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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

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DeciLS-PBO: an effective local search method for pseudo-Boolean optimization

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Frontiers of Computer Science 2024年第2期18卷 239-241页

作者： Luyu JIANG Dantong OUYANG Qi ZHANG Liming ZHANG College of Computer Science and Technology Jilin UniversityChangchun 130012China key laboratory of Symbolic Computation and Knowledge Engineering(Ministry of Education) Jilin UniversityChangchun 130012China

1 Introduction Local search method is a rising star for solving combinatorial optimization problems in recent years,and the state-of-the-art local search-based incomplete Maximum Satisfiability(MaxSAT)solversshowpromi... 详细信息

关键词： Max optimization local

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

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Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng state key laboratory of Genetic Evolution&Animal Models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Light/pH dual-responsive magnetic metal-organic frameworks composites for phosphorylated peptide enrichment

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Chinese Chemical Letters 2024年第7期35卷 222-226页

作者： Rui Wang He Qi Haijiao Zheng Qiong Jia College of Chemistry Jilin UniversityChangchun 130012China key laboratory for Molecular Enzymology and Engineering of Ministry of Education School of Life SciencesJilin UniversityChangchun 130012China

Metal-organic frameworks(MOFs)combined with specific ligands are highly adaptable smart materials that can respond to external and physiological *** this study,we introduced a pyridinyl zwitterionic ligand with light/pH dual response into magnetic MOF composite(Fe_(3)O_(4)@ZW-MOF)for enrichment of phosphorylated peptides for the first *** introduction of the developed ligand gives MOF material dual response *** stimulation affects the generation/disappearance of free radicals of the pyridine derivative,resulting in a change in the charge gradient of the zwitterion,and zwitterion can also regulate the p H of the solution by adding acid or ***,the reversible capture and release of phosphorylated peptides can be easily achieved by adjusting light and *** established phosphorylated peptide enrichment platform exhibits high sensitivity(detection limit of 1 fmol),high selectivity(β-casein:BSA,1:1000),and good reusability(7 cycles).In addition,the method was applied to the enrichment of phosphorylated peptides in complex systems(non-fat milk and human serum),demonstrating the feasibility of this method for phosphoproteom *** conclusion,the synthesized Fe_(3)O_(4)@ZW-MOF is a promising MOF material,which provides the possibility to advance the application of responsive MOFs materials in proteomics.

关键词： Light pH Dual-response Metal-organic frameworks Phosphorylated peptide

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基于最先进的光钟直接演示自旋压缩引起的计量增强

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Science Bulletin 2024年第10期69卷 1359-1361页

作者：陈景标于得水 state key laboratory of Advanced Optical Communication System and NetworkSchool of ElectronicsPeking UniversityBeijing 100871China National Time Service Center Chinese Academy of SciencesXi’an 710600China key laboratory of Time Reference and Applications Chinese Academy of SciencesXi’an 710600China

Benefiting from the recent progress in precise engineering of quantum states and sub-10 mHz linewidth lasers,the stability and accuracy of optical atomic clocks have reached and even exceeded the 1018 level,surpassing their microwave counterparts by over two orders of magnitude[1,2].These advances lead to an anticipated redefinition of the international system of units(SI)second in terms of an optical reference transition as early as 2026.

关键词： optical 光钟自旋压缩

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Aloin ameliorates cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating gut microbiota

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Food Science and Human Wellness 2024年

作者： Jingqian Su Jianbin Xiao Siyuan Chen Heng Zhao Xiaoni Zhang Zhihua Feng Kunsen Chen Biyun Guan Wenzhi Chen Youqiang Chen Duo Chen Qi Chen Fujian key laboratory of Innate Immune Biology Biomedical Research Center of South China College of Life Science Fujian Normal University The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the state Oceanic Administration Fujian key laboratory of Special Marine Bioresource Sustainable Utilization Southern Institute of Oceanography College of Life Science Fujian Normal University

Most Aloe species are used as new food or functional food ingredient. Even though widely known for its health benefits， the anti-inflammatory effects and underlying mechanisms of Aloin (Alo)， an anthraquinone compound isolated from plant species of the genus Aloe， remain unidentified. Here， we investigated the protective effects of Alo against cecal ligation and puncture (CLP)-induced sepsis and microflora in mice. Alo significantly improved CLP-induced sepsis and the survival rate of septic mice， downregulated the expression of proinflammatory factors， and decreased the infiltration of inflammatory cells in tissues. Alo upregulated the proportion of peritoneal macrophages， reduced the number of peritoneal bacteria， decreased the content of short-chain fatty acids and bile acids in the abdominal cavity， and suppressed TLR-2/4/NF-κB/NLRP3/Caspase-1/3/8 signaling. Furthermore， Alo altered the composition of the microbiome and promoted the growth of Lactobacillus， which showed a stronger anti-inflammatory effect. Whole-genome analysis identified the genes Saa3， Il10， Fpr1， and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis. Overall， our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.

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Seeing is believing: observation of migrasomes

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Biophysics Reports 2024年第2期10卷 67-81页

作者： Yuwei Huang Li Yu School of Basic Medical Sciences Translational Medicine Institute Xi'an Jiaotong University state key laboratory of Membrane Biology Tsinghua University-Peking University Joint Center for Life SciencesBeijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University

Migrasomes are a novel type of cell organelle that form on the retraction fibers at the rear of migrating cells. In recent years, numerous studies have unveiled the mechanisms of migrasome formation and have highlighted significant roles of migrasomes in both physiological and pathological *** upon the strategies outlined in published works and our own research experiences, we have compiled a comprehensive set of protocols for observing migrasomes. These step-by-step instructions encompass various aspects such as cell culture, labeling, imaging, in vitro reconstitution, and statistical analysis. We believe that these protocols serve as a valuable resource for researchers exploring migrasome biology.

关键词： Migrasome Labeling Imaging In vitro reconstitution

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Synthesis,structure,and thermal expansion in CaZrF6 with two polymorphs

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Nano Research 2024年第9期17卷 8618-8626页

作者： Peixian Zhang Yongqiang Qiao Kaiyue Zhao Qingjie Wang Huan Zhao Juan Guo Erjun Liang Tao Sun Jiangwei Zhang Qilong Gao key laboratory of Materials Physics of Ministry of Education School of Physics and MicroelectronicsZhengzhou UniversityZhengzhou 450052China College of Energy Materials and Chemistry Inner Mongolia UniversityHohhot 010021China First Affiliated Hospital of Dalian Medical University 222 Zhongshan RoadDalian 116011China Ordos laboratory Ordos 017000China

Due to the high structural flexibility and controllable thermal expansion,cubic double ReO_(3)-type negative thermal expansion(NTE)fluorides provide a solution for solving the prominent phenomenon of thermal expansion mismatch between ***,the expensive raw materials and complex synthesis steps limit its practical *** this work,we have designed a more advantageous method for the synthesis of NTE material CaZrF6,and it is expected to be generalized to the synthesis of other double ReO_(3)-***,a new orthorhombic phase CaZrF6 has been synthesized via this method in a lower *** the strong isotropic NTE of the cubic phase CaZrF6,the orthorhombic phase shows the strong anisotropic positive thermal expansion(PTE).The combined analysis of temperature-dependent X-ray diffraction(XRD),Raman spectra,and first-principles calculations shows that the low frequency phonon vibration mode with negative Grüneisen parameter in cubic CaZrF6 are strongly correlated with the transverse thermal vibration of F atoms and dominates the NTE of the material.

关键词： negative thermal expansion fluorides polymorph lattice dynamics first principles calculations

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Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3086-3109页

作者： Yihang Hao Haofan Wang Xianggen Liu Wenrui Gai Shilong Hu Wencheng Liu Zhuang Miao Yu Gan Xianghua Yu Rongjia Shi Yongzhen Tan Ting Kang Ao Hai Yi Zhao Yihang Fu Yaling Tang Ling Ye Jin Liu Xinhua Liang Bowen Ke state key laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China College of Computer Science Sichuan UniversityChengdu 610065China Department of Anesthesiology Laboratory of Anesthesia and Critical Care MedicineNational-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic *** primary challenge is to integrate diverse pharmacophores within a single-molecule *** address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local *** integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound *** framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent *** a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal *** insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome *** findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.

关键词： Multifunctional drugs Deep simulated annealing Molecule generation Articaine derivatives AI-enhanced drug discovery

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First identification of the oxazolidinone/phenicol resistance gene optrA in Streptococcus pluranimalium worldwide

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Journal of Integrative Agriculture 2024年第2期23卷 731-734页

作者： Kuan Zhao Longyu Zhou Shixia Zhang Wanjiang Zhang Yao Zhu College of Veterinary Medicine Hebei Agricultural UniversityBaoding 071001China state key laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Xinjiang Agricultural UniversityUrumqi 830052China

Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.

关键词： resistance prevalence

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