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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： Kevin Tak-Pan Ng Li Pang Jia-Qi Wang wong Hoi She Simon Hing-yin Tsang Chung Mau Lo kwan Man Tan To Cheung Department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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Unraveling adaptive changes in electric vehicle charging behavior toward the postpandemic era by federated meta-learning

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The Innovation 2024年第2期5卷 21-23页

作者： Linlin You Rui Zhu Mei-Po kwan Min Chen Fan Zhang Bisheng Yang Man Sing wong Zheng Qin School of Intelligent Systems Engineering Sun Yat-Sen UniversityShenzhen 518107China Institute of High Performance Computing(IHPC) Agency for ScienceTechnology and Research(A*STAR)1 Fusionopolis WaySingapore 138632Republic of Singapore Institute of Space and Earth Information Science Chinese University of Hong KongHong KongChina Key Laboratory of Virtual Geographic Environment(Ministry of Education) Nanjing Normal UniversityNanjing 210023China Institute of Remote Sensing and Geographical Information System School of Earth and Space SciencesPeking UniversityBeijing 100871China State Key Laboratory of Information Engineering in Surveying Mappingand Remote SensingWuhan UniversityWuhan 430079China Department of Land Surveying and Geo-Informatics The Hong Kong Polytechnic UniversityHong KongChina

Dear Editor,Electric vehicle(EV)sales have significantly grown over the years to fulfill growing demands for economic travel and greenhouse gas mitigation.1 However,the surge in the number of EVs has led to charging anxiety as users struggle to find an available charging station before running out of electricity,resulting in longer reserve and waiting times.2 Moreover,severe mobility restrictions caused by infectious diseases,such as coronavirus disease 2019(COVID-19),have greatly affected people’s travel behavior3,4 and hindered their willingness to use EVs,given that charging in public spaces consumes time and increases the risk of contracting the virus.5 This implies that in the postpandemic era,in which individuals coexist with the virus,the interplay between the two important trends,namely vehicle electrification and mobility restrictions,can extensively affect people’s daily commuting by using EVs.

关键词： travel behavior charging

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Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2300-2314页

作者： Piao Luo Dandan Liu Qian Zhang Fan Yang yin-kwan wong Fei Xia Junzhe Zhang Jiayun Chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang Artemisinin Research Center Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524037China Department of Urology the Second Clinical Medical CollegeJinan University(Shenzhen People’s Hospital)Shenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Faculty of Health Sciences University of MacaoTaipaMacao 999078China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

关键词： Celastrol Ferroptosis Peroxiredoxin HO-1 Hepatic fibrosis ABPP Anti-oxidant Reactive oxygen species

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Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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药物分析学报:英文版 2023年第7期13卷 817-829页

作者： Jiayun Chen Xueling He Yunmeng Bai Jing Liu yin kwan wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu Qiuyan Guo Guangqing Cheng Chen Wang Jigang Wang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

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Mitochondria-targeted atovaquone promotes anti-lung cancer immunity by reshaping tumor microenvironment and enhancing energy metabolism of anti-tumor immune cells

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Cancer Communications 2024年第3期44卷 448-452页

作者： Donghai Xiong Zheng yin Mofei Huang Yian Wang Micael Hardy Balaraman Kalyanaraman Stephen T wong Ming You Center for Cancer Prevention Houston Methodist Neal Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Department of Systems Medicine and Bioengineering Houston Methodist Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Aix Marseille Univ Centre Nationaldela Recherche Scientifique(CNRS)Institut de Chimie Radicalaire(ICR)UnitéMixte de Recherche(UMR)7273MarseilleFrance Department of Biophysics Medical College of WisconsinMilwaukeeWisconsinUSA

Dear Editor,Atovaquone(ATO),a mitochondrial inhibitor,has anti-cancer effects[1].Based on ATO,we developed mitochondria-targeted atovaquone(Mito-ATO)that had even stronger anti-tumor efficacy than ATO[2].We syn-thesized Mito-ATO by attaching the bulky triphenylphos-phonium(TPP)group to ATO via a ten-carbon alkyl chain(Supplementary file of methods;Supplementary Figure S1).

关键词： metabolism immunity targeted

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MXenes and heterostructures-based electrocatalysts for hydrogen evolution reaction:Recent developments and future outlook

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Journal of Energy Chemistry 2024年第5期92卷 176-206页

作者： Abdul Hanan Hafiz Taimoor Ahmed Awan Faiza Bibi Raja Rafidah Raja Sulaiman Wai yin wong Rashmi Walvekar Seema Singh Mohammad Khalid Sunway Centre for Electrochemical Energy and Sustainable Technology(SCEEST) School of Engineering and TechnologySunway UniversityNo.5 Jalan UniversitiBandar Sunway47500 Petaling JayaSelangorMalaysia Fuel Cell Institute Universiti Kebangsaan Malaysia43600 UKM BangiSelangorMalaysia Faculty of Innovation and Technology School of EngineeringChemical Engineering ProgrammeNo.1 Jalan Taylor’sTaylor’s University Malaysia47500 Subang JayaSelangorMalaysia Chitkara Centre for Research and Development Chitkara UniversityHimachal Pradesh 174103India School of Applied and Life Sciences Uttaranchal UniversityDehradunUttarakhand 248007India Manipal Institute of Technology Manipal Academy of Higher EducationManipal 576104KarnatakaIndia Centre of Research Impact and Outcome Chitkara UniversityPunjab 140401India

The increasing focus on electrocatalysis for sustainable hydrogen(H_(2))production has prompted significant interest in MXenes,a class of two-dimensional(2D)materials comprising metal carbides,carbonitrides,and nitrides.These materials exhibit intriguing chemical and physical properties,including excellent electrical conductivity and a large surface area,making them attractive candidates for the hydrogen evolution reaction(HER).This scientific review explores recent advancements in MXene-based electrocatalysts for HER kinetics.It discusses various compositions,functionalities,and explicit design principles while providing a comprehensive overview of synthesis methods,exceptional properties,and electro-catalytic approaches for H_(2) production via electrochemical reactions.Furthermore,challenges and future prospects in designing MXenes-based electrocatalysts with enhanced kinetics are highlighted,emphasizing the potential of incorporating different metals to expand the scope of electrochemical reactions.This review suggests possible efforts for developing advanced MXenes-based electrocatalysts,particularly for efficient H_(2) generation through electrochemical water-splitting reactions..

关键词： MXenes Electrocatalyst Water Splitting Hydrogen Generation Clean Energy

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18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

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Journal of Pharmaceutical Analysis 2022年第4期12卷 570-582页

作者： Qian Zhang Piao Luo Liuhai Zheng Jiayun Chen Junzhe Zhang Huan Tang Dandan Liu Xueling He Qiaoli Shi Liwei Gu Jiahao Li Qiuyan Guo Chuanbin Yang yin kwan wong Fei Xia Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of SingaporeSingapore117543Singapore Department of Geriatrics Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen518020China

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.

关键词： Glycyrrhetinic acid Hepatic fibrosis Peroxiredoxin Reactive oxygen species Apoptosis

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The electroweak monopole–antimonopole pair in the standard model

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Communications in Theoretical Physics 2024年第3期76卷 113-119页

作者： Dan Zhu Khai-Ming wong Guo-Quan wong School of Physics Universiti Sains Malaysia11800 USMPenangMalaysia

We present the first numerical solution that corresponds to a pair of Cho–Maison monopoles and antimonopoles(MAPs) in the SU(2) × U(1) Weinberg–Salam(WS) theory.The monopoles are finitely separated,while each pole carries a magnetic charge ±4π/e.The positive pole is situated in the upper hemisphere,whereas the negative pole is in the lower hemisphere.The Cho–Maison MAP is investigated for a range of Weinberg angles,0.4675≤ tan θ_(W)≤10,and Higgs self-coupling,0 ≤ β ≤ 1.7704.The magnetic dipole moment(μm) and pole separation(d_(z)) of the numerical solutions are calculated and analyzed.The total energy of the system,however,is infinite due to point singularities at the locations of monopoles.

关键词： magnetic monopole Cho-Maison monopole Weinberg-Salam model

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Chemical proteomic profiling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin

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Chinese Chemical Letters 2023年第12期34卷 486-491页

作者： Peng Gao Jiayun Chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang Chen Wang yin kwan wong yinhua Zhu Chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Pharmaceutical College Henan University Shandong Academy of Chinese Medicine Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and Technology

Present research on the antimalarial mechanisms of artemisinin(ART) is mainly focused on covalent drug binding targets alkylated by free radicals, while non-covalent binding targets have rarely been reported.Here, we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics. The results demonstrated that ART can bind to parasite proteins by both covalent and non-covalent modification, and these may jointly contribute to the antimalarial effects. Our work enriches the research on the antimalarial targets of ART, and provides a new perspective for further exploring the antimalarial mechanism of ART.

关键词： Antimalarial Artemisinin Chemical proteomic Photoaffinity probe Target identification

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Navigating reflux disease after achalasia treatments:Balancing risks and benefits

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World Journal of Gastroenterology 2024年第21期30卷 2740-2743页

作者： Ewen A Griffiths Enoch wong Department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWWest MidlandsUnited Kingdom Department of Immunology and Immunotherapy University of BirminghamBirmingham B152TTWest MidlandsUnited Kingdom

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia.Alongside its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved.In this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after POEM.POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure.Certain patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them.This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

关键词： Achalasia Gastro-esophageal reflux disease Laparoscopic heller’s myotomy Peroral endoscopic myotomy Fundoplication

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