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DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang yan Pan Haohao Zhang Kun Liu Jun Yu Linbin {2. Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang Shundong Cang Yuanyuan {2. yanglin Pan yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 732.1.of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western china(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) ***: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published ***: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P 1), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and ***: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

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Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2970-2983页

作者： Qi yang Bao Xue Fengjiang Liu Yongzhi lu Jielin Tang Mengrong yan Qiong Wu Ruyi Chen Anqi zhou Lijie Liu Junjun Liu Changbin Qu Qingxin Wu Muqing Fu Jiayi Zhong Jianwei Dong Sijie Chen Fan Wang Yuan zhou Jie Zheng Wei Peng Jinsai Shang Xinwen Chen Guangzhou National Laboratory Guangzhou 510005China State Key Laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhou 511436China Wuhan institute of Virology Chinese Academy of SciencesWuhan 430071China School of Basic Medical Sciences Guangzhou Medical UniversityGuangzhou 511436China GMUGIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 511436China Guangzhou institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Shanghai institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmaceutical Science and Technology Hangzhou lnstitute for Advanced StudyUCASHangzhou 310024China

Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the *** are currently no approved RSV-specific therapeutic small molecules *** high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion *** exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2.and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral ***-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion *** at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody ***,lonafarnib dose-dependently reduced the replication of RSV in BALB/c ***,lonafarnib could be a potential fusion inhibitor for RSV infection.

关键词： neutral metastable approved

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The relationship between compartment models and their stochastic counterparts:A comparative study with examples of the COVID-19 epidemic modeling

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Journal of Biomedical Research 2024年第2期38卷 175-188,I0016-I0018页

作者： Ziyu Zhao Yi zhou Jinxing Guan yan yan Jing Zhao Zhihang Peng Feng Chen yang Zhao Fang Shao Department of Biostatistics School of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China nanjing Hanwei Public Health Research institute Co. LtdNanjingJiangsu 210005China china International Cooperation Center for Environment and Human Health Center for Global HealthNanjing Medical UniversityNanjingJiangsu 211166China The Center of Biomedical Big Data and the Laboratory of Biomedical Big Data Nanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Deterministic compartment models(CMs)and stochastic models,including stochastic CMs and agent-based models,are widely utilized in epidemic ***,the relationship between CMs and their corresponding stochastic models is not well *** present study aimed to address this gap by conducting a comparative study using the susceptible,exposed,infectious,and recovered(SEIR)model and its extended CMs from the coronavirus disease 2.1. modeling *** demonstrated the equivalence of the numerical solution of CMs using the Euler scheme and their stochastic counterparts through theoretical analysis and *** on this equivalence,we proposed an efficient model calibration method that could replicate the exact solution of CMs in the corresponding stochastic models through parameter *** advancement in calibration techniques enhanced the accuracy of stochastic modeling in capturing the dynamics of ***,it should be noted that discrete-time stochastic models cannot perfectly reproduce the exact solution of continuous-time ***,we proposed a new stochastic compartment and agent mixed model as an alternative to agent-based models for large-scale population simulations with a limited number of *** model offered a balance between computational efficiency and *** results of this research contributed to the comparison and unification of deterministic CMs and stochastic models in epidemic ***,the results had implications for the development of hybrid models that integrated the strengths of both ***,the present study has provided valuable epidemic modeling techniques and their practical applications for understanding and controlling the spread of infectious diseases.

关键词： compartment models agent-based models compartment-agent mixed models comparative study COVID-19

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Enhanced activity and durability of FeCoCrMoCBY nanoglass in acidic hydrogen evolution reaction

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Journal of Materials Science & Technology 2024年第3期170卷 212-220页

作者： Mengyang yan Shuangqin Chen Shangshu Wu Xuechun {2. Shu Fu Di Wang Christian Kübel Horst Hahn Si Lan Tao Feng Herbert Gleiter institute of Nanoscience School of Material Science and EngineeringNanjing University of Science and TechnologyNanjing 210094China institute of Nanotechnology Karlsruhe Institute of TechnologyKarlsruhe 76021Germany

In the present work,a multi-element nanoglass(m-NG)of FeCoCrMoCBY is obtained first time by the laser ablation combined with inert gas condensation(laser-IGC)*** with the conventional rapid-quenched metallic glass(MG)with identical composition,the Fe-based m-NG demonstrates a superior performance as a self-supported electrocatalyst for hydrogen evolution reaction(HER)in acidic *** enhanced HER activity of m-NG is proposed to be closely related to its high en-ergy states,which is originated from the unique inhomogeneous nanostructures with a high density of low-coordinated ***,the Fe-based m-NG exhibits an outstanding comprehensive catalytic performance even beyond the commercial Pt/C catalyst in long-term test due to its self-optimization *** work not only opens the way to the preparation of m-NGs by the novel laser-IGC technique,but also makes a great contribution to developing low-cost,high-efficient,and super-durable HER electrocat-alysts in acidic environment.

关键词： Nanoglass Inert gas condensations High energy states Hydrogen evolution reactions

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Evolutionary Diversity of Coxsackievirus A6 Causing Severe Hand,Foot,and Mouth Disease—china,{2.-2.2.

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china CDC weekly 2024年第20期6卷 442-449页

作者： Huanhuan lu Jinbo Xiao Wenhui Wang Dongmei yan Tianjiao Ji Qian yang Haiyan Wei yanhua Du Yunting Zeng Jun Guo Jianhua Chen Hanri Zeng Yingying Liu Shuaifeng zhou Hong Ji Jianxing Wang Xiaofang zhou Yong Zhang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases World Health Organization Polio Reference Laboratory for the Western Pacific RegionKey Laboratory of Laboratory BiosafetyNational Health and Key Laboratory of Laboratory Biosafety of the National Health CommissionNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Linyi Center for Disease Control and Prevention Linyi CityShandong ProvinceChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina Shaanxi Provincial Center for Disease Control and Prevention Xi’an CityShaanxi ProvinceChina Hainan Provincial Center for Disease Control and Prevention Haikou CityHainan ProvinceChina Guizhou Provincial Center for Disease Control and Prevention Guiyang CityGuizhou ProvinceChina Gansu Provincial Center for Disease Control and Prevention Lanzhou CityGansu ProvinceChina Guangdong Provincial Center for Disease Control and Prevention Guangzhou CityGuangdong ProvinceChina Hebei Provincial Center for Disease Control and Prevention Shijiazhuang CityHebei ProvinceChina Hunan Provincial Center for Disease Control and Prevention Changsha CityHunan ProvinceChina Jiangsu Provincial Center for Disease Control and Prevention Nanjing CityJiangsu ProvinceChina Shandong Provincial Center for Disease Control and Prevention Jinan CityShandong ProvinceChina Yunnan Provincial Center for Disease Control and Prevention Kunming CityYunnan ProvinceChina

Introduction:Coxsackievirus A6(CVA6)has emerged as a significant pathogen responsible for severe cases of hand,foot,and mouth disease(HFMD).This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6,thereby assisting in its surveillance and ***:In this investigation,74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2.1. and *** VP1 gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST,DnaSP6,and ***:A significant portion(94.4%)of severe CVA6-associated HFMD cases(51 out of 54,with 2. lacking age information)were children under 5 years *** the 74 CVA6 strains analyzed,72.belonged to the D3a sub-genotype,while only two strains were D2.*** average genetic distance between VP1 sequences prior to 2.1. was 0.02.,which increased to 0.051 when compared to sequences *** population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2.1.-2.1.,2.1.-2.1.,and 2.1.-2.2.,resulting in the formation of 65 distinct *** with the MCC tree findings,transitioning between regional haplotypes required multiple base substitutions,showcasing an increase in population diversity during the evolutionary process(from 14 haplotypes in 2.1. to 55 haplotypes over the subsequent decade).Conclusions:CVA6,associated with severe HFMD,is evolving and presents a risk of outbreak ***,enhanced surveillance of severe HFMD is imperative.

关键词： thereby subsequent finding

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Mutual feedback between algal blooming and global warming

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Journal of Oceanology and Limnology 2024年第3期42卷 787-801页

作者： Jianrong MA Guijun yanG Xianfu ZHAO Boqiang QIN Kun SHAN Botian zhou yan ZENG Jingfu WANG Jingan CHEN Chongqing institute of Green and Intelligent Technology Chinese Academy of SciencesChongqing 400714China State Key Laboratory of Environmental Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550002China School of Environment and Ecology Jiangnan UniversityWuxi 214122China Key Laboratory of Ministry of Water resources for Ecological Impacts of Hydraulic-projects and Restoration of Aquatic Ecosystem Institute of HydroecologyMinistry of Water Resources&Chinese Academy of SciencesWuhan 430079China State Key Laboratory of Lake Science and Environment Nanjing Institute of Geography and LimnologyChinese Academy of SciencesNanjing 210008China

Global warming and algal blooms have been two of the most pressing problems faced by the world *** recent decades,numerous studies indicated that global warming promoted the expansion of algal ***,research on how algal blooms respond to global warming is *** warming coupled with eutrophication promoted the rapid growth of phytoplankton,which resulted in an expansion of algal *** blooms are affected by the combined effects of global warming,including increases in temperatures,CO_(2.concentration,and nutrient input to aquatic systems by extreme weather *** the growth of phytoplankton requires CO_(2.,they appear to act as a carbon ***,algal blooms will release CH4,CO_(2.,and inorganic nitrogen when they die and *** substrate nitrogen increases from decompose algal biomass,more N2. will be released by nitrification and *** comparison to CO_(2.,CH4has 2.-fold and N2. has 2.5-fold greenhouse ***,algal blooms in the polar regions may contribute to melting glaciers and sea ice(will release greenhouse gas,which contribute to global warming)by reducing surface albedo,which consequently would accelerate global ***,algal blooms and global warming could form feedback loops which prevent human survival and *** researches shall examine the mechanism,trend,strength,and control strategies involved in this mutual ***,it will promote global projects of environmental protection combining governance greenhouse gas emissions and algal blooms,to form a geoengineering for regulating the cycles of carbon,nitrogen,and phosphorus.

关键词： climate change carbon neutrality eutrophication greenhouse gas glaciers melting geoengineering

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Design and prototyping of the readout electronics for the transition radiation detector in the high energy cosmic radiation detection facility

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Nuclear Science and Techniques 2024年第4期35卷 189-199页

作者： Jie-Yu Zhu yang-zhou Su Hai-Bo yang Fen-Hua lu yan yang Xi-Wen Liu Ping Wei Shu-Cai Wan Hao-Qing Xie Xian-Qin Li Cong Dai Hui-Jun Hu Hong-Bang Liu Shu-Wen Tang Cheng-Xin Zhao institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China

The high energy cosmic-radiation detection(HERD)facility is planned to launch in 2.2. and scheduled to be installed on the china Space *** serves as a dark matter particle detector,a cosmic ray instrument,and an observatory for high-energy gamma rays.A transition radiation detector placed on one of its lateral sides serves dual purpose,(ⅰ)calibrating HERD's electromagnetic calorimeter in the TeV energy range,and(ⅱ)serving as an independent detector for high-energy gamma *** this paper,the prototype readout electronics design of the transition radiation detector is demonstrated,which aims to accurately measure the charge of the anodes using the SAMPA application specific integrated circuit *** electronic performance of the prototype system is eva{2.ated in terms of noise,linearity,and *** the presented design,each electronic channel can achieve a dynamic range of 0–100 fC,the RMS noise level not exceeding 0.15 fC,and the integral nonlinearity was2..To further verify the readout electronic performance,a joint test with the detector was carried out,and the results show that the prototype system can satisfy the requirements of the detector's scientific goals.

关键词： HERD Dark matter particle detection TRD Readout electronics SAMPA Data acquisition Performance test

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Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

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General Psychiatry 2024年第1期37卷 53-63页

作者： Xingqi Wu Yibing yan Panpan Hu lu Wang Yue Wu Pan Wu Zhi Geng Guixian Xiao Shanshan {2. Gongjun Ji Bensheng Qiu Ling Wei yanghua Tian Hesheng Liu Kai Wang Department of Neurology First ffiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina School of Mental Health and Psychological Sciences Anhui Medical UniversityHefeiAnhuiChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhuiChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhuiChina Department of Psychology and Sleep Medicine The Second Affliated Hospital of Anhui Medical UniversityHefeiAnhuiChina Center for Biomedical Imaging University of Science and Technology of ChinaHefeiAnhuiChina institute of Artificial Intlligence Hefei Comprehensive National Science CenterHefeiAnhuiChina Department of Neuroscience Medical University of South CarolinaCharlestonSouth CarolinaUSA

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for ***,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD *** We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with *** In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42.patients with AD for 14days every *** included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the *** were evaluated at baseline and after *** longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over *** The iTBS group maintained MoCA scores relative to the control group(t=3.2.,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale *** baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at ***,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p2.)and right(r=0.36,p=0.02.)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32.p=0.041)*** D

关键词： stimulation Alzheimer maintained

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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia yan Ruonian Liu Jiarui Li Zhuolong zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin {2. Guohui Wan Zunfu Ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of Hepatic Surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR Liver cancer

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Recent progress and strategies of cathodes toward polysulfides shuttle restriction for lithium-sulfur batteries

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Rare Metals 2024年第9期43卷 4132-4161页

作者： Xing-You Rao Shuang-Fei Xiang Jian zhou Zhen Zhang Xiang-Yu Xu Yuan-Yuan Xu Xin-Chi zhou Zheng-Dao Pan Su-Chong Tan Shi-Xing Dong zhou-lu Wang Yu-Tong Wu Yun-Lei zhou Xiang Liu Yi Zhang Shan Jiang School of Energy Sciences and Engineering Nanjing Tech University School of Materials Science and Engineering and institute of Smart Fiber Materials Zhejiang Sci-Tech University JiangSu Sailboat Petrochemical Co. Ltd Hangzhou institute of Technology Xidian University

Lithium-sulfur batteries(LSBs) have already developed into one of the most promising new-generation high-energy density electrochemical energy storage systems with outstanding features including high-energy density, low cost, and environmental friendliness. However, the development and commercialization path of LSBs still presents significant limitations and challenges, particularly the notorious shuttle effect triggered by soluble longchain lithium polysulfides(LiPSs), which inevitably leads to low utilization of cathode active sulfur and high battery capacity degradation, short cycle life, etc. Substantial research efforts have been conducted to develop various sulfur host materials capable of effectively restricting the shuttle effect. This review firstly introduces the fundamental electrochemical aspects of LSBs, followed by a comprehensive analysis of the mechanism underlying the shuttle effect in Li–S batteries and its profound influence on various battery components as well as the overall battery performance. Subsequently, recent advances and strategies are systematically reviewed, including physical confinement, chemisorption, and catalytic conversion of sulfur hosts for restricting LiPSs shuttle effects. The interplay mechanisms of sulfur hosts and LiPSs are discussed in detail and the structural advantages of different host materials are highlighted. Furthermore, key insights for the rational design of advanced host materials for LSBs are provided, and the upcoming challenges and the prospects for sulfur host materials in lithium-sulfur batteries are also explored.

关键词： Host Lithium-sulfur batteries Polysulfides Shuttle effect

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