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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 ***-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

Multifunctional catalytic sites regulation of atomic-scale iridium on orthorhombic-CoSe_(2)for high efficiency dual-functional alkaline hydrogen evolution and organic degradation

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Journal of Energy Chemistry 2024年第5期92卷 271-281页

作者： Jingjing Huang Chenglin Zhong Yanjie Xia Jia Liu Guizhen Li Chao Yang Jiahong Wang Qian Wang Zhenbao Zhang Feng Yan Jianghua Wu Yu Deng Zhenjiang Zhou Xingchen He Paul K.chu Woon-Ming lau Xue-Feng Yu College of Chemistry and Chemical Engineering Linyi UniversityLinyi 276005ShandongChina Shenzhen Engineering Center for the Fabrication of Two-Dimensional Atomic Crystals Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055GuangdongChina National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional MaterialsCollege of Engineering and Applied Sciences and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093JiangsuChina College of Biosystems Engineering and Food Science Zhejiang UniversityHangzhou 310058ZhejiangChina Department of Physics Department of Materials Science and EngineeringDepartment of Biomedical EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina

The earth-abundant and high-performance catalysts are crucial for commercial implementation of hydrogen evolution reaction(HER).Herein,a multifunctional site strategy to construct excellent HER catalysts by incorporating iridium(Ir)ions on the atomic scale into orthorhombic-CoSe2(Ir-CoSe_(2))was *** hydrogen evolution activity in alkaline media such as a low overpotential of 48.7 mV at a current density of 10 mA cm^(-2)and better performance than commercial Pt/C catalysts at high current densities were found in the Ir-CoSe_(2) *** the experiments and theoretical calculations,it was revealed that Ir enabled CoSe_(2)to form multifunctional sites to synergistically catalyze alkaline HER by promoting the adsorption and dissociation of H_(2)O(Ir sites)and optimizing the binding energy for H^(*)on Co *** was noticeable that the electrolytic system comprising the Ir-CoSe_(2)electrode not only produced hydrogen efficiently via HER,but also degraded organic pollutants(Methylene blue).The cell voltage of the dual-function electrolytic system was 1.58 V at the benchmark current density of 50 mA cm^(-2),which was significantly lower than the conventional water splitting *** was indicated that this method was a novel strategy for designing advanced HER electrocatalysts by constructing multifunctional catalytic sites for hydrogen production and organic degradation.

关键词： Orthorhombic-CoSe_(2) Multifunctional sites design Hydrogen evolution reaction Synergistically catalyze Methylene blue oxidation

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 *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,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 *** 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

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 *** 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 *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** 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,*** 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 *** 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 *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** 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

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

How to secure the connection between thoracostomy tube and drainage system?

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World Journal of Emergency Medicine 2014年第4期5卷 259-263页

作者： Ka Ki Pat Li Kit Shing John Wong Yau Hang Henry Wong Ka Lok Cheng Fung Ling So chu leung lau Chak Wah Kam Department of Accident and Emergency Medicine Pok Oi Hospital Department of Accident and Emergency Medicine Tuen Mun Hospital Clinical Skills Training Centre Tuen Mun Hospital

BACKGROUND: Thoracostomy tube insertion is one of the common bedside procedures in emergency medicine and many acute specialties. Dislodgement of thoracostomy tube from the connection tube of chest drainage system is an important problem with potential complications such as contamination, infection and pneumothorax. Besides, mere loosening can also lead to malfunction. It is a common practice to tape the connection of the system. This study aimed to evaluate the materials and methods of connection of chest drain system to minimize drainage dislodgement. METHODS: We conducted an experimental study to assess the tightness of the connection with various taping materials and methods. We selected three commonly used adhesive materials(3M^(tm) Transpore^(tm) Medical tape, 3M^(tm) Micropore^(tm) Medical tape, 3M^(tm) Soft Cloth Tape on Liner) and three different methods(cross method, straight method, nylon band) to secure the junction between the thoracostomy tube and the bi-conical adaptor in the drainage system. The measured outcome was the weight causing visible loosening of the junction between thoracotomy tube and the ***: For each taping material and taping method, 10 trials were performed. The median weight required to disconnect the junction is 26.22 lb for Transpore^(tm), 31.29 lb for Micropore^(tm) and 32.44 lb for Soft Cloth Tape on Liner. A smaller force was required to disconnect if Transpore^(tm) is used(P<0.001). There was no statistical signifi cant difference between Micropore^(tm) and Soft Cloth Tape on Liner(P=0.98). The median disconnecting force is 32.44 lb for straight taping method, 40.55 lb for cross taping method and 21.15 lb for plastic band. The cross-taping method was the more secure method(P<0.0001 when compared with plastic band)(P=0.033 when compared with straight method).CONCLUSION: Cross-taping is the most secure method among the tested varieties in connecting the thoracostomy tube to the chest drainage system. Transpore^(tm) is

关键词： Thoracostomy tube Drainage system Cross-taping

New tricyanoiron(Ⅲ) building blocks for the construction of molecule-based magnets

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Science China Chemistry 2010年第10期53卷 2106-2111页

作者： lau Pui-Ha WONG Wing-Tak lau Tai-chu Department of Biology and Chemistry City University of Hong Kong Department of Chemistry The University of Hong Kong

A series of tricyanoiron(Ⅲ) complexes with the general formula mer-[FeⅢ(5-Xsap)(CN)3]2-(X = H, Me, MeO, Cl or Br, sapH2 = N-salicylidene-o-aminophenol) have been synthesized. These complexes were characterized by IR, ESI-MS, UV/Vis, elemental analysis and magnetic measurements. The structures of (PPh4)2[FeⅢ(sap)(CN)3] and (PPh4)2[FeⅢ(5-Mesap)(CN)3] have been determined by X-ray crystallography. These low-spin d5 tricyanoiron(Ⅲ) complexes are potential building blocks for the construction of molecule-based magnets.

关键词： cyano iron Schiff base building block molecule-based magnet

Advances in antithrombin therapy for ST-elevation myocardial infarction

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Chinese Medical Journal 2003年第11期116卷 1760-1763页

作者： Wai-hong Chen chu-Pak lau Department of Medicine Queen Mary Hospital Hong Kong ChinaDepartment of Medicine Queen Mary Hospital Hong Kong China

Thrombin is a pivotal molecule in acute myocardial infarction ( Ml) because of its extensive procoagulant and prothrombotic actions. Antithrombin therapy is an important component of the pharmacotherapy for acute Ml. The standard agent used in clinical practice, unfractionated heparin (UFH), is associated with the disadvantages of variable anticoagulant effect, inability to inhibit clot-bound thrombin, neutralization by platelet factor 4, and the propensity to cause thrombocytopenic complications. Novel thrombin inhibitors have been developed to overcome these disadvantages. Although possessing the property of inhibiting both fluid-phase and clot-bound thrombin, the direct thrombin inhibitor hirudin has been shown to give marginal benefits over UFH as adjunct to fibrinolysis in ST-elevation Ml. Bivalirudin, another direct thrombin inhibitor, is able to reduce reinfarction in patients treated with streptokinase and is a new anticoagulant treatment option in this setting. The pharmacokinetic characteristics of better availability, longer half-life, and dose-independent clearance together with the ability of inhibiting both thrombin generation and activity make the low-molecular-weight heparins (LMWHs) an attractive alternative to UFH. The favorable benefit/risk profile of the LMWHs as adjunct to different generations of fibrinolytic agents is setting the stage for larger clinical trials to confirm their role as the antithrombin agent of choice for STEMI.

关键词： thrombin antithrombotic therapy myocardial infarction

Regulation of cytohesins by their interactors in the nervous system

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Neural Regeneration Research 2023年第10期18卷 2186-2187页

作者： Yuqi Zhai King To leung Kwok-Fai lau School of Life Sciences Faculty of ScienceThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

Adenosine diphosphate ribosylation factors(ARFs) are small GTP-binding proteins of the Ras superfamily which are involved in membrane trafficking and actin cytoskeleton *** other small GTPases,their functions are attributed to the cycling of ARF between GTP(active) and GDP (inactive) states through the actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins,respectively.

关键词： Adenosine cycling attributed

Cosmic microwave background constraints on the tensor-to-scalar ratio

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Research in Astronomy and Astrophysics 2014年第6期14卷 635-647页

作者： King lau Jia-Yu Tang Ming-chung chu Department of Physics and Institute of Theoretical Physics The Chinese University of Hong Kong

One of the main goals of modern cosmic microwave background （CMB） missions is to measure the tensor-to-scalar ratio r accurately to constrain inflation models. Due to ignorance about the reionization history Xe （z）, this analysis is usu- ally done by assuming an instantaneous reionization Xe （z） which, however, can bias the best-fit value of r. Moreover, due to the strong mixing of B-mode and E-mode polarizations in cut-sky measurements, multiplying the sky coverage fraction fsky by the full-sky likelihood would not give satisfactory results. In this work, we forecast constraints on r for the Planck mission taking into account the general reionization scenario and cut-sky effects. Our results show that by applying an N-point interpo- lation analysis to the reionization history, the bias induced by the assumption of in- stantaneous reionization is removed and the value of r is constrained within 5% error level, if the true value of r is greater than about 0.1.

关键词： cosmology: cosmic microwave background -- cosmology: cosmologicalparameters -- cosmology: early universe -- gravitational waves