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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 glands.Sixty-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 pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The 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 week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results 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 activities.Moreover,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 in activating the anti-tumor immune response(P<

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

Mass and charge transport relevant to the formation of toroidal lithium peroxide nanoparticles in an aprotic lithium-oxygen battery： An experimental and theoretical modeling study

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Nano Research 2017年第12期10卷 4327-4336页

作者： Xiangyi Luo Rachid Amine kah chun lau Jun Lu chun Zhan Larry A. Curtiss Said AI Hallaj Brian P. Chaplin Khalil Amine Chemical Sciences and Engineering Division Argonne National Laboratory 9700 South Cass Avenue Lemont IL 60439 USA Materials Science Division Argonne National Laboratory 9700 South Cass Avenue Lemont IL 60439 USA Department of Chemical Engineering University of Illinois at Chicago 810 S. Clinton Chicago IL 60607 USA Department of Physics and Astronomy California State University Northridge 18111 Nordhoff Street Northridge CA 91330 USA

The discharge and charge mechanisms of rechargeable Li-O2 batteries have been the subject of extensive investigation recently. However, they are not fully understood yet. Here we report a systematic study of the morphological transition of Li2O2 from a single crystalline structure to a toroid like particle during the discharge-charge cycle, with the help of a theoretical model to explain the evolution of the Li2O2 at different stages of this process. The model suggests that the transition starts in the first monolayer of Li2O2, and is subsequently followed by a transition from particle growth to film growth if the applied current exceeds the exchange current for the oxygen reduction reaction in a Li-O2 cell. Furthermore, a sustainable mass transport of the diffusive active species （e.g., O2 and Li＋） and evolution of the underlying interfaces are critical to dictate desirable oxygen reduction （discharge） and evolution （charge） reactions in the oorous carbon electrode of a Li-O2 cell.

关键词： rechargeable Li-O2 battery,electrocatalyst,nanocomposite,lithium peroxide

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet chung Tsun Ming lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.Humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4+,SNM-specific IL-2+CD8+,S-specific IL-2+CD8+,N-specific IL-2+CD4+,N-specific IL-2+CD8+and M-specific IL-2+CD4+responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2+CD4+,interferon-γ+CD8+and IL-2+CD8+responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching Chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam lau Ying Lo Law Chi Seng Leung chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Symmetry-driven half-integer conductance quantization in Cobalt–fulvalene sandwich nanowire

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npj Computational Materials 2023年第1期9卷 314-321页

作者： Zhuoling Jiang kah-Meng Yam Yee Sin Ang Na Guo Yongjie Zhang Hao Wang chun Zhang Department of Physics and Centre for Advanced 2D Materials National University of SingaporeSingapore 117551Singapore Science Mathematics and Technology(SMT)ClusterSingapore University of Technology and DesignSingapore 487372Singapore Department of Chemistry National University of SingaporeSingapore 117543Singapore National University of Singapore Chongqing Research Institute 401123 ChongqingChina

Precise manipulation and monitoring spin transport in one-dimensional (1D) systems is a long-sought goal in the field of nano-spintronics. Based on first-principles calculations, we report the observation of half-integer conductance quantization in the Cobalt-fulvalene sandwich nanowire. Compared with a pure monatomic Cobalt wire, the introduction of fulvalene molecules leads to threeimportant features: Firstly, the strong coupling between the fulvalene and the Cobalt prevents the contamination of the ambientair, ensuring both chemical and physical stabilities;Secondly, the fulvalene symmetry-selectively filters out most of the d-typeorbitals of the Cobalt while leaving a single d-type orbital to form an open spin channel around the Fermi level, which offers amechanism to achieve the observed half-integer conductance;Thirdly, it maintains a superexchange coupling between adjacent Coatoms to achieve a high Curie temperature. Spin transport calculations show that this half-metallic nanowire can serve as a perfectspin filter or a spin valve device, thus revealing the potential of Cobalt-fulvalene sandwich nanowire as a promising building blockof high-performance spintronics technology.

关键词： sandwich coupling transport

Matrisomal genes in squamous cell carcinoma of head and neck influence tumor cell motility and response to cetuximab treatment

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Cancer Communications 2022年第4期42卷 355-359页

作者： kah Yee Goh kah Weng lau Terence You De Cheng Su Chin Tham Chwee Teck Lim Narayanan Gopalakrishna Iyer Su Bin Lim Darren Wan-Teck Lim Division of Medical Oncology National Cancer Centre SingaporeSingapore 169610 Department of Pathology National University HospitalSingapore 119074 A*STAR ProteosInstitute of Molecular and Cell BiologySingapore 138673 Department of Biomedical Engineering Mechanobiology InstituteNational University of SingaporeT-LabSingapore 117411 Institute for Health Innovation and Technology(iHealthtech) National University of SingaporeMD6Singapore 117599 Department of Head and Neck Surgery National Cancer Centre Singapore11 Hospital CrescentSingapore 169610 Office of Academic and Clinical Development Duke-NUS Medical SchoolSingapore 169857 Department of Biochemistry and Molecular Biology Ajou University School of MedicineYeongtong-GuSuwon 16499South Korea

Dear Editor,Head and neck squamous cell carcinoma(HNSCC)is the sixth most common cancer globally[1,2].Despite the improvement in treatment modalities,up to 50%of HNSCC patients still develop recurrent/metastatic(R/M)disease[3],and platinum-based chemotherapy with cetuximab and/or pembrolizumab has become the standard of care[4].However,R/M HNSCC is challenging to treat,the prognosis is poor,and there is an unmet need for new therapeutic targets.

关键词： chemotherapy cetuximab treatment

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关于纳米弹性窄带的回弹时间研究

Acta Mechanica Sinica 2022年第4期38卷 21-28,I0001页

作者：赵子煜刘金兴 Ai kah Soh 唐淳 Faculty of Civil Engineering and Mechanics Jiangsu UniversityZhenjiang 212013China School of Engineering Monash University MalaysiaSelangor Darul Ehsan 47500Malaysia

我们通过数值模拟和理论建模两种方法研究了纳米尺寸单晶铜窄带的回弹行为,分析了回弹时间的各种影响因素.通过固定窄带两端并于其中点施加静荷载,使窄带产生初始弯曲.随后通过移除中点静何载促使回弹行为发生.本研究分别使用分子动力... 详细信息

我们通过数值模拟和理论建模两种方法研究了纳米尺寸单晶铜窄带的回弹行为,分析了回弹时间的各种影响因素.通过固定窄带两端并于其中点施加静荷载,使窄带产生初始弯曲.随后通过移除中点静何载促使回弹行为发生.本研究分别使用分子动力学模拟软件LAMMPS和考虑表面张力的连续力学模型对纳米弹性窄带回弹进行了研究.研究发现表面张力的增加会导致回单时间的增加.研究结果还表明回弹行为与窄带初始弯曲程度和窄带厚度均具有密切联系.此外,对比分子动力学模拟和连续模型所得结果,我们还发现两种方法获得的回弹时间处于同一量级.这一结论十分独特且有意义,因为目前分子动力学模拟结果在时间尺度上往往与实验结果存在巨大差异、我们相信,本研究关于回弹这一自发运动的研究有助于在一定程度上阐述分子动力学模拟所得的变形行为时间尺度远小于实验结果的原因.

关键词： Snap-through Characteristic time Continuum modeling Molecular dynamics simulation Surface stress

Site-directed deuteration of dronedarone preserves cytochrome P4502J2 activity and mitigates its cardiac adverse effects in canine arrhythmic hearts

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3905-3923页

作者： Aneesh V.Karkhanis Gopalakrishnan Venkatesan Ryuichi Kambayashi Jacqueline Wen Hui Leow Marcus Qingrui Han Hiroko Izumi-Nakaseko Ai Goto Jeremy kah Sheng Pang Boon Seng Soh Pipin Kojodjojo Atsushi Sugiyama Eric chun Yong Chan Department of Pharmacy Faculty of ScienceNational University of SingaporeSingapore 117543Singapore Department of Pharmacology Faculty of MedicineToho UniversityTokyo 143-8540Japan Institute of Molecular and Cell Biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Department of Biological Sciences Faculty of ScienceNational University of SingaporeSingapore 117558Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

Cytochrome P4502J2(CYP2J2)metabolizes arachidonic acid(AA)to cardioprotective epoxyeicosatrienoic acids(EETs).Dronedarone,an antiarrhythmic drug prescribed for treatment of atrial fibrillation(AF)induces cardiac adverse effects(AEs)with poorly understood mechanisms.We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly,disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable via EET enrichment.In this study,we investigated if mitigation of CYP2J2 inhibition prevents dronedarone-induced cardiac AEs.We first synthesized a deuterated analogue of dronedarone(termed poyendarone)and demonstrated that it neither inactivates CYP2J2,disrupts AA-EETs metabolism nor causes cardiac mitochondrial toxicity in vitro.Our patch-clamp experiments demonstrated that pharmacoelectrophysiology of dronedarone is unaffected by deuteration.Next,we show that dronedarone treatment or CYP2J2 knockdown in spontaneously beating cardiomyocytes indicative of depleted CYP2J2 activity exacerbates beat-to-beat(BTB)variability reflective of proarrhythmic phenotype.In contrast,poyendarone treatment yields significantly lower BTB variability compared to dronedarone in cardiomyocytes indicative of preserved CYP2J2 activity.Importantly,poyendarone and dronedarone display similar antiarrhythmic properties in the canine model of persistent AF,while poyendarone substantially reduces beat-to-beat variability of repolarization duration suggestive of diminished proarrhythmic risk.Our findings prove that deuteration of dronedarone prevents CYP2J2 inactivation and mitigates dronedarone-induced cardiac AEs.

关键词： Arachidonic acid Atrial fibrillation CYP2J2 Drug-induced proarrhythmia Epoxyeicosatrienoic acids Mechanism-based inactivation Dronedarone

应用人工智能和终端用户工具开发护士自动排班系统

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International Journal of Nursing Sciences 2022年第3期9卷 373-377页

作者： Franklin Leung Yee-chun lau Martin Law Shih-Kien Djeng Science and Technology Section School of Continuing and Professional EducationCity University of Hong KongHKSARChina Department of Rehabilitation Kowloon HospitalHKSARChina Proton Therapy Pte Ltd 1 Biopolis DriveSingapore

目的医院病房每月均需编制护士排班表。病房管理者需要根据员工要求和医院政策进行排班和调整,花费时间较长。本研究旨在开发一个护士自动排班系统,使用开放式操作工具,兼顾医院要求和护士个人需求,快速生成排班表。方法应用人工智能和... 详细信息

目的医院病房每月均需编制护士排班表。病房管理者需要根据员工要求和医院政策进行排班和调整,花费时间较长。本研究旨在开发一个护士自动排班系统,使用开放式操作工具,兼顾医院要求和护士个人需求,快速生成排班表。方法应用人工智能和终端用户工具运筹学工具编写护士排班系统代码。与以往的排班系统算法相比,本研究开发的系统使用开放式架构,在某医院一个病房根据实际排班需求进行应用和评估。结果排班表在1分钟内生成,可满足所有硬性规定及大多数护士的软性需求。与传统手工排班相比,该排班系统具备护士和病房管理者之间的实时交互功能,并能进行排班表优化调整。系统生成的排班表可灵活应对病房工作人员日常排班变化,保障安全的人员配置水平。结论采用开源运筹学方法开发的护士自动排班系统经济、高效、用户友好,使用顺畅。该系统可在医院的不同病房使用,并可由受过培训的医院信息工作定期更新医院政策规定和护士人力配置以适应实际工作需要。

关键词：人工智能计算机护士护士排班表开源软件