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Thiol-Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal Microenvironment in Colitis

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Research 2024年第2期6卷 285-300页

作者： Junna Lu Tongfei Shi Chengxin Shi Fangman Chen Chao Yang Xiaochun Xie Zheng wang He Shen Jiaqi Xu Kam w.leong Dan Shao School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhouGuangdong 510006China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangdong 510006China Department of Plastic and Aesthetic Center The First Affliated Hospital of Zhejiang UniversityHangzhou 310000China Department of Biomedical Engineering Columbia UniversityNew YorkNY 10027USA School of Medicine South China University of TechnologyGuangzhouGuangdong 510006China CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and NanoBionicsChinese Academy of SciencesSuzhou 215123China CAS Key Laboratory for Biomedical Efects of Nanomaterials&Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Guangdong Provincial Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhou 510006China

The cell-specific functions of nitric oxide(NO)in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative *** most biomaterials show promise by eliciting the characteristics of NO,the insufficient storage,burst release,and pro-inflammatory side effects of NO remain as ***,we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles(MONs)that improve the storage and sustained release of NO,broadening the therapeutic window of NO-based therapy against *** tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone(Dex)in the intestinal microenvironment,specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage ***,such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide ***,the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid,even after delayed ***,our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.

关键词： sustained release disulfide

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BIODEGRADABLE POLYMERS wITH A PHOSPHORYL-CONTAINING BACKBONE:TISSUE ENGINEERING AND CONTROLLED DRUG DELIVERY APPLICATIONS

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Chinese Journal of Polymer Science 1995年第4期13卷 289-314页

作者： Kam w.leong 毛海泉卓仁禧 Department of Biomedical Engineering School of Medicine The Johns Hopkins University Baltimore MD 21205 USA Department of Chemistry Wuhan University Wuhan 430072

This review provides a glimpse of the potential of the biodegradable phos-phoryl-containing polymers in medical applications. Undoubtedly these polymerspossess unique properties that are yet to be fully understood. Many areas warrantfurther investigation and much optimization remains to be done. The fascinatingchemistry of phosphorus poses interesting hurdles but at the same time leavesample room for polymer scientists to exercise their creativity in designinginteresting biomaterials. As the mutual understanding between basic and clinicalscientists on the need of medical devices and the capabilities of these newbiomaterials expands, imaginative application of new biomaterials to other medi-cal applications can be expected.

关键词： biodegradable polymers phosphoryl-containing backbone controlled drug delivery

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Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases

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world Journal of Gastroenterology 2014年第5期20卷 1238-1247页

作者： Yanna Ko Rhys Butcher Rupert w leong Concord Hospital Gastroenterology and Liver Services and The University of New South Wales

Inflammatory bowel diseases(IBD)are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk *** genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory *** differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of *** are few opportunities that have been offered so *** aim to review the available migration studies on IBD,evaluate the known environmental factors associated with IBD,and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.

关键词： Inflammatory bowel disease, Crohn’ s disease, Ulcerative colitis, Epidemiology, Risk factor, Environment, Hygiene hypothesis

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Can microfluidics address biomanufacturing challenges in drug/gene/cell therapies?

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Regenerative Biomaterials 2016年第2期3卷 87-98页

作者： Hon Fai Chan Siying Ma Kam w.leong Department of Biomedical Engineering Department of Systems BiologyColumbia UniversityNew YorkNY 10032USA

Translation of any inventions into products requires *** of drug/gene/cell delivery systems will eventually face manufacturing challenges,which require the establishment of standardized processes to produce biologically-relevant products of high quality without incurring prohibitive *** technologies present many advantages to improve the quality of drug/gene/cell delivery *** also offer the benefits of *** remains unclear is whether they can meet the scale-up *** this perspective,we discuss the advantages of microfluidic-assisted synthesis of nanoscale drug/gene delivery systems,formation of microscale drug/cell-encapsulated particles,generation of genetically engineered cells and fabrication of macroscale drug/cell-loaded micro-/*** also highlight the scale-up challenges one would face in adopting microfluidic technologies for the manufacturing of these therapeutic delivery systems.

关键词： microfluidics biomanufacturing nanoparticle microencapsulation microfiber

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Projection of the Zhujiang(Pearl) River Delta's potential submerged area due to sea level rise during the 21st century based on CMIP5 simulations

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Acta Oceanologica Sinica 2015年第9期34卷 78-84页

作者： XIA Jiangjiang YAN Zhongwei ZHOU wen FONG Soi Kun leong Ka Cheng TANG Iu Man CHANG S w leong w K JIN Shaofei Key Laboratory of Regional Climate-Environment for Temperate East Asia Institute of Atmospheric PhysicsChinese Academy of Sciences Guy Carpenter Asia-Pacific Climate Impact Centre School of Energy and EnvironmentCity University of Hong Kong Macao Meteorological and Geophysical Bureau

Projections of potential submerged area due to sea level rise are helpful for improving understanding of the influence of ongoing global warming on coastal areas. The Ensemble Empirical Mode Decomposition method is used to adaptively decompose the sea level time series in order to extract the secular trend component. Then the linear relationship between the global mean sea level （GMSL） change and the Zhujiang （Pearl） River Delta （PRD） sea level change is calculated： an increase of 1.0 m in the GMSL corresponds to a 1.3 m （uncertainty interval from 1.25 to 1.46 m） increase in the PRD. Based on this relationship and the GMSL rise projected by the Coupled Model Intercomparison Project Phase 5 under three greenhouse gas emission scenarios （representative concentration pathways, or RCPs, from low to high emission scenarios RCP2.6, RCP4.5, and RCP8.5）, the PRD sea level is calculated and projected for the period 2006-2100. By around the year 2050, the PRD sea level will rise 0.29 （0.21 to 0.40） m under RCP2.6, 0.31 （0.22 to 0.42） m under RCP4.5, and 0.34 （0.25 to 0.46） m under RCP8.5, respectively. By 2100, it will rise 0.59 （0.36 to 0.88） m, 0.71 （0.47 to 1.02） m, and 1.0 （0.68 to 1.41） m, respectively. In addition, considering the extreme value of relative sea level due to land subsidence （i.e., 0.20 m） and that obtained from intermonthly variability （i.e., 0.33 m）, the PRD sea level will rise 1.94 m by the year 2100 under the RCP8.5 scenario with the upper uncertainty level （i.e., 1.41 m）. Accordingly, the potential submerged area is 8.57x103 km2 for the PRD, about 1.3 times its present area.

关键词： sea level Zhujiang (Pearl) River Delta (PRD) representative concentration pathways (RCPs) CMIP5 submerged area Ensemble Empirical Mode Decomposition (EEMD)

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Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease:A case report and review of literature

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world Journal of Clinical Cases 2022年第8期10卷 2569-2576页

作者： Michael Au Nikola Mitrev Rupert w leong Viraj Kariyawasam Department of Gastroenterology and Hepatology Blacktown and Mt Druitt HospitalsWestern Sydney Local Health DistrictSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversityBlacktown 2148New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustralia Endoscopy Department and Inflammatory Bowel Disease Service Concord HospitalSydney 2137New South WalesAustralia Concord Clinical School University of SydneySydney 2137New South WalesAustralia Inflammatory Bowel Disease Service Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustria

BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated *** had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with *** CD diagnosis was confirmed radiologically,endoscopically,histologically,and *** patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on *** adverse reactions were observed for the duration of *** safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was *** DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated *** biologics,which have improved safety profiles and gut specificity,may provide promising avenues for ***,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy *** evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary *** research from controlled trials is needed to better understand the safety profile of DBT in *** immunopathological mechanisms underlying DBT also remain to be clarified.

关键词： Dual biologic therapy Combination Immunosuppression Safety Autoimmune Case report

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Development and clinical trial of a novel bioactive bone cement

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Frontiers of Medicine 2008年第2期2卷 117-126页

作者： John CY leong Zhaoyang LI william w LU The Open University of Hong Kong Hong Kong SAR.China Department of Orthopaedics and Traumatology The University of Hong KongHong Kong SAR.China

Strontium(Sr)and related compounds have become more attractive in the prevention and treatment of ***,we developed a novel bioactive bone cement which is mainly composed of strontium-con-taining hydroxyapatite(Sr-HA)filler and bisphenol A diglycidylether dimethacrylate(Bis-GMA)*** bone cement is superior to conventional polymethylmethacrylate(PMMA)bone cement in bioactivity,biocompatibility,and *** also has shown sufficient mechanical strength properties for its use in percutaneous vertebro-plasty(PVP)and total hip replacement(THR).In this paper,we review the in vitro,in vivo and clinical evidence for the effectiveness of this bioactive bone cement.

关键词： Strontium osteoporosis bioactive bone cement vertebroplasty total hip replacement

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Faecal microbiota transplantation as an elixir of youth

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 488-489页

作者： Craig Haifer Sudarshan Paramsothy Rupert w.leong Concord Clinical School The University of SydneySydneyAustralia Gastroenterology and Liver Services Concord Repatriation General HospitalSydneyAustralia South western Clinical School UNSWSydneyAustralia

The intestinal microbiota has been increasingly seen to be responsible for various gastrointestinal disorders such as inflammatory bowel diseases(1).However,their effects on systemic physiological processes unrelated ... 详细信息

关键词： diseases gastrointestinal unrelated

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基于反射镜光管理结构的高响应有机光电探测器

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太赫兹科学与电子信息学报 2024年第9期22卷 1009-1013页

作者：崔久朋梁浩琪孙华斌于志浩吴洁 TAN Chee leong 徐勇南京邮电大学集成电路科学与工程学院江苏南京210003

与无机材料光电探测器相比,使用有机半导体材料制备的光电探测器具有制作工艺简单、易于集成、柔性好、延展性好、性能稳定等优点,但由于吸收层较薄,外部量子效率(EQE)和响应度通常较低。因此,如何利用不同的光学结构最大化有机薄膜吸... 详细信息

与无机材料光电探测器相比,使用有机半导体材料制备的光电探测器具有制作工艺简单、易于集成、柔性好、延展性好、性能稳定等优点,但由于吸收层较薄,外部量子效率(EQE)和响应度通常较低。因此,如何利用不同的光学结构最大化有机薄膜吸收层的吸收率被广泛研究。本文成功制备出一种基于光管理结构的高响应度有机光电探测器。实验结果表明,在-10 V的偏压下,暗电流低至3.2 nA。对于有机吸收薄层,在260~980 nm波长下均具有良好的光电流响应,尤其在850 nm波长下获得了0.03 A/w响应度。与普通的有机光电探测器相比,具有光管理结构的有机光电探测器响应度显著提高了530%,比探测率增加了一个数量级,整体量子效率提高了200%。以上实验结果证明了光学增强结构对这种薄膜吸收层光电探测器的重要性,其性能尚可进一步提高,可媲美传统厚膜吸收层光电探测器。

关键词：有机光电探测器反射光管理结构光电导体

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Creation of biomimetic microenvironments for regenerative medicine by polymer nanoengineering

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医用生物力学 2013年第S1期28卷 80-83页

作者： Yong Yang Karina Kulangara Kam w.leong Department of Chemical Engineering West Virginia University Biomedical Engineering Department Duke University

Introduction Regenerative medicine holds great promise for the treatment of diseases that are unbeatable at present,such as various gene and neurological disorders,cardiovascular diseases,as well as hematological *** of this potential remains limited by current challenges associated with the control of cell phenotype and function in cell *** this respect,the fate of cells is dictated by the in vivo microenvironment where these cells interact with both the extracellular matrix(ECM)and with neighboring *** ECM serves as a structural support for cells and provides,in concert with spatio-temporally arranged biochemical cues such as soluble factors,topographical and mechanical cues that direct cell adhesion,spreading,migra-

关键词： cardiovascular neurological biochemical regenerative PDMS interact phenotype Creation holds osteogenesis

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