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EZh2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-hasani Safiya Naina Marikar harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas kay.Assam El-Osta Epigenetics in human health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in human health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZh2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZh2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent h3K27me3 and h3K4me3 chromatin *** EZh2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZh2 struction inhibitors

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A study of different annealing schedules in SARNA-predict A permutation based SA algorithm for RNA folding

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International Journal of Intelligent Computing and Cybernetics 2015年第2期8卷 152-171页

作者： herbert h.Tsang kay.C.Wiese Applied Research Lab Trinity Western UniversityLangleyCanada School of Computing Science Simon Fraser UniversitySurreyCanada

Purpose–The purpose of this paper is to present a study of the effect of different types of annealing schedules for a ribonucleic acid(RNA)secondary structure prediction algorithm based on simulated annealing(SA).Design/methodology/approach–An RNA folding algorithm was implemented that assembles the final structure from potential substructures(helixes).Structures are encoded as a permutation of *** SA searches this space of *** and annealing schedules were studied and fine-tuned to optimize algorithm ***–In comparing with mfold,the SA algorithm shows comparable results(in terms of F-measure)even with a less sophisticated thermodynamic *** terms of average specificity,the SA algorithm has provided surpassing *** limitations/implications–Most of the underlying thermodynamic models are too simplistic and incomplete to accurately model the free energy for larger *** is the largest limitation of free energy-based RNA folding algorithms in *** implications–The algorithm offers a different approach that can be used in practice to fold RNA sequences ***/value–The algorithm is one of only two SA-based RNA folding *** authors use a very different encoding,based on permutation of candidate *** in depth study of annealing schedules and other parameters makes the algorithm a strong *** benefit is that new thermodynamic models can be incorporated with relative ease(which is not the case for algorithms based on dynamic programming).

关键词： Annealing schedule Simulated annealing RNA secondary structure prediction Ribonucleic acid RNA folding Permutation

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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai Yin Chan Ching Lung Cheung Ivan Chi ho Au Xi Xiong Wai-kay.Seto Man-Fung Yuen Carlos King ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for health(D24h) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(hCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to hCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident hCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for hCC(IRR:1.60,95%CI:1.46-1.75,Ph acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,Phepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,Phough CLD patients with SARS-CoV-2 infection were not associated with increased risk of hCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis hepatocellular carcinoma

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Dzyaloshinskii–Moriya interaction in noncentrosymmetric superlattices

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npj Computational Materials 2021年第1期7卷 1164-1170页

作者： Woo Seung ham Abdul-Muizz Pradipto kay.Yakushiji Kwangsu Kim Sonny h.Rhim Kohji Nakamura Yoichi Shiota Sanghoon Kim Teruo Ono Institute for Chemical Research Kyoto UniversityUjiKyotoJapan Department of Physics Engineering Mie UniversityTsuMieJapan Faculty of Mathematics and Natural Sciences Institut Teknologi BandungBandungIndonesia National Institute of Advanced Industrial Science and Technology(AIST) TsukubaIbarakiJapan Department of Physics University of UlsanUlsanSouth Korea

Dzyaloshinskii–Moriya interaction(DMI)is considered as one of the most important energies for specific chiral textures such as magnetic *** keys of generating DMI are the absence of structural inversion symmetry and exchange energy with spin–orbit ***,a vast majority of research activities about DMI are mainly limited to heavy metal/ferromagnet bilayer systems,only focusing on their ***,we report an asymmetric band formation in a superlattices(SL)which arises from inversion symmetry breaking in stacking order of atomic layers,implying the role of bulk-like *** bulk DMI is more than 300%larger than simple sum of interfacial ***,the asymmetric band is largely affected by strong spin–orbit coupling,showing crucial role of a heavy metal even in the non-interfacial origin of *** work provides more degrees of freedom to design chiral magnets for spintronics applications.

关键词： interaction symmetry chiral

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MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2101-2113页

作者： Loraine kay.D Cabral Cynthia A Mapua Filipinas F Natividad Caecilia h C Sukowati Edgardo R Cortez Ma Luisa D Enriquez Research and Biotechnology Group St.Luke's Medical CenterQuezon City 1112Philippines Centro Studi Fegato Fondazione Italiana Fegato ONLUSTrieste 34149Italy Department of Surgery St.Luke's Medical CenterQuezon City 1112Philippines Center for Natural Science and Environmental Research De La Salle UniversityManila 1004Philippines

BACKGROUND Colorectal cancer(CRC)ranks third in terms of incidence and second in mortality *** CRC,the silencing of mismatch repair genes,including the mutL homolog 1(hMLh1)has been linked to microsatellite instability(MSI),the lengthening or shortening of microsatellite *** limited data have been presented so far on the link of hMLh1 methylation and MSI in Southeast Asia populations with sporadic CRC,and on its clinical *** To investigate the significance of the MSI status and hMLh1 methylation in CRC Filipino *** Fifty-four sporadic CRC patients with complete clinical data were included in this *** DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting(hRM)analysis using the Bethesda Panel of Markers(BAT25,BAT26,D2S123,D5S346,and D17S250).hMLh1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain *** analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance(Kaplan-Meier curves and the log-rank test).RESULTS hMLh1 methylation was observed in 9%and 35%of CRC and normal samples,*** incidence of consistently methylated hMLh1 found in both normal and CRC was noticed for relation to location of tumor(Phe most common unstable microsatellite and MSI-high(MSIh)was the most common MSI profile,counted for 46%and 50%of normal and CRC tissues,*** presence of MSI-low(MSI-L)and microsatellite stable(MSS)was 43%and 11%for normal,and 31%and 19%for CRC *** mean month of patients’survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLh1 and with MSI-h compared to those with MSI-L/MSS(Phis was supported by significant difference in Kaplan-Meier with log-rank *** data indicated that hMLh1 methylation

关键词： Sporadic colorectal cancer DNA methylation Microsatellite instability Population genetic Colorectal cancer

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Synergistic interaction of metal–acid sites for phenol hydrodeoxygenation over bifunctional Ag/TiO_2 nanocatalyst

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Chinese Journal of Chemical Engineering 2019年第2期27卷 349-361页

作者： Andrew Ng kay.Lup Faisal Abnisa Wan Mohd Ashri Wan Daud Mohamed Kheireddine Aroua Department of Chemical Engineering Faculty of Engineering University of Malaya Centre for Carbon Dioxide Capture and Utilization School of Science and Technology Sunway University Department of Engineering Lancaster University

The use of silver metal for hydrodeoxygenation(hDO) applications is scarce and different studies have indicated of its varying hDO activity. Several computational studies have reported of silver having almost zero turnover frequency for hDO owing to its high C\\O bond breaking energy barrier and low carbon and oxygen binding *** this work, titania supported silver catalysts were synthesized and firstly used to examine its phenol hDO activity via experimental reaction runs. BET, XRD, FESEM, TEM, EDX, ICP–OES, Pyridine-FTIR, Nh_3-TPD and h_2-TPD analyses were done to investigate its physicochemical properties. Phenomena of hydrogen spillover and metal–acid site synergy were examined in this study. With the aid of TiO_2 reducible support, hydrogen spillover and metal–acid site interactions were observed to a certain extent but were not as superior as other Pt, Pd, Ni-based catalysts used in other hDO studies. The experimental findings showed that Ag/TiO_2 catalyst has mediocre phenol conversion but high benzene selectivity which confirms the explanation from other computational studies.

关键词： Silver based catalyst Physicochemical properties hydrogen spillover Metal-acid sites hydrodeoxygenation

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Detection of h pylori infection by ELISA and Western blot techniques and evaluation of anti CagA seropositivity in adult Turkish dyspeptic patients

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World Journal of Gastroenterology 2006年第33期12卷 5375-5378页

作者： zlem Yilmaz Nazime ■en Ahmet Ali Küpelio■lu kay.■im■ek Department of Microbiology and Clinical Microbiology Faculty of Medicine Dokuz Eylül University Inciralti-35340 Izmir Turkey Department of Pathology Faculty of Medicine Dokuz Eylül University Inciralti-35340 Izmir Turkey Department of Gastroenterology Faculty of Medicine Dokuz Eylül University Inciralti-35340 Izmir Turkey

AIM: To detect h pylori infection and to evaluate the anti CagA seropositivity in adult Turkish dyspeptic patients. METhODS: We evaluated anti-h pylori IgA, IgG and anti-CagA antibodies using commercial enzyme-linked immunoassay (ELISA) and Western blot in dyspeptic Turkish patients. h pylori status was determined by histology and rapid urease testing. RESULTS: Fifty-six patients were entered. Forty-eight (85.7%) out of the 56 patients were positive for h pylori. h pylori IgG seropositivity was 82.1%, IgA seropositivity 48.2%. CagA ELISA showed that IgG was positive in 50% and IgA in 30.4% of those with h pylori infections. Western blot showed that IgG seropositivity was 80.4% and IgA seropositivity 33.9%. Western blot detected IgG antibodies with reactivity to CagA in 50%, VacA in 62.5%, UreB in 87.5%, UreA in 80.4%, and OMP in 57.1%. None of the tests had a sensitivity and specifi city above 80%. CONCLUSION: None of these commercial tests seems clinically useful for h pylori detection in adult dyspeptic patients, while Western blot can give seropositivity and determine anti-CagA, VacA virulence factor status of Turkish dyspeptic patients in the Izmir region.

关键词： h pylori, Serum CagA, Enzyme-linked immunoassay Western blot Serodiagnosis Dyspepticpatients

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Strain Sensitivity Enhancement in Suspended Core Fiber Tapers

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Photonic Sensors 2013年第2期3卷 118-123页

作者： Ricardo M. ANDRE Susana O. SILVA Martin BECKER kay.SChUSTER M. ROThARDT h. BARTELT Manuel B. MARQUES Orlando FRAZAO INESC Porto Rua do Campo Alegre 687 4169-007 Porto Portugal Departamento de Fisica e Astronomia da Faculdade de Ciencias da Universidade do Porto Rua do Campo Alegre 687 4169-007 Porto Portugal PhT Institute for Photonic Technology Jena Albert-Einstein-Str. 9 07745 Jena Germany

Suspended core fiber tapers with different cross sections （with diameters from 70μm to 120 μm） are produced by filament heating. Before obtaining the taper, the spectral behavior of the suspended core fiber is a multimode interference structure. When the taper is made, an intermodal interference between a few modes is observed. This effect is clearly visible for low taper core dimensions. Since the core and cladding do not collapse, two taper regions exist, one in the core and the other in the cladding. The cladding taper does not affect the light transmission, only the core is reduced to a microtaper. The spectral response of the microtaper based-suspended core fiber is similar to a beat of two interferometers. The strain is applied to the microtaper, and with the reduction in the transverse area, an increase in sensitivity is observed. When the taper is immersed in a liquid with a different index of refraction or subjected to temperature variations, no spectral change Occurs.

关键词： Optical fiber sensor taper microstructured fiber

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Electro-acupuncture to prevent prolonged postoperative ileus:A randomized clinical trial

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World Journal of Gastroenterology 2010年第1期16卷 104-111页

作者： M kay.Garcia Joseph S Chiang Bob Thornton J Lynn Palmer Jennifer McQuade Lorenzo Cohen Department of Anesthesiology and Pain Medicine/Integrative Medicine M.D.Anderson Cancer CenterThe University of Texas Department of Anesthesiology and Pain Medicine M.D.Anderson Cancer CenterThe University of Texas Department of Palliative Care and Rehabilitation Medicine M.D.Anderson Cancer CenterThe University of Texas Department of Behavioral Science M.D.Anderson Cancer CenterThe University of Texas Department of GI Medical Oncology M.D. Anderson Cancer CenterThe University of Texas

AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METhODS:Ninety patients were recruited from the Fudan University Cancer hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual *** was defined as an inability to pass flatus or have a bowel movement by 96 h after *** main outcomes were time to first flatus,time to first bowel movement, and *** outcomes were quality of life(QOL)measures,including pain, nausea,insomnia,abdominal distension/fullness,and sense of well-being. RESULTS:No significant differences in PPOI on day 4 (P=0.71)or QOL measures were found between the *** were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5(P=0.69)or day 6(P= 0.88).No adverse events related to acupuncture were reported. CONCLUSION:Acupuncture did not prevent PPOI andwas not useful for treating PPOI once it had developed in this population.

关键词： Acupuncture Gastrointestinal motility Gastrointestinal disorders Gastrointestinal neoplasms

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Land-walking ***-walking interventions in older adults:Effects on aerobic fitness

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Journal of Sport and health Science 2020年第3期9卷 274-282页

作者： Andrew haynes Louise h.Naylor howard h.Carter Angela L.Spence Elisa Robey kay.L.Cox Barbara A.Maslen Nicola T.Lautenschlager Nicola D.Ridgers Daniel J.Green School of human Sciences(Exercise and Sport Science) The University of Western AustraliaPerthWA 6009Australia School of Physiotherapy and Exercise Science Curtin UniversityPerthWA 6102Australia School of Medicine The University of Western AustraliaPerthWA 6009Australia Academic Unit for Psychiatry of Old Age Department of PsychiatryThe University of MelbourneMelbourneVIC 3010Australia North Western Mental health Melbourne HealthMelbourneVIC 3010Australia Division of Psychiatry WA Centre for Health&AgeingThe University of Western AustraliaPerthWA 6009Australia Institute for Physical Activity and Nutrition(IPAN) School of Exercise and Nutrition SciencesDeakin UniversityGeelongVIC 3125Australia

Background:Low cardiorespiratory fitness is an independent predictor of all-cause and cardiovascular mortality,and interventions that increase fitness reduce ***-walking decreases musculoskeletal impact and risk of falls in older individuals,but it is unclear whether water-walking improves aerobic fitness in the same way as weight-dependent *** randomized controlled trial involved 3 intervention groups—a no-exercise control group(CG),a land-walking(LW)group,and a water-walking(WW)group—to investigate the comparative impacts of LWandWWto CG on ***:Both exercise groups attended individually tailored,center-based,intensity-matched 3×weekly sessions for 24 weeks,which progressed to 150 min of exercise per *** was followed by a 24-week no-intervention *** graded exercise tests were performed on a treadmill at Weeks 0,24,and ***:Maximal oxygen uptake increased from Week 0 to Week 24 in both exercise groups(0.57±0.62 mL/kg/min,0.03±0.04 L/min for LW;0.93±0.75 mL/kg/min,0.06±0.06 L/min for WW,mean±SE)compared to the CG(-1.75±0.78 mL/kg/min,-0.16±0.05 L/min)(group×time,phaustion increased significantly following LW only(123.4±25.5 s),which was significantly greater(p=0.001)than the CG(24.3±18.5 s).By Week 48,the training-induced adaptations in the exercise groups returned to near baseline ***:Our study supports current physical-activity recommendations that 150 min/week of moderate-intensity exercise produces improvements in fitness in previously sedentary older ***,LW andWW elicit similar improvements in fitness if conducted at the same relative ***-na?ve older individuals can benefit from the lower impact forces and decreased risk of falls associated withWWwithout compromising improvements in cardiorespiratory fitness.

关键词： Cardiorespiratory fitness Graded exercise test Physical activity Water exercise

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