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Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

Science China(life Sciences) 2024年第6期67卷 1170-1182页

作者： Jiaming liu liangkui li Dijin xu Yuqi li Tao Chen Yeyang liu Yuqian Bao Yan Wang Longyan Yang Peng li li xu State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for life Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Shanghai Qi Zhi Institute Shanghai 200232China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou UniversityZhengzhou 450001China Department of Physiology School of Basic Medical SciencesGannan Medical UniversityGanzhou 341000China Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai 200025China Center for Endocrine Metabolism and Immune Diseases Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China Beijing Key Laboratory of Diabetes Research and Care Beijing 101149China

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain elusive.Rab18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and maturation.In the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice.Rab18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype mice.When subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in SAT.In contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic inflammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid toxicity.Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT.In conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关键词： Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) lipotoxicity ER stress ectopic lipid storage LD-ER contact

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Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period

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Signal Transduction and Targeted Therapy 2024年第1期9卷 19-35页

作者： Danyi Ao xuemei He Jian liu li xu State Key Laboratory of Biotherapy West China HospitalSichuan University610041 SichuanPeople’s Republic of China

The spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in significant casualties and put immense strain on public health systems worldwide,leading to economic recession and social unrest.In response,various prevention and control strategies have been implemented globally,including vaccine and drug development and the promotion of preventive measures.Implementing these strategies has effectively curbed the transmission of the virus,reduced infection rates,and gradually restored normal social and economic activities.However,the mutations of SARS-CoV-2 have led to inevitable infections and reinfections,and the number of deaths continues to rise.Therefore,there is still a need to improve existing prevention and control strategies,mainly focusing on developing novel vaccines and drugs,expediting medical authorization processes,and keeping epidemic surveillance.These measures are crucial to combat the Coronavirus disease(COVID-19)pandemic and achieve sustained,long-term prevention,management,and disease control.Here,we summarized the characteristics of existing COVID-19 vaccines and drugs and suggested potential future directions for their development.Furthermore,we discussed the COVID-19-related policies implemented over the past years and presented some strategies for the future.

关键词： prevention sustained approval

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A Review of Hybrid Cyber Threats Modelling and Detection Using Artificial Intelligence in IIoT

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1233-1261页

作者： Yifan liu Shancang li Xinheng Wang li xu School of Computer Science and Informatics Cardiff UniversityCardiffCF244AGUK Department of Mechatronics and Robotics Xi’an Jiaotong-Liverpool UniversitySuzhou215123China Department of Information Technology&Decision Sciences Old Dominion UniversityNorfolk23529USA

The Industrial Internet of Things(IIoT)has brought numerous benefits,such as improved efficiency,smart analytics,and increased automation.However,it also exposes connected devices,users,applications,and data generated to cyber security threats that need to be addressed.This work investigates hybrid cyber threats(HCTs),which are now working on an entirely new level with the increasingly adopted IIoT.This work focuses on emerging methods to model,detect,and defend against hybrid cyber attacks using machine learning(ML)techniques.Specifically,a novel ML-based HCT modelling and analysis framework was proposed,in which L1 regularisation and Random Forest were used to cluster features and analyse the importance and impact of each feature in both individual threats and HCTs.A grey relation analysis-based model was employed to construct the correlation between IIoT components and different threats.

关键词： Cyber security Industrial Internet of Things artificial intelligence machine learning algorithms hybrid cyber threats

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Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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Neural Regeneration Research 2025年第2期20卷 354-365页

作者： li xu Huiming xu Changyong Tang Department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

关键词： aquaporin-4 experimental model neuromyelitis optica spectrum disorder pathogenesis

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Electronic structure and spin state regulation of vanadium nitride via a sulfur doping strategy toward flexible zinc-air batteries

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Journal of Energy Chemistry 2024年第2期89卷 239-249,I0007页

作者： Daijie Deng Honghui Zhang Jianchun Wu Xing Tang Min ling Sihua Dong li xu Henan li Huaming li Institute for Energy Research Institute of Quantum and Sustainable TechnologySchool of Chemistry and Chemical EngineeringSchool of Materials Science and EngineeringJiangsu Province and Education Ministry Co-Sponsored Synergistic Innovation Center of Modern Agricultural EquipmentJiangsu UniversityZhenjiang 212013JiangsuChina Key Laboratory of Radio Frequency and Micro-Nano Electronics of Jiangsu Province Nanjing 210023JiangsuChina Zhenjiang Kangyuan Electrical Appliance Co. Ltd.Zhenjiang 212013JiangsuChina College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027ZhejiangChina YTO Group Corporation Dongfanghong(Henan)Agricultural Service Technology Co. Ltd.Luoyang 471033HenanChina

Owing to the distinctive structural characteristics,vanadium nitride(VN)is highly regarded as a catalyst for oxygen reduction reaction(ORR)in zinc-air batteries(ZABs).However,VN exhibits limited intrinsic ORR activity due to the weak adsorption ability to O-containing species.Here,the S-doped VN anchored on N,S-doped multi-dimensional carbon(S-VN/Co/NS-MC)was constructed using the solvothermal and in-situ doping methods.Incorporating sulfur atoms into VN species alters the electron spin state of vanadium in the S-VN/Co/NS-MC for regulating the adsorption energy of vanadium sites to oxygen molecules.The introduced sulfur atoms polarize the V 3d_(z)^(2) electrons,shifting spin-down electrons closer to the Fermi level in the S-VN/Co/NS-MC.Consequently,the introduction of sulfur atoms into VN species enhances the adsorption energy of vanadium sites for oxygen molecules.The*OOH dissociation transitions from being unspontaneous on the VN surface to a spontaneous state on the S-doped VN surface.Then,the ORR barrier on the S-VN/Co/NS-MC surface is reduced.The S-VN/Co/NS-MC demonstrates a higher half-wave potential and limiting current density compared to the VN/Co/N-MC.The S-VN/Co/NS-MC-based liquid ZABs display a power density of 195.7 m W cm^(-2),a specific capacity of 815.7 m A h g^(-1),and a cycling stability exceeding 250 h.The S-VN/Co/NS-MC-based flexible ZABs are successfully employed to charge both a smart watch and a mobile phone.This approach holds promise for advancing the commercial utilization of VN-based catalysts in ZABs.

关键词： S-doped VN Electronic structures Spin state regulation Oxygen reduction reaction Zinc-air batteries

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Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

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World Journal of Hepatology 2024年第5期16卷 703-715页

作者： li xu Yu-Hong Fan Xiao-Jing Zhang Lan Bai State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases Gannan Innovation and Translational Medicine Research InstituteGannan Medical UniversityGanzhou 341000China School of Basic Medical Sciences Wuhan UniversityWuhan 430060China

Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits.Its complexity stems from genetic predisposition,environmental influences,and metabolic factors.Epigenetic processes govern various cellular functions such as transcription,chromatin structure,and cell division.In NAFLD,these epigenetic tendencies,especially the process of histone methylation,are intricately intertwined with fat accumulation in the liver.Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis.While early-stage NAFLD is reversible,its progression to severe stages becomes almost irreversible.Therefore,early detection and intervention in NAFLD are crucial,and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

关键词： Non-alcoholic fatty liver disease Mechanism Histone methylation Methyltransferases Demethytrasferases Epigenetic modification Adipogenesis

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Regulating atomic Fe-Rh site distance for efficient oxygen reduction reaction

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Science China Chemistry 2024年第4期67卷 1352-1359页

作者： Tong liu Yudan Chen Airong xu Xiaokang liu Dong liu Sicheng li Hui Huang li xu Shuaiwei Jiang Qiquan Luo Tao Ding Tao Yao National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Key Laboratory of Precision and Intelligent Chemistry Hefei National Research Center for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230026China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China

Exploring the atomic interaction mechanisms of dense single-atom catalysts(SACs)is of great significance for their application in oxygen reduction reaction(ORR).However,the intrinsic mechanism of the site-distance effect on the catalytic performance has been largely ignored.Here,we demonstrate the site-distance effect of Fe-Rh_(x)@NC catalysts in ORR theoretically and experimentally.Bader charge analysis reveals that the strong interaction between Fe and Rh atoms at a certain atomic distance(dFe-Rh)alters the catalytic electronic structure,facilitating the optimization of catalyst adsorption strength.Motivated by the theoretical calculations,we designed and synthesized the Fe-Rhx@NC catalysts through a spatial confinement strategy.The characterization results prove that the Fe-Rh_(2)@NC has the optimal d_(Fe-Rh),which improves its intrinsic ORR activity,providing a half wave potential of 0.91 V,higher than that of the commercial Pt/C(0.86 V).This study emphasizes the importance of determining the basic mechanism of the site-distance effect in dissimilar metal atoms catalysts,which is conducive to the design of efficient catalyst systems for practical applications.

关键词： Density functional theory single-atom catalyst in-situ encapsulating site-distance effect oxygen reduction reaction

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Efficacy and Safety of Chinese Herbal Medicines Combined with Chemical Drugs for Alzheimer's Disease:A Systematic Review and Meta-Analysis

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 1-13页

作者： li xu Wen-Jun Chen Cai-Jun Tian Yan Zhang Yan Ma Tian-Hao li Hong-Jie liu Zhe Zhang Department of the First College English College of Foreign LanguageShandong University of Traditional Chinese MedicineJinanChina Department of Oncology Linyi People's HospitalLinyiChina Department of Internal Medicine of Traditional Chinese Medicine The First Clinical CollegeShandong University of Traditional Chinese MedicineJinanChina Department of Chinese Materia Medica College of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina Department of Medicinal Chemistry College of PharmacyShandong University of Traditional Chinese MedicineJinanChina Community Healthcare Center Shenzhen Traditional Chinese Medicine HospitalShenzhenChina Department of Fundamentals of Traditional Chinese Medicine School of Traditional Chinese MedicineJinan UniversityGuangzhouChina Shandong Co-Innovation Center of Classic TCM Formula College of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina

Objective:To evaluate the efficacy and safety of Chinese herbal medicines(CHMs)combined with chemical drugs for the treatment of Alzheimer's disease(AD).Materials and Methods:Databases were searched to retrieve randomized controlled trials(RCTs)of CHMs combined with tacrine,galantamine,rivastigmine,donepezil,or memantine,following strict inclusion and exclusion criteria.Only research papers published in English,Chinese,and Japanese were considered.The primary outcome was the mini-mental state examination(MMSE)score and the secondary outcomes were AD assessment scale cognitive subscale(ADAS-Cog)score and safety evaluation.Meta-analysis was carried out using Rev Man 5.3 and subgroup analysis was conducted to identify the sources of heterogeneity.Results:A total of 15 RCTs with 1386 participants were included in this study.Only donepezil was used in the retrieved literature.Meta-analyses showed that the combination of CHMs with donepezil led to significant improvement in the MMSE score(Z=9.45;Plieved adverse events such as insomnia(risk ratio[RR]=0.20,95%CI:0.06-0.68;P=0.01)and hive(RR=0.10;95%CI:0.01-0.73;P=0.02).Conclusions:The combination of CHMs with a chemical drug like donepezil led to significant improvements in patient cognition as well as a better safety profile when compared to the application of a chemical drug alone.

关键词： Alzheimer's disease Chinese herbal medicine donepezil memantine meta-analysis randomized controlled trials rivastigmine

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Application and Satisfaction Analysis of Humanized Quality Nursing Intervention in the Care of Patients with Critical Respiratory Failure

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Journal of Clinical and Nursing Research 2024年第5期8卷 200-205页

作者： li xu Department of Critical Care Medicine Shiyan Yunyang District People’s HospitalShiyan 442500HubeiChina

Objective:To implement humanized quality care in critical respiratory failure nursing,observe the effect,and analyze the satisfaction.Methods:80 patients with severe respiratory failure were divided into 40 cases per group(admitted from February 2022 to December 2023)by double-blind method,the control group performed routine care,and the observation group was given humanized quality care.Results:After the nursing care,two respiratory function indexes of the observation group were lower than those of the control group,and two pulmonary function indexes were higher than those of the control group(Plication situation,the incidence rate of the observation group was lower(Plication of a humanized quality nursing intervention model in the care of critical respiratory failure can actively improve patients’respiratory status and lung function,reduce complications,and satisfy patients.

关键词： Critical respiratory failure Humanized quality nursing Nursing satisfaction

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Selenium Differentially Regulates Flavonoid Accumulation and Antioxidant Capacities in Sprouts of Twenty Diverse Mungbean(Vigna radiata(L.)Wilczek)Genotypes

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Phyton-International Journal of Experimental Botany 2024年第3期93卷 611-625页

作者： Fenglan Zhao Jizhi Jin Meng Yang Franklin Eduardo Melo Santiago Jianping xue li xu Yongbo Duan Anhui Provincial Engineering Laboratory for Efficient Utilization of Featured Resource Plants College of Life SciencesHuaibei Normal UniversityHuaibei235000China Department of Soil Science Federal Institute of PiauiUruçuíPiauí64860-000Brazil The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang550003China

Seed germination with selenium(Se)is promising for producing Se-biofortiﬁed foods.Mungbean(Vigna radiata(L.)Wilczek)sprout is freshly eaten as a salad dressed with sauce,making it superior for Se biofortiﬁcation.Since the Se safety range for the human body is extremely narrow,it is imperative to evaluate the genotypic responses of mungbean sprouts to Se.This study evaluated the Se enrichment capacity and interaction withﬂavonoids and antioxidant systems in sprouts of 20 mungbean germplasms.Selenium treatment was done by immersing mung-bean seeds in 20μM sodium selenite solution for 8 h.Afterward,the biomass,Se amounts,ﬂavonoid(particularly vitexin and isovitexin)contents,antioxidant capacity,and key biosynthetic gene expressions were measured.Sprout Se content was 2.0-7.0μg g^(-1) DW among the 20 mungbean germplasms.Selenium treatment differentially affected the biomass,totalﬂavonoid,vitexin,isovitexin,antioxidant enzyme activities,and antioxidant capacities of the mungbean germplasms.Eight germplasms showed increased biomass(plization.

关键词： Antioxidant capacity gene expression genotypic variation isovitexin vitexin selenium

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