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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

Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung leung Chun-kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy Yuen-Chun Teoh Samson Yun-Sang chan Ho-Man Tam Chi-kwok chan Chi-Fai Ng Peter Ka-Fung Chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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)

Global collaboration of eye research--personal experience

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 985-990页

作者： Chi-Chao chan Laboratory of Immunology National Eye InstituteNational Institutes of HealthBethesdaMD 20892-1858USA Zhongshan Ophthalmic Center Sun Yat-sen UniversityGuangzhou 5410060Guangdong ProvinceChina

On December 9,2023,I was privileged to be honored and participate in the *** Chao chan Symposium on Global Collaboration of Eye Research as the Global Eye Genetic Consortium(GEGC)session,which was held in the 16th Congress of the Asia-Pacific Vitreo-Retina Society(APVRS)in Hong *** with my talk on“Global collaboration of eye research:personal experience”,other prominent international speakers provided their own perspectives on opportunities for networking,collaboration,and exchange of ideas with global leaders and experts in ophthalmic practice,research,and education.

关键词： speakers collaboration Global

Tetradentate Pt(Ⅱ)complex as a singlet exciton sensitizing host for highly efficient green fluorescent organic light-emitting diodes

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Science China Materials 2024年第8期67卷 2618-2627页

作者： Unhyeok Jo Seung chan Kim chan Hee Ryu Kang Mun Lee Jae-Min Kim Jun Yeob Lee School of Chemical Engineering Sungkyunkwan University2066Seobu-roJangan-guSuwon-siGyeonggi-do 16419Republic of Korea Department of Chemistry Institute for Molecular Science and Fusion TechnologyKangwon National UniversityChuncheonGangwon 24341Republic of Korea Department of Advanced Materials Engineering Chung-Ang University4726Seodong-daeroDaedeok-myeonAnseong-siGyeonggi-do 17546Republic of Korea SKKU Advanced Institute of Nano Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea SKKU Institute of Energy Science and Technology Sungkyunkwan University2066Seobu-roJangan-guSuwonGyeonggi 16419Republic of Korea

Efficient green fluorescent organic light-emitting diodes were designed with a phosphorescent metal complex as a singlet exciton sensitizing host(SESH)for achieving high efficiency and low efficiency roll-off through exciton and polaron *** Pt(Ⅱ)complex(Pt-Trz)possessing a tetradentate ligand with a bulky blocking group not only suppresses the severe formation of excimer or dimer itself but also transfers radiative excitons to fluorescent dopant *** SESH assisted fluorescence(SESHF)device with Pt-Trz as the host exhibits the maximum external quantum efficiency of 13.3%and a lower efficiency roll-off compared with exciplex host device which is a general approach for harvesting triplet *** exciton dynamics modeling unravels that the SESHF device effectively utilizes triplet excitons in the host by intersystem crossing and resonance energy transfer from the triplet state of the host to the singlet state of the terminal *** quenching rates of the SESHF device are reduced by 11 times for triplet-triplet annihilation and 1.8 times for tripletpolaron annihilation compared with the exciplex device,which demonstrates that Pt-Trz could be a platform to be used as an efficient host for fluorophores.

关键词： singlet annihilation polaron

Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder:a highrisk study in the Chinese population

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General Psychiatry 2024年第3期37卷 388-400页

作者： Binbin Lei Hongliang Feng Lulu Yang Jing Wang Jie Chen Weidong Song Chao Jiang Kun Zhang Qunfeng Wang Jessie Chi Ching Tsang Ngan Yin chan Yaping Liu Joey W.Y.chan Jiyang Pan Bin Zhang Tao Li Kathleen Ries Merikangas Jihui Zhang Yun kwok Wing Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina Guangdong Mental Health Center Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdongChina Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong KongChina Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongNew TerritoriesHong KongChina Key Laboratory of Neurogenetics and channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdongChina Shenzhen Nanshan Center for Chronic Diseases Control(Shenzhen Nanshan Mental Health Center) ShenzhenChina Department of Clinical Psychology Shenzhen Fuyong People's HospitalShenzhenChina Department of Mental Illness Prevention and Treatment Shenzhen Longgang Center for Chronic Diseases ControlShenzhenChina Department of Neurology Zhongnan Hospital of Wuhan UniversityWuhanHubeiChina Sleep Medical Center The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina Department of Psychiatry Nanfang HospitalSouthern Medical UniversityGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangzhouGuangdongChina Department of Neurobiology Affiliated Mental Health Center&Hangzhou Seventh People's HospitalZhejiang University School of MedicineHangzhouZhejiangChina Genetic Epidemiology Research Branch Intramural Research ProgramNational Institute of Mental HealthBethesdaMarylandUSA

Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar ***,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and *** To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,*** diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,*** estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the *** Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than *** analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD

关键词： prevention dysfunction bipolar

An Overview of Chemical Constituents, Medicinal Properties, Clinical Trials, and Patents of Twigs of Morus alba(Ramulus Mori)

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 149-158页

作者： Eric Wei Chiang chan Hung Tuck chan Siu Kuin Wong Department of Food Science and Nutrition Faculty of Applied SciencesUCSI UniversityCherasKuala LumpurMalaysia Secretariat of International Society for Mangrove Ecosystems Faculty of AgricultureUniversity of the RyukyusOkinawaJapan School of Foundation Studies Xiamen University MalaysiaSepangSelangorMalaysia

The rich chemical constituents and diverse pharmacological properties of Ramulus Mori(RM) or the twig of Morus alba with evidence supported by clinical trials and patents are reviewed. Known as Sangzhi in Chinese, RM is widely used in traditional Chinese medicine to treat gout, arthritis, and rheumatism. Chemical constituents include flavonoids, benzofurans, alkaloids, stilbenes, chalcones, phenolic acids, and coumarins. Bioactivities of RM include antidiabetic, anti-obesity, anti-inflammatory, antityrosinase, neuroprotective, antioxidant, hepatoprotective, cytoprotective, renoprotective, antihyperuricemic, analgesic, antifungal, DNA protective, anticancer, gastroprotective, cardioprotective, anti-hair aging, anti-arthritic, and antiplatelet aggregation properties. The most active compounds from RM are mulberrin, oxyresveratrol, and mulberroside A. All four clinical trials on RM are focused on the treatment of diabetes. The patents entail using RM extracts as cosmetics for skin whitening and as agents for hypoglycemia. Topics for further research on RM are suggested.

关键词： Clinical trials mulberrin mulberroside A oxyresveratrol patents Sangzhi

Construction of a High‑Performance Composite Solid Electrolyte Through In‑Situ Polymerization within a Self‑Supported Porous Garnet Framework

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Nano-Micro Letters 2024年第5期16卷 56-70页

作者： An‑Giang Nguyen Min‑Ho Lee Jaekook Kim chan‑Jin Park Department of Materials Science and Engineering Chonnam National University77 Yongbong‑roBuk‑guGwangju 61186South Korea

Composite solid electrolytes(CSEs)have emerged as promising candidates for safe and high-energy–density solid-state lithium metal batteries(SSLMBs).However,concurrently achieving exceptional ionic conductivity and interface compatibility between the electrolyte and electrode presents a significant challenge in the development of high-performance CSEs for *** overcome these challenges,we present a method involving the in-situ polymerization of a monomer within a self-supported porous Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZT)to produce the *** synergy of the continuous conductive LLZT network,well-organized polymer,and their interface can enhance the ionic conductivity of the CSE at room ***,the in-situ polymerization process can also con-struct the integration and compatibility of the solid electrolyte–solid electrode *** synthesized CSE exhibited a high ionic conductivity of 1.117 mS cm^(-1),a significant lithium transference number of 0.627,and exhibited electrochemical stability up to 5.06 V ***/Li+at 30℃.Moreover,the Li|CSE|LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2) cell delivered a discharge capacity of 105.1 mAh g^(-1) after 400 cycles at 0.5 C and 30℃,corresponding to a capacity retention of 61%.This methodology could be extended to a variety of ceramic,polymer electrolytes,or battery systems,thereby offering a viable strategy to improve the electrochemical properties of CSEs for high-energy–density SSLMBs.

关键词： Scalable tape-casting method Self-supported porous Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12) Composite solid electrolyte LiF-and B-rich interphase layers