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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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Probing turbulence in galaxies with fast radio burst scintillation

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Science China(Physics,mechanics & Astronomy) 2024年第1期67卷 177-178页

作者： james m.Cordes Department of Astronomy the Cornell Center for Astrophysics and Planetary ScienceCornell UniversityIthaca NY 14853USA

Interstellar scintillation(ISS)is a well-known phenomenon observed from pulsars in the milky *** comprises intensity variations *** and frequency caused by constructive and destructive interference from multipath propagation,which is due to diffraction from fluctuations in electron density in the interstellar medium(ISm)on scales as small as~100 *** density fluctuations appear to be part of a turbulence process combined with discrete structures in electron density from other astrophysical processes;together these fluctuations extend to scales of pc or larger.

关键词： scales galaxies turbulence

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Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

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World Journal of Diabetes 2024年第3期15卷 311-317页

作者： Dania Blaibel Cornelius james Fernandez Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(Dm)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated ***,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also *** World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et *** is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical *** editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled Dm during rapid glycaemic control.

关键词： Diabetes mellitus microvascular complications Diabetic retinopathy Treatment induced neuropathy of diabetes Diabetic nephropathy Charcot’s neuropathy

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Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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World Journal of Diabetes 2024年第4期15卷 579-585页

作者： Dania Blaibel Cornelius james Fernandez Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease *** pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not ***,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest *** is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment *** previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are ***,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

关键词： Diabetic peripheral neuropathy Diabetes mellitus Pharmacotherapy Acupuncture Neuropathic pain Nonpharmacological intervention

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A holistic approach to improving safety for battery energy storage systems

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Journal of Energy Chemistry 2024年第5期92卷 422-439页

作者： james Close Jonathan E.Barnard Y.m.John Chew Semali Perera Department of Chemical Engineering Centre for DigitalManufacturing&DesignUniversity of BathBath BA27AYUK iomosaic International Limited 16-18 Queen SquareBath BA12HNUK

The integration of battery energy storage systems(BESS)throughout our energy chain poses concerns regarding safety,especially since batteries have high energy density and numerous BESS failure events have *** spread adoption will only increase the prevalence of these failure events unless there is a step change in the management and design of *** understand the causes of failure,the main challenges of BESS safety are *** consequences and failure events are discussed,including specific focus on the chain of events causing thermal runaway,and a case study of a BESS explosion in Surprise Arizona is *** on the technology and past events,a paradigm shift is required to improve BESS *** this review,a holistic approach is *** combines currently adopted approaches including battery cell testing,lumped cell mathematical modelling,and calorimetry,alongside additional measures taken to ensure BESS safety including the requirement for computational fluid dynamics and kinetic modelling,assessment of installation level testing of the full BESS system and not simply a single cell battery test,hazard and layers of protection analysis,gas chromatography,and composition *** holistic approach proposed in this study aims to address challenges of BESS safety and form the basis of a paradigm shift in the safety management and design of these systems.

关键词： Energy storagesystems Process safety Battery safety Thermal safety

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Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now

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World Journal of Diabetes 2024年第5期15卷 797-809页

作者： Joseph m Pappachan Cornelius james Fernandez Ambika P Ashraf Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Division of Pediatric Endocrinology and Diabetes Department of PediatricsUniversity of Alabama at BirminghamBirminghamAL 35233United States

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic *** has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and *** looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most *** there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this *** article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.

关键词： Childhood obesity Diabesity Type 2 diabetes mellitus Adolescence Cardiovascular disease Pharmacotherapy

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Ranking environmental and edaphic attributes driving soil microbial community structure and activity with special attention to spatial and temporal scales

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mLife 2024年第1期3卷 21-41页

作者： Vadakattu V.S.R.Gupta james m.Tiedje CSIRO Agriculture&Food UrrbraeSouth AustraliaAustralia Centre for microbial Ecology Michigan State UniversityEast LansingMichiganUSA

The incredibly complex soil microbial communities at small scales make their analysis and identification of reasons for the observed structures *** community structure is mainly a result of the inoculum(dispersal),the selective advantages of those organisms under the habitat-based environmental attributes,and the ability of those colonizers to sustain themselves over *** soil is protective,and its microbial inhabitants have long adapted to varied soil conditions,significant portions of the soil microbial community structure are likely ***,a substantial portion of the community will not correlate to often measured soil *** suggest that the drivers be ranked on the basis of their importance to the fundamental needs of the microbes:(i)those that supply energy,i.e.,organic carbon and electron acceptors;(i)environmental effectors or stressors,i.e.,pH,salt,drought,and toxic chemicals;(ii)macro-organism associations,i.e.,plants and their seasonality,animals and their fecal matter,and soil fauna;and(iv)nutrients,in order,N,P,and probably of lesser importance,other micronutrients,and *** relevance of drivers also varies with spatial and time scales,for example,aggregate to field to regional,and persistent to dynamic populations to transcripts,and with the extent of phylogenetic difference,hence phenotypic differences in organismal *** present a summary matrix to provide guidance on which drivers are important for particular studies,with special emphasis on a wide range of spatial and temporal scales,and illustrate this with genomic and population(rRNA gene)data from selected studies.

关键词： abundance community structure diversity functional microbiome microorganisms

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metabolic-associated fatty liver disease and sarcopenia:A double whammy

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World Journal of Hepatology 2024年第2期16卷 152-163页

作者： Aditya Viswanath Sherouk Fouda Cornelius james Fernandez Joseph m Pappachan School of medicine Leicester UniversityLeicester LE17RHUnited Kingdom School of Health and Biomedical Sciences Rmit UniversityMelbourne VICAustralia Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The prevalence of metabolic-associated fatty liver disease(mAFLD)has increased substantially in recent years because of the global obesity ***,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and *** the interplay between mAFLD and these comorbidities is important to design optimal therapeutic *** can be either part of the disease process that results in mAFLD(e.g.,obesity or adiposity)or a consequence of mAFLD,especially in the advanced stages such as fibrosis and *** can also worsen mAFLD by reducing exercise capacity and by the production of various muscle-related chemical ***,it is crucial to thoroughly understand how we deal with these diseases,especially when they *** explore the pathobiological interlinks between mAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

关键词： metabolic-associated fatty liver disease Sarcopenia Sarcopenic obesity Lean metabolic-associated fatty liver disease Cardiovascular disease Liver-muscle axis

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management of male obesity-related secondary hypogonadism:A clinical update

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World Journal of Experimental medicine 2024年第2期14卷 11-28页

作者： mohan T Shenoy Sunetra mondal Cornelius james Fernandez Joseph m Pappachan Department of Endocrinology Sree Gokulam Medical Collegeand Research FoundationTrivandrum 695607KeralaIndia Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(mOSH)with emerging evidence on the role of testosterone *** aim to provide an updated and practical approach towards its *** did a comprehensive literature search across mEDLINE(via Pubmed),Scopus,and Google Scholar databases using the keywords“mOSH”OR“Obesity-related hypogonadism”OR“Testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERm”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was *** weight loss is the ideal therapeutic strategy for patients with mOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world ***,androgen administration is often necessary in the management of hypogonadism in patients with mOSH which also improves many other comorbidities related to ***,there is conflicting evidence for the appropriate use of testosterone replacement therapy(TRT),and it can also be associated with *** evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with *** starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight *** should be coupled with the management of other comorbidities related to obesity in mOSH *** the risks and benefits of TRT should be considered in every patient before and during longterm management.

关键词： male obesity-related secondary hypogonadism Androgen therapy Testosterone replacement therapy Obesity Cardiovascular benefits

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Targeting muscle to treat Charcot-marie-Tooth disease

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Neural Regeneration Research 2024年第8期19卷 1653-1654页

作者： David Villarroel-Campos james N.Sleigh Department of Neuromuscular Diseases and UCL Queen Square motor Neuron Disease Centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK UK Dementia Research Institute University College LondonLondonUK

Charcot-marie-Tooth disease(CmT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb *** patients display gait abnormalities,foot deformities,loss of sens... 详细信息

关键词： marie sensation neuropathy

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