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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 vaccination.The 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 strain.Here,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-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 clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5.Together,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

Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM_(2.5)-aggravated COPD airway remodeling by enhancing myofibroblast differentiation

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Science China(life Sciences) 2024年第5期67卷 970-985页

作者： Huaqi Guo Luo Fei Hengyi Yu Yan li Yan Feng shaowei Wu Yan Wang The Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200011China School of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200020China Department of Occupational and Environmental Health Sciences School of Public HealthXi’an Jiao Tong University Health Science CenterXi’an 710049China

Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.

关键词： PM2.5 exosomal lncRNAs HOTAIRM1 chronic obstructive pulmonary disease

Review of the SBAS InSAR Time-series algorithms, applications, and challenges

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Geodesy and Geodynamics 2022年第2期13卷 114-126页

作者： shaowei li Wenbin Xu Zhiwei li School of Geosciences and Info-Physics Central South UniversityChangsha 410083China

In the past 30 years,the small baseline subset(SBAS)InSAR time-series technique has emerged as an essential tool for measuring slow surface displacement and estimating geophysical parameters.Because of its ability to monitor large-scale deformation with millimeter accuracy,the SBAS method has been widely used in various geodetic fields,such as ground subsidence,landslides,and seismic activity.The obtained long-term time-series cumulative deformation is vital for studying the deformation mecha-nism.This article reviews the algorithms,applications,and challenges of the SBAS method.First,we recall the fundamental principle and analyze the shortcomings of the traditional SBAS algorithm,which provides a basic framework for the following improved time series methods.Second,we classify the current improved SBAS techniques from different perspectives:solving the ill-posed equation,increasing the density of high-coherence points,improving the accuracy of monitoring deformation and measuring the multi-dimensional deformation.Third,we summarize the application of the SBAS method in monitoring ground subsidence,permafrost degradation,glacier movement,volcanic activity,landslides,and seismic activity.Finally,we discuss the difficulties faced by the SBAS method and explore its future development direction.

关键词： InSAR Small baseline subset Time-series InSAR Deformation

Energy dissipation mechanism and ballistic characteristic optimization in foam sandwich panels against spherical projectile impact

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Defence Technology（防务技术） 2024年第5期35卷 108-122页

作者： Jianqiang Deng Tao liu liming Chen Xin Pan Jingzhe Wang shaowei Zhu Weiguo li College of Aerospace Engineering Chongqing UniversityChongqing 400030China State Key Laboratory of Coal Mine Disaster Dynamics and Control Chongqing UniversityChongqing 400030China Chongqing Key Laboratory of Heterogeneous Material Mechanics Chongqing UniversityChongqing 400030China State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China

This study systematically examines the energy dissipation mechanisms and ballistic characteristics of foam sandwich panels(FSP)under high-velocity impact using the explicit non-linear finite element method.Based on the geometric topology of the FSP system,three FSP configurations with the same areal density are derived,namely multi-layer,gradient core and asymmetric face sheet,and three key structural parameters are identified:core thickness(t_(c)),face sheet thickness(t_(f))and overlap face/core number(n_(o)).The ballistic performance of the FSP system is comprehensively evaluated in terms of the ballistic limit velocity(BLV),deformation modes,energy dissipation mechanism,and specific penetration energy(SPE).The results show that the FSP system exhibits a significant configuration dependence,whose ballistic performance ranking is:asymmetric face sheet>gradient core>multi-layer.The mass distribution of the top and bottom face sheets plays a critical role in the ballistic resistance of the FSP system.Both BLV and SPE increase with tf,while the raising tcor noleads to an increase in BLV but a decrease in SPE.Further,a face-core synchronous enhancement mechanism is discovered by the energy dissipation analysis,based on which the ballistic optimization procedure is also conducted and a design chart is established.This study shed light on the anti-penetration mechanism of the FSP system and might provide a theoretical basis for its engineering application.

关键词： Sandwich panel Numerical simulation Ballistic resistance Specific penetration energy Energy analysis

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An underwater vest containing an antioxidant MXene hydrogel for sensitive recognition of fish locomotion

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Microsystems & Nanoengineering 2024年第2期10卷 115-131页

作者： Chengxiu Yang Jiafei Hu lihui liu shaowei Wu Mengchun Pan Yan liu Haomiao Wang Peisen li Qi Zhang Weicheng Qiu Huihui Luo College of Intelligence Science and Technology National University of Defense TechnologyChangsha410073China

The perception of fish locomotion is important for understanding their adaptive behaviors and ethological characteristics.However,the main strategy used for extracting fish attitudes involves the use of a vision-based monitoring system,which is limited in its range of observation and cannot perform tracking for long times.Here,we report the use of a wearable tagging electronic device,referred to as an underwater vest,to capture the surrounding flow field disturbances triggered by swimming or momentary postural changes.All of these goals were achieved by integrating a pair of pseudocapacitive pressure-sensing units and a flexible circuit board.Notably,additional conditions,such as variable hydraulic pressures and minimal changes in fish posture,require high stability and sensitivity of the sensing units.Thus,hybrid hydrogel electrodes were developed through cross-linking MXene with holey-reduced graphene oxide nanosheets and further modification with 1-ethyl-3-methylimidazolium dicyanamide ionic liquids,which increased the interfacial capacitance and long-term interfacial activity of the MXene.Consequently,the sensing unit exhibited ultrahigh sensitivity(S_(max)~136,207 kPa^(−1))in an aquatic environment for 60 days and superior high-pressure resolution(10 Pa)within a wide working range of 1 MPa.Ultimately,an underwater vest integrated with such sensing units clearly distinguished and recorded fish locomotion.We believe that the designed device may open avenues in flow field monitoring and ocean current detection and provide new insights into the development of sensitive underwater tagging.

关键词： underwater fish linking

Noncovalent cross-linked engineering hydrogel with low hysteresis and high sensitivity for flexible self-powered electronics

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Journal of Energy Chemistry 2024年第7期94卷 136-147页

作者： Hang Yuan shaowei Han Jia Wei Songwei li Peipei Yang Hao-Yang Mi Chuntai liu Changyu Shen National Engineering Research Center for Advanced Polymer Processing Technology Key Laboratory of Materials Processing and Mold(Ministry of Education)Zhengzhou UniversityZhengzhou450002HenanChina Yunnan TobaccoQuality Inspection&Supervision Station Kunming 650106YunnanChina

In this study,the hydrogel network was reinforced by covalent-like hydrogen bonding,and the strong binding ability of boron-nitrogen coordination served as the main driving force.Among them,acrylamide(AM)and 3-acrylamidophenylboronic acid(AAPBA)were the main body,and the numerous hydroxyl groups in the trehalose(Treh)molecule and other polymer groups formed strong hydrogen bonding interactions to improve the mechanical properties of the PAM/PAAPBA/Treh(PAAT)hydrogel and ensured the simplicity of the synthesis process.The hydrogel possessed high strain at break(1239%),stress(64.7 kPa),low hysteresis(100%to 500%strain,corresponding to dissipation energy from 1.37 to 7.80 kJ/m^(3)),and outstanding cycling stability(retained more than 90%of maximum stress after 200 ten-sile cycles).By integrating carbon nanotubes(CNTs)into PAAT hydrogel(PAATC),the PAATC hydrogel with excellent strain response performance was successfully constructed.The PAATC conductive hydro-gel exhibited high sensitivity(gauge factor(GF)=10.58 and sensitivity(S)=0.304 kPa^(-1)),wide strain response range(0.5%-1000%),fast response time(450 ms),and short recovery time(350 ms),excellent fatigue resistance,and strain response stability.Furthermore,the PAATC-based triboelectric nanogener-ator(TENG)displayed outstanding energy harvesting performance,which shows its potential for appli-cation in self-powered electronic devices.

关键词： Low hysteresis Covalent-like hydrogen bonding Boron-nitrogen coordination Hydrogel sensor Triboelectric nanogenerator

Advances in extracellular vesicle-based combination therapies for spinal cord injury

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Neural Regeneration Research 2024年第2期19卷 369-374页

作者： Tingting Wang Guohao Huang Zhiheng Yi Sihan Dai Weiduan Zhuang shaowei Guo Department of Neurology The First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina Department of Biomedical Engineering Shantou UniversityShantouGuangdong ProvinceChina

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

关键词： biomaterials combination therapy drug delivery exosomes extracellular vesicles functional recovery hydrogels scaffolds spinal cord injury tissue engineering

Current progress in the development of prophylactic and therapeutic vaccines

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Science China(life Sciences) 2023年第4期66卷 679-710页

作者： Tingting li Ciying Qian Ying Gu Jun Zhang shaowei li Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases Xiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China The Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences Xiamen 361102China

Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population.Emerging infectious diseases and outbreaks pose new challenges for vaccine development,requiring the rapid design and production of safe and effective vaccines against diseases with limited resources.Here,we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer,providing a comprehensive overview of recent advances in eight different vaccine forms(live attenuated vaccines,inactivated vaccines,polysaccharide and polysaccharide conjugate vaccines,recombinant subunit vaccines,virus-like particle and nanoparticle vaccines,polypeptide vaccines,DNA vaccines,and m RNA vaccines)and the therapeutic vaccines against five solid tumors(lung cancer,breast cancer,colorectal cancer,liver cancer and gastric cancer),three infectious diseases(human immunodeficiency virus,hepatitis B virus and human papillomavirus-induced diseases)and three common chronic diseases(hypertension,diabetes mellitus and dyslipidemia).We aim to provide new insights into vaccine technologies,platforms,applications and understanding of potential next-generation preventive and therapeutic vaccine technologies,paving the way for the vaccines design in the future.

关键词： prophylactic vaccine therapeutic vaccine immune response infectious diseases cancers chronic diseases

Improvement of hydrogen permeation barrier performance by iron sulphide surface films

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International Journal of Minerals,Metallurgy and Materials 2023年第9期30卷 1792-1800页

作者： Pengpeng Bai shaowei li Jie Cheng Xiangli Wen Shuqi Zheng Changfeng Chen Yu Tian State Key Laboratory of Tribology Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China School of Mechanical Engineering University of Science and Technology BeijingBeijing 100083China School of Mechanical Electronic&Information Engineering China University of Mining and Technology-BeijingBeijing 100083China State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing 102249China

Fe–S compounds with hexagonal crystal structure are potential hydrogen permeation barrier during H2S corrosion. Hexagonal system Fe–S films were prepared on carbon steel through corrosion and CVD deposition, and the barrier effect of different Fe–S films on hydrogen permeation was tested using electrochemical hydrogen permeation method. After that, the electrical properties of Fe–S compound during phase transformation were measured using thermoelectric measurement system. Results show that the mackinawite has no obvious barrier effect on hydrogen penetration, as a p-type semiconductor, and pyrrhotite (including troilite) has obvious barrier effect on hydrogen penetration,as an n-type semiconductor. Hydrogen permeation tests showed peak permeation performance when the surface was deposited with a continuous film of pyrrhotite (Fe_(1–x)S) and troilite. The FeS compounds suppressed hydrogen permeation by the promotion of the hydrogen evolution reaction, semiconducting inversion from p-to n-type, and the migration of ions at the interface.

关键词： hydrogen permeation barrier iron sulfide pyrrhotite semiconductor