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Diabetes pathogenesis and management:the endothelium comes of age

Journal of Molecular Cell Biology 2021年第7期13卷 500-512页

作者： kaitlin M.Love Eugene J.Barrett steven k.malin Jane E.B.Reusch Judith G.Regensteiner Zhenqi Liu Division of Endocrinology and Metabolism Department of MedicineUniversity of Virginia Health SystemCharlottesvilleVA 22908USA Department of kinesiology and Health Rutgers UniversityNew BrunswickNJUSA Division of Endocrinology Metabolism and NutritionRutgers UniversityNew BrunswickNJUSA New Jersey Institute for Food Nutrition and HealthRutgers UniversityNew BrunswickNJUSA Institute of Translational Medicine and Research Rutgers UniversityNew BrunswickNJUSA Center for Women’s Health Research University of Colorado School of MedicineAuroraCOUSA Department of Medicine University of ColoradoAnschutz Medical CampusAuroraCOUSA Rocky Mountain Regional Veterans Affairs Medical Center AuroraCOUSA

Endothelium,acting as a barrier,protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered *** insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease,can co-exist with and even contribute to the development of metabolic insulin resistance,and promote vascular complications in those *** impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location,resulting in decreased arterial plasticity,increased atherosclerosis and vascular resistance,and decreased tissue *** with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease,likely related to differential sex-hormone endothelium ***,reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications,in the resistance arteries lead to better blood pressure control,and in the microvasculature lead to less microvascular complications and more effective tissue *** diabetes therapeutic modalities,including medications and exercise training,improve endothelial insulin action and vascular *** action may delay the onset of type 2 diabetes and/or its complications,making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.

关键词： diabetes insulin resistance endothelium vascular function

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus k Jacobs steven D Morley kay Samuel katie Morgan Lyndsey Boswell Timothy J kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACkGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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A Powerful Partnership Two industry behemoths have teamed up to help teachers make learning fun

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空中英语教室（高级版．彭蒙惠英语） 2024年第11期 12-13,41页

作者： steven Melendez 不详

khan Academy's AI assistant will now be free to k-12 teachers in the *** to a new deal with Microsoft,the companies said during Microsoft's Build conference[in May].Microsoft is donating access to its Microsoft Azure infrastructure to give teachers free use of the tool,which previously required a subscription to pay for the cost of the underlying AI service.

关键词： Azure service companies

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Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

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World Journal of Gastroenterology 2024年第3期30卷 268-279页

作者： Lie-Qi Tang Johnathan Fraebel Shi Jin steven P Winesett Jane Harrell Wen-Han Chang Sam Xianjun Cheng Department of Pediatrics University of FloridaGainesvilleFL 32610United States College of Medicine University of FloridaGainesvilleFL 32610United States Applied Physiology and kinesiology University of FloridaGainesvilleFL 32610United States Brain Rehabilitation Research Center Malcom Randall VA Medical CenterGainesvilleFL 32610United States Department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States Department of Pediatric Gastroenterology Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

BACkGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous ***-sensing receptor(CaSR)inhibits both *** latter has been well documented in vitro but not in *** hypothesis to be tested was that activating CaSR inhibits diarrhea in *** To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in *** CTX was given orally to C57BL/6 mice to induce *** and calci-mimetic R568 were used to activate *** maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal *** verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR *** outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in ***,calcium and R568 were each able to ameliorate diarrhea when applied to diseased *** CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global *** advances in diarrhea research,few have been made in the realm of diarrhea *** therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might

关键词： Cholera Enteric nervous system Secretory diarrhea Oral rehydration solution Calcium-sensing receptor Gene knockout

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Physical characteristics of conditioned anaerobic digested sludge-A fractal, transient and dynamic rheological viewpoint

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Journal of Environmental Sciences 2011年第8期23卷 1266-1273页

作者： Yili Wang Emilie Dieude-Fauvel steven k Dentel College of Environmental Science and Engineering Beijing Forestry University Beijing 100083 China. Department of Civil and Environmental Engineering University of Delaware Newark Delaware 19711 USA Cemagref Les Palaquins 03150 Montoldre Paris France

The changes in the physical characteristics of unconditioned and conditioned anaerobic digested sludge （ADS） biosolids, such as capillary suction time （CST）, yield stress, average size and fractal dimensions, were investigated through a CST test, transient and dynamic rheological test and image analysis. The results showed that the optimum polymer dose range was observed when CST or its reciprocal value was employed as an indicator. There were good correlations between the yield stresses determined from both a controlled shear stress test and a strain amplitude sweep test. The yield stress and storage modulus （G＇） increased as the polymer dose increased in most cases. A frequency sweep test revealed that polymer conditioning could extend the frequency sweep ranges for their elastic behaviors over viscous behaviors as well as the gel-like structure in the linear viscoelastic range. These results implied that more deformation energy was stored in this rigid structure, and that elastic behavior became increasingly dominant with the addition of the polymer in most cases, In addition, both the average sizes and two-dimensional fractal dimensions for conditioned ADS biosolids presented a similar up-climax-down variation trend as the polymer doses increased, whereas the critical polymer doses at the highest average sizes or two-dimensional fractal dimensions, were different. Correlation analysis revealed that the conditioned ADS dewaterability was not correlated with the yield stresses, while the average sizes or the two-dimensional fractal dimensions for conditioned ADS biosolids could be taken as the indication parameters for ADS dewaterability.

关键词： anaerobic digested sludge conditioning dynamic oscillatory test yield stress fractal dimensions polymer dose

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CFD-DEM-VDGM method for simulation of particle fluidization behavior in multi-ring inclined-hole spouted fluidized bed

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Particuology 2021年第4期19卷 112-126页

作者： Meng Chen Zhao Chen Ming Gong Yaping Tang malin Liu Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084China School of Chemical Engineering Northwest UniversityXi’an 710069China

The simulation of particle fluidization behavior in a complex geometry with a large number of particles is challenging owing to the complexity of unstructured computational grids and high computational *** this study,a virtual dual-grid model(VDGM)is proposed to calculate the solid volume fraction in unstructured grids and speed up the *** VDGM is coupled with a computational fluid dynamics-discrete element method model to simulate particle fluidization behavior in a multi-ring inclined-hole spouted fluidized bed with 4.2 million particles under a high temperature of 1423 k.A computational fluid dynamics-discrete element method-virtual dual-grid model(CFD-DEM-VDGM)coupling model is implemented based on commercial software Fluent and *** time step settings in Fluent and EDEM and the pattern of particle data transfer in Fluent are improved to speed up the *** is discovered that the VDGM can calculate the solid volume fraction in unstructured grids of complex geometry and speed up the calculation *** calculation speed increased by more than 10 times compared with that of the segmentation sampling *** new pattern of particle data transfer in Fluent can reduce data transfer time by more than 90%.The fluidization behavior of 4.2 million high-density particles in the multi-ring inclined-hole spouted fluidized bed is obtained and analyzed in *** CFD-DEM-VDGM coupling method is validated for the bed expansion height and spouting cycle time in a spouted fluidized bed via experimental results.

关键词： Virtual dual-grid model CFD-DEM-VDGM Spouted fluidized bed Unstructured grids Particle fluidization

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Autophagy gets in on the regulatory act

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分子细胞生物学报:英文版 2011年第2期3卷 76-77页

作者： steven k.Backues Daniel J.klionsky Life Sciences Institute University of MichiganAnn ArborMI 48109-2216USA

Autophagy down-regulates the Wnt signal transduction pathway via targeted degradation of a key signaling *** may provide an explanation for autophagy’s role in tumor *** eukaryotic cell has at its disposal two primar... 详细信息

关键词： Autophagy targeted explanation

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Pelage color of red bats Lasiurus borealis varies with body size:An image analysis of museum specimens

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Current Zoology 2010年第4期56卷 401-405页

作者： Andrew k.DAVIS steven B.CASTLEBERRY D.B. Warnell School of Forestry and Natural Resources The University of Georgia

Mammalian pelage color can vary among individuals of many species, although this intraspecific variation is oftenoverlooked by researchers, perhaps because of its sometimes subtle nature and difficulty in assessing it quantitatively. Thus, suchvariation is rarely studied in mammals, and this is especially true within the order Chiroptera, where there has been very little empiricalresearch. We examined museum specimens of red bats (Lasiurus borealis, family Vespertilionidae) from Georgia, USA, todetermine the extent of sexual dimorphism in pelage color and to explore possible associations between body size and pelagecolor. We photographed 54 specimens under uniform lighting, and used an image analysis program to measure pelage hue on theuropatagium region, which is fully furred in members of the genus Lasiurus. Statistical analyses of pelage hue scores showedmales had significantly redder pelage than females when considered alone, but when examined together with effects of body sizeand collection year, sex was not significant, and collection year and body size were. More recent specimens tended to be less redthan older specimens, which might indicate a wearing of the buffy tips of hairs from older specimens, and smaller bats of bothsexes tended to be more red. These interesting findings are encouraging and we suggest that future explorations into intraspecificvariation in pelage color of bats using this or similar approaches are warranted to clarify the significance of the patterns. Thisstudy also demonstrated that care must be taken in analyses of mammalian pelage color from older museum skins, or at least thatresearchers must take into account the age of the specimens .

关键词： Pelage color Sexual dimorphism Red bats Lasiurus borealis Image analysis

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher Michael J.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick steven P.Hooker Humberto Parada Jr. John Bellettiere Arun kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

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Effects of Additional Rifle-Carriage Training on Physiological Markers and Roller-Skiing Performance in Well-Trained Biathletes

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Journal of Science in Sport and Exercise 2021年第3期3卷 292-302页

作者： malin Jonsson karstrom kerry McGawley Marko S.Laaksonen Department of Health Science Swedish Winter Sports Research CentreMid Sweden UniversityÖstersundSweden

Purpose The purpose was to investigate whether an increased amount of training while carrying the rifle affects skiing in well-trained biathletes at submaximal and maximal workloads during a pre-season period lasting a minimum of 12 *** Seventeen well-trained biathletes(9 females,8 males)were assigned to an intervention(IG,n=10)or control(CG,n=7)***(T1)and after(T2)the training intervention all participants performed,using treadmill roller-skiing,a submaximal test without the rifle on one day and two submaximal workloads and a maximal time trial(TT)with the rifle on a subsequent *** T1 and T2 all participants performed a minimum of 12 weeks of normal training,the only difference between groups being that IG performed more of their training sessions carrying the *** IG performed more training compared to CG(15.4±1.1 vs.11.2±2.6 h/week,Pk,Pk does not appear to improve skiing performance in well-trained *** addition,physiological markers at submaximal and maximal intensities while carrying the rifle were not affected after the training intervention.

关键词： Anaerobic energy contribution Gross efficiency Lactate threshold Nordic skiing Oxygen uptake Training intervention

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