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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 j.n Okabe Ishant Khurana Thomas Karagiannis j.lia 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 j.venile 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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j.urnal 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 j.cob 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.j.hn 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 *** obj.ctive 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 conj.nction 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

Macroalgal deep genomics illuminate multiple paths to aquatic,photosynthetic multicellularity

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Molecular Plant 2024年第5期17卷 747-771页

作者： David R.Nelson Alexandra Mystikou Ashish j.iswal Cecilia Rad-Menendez Michael j.preston Frederik De Boever Diana C.El Assal Sarah Daakour Michael W.Lomas j.an-Claude Twizere David H.Green William C.Ratcliff Kourosh Salehi-Ashtiani Division of Science and Math New York University Abu DhabiAbu DhabiUAE Center for Genomics and Systems Biology(CGSB) New York University Abu DhabiAbu DhabiUAE Biotechnology Research Center Technology Innovation InstitutePO Box 9639Masdar CityAbu DhabiUAE Culture Collection of Algae and Protozoa Scottish Association for Marine ScienceObanScotlandUK National Center for Marine Algae and Microbiota Bigelow Laboratory for Ocean SciencesEast BoothbayMEUSA Laboratory of Viral Interactomes GIGA InstituteUniversity of LiegeLiegeBelgium School of Biological Sciences Georgia Institute of TechnologyAtlantaGAUSA

Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity ***,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain *** this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal *** for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three maj.r phyla,constituting conserved and unique gene sets supporting multicellular *** genes show phylum-and climate-specific expansions that may facilitate niche ***,our study reveals genetic determinants of convergent and divergent evolutionary traj.ctories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.

关键词： macroalgae multicellularity comparative genomics evolution adhesome endogenous viral elements

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

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j.urnal 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

Increased β-Cyanoalanine Nitrilase Activity Improves Cyanide Tolerance and Assimilation in Arabidopsis

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Molecular Plant 2014年第1期7卷 231-243页

作者： Brendan O'Leary GaU M. preston Lee j. Sweetlove Department of Plant Sciences University of Oxford Oxford UK

Plants naturally produce cyanide （CN） which is maintained at low levels in their cells by a process of rapid assimilation. However, high concentrations of environmental CN associated with activities such as industrial pollution are toxic to plants. There is thus an interest in increasing the CN detoxification capacity of plants as a potential route to phytoremediation. Here, Arabidopsis seedlings overexpressing the Pseudomonas fluorescens β-cyanoalanine nitrilase pinA were compared with wild-type and a β-cyanoalanine nitrilase knockout line （△Atnit4） for growth in the presence of exogenous CN. After incubation with CN, ＋PfpinA seedlings had increased root length, increased fresh weight, and decreased leaf bleaching compared with wild-type, indicating increased CN tolerance. The increased tolerance was achieved without an increase in β-cyanoalanine synthase activity, the other enzyme in the cyanide assimilation pathway, suggesting that nitrilase activity is the limiting factor for cyanide detoxification. Labeling experiments with [^13C] KCN demonstrated that the altered CN tolerance could be explained by differences in flux from CN to Asn caused by altered β-cyanoalanine nitrilase activity. Metabolite profiling after CN treatment provided new insight into downstream metabolism, revealing onward metabolism of Asn by the photorespiratory nitrogen cycle and accumulation of aromatic amino acids.

关键词： cyanide β-cyanoalanine cyanide detoxification asparagine metabolism nitrilase

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

Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine

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Sports Medicine and Health Science 2024年第1期6卷 1-15页

作者： Stuart j.Hesketh University of Central Lancashire School of MedicinePrestonUK

Muscle atrophy exacerbates disease outcomes and increases mortality,whereas the preservation of skeletal muscle mass and function play pivotal roles in ensuring long-term health and overall *** atrophy represents a significant clinical challenge,involving the continued loss of muscle mass and strength,which frequently accompany the development of numerous types of *** cachexia is a highly prevalent multifactorial syndrome,and although cachexia is one of the main causes of cancer-related deaths,there are still no approved management strategies for the *** etiology of this condition is based on the upregulation of systemic inflammation factors and catabolic stimuli,resulting in the inhibition of protein synthesis and enhancement of protein *** necessary cellular processes are disrupted by cachectic pathology,which mediate intracellular signalling pathways resulting in the net loss of muscle and ***,the exact underpinning molecular mechanisms of how these changes are orchestrated are incompletely *** work is still required,but structured exercise has the capacity to counteract numerous detrimental effects linked to cancer *** through the stimulation of muscle protein synthesis,enhancement of mitochondrial function,and the release of *** a result,muscle mass and strength increase,leading to improved mobility,and *** review summarises existing knowledge of the complex molecular networks that regulate cancer cachexia and exercise,highlighting the molecular interplay between the two for potential therapeutic ***,the utility of mass spectrometry-based proteomics is considered as a way of establishing early diagnostic biomarkers of cachectic patients.

关键词： Cancer cachexia Exercise Muscle atrophy Molecular medicine Omics

Effectiveness of royal j.lly supplementation in glycemic regulation:A systematic review

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World j.urnal 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 j.lly(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 maj.r limitation affecting evidence quality is the heterogeneity among included *** blood glucose and glucose clearance a

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

A mechanochemical two for one:Mechanical activation of norborn-2-en-7-one releases carbon monoxide and switches on aggregation-induced emission

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Aggregate 2022年第2期3卷 1-2页

作者： Ross W.Barber maxwell j.Robb Division of Chemistry and Chemical Engineering California Institute of TechnologyPasadenaCaliforniaUSA

Mechanical forces are typically considered to be destructive in polymeric materials,leading to degradation via nonspecific chain ***,the emergence of the mechanophore hypothesis has enabled the design of polymers that... 详细信息

关键词： mechanophore polymer mechanochemistry molecular release