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Cell Research 2004年第3期14卷 234-240页

作者： steven j neill Centre for Research in Plant Science University of the West of England Bristol Coldharbour Lane Bristol BS16 1QY UK

Responses to oligogalacturonic acid （OGA） were determined in transgenic Arabidopsis thaliana seedlings expressing the calcium reporter protein aequorin. OGA stimulated a rapid, substantial and transient increase in the concentration of cytosolic calcium （[Ca2+]cyt） that peaked after ca. 15 s. This increase was dose-dependent, saturating at ca. 50 μg Gal equiv/ml of OGA. OGA also stimulated a rapid generation of H2O2. A small, rapid increase in H2O2 content was followed by a much larger oxidative burst, with H2O2 content peaking after ca. 60 min and declining thereafter. Induction of the oxidative burst by OGA was also dose-dependent, with a maximum response again being achieved at ca. 50 μg Gal equiv/mL. Inhibitors of calcium fluxes inhibited both increases in [Ca2+]cyt and [H2O2], whereas inhibitors of NADPH oxidase blocked only the oxidative burst. OGA increased strongly the expression of the defence-related genes CHS, GST, PAL and PR-1. This induction was suppressed by inhibitors of calcium flux or

关键词： Arabidopsis thaliana cytosolic calcium defence gene expression hydrogen peroxide OGA.

Mitogen-activated protein kinases mediate the oxidative burst and saponin synthesis induced by chitosan in cell cultures of Panax ginseng

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Science China(Life Sciences) 2004年第4期47卷 303-312页

作者： steven j. neill Centre for Research in Plant Science University of the West of England Bristol Coldharbour Lane Bristol BS16 1QY United Kingdom

Chitosan (CHN) specially induced the activities of 39 kD and 42 kD protein kinases in ginseng cells, which could be suppressed by an inhibitor of mitogen-activated protein kinase (MAPK) pathway, PD98059. The immunoprecipitation (IP) using MAPK antibody or kinase assay in vitro also showed that CHN-induced 42 kD and 39 kD protein kinases belonged to the MAPK family. PD98059 suppressed CHN-induced transcriptions of ginseng squalene synthase and ginseng squalene epoxidase genes (gss and gse), CHN-induced accumulation of b-Amyrin synthase (b-AS) and synthesis of saponin. These results showed that CHN-induced activities of MAPKs were necessary for the CHN-induced saponin synthesis. EGTA and LaCl3 suppressed CHN-induced 39 kD and 42 kD MAPK activities. Ruthenium red (RR) could suppress CHN-induced 39 kD activity. All of them suppressed CHN-induced saponin synthesis. These results indicated that CHN-induced increment of cytosolic calcium was necessary for CHN-induced saponin synthesis. PD98059 also suppressed CHN-induced oxidative burst (in-cluding the increment of activity of plasma membrane NADPH oxidase and production of H2O2), but diphenylene iodonium (DPI), dimethylthiourea (DMTU) and 2,5-dihydroxycinnamic acid methyl ester (DHC) could not suppress CHN-induced MAPK activities, which indicated that MAPK was possibly function upstream of CHN-induced oxidative burst.

关键词： mitogen-activated protein kinase,chitosan,saponin.

质膜NADPH氧化酶的活化与H_2O_2的产生介导内源激发子诱导人参悬浮细胞中PAL活性的提高与人参皂甙的积累(英文)

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Acta Botanica Sinica 2003年第12期45卷 1434-1441页

作者：胡向阳 steven j neill 蔡伟明汤章城中国科学院上海生命科学研究院植物生理生态研究所上海200032 CentreforResearchinPlantScience UniversityoftheWestofEnglandBristolColdharbourLaneBristolBS161QYUnitedKingdom

利用纤维素酶降解人参(Panax ginseng ***)悬浮细胞的细胞壁制备了内源激发子(CDW)。CDW体外诱导了游离人参细胞质膜NADPH氧化酶的活性,激发了活体人参悬浮细胞产生H2O2。CDW还可以诱导提高苯丙氨酸解氨酶(PAL)活性,促进人参鲨烯环氧酶... 详细信息

利用纤维素酶降解人参(Panax ginseng ***)悬浮细胞的细胞壁制备了内源激发子(CDW)。CDW体外诱导了游离人参细胞质膜NADPH氧化酶的活性,激发了活体人参悬浮细胞产生H2O2。CDW还可以诱导提高苯丙氨酸解氨酶(PAL)活性,促进人参鲨烯环氧酶基因(sqe)的转录与人参皂甙的积累。NADPH氧化酶的抑制剂不仅可以抑制CDW体外诱导的质膜NADPH活性而且还可以抑制CDW诱导人参细胞产生H2O2。进而,这些抑制剂还可以抑制CDW诱导PAL活性的提高,以及sqe的转录与人参皂甙的合成。过氧化氢酶与H2O2的粹灭剂也可以抑制CDW激发产生的这些诱导效应。上述结果表明CDW激发质膜NADPH氧化酶的活化与H2O2的产生在介导CDW诱导人参细胞抗性反应中,包括PAL活性的提高与人参皂甙的积累,起了重要的信号转导作用。

关键词：质膜NADPH氧化酶活化 H2O2 内源激发子人参悬浮细胞 PAL活性人参皂甙

质膜NAD(P)H氧化酶参予金瓜炭疽(Colletotrichum lagerarium)细胞壁激发子诱导人参细胞产生激发反应(英文)

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Acta Botanica Sinica 2003年第1期45卷 32-39页

作者：胡向阳 steven j.neill 方建颖蔡伟明汤章城中国科学院上海生命科学研究院植物生理生态研究所上海200032 Centre for Research in Plant Science University of the West of England BristolColdharbour LaneBrisiol BS16 1QYUnited Kingdom

在人参(Panax ginseng ***)悬浮细胞质膜上测出了NAD(P)H氧化酶活性。这类NAD(P)H氧化酶活性可以被金瓜炭疽细胞壁激发子(Cle)诱导。Cle处理还能诱导人参悬浮细胞的氧进发、促进人参悬浮细胞的皂苷合成、提高苯丙氨酸解氨酶(PAL)的活力... 详细信息

在人参(Panax ginseng ***)悬浮细胞质膜上测出了NAD(P)H氧化酶活性。这类NAD(P)H氧化酶活性可以被金瓜炭疽细胞壁激发子(Cle)诱导。Cle处理还能诱导人参悬浮细胞的氧进发、促进人参悬浮细胞的皂苷合成、提高苯丙氨酸解氨酶(PAL)的活力、以及诱导查尔式酮酶(CHS)的累积和细胞壁上抗性相关蛋白基因脯氨酸富裕蛋白基因hrgp(Hydroxyprolin-rich glycoproleins)的表达。当用哺乳动物白细胞质膜NADPH氧化酶的特异性抑制剂二亚苯基碘(Diphenylene iodonium,DPI)与奎吖因(quinacrine)预处理人参悬浮细胞30 min 后,Cle诱导的H2O2释放与Cle激活的质膜NAD(P)H氧化酶活性被抑制,同时Cle诱导的PAL活性及CHS的积累下降,皂苷合成与hrgp的表达被抑制。由此推测:人参细胞质膜NAD(P)H氧化酶与哺乳动物白细胞质膜NADPH氧化酶有很大的相似性。在Cle激发人参悬浮细胞产生氧进发的过程中,NAD(P)H氧化酶活性被诱导从而导致H2O2的产生,H2O2作为第二信使,激活苯丙氨酸途径,诱发人参皂苷的合成及hrgp防御基因的表达。这一过程中还涉及到Ca2+内流,胞内Ca2+浓度的升高,蛋白磷酸化与去磷酸化。人参细胞质膜NAD(P)H氧化酶在人参细胞对Cle的反应过程中起一种介导作用。因此可能存在由Cle刺激,NAD(P)H氧化酶被诱导,H2O2释放,到人?

关键词：质膜NAD(P)H氧化酶金瓜炭疽人参皂苷细胞壁激发子诱导人参细胞激发反应信号转导

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

Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

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World journal of Orthopedics 2024年第2期15卷 129-138页

作者： Albert T Anastasio Anthony N Baumann Kempland C Walley Kyle j Hitchman Conor O’neill jonathan Kaplan Samuel B Adams Department of Orthopedic Surgery Duke University HospitalDurhamNC 27710United States College of Medicine Northeast Ohio Medical UniversityRootstownOH 44272United States Department of Orthopedic Surgery University of MichiganAnn ArborMI 48109United States School of Osteopathic Medicine Campbell UniversityLillingtonNC 27546United States

BACKGROUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery *** metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical *** To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United *** This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship *** productivity was defined via H-index and recorded from the Scopus *** earnings were recorded from the *** Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were *** individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(P<0.001;Spearman’s rho=0.334)and a significant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).CONCLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United *** observation is true on an individual physician level as well as on a fellowship level.

关键词： Sunshine act Foot and ankle Orthopedic surgery Orthopedic fellowship Industry earnings

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

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

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

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