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Understanding neutralising antibodies against SARS-CoV-2 and theirimplications in clinical practice

Military Medical Research 2022年第2期9卷 215-230页

作者： Natalie Yan-Lin Pang Alexander Shao-Rong Pang Vincent T.Chow De-Yun Wang Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore Department of Microbiology and Immunology National University of SingaporeScience Drive 2Singapore 117545Singapore Infectious Diseases translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore Department of Otolaryngology Yong Loo Lin School of MedicineNational University of Singapore1E Kent Ridge RoadSingapore 119228Singapore

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. this rapidly evolving and unrelenting SARS-CoV-2has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies(NAbs) and their implications in clinical practice. the aspects include the pathophysiology of the immune response,particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.

关键词： Severe acute respiratory syndrome coronavirus Coronavirus disease 2019 Neutralising antibodies Persistence Spike glycoprotein Receptor-binding domain B cells t cells Convalescent plasma

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Evaluation of antiviral activities of Houttuynia cordata thunb.extract,quercetin,quercetrin and cinanserin on murine coronavirus and dengue virus infection

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Asian Pacific Journal of tropical Medicine 2016年第1期9卷 1-7页

作者： K.H.Chiow M.C.Phoon thomas Putti Benny K.H.tan Vincent T.Chow Department of Microbiology Department of Pathologyand Department of PharmacologyYong Loo Lin School of MedicineNational University Health SystemNational University of Singapore

Objective:to evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(H.cordata) thunb.(Saururaceae) and three of its constituent flavonoids(quercetin.quercitrin and rutin) against murine coronavirus and dengue virus(DENV).Methods:the antiviral activities of various concentrations of the EA fraction of H.cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus(MHV) and DENV type 2(DENV-2).Cinanserin hydrochloride was also tested against MHV.the EA fraction of H.cordata was tested for acute oral toxicity in C57BL/6 mice.Results:the EA fraction of H.cordata inhibited viral infectivity up to 6 d.Cinanserin hydrochloride was able to inhibit MHV for only 2 d.the 50%inhibitory concentrations(IC_(50)) of the EA fraction of H.cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2with absence of cytotoxicity.the mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity,with normal histological features of major organs.Certain flavonoids exhibited comparatively weaker antiviral activity,notably quercetin which could inhibit both MHV and DENV-2.this was followed by quercitrin which could inhibit DENV-2but not MHV,whereas rutin did not exert any inhibitory effect on either virus.When quercetin was combined with quercitrin,enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed.However,the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction.Conclusions:the compounds in H.cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vim.H.cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.

关键词： Houttuynia cordata Murine coronavirus Dengue virus Quercetin Quercetrin Cinanserin

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Inhibitory activities of extracts of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa, Ziziphus mauritiana as well as their compounds of gallic acid and emodin against dengue virus

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Asian Pacific Journal of tropical Medicine 2018年第4期11卷 265-271页

作者： Riffat Batool Ejaz Aziz tariq Mahmood Benny KH tan vincent tK chow Department of Plant Sciences Faculty of Biological Sciences Quaid-i-Azam University Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Department of Microbiology and Immunology Yong Loo Lin School of Medicine National University of Singapore

Objective: to investigate the inhibitory effects against dengue virus serotype 2(DENV-2) by five different fractions(extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents(gallic acid, emodin, and isovanillic acid). Methods: All the samples were tested for cytotoxicity on baby hamster kidney cells by Mtt assay and for anti-DENV-2 activity by plaque reduction neutralization assay using two DENV-2 doses(45 and 90 plaqueforming units or PFU). Results: All the samples except isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity(without cytotoxicity) when administered to cells before infection, but were not effective when given 6 h post-infection. the methanol extract of Rumex dentatus demonstrated the highest antiviral efficacy by inhibiting DENV-2 replication, with IC_(50) of 0.154 μg/mL and 0.234 μg/mL, when added before infection with 45 and 90 PFU of virus, respectively. Gallic acid also exhibited significant antiviral effects by prophylactic treatment prior to virus adsorption on cells, with IC_(50) of 0.191 μg/mL and 0.522 μg/mL at 45 and 90 PFU of DENV-2 infection, respectively. Conclusions: the highly potent activities of the extracts and constituent compounds of these plants against DENV-2 infectivity highlight their potential as targets for further research to identify novel antiviral agents against dengue.

关键词： Dengue virus Rumex dentatus Commelina benghalensis Ajuga bracteosa Ziziphus mauritiana Gallic acid

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Reverse Genetic Analysis of Adaptive Mutations within the Capsid Proteins of Enterovirus 71(EV-A71) Strains Necessary for Infection of CHO-K1 Cells

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Virologica Sinica 2020年第1期35卷 110-114页

作者： Carla Bianca Luena Victorio Yishi Xu Qimei Ng vincent t.K.chow Kaw Bing Chua temasek Lifesciences Laboratory 1 Research LinkNational University of SingaporeSingapore 117604Singapore Host and Pathogen Interactivity Laboratory Department of MicrobiologyYong Loo Lin School of MedicineNational University Health SystemNational University of SingaporeSingapore 117545Singapore Present Address:Laboratory for translational and Molecular Imaging Cancer and Stem Cell Biology ProgrammeDuke-NUS Medical SchoolSingapore 169857Singapore

Dear Editor,Previous studies had described the adaptation of enterovirus 71(EV-A71)strains that enabled entry and viral replication in Chinese Hamster Ovary(CHO)cell line(Zaini and McMinn 2012;Zaini et al.2012).these adapted strains derived from serial passage of a clinical isolate in CHO cells exhibited an amino acid substitution at VP2149,which enhanced viral replication by 100*1000-fold compared to the clinical isolate.the VP2149 mutation was claimed responsible for adaptation to CHO-K1 cells without performing detailed molecular analyses to support these claims.In this study,we evaluate various VP1 and VP2 mutations in two CHO-adapted EV-A71 strains derived in our lab to assess their contribution to the phenotype of CHO cell adaptation.

关键词： adapted passage claimed

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the host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2039-2055页

作者： Kan Xing Wu thinesshwary Yogarajah Marcus Wing Choy Loe Parveen Kaur Regina Ching Hua Lee Chee Keng Mok Yi Hao Wong Patchara Phuektes Li Sze Yeo vincent t.K.chow Yong Wah tan Justin Jang Hann Chu Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University Health SystemNational University of SingaporeSingapore 117597Singapore Department of Pathobiology Faculty of Veterinary MedicineKhonkaen UniversityKhonkaen 40002Thailand Infectious Disease Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A∗STAR)Singapore 138648Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore NUSMed Biosafety Level 3 Core Facility Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore

Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.the ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at threonine 1337(t1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.these findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.

关键词： Positive-sense RNA viruses Peruvoside Antiviral CDKI signaling Viral factories Calcium efflux Broad-spectrum Golgi apparatus

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Neurovascular ageing:transcriptomic readout and implications on therapeutic targeting in Alzheimer’s disease

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Neural Regeneration Research 2021年第12期16卷 2411-2412页

作者： Zhongqi Li Bonaventure Ip vincent C.t.Mok Ho Ko Division of Neurology Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina(Li ZKo H)Margaret K.L.Cheung Research Centre for Management of ParkinsonismThe Chinese University of Hong KongHong Kong Special Administrative RegionChina chow Yuk Ho technology Centre for Innovative Medicine The Chinese University of Hong KongHong Kong Special Administrative RegionChina Gerald Choa Neuroscience Centre School of Biomedical SciencesDepartment of PsychiatryPeter Hung Pain Research InstituteFaculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative RegionChina

Ageing is one of the greatest risk factors for neurodegenerative diseases.How the complex biological changes in ageing increase the brain’s susceptibility to neurodegeneration remains incompletely understood.Research into neurodegenerative disorders has shifted from a neuron-centric approach,to the contributing roles of age-related neurovascular and glial cell dysfunction.

关键词： incomplete susceptibility ageing

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Magnetic resonance imaging manifestations of cerebral small vessel disease:automated quantification and clinical application

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Chinese Medical Journal 2021年第2期134卷 151-160页

作者： Lei Zhao Allan Lee Yu-Hua Fan vincent C.t.Mok Lin Shi BrainNow Research Institute ShenzhenGuangdong 518000China Department of Neurology The First Affiliated HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological DiseasesNational Key Clinical Department and Key Discipline of NeurologyGuangzhouGuangdong 510080China Department of Medicine and therapeutics The Chinese University of Hong KongHong Kong 999077China Gerald Choa Neuroscience Centre Margaret KL Cheung Research Centre for Management of ParkinsonismTherese Pei Fong Chow Research Centre for Prevention of DementiaLui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong Kong 999077China

the common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.the CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.this review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.the added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

关键词： Cerebral small vessel disease Neuroimaging manifestations Automated quantification Clinical relevance

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Upfront consolidation treatment with 131I-mIBG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma

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Pediatric Investigation 2020年第3期4卷 168-177页

作者： Jianhua Feng Frankie Wt Cheng Alex WK Leung vincent Lee Eva WM Yeung Hoi Ching Lam Jeanny Cheung Grace KS Lam terry tW chow Carol LS Yan Chi Kong Li Department of Paediatrics The Chinese University of Hong KongHong KongChina Department of Paediatrics The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Paediatrics and Adolescent Medicine Hong Kong Children’s HospitalHong KongChina Department of Clinical Oncology Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina

Importance:131I-metaiodobenzylguanidine(131I-mIBG)has a significant targeted antitumor effect for neuroblastoma.However,currently there is a paucity of data for the use of 131I-mIBG as a"front-line"therapeutic agent in those patients with newly diagnosed high-risk neuroblastoma as part of the conditioning regimen for myeloablative chemotherapy(MAC).Objective:to evaluate the feasibility of upfront consolidation treatment with 131I-mIBG plus MAC and hematopoietic stem cell transplantation(HSCt)in high-risk neuroblastoma patients.Methods:A retrospective,single-center study was conducted from 2003-2019 on newly diagnosed high-risk neuroblastoma patients without progressive disease(PD)after the completion of induction therapy.they received 131I-mIBG infusion and MAC followed by HSCt.Results:A total of 24 high-risk neuroblastoma patients were enrolled with a median age of 3.0 years at diagnosis.After receiving this sequential consolidation treatment,3 of 13 patients who were in partial response(PR)before 131I-mIBG treatment achieved either complete response(CR)(n=1)or very good partial response(VGPR)(n=2)after HSCt.With a median follow-up duration of 13.0 months after 131I-mIBG therapy,the 5-year event-free survival and overall survival rates estimated were 29%and 38%for the entire cohort,and 53%and 67%for the patients who were in CR/VGPR at the time of 131I-mIBG treatment.Interpretation:Upfront consolidation treatment with 131I-mIBG plus MAC and HSCt is feasible and tolerable in high-risk neuroblastoma patients,however the survival benefit of this 131I-mIBG regimen is only observed in the patients who were in CR/VGPR at the time of 131I-mIBG treatment.

关键词： Neuroblastoma 131I-mIBG transplantation

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New Characterizations of the Dual Spaces of Hardy-amalgam Spaces

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Acta Mathematica Sinica,English Series 2022年第3期38卷 519-546页

作者： Zobo vincent de Paul ABLE Justin FEUtO Laboratoire de Mathématiques Fondamentales UFR Mathématiques et InformatiqueUniversitéFélixHouphouët-Boigny Abidjan-Cocody22B.P.582Abidjan 22Côte d’Ivoire Laboratoire de Mathématiques Fondamentales UFR Mathématiques et InformatiqueUniversitéFélixHouphouët-Boigny Abidjan-Cocody22B.P.1194Abidjan 22Côte d’Ivoire

In this paper,carrying on with our study of the Hardy-amalgam spaces H^((q,p)) and H^((q,p))_(loc)(0terization of their dual spaces whenever 0these ch... 详细信息

In this paper,carrying on with our study of the Hardy-amalgam spaces H^((q,p)) and H^((q,p))_(loc)(0terization of their dual spaces whenever 0these characterizations coincide with those obtained in our earlier papers.

关键词： Amalgam spaces Hardy-amalgam spaces duality Pseudo-differential operators

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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 disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.the objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FASt),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value oftively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(Pthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(Pth patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(Ptifying NAFLD patients with high risk of CKD.Early 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

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