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Metabolic memory:mechanisms and diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao wai Keung leung Qi Wang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and Implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens *** from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic *** long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and *** molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting *** elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and ***,we retrace the history of relevant research on metabolic memory and summarize its salient *** provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic ***,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu wai Nok Chan Fuda Xie yigan Zhang Li Liang Kam Tong leung Kwok wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

Heterogeneous Cu_(x)O Nano‑Skeletons from Waste Electronics for Enhanced Glucose Detection

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Nano-Micro Letters 2024年第11期16卷 554-568页

作者： Yexin Pan Ruohan Yu Yalong Jiang Haosong Zhong Qiaoyaxiao Yuan Connie Kong wai Lee Rongliang Yang Siyu Chen yi Chen Wing Yan Poon Mitch Guijun Li Center on Smart Manufacturing Division of Integrative Systems and DesignThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong SAR 999077People’s Republic of China The Sanya Science and Education Innovation Park of Wuhan University of Technology Sanya 572000People’s Republic of China State Key Laboratory of New Textile Materials and Advanced Processing Technologies Wuhan Textile UniversityWuhan 430200People’s Republic of China

Electronic waste(e-waste)and diabetes are global challenges to modern ***,solving these two challenges together has been challenging until ***,we propose a laser-induced transfer method to fabricate portable glucose sensors by recycling copper from *** bring up a laser-induced full-automatic fabrication method for synthesizing continuous heterogeneous Cu_(x)O(h-Cu_(x)O)nano-skeletons electrode for glucose sensing,offering rapid(yields exceptional glucose-sensing performance(sensitivity:9.893 mA mM^(-1) cm^(-2);detection limit:0.34μM),outperforming most previously reported glucose *** functional theory analysis elucidates that the heterogeneous structure facilitates gluconolactone *** glucose detection device has also been downsized to optimize its scalability and portability for convenient integration into people’s everyday lives.

关键词： Copper oxide Electron 3D tomography E-waste Glucose detection Electrochemical activation

Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies

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Asian Journal of Andrology 2024年第1期26卷 20-24页

作者： John Shung-Lai leung wai-Kit Ma Brian Sze-Ho Ho Stacia Tsun-Tsun Chun Rong Na Yongle Zhan Chi-Yuen Ng Chi-Ho Ip Ada Tsui-Lin Ng yiu-Chung Lam Division of Urology Department of SurgeryQueen Mary HospitalUniversity of Hong KongHong KongChina Division of Urology Department of SurgeryPrincess Margaret HospitalHongKongChina

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance *** with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers(Queen Mary Hospital and Princess Margaret Hospital,Hong Kong,China)between January 2017 and June 2022 were ***-magnetic resonance imaging fusion biopsies were performed after prostate health index *** who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were *** of the 747 patients,47.3%had Prostate Imaging Reporting and Data System score 3 lesions *** detection rate of clinically significant prostate cancer in this group was 15.0%.The cancer detection rates of clinically significant prostate cancer had statistically significant differences:5.3%in prostate health index<25.0,7.4%in prostate health index 25.0-34.9,17.9%in prostate health index 35.0-54.9,and 52.6%in prostate health index≥55.0(P<0.01).Among the patients,26.9%could have avoided a biopsy with a prostate health index<25.0,at the expense of a 5.3%risk of missing clinically significant prostate *** health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 *** could be avoided in patients with low prostate health index,with a small risk of missing clinically significant prostate cancer.

关键词： biopsy fusion biopsy magnetic resonance imaging prostate cancer prostate health index

NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang Ma Jing-Ping Yun Judy wai Ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong wai-Kay Seto yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value ofying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

“中文+常识”在香港非华语小学生中文教学中的应用研究

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语言教学与研究 2024年第5期 26-36页

作者：梁慧敏王莎香港理工大学中文及双语学系中国香港

香港特区非华语学生在使用中文学习其他科目时面临着学科和语言的双重障碍。对非华语学生而言,中文是他们的第二语言或外语,如果中文欠佳,势必影响学科知识的学习。本研究采用“内容与语言整合学习”的4Cs模式,为香港地区的非华语小学... 详细信息

香港特区非华语学生在使用中文学习其他科目时面临着学科和语言的双重障碍。对非华语学生而言,中文是他们的第二语言或外语,如果中文欠佳,势必影响学科知识的学习。本研究采用“内容与语言整合学习”的4Cs模式,为香港地区的非华语小学三年级学生设计了一套融合常识科内容的中文学习材料和框架,聚焦于小学常识科的六大学习范畴,展开跨学科协作模式,统整学科与中文作为第二语言的学习内容。创新的“中文+常识”课程旨在融合学科教育来提升学生中文水平,同时透过针对性语言教学深化学科知识的掌握。本研究的意义在于,首先让香港非华语中文教学突破单一的语言课堂,平衡“目标语言”和“工具语言”的教学,增强学生通过中文学习常识等其他学科的能力﹔其次,亦希望本课题可以抛砖引玉,为国际中文教育中“中文+其他学科”的教学模式提供香港地区经验。

关键词：香港非华语小学生中文+常识内容与语言整合学习 4Cs教学框架

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi wai Man Tao Zhang yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way yin Ng Grace Lui Lowell Ling Agnes S.Y.leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)