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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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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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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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Dendritic cell-mimicking scaffolds for ex vivo T cell expansion

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Bioactive Materials 2023年第3期21卷 241-252页

作者： Hye Sung Kim Tzu-Chieh Ho Moshe J.willner Michael w.Becker Hae-won Kim kam w.leong Department of Biomedical Engineering Columbia UniversityNew YorkNYUSA Institute of Tissue Regeneration Engineering Dankook UniversityCheonanRepublic of Korea wilmot Cancer Institute University of Rochester Medical CenterRochesterNYUSA Department of Regenerative Dental Medicine College of DentistryDankook UniversityCheonanRepublic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonanRepublic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonanRepublic of Korea Department of Systems Biology Columbia University Irving Medical CenterNew YorkNY10032USA

we propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory *** DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in *** demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized *** importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing *** addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient ***,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.

关键词： Adoptive cell therapy Ex vivo T cell expansion Cytotoxic T cell Dendritic cell membrane Cell membrane coating Scaffold

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Degradation-resistant implanted biomaterials establish an immunosuppressive microenvironment that induces T cell exhaustion by recruiting myeloid cells

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Fundamental Research 2022年第4期2卷 648-658页

作者： Qin Fan Huaxing Dai Jinyu Bai Jialu Xu Qingle Ma Ziying Fei Xiaozhong Zhou kam w.leong Chao wang Institute of Functional Nano&Soft Materials Jjangsu Key Laboratory for Carbon-based Functional Materials and evices Soochow UniversitySuzhou 215123China Department of Orthopedics The Second Affliated Hospital of Soochow UniversitySuzhou 215004China Department f Biomedical Enginering Columbia UniversityNew YorkNY 10027USA

Implanted biomaterials have transformed healthcare and the treatment of injury and disease,but their infuence on the local immune landscape remains *** we discovered that degradation-resistant titanium-based implants establish an immunosuppressive microenvironment by recruiting myeloid cells,including monocytes,macrophages,neutrophils,and myeloid-lineage dendritic *** normal tissues,the tissues nearby implants exhibit an chronic inflamed and immunosuppressive status characterised by myeloid-rich,T cell-exhaustion gene signature by single-cell RNA *** C treatment provides an effective strategy to rescue the immunosuppressive microenvironment,which can be used as a regular supplement to reduce the risk of malignant cell survival around the implants.

关键词： TiO_(2)nanoparicles Immune microenvironment Myeloid cells mplants Immunosuppressive

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Material Engineering in Gut Microbiome and Human Health

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Research 2022年第3期2022卷 145-176页

作者： Letao Yang Lin Y.Hung Yuefei Zhu Suwan Ding Kara G.Margolis kam w.leong Department of Biomedical Engineering Columbia UniversityNew YorkNYUSA Department of Pediatrics Columbia UniversityNew YorkNew YorkUSA Department of Systems Biology Columbia UniversityNew YorkNYUSA

Tremendous progress has been made in the past decade regarding our understanding of the gut microbiome’s role in human ***,however,a comprehensive and focused review marrying the two distinct fields of gut microbiome and material research is *** bridge the gap,the current paper discusses critical aspects of the rapidly emerging research topic of“material engineering in the gut microbiome and human health.”By engaging scientists with diverse backgrounds in biomaterials,gut-microbiome axis,neuroscience,synthetic biology,tissue engineering,and biosensing in a dialogue,our goal is to accelerate the development of research tools for gut microbiome research and the development of therapeutics that target the gut *** this purpose,state-of-the-art knowledge is presented here on biomaterial technologies that facilitate the study,analysis,and manipulation of the gut microbiome,including intestinal organoids,gut-on-chip models,hydrogels for spatial mapping of gut microbiome compositions,microbiome biosensors,and oral bacteria delivery *** addition,a discussion is provided regarding the microbiome-gut-brain axis and the critical roles that biomaterials can play to investigate and regulate the ***,perspectives are provided regarding future directions on how to develop and use novel biomaterials in gut microbiome research,as well as essential regulatory rules in clinical *** this way,we hope to inspire research into future biomaterial technologies to advance gut microbiome research and gut microbiome-based theragnostics.

关键词： biomaterials directions biome

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A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors

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Journal of Integrative Plant Biology 2024年第5期66卷 1007-1023页

作者： Meijing Yang Shuai Chen Shey-Li Lim Lang Yang Jia Yi Zhong Koon Chuen Chan Zhizhu Zhao kam-Bo wong Junqi wang Boon leong Lim School of Biological Sciences University of Hong KongPokfulam 999077Hong KongChina Department of Biology Southern University of Science and TechnologyShenzhen 518055China School of Biomedical Engineering Shenzhen UniversityShenzhen 518060China School of Life Sciences The Chinese Universityof Hong KongShatin 999077HongKongChina State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongShatin 999077Hong KongChina HKU Shenzhen Institute of Research and Innovation Shenzhen 518052China

In plants,thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC(translocon on the outer chloroplast membrane)and the TOM(translocon on the outer mitochondrial membrane)complexes for import into those *** degradation pathways for these receptors are ***,we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored *** receptors are ubiquitinated by E3 ligase(s)and pulled from the outer membranes by the AAA+adenosine triphosphatase CDC48,after which a previously uncharacterized cytosolic protein,transmembrane domain(TMD)-binding protein for tail-anchored outer membrane proteins(TTOP),binds to the exposed TMDs at the C termini of the receptors and CDC48,and delivers these complexes to the 26S proteasome.

关键词： 26S proteasome CDC48 SP1 TOC TOM ubiquitination

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Single-pilot operations in commercial flight:Effects on neural activity and visual behaviour under abnormalities and emergencies

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Chinese Journal of Aeronautics 2024年第8期37卷 277-292页

作者： Qinbiao LI Chun-Hsien CHEN kam K.H.NG Xin YUAN Cho Yin YIU Human Factors and Ergonomics Laboratory Department of Aeronautical and Aviation EngineeringThe Hong Kong Polytechnic UniversityHong Kong Special Administrative Region 100872China School of Mechanical&Aerospace Engineering Nanyang Technological UniversitySingapore 639798Singapore

with cutting-edge technologies and considering airline human-resource-saving,a single pilot in commercial jets could be technically *** changes in captains’natural behaviours are initially required to comprehend the specific safe human performance envelope for safeguarding single-pilot flight,particularly in high-risk *** paper investigates how captains’performance transforms for fixing emergencies when operating from Dual-Pilot Operations(DPO)to Single-Pilot Operations(SPO)through a physiological-based *** pilots flew an emergency-included flight with/without first officers’*** neural activities and scanning behaviours were recorded using a 32-channel Electroencephalogram(EEG)and glasses-based eye tracker,with the observation and post-experiment questionnaires to evaluate the flight operations and pilots’*** alone,there was a significantly increased cortical activity in h and b waves over the frontal,parietal,and temporal lobes during the more complicated emergencies,and pilots focused less on the primary flight display while spending significantly more time scanning the other *** physiological fluctuating patterns associated with risky operations in SPO were highlighted by cross-correlating multimodal *** experimental-based noteworthy insights may wish to inform commercial SPO measures to lessen the persistent physiological fluctuation,assisting airlines in creating SPO-oriented intelligent flight systems to give captains adequate support for assuring safer air transportation.

关键词： Aviation engineering Single pilot operations Behaviour changes Eye tracker Electroencephalogram

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Medical Additive Manufacturing: From a Frontier Technology to the Research and Development of Products

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Engineering 2020年第11期6卷 1217-1221页

作者： Guixing Qiu wenjiang Ding wei Tian Ling Qin Yu Zhao Lianmeng Zhang Jian Lu Daijie Chen Guangyi Yuan Chengtie wu Bingheng Lu Ruxu Du Jimin Chen Mo Elbestawi Zhongwei Gu Dichen Li wei Sun Yuanjin Zhao Jie He Dadi Jin Bin Liu Kai Zhang Jianmo Li kam wleong Dewei Zhao Dingjun Hao Yingfang Ao Xuliang Deng Huilin Yang ShaoKeh Hsu Yingqi Chen Long Li Jianping Fan Guohui Nie Yun Chen Hui Zeng wei Chen Yuxiao Lai Department of Orthopedics Peking Union Medical College HospitalChinese Academy of Medical Science 8 Peking Union Medical CollegeBejjing 100730.China National Engineering Research Center of Light Alloys Net Forming&State Key Laboratony of Metal Matrix Composite Shanghai Jiao Tong UniversityShanghai 200240China Notional Engineering Research Center of Mg Materials and Applicarions and School of Materials Science 8r Engineering.Shanghai Jlao Tong University Shanghai 200240China Department of Spine Surgery Beijing Jishuitan HospitalBeijing 100035China Center for Troanslational Medicine Research and Development Institute of Biomedical and Health EngineeringShenzhen Insitute of Advanced Technology.Chinese Academy of SciencesShenzhen 518055China Guangdong Engineering Laboratony of Biomaterials Additive Manufacturing Guangdong 518055China Musculoskeletal Research Laboratory of the Department of Orthopedics 8 Traumatology and Innovative Orthopedic Biomaterial and Drug Translational Research Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077.China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Center for Advanced Structural Materials City University of Hong Kong Shenzhen Research InstiuteShenzhen 518057.China Hong Kong Branch of National Precious Metals Material Engineering Research Center Department of Material Science and EngineeringCity Untiversity of Hong KongHong Kong 999077.China Department of Mechanical Engineering ity Untiversity of Hong Kong.Hong Kong 9977 China School of Pharmacy.Shanghai Jiao Tong University Shanghai 200240China China State Instute of Pharmaceutical Industry Shanghai Institute of Pharmaceutical IndustryShonghai 201203China Shanghai Innovation Instinute for Materials Shanghai 200444.China State Key Laboratory of High-Performance Ceramies and Superfine Microstructure Shanghai Institute of CeramicsChinese Acadermy 0f SciencesShanghai 200050Ch

*** and development(R&D)and the challenges of raw materials for medical additive manufacturing Raw materials for medical additive manufacturing have a wide range of commonalities that are also seen in many other fields,making them an important basis in the field of three-dimensional(3D)*** and challenges related to material types,powder properties,formability,viscoelasticity,and so forth also share common *** example,many metal materials are used in the field of aviation,while metals,polymers,and inorganic materials are used in the field of *** most widely used materials in biomedicine are *** homogeneous and non-homogeneous composites are also available for 3D printing,and impose an additional challenge in additive manufacturing;the use of heterogeneous composites in 3D printing is particularly challenging.

关键词： composites printing additive

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