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Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy

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Science China(Life Sciences) 2015年第6期58卷 521-530页

作者： LIU Jin yeung patrick ka kit CHENG Lu LO Amy Cheuk Yin CHUNG Stephen Sum Man CHUNG Sookja Kim Department of Anatomy Li Ka Shing Faculty of Medicine The University of Hong Kong Department of Ophthalmology Li Ka Shing Faculty of Medicine The University of Hong Kong Research Centre of Heart Brain Hormone and Healthy Aging Li Ka Shing Faculty of Medicine The University of Hong Kong Division of Science and Technology United International College Zhuhai 519085 China State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac 1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion （tMCAO） was performed on Epacl-deficient （Epacl-/- ） mice, Epac2-deficient （Epac2-/-） mice, and their wild type counter-parts （Epacl＋/＋ and Epac2＋/＋）. Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neu-ronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 （AQP4）, glial fibrillary acidic protein （GFAP）, peroxiredoxin 6 （Prx6） were observed in ipsilateral retinae. Epac2 / ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2＋/＋. However, Epacl-/- ipsilateral retinae displayed similar pathology as those in Epacl＋/＋ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.

关键词： Epac retina ischemia retinopathy

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Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one- compound peptide libraries

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Cellular & Molecular Immunology 2017年第3期14卷 308-318页

作者： Nicki YH Leung Christine YY Wai Marco HK Ho Ruiwu Liu kit S Lam Jin Jun Wang Shang An Shu ka Hou Chu patrick SC Leung School of Life Sciences The Chinese University of Hong Kong Shatin N.T. Hong Kong SAR China Department of Pediatrics and Adolescent Medicine Queen Mary Hospital The University of Heng Kong Pokfulam Hong Kong SAR China Department of Biochemistry and Molecular Medicine University of California Davis CA 95616 USA Division of Rheumatology/Allergy School of Medicine University of California Davis CA 95616 USA

The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.

关键词： epitope mimotope OBOC peptide library tropomyosin

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Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy

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Gastroenterology Report 2020年第1期8卷 25-30,I0001页

作者： Eva Rajha patrick Chaftari Mona kamal Julian Maamari Christopher Chaftari Sai-Ching Jim yeung Department of Emergency Medicine The University of Texas MD Anderson Cancer CenterHoustonTXUSA Schoool of Medicine Lebanese American UniversityByblosLebanon Biomedical Engineering College of EngineeringTexas A&M UniversityCollege StationTXUSA

Immunotherapy with checkpoint inhibitors has revolutionized cancer therapy and is now the standard treatment for several different types of cancer,supported by favorable outcomes and good ***,it is linked to multiple immune manifestations,referred to as immune-related adverse events(irAEs).These adverse events frequently affect the skin,colon,endocrine glands,lungs,and *** gastrointestinal system is one of the most commonly affected organ systems and is responsible for the most frequent emergency visits resulting from ***,because immune checkpoint inhibitors are a recent addition to our arsenal of cancer drugs,many health-care providers remain unfamiliar with the management of *** involved in the treatment of oncology patients who have received checkpoint inhibitors are currently encountering cases of abdominal pain,diarrhea,and other nonspecific symptoms that may be challenging to *** article reviews the gastrointestinal,hepatic,and pancreatic toxicities of checkpoint inhibitors and provides an approach to their diagnosis and recommended *** also highlights the management of irAEs according to their toxicity grading and specifically discusses the instances in which corticosteroids should be administered and/or the immune checkpoint inhibitors should be withheld.

关键词： immune checkpoint inhibitor immune-related adverse events colitis enterocolitis liver toxicity pancreatic toxicity

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Atypical electrocardiographic manifestations of ischemia: a case of dynamic Wellens patterns

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Journal of Geriatric Cardiology 2018年第11期15卷 710-712页

作者： Alex Tsz Lai Ngan RN Cynthia yeung Lorraine Chiang Tong LIU Gary Tse ka Hou Christien Li Department of Medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong China Li ka Shing Institute of Health Sciences Faculty of Medicine Chinese University of Hong Kong Hong Kong China Department of Medicine Queen's University Kingston Ontario Canada Li ka Shing Faculty of Medicine University of Hong Kong Hong Kong China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of Cardiology Tianjin Institute of Cardiology the Second Hospital of Tianjin Medical University Tianjin China Faculty of Medicine Newcastle University NewcastleUK

A 55-year-old male with hypertension, hyperlipidemia, impaired fasting glucose, obesity, gout, and osteoarthritis, statin-induced myopathy, but no known cardiac disease, presented with a one day history of intermittent exertional chest discomfort without radiation. Symptoms included sweating, dyspnea, dizziness, and upper limb numbness.

关键词： Dynamic pattern Ischemia Wellens

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Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

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Biomedical and Environmental Sciences 2009年第4期22卷 269-277页

作者： ka-YING MA ZE-SHENG ZHANG SHU-XIN ZHAO QI CHANG YIN-MEI WONG SAI YING VENUS yeung Yu HUANG AND ZHEN-YU CHEN Food and Nutritional Sciences Program Department of Biochemistry The Chinese University of Hong Kong Shatin New Territories Hong Kong China Faeulty of Food Engineering & Biotechnology Tianjin University of Science and Technology Tianjin 300457 China Institute of Medicinal Plant Development Chinese Academy of Medical Science & Peking Union Medical College Beijing 100193 China Department of Physiology The Chinese University of Hong Kong Shatin New Territories Hong Kong China

Objective To investigate the hypocholesterolemic activity of red yeast rice （RYR） and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR （0.1RYR） or 0.3% RYR （0.3RYR）. Blood （0.5 mL） was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, fiver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 34 folds compared with the conlrol value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

关键词： Bile acid Cholesterol Monacolin Red yeast rice Triacylglcerols

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Perfluorooctane sulfonate(PFOS) and related fluorochemicals in chicken egg in China

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Chinese Science Bulletin 2008年第4期53卷 501-507页

作者： WANG Yuan yeung Leo Wai Yin YAMASHITA Nobuyoshi TANIYASU Sachi SO Man ka Margaret B. MURPHY LAM Paul Kwan Sing Centre for Coastal Pollution and Conservation Department of Biology and Chemistry City University of Hong Kong 83 Tat Chee Avenue Kowloon Tong HKSAR China National Institute of Advanced Industrial Science and Technology (AIST) 16-10nogawa Tsukuba Ibaraki 305-8569 Japan

The ubiquitous occurrence of perfluorinated compounds(PFCs) in environmental samples has drawn much *** human exposure studies found relatively high perfluorooctane sulfonate(PFOS) concentrations in blood samples from several cities in China when compared with other *** objectives of the present study were:(1) to measure PFC concentrations and compositions in chicken egg samples from local markets in China;and(2) to conduct a preliminary human health risk assessment of egg *** pooled egg samples from eight locations were analyzed for 11 *** results showed that close to 100% of the PFOS in the egg was distributed in egg yolk and PFOS was not detected in egg white(<0.08 ng/g wet weight,w/w).Of the perfluoroalkylsulfonates,only PFOS was detected in all egg samples,while of the perfluoroalkylcarboxylates,perfluoroundecanoic acid(PFUnDA) was detected in all samples,followed by perfluorooctanoate(PFOA)(75% occurrence) and perfluorodecanoic acid(PFDA)(50% occurrence).PFOS concentrations in egg ranged from 45.0 to 86.9 ng/g w/*** results suggested that current concentrations of PFOS in domestic chicken eggs are unlikely to cause immediate harm to Chinese populations.

关键词：中国鸡蛋人体健康风险评估污染物含氟化合物全氟辛烷磺酸

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THROUGH & COMBINED TRANSPORT BILLS OF LADING

THROUGH & COMBINED TRANSPORT BILLS OF LADING

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中国律师2005年海商法研讨会

作者： patrick yeung Holman Fenwick & Willan

A. INTRODUCTION TO MULTIMODAL TRANSPORT BILLS OF LADING 1. Commercial Context 1.1 Creature of containerisation, "the late twentieth century transport revolution". 1.2 Container operators, who only account for about 10% of world tonnage in deadweight terms, now carry about 65% of world cargo by value. 1.3 With containers and different modes of transport, cargoes can be carried door-to-door. 1.4 Generally, numerous parties are involved in a door-to-door movement including:

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Appadtion of the NAC Transcription Factors Predates the Emergence of Land Plants

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Molecular Plant 2016年第9期9卷 1345-1348页

作者： Aude Maugarny-Cales Beatriz Gonqalves Stefan Jouannic Michael Melkonian Gane ka-Shu Wonge patrick Laufs Institut Jean-Pierre Bourgin INRA AgroParisTech CNRS Universite ParisSaclay RD10 78026 Versailles Cedex France Univ. Pads-Sud Universite Paris-Saclay 91405 Orsay France IRD UMR DIADE 911 Avenue Agropolis BP6450134394 Mbntpellier Cedex 5 France LMI RICE IRD USTH National Key Laboratory for Plant Cell Biotechnology Agronomical Genetics Institute Pham Van Dong Road Hanoi Vietnam Botany Department Cologne Biocenter University of Cologne 50674 Cologne Germany Beijing Genomics Institute-Shenzhen Shenzhen 518083 China Department of Biological Sciences University of Alberta Edmonton AB T6G 2E9 Canada Department of Medicine University of Alberta Edmonton AB T6G 2E Canada These authors contributed equally to this article.

Dear Editor The NAC （for NO APICAL MERISTEM [NAM], Arabidopsis TRANSCRII^TION ACTIVATOR FACTOR [ATAF] and CUP- SHAPED COTYLEDON [CUC]） proteins are one of the largest families of plant-specific transcription factors （Nagata et aL, 2015）. They are involved in many different biological processes including development and the response to biotic and abiotic stresses. To date, NAC transcription factors have only been identified in land plants （Zhu et al., 2012; Nagata et al., 2015）; and some of them control land-plant-specific processes, such as the formation of specialized water-conducting systems （Xu et al., 2014）. Therefore, it has been suggested that their appearance accompanied the emergence of land plants. Here, we exploited the transcriptomic data generated within the 1000 plants project （***, Wickett et al., 2014） to revisit the origin of NAC proteins. Our careful analysis shows that NAC transcription factors appeared before the ernergence of land plants as we detected their homologs in several groups of streptophyte green algae. The possible significance of this finding is discussed.

关键词： @@

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Mimotope-based allergen-specific immunotherapy: ready for prime time?

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Cellular & Molecular Immunology 2019年第11期16卷 890-891页

作者： Nicki Y.H.Leung Christine Y.Y.Wai ka Hou Chu patrick S.C.Leung Department of Paediatrics The Chinese University of Hong KongShatinHong KongChina School of Life Sciences The Chinese University of Hong KongShatinHong KongChina Division of Rheumatology/Allergy School of MedicineUniversity of CaliforniaDavisCA 95616USA

INTRODUCTION Allergen-specific immunotherapy(AIT)is a therapeutic strategy to restore the normal immune response by suppressing inflammatory effector cells and inducing regulatory cells specific to the culprit ***,AIT is achieved by administering escalating doses of allergen over a long treatment ***,the use of unmodified allergens for AIT often results in severe anaphylactic side effects,and alternative approaches such as hypoallergens and T-cell epitopes with enhanced safety have been *** use of mimotopes in AIT is a relatively new concept,but earlier proof-ofconcept studies showed promising results for mimotopes,with decent safety profiles and immunomodulatory *** the treatment of cancer with mimotope-based immunotherapy has already been tested in clinical trials2,mimotope-based AIT remains largely in the preclinical ***,we revisit the pros and cons of mimotope-based AIT and describe recent findings concerning the use of mimotopes in AIT.

关键词： immunotherapy doses treatment

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A MULTIPLE INTELLIGENT AGENT SYSTEM FOR CREDIT RISK PREDICTION VIA AN OPTIMIZATION OF LOCALIZED GENERALIZATION ERROR WITH DIVERSITY

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Journal of Systems Science and Systems Engineering 2007年第2期16卷 166-180页

作者： Daniel S. yeung Wing W. Y. NG Aki P. F. CHAN patrick P. K. CHAN Michael FIRTH Eric C. C. TSANG Media and Life Science Computing Laboratory Shenzhen Graduate School Harbin Institute of Technology Shenzhen 518055 China Department of Computing Hong Kong Polytechnic University Hong Kong China Department of Finance and Insurance Lingnan University Hong Kong

Company bankruptcies cost billions of dollars in losses to banks each year. Thus credit risk prediction is a critical part of a bank＇s loan approval decision process. Traditional financial models for credit risk prediction are no longer adequate for describing today＇s complex relationship between the financial health and potential bankruptcy of a company. In this work, a multiple classifier system （embedded in a multiple intelligent agent system） is proposed to predict the financial health of a company. In our model, each individual agent （classifier） makes a prediction on the likelihood of credit risk based on only partial information of the company. Each of the agents is an expert, but has limited knowledge （represented by features） about the company. The decisions of all agents are combined together to form a final credit risk prediction. Experiments show that our model out-performs other existing methods using the benchmarking Compustat American Corporations dataset.

关键词： Credit rating business intelligence localized generalization error multiple classifier system feature grouping

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