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

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

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Solid-state synthesis and ion transport characteristics of the β-KSbF_(4) for all-solid-state fluoride-ion batteries

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Journal of Energy Chemistry 2024年第7期94卷 758-767页

作者： Jiali Liu Huahui Zhao Jingcheng Xia Lingguang Yi Xiaoyi Chen Dongdu Li Shuhan Ni xinyi Su Yixuan Chen Min Liu Xianyou Wang National Base for International Science&Technology Cooperation National Local Joint Engineering Laboratory for Key Materials of New Energy Storage BatteryHunan Province Key Laboratory of Electrochemical Energy Storage&ConversionSchool of ChemistryXiangtan UniversityXiangtan 411105HunanChina College of New Energy Ningbo University of TechnologyNingbo 315336ZhejiangChina

All-solid-state fluoride ion batteries(FIBs)have been recently considered as a post-lithium-ion battery system due to their high safety and high energy *** like all solid-state lithium batteries,the key to the development of FIBs lies in room-temperature electrolytes with high ionic conductivity.β-KSbF_(4) is a kind of promising solid-state electrolyte for FIBs owing to its rational ionic conductivity and relatively wide electrochemical stability window at room ***,the previous synthesis routes ofβ-KSbF_(4) required the use of highly toxic hydrofluoric acid and the ionic conductivity of as-prepared product needs to be further ***,the β-KSbF_(4) sample with an ionic conductivity of 1.04×10^(-4)s cm^(-1)(30°C)is synthesized through the simple solid-state *** order to account for the high ionic conductivity of the as-synthesizedβ-KSbF_(4),X-ray diffraction(XRD),scanning electron microscopy(SEM),and energy dispersive X-ray spectroscopy(EDS)are used to characterize the physic-ochemical *** results show that the as-synthesizedβ-KSbF_(4) exhibits higher carrier concentra-tion of 1.0×10^(-6)S cm-Hz^(-1)K and hopping frequency of 1.31×10^(6)Hz at 30°C due to the formation of the fluorine ***,the hopping frequency shows the same trend as the changes of ionic conductivity with the changes of temperature,while the carrier concentration is found to be almost *** two different trends indicate the hopping frequency is mainly responsible for the ionic conduc-tion behavior withinβ-KSbF_(4).Furthermore,the all-solid-state FIBs,in which Ag and Pb+PbF_(2) are adopted as cathode and anode,andβ-KSbF_(4) as fluoride ion conductor,are capable of reversible charge and *** assembled FIBs show a discharge capacity of 108.4 mA h g^(-1) at 1st cycle and 74.2 mA h g^(-1) at 50th *** on an examination of the capacity decay mechanism,it has been found that deterioration of the electrolyte/electrode int

关键词： Solid-state electrolyte Carrier concentration Hopping frequency β-KSbF_(4) All-solid-state fluoride ion batteries

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Hydrogen bond-induced elastic polyzwitterion electrolytes constructed by mussel-inspired autopolymerization for zinc-ion battery

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Science China Chemistry 2024年第10期67卷 3438-3449页

作者： Shi Wang xinyi Wu Chao Liu Lingjun He Shuanghan Li Yuqi Miao Mingrui Cai Yi Li Zheng-Dong Huang Wen-Yong Lai State Key Laboratory of Organic Electronics and Information Displays(SKLOEID) Institute of Advanced Materials(IAM)School of Chemistry and Life SciencesNanjing University of Posts&TelecommunicationsNanjing 210023China

Aqueous zinc-ion batteries(ZIBs)have attracted much interest to realize safe rechargeable batteries with high safety and high energy ***,it is still challenging to address dendrite growth and parasitic reactions in zinc *** propose herein the design concept of hydrogen bond-induced elastic polyzwitterion electrolytes with zincophilic groups for achieving robust ***-inspired autopolymerization has been developed to construct the polyzwitterion electrolytes at room temperature by inducing electron density delocalization atα-position of C=C bond in zwitterion monomer by Zn^(2+).Specifically,the zwitterionic functional groups construct ion transport channels,and the unique–NH–and SO_(3)^(-)groups co-compete with H_(2)O for coordination with Zn^(2+)and promote the desolvation of hydrated Zn^(2+),thus achieving a high room temperature ionic conductivity(6.7 mS cm^(-1))and an increased Zn^(2+)migration number(0.65)for the polyzwitterion *** addition,various interactions such as hydrogen bonding and electrostatic interactions between electrolyte ions and zwitterionic groups impart high stretchability and strength to the polyzwitterion electrolytes,which,combined with SO_(3)^(-)philic(002)crystallographic properties,effectively inhibit the growth of zinc *** a result,rigid/wearable solid-state ZIBs exhibit excellent cycling and C-rate *** believe that the strategy of constructing polyzwitterionic electrolytes with zincophilic groups and ion transport channels opens up a new direction in polymer electrolyte engineering towards safe and high energy batteries.

关键词： flexible electronics wearable electronics polyzwitterion electrolytes self-polymerization zinc-ion batteries

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Regulation of 2-acetyl-1-pyrroline and grain quality in early-season indica fragrant rice by nitrogen and silicon fertilization under different plantation methods

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Journal of Integrative Agriculture 2024年第2期23卷 511-535页

作者： Yongjian Chen Lan Dai Siren Cheng Yong Ren Huizi Deng xinyi Wang Yuzhan Li Xiangru Tang Zaiman Wang Zhaowen Mo State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources College of AgricultureSouth China Agricultural UniversityGuangzhou 510642China Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology Yulin Normal UniversityYulin 537000China Key Laboratory for Conservation and Utilization of Subtropical Bio-Resources Education Department of Guangxi Zhuang Autonomous Region/College of Biology and PharmacyYulin Normal UniversityYulin 537000China Scientific Observing and Experimental Station of Crop Cultivation in South China Ministry of Agriculture and Rural AffairsGuangzhou 510642China Guangzhou Key Laboratory for Science and Technology of Fragrant Rice Guangzhou 510642China Key Laboratory of Key Technology for South Agricultural Machine and Equipment Ministry of Education/College of EngineeringSouth China Agricultural UniversityGuangzhou 510642China

Fragrant rice has a high market value,and it is a popular rice type among consumers owing to its pleasant *** methods,nitrogen(N)fertilizers,and silicon(Si)fertilizers can affect the grain yield and fragrance of fragrant ***,the core commercial rice production attributes,namely the head rice yield(HRY)and 2-acetyl-1-pyrroline(2-AP)content of fragrant rice,under various nitrogen and silicon(N-Si)fertilization levels and different plantation methods remain *** field experiment in this study was performed in the early seasons of 2018 and 2019 with two popular indica fragrant rice cultivars(Yuxiangyouzhan and Xiangyaxiangzhan).They were grown under six N-Si fertilization treatments(combinations of two levels of Si fertilizer,0 kg Si ha^(−1)(Si0)and 150 kg Si ha^(−1)(Si1),and three levels of N fertilizer,0 kg N ha^(−1)(N0),150 kg N ha^(−1)(N1),and 220 kg N ha^(−1)(N2))and three plantation methods(artificial transplanting(AT),mechanical transplanting(MT),and mechanical direct-seeding(MD)).The results showed that the N-Si fertilization treatments and all the plantation methods significantly affected the HRY and 2-AP content and related parameters of the two different fragrant rice *** with the Si0N0 treatment,the N-Si fertilization treatments resulted in higher HRY and 2-AP *** rates of brown rice,milled rice,head rice,and chalky rice of the fragrant rice also improved with the N-Si fertilization *** N-Si fertilization treatments increased the activities of N metabolism enzymes and the accumulation of N and Si in various parts of the fragrant rice,and affected their antioxidant response *** key parameters for the HRY and 2-AP content were assessed by redundancy ***,the structural equation model revealed that the Si and N accumulation levels indirectly affected the HRY by affecting the N metabolism enzyme activity,N use efficiency,and grain quality of fragrant ***,high N

关键词： fragrant rice 2-AP content head rice yield mechanical planting nitrogen silicon

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The foodborne toxin perfringolysin O targets mitochondrial destabilization for NLRP3 inflammasome activation

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Food Science and Human Wellness 2024年

作者： xinyi Wang Ying Ren Bo Wang Beizhong Han Yansong Xue Beijing Laboratory for Food Quality and Safety， College of Food Science and Nutritional Engineering， China Agricultural University State Key Laboratory of Animal Nutrition and Feeding， Department of Animal Nutrition and Feed Science， College of Animal Science and Technology， China Agricultural University Key Laboratory of Food Bioengineering (China National Light Industry)， College of Food Science and Nutritional Engineering， China Agricultural University

Foodborne pathogens are the leading causes of human diseases that result in hundreds of thousands of deaths annually. Clostridium perfringens （C. perfringens） is a notorious foodborne pathogen of global significance that is known to produce a large repertoire of toxic factors， several of which can severely destroy the gut lining to lead to abdominal pain， diarrhea， and even death. However， like many other foodborne pathogens， there is no specific treatment for infections caused by C. perfringens and rehydration therapy is largely ineffective at reducing symptoms and preventing transmission. Given this， there is an urgent need to discover new therapeutic targets that can be harnessed to treat C. perfringens infection. We recently discovered that a highly toxic factor produced by C. perfringens named perfringolysin O （PFO） activates the innate immune sensor NLRP3. We characterized that PFO is the specific agonist of NLRP3 inflammasome and mechanistically， the intracellular entrance of PFO is required for active assembly of NLRP3 inflammasome. Further， PFO targets the mitochondria resulting in mitochondrial destabilization and ROS release. Mito-TEMPO scavenging mtROS specifically inhibits the level of caspase-1 p20 and IL-1β in both in vitro and in vivo models. Additionally， 5-hydroxydecanoate （5-HD）， a selective mitochondrial ATP-sensitive potassium channel (KATP) inhibitor， could relieve PFO-induced NLRP3 inflammasome activation as well as mitochondrial destabilization， indicating that potassium ion flux is necessary for mitochondrial damage upstream of NLRP3 inflammasome activation. We expect that the information gathered from this study will develop insights into features of the immune response that can be targeted for the treatment of food poisoning and other foodborne pathogenic infections.

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基于风力机功率特性的风资源评估δ指标体系

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太阳能学报 2017年第2期38卷 498-502页

作者：张家安刘宁吴林林李志刚刘辉孟心怡河北工业大学控制科学与工程学院天津300130 河北工业大学电气工程学院天津300130 国网冀北电力有限公司电力科学研究院北京100045

基于风力机功率特性提出风电场风资源评估的δ指标体系,该指标体系包含风力机限值风速、风力机限值风功率密度和δ指标。风力机限值风速和风力机限值风功率密度反映风力经风力机转换为电能的风资源效能;δ指标为有功风功率密度与风力机... 详细信息

基于风力机功率特性提出风电场风资源评估的δ指标体系,该指标体系包含风力机限值风速、风力机限值风功率密度和δ指标。风力机限值风速和风力机限值风功率密度反映风力经风力机转换为电能的风资源效能;δ指标为有功风功率密度与风力机限值风功率密度的差值,反映风力经风力机转换为电能后的再发电能力。算例分析表明,δ指标体系可准确地描述风资源与风电场发电量的相关关系。

关键词：风资源评估风力机限值风速风力机限值风功率密度 δ指标

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Value of Metagenomic Next-Generation Sequencing in Clinical Diagnosis and Targeted Therapy of Nontuberculous Mycobacteria Infection

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Infectious Microbes & Diseases 2024年第2期6卷 100-102页

作者： Lanlan Xiao Shuai Zhao Hongjuan Wang Liang Yu Jing Guo xinyi Wu Xiaowei Xu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Affiliated Hospital of Nantong University NantongChina Zhejiang University City College HangzhouChina

The purpose of this study was to assess the value of metagenomic next-generation sequencing(mNGS)for rapid diagnosis of diseases caused by nontuberculous mycobacteria(NTM).We retrospectively reviewed four NTM-infected cases diagnosed by smear microscopy,mycobacterial culture and mNGS *** found that the mNGS method not only had a shorter detection turnaround time(3–4 days)than Mycobacterium culture(15–20 days)but also had higher sensitivity and specificity to identify NTM compared with conventional detection *** addition,mNGS was able to identify coinfections by NTM and other bacteria,fungi or ***,diagnosis of NTM by mNGS can provide timely and precise guidance for subsequent clinical treatment of NTM infections.

关键词： nontuberculous mycobacteria metagenomic next-generation sequencing mycobacterial culture turnaround time

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Hybrid Gaussian Network Intrusion Detection Method Based on CGAN and E-GraphSAGE

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Instrumentation 2024年第2期11卷 24-35页

作者： xinyi Liang Hongyan Xing Wei Gu Tianhao Hou Zhiwei Ni xinyi Wang School of Electronics Information Engineering Nanjing University of Information Science&TechnologyNanjing 210044

The rapid development of the Internet of Things(IoT)and modern information technology has led to the emergence of new types of *** poses a great potential danger to network ***,protecting against network attacks has become a pressing issue that requires urgent *** is crucial to find practical solutions to combat such malicious behavior.A network intrusion detection(NID)method,known as GMCE-GraphSAGE,was proposed to meet the detection demands of the current intricate network *** data is mapped into gaussian distribution,which helps to ensure that subsequent models can effectively learn the features of traffic *** conditional generative adversarial network(CGAN)can generate attack samples based on specified labels to create balanced traffic *** addition,we constructed a communication interaction graph based on the connection patterns of traffic *** E-GraphSAGE is designed to capture both the topology and edge features of the traffic *** it,global behavioral information is combined with traffic features,providing a solid foundation for classifying and *** on the UNSW-NB15 dataset demonstrate the great detection advantage of the proposed *** binary and multi-classification F1-score can achieve 99.36%and 89.29%,*** GMCE-GraphSAGE effectively improves the detection rate of minority class samples in the NID task.

关键词： network intrusion detection IoT deep learning

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Movement of ACC oxidase 3 mRNA from seeds to flesh promotes fruit ripening in apple

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Molecular Plant 2024年第8期17卷 1221-1235页

作者： Ting Wang Yi Zheng Chen Xu Yulin Deng xinyi Hao Zicheng Chu Ji Tian Yi Wang Xinzhong Zhang Zhenhai Han Ting Wu College of Horticulture China Agricultural UniversityBeijingChina Plant Science and Technology College Bioinformatics CenterBeijing University of AgricultureBeijingChina

Xenia,the phenomenon in which the pollen genotype directly affects the phenotypic characteristics of maternal tissues(i.e.,fruit ripening),has applications in crop production and ***,the underlying molecular mechanism has yet to be ***,we investigated whether mobile mRNAs from the pollen affect the ripening and quality-related characteristics of the fruit using cross-pollination between distinct Malus domestica(apple)*** demonstrated that hundreds of mobile mRNAs originating fromthe seeds are deliveredto *** themovementof one of these mRNAs,AcC oxidase 3(MdAco3),is coordinated with fruit *** acid treatment,which can cause plasmodesmal closure,blocks MdAcO3 movement,indicating that MdAcO3 transcripts may move through the *** assess the role of mobile MdAcO3 transcripts in apple fruit,we created MdACO3-GFP-expressing apple seeds using MdACO3-GFP-overexpressing pollen for pollination and showed that MdACO3 transcripts in the transgenic seeds move to the flesh,where they promote fruit ***,we demonstrated that MdAco3 can be transported from the seeds to fruit in the fleshy-fruited species tomato and *** results underscore the potential of mobile mRNAs from seeds to influence fruit characteristics,providing an explanation for the xenia ***,our findings highlight the feasibility of leveraging diverse pollen genomic resources,without resorting to genome editing,to improve fruitquality.

关键词： fruit ripening xenia ACO3 mobile RNA seed(to flesh)

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RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 581-593页

作者： xinyi WEI Conghui WANG Sangsang TANG Qian YANG Zhangjin SHEN Jiawei ZHU Xiaodong CHENG Xinyu WANG Xing XIE Junfen XU Weiguo LU Women's Reproductive Health Laboratory of Zhejiang Province Women�s HospitalZhejiang University School of MedicineHangzhou 310006China Department of Gynecologic Oncology Women�s HospitalZhejiang University School of MedicineHangzhou 310006China Cancer Center Zhejiang UniversityHangzhou 310058China Department of Obstetrics and Gynecology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology Hangzhou 310006China

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely *** investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of *** proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry *** xenograft models were established for the detection of *** results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC ***51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to *** prediction analysis revealed that the only target gene of RAD51B-AS1 was *** gene function experiments revealed that RAD51B exerts the same biological effects as *** experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in ***,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B ***51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

关键词： Ovarian cancer(OC) Long non-coding RNA(LncRNA) Metastasis Anoikis

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