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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of pKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand p.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky kelvin p.lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and pathogenesis program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:Massachusetts Institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of pKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,pKM alternative splicing occurred independently of CD28-driven pI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 pKM2

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Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren Tan Mary C.Stephenson Sharifah Badriyah Alhadad kelvin W.Z.Loh Tuck Wah Soong Jason K.W.lee Ivan C.C.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human potential Translational Research programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Centre for Translational Magnetic Resonance Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and performance Centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore Campus for Research Excellence and Technological Enterprise(CREATE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity Cognition Heat stress Hyperthermia Motor function

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On the quality requirements of demand prediction for dynamic public transport

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Communications in Transportation Research 2021年第1期1卷 50-60页

作者： Inon peled kelvin lee Yu Jiang Justin Dauwels Francisco C.pereira Danmarks Tekniske Universitet(DTU) TechnologyManagement and Economics Dept.Kgs.Lyngby2800Denmark Nanyang Technological University(NTU) Graduate College50 Nanyang AvenueSingapore637553 Delft University of Technology(TU Delft) Microelectronics Dept.2600Netherlands

As public Transport(pT)becomes more dynamic and demand-responsive,it increasingly depends on predictions of transport *** how accurate need such predictions be for effective pT operation?We address this question through an experimental case study of pT trips in Metropolitan Copenhagen,Denmark,which we conduct independently of any specific prediction ***,we simulate errors in demand prediction through unbiased noise distributions that vary considerably in *** the noisy predictions,we then simulate and optimize demand-responsive pT fleets via a linear programming formulation and measure their *** results suggest that the optimized performance is mainly affected by the skew of the noise distribution and the presence of infrequently large prediction *** particular,the optimized performance can improve under non-Gaussian *** *** also find that dynamic routing could reduce trip time by at least 23%*** *** reduction is estimated at 809,000€/year in terms of Value of Travel Time Savings for the case study.

关键词： Dynamic public transport Demand forecasting Non-Gaussian noise predictive optimization

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A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis

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Bioactive Materials 2023年第9期27卷 429-446页

作者： John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Yin Lau lee Kai-Fai lee Stephen Cho Wing Sze Wei Qiao kelvin Wai-Kwok Yeung Department of Orthopaedics and Traumatology Li Ka Shing Faculty of MedicineThe University of Hong Kong(HKU)Hong Kong S.A.R.PR China Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma HKU-Shenzhen HospitalShenzhen518053PR China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineHKU21 Sassoon RoadHong Kong S.A.RPR China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterHKU-Shenzhen HospitalShenzhenPR China Department of Biology Faculty of ScienceHong Kong Baptist UniversityKowloon TongHong Kong S.A.RPR China Golden Meditech Center for NeuroRegeneration Sciences Hong Kong Baptist UniversityKowloon TongHong Kong S.A.RPR China Applied Oral Sciences and Community Dental Care Faculty of DentistryHong Kong S.A.RPR China

Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMp-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMp-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLpGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

关键词： Dioscorea spp protein Mesenchymal stem cells(MSCs) Osteoblast differentiation Bone mineral density(BMD) Bone defect repair mTOR signaling pathway

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Feasibility of gallbladder preservation during robotic left hepatectomy:A retrospective comparative study

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第3期5卷 100-105页

作者： Kit-Fai lee Andrew KY.Fung Hon-Ting Lok Janet WC.Kung Eugene YJ.Lo Charing CN.Chong John Wong kelvin KC.Ng Division of Hepatobiliary and pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina

Objective:Traditionally,gallbladder is routinely removed during left hepatectomy even if there is no gallbladder ***,adverse consequence after cholecystectomy,though rare,still occa-sionally *** study aims to evaluate the feasibility of gallbladder preservation during robotic left ***:All consecutive robotic left hepatectomy cases between December 2010 and January 2022 in prince of Wales Hospital,the Chinese University of Hong Kong were retrieved from a prospectively collected *** gallbladder was preserved by moving the liver transection line just away from the gallbladder *** were divided into two groups:gallbladder preservation(GBp)and non-gallbladder preservation(NGBp).Operative results and long-term outcomes were compared between these two ***:There were 11 cases in the GBp group and 25 cases in the NGBp *** two groups were comparable in terms of the patient demographics and disease *** was no operative *** was no difference between the two groups in operative time(GBp 270 min *** 332 min,p=0.132),blood loss(GBp 50 mL *** 150 mL,p=0.115)or complication rate(GBp 27.3%*** 24.0%,p>0.999).There was also no difference in 5-year overall *** the GBp group,no patient developed specific symptoms or complications related to the preserved ***-up ultrasound or computed tomography revealed a normal appearance of the preserved gallbladders except in one patient who developed a 3-mm gallbladder *** the other hand,one(4%)patient in the NGBp group developed troublesome diarrhoea after ***:Gallbladder preservation is safe and feasible during robotic left *** preserved gallbladder does not lead to any symptoms,while postcholecystectomy diarrhoea can be avoided.

关键词： Robotic left hepatectomy Gallbladder preservation Cholecystectomy

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percutaneous tumor ablation 1 Har/Dvdr

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2011年

作者： kelvin. Hong

ISBN: (数字)9781604063523

ISBN: (纸本)9781604063066

Radiofrequency ablation : mechanism of action and devices / kelvin Hong and Christos S. Georgiades -- Cryoablation : mechanism of action and devices / Christos S. Georgiades and Jonathan K. Marx -- Microwave ablation : mechanism of action and devices / Farrah Wolf and Damian E. Dupuy -- Irreversible electroporation ablation : mechanism of action and devices / Edward W. lee, Mariam Totonchy, and St

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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

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Real-time electrical detection of epidermal skin MoS2 biosensor for point-of-care diagnostics

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Nano Research 2017年第3期10卷 767-775页

作者： Geonwook Yoo Heekyeong park Minjung Kim Won Geun Song Seokhwan Jeong Min Hyung Kim Hyungbeen lee Sang Woo lee Young KiHong Min Goo lee Sungho lee Sunkook Kim School of Electronic Engineering Soongsil University Seou106978 Republic of Korea Multi-Functional Nano/Bio Electronics Lab. Kyung Hee University Gyeonggi 17104 Republic of Korea Department of Biomedical Engineering Yonsei University Wonju 26493 Republic of Korea Korea Electronics Technology Institute Gyeonggi 13488 Republic of Korea

Various approaches have been proposed for point-of-care diagnostics, and in particular, optical detection is preferred because it is relatively simple and fast. At the same time, field-effect transistor （FET）-based biosensors have attracted great attention because they can provide highly sensitive and label-free detection. In this work we present highly sensitive, epidermal skin-type point-of-care devices with system-level integration of flexible MOS2 FET biosensors, read-out circuits, and light-emitting diode （LEDs） that enable real-time detection of prostate cancer antigens （pSA）. Regardless of the physical forms or mechanical stress conditions, our proposed high-performance MoS2 biosensors can detect a pSA concentration of 1 ***-1 without specific surface treatment for anti-pSA immobilization on the MoS2 surface on which we characterize and confirm physisorption of anti-pSA using kelvin probe force microscopy （KpFM） and tapping-mode atomic force microscopy （tm-AFM）. Furthermore, current modulation induced by the binding process was stably maintained for longer than 2-3 min. The results indicate that flexible MoS2-based FET biosensors have great potential for point-of-care diagnostics for prostate cancer as well as other biomarkers.

关键词： epidermal skin biomarker MoS2 biosensor real-time point-of-care diagnostics

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在阅读与诠释之间

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城市住宅 1998年第1期5卷 40-45页

作者： kelvin lee 黄浩然李慧欣世界萧鸿生展览工程有限公司正本广告摄影制作

面积:约11 2平方米(建筑面积)间隔:四室两厅就在房子大门的一侧,那大圆玻璃餐桌旁,设计师殷殷地打开带来的图则,开展了对房子的解读。整个设计有三个值得留意的地方,第一个是那道以白色框架包嵌。

关键词：居室室内装饰室内设计

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A Retrospective Study of Radiographic Anatomy of Wrist in Chinese population

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E-Health Telecommunication Systems and Networks 2018年第3期7卷 57-65页

作者： Chris Yuk Kwan Tang Fung Kwok Keung Boris Fok Margaret Woon Man lee Juliana Tsz Yan Aslam Muhammad Zeeshan Fang Benjamin Wong Joyce Yeung kelvin Department of Orthopaedics and Traumatology University of Hong Kong Medical Centre Queen Mary Hospital Hong Kong China Department of Radiology Queen Mary Hospital Hong Kong China

In wrist pathology, there is a need to establish the normal range of radiographic measurement parameters. previous study showed that the contralateral wrist might not be valid as a reference for all parameters. There is a lack of literature describing the normal range of wrist radiographic parameters in literature. As a result, a retrospective study was carried out. patients who underwent standard wrist x-rays during the period February 2012 to February 2013 (one single year) were retrospectively reviewed. 71 patients were included. Scapholunate angle was 54.7° (±6.5°). Scapholunate interval was 2.0 mm (±0.4 mm). Ulnar variance was +1.0 mm (±1.8 mm). Carpal height was 31.8 mm (±3.0 mm). Radial inclination was 25.1° (±2.1°). All 71 patients had 1 sesamoid bone at first metacarpal. 16.9% (12 out of 71) patients had positive cortical ring signs. All these parameters are valuable clinically, especially in monitoring of the wrist disease progression, in the design of wrist implants and for future clinical research.

关键词： Radiographic Anatomy Wrist Chinese

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