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Peptidic defective interfering gene nanoparticles against Omicron,Delta SARS-CoV-2 variants and influenza A virus in vivo

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3484-3493页

作者： Hanjun Zhao Chuyuan Zhang Hoiyan lam Xinjie Meng Zheng Peng Man Lung Yeung Jasper Fuk-Woo Chan Kelvin kai-Wang To Kwok-Yung Yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina Department of Infectious Disease and Microbiology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinceChina Carol Yu Centre for Infection The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina

Defective interfering genes(DIGs)are short viral genomes and interfere with wild-type viral ***,we demonstrate that the new designed SARS-CoV-2 DIG(CD3600)can significantly inhibit the replication of SARS-CoV-2 including Alpha,Delta,kappa and Omicron variants in human HK-2 cells and influenza DIG(PAD4)can significantly inhibit influenza virus replication in human A549 *** dose of influenza DIGs prophylactically protects 90%mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral *** further investigate the gene delivery vector in the respiratory tract,a peptidic TAT2-P1&LAH4,which can package genes to form small spherical nanoparticles with high endosomal escape ability,is demonstrated to dramatically increase gene expression in the lung ***2-P1&LAH4,with the dual-functional TAT2-P1(gene-delivery and antiviral),can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster *** peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo,which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.

关键词： influenza vivo Delta

Time Series Forecasting of Hong Kong Inter-bank Offered Rate(HIBOR)using Exponential Smoothing State Space Model

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Economics World 2023年第1期10卷 43-48页

作者： Andy Tai ka-ming lam Hong Kong Polytechnic University Hong KongChina Hong Kong Nang Yan College of Higher Education Hong KongChina

This paper set out to analyze and forecast the Hong Kong Interbank Interest Rate(HIBOR)for a period 2006 to *** main objective of this study is to propose an appropriate time series forecasting model for *** conceptually captures the interaction between demand and supply of Hong Kong dollar in the interbank *** volatility of HIBOR reflects market sentiment,changes in underlying macroeconomic environment,random events and even political ***,the time series data of HIBOR appears to have multiple seasonality during the aforesaid *** TBATS model,the state space modeling framework developed by De Livera,Hyndman and Snyder(2010)is adopted for this study to improve the accuracy and efficiency of the time series modeling and forecasting of *** TBATS model incorporates Box-Cox transformations,Fourier representations with time varying coefficients,and ARMA error *** evaluation and analytical expressions for point forecasts and interval predictions under the assumption of Gaussian errors are derived,leading to a simple,comprehensive approach to forecasting complex seasonal time *** addition,the trigonometric formulation is used as a means of decomposing complex seasonal time series,which helps to identify and extract seasonal components which are otherwise not apparent in the time series plot *** performance of the TBATS model as evaluated by measures of forecast error are presented.

关键词： HIBOR forecast multiple seasonal

Uncompromised NK cell activation is essential for virus-specific CTL activity during acute influenza virus infection

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Cellular & Molecular Immunology 2018年第9期15卷 827-837页

作者： Yuan Liu Jian Zheng Yinping Liu Liyan Wen Lei Huang Zheng Xiang Kwok-Tai lam Aizhen Lv Huawei Mao Yu-Lung Lau Wenwei Tu Department of Pediatrics and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Medical Genetic Center Guangdong Women and Children HospitalGuangzhou 511400China Department of Radiology Georgia Regents UniversityAugustaGA 30912USA GRU Cancer Center Georgia Regents UniversityAugustaGA 30912USA Department of Pediatrics The University of Hong Kong—Shenzhen HospitalShenzhen 518053China

Natural killer (NK) cells are indispensable components of both the innate and adaptive immune response. However,their precise roles in the cross-talk between innate and adaptive immunity during influenza virus infection remaincontroversial. By comparing NK cell dynamics and activity under a sub-lethal dose and high dose of influenza virusinfection, we showed that influenza virus PR8 directly infected NK cells during natural infection, which wasconsistent with our previous findings obtained from an in vitro investigation of human NK cells. The impairments incytotoxicity and IFN-γ production by spleen NK cells following high-dose infection were accompanied by decreasedvirus-specific killing mediated by cytotoxic T lymphocytes (CTLs). Importantly, the weakened CTL activity could bereversed by adoptive transfer of spleen NK cells harvested from low-dose-infected mice but not healthy *** together, our data provide direct evidence supporting the contribution of NK cells to antiviral T-cellresponses. This study also indicates that a novel NK-targeted immune evasion strategy is used by influenza virusto shrink both innate and adaptive immune responses.

关键词： CTL influenza NK cell

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5085-5095页

作者： Ye Peng Lin Zhang Chris K.P.Mok Jessica Y.L.Ching Shilin Zhao Matthew K.L.Wong Jie Zhu Chunke Chen Shilan Wang Shuai Yan Biyan Qin Yingzhi Liu Xi Zhang Chun Pun Cheung Pui Kuan cheong ka Long Ip Adrian C.H.Fung Kenneth K.Y.Wong David S.C.Hui Francis K.L.Chan Siew C.Ng Hein M.Tun Microbiota I-Center(MaglC) Hong KongChina Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong KongChina Li ka Shing Institute of Health Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery LKS Faculty of MedicineThe University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina Centre for Gut Microbiota Research The Chinese University of Hong KongHong KongChina

The role of gut microbiota in modulating the durability of cOVID-19 vaccine immunity is yet to be *** this cohort study,we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline,1 month,and 6 months post vaccination(p.v).Neutralisation antibody,plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition.

关键词： vaccine immunity vaccines

论香港中文书面语的应用问题--港式中文阅读理解调查问卷分析

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中国语言战略 2017年第1期4卷 1-9,18页

作者：田小琳秦嘉丽山东大学香港社会大学持续教育学院

港式中文是香港中文书面语的一种流行形式,以夹用粤语语句和英语语句为主要特点。本文通过对港式中文阅读理解调查问卷的分析,讨论港式中文流行中存在的问题,谋求港式中文的健康发展。

关键词：港式中文通用中文粤式中文阅读理解调查问卷

Donor ductal anomaly is not a contraindication to right liver lobe donation

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 343-347页

作者： Kenneth SH Chok James YY Fung Wing Chiu Dai Sui Ling Sin ka Wing Ma Albert CY Chan Tan To Cheung Chung Mau Lo Department of Surgery The University of Hong Kong102 Pok Fu Lam RoadHong KongChina State Key Laboratory for Liver Research The University of Hong Kong102 Pok Fu Lam RoadHong KongChina Department of Medicine The University of Hong Kong102 Pok Fu Lam RoadHong KongChina

Background:Data of living-donor liver transplantation(LDLT)suggested that donor ductal anomaly may contribute to postoperative biliary complications in recipients and in *** retrospective study aimed to determine if the occurrence of postoperative biliary stricture in donors or recipients in rightlobe LDLT(RLDLT)is related to donor biliary anatomy ***:We analyzed our RLDLT recipients’clinical data and those of their graft *** recipients were divided into 2 groups:with and without postoperative biliary *** 2 groups were *** primary endpoints were donor biliary anatomy type and postoperative biliary complication incidence;the secondary endpoints were 1-,3-and 5-year graft and patient survival ***:Totally 127 patients were included in the study;25(19.7%)of them developed biliary anastomotic *** these 25 patients,16 had type A biliary anatomy,3 had type B,2 had type C,3 had type D,and 1 had type *** the 127 donors,96(75.6%)had type A biliary anatomy,13(10.2%)had type B,6(4.7%)had type C,10(7.9%)had type D,and 2(1.6%)had type *** stricture was seen in 2 donors,who had type A biliary *** of the recipients or donors developed bile *** association between the occurrence of postoperative biliary stricture and donor biliary anatomy type was found(P=0.527).Conclusions:The incidence of biliary stricture in donors or recipients after RLDLT was not related to donor biliary anatomy *** postoperative complications were similar in whatever type of donor bile duct anatomy,donor ductal anomaly should not be considered a contraindication to donation of right liver lobe.

关键词： Living donor liver transplantation Right liver donation Biliary complications Cholangiograms Ductal anomaly

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近红外荧光成像在小动物体内探测深度研究

航天医学与医学工程 2009年第4期22卷 277-280页

作者：欧嘉昌胡刚姚俊杰白净清华大学生物医学工程系北京100084

目的获取小动物体内近红外荧光深针的荧光图像,找出体内探测深度与荧光深针浓度两者之间的关系。方法采用低温制冷高灵敏度CCD作为系统的深测器,通过探测器采集出荧光探针在小动物体内,以及液态仿体内不同深度的荧光信号。结果得到了不... 详细信息

目的获取小动物体内近红外荧光深针的荧光图像,找出体内探测深度与荧光深针浓度两者之间的关系。方法采用低温制冷高灵敏度CCD作为系统的深测器,通过探测器采集出荧光探针在小动物体内,以及液态仿体内不同深度的荧光信号。结果得到了不同浓度的荧光探针在不同探测深度的荧光强度信息。结论找到了小鼠体内不同位置及深度的荧光强度关系。近似地找出了荧光探针浓度与探测强度的线性关系,可作为日后实验系统的参考。

关键词：荧光分子成像光学成像荧光强度

Aberrant methylation of Glutathione S-transferase P1 and E-cadherin in invasive ductal breast carcinoma and fibroadenoma

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中华乳腺病杂志（电子版） 2010年第5期4卷 14-19页

作者： Wings Tjing Yung Loo Mary Ngan Bing Cheung Louis Wing cheong Chow UNIMED Medical Institute Organisation for Oncology and Translational Research Hong Kong School of Chinese Medicine The University of Hong Kong Clinical Trial Centre Li Ka Shing Faculty of MedicineThe University of Hong Kong

Objective To investigate the hypermethylation status of glutathione transferase P1(GSTP1)and E-cadherin(ECAD),TSGs(tumor suppressor genes)in our breast cancer samples and explore their correlation with clinicopathological features of corresponding cancer *** One hundred and thirty-six IDC(invasive ductal carcinoma)patients were recruited for analysis and 16 fibroadenoma patients acted as *** extraction and methylation-specific PCR(MSP)were subsequently performed preceded by pathological *** The percentage of hypermethylated GSTP1 in carcinoma and fibroadenoma groups was 34.92% and 15.79% respectively and the percentage of hypermethylated ECAD in carcinomas and fibroadenomas was 18.00% and 0.00% *** had the highest percentage of c-erbB2 overexpression being 54.55% among the clinicopathological *** Hypermethylation patterns are frequent in IDC and seem to relate to c-erbB2 overexpression,and such epigenetic change should not be neglected in *** methylation status in cancer patients can be determined at early stage and it may be a reference for better treatment planning.

关键词：乳腺癌临床治疗疗效

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan ka Fai To Stephen lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell