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Pharmacologic inhibition of mTORC1 mimics dietary protein restriction in a mouse model of lactation

journal of Animal Science and Biotechnology 2021年第2期12卷 729-738页

作者： Virginia L.Pszczolkowski steven j.halderson Emma j.Meyer Amy Lin Sebastian I.Arriola Apelo Department of Animal and Dairy Sciences University of Wisconsin-MadisonMadisonWIUSA Endocrinology and Reproductive Physiology Graduate Training Program University of Wisconsin-MadisonMadisonWIUSA

Background:Understanding the mechanisms of N utilization for lactation can lead to improved requirement estimates and increased efficiency,which modern dairy diets currently fail to *** mechanistic target of rapamycin complex 1(mTORC1)is a central hub of translation regulation,processing extra-and intra-cellular signals of nutrient availability and physiological state,such as amino acids and *** hypothesized that dietary amino acids regulate lactation through mTORC1,such that inhibition of mTORC1 will lead to decreased lactation performance when amino acids are not *** objectives were to assess lactation performance in lactating mice undergoing dietary and pharmacologic interventions designed to alter mTORC1 ***:First lactation mice(N=18;n=6/treatment)were fed an adequate protein diet(18%crude protein),or an isocaloric protein-restricted diet(9%crude protein)from the day after parturition until lactation day 13.A third group of mice was fed an adequate protein diet and treated with the mTORC1 inhibitor rapamycin(4 mg/kg every other day)intraperitoneally,with the first two groups treated with vehicle as *** and pups were weighed daily,and feed intake was recorded every other *** production was measured every other day beginning on lactation day 4 by the weigh-suckle-weigh *** were collected after fasting and ***:Milk production and pup weight were similarly decreased by both protein restriction and rapamycin treatment,with final production at 50%of control(P=0.008)and final pup weight at 85%of control(P<0.001).Mammary phosphorylation of mTORC1’s downstream targets were decreased by protein restriction and rapamycin treatment(P<0.05),while very little effect was observed in the liver of rapamycin treated mice,and none by protein ***:Overall,sufficient supply of dietary amino acids was unable to maintain lactation performance status in mice with pharmacologically reduced mam

关键词： Amino acids Lactation Mammary Mouse model mTORC1 Rapamycin

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Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee j Dufault Katherine M Adler David O Carpenter steven G Gilbert Raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their *** may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics *** To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food *** The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ***-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)*** test group participated in the six-week online nutritional epigenetics tutorial,while the control group did *** efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention *** intake scores were derived for both ultra-processed and whole/organic *** sample t-tests were conducted to determine any differences in mean diet scores within each *** There was a significant difference in the diet scores of the test group between the pre-and post-intervention *** parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

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A glycine-rich nuclear effector VdCE51 of Verticillium dahliae suppresses plant immune responses by inhibiting the accumulation of GhTRXH2

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The Crop journal 2024年第4期12卷 1137-1149页

作者： Chi Li Yingqi Huang Wenjing Shang jieyin Chen steven j.Klosterman Krishna V.Subbarao jun Qin Xiaoping Hu State Key Laboratory of Crop Stress Resistance and High-Efficiency Production Key Laboratory of Plant Protection Resources and Pest Management of Ministry of EducationKey Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural AffairsCollege of Plant ProtectionNorthwest A&F UniversityYangling 712100ShaanxiChina State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Western Agricultural Research Center Chinese Academy of Agricultural SciencesChangji 831100XinjiangChina Agricultural Research Service United States Department of AgricultureSalinasCA 93905USA Department of Plant Pathology University of CaliforniaDavisc/o United States Agricultural Research StationSalinasCA 93905USA

Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash *** of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A glycine-rich nuclear effector,VdCE51,was able to suppress immune responses in tobacco against Botrytis cinerea and Sclerotinia *** effector was a required factor for full virulence of ***,and its nuclear localization was a requisite for suppressing plant *** thioredoxin GhTRXH2,identified as a positive regulator of plant immunity,was a host target of *** findings show a virulence regulating mechanism whereby the secreted nuclear effector VdCE51 interferes with the transcription of PR genes,and the SA signaling pathway by inhibiting the accumulation of GhTRXH2,thus suppressing plant immunity.

关键词： Verticillium dahliae Plant immunity Effector Thioredoxin

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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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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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Reprogramming cholesterol metabolism in macrophages and its role in host defense against cholesterol-dependent cytolysins

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Cellular & Molecular Immunology 2022年第3期19卷 327-336页

作者： Min-Sub Lee steven j.Bensinger Department of Molecular and Medical Pharmacology University of CaliforniaLos AngelesCA90095USA Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA90095USA

Cholesterol is a critical lipid for all mammalian cells,ensuring proper membrane integrity,fluidity,and biochemical *** evidence indicates that macrophages rapidly and profoundly reprogram their cholesterol metabolism in response to activation signals to support host defense ***,our understanding of the molecular details underlying how and why cholesterol homeostasis is specifically reshaped during immune responses remains less well *** review discusses our current knowledge of cellular cholesterol homeostatic machinery and introduces emerging concepts regarding how plasma membrane cholesterol is partitioned into distinct *** then discuss how proinflammatory signals can markedly reshape the cholesterol metabolism of macrophages,with a focus on the differences between MyD88-dependent pattern recognition receptors and the interferon signaling *** also discuss recent work investigating the capacity of these proinflammatory signals to selectively reshape plasma membrane cholesterol *** examine how these changes in plasma membrane cholesterol metabolism influence sensitivity to a set of microbial pore-forming toxins known as cholesterol-dependent cytolysins that specifically target cholesterol for their effector *** also discuss whether lipid metabolic reprogramming can be leveraged for therapy to mitigate tissue damage mediated by cholesterol-dependent cytolysins in necrotizing fasciitis and other related *** expect that advancing our understanding of the crosstalk between metabolism and innate immunity will help explain how inflammation underlies metabolic diseases and highlight pathways that could be targeted to normalize metabolic homeostasis in disease states.

关键词： Cholesterol Macrophages Innate Immunity Metabolism

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Adding Value to Crop Production Systems by Integrating Forage Cover Crop Grazing

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American journal of Plant Sciences 2024年第3期15卷 180-192页

作者： Robert B. Mitchell Daren D. Redfearn Kenneth P. Vogel Terry j. Klopfenstein Galen Erickson P. Stephen Baenziger Bruce E. Anderson Mary E. Drewnoski jay Parsons steven D. Masterson Marty R. Schmer Virginia L. jin USDA-ARS Wheat Sorghum and Forage Research Unit University of Nebraska-Lincoln Lincoln NE USA Department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE USA Department of Animal Science University of Nebraska-Lincoln Lincoln NE USA Department of Agricultural Economics University of Nebraska-Lincoln Lincoln NE USA USDA-ARS Agroecosystem Management Research Unit University of Nebraska-Lincoln Lincoln NE USA

In addition to their value as cereal grains, wheat (Triticum aestivum L.) and triticale (× Triticosecale Wittmack) are important cool-season annual forages and cover crops. Yearling steer (Bos taurus) performance was compared in the spring following autumn establishment as for age cover crops after soybean [Glycine max (L.) Merr.] grain harvest. Replicated pastures (0.4 ha) were no-till seeded in three consecutive years into soybean stubble in autumn, fertilized, and grazed the following spring near Ithaca, NE, USA. Each pasture (n = 3) was continuously stocked in spring with four yearling steers (380 ± 38 kg) for 17, 32, and 28 d in 2005, 2006, and 2007, respectively. In 2005, average daily gain (ADG) for steers grazing triticale exceeded the ADG for wheat by 0.31 kghd-1d-1. In 2006, wheat ADG exceeded that for triticale by 0.12 kghd-1d-1. In 2007, steers grazing wheat lost weight, while steers grazing triticale gained 0.20 kghd-1d-1. Based on the 3-year average animal gains valued at $1.32 kg-1, mean net return ($ ha-1 yr-1) was $62.15 for triticale and $22.55 for wheat. Since these grazed cover crops provide ecosystem services in addition to forage, grazing could be viewed as a mechanism for recovering costs and adds additional value to the system. Based on this 3-year grazing trial, triticale was superior to wheat and likely will provide the most stable beef yearling performance across years with variable weather for the western Cornbelt USA.

关键词： Cover crops Soybean Triticale Wheat

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High-energy sodium-ion hybrid capacitors through nanograin-boundary-induced pseudocapacitance of Co_(3)O_(4) nanorods

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journal of Energy Chemistry 2022年第6期31卷 338-346,I0009页

作者： Wenliang Feng Venkata Sai Avvaru steven jHinder Vinodkumar Etacheri IMDEA Materials Institute C/Eric Kandel 2GetafeMadrid 28906Spain Universidad Politécnica de Madrid E.T.S.de Ingenieros de Caminos28040 MadridSpain Universidad Autónoma de Madrid C/Francisco Tomás y Valiente728049 MadridSpain Surface Analysis Laboratory Faculty of Engineering and Physical Sciences University of Surrey GuildfordSurrey GU27XHUnited Kingdom

Sodium-ion hybrid capacitors (SICs) have been proposed to bridge performance gaps between batteries and supercapacitors,and thus realize both high energy density and power density in a single ***,applications of SICs are severely restricted by their insufficient energy densities (<100Wh/kg) resulted from the kinetics imbalance between cathodes and ***,we report a nanograin-boundary-rich hierarchical Co_(3)O_(4) nanorod anode composed of~20 nm *** pseudocapacitance (up to 72%@1.0 mV/s) is achieved through nanograin-boundary-induced pseudocapacitive-type Na^(+) storage ***_(3)O_(4) nanorod anode delivers in this case highly reversible capacity (810 mAh/g@0.025 A/g),excellent rate capability (335 mAh/g@5.0 A/g),and improved cycle stability (100 cycles@1.0 A/g with negligible capacity degradation).The outstanding performance can be credited to the hierarchical morphology of Co_(3)O_(4) nanorods and the well-designed nanograinboundaries between nanocrystallites that avoid particle agglomeration,induce pseudocapacitive-type Na^(+) storage,and accommodate volume variation during sodiation-desodiation *** of the Co_(3)O_(4) nanorods not only generates defects for extra surficial Na^(+) storage but also increases the electronic conductivity for efficient charge separation and lowers energy barrier for Na^(+) *** of conventional reaction mechanism and pseudocapacitive-type Na^(+) storage enables high specific capacity,rapid Na^(+) diffusion,and improved structural stability of the Co_(3)O_(4) nanorod *** SIC integrating this highly pseudocapacitive anode and activated carbon cathode delivers exceptional energy density (175 Wh/kg@40 W/kg),power density (6632 W/kg@37 Wh/kg),cycle life (6000 cycles@1.0 A/g with a capacity retention of 81%),and coulombic efficiency (~100%).

关键词： Sodium-ion hybrid capacitor Cobalt oxide nanorod Nanograin-boundary Pseudocapacitance

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Pelviureteric junction obstruction in adults:A systematic review of the literature

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当代泌尿学（英文） 2023年第2期17卷 86-91页

作者： Niall j.O'Sullivan steven Anderson Department of Urology Tallaght University HospitalDublinIreland Department of Urology Beaumont HospitalDublinIreland

Background:Pelviureteric junction obstruction(PUjO)is a common urological disorder that can present at any stage of *** underlying etiology in children has been well studied;however,a gap exists in the literature for the adult ***,we performed a systematic review of the literature to evaluate the current evidence on the underlying etiologies of adult patients pre-senting with PUjO.Materials and methods:Four electronic databases were searched for relevant studies assessing the underlying etiologies of pelviureteric junction obstruction in *** were assessed for eligibility based on predefined inclusion and exclusion criteria,and a critical ap-praisal of methodological quality and risk of bias was ***,qualitative and quantitative data analyses were performed.Results:Twelve studies comprising a total of 51 3 patients with radiologically confirmed PUjO met the inclusion criteria and were in-cluded in our *** most common finding was crossing vessels,which were observed in 50.5％of patients,followed by intrinsic ureteral stenosis(27.1％),adhesions(15.3％),and high insertion of the ureter(10.1％).Conclusions:The underlying etiologies of PUjO in adults remain *** studyindicated that obstruction secondary to crossing vessels is the most common cause of obstruction in adults and occurs more frequently than in the pediatric population.

关键词： Adults Etiology Pelviureteric junction obstruction Ureteropelvic junction obstruction

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Benchmark Computations of the Phase Field Crystal and Functionalized Cahn-Hilliard Equations via Fully Implicit,Nesterov Accelerated Schemes

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Communications in Computational Physics 2023年第2期33卷 367-398页

作者： jea-Hyun Park Abner j.Salgado steven M.Wise Department of Mathematics University of California Santa BarbaraCA 93106USA Department of Mathematics University of Tennessee KnoxvilleTN 37996USA.

We introduce a fast solver for the phase field crystal(PFC)and functionalized Cahn-Hilliard(FCH)equations with periodic boundary conditions on a rectangular domain that features the preconditioned Nesterov’s accelerated gradient descent(PAGD)*** discretize these problems with a Fourier collocation method in space,and employ various second-order schemes in *** observe a significant speedup with this solver when compared to the preconditioned gradient descent(PGD)*** the PAGD solver,fully implicit,second-order-in-time schemes are not only feasible to solve the PFC and FCH equations,but also do so more efficiently than some semi-implicit schemes in some cases where accuracy issues are taken into *** computations of four different schemes for the PFC and FCH equations are conducted and the results indicate that,for the FCH experiments,the fully implicit schemes(midpoint rule and BDF2 equipped with the PAGD as a nonlinear time marching solver)perform better than their IMEX versions in terms of computational cost needed to achieve a certain *** the PFC,the results are not as conclusive as in the FCH experiments,which,we believe,is due to the fact that the nonlinearity in the PFC is milder nature compared to the FCH *** also discuss some practical matters in applying the *** introduce an averaged Newton preconditioner and a sweeping-friction strategy as heuristic ways to choose good preconditioner *** sweeping-friction strategy exhibits almost as good a performance as the case of the best manually tuned parameters.

关键词： Phase field crystal functionalized Cahn-Hilliard preconditioning Nesterov acceleration nonlinear solver.

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