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Engineering 2024年第7期38卷 69-76页

作者： Xi Lu Guoqing Li Jing Pang Xinyi Yang Colette Cywes-Bentley xuefu You Gerald B.Pier Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division of Infectious Diseases Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

The b-1-6-linked poly-N-acetylglucosamine(PNAG)polymer is a conserved surface polysaccharide produced by many bacteria,fungi,and protozoan(and even filarial)*** wide-ranging expression makes PNAG an attractive target for vaccine development,as it potentially encompasses a broad range of *** progress has been made in discovering important properties of the biology of PNAG expression in recent *** molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many *** addition,the physiological function of PNAG has been further ***-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical ***,clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals,and the results are *** it is not destined to be a smooth road,we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

关键词： Poly-N-acetylglucosamine Conjugate vaccine Monoclonal antibody

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of Pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division for Medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

生成式人工智能服务信息内容安全的三类标准--基于《生成式人工智能服务管理暂行办法》的分析

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中国行政管理 2024年第4期40卷 120-128页

作者：张学府中国政法大学政治与公共管理学院北京100088

《生成式人工智能服务管理暂行办法》以信息内容安全为规范重点,相关条款可分为绩效标准、设计标准、内部管理型标准。绩效标准设定了“提供者、使用者不得生成特定信息”等结果义务,不匹配生成结果的不可控性,合规成本畸高;设计标准明... 详细信息

《生成式人工智能服务管理暂行办法》以信息内容安全为规范重点,相关条款可分为绩效标准、设计标准、内部管理型标准。绩效标准设定了“提供者、使用者不得生成特定信息”等结果义务,不匹配生成结果的不可控性,合规成本畸高;设计标准明定提供者应采取的技术、行为,但部分设计标准却针对“发现违法行为、信息”这一或然事件缺乏针对性,内部管理型标准要求提供者自主选取提高信息质量的措施,可匹配生成式人工智能的不可控性、快速迭代性、大数据特性,但对有效执行提出较高要求。可通过转换标准类型、构建执行环境、以规制学习促进标准体系成熟等方法,提高生成式人工智能服务管理的有效性。

关键词：生成式人工智能绩效标准设计标准内部管理型标准规制标准

A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3449-3466页

作者： Xixi Guo Xiaosa Zhao Xi Lu Liping Zhao Qingxuan Zeng Fenbei Chen Zhimeng Zhang Mengyi Xu Shijiao Feng Tianyun Fan Wei Wei Xin Zhang Jing Pang xuefu You Danqing Song Yanxiang Wang Jiandong Jiang Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College100050 BeijingChina School of Information Science and Technology Northeast Normal UniversityChangchun 130117China Department of Pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272029 ShandongChina Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei230601AnhuiChina

Helicobacter pylori(***)is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis,and its high prevalence and resistance make it difficult to tackle.A graph neural network-based deep learning model,employing different training sets of 13,638 molecules for pre-training and fine-tuning,was aided in predicting and exploring novel molecules against ***.A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant *** strains with minimum inhibitory concentrations(MICs)of 0.25-0.5μg/*** studies demonstrated an ideal gastric retention of 8,with the stomach concentration significantly higher than its MIC at 24 h post *** administration of 8 and omeprazole(OPZ)showed a comparable gastric bacterial reduction(2.2-log reduction)to the triple-therapy,namely OPZ+amoxicillin(AMX)+clarithromycin(CLA)without obvious disturbance on the intestinal flora.A combination of OPZ,AMX,CLA,and 8 could further decrease the bacteria load(2.8-log reduction).More importantly,the mono-therapy of 8 exhibited comparable eradication to both triple-therapy(OPZ+AMX+CLA)and quadrupletherapy(OPZ+AMX+CLA+bismuth citrate)*** and BamD,playing a major role in outer membrane protein(OMP)transport and assembling,were identified and verified as the direct targets of 8 by employing the chemoproteomics technique.n summary,by targeting the relatively conserved OMPs transport and assembling system,8 has the potential to be developed as a novel *** candidate,especially for the eradication of drug-resistant strains.

关键词： berberine stomach retention

山西省杏地方品种资源表型性状的遗传多样性分析

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分子植物育种 2024年第10期22卷 3335-3347页

作者：狄红梅王学府张春芬晋中职业技术学院晋中030600 山西农业大学果树研究所太原030000

为了充分保护和开发利用地方杏种质资源,更多地了解和掌握该资源多样性和变异规律,本研究以山西省的59个杏地方品种为试验材料,对42个表型性状进行了遗传多样性分析,对19个数量性状进行了相关性、聚类和主成分分析。结果表明,23个质量... 详细信息

为了充分保护和开发利用地方杏种质资源,更多地了解和掌握该资源多样性和变异规律,本研究以山西省的59个杏地方品种为试验材料,对42个表型性状进行了遗传多样性分析,对19个数量性状进行了相关性、聚类和主成分分析。结果表明,23个质量性状的遗传多样性指数范围为0.20~1.71;19个数量性状的变异系数是11.11%~58.59%,平均值为34.23%。对19个数量性状的相关性分析,发现除枝条长度外,其他性状彼此间多存在一定的显著或极显著相关性。通过主成分分析,提取前6个主成分的累计贡献率为79.451%。依据19个数量性状对供试材料聚类分析,在欧式距离为18.5处,得到4个类群,其中第Ⅰ类叶片面积最大,可作为丰产品种加以开发;第Ⅱ类可作为培育高品质杏的种质资源;第Ⅲ类育种改良的潜力较大;第Ⅳ类育种价值独特。本研究表明山西省杏地方品种资源存在丰富的变异,为拓展杏育种亲本材料提供了有力的遗传物质保证,也为分子遗传学研究提供了大量表型数据。

关键词：山西省杏地方品种表型性状遗传多样性

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“双减”背景下初中生物高效课堂的构建探讨

成才之路 2024年第3期 125-128页

作者：钟学富福建省龙岩市上杭县下都中学福建上杭364200

目前,初中生物教学还存在教师不能将“双减”政策与初中生物教学进行联系、“双减”政策与初中生物的结合浮于表面的问题。为落实“双减”政策要求,提高生物教学质量,初中生物教学可采取增强教师改革观念、引领课堂教学发展,课前做好充... 详细信息

目前,初中生物教学还存在教师不能将“双减”政策与初中生物教学进行联系、“双减”政策与初中生物的结合浮于表面的问题。为落实“双减”政策要求,提高生物教学质量,初中生物教学可采取增强教师改革观念、引领课堂教学发展,课前做好充分准备、为教学活动的开展做铺垫,课中多种措施并用、提高课堂教学效果,优化课后作业布置、提高复习成效等策略,提高初中生物教学效果和质量,构建初中生物高效课堂,落实“双减”政策要求,为初中生物教学改革提供借鉴。

关键词： “双减”背景初中生物高效课堂教学改革教学效果

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技术创新要素及其关联识别方法研究——以合成生物学为例

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图书情报工作 2024年第17期68卷 68-83页

作者：邬金鸣姚茹吴俣林巧张学福中国农业科学院农业信息研究所北京市农林科学院数据科学与农业经济研究所

[目的/意义]技术创新是一项涉及多种技术创新要素协同作用的复杂系统工程。从技术文本中识别出技术创新要素及其关联，进而分析要素及其关联随时间的动态变化以及要素的跨领域相互作用等，可在微观层面揭示技术创新过程与规律，为预测... 详细信息

[目的/意义]技术创新是一项涉及多种技术创新要素协同作用的复杂系统工程。从技术文本中识别出技术创新要素及其关联，进而分析要素及其关联随时间的动态变化以及要素的跨领域相互作用等，可在微观层面揭示技术创新过程与规律，为预测融合创新机会奠定基础。其中首要问题是如何从技术文本中识别出技术创新要素及其关联。[方法/过程]为解决识别对象的问题，在先前研究中构建面向技术创新过程表征和描述的要素关联概念模型；为解决识别方法的问题，以合成生物学领域为例，面向概念模型中要素及其关联的文本特征，构建以专利为主、论文为辅，综合文本内容挖掘和引用分析的技术创新要素及其关联识别方法，以揭示技术创新过程中来源于相同或不同领域的技术创新要素之间相互作用、不同技术创新要素在不同技术创新事件中作用等。[结果/结论 ]在6 435篇专利及其参考论文中，识别7 633个技术对象要素、3 420个技术方法要素、3 919个技术应用要素、5 393个技术理论要素及其领域、时间属性信息，以及25 647条6种不同要素关联。该方法可以为基于要素关联揭示技术创新过程和规律（特别是交叉融合领域技术创新过程与规律）、进而预测融合创新机会奠定基础。

关键词：技术创新技术创新要素要素关联要素识别技术创新事件

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三参数W变换的可逆性

石油地球物理勘探 2024年第3期59卷 433-442页

作者：刘保童刘启源黄翼坚康学福刘东林姜英爽天水师范学院电子信息与电气工程学院甘肃天水741001 四川大学数学学院四川成都610064 西北大学地质学系大陆动力学国家重点实验室陕西西安710069

三参数W变换(TPWT)是分析非平稳信号的有效工具,已成功应用于油气储层识别。然而,前人没有详细论述TPWT的可逆性。为此,首先回顾了TPWT的基本原理,然后从理论上探讨了TPWT的可逆性。理论分析与数值计算结果表明:(1)TPWT既解决了S变换(ST... 详细信息

三参数W变换(TPWT)是分析非平稳信号的有效工具,已成功应用于油气储层识别。然而,前人没有详细论述TPWT的可逆性。为此,首先回顾了TPWT的基本原理,然后从理论上探讨了TPWT的可逆性。理论分析与数值计算结果表明:(1)TPWT既解决了S变换(ST)的低频时间分辨率低与时—频谱能量分布中心向高频偏移的问题,也克服了W变换(WT)时—频谱在主频处的振幅分裂现象,能更准确地描述油气储层,更有利于地震解释。(2)在理论上TPWT不是严格可逆的,而是一种近似可逆的变换工具,这与傅里叶变换(FT)、ST不同。(3)合成地震数据与实际地震记录的数值计算结果显示,与原始地震数据相比,利用逆TPWT重建地震数据的相对误差为11.47%~21.35%,即理论上的不可逆导致较大的重建误差,严重影响TPWT的应用范围,在去噪、高分辨率处理等需要重建数据的处理领域不宜使用。

关键词：时—频谱三参数W变换振幅分裂重建地震数据

γδ T cells in liver diseases

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Frontiers of Medicine 2018年第3期12卷 262-268页

作者： xuefu Wang Zhigang Tian School of Pharmacy Anhui Medical University Hefei 230032 China Institute of Immunology and CAS Key Laboratory of Innate Immunityand Chronic Disease School of Life Sciences and Medical Center University of Science and Technology of China Hefei 230027 China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment ofInfectious Diseases First Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310003 China

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues, γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and fiver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδ T cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration