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Genes & Diseases 2024年第1期11卷 19-22页

作者： Zhenhai Li Wenchao Xu Feng Chen Jun Zhang Wei-Guo Zhu Guangdong Key laboratory of Genome Instability and Human Disease Prevention Department of Biochemistry and Molecular BiologyShenzhen University School of MedicineShenzhenGuangdong 518055China School of Pharmaceutical Sciences Shenzhen University Health Science CenterShenzhenGuangdong 518055China Base for International Science and Technology Cooperation:Carson Cancer Stem Cell vaccines R&D Center International Cancer CenterShenzhen University Health Science CenterShenzhenGuangdong 518055China Shenzhen Bay laboratory Shenzhen University School of MedicineShenzhenGuangdong 518055China Marshall laboratory of Biomedical Engineering Shenzhen University School of MedicineShenzhenGuangdong 518055China

Etoposide is widely used for cancer chemotherapy in the ***,long-term etoposide treatment can lead to adverse effects or drug *** improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer ***,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.

关键词： etoposide damage cancer

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key laboratory for Quality Monitoring and Evaluation of vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key laboratory of vaccines for Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine laboratory Xiamen 361102China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

Cationic engineered nanodiamonds for efficient antibacterial surface with strong wear resistance

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Nano Research 2024年第3期17卷 939-948页

作者： Fu-Kui Li Wen-Bo Zhao Yong Wang Wen-Tao Huang Ya-Lun Ku Hang Liu Rui Guo Hui-Hui Yu Kai-Kai Liu Chong-Xin Shan Henan Key laboratory of Diamond Optoelectronic Materials and Devices Key Laboratory of Materials PhysicsMinistry of Educationand School of Physics&MicroelectronicsZhengzhou UniversityZhengzhou 450052China

The spread of diseases caused by bacterial adhesion and immobilization in public places constitutes a serious threat to public *** of bacteria spread by the construction of an antibacterial surface takes precedence over post-infection ***,we demonstrate an effective antibacterial surface with strong wear resistance by constructing cationic engineered nanodiamonds(C-NDs).The C-NDs with positive surface potentials interact effectively with bacteria through electrostatic interactions,where the C-NDs act on the phospholipid bilayer and lead to bacterial membrane collapse and rupture through hydrogen bonding and residual surface oxygen-containing reactive *** this case,bactericidal rate of 99.99%and bacterial biofilm inhibition rate of more than 80%can be achieved with the C-NDs concentration of 1 mg/*** addition,the C-NDs show outstanding antibacterial stability,retaining over 87%of the antibacterial effect after stimulation by adverse environments of heat,acid,and external ***,an antibacterial surface with high wear resistance obtained by integrating C-NDs with commercial plastics has been *** antibacterial surface with a mass fraction of 1 wt.%C-NDs improved abrasion resistance by 3981 times,with 99%killing of adherent *** work provides an effective strategy for highly efficient antibacterial wear-resistant surface,showing great practical applications in public health environments.

关键词： antibacterial surface cationic engineered nanodiamonds wear-resistant

Essential oils improve nursery pigs' performance and appetite via modulation of intestinal health and microbiota

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Animal Nutrition 2024年第1期16卷 174-188页

作者： Bi-Chen Zhao Tian-Hao Wang Jian Chen Bai-Hao Qiu Ya-Ru Xu Jin-Long Li College of Veterinary Medicine Northeast Agricultural University Heilongjiang Key laboratory for laboratory Animals and Comparative Medicine Northeast Agricultural University Key laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment Northeast Agricultural University

Optimal intestinal health and functionality are essential for animal health and performance,and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control *** the potential of essential oil (EO) in improving animal performance and improving feed palatability,we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and *** (100 mg/kg),carvacrol (100 mg/kg),and their mixtures(including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol) were supplemented into the diets of 240 nursery pigs for 42 d,and data related to performance were ***,the influence of EO on intestinal health,appetite and gut microbiota and their correlations were *** supplementation increased (Pbacterial structure and appetite-related *** findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving int

关键词： Nursery pig Essential oil Intestinal health Appetite Microbiota

表位结构指导免疫优势转移的HPV交叉疫苗的理性设计

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Science Bulletin 2024年第4期69卷 512-525页

作者：王致萍王大宁陈洁高飞江雅楠杨澄宇钱兹英池鑫张姝玥许钰洁卢一涵沈璟佳张承宗李瑾瑾周立志李婷婷郑清炳俞海李少伟夏宁邵顾颖 State Key laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCollaborative Innovation Center of Biologic ProductsNational Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen 361102China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China Xiamen Innovax Biotech Co. Ltd.Xiamen 361022China

In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance *** immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization ***,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly *** this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and *** nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface *** interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and *** Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to *** swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI ***,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human *** approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

关键词： Human papillomavirus Cross-neutralization antibody Immunodominance shift Vaccine design

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Advanced nano-based strategies for mRNA tumor vaccine

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Acta Pharmaceutica Sinica B 2024年第1期14卷 170-189页

作者： Yangqi Qu Jingjing Xu Tong Zhang Qinjun Chen Tao Sun Chen Jiang Key laboratory of Smart Drug Delivery(Ministry of Education) Minhang HospitalState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune *** with the technological breakthroughs in genetic engineering and delivery systems,messenger ribonucleic acid(mRNA)technology has achieved unprecedented development and application over the last few years,especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic,which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in ***,unlike infectious disease vaccines,which mainly induce humoral immunity,tumor vaccines also need to activate potent cellular immunity to control tumor growth,which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells(APCs).Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges,as well as future considerations of mRNA tumor vaccines and their delivery systems.

关键词： mRNA vaccine Nanoparticle Tumor vaccine Delivery system Stability Targeting Transfection Immunogenicity

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Peroxidase-like active Cu-ZIF-8 with rich copper(I)-nitrogen sites for excellent antibacterial performances toward drug-resistant bacteria

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Nano Research 2024年第8期17卷 7427-7435页

作者： Xiaoze Wang Hui Wang Jingkun Zhang Ning Han Wenjun Ma Donghai Zhang Mingshui Yao Xianliang Wang Yunfa Chen State Key laboratory of Mesoscience and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China University of the Chinese Academy of Sciences Beijing 100049China laboratory of Theoretical and Computational Nanoscience CAS Key Laboratory of Nanosystem and Hierarchial FabricationCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China China CDC Key laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China

bacterial pathogens pose a serious threat to human health,and there is an urgent need to develop highly effective antibacterial materials to eliminate the increasingly serious contamination of drug-resistant ***,a Cu-doped ZIF-8 particle with unsaturated copper exhibits high peroxidase-like activity.99.998%antibacterial efficiency against *** can be achieved for 30 min at a low concentration of 50μg·mL^(−1),as well as complete sterilization against ***(up to 8 log).99.999%antibacterial efficiency against Methicillin-resistant Staphylococcus aureus can be achieved,performing orders of magnitude higher than *** mechanism shows that the unsaturated Cu-Nx sites are enzyme-like active centers,which could promote the consumption of bacteria reducing substances by H_(2)O_(2),and the generated*OH further aggravates bacterial oxidative stress and membrane *** importantly,the oxidation activity of adsorbed oxygen species on Cu-ZIF-8 is enhanced by charge transfer and structural changes between the ligand and copper center like natural ***-doped ZIF-8 with peroxidase-like activity shows great potential in antibacterial application and the revealed catalytic mechanism is helpful for understanding the high antibacterial activity of nanoparticles with Cu-Nx sites.

关键词： Cu-doped ZIF-8 peroxidase-like reactive oxygen species(ROS) catalytic mechanism antibacterial activity

Modularized viromimetic polymer nanoparticle vaccines(VPNVaxs) to elicit durable and effective humoral immune responses

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National Science Review 2024年第3期11卷 200-214页

作者： Zichao Huang Xinyu Zhuang Liping Liu Jiayu Zhao Sheng Ma Xinghui Si Zhenyi Zhu Fan Wu Ningyi Jin Mingyao Tian Wantong Song Xuesi Chen Key laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Applied Chemistry and Engineering University of Science and Technology of China Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Jilin Biomedical Polymers Engineering laboratory State Key laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Virus-like particle(VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However,the time-consuming and complicated processes in establishing a current recombinant-protein–based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine(VPNVax), with subunit receptor-binding domain(RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid(PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%–25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

关键词： vaccine polymer nanomaterials SARS-CoV-2

Ultrastable graphene isolated Au Ag nanoalloy for SERS biosensing and photothermal therapy of bacterial infection

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Chinese Chemical Letters 2024年第3期35卷 198-203页

作者： Shengkai Li Zhiyang Li Qing Hao Shen Wang Yanxia Yang Jieqiong Xu Zhiwei Yin Liang Zhang Zhuo Chen Molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China School of Chemistry and Chemical Engineering/Guangzhou Key laboratory for Clean Energy and Materials/Key laboratory for Water Quality and Conservation of the Pearl River Delta Ministry of EducationGuangzhou UniversityGuangzhou 510006China

Plasmonic metal nanomaterials with intrinsic surface–enhanced Raman scattering(SERS)and photothermal properties,especially AuAg nanoalloys with both the outstanding merits of Au and Ag nanocrystals,show huge application prospects in bacterial ***,the direct exposure of AuAg nanoalloys in external conditions probably cause undesirable reactions and poisonous metal ion leakage during SERS detection and photothermal antibacterial therapy process,which severely hinder bacterial theranostics ***,we report an ultrastable graphene–isolated AuAg nanoalloy(GAA)with AuAg core confined in few–layer graphitic shell as a versatile platform for bacterial detection and *** encapsulation of graphene ensures the good stability of AuAg core,that its superior SERS and photothermal properties are therefore further *** is used for SERS detection of two vital bacterial biomarkers(including corrosive cyanide and pyocyanin),exhibiting good SERS quantitative and multiplexing *** is further used for photothermal antibacterial therapy application,and ultrahigh antibacterial efficacies for both Gram–negative Escherichia coli and Gram–positive Staphylococcus aureus are achieved under 808 nm laser *** work proposes a valuable method to develop robust bacterial theranostic platform.

关键词： Localized surface plasmon resonance Graphitic shell isolated AuAg nanoalloy(GAA) Surface–enhanced Raman scattering(SERS) bacterial biomarker detection Photothermal antibacterial therapy

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