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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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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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Diagnostic tools in male infertility--the question of sperm dysfunction

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Asian Journal of Andrology 2011年第1期13卷 53-58页

作者： Christopher LR Barratt steven Mansell Catherine Beaton Steve Tardif Senga k Oxenham Reproductive and Developmental Biology Maternal and Child Health Science Laboratories Centre for Oncology and Molecular Medicine Ninewells Hospital University of Dundee Dundee DD1 9SY Scotland UK Assisted Conception Unit NHS Tavside Ninewelts Hospital. Dundee. DD1 9SY. Scotland. UK

Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that：（i） there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; （ii） technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap （or more appropriately termed cost effective）, easy to use and clinically useful; and （iii） clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.

关键词： gamete biomarker male fertility sperm biomarker sperm dysfunction

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Fusobacterium 's link to colorectal neoplasia sequenced: A systematic review and future insights

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World Journal of Gastroenterology 2017年第48期23卷 8626-8650页

作者： Hisham Hussan steven k Clinton kristen Roberts Michael T Bailey Division of Gastroenterology Hepatology and NutritionDepartment of Internal MedicineThe Ohio State University Wexner Medical Center Comprehensive Cancer Center The Ohio State University Division of Medical Oncology Department of Internal MedicineThe Ohio State University Wexner Medical Center Department of Pediatrics OSU College of Medicine And Center for Microbial PathogenesisThe Research Institute at Nationwide Children’s Hospital

AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia *** Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above *** Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with a

关键词： Colon microbiota Fusobacterium Systematic review Fusobacterium nucleatum Colorectal cancer Colorectal polyps Carcinogenesis

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Color-coded perfluorocarbon nanodroplets for multiplexed ultrasound and photoacoustic imaging

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Nano Research 2019年第4期12卷 741-747页

作者： Daniela Y. Santiesteban kristina A. Hallam steven k. Yarmoska Stanislav Y. Emelianov Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USA School of Electrical & Computer Engineering Georgia Institute of Technology Atlanta GA 30332 USA

Laser-activated perfluorocarb on n anodroplets are an emerging class of phase-cha nge, dual-c ontrast age nts that can be utilized in ultraso und and photoacoustic imaging. Through the ability to differe ntiate subpopulations of nano droplets via laser activatio n at differe nt wavelengths of n ear-infrared light, optically-triggered color-coded perfluorocarb on nano droplets prese nt themselves as an attractive tool for multiplexed ultrasound and photoacoustic imaging. In particular, laser-activated droplets can be used to provide quantitative spatiotemporal information regarding distinct biological targets, allowing for their potential use in a wide range of diagnostic and therapeutic applications. In the work prese nted, laser-activated color-coded perfluorocarb on nan odroplets are syn thesized to selectively resp ond to laser irradiati on at corresp on ding wavele ngths. The dyn amic ultraso und and photoacoustic signals produced by laser-activated perfluorocarbon nano droplets are evaluated in situ prior to implementation in a murine model. In vivo, these particles are used to distinguish unique particle trafficking mechanisms and are show n to provide ultraso und and photoacoustic contrast for up to 72 hours within lymphatics. Overall, the con ducted studies show that laser-activated color-coded perfluorocarbo n nano droplets are a promising agent for multiplexed ultraso und and photoacoustic imaging.

关键词： multiplexed imaging perfluorocarbon nanodroplets photoacoustic imaging ultrasound imaging molecular targets

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