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The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai yang Cai yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang jianjun Liu Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for Molecular Imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision ***,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical *** bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled *** specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in *** preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human *** advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

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中亚东干诗歌中的列宁形象比较研究

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外国文学研究 2022年第2期44卷 135-145页

作者：杨建军兰州大学文学院

中亚东干文学,是丝绸之路沿线中亚三国华裔族群创作的文学,已引起多国学者关注。东干诗歌中的列宁形象与俄苏诗歌、中国诗歌中的列宁形象共时存在,三者之间有或显或隐的影响关系。东干诗歌中的列宁形象书写多采用自然意象,常把列宁比作... 详细信息

中亚东干文学,是丝绸之路沿线中亚三国华裔族群创作的文学,已引起多国学者关注。东干诗歌中的列宁形象与俄苏诗歌、中国诗歌中的列宁形象共时存在,三者之间有或显或隐的影响关系。东干诗歌中的列宁形象书写多采用自然意象,常把列宁比作春天和太阳,也常把列宁比作父亲,列宁的革命者人格还被东干诗人升华为民族精神的象征。东干诗歌与俄苏诗歌中的列宁形象有一致性,自然意象采用和人道主义关怀是两者共性,但在诗歌话语、自然情感、精神内涵等方面,东干诗歌有自身特性。东干诗歌与中国诗歌都受到俄苏文化影响,两者都致力表现列宁对革命建设带来的重要变革,中国诗歌偏向表现精神层面影响,东干诗歌偏重表现物质生活影响。东干诗歌中的列宁形象书写在海外华语文学中的启示性意义有四个方面:文学资源、文学互动、身份认同、读者接受。

关键词：中亚东干诗歌列宁形象海外华语文学俄苏诗歌中国诗歌

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Single transmembrane GPCR modulating proteins:neither single nor simple

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Protein & Cell 2024年第6期15卷 395-402页

作者： Meng Wang jianjun Lyu Chao Zhang Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Hubei Topgene Research Institute of Hubei Topgene Biotechnology Co. LtdEast Lake High-Tech Development ZoneWuhan 430205China Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center)Tongji UniversityShanghai 200092China

The discovery of G-protein coupled receptor(GPCR)accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling,demonstrating a more complex molecular basis for receptor specificity on the plasma membrane and impressionable downstream intracellular *** accessory proteins not only contribute to the proper folding and trafficking of receptors but also exhibit selectable receptor preferences.

关键词： specificity GPCR neither

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Grassland-type ecosystem stability in China differs under the influence of drought and wet events

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Journal of Arid Land 2024年第5期16卷 615-631页

作者： CAO Wenyu BAI jianjun YU Leshan School of Geography and Tourism Shaanxi Normal UniversityXi'an 710119China International Business School Shaanxi Normal UniversityXi'an 710119China

Ecological stability is a core issue in ecological research and holds significant implications forhumanity. The increased frequency and intensity of drought and wet climate events resulting from climatechange pose a major threat to global ecological stability. Variations in stability among different ecosystemshave been confirmed, but it remains unclear whether there are differences in stability within the sameterrestrial vegetation ecosystem under the influence of climate events in different directions and ***'s grassland ecosystem includes most grassland types and is a good choice for studying this *** study used the Standardized Precipitation Evapotranspiration Index-12 (SPEI-12) to identify thedirections and intensities of different types of climate events, and based on Normalized DifferenceVegetation Index (NDVI), calculated the resistance and resilience of different grassland types for 30consecutive years from 1990 to 2019 (resistance and resilience are important indicators to measurestability). Based on a traditional regression model, standardized methods were integrated to analyze theimpacts of the intensity and duration of drought and wet events on vegetation stability. The resultsshowed that meadow steppe exhibited the highest stability, while alpine steppe and desert steppe had thelowest overall stability. The stability of typical steppe, alpine meadow, temperate meadow was at anintermediate level. Regarding the impact of the duration and intensity of climate events on vegetationecosystem stability for the same grassland type, the resilience of desert steppe during drought was mainlyaffected by the duration. In contrast, the impact of intensity was not significant. However, alpine steppewas mainly affected by intensity in wet environments, and duration had no significant impact. Ourconclusions can provide decision support for the future grassland ecosystem governance.

关键词： grassland ecosystem stability resistance resilience different climate types drought climate event wet climate event

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Design and synthesis of thiol-terminated imidothioether oligomer as thermally latent hardener and modifier for high-performance epoxy/thiol thermosets

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Science China Chemistry 2024年第2期67卷 632-641页

作者： Xing Liu jianjun Zhou Shumei Liu Jianqing Zhao School of Materials Science and Engineering South China University of TechnologyGuangzhou510640China Key Lab Guangdong High Property&Functional Polymer Materials Key Laboratory of Polymer Processing EngineeringMinistry of EducationGuangzhou510640China

Conventional base-catalyzed epoxy/aliphatic thiol systems have a poor storage stability,and are impossible to be one-pot systems.A widely accepted solution is to use the latent catalysts,which are usually insoluble anionic initiators sensitive to impurities and moisture,and have many limitations in practical *** this work,a soluble thiol-terminated imidothioether oligomer(TPI) was synthesized and used as a latent hardener and modifier to prepare one-pot epoxy/thiol systems without the latent *** latent behavior and curing mechanism of epoxy systems(EP/TPI series),consisted of bisphenol A diglycidyl ether(DGEBA),pentaerythritol tetrakis(mercaptoacetate)(PETMP) and TPI,were *** thiol exchange reaction between TPI and PETMP preceded the curing reaction of DGEBA,and produced aromatic thiols,which were unreactive at ambient conditions and reacted with DGEBA to form the thermosets at temperatures above 130 ℃.At the loading of 24.4 wt%TPI,the epoxy system(EP/TPI-3) had a shelf life of 13 days and was completely cured within 20 min at 180 ℃.Meanwhile,the catalyst-free curing process of EP/TPI-3 system was insensitive to impurities and ***,the thermal and mechanical properties of EP/TPI-3 thermoset were simultaneously improved,thereinto,the glass transition temperature,Young's modulus and ultimate tensile strength were increased by 16.7 ℃,12.9%,and 13.6%,respectively,compared with those of the commercial DGEBA/PETMP *** work shows that TPI has the potential to be a powerful alternative to commercial latent catalysts,and EP/TPI thermosets with high performance have broad application prospects.

关键词： thiol-terminated imidothioether oligomer epoxy systems thiol exchange reaction thermal latency high performance

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Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu Qiang Xu jianjun Zou yang Sun Wenjie Guo State Key Laboratory of Pharmaceutical Biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of Clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th17 Colitis Allosteric activator

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A Planning Method for Operational Test of UAV Swarm Based on Mission Reliability

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1889-1918页

作者： Jingyu Wang Ping Jiang jianjun Qi College of Systems Engineering National University of Defense TechnologyChangsha410073China Beijing Special Engineering Design Institution Beijing100028China

The unmanned aerial vehicle(UAV)swarm plays an increasingly important role in the modern battlefield,and the UAV swarm operational test is a vital means to validate the combat effectiveness of the UAV *** to the high cost and long duration of operational tests,it is essential to plan the test in *** solve the problem of planning UAV swarm operational test,this study considers the multi-stage feature of a UAV swarm mission,composed of launch,flight and combat stages,and proposes a method to find test plans that can maximize mission ***,a multi-stage mission reliability model for a UAV swarm is proposed to ensure successful implementation of the mission.A multi-objective integer optimization method that considers both mission reliability and cost is then formulated to obtain the optimal test *** study first constructs a mission reliability model for the UAV swarm in the combat ***,the launch stage and flight stage are integrated to develop a complete PMS(Phased Mission Systems)reliability ***,the Binary Decision Diagrams(BDD)and Multi Objective Quantum Particle Swarm Optimization(MOQPSO)methods are proposed to solve the *** optimal plans considering both reliability and cost are *** proposed model supports the planning of UAV swarm operational tests and represents a meaningful exploration of UAV swarm test planning.

关键词： UAV swarm PMS MOQPSO BDD mission reliability operational test planning

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人工智能法:必要性与可行性

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北京航空航天大学学报（社会科学版） 2024年第3期37卷 162-174页

作者：杨建军张凌寒周辉程莹郑志峰韩旭至赵精武周瑞珏西北政法大学陕西西安710063 中国政法大学北京100088 中国社会科学院北京100009 中国信息通信研究院北京100083 西南政法大学重庆401120 华东政法大学上海201620 北京航空航天大学北京100083

近期,《人工智能法(学者建议稿)》《人工智能示范法2.0(专家建议稿)》等人工智能立法建议稿相继涌现,加速推动人工智能立法成为学界主流观点。然而,人工智能立法的立法目标、立法体系、具体规则等事项依然存在较大争议。为此,本刊特刊... 详细信息

近期,《人工智能法(学者建议稿)》《人工智能示范法2.0(专家建议稿)》等人工智能立法建议稿相继涌现,加速推动人工智能立法成为学界主流观点。然而,人工智能立法的立法目标、立法体系、具体规则等事项依然存在较大争议。为此,本刊特刊发专题笔谈,邀请了来自北京航空航天大学、中国政法大学、西北政法大学、中国信息通信研究院、中国社会科学院、华东政法大学、西南政法大学等多所院校的知名专家,就人工智能立法的立法逻辑、立法体系、内容模块等核心议题进行了深入的理论探讨和观点交流。

关键词：立法体系人工智能立法目标中国政法大学信息通信西南政法大学中国社会科学院西北政法大学

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Effect of hot isostatic pressure on the microstructure and tensile properties of γ'-strengthened superalloy fabricated through induction-assisted directed energy deposition

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International Journal of Minerals,Metallurgy and Materials 2024年第5期31卷 1089-1097页

作者： jianjun Xu Hanlin Ding Xin Lin Feng Liu Analytical&Testing Center Northwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China

The microstructure characteristics and strengthening mechanism of Inconel738LC(IN-738LC) alloy prepared by using induction-assisted directed energy deposition(IDED) were elucidated through the investigation of samples subjected to IDED under 1050℃ preheating with and without hot isostatic pressing(HIP,1190℃,105 MPa,and 3 h).Results show that the as-deposited sample mainly consisted of epitaxial columnar crystals and inhomogeneously distributed γ’ phases in interdendritic and dendritic core *** HIP,grain morphology changed negligibly,whereas the size of the γ’ phase became increasingly *** further heat treatment(HT,1070℃,2 h + 845℃,24 h),the γ’ phase in the as-deposited and HIPed samples presented a bimodal size distribution,whereas that in the as-deposited sample showed a size that remained *** comparison of tensile properties revealed that the tensile strength and uniform elongation of the HIP + HTed sample increased by 5% and 46%,respectively,due to the synergistic deformation of bimodal γ’phases,especially large cubic γ’ ***,the relationship between phase transformations and plastic deformations in the IDEDed sample was discussed on the basis of generalized stability theory in terms of the trade-off between thermodynamics and kinetics.

关键词： directed energy deposition Ni-based superalloys high-temperature preheating hot isostatic pressing microstructure tensile properties

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权力监督制约的第三种模式

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法学论坛 2022年第4期37卷 61-74页

作者：杨建军西北政法大学法治学院陕西西安710063

如果依照权力监督制约所依托的规范来划分,则人类历史上曾经诞生过依托法律规范的权力监督制约、依托道德规范的权力监督制约和依托党内法规的权力监督制约三种模式或者说三种“理想类型”。其中,以党规党纪监督制约权力,是中国共产党... 详细信息

如果依照权力监督制约所依托的规范来划分,则人类历史上曾经诞生过依托法律规范的权力监督制约、依托道德规范的权力监督制约和依托党内法规的权力监督制约三种模式或者说三种“理想类型”。其中,以党规党纪监督制约权力,是中国共产党开创的权力监督制约的新模式:权力监督制约的主体不是国家或社会,而是执政党;权力监督制约的规范是执政党制定的系统的党内法规规范体系而不限于法律规范或道德规范;既强调对权力监督制约对象的全覆盖又强调抓住“关键少数”;此外,还有独特的党内法规监督实施机制和责任承担方式。第三种权力监督制约模式既有对基于法律规范的权力监督制约模式和基于道德规范的权力监督制约模式理念、制度的承继,也有对两种模式的理念、制度的超越。相比世界各主要政党的章程或者“规矩”,中国共产党创立的依靠党内法规对权力监督制约的模式,在世界上是独一无二的。

关键词：权力监督制约党内法规模式

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