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Zhuifeng tougu capsules (追风透骨胶囊) improve rheumatoid arthritis symptoms in rats by regulating the toll-like receptor 2/4-nuclear factor kappa-B signaling pathway

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Journal of Traditional Chinese Medicine 2021年第3期41卷 447-454页

作者： GONG Hui KUANG Gaoyan wu yongrong LU Fangguo DENG Yihui HE Yanlin WANG Hengxin Department of oncology Hunan university of Chinese medicine integrated Chinese and Western Affiliated HospitalChangsha 410007China Department of orthopedics the First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410007China Postdoctoral Research station Hunan University of Chinese MedicineChangsha 410208China Postdoctoral Research Worksta-tion Hinye Pharmaceutical Co.Ltd.Hinye Pharmaceutical Co.Ltd.Changsha 410331China

OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules(追风透骨胶囊, ZFTG) in the treatment of rheumatoid arthritis(RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B(TLR2/4-NF-κB) signaling pathway.METHODS: TypeⅡ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-,and low-dose ZFTG groups. The methotrexate(MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index(AI) score were measured. The production of C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), and rheumatoid factors(RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by Western blotting, and the m RNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction.RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased(P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident(P < 0.01).CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway.

关键词： arthritis rheumatoid wind-cold-dampness syndrome toll-like receptors NF-kappa B Zhuifeng tougu capsule

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补肾活血汤治疗膝骨关节炎的作用机制研究进展

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基层中医药 2024年第1期3卷 118-124页

作者：瞿陈晨邝高艳李若琪罗佳邱明霞梁智蓉吴泳蓉湖南中医药大学湖南长沙410208 湖南中医药大学第一附属医院湖南长沙410007

补肾活血汤是治疗膝骨关节炎的临床常用方剂,对膝骨关节炎的疗效确切且不良反应少。近年来,针对补肾活血汤治疗膝骨关节炎的分子机制的研究成为热点,很多学者的研究显示补肾活血汤可以通过调控炎症因子、促进软骨细胞增殖分化及抑制软... 详细信息

补肾活血汤是治疗膝骨关节炎的临床常用方剂,对膝骨关节炎的疗效确切且不良反应少。近年来,针对补肾活血汤治疗膝骨关节炎的分子机制的研究成为热点,很多学者的研究显示补肾活血汤可以通过调控炎症因子、促进软骨细胞增殖分化及抑制软骨基质降解等途径发挥作用。文章筛选了近年来的相关文献,对补肾活血汤治疗膝骨关节炎机制的研究进展做一综述。

关键词：补肾活血汤膝骨关节炎机制综述

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Therapeutic genome editing of an aberrant splice site inβ-thalassemia by CRISPR/Cas9 with multiple sgRNAs

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Genes & Diseases 2024年第1期11卷 15-18页

作者： Fei Yang Shuqian Xu Chao Huang Zhiqiang Shao Yuefen Hu Yang Yang yongrong Lai Qing Ke Dan Liang Yuxuan wu Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) HefeiAnhui 230032China Department of Hematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China BRLMedicine Inc. Shanghai 201108China Department of Hematology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530000China Department of Neurology The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China

Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human diseases.Ivs2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of the most common diseases in Southeast Asia and China."In our previous work,we found a TTTV protospacer adjacent motif(PAM)by the Cas12a system and the editing efficiency of Ivs2-654 C>T achieving 76.7%.

关键词： CRISPR/Cas9 China thalassemia

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Cobalt doping amount determines dominant reactive species in peroxymonosulfate activation via porous carbon catalysts co-doped by cobalt and nitrogen

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Journal of Environmental Sciences 2024年第4期138卷 212-226页

作者： Xiang Li Limeng wu Aiqin Zhang Shaohua wu Yan Lin Chunping Yang Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle Nanchang Hangkong UniversityNanchang 330063China Academy of Environmental and Resource Sciences School of Environmental Science and EngineeringGuangdong University of Petrochemical TechnologyMaoming 525000China College of Environmental Science and Engineering Hunan University and Key Laboratory of Environmental Biology and Pollution Control(Hunan University)Ministry of EducationChangsha 410082China

Switching the reaction routes in peroxymonosulfate(PMS)-based advanced oxidation processes have attracted much attention but remain challenging.Herein,a series of Co-N/C catalysts with different compositions and structures were prepared by using bimetallic zeolitic imidazolate frameworks based on ZIF-8 and ZIF-67(x Zn/Co-ZIFs).Results show that Co doping amount could mediate the transformation of the activation pathway of PMS over CoN/C.When Co doping amount was less than 10%,the constructed x Co-N/C/PMS system(x≤10%)was singlet oxygen-dominated reaction;however further increasing Co doping amount would lead to the generation and coexistence of sulfate radicals and high-valent cobalt,besides singlet oxygen.Furthermore,the nitrogen-coordinated Co(Co-NX)sites could serve as main catalytically active sites to generate singlet oxygen.While excess Co doping amount caused the formation of Co nanoparticles from which leached Co ions were responsible for the generation of sulfate radicals and high-valent cobalt.Compared to undoped N/C,Co doping could significantly enhance the catalytic performance.The 0.5%Co-N/C could achieve the optimum degradation(0.488 min^(-1))and mineralization abilities(78.4%)of sulfamethoxazole among the investigated Co-N/C catalysts,which was superior to most of previously reported catalysts.In addition,the application prospects of the two systems in different environmental scenarios(pH,inorganic anions and natural organic matter)were assessed and showed different degradation behaviors.This study provides a strategy to regulate the reactive species in PMS-based advanced oxidation process.

关键词： Peroxymonosulfate Sulfate radical Singlet oxygen Cobalt Zeolitic imidazolate framework Advanced oxidation process

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The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration Research 2024年第11期19卷 2411-2420页

作者： Shuangchan wu Wensheng Lin Department of Neuroscience University of MinnesotaMinneapolisMNUSA Institute for Translational Neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

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LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

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Chinese Medical Journal 2024年第2期137卷 190-199页

作者： Muchen wu Jing wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan wu Qinghua Meng Department of Liver Disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion:We demonstrated that gluconeogenesis dysfunc

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

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Ballistic performances of the hourglass lattice sandwich structures under high-velocity fragments

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Defence Technology（防务技术） 2024年第1期31卷 312-325页

作者： He-xiang wu Jia Qu Lin-zhi wu Key Laboratory of Advanced Ship Materials and Mechanics College of Aerospace and Civil EngineeringHarbin Engineering UniversityHarbin150001China School of Civil Engineering Northeast Forestry UniversityHarbin150040China

In this paper,the numerical simulation method is used to study the ballistic performances of hourglass lattice sandwich structures with the same mass under the vertical incidence of fragments.Attention is paid to elucidating the influences of rod cross-section dimensions,structure height,structure layer,and rod inclination angle on the deformation mode,ballistic performances,and ability to change the ballistic direction of fragments.The results show that the ballistic performances of hourglass lattice sandwich structures are mainly affected by their structural parameters.In this respect,structural parameters optimization of the hourglass lattice sandwich structures enable one to effectively improve their ballistic limit velocity and,consequently,ballistic performances.

关键词： Hourglass lattice sandwich structures Ballistic performances high-velocity Finite element analysis

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Resilience-incorporated seismic risk assessment of precast concrete frames with“dry”connections

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 403-425页

作者： wu Chenhao Tang Yuchuan Cao Xuyang wu Gang Key Laboratory of Concrete and Prestressed Concrete Structures of the Ministry of Education Nanjing 211102China Department of Civil and Environmental Engineering University of CaliforniaLos AngelesCA 90095USA School of Civil Engineering Southeast UniversityNanjing 211102China College of Civil and Transportation Engineering Hohai UniversityNanjing 210024China

A resilience-incorporated risk assessment framework is proposed and demonstrated in this study to manifest the advantageous seismic resilience of precast concrete frame(PCF)structures with“dry”connections in terms of their low damage and rapid recovery.The framework integrates various uncertainties in the seismic hazard,fragility,capacity,demand,loss functions,and post-earthquake recovery.In this study,the PCF structures are distinguished from ordinary reinforced concrete frame(RCF)structures by characterizing multiple limit states for the PCF based on its unique damage mechanisms.Accordingly,probabilistic story-wise pushover analyses are performed to yield story-wise capacities for the predefined limit states.In the seismic resilience analysis,a step-wise recovery model is proposed to idealize the functionality recovery process,with separate considerations of the repair and non-repair events.The recovery model leverages the economic loss and downtime to delineate the stochastic post-earthquake recovery curves for the resilience loss estimation.As such,contingencies in the probabilistic post-earthquake repairs are incorporated and the empirical judgments on the recovery parameters are largely circumvented.The proposed framework is demonstrated through a comparative study between two“dry”connected PCFs and one RCF designed as alternative structural systems for a prototype building.The results from the risk quantification indicate that the PCFs show reduced loss hazards and lower expected losses relative to the RCF.Particularly,the PCF equipped with energy dissipation devices at the“dry”connections largely reduces the expected economic loss,downtime,and resilience loss by 29%,56%,and 60%,respectively,compared to the RCF.

关键词： precast concrete frame non-emulative precast system seismic resilience seismic risk functional recovery

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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi Zhang Zhi-Ying wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

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Multi-endpoint assays reveal more severe toxicity induced by chloraminated effluent organic matter than chloraminated natural organic matter

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Journal of Environmental Sciences 2024年第1期135卷 310-317页

作者： Hai-Yan Wang De-Xiu wu Ye Du Xiao-Tong Lv Qian-Yuan wu State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Environmental Protection Key Laboratory of Microorganism Application and Risk Control Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental SafetyTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China College of Architecture and Environment Sichuan UniversityChengdu 610000China

Disinfection by chloramination produces toxic byproducts and the difference in toxicity of reclaimed and drinking water treated by chloramination remains unclear.This study investigated cytotoxic effects at the same concentrations of dissolved organic matter and showed that chloraminated effluent organic matter(EfOM)induced 1.7 times higher cytotoxicity than chloraminated natural organic matter(NOM)applied to simulate drinking water.Chloraminated EfOM induced more reactive nitrogen species than chloraminated NOM,and chloraminated EfOM and NOM induced similar and higher levels of reactive oxygen species than the negative control,respectively.Consequently,intracellular macromolecule damage indicated by DNA/RNA damage marker 8–hydroxy-(deoxy)guanosine and the intracellular protein carbonyl concentration induced by chloraminated EfOM was higher and slightly more than that induced by chloraminated NOM,respectively.These data were consistent with the effects on cell physiological processes.Cell cycle arrest mainly occurred in G2 phase by chloraminated EfOM and NOM.Early apoptotic cells,which could return to normal,increased upon exposure to high concentrations of chloraminated EfOM and NOM.Moreover,necrotic cells were significantly increased from 0.5%to 2.5%when the concentration increased from 20-to 60-fold chloraminated EfOM,but were not obviously changed by chloraminated NOM.These results indicated that the comprehensive intracellular changes induced by toxic substances in chloraminated EfOM were more irreversible and induced more cell death than chloraminated NOM.

关键词： Cytotoxicity Intracellular active nitrogen/oxygen Intracellular oxidative damage Cell necrosis Reclaimed water

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