中国哲学史主体性

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乡村教师专业发展的文化回应性审思——走向文化理解、反思与实践

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教育研究 2024年第4期45卷 84-95页

作者：全晓洁蔡其勇重庆师范大学教育科学学院重庆401331 重庆市教育科学研究院重庆400015

以文化回应性理念审视乡村教师专业发展,使专业成长充分与乡村教师工作的社会环境、教育对象、场域特质相结合。这种文化回应性转向,有益于促进乡村教师向城性发展中话语权让渡后的再握,重构乡村学生城市镜像熏染下文化迷惘后的憧憬,推... 详细信息

以文化回应性理念审视乡村教师专业发展,使专业成长充分与乡村教师工作的社会环境、教育对象、场域特质相结合。这种文化回应性转向,有益于促进乡村教师向城性发展中话语权让渡后的再握,重构乡村学生城市镜像熏染下文化迷惘后的憧憬,推动乡村社会线性发展语境下文化断裂后的复归。文化回应性理念下的乡村教师专业发展,其要旨在于,从宏观上,追逐现代性和乡土性融合的专业理想;从中观上,实现文化理解型反思性实践者的角色期待;从微观上,重申公共性和专业性的话语特质。乡村教师作为文化理解型反思性实践者,应具有厚植乡土情怀的精神沃土、充盈乡土故事的知识图谱、扎根场域的回应性教学能力、适应本土的课程开发能力、理解“非我”和反思“自我”的文化敏感性。为此,须构建滋养文化理解的公共交往关系,引导基于文化反思的教育叙事探究,聚焦教育实践的关键情境搭建教研体系,紧扣历史文化的特殊履历设计课程,立足乡村教师的身份特质优化评价机制。

关键词：乡村教师教师专业发展文化回应性教育文化理解型反思性实践者教师素养结构

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全球消除疟疾的生物学挑战Ⅳ媒介按蚊入侵

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中国血吸虫病防治杂志 2024年第3期36卷 247-250页

作者：刘起勇传染病溯源预警与智能决策全国重点实验室、中国疾病预防控制中心传染病预防控制所北京102206

在国际交流与气候变化的驱动下,媒介按蚊入侵与扩散给全球疟疾消除目标的实现带来了新挑战。本文以斯氏按蚊入侵加重非洲疟疾流行为例,对全球按蚊入侵现状进行了梳理,结合媒介按蚊潜在入侵风险预估,揭示全球疟疾消除的困难与挑战,为各... 详细信息

在国际交流与气候变化的驱动下,媒介按蚊入侵与扩散给全球疟疾消除目标的实现带来了新挑战。本文以斯氏按蚊入侵加重非洲疟疾流行为例,对全球按蚊入侵现状进行了梳理,结合媒介按蚊潜在入侵风险预估,揭示全球疟疾消除的困难与挑战,为各国加强媒介按蚊入侵预警、媒介按蚊入侵的可持续精准防控提供参考。

关键词：疟疾消除按蚊入侵媒介控制

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Mutations and intron polymorphisms in voltage-gated sodium channel genes of different geographic populations of Culex pipiens pallens/Culex pipiens quinquefasciatus in China

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Infectious Diseases of Poverty 2024年第2期13卷 6-16页

作者： Wenyu Li Delong Ma Qunzheng Mu Xinxin Zhou Dongdong Hua Chunchun Zhao qiyong Liu Jun Wang Fengxia Meng State Key Laboratory of Infectious Disease Prevention and Control Department of Vector Biology and ControlNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionWHO Collaborating Centre for Vector Surveillance and ManagementBeijing 102206People’s Republic of China Ningxia Center for Disease Prevention and Control YinChuan 750004NingXiaPeople’s Republic of China Jinan Shizhong Center for Disease Control and Prevention Jinan 250000ShandongChina Vanke School of Public Health Tsinghua UniversityBeijingPeople’s Republic of China Weifang No.2.People’s Hospital Weifang 261000ShandongPeople’s Republic of China Beijing Daxing Center for Disease Control and Prevention Beijing 102600People’s Republic of China Jinan Second Maternal and Child Health Hospital Jinan 250000ShandongChina

Background Culex pipiens pallens and Culex pipiens quinquefasciatus are the dominant species of Culex mosquitoes in China and important disease ***-term use of insecticides can cause mutations in the voltage-gated sodium channel(vgsc)gene of mosquitoes,but little is known about the current status and evolutionary origins of vgsc gene in different geographic ***,this study aimed to determine the current status of vgsc genes in *** and *** in China and to investigate the evolutionary inheritance of neighboring downstream introns of the vgsc gene to determine the impact of insecticides on long-term *** Sampling was conducted from July to September 2.2. in representative habitats of 2. provincial-level administrative divisions in *** DNA was extracted from 1308 mosquitoes,the IIS6 fragment of the vgsc gene on the nerve cell membrane was amplified using polymerase chain reaction,and the sequence was used to evaluate allele frequency and knockdown resistance(kdr)*** 11 was used to construct neighborjoining(NJ)*** was used to build a TCS *** There were 6 alleles and 6 genotypes at the L1014 locus,which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F,TTC/F,TCT/S and TCA/*** geographic populations with a kdr frequency less than 2..00%were mainly concentrated in the regions north of 38°N,and the geographic populations with a kdr frequency greater than 80.00%were concentrated in the regions south of 30°*** frequency increased with decreasing *** within the same latitude,the frequency of kdr in large cities is relatively *** were correlated with the number of *** mutant allele TCA/S has only one intron,the mutant allele TTT/F has three introns,and the wild-type allele TTA/L has 17 *** *** and *** have developed resistance to insecticides in most regions of *** nei

关键词： Culex pipiens pallens Culex pipiens quinquefasciatus vgsc gene Mutation Frequency Intron Haplotype China

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