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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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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

A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors(PPARCS)

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journal of Sport and Health Science 2024年第1期13卷 81-89页

作者： Sarah j.Hardcastle Chloe maxwell-Smith Vinicius Cavalheri Terry Boyle Marta Leyton Román Cameron Platell Michael Levitt Christobel Saunders Frank Sardelic Sophie Nightingale jacob McCormick Craig Lynch Paul A.Cohen Max Bulsara Dana Hince Sport and Physical Activity Research Centre Sheffield Hallam UniversitySheffieldS102BPUK Institute for Health Research The University of Notre DameFremantleWA 6959Australia Curtin School of Population Health Curtin UniversityPerthWA 6845Australia Curtin School of Allied Health Curtin UniversityPerthWA 6845Australia Allied Health South Metropolitan Health ServiceMurdochWA 6150Australia Australian Centre for Precision Health University of South AustraliaAdelaideSA 5001Australia Department of Didactics of Musical Plastic and Body ExpressionUniversity of ExtremaduraCaceres 10071Spain St.john of God Subiaco Hospital PerthWA 6008Australia Department of Surgery University of MelbourneMelbourneVIC 3010Australia Tamara Private Hospital TamworthNSW 2340Australia Peter MacCallum Cancer Centre MelbourneVIC 3000Australia College of Health and Medicine Australian National UniversityCanberraACT 2600Australia Division of Obstetrics and Gynaecology Medical SchoolUniversity of Western AustraliaPerthWA 6009Australia

Background:Physical activity(PA)is important for cancer *** of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer *** objective of this study was to ascertain whether wearable technology,coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in ***:Cancer survivors from 5 states were randomized to intervention and control *** participants were given a Fitbit Charge 2TMand received up to 6 telephone health coaching *** participants received PA print *** assessments at baseline and 12 weeks measured moderate-to-vigorous PA(MVPA),light PA,and sedentary ***:Eighty-seven participants were recruited(age=63±11 years;74(85%)female).There was a significant net improvement in MVPA of 49.8 min/week,favoring the intervention group(95%confidence interval(95%CI):13.6-86.1,p=0.007).There was also a net increase in MVPA bouts of 39.5 min/week(95%CI:11.9-67.1,p=0.005),favoring the intervention *** groups improved light PA and sedentary behavior,but there were no between-group ***:This’s the first study to demonstrate that,when compared to standard practice(i.e.,PA education),a wearable technology intervention coupled with distance-based health coaching,improves MVPA in non-metropolitan cancer *** results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

关键词： Behavior change Exercise Health disparities Oncology Wearable technology

A decomposition of light’s spin angular momentum density

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Light(Science & Applications) 2024年第8期13卷 1578-1589页

作者： Alex j.Vernon Sebastian Golat Claire Rigouzzo Eugene A.Lim Francisco j.Rodríguez-Fortuño Department of Physics King’s College LondonStrandLondon WC2R 2LSUK London Centre for Nanotechnology LondonUK

Light carries intrinsic spin angular momentum(SAM)when the electric or magnetic field vector rotates over time.A familiar vector equation calculates the direction of light’s SAM density using the right-hand rule with reference to the electric and magnetic polarisation *** maxwell’s equations,this vector equation can be decomposed into a sum of two distinct terms,akin to the well-known Poynting vector decomposition into orbital and spin *** present the first general study of this spin decomposition,showing that the two terms,which we call canonical and Poynting spin,are chiral analogies to the canonical and spin momenta of light in its interaction with *** canonical momentum,canonical spin is directly *** canonical and Poynting spin incorporate spatial variation of the electric and magnetic fields and are influenced by optical *** decomposition allows us to show that a linearly polarised vortex beam,which has no total SAM,can nevertheless exert longitudinal chiral pressure due to equal and opposite canonical and Poynting spins.

关键词： canonical momentum angular

Effectiveness of royal jelly supplementation in glycemic regulation:A systematic review

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World journal of Diabetes 2019年第2期10卷 96-113页

作者： Kamel Omer maxwell j Gelkopf Genevieve Newton Department of Human Health and Nutritional Sciences University of Guelph

BACKGROUND Royal jelly(Rj)has been observed to have therapeutic properties in diabetic individuals,including the reduction of high blood *** systematic review synthesized existing evidence to investigate the effectiveness of Rj supplementation in managing measures of blood *** To determine the effectiveness of Rj supplementation on glycemic responses in healthy and non-insulin dependent diabetic adults,as well as animal models of *** This was a systematic review employing the PRISMA ***-reviewed,published articles were extracted from several databases using key words related to target population,intervention and outcome and hand-selected for *** articles proceeded to data extraction phase,where information on target parameters and effectiveness of treatment was *** this,the risk of bias for each included study was ***,the long-term and immediate effectiveness of Rj supplementation in glycemic control were assessed using the Grading of Recommendations,Assessment,Development and Evaluations(GRADE)tool,which rates the quality of *** Of 168 articles extracted from database searching,eighteen were included for analysis in this systematic *** the studies,studied populations,intervention styles and outcome measures were largely *** this,the results in studies indicate a general trend of positive effect of Rj in glycemic regulation in vitro and in ***,some dose-dependent glycemic effects were observed,along with some large effect *** risk of bias for human and animal studies is generally low-unclear risk,although lack of blinding is a serious concern in both ***,as per the GRADE tool,the quality of evidence is low,and very low for long-term and immediate effectiveness of Rj,respectively.A major limitation affecting evidence quality is the heterogeneity among included *** blood glucose and glucose clearance a

关键词： Royal jelly Type 2 diabetes Dietary supplement Glycemic control 10-hydroxy-trans-2-decenoic acid Hyperglycemia Adults Animals

Spatially resolved and multiplexed MicroRNA quantification from tissue using nanoliter well arrays

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Microsystems & Nanoengineering 2020年第1期6卷 1007-1015页

作者： maxwell B.Nagarajan Augusto M.Tentori Wen Cai Zhang Frank j.Slack Patrick S.Doyle Department of Chemical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA HMS Initiative for RNA Medicine Department of PathologyHarvard Medical SchoolBeth Israel Deaconess Medical CenterBostonMA 02215USA

Spatially resolved gene expression patterns are emerging as a key component of medical studies,including companion diagnostics,but technologies for quantification and multiplexing are *** present a method to perform spatially resolved and multiplexed microRNA(miRNA)measurements from formalin-fixed,paraffin-embedded(FFPE)*** nanoliter well arrays to pixelate the tissue section and photopatterned hydrogels to quantify miRNA,we identified differentially expressed miRNAs in tumors from a genetically engineered mouse model for non-small cell lung cancer(K-ras&(LSL-G12D/+);p53^(fl/fl)).This technology could be used to quantify heterogeneities in tissue samples and lead to informed,biomarker-based diagnostics.

关键词： resolved Spatial lung

Evaluating the Effects of Graviton Redshift upon Spiral Galaxy Rotation Curves, Surface Brightness Magnitudes and Gravitational Lensing

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journal of High Energy Physics, Gravitation and Cosmology 2024年第3期10卷 967-985页

作者： Firmin j. Oliveira East Asian Observatory James Clerk Maxwell Submillimetre Telescope Hilo USA

The effects of the gravitational redshift of gravitons upon spiral galaxy rotation energy are compared to the standard mass to light analyses in obtaining rotation curves. The derivation of the total baryonic matter compares well with the standard theory and the rotation velocity is matched to a high precision. The stellar mass distributions obtained from the fit with graviton energy loss are used to derive the surface brightness magnitudes for the galaxies, which agree well with the observed measurements. In a new field of investigation, the graviton theory is applied to the observations of gravitational lenses. The results of these applications of the theory suggest that it can augment the standard methods and may eliminate the need for dark matter.

关键词： Gravitons Gravitational Redshift Surface Brightness Gravitational Lens Lens Mass

Machine Learning Chemical Guidelines for Engineering Electronic Structures in Half-Heusler Thermoelectric Materials

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Research 2020年第1期2020卷 978-985页

作者： maxwell TDylla Alexander Dunn Shashwat Anand Anubhav jain G.jeffrey Snyder Department of Materials Science and Engineering Northwestern UniversityIL 60208USA Department of Materials Science and Engineering UC BerkeleyCA 94720USA Lawrence Berkeley National Laboratory Energy Technologies AreaCA 94720USA

Half-Heusler materials are strong candidates for thermoelectric applications due to their high weighted mobilities and power factors,which is known to be correlated to valley degeneracy in the electronic band ***,there are over 50 known semiconducting half-Heusler phases,and it is not clear how the chemical composition affects the electronic *** all the n-type electronic structures have their conduction band minimum at either theΓ-or X-point,there is more diversity in the p-type electronic structures,and the valence band maximum can be at either theΓ-,L-,or ***,we use high throughput computation and machine learning to compare the valence bands of known half-Heusler compounds and discover new chemical guidelines for promoting the highly degenerate W-point to the valence band *** do this by constructing an“orbital phase diagram”to cluster the variety of electronic structures expressed by these phases into groups,based on the atomic orbitals that contribute most to their valence ***,with the aid of machine learning,we develop new chemical rules that predict the location of the valence band maximum in each of the *** rules can be used to engineer band structures with band convergence and high valley degeneracy.

关键词： structure valence bands

Doped graphene/carbon black hybrid catalyst giving enhanced oxygen reduction reaction activity with high resistance to corrosion in proton exchange membrane fuel cells

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journal of Energy Chemistry 2022年第5期31卷 143-153页

作者： Zhaoqi ji jianuo Chen María Pérez-Page Zunmin Guo Ziyu Zhao Rongsheng Cai maxwell T.P.Rigby Sarah j.Haigh Stuart M.Holmes School of Automotive Engineering Harbin Institute of TechnologyWeihai264209ShandongChina Department of Chemical Engineering and Analytical Science The University of ManchesterManchester M139PLUK Department of Materials The University of ManchesterManchester M139PLUK

Nitrogen doping of the carbon is an important method to improve the performance and durability of catalysts for proton exchange membrane fuel cells by platinum–nitrogen and carbon–nitrogen bonds. This study shows that p-phenyl groups and graphitic N acting bridges linking platinum and the graphene/carbon black(the ratio graphene/carbon black = 2/3) hybrid support materials achieved the average size of platinum nanoparticles with(4.88 ± 1.79) nm. It improved the performance of the lower-temperature hydrogen fuel cell up to 0.934 W cm^(-2) at 0.60 V, which is 1.55 times greater than that of commercial Pt/C. Doping also enhanced the interaction between Pt and the support materials, and the resistance to corrosion, thus improving the durability of the low-temperature hydrogen fuel cell with a much lower decay of 10 mV at 0.80 A cm^(-2) after 30 k cycles of an in-situ accelerated stress test of catalyst degradation than that of 92 mV in Pt/C, which achieves the target of Department of Energy(<30 mV). Meanwhile,Pt/Nr EGO_(2)-CB_(3) remains 78% of initial power density at 1.5 A cm^(-2) after 5 k cycles of in-situ accelerated stress test of carbon corrosion, which is more stable than the power density of commercial Pt/C, keeping only 54% after accelerated stress test.

关键词： Nitrogen doped graphene Low-temperature hydrogen fuel cell Catalyst degradation Carbon corrosion

Graphene/carbon structured catalyst layer to enhance the performance and durability of the high-temperature proton exchange membrane fuel cells

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journal of Energy Chemistry 2022年第12期75卷 399-407,I0011页

作者： Zhaoqi ji jianuo Chen Zunmin Guo Ziyu Zhao Rongsheng Cai maxwell T.P.Rigby Sarah j.Haigh Maria Perez-Page Yitao Shen Stuart M.Holmes School of Automotive Engineering Harbin Institute of Technology(Weihai)Weihai 264209ShandongChina Department of Chemical Engineering The University of ManchesterManchester M139PLUK Department of Materials The University of ManchesterManchester M139PLUK

In this study,nitrogen doped electrochemically exfoliated reduced graphene oxide and carbon black supported platinum(Pt/Nr EGO_(2)-CB_(3))has been prepared to enhance the performance and durability of hightemperature PEMFCs with lower Pt *** the one hand,Pt/Nr EGO_(2)-CB_(3)with the strong interaction between the Pt and nitrogen(N)prevent agglomeration of Pt particles and Pt particles is 5.46±1.46 nm,which is smaller than that of 6.78±1.34 nm in Pt/***,ECSA of Pt/Nr EGO_(2)-CB_(3)decrease 13.65%after AST,which is much lower than that of 97.99%in Pt/*** the other hand,the Nr EGO flakes in MEAac act as a barrier to mitigate phosphoric acid redistribution,which improves the formation of triple-phase boundaries(TPBs)and gives stable operation of the MEAacwith a lower decay rate of 0.02 mV h^(-1)within100 *** steady-state operation,the maximum power density of Pt/Nr EGO_(2)-CB_(3)(0.411 W cm^(-2))is three times higher than that of conventional Pt/C(0.134 W cm^(-2))in high-temperature *** AST,the mass transfer resistance of Pt/Nr EGO_(2)-CB_(3)electrode(0.560Ωcm^(2))is lower than that in Pt/C(0.728Ωcm^(2)).

关键词： High-temperature proton exchange membrane fuel cell Phosphoric acid loss Pt catalyst degradation Accelerated stress test Durability