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World Journal of Gastroenterology 2020年第15期26卷 1683-1690页

作者： Paul Brennan Kathleen Clare Jacob George john f dillon Department of Molecular and Clinical Medicine University of DundeeNinewells Hospital and Medical SchoolDundee DD19SYUnited Kingdom Department of Neurology Queen Elizabeth HospitalGlasgow G514TFUnited Kingdom

There has long been a recognised association between non-alcoholic fatty liver disease(NAfLD)and the composite aspects of the metabolic *** of this association highlighted the supposed co-existence of elevated uric acid levels in those with *** is interest in exploitation of this as a putative diagnostic and prognostic biomarker in *** the increased economic and health burden associated with the NAfLD epidemic,improved methods of population-based,minimally-invasive methods and biomarkers are clearly highly sought and *** this opinion review we review the proposed role of uric acid in the pathogenesis of NAfLD and its potential utilisation in the diagnosis and monitoring of the disease process.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Uric acid Urate Non-invasive fibrosis markers fatty liver index

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis of MAfLD

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 939-946页

作者： Kathleen Clare john f.dillon Paul N.Brennan Royal Alexandra Hospital PaisleyNHS Greater Glasgow and ClydePA29PNUK University of Dundee Ninewells Hospital and Medical SchoolDundeeDD19SYUK University of Edinburgh Edinburgh BioQuarter5 Little France DriveEH164UUUK

The pathogenesis of metabolic-associated fatty liver disease(MAfLD)is complex and thought to be dependent on multiple parallel hits on a background of genetic *** evidence suggests that MAfLD progression is a dynamic two-way process relating to repetitive bouts of metabolic stress and inflammation interspersed with endogenous anti-inflammatory reparative *** MAfLD,excessive hepatic lipid accumulation causes the production of lipotoxins that induce mitochondrial dysfunction,endoplasmic reticular stress,and over production of reactive oxygen species(ROS).Models of MAfLD show marked disruption of mitochondrial function and reduced oxidative capacitance with impact on cellular processes including mitophagy,oxidative phosphorylation,and mitochondrial *** excess,ROS modify insulin and innate immune signaling and alter the expression and activity of essential enzymes involved in lipid *** can also cause direct damage to intracellular structures causing hepatocyte injury and *** select cases,the use of anti-oxidants and ROS scavengers have been shown to diminish the proapoptopic effects of fatty *** this link,endogenous anti-oxidant pathways have been a target of interest,with Nrf2 activation showing a reduction in oxidative stress and inflammation in models of *** hormone receptorβ(THRβ)agonists and nuclear peroxisome proliferationactivated receptor(PPAR)family have also gained interest in reducing hepatic lipotoxicity and restoring hepatic function in models of ***,the true interplay between the clinical and molecular components of MAfLD progression remain only partly *** recently,multiomics-based strategies are being adopted for hypothesis-free analysis of the molecular changes in *** profiling maps the unique genotype-phenotype associations in MAfLD and with various single-cell tran scriptome-based projects underway,there is hope of novel physiological insigh

关键词： fatty liver disease Metabolic-associated fatty liver disease Nonalcoholic steatohepatitis Reactive oxidation species Oxidative stress

Association of serum bilirubin and non-alcoholic fatty liver disease: A feasible therapeutic avenue?

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World Journal of Pharmacology 2014年第4期3卷 209-216页

作者： Mohamed S Anwar john f dillon Michael H Miller Gut Group Medical Research Institute Ninewells Hospital and Medical School University of Dundee Dundee DD1 9SY United Kingdom

AIM： To the look at the current strength of evidence and the potential application of anti-oxidants in this ***： Two electronic databases （PubMed and Web of Knowledge） were searched to January 2013 to find studies addressing serum bilirubin levels in non-alcoholic fatty liver disease （NAfLD）. The search used key word combinations in relation to NAfLD and serum bilirubin specifc to human adults only. After screening selected studies were reviewed in depth by two inde-pendent reviewers. Data synthesis with further metaanalysis was planned but not possible due to the het-erogeneity of the outcome measures in these ***： Out of 416 studies screened only seven studies were considered suitable for inclusion. All seven studies consistently reported an inverse association of bilirubin with NAfLD despite the heterogeneous sample of studies. Only two studies were prospective. No negative studies were ***： Most studies suggest a correlation between high bilirubin levels of any type are inversely correlated with NAfLD. But to date most of these stud-ies have been poorly designed to allow meaningful con-clusions, except one cohort study. There is a need for a large prospective cohort study in multiple populations to test this hypothesis fully before mechanistic associa-tions can be established and therapeutic options of the apparent anti-oxidant effect of bilirubin be explored in NAfLD. furthermore these studies should include analysis of UGT1A1 gene to expound upon underlying cause of unconjugated hyperbilirubinaemia.

关键词： Review Systematic Bilirubin Hyperbiliru-binemia Anti-oxidants Adult Non-alcoholic fatty liver disease

fifty Years of Water Sensitive Urban Design, Salisbury, South Australia

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frontiers of Environmental Science & Engineering 2017年第4期11卷 63-72页

作者： john C. Radcliffe Declan Page Bruce Naumann Peter dillon CSIRO Land and Water Private Bag 2 Glen Osmond South Australia 5064 Australia City of Salisbury 12 James St Salisbury South Australia 5108 Australia

Australia has developed extensive policies and guidelines for the management of its water. The City of Salisbury, located within metropolitan Adelaide, South Australia, developed rapidly through urbanisation from the 1970s. Water sensitive urban design principles were adopted to maximise the use of the increased rim-off generated by urbanisation and ameliorate flood risk. Managed aquifer recharge was introduced for storing remediated low-salinity stormwater by aquifer storage and recovery （ASR） in a brackish aquiter for subsequent lrngatlon. Ibis paper outlines now a municipal government has progressively adopted principles of Water Sensitive Urban Design during its development within a framework of evolving national water policies. Salisbury＇s success with stormwater harvesting led to the formation of a pioneering w aterbusiness that includes linking projects from nine sites to provide a non-potable supply of 5 ×10^6 m^3 year. These installations hosted a number of applied research projects addressing well configuration, water quality, reliability and economics and facilitated the evaluation of its system as a potential potable water source. The evaluation showed that while untreated stonnwater contained contaminants, subsurface storage and end-use controls were sufficient to make recovered water sale for public open space irrigation, and with chlorination acceptable lbr third pipe supplies. Drinking water quality could be achieved by adding microfiltration, disinfection with UV and chlorination. The costs that would need to be expended to achieve drinking water safety standards were found to be considerably less than the cost of establishing dual pipe distribution systems. The full cost of supply was determined to be AUD$1.57 m ＂ for non-potable water for pubhc open space lrngatlon much cheaper than mares water, AUD $3.45 m at that time. Producing and storing potable water was found to cost AUDS1.96 to $2.24 m .

关键词： Managed Aquifer Recharge (MAR) Stormwater harvesting Water recycling drinking water Low impact development Water sensitive urban design

Proteomic and genomic studies of non-alcoholic fatty liver disease-clues in the pathogenesis

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World Journal of Gastroenterology 2014年第26期20卷 8325-8340页

作者： Jun Wei Lim john dillon Michael Miller Department of Gas-troenterology University of DundeeNinewells Hospital and Medical School

Non-alcoholic fatty liver disease(NAfLD)is a widely prevalent hepatic disorder that covers wide spectrum of liver *** is strongly associated with liver inflammation,metabolic hyperlipidaemia and insulin ***,NAfLD has been considered as the hepatic manifestation of metabolic *** pathophysiology of NAfLD has not been fully *** patients can remain in the stage of simple steatosis,which generally is a benign condition;whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular *** mechanism behind the progression is still not fully *** ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of *** genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease ***,NAfLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic *** paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAfLD *** proteomics section,this review highlighted functional proteins that involved in:(1)transportation;(2)metabolic pathway;(3)acute phase reaction;(4)antiinflammatory;(5)extracellular matrix;and(6)immune *** the genomic studies,this review will discuss genes which involved in:(1)lipolysis;(2)adipokines;and(3)cytokines production.

关键词： Non-alcoholic fatty liver disease Proteomics Genomics Metabolic syndrome Pathophysiology

Synchronous formation of the‘forearc’Bay of Islands ophiolite and its basal high-temperature metamorphic sole constrained by U-Pb zircon ages

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Geoscience frontiers 2023年第6期14卷 234-272页

作者： Weiyao Yan john f.Casey Department of Earth and Atmospheric Sciences University of HoustonHoustonTXUSA

The welded metamorphic sole at the base of the Bay of Islands Ophiolite Complex(BOIC)in the Northern Appalachians of Newfoundland shows a typical inverted pressure-temperature(P-T)metamorphic gradient from HT-MP granulite to LT-LP greenschist *** incorporates mafic volcanic/plutonic protoliths mixed with pelagic,hemi-pelagic and coarser epiclastic sedimentary *** LA-ICP-MS U–Pb concordia ages,trace elements,and Ti-in-zircon geothermometry for -250 zircon analyses from three metabasites of the upper HT sole amphibolites with N-MORB-like protoliths are *** samples collected within meters of the ophiolite peridotite-sole contact of the Blow Me Down Mountain and North Arm Mountain massifs yielded the oldest comparable concordia ages of 487.7±2.6 Ma and 489.1±3.1 Ma,respectively,that are both within error of the igneous age of 488.3±1.5 Ma of the directly overlying BOIC ophiolite,which formed at a supra-subduction zone(SSZ)forearc spreading center.A third slightly younger age of 484.2±2.4 Ma was obtained for an upper HT amphibolite sample with similar phase assemblages but collected30 m below the peridotite contact of the Table Mountain *** crystals analyzed have similar size and morphologies,subparallel rare earth element(REE)variation patterns,and steep heavy REE-enrichments((Lu/Gd)_(cn)>20),significant positive Ce anomalies(dominantly>5)and slight positive to dominantly negative Eu anomalies(1.2–0.4).Zircon shows Th/U mean values of 0.37–0.48 with little to no rim to core *** Ti-in-zircon mean crystallization temperatures range from764–787℃.These neocrystallized zircon crystals appear to be derived from thin leucosomes within the three *** other samples also from the upper HT sole show evidence of inherited detrital zircon with core dates spanning the Cambrian Notre Dame Arc through older Laurentian-like basement and rift age *** of the sole took place below a hot forearc asthenospheric wed

关键词： Ophiolite metamorphic sole U-Pb zircon ages Hot subduction interface Supra-subduction forearc spreading center Arc-continent collision Taconic Orogeny

Xylose: absorption, fermentation, and post-absorptive metabolism in the pig

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Journal of Animal Science and Biotechnology 2018年第1期9卷 1-9页

作者： Nichole f.Huntley john f.Patience Department of Animal Science 213 Kildee HallIowa State University Department of Animal Science 201B Kildee HallIowa State University

Xylose, as β-1,4-linked xylan, makes up much of the hemicel ulose in cel wal s of cereal carbohydrates fed to pigs. As inclusion of fibrous ingredients in swine diets continues to increase, supplementation of carbohydrases, such as xylanase,is of interest. However, much progress is warranted to achieve consistent enzyme efficacy, including an improved understanding of the utilization and energetic contribution of xylanase hydrolysis product（i.e. xylooligosaccharides or monomeric xylose）. This review examines reports on xylose absorption and metabolism in the pig and identifies gaps in this knowledge that are essential to understanding the value of carbohydrase hydrolysis products in the nutrition of the pig. Xylose research in pigs was first reported in 1954, with only sporadic contributions since. Therefore, this review also discusses relevant xylose research in other monogastric species, including humans. In both pigs and poultry, increasing purified D-xylose inclusion general y results in linear decreases in performance, efficiency, and diet digestibility. However,supplementation levels studied thus far have ranged from 5% to 40%, while theoretical xylose release due to xylanase supplementation would be less than 4%. More than 95% of ingested D-xylose disappears before the terminal ileum but mechanisms of absorption have yet to be ful y elucidated. Some data support the hypothesis that mechanisms exist to handle low xylose concentrations but become overwhelmed as luminal concentrations increase. Very little is known about xylose metabolic utilization in vertebrates but it is wel recognized that a large proportion of dietary xylose appears in the urine and significantly decreases the metabolizable energy available from the diet. Nevertheless, evidence of labeled D-xylose-1-^（14）C appearing as expired^（14）CO_2 in both humans and guinea pigs suggests that there is potential,although small, for xylose oxidation. It is yet to be determined if pigs develop increased xy

关键词： Pentose utilization Swine Threitol Xylose absorption Xylose metabolism

Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury

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Hepatobiliary & Pancreatic Diseases International 2005年第1期4卷 126-129页

作者： Gavin O'Brien Conor J Shields Desmond C Winter john P dillon Department Of Academic Surgery Cork University Hospital and National University of Ireland Cork Ireland William O Kirwan and H. Paul RedmondCork Ireland

BACKGROUND: The exact mechanism by which cyclooxy- genase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreati- tis , a disease process characterized by a systemic inflamma- tory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Daw- ley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group); controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg) at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung inju- ries were assessed histologically. Lung injury was assessed utilizing wet;dry ratio and myeloperoxidase activity to in- dicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancrea- tic tissue. RESULTS: The animals treated with COX-2 inhibitors dis- played significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P ficantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (Pfirmed attenuated COX-2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significandy attenu- ates the severity of both pancreatitis and its associated sys- temic inflammatory response and end-organ injury.

关键词： cyclooxygenase-2 pancreatitis genesis lung injury

The Use of VGPM to Estimate Oceanic Primary Production:A“Tango”Difficult to Dance

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Journal of Remote Sensing 2022年第1期2022卷 139-145页

作者： Zhongping Lee john f.Marra State Key Lab of Marine Environmental Science College of Earth and Ocean SciencesXiamen UniversityXiamenChina School for the Environment University of Massachusetts BostonBostonMA 02125USA Brooklyn College of the City University of New York BrooklynNY 11210USA

One of the primary goals of launching an ocean color satellite is to obtain over the global ocean synoptic measurements of primary production(PP),a measure of phytoplankton *** reach this ultimate goal,in addition to precise measurements of radiance at the satellite altitude and robust data processing systems,a key requirement is to link primary production with satellitederived products,where a model must be developed and *** many models have been developed in the past decades,the vertically generalized production model(VGPM)developed by Behrenfeld and falkowski,due to its simplicity and ease of use with satellite products,has been a de facto“standard”for the estimation of PP from ocean color measurements over the past 20+***,it has significantly influenced the ocean color remote sensing and the biological oceanographic *** this article,we discuss the limitations of VGPM(and PP models based on chlorophyll concentration)in estimating primary production.

关键词： Dance simplicity precise

Lipopolysaccharide immune stimulation but not β-mannanase supplementation affects maintenance energy requirements in young weaned pigs

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Journal of Animal Science and Biotechnology 2018年第4期9卷 901-916页

作者： Nichole f.Huntley C.Martin Nyachoti john f.Patience Department of Animal Science Iowa State University Department of Animal Science University of Manitoba

Background: Pathogen or diet-induced immune activation can partition energy and nutrients away from growth,but clear relationships between immune responses and the direction and magnitude of energy partitioning responses have yet to be elucidated. The objectives were to determine how β-mannanase supplementation and lipopolysaccharide(LPS) immune stimulation affect maintenance energy requirements(MEm) and to characterize immune parameters, digestibility, growth performance, and energy ***: In a randomized complete block design, 30 young weaned pigs were assigned to either the control treatment(CON; basal corn, soybean meal and soybean hul s diet), the enzyme treatment(ENZ; basal diet + 0.056% β-mannanase),or the immune system stimulation treatment(ISS; basal diet + 0.056% β-mannanase, chal enged with repeated increasing doses of Escherichia coli LPS). The experiment consisted of a 10-d adaptation period, 5-d digestibility and nitrogen balance measurement, 22 h of heat production(HP) measurements, and 12 h of fasting HP measurements in indirect calorimetry chambers. The immune chal enge consisted of 4 injections of either LPS(ISS) or sterile saline(CON and ENZ), one every48 h beginning on d 10. Blood was collected pre-and post-challenge for complete blood counts with differential,haptoglobin and mannan binding lectin, 12 cytokines, and glucose and insulin ***: Beta-mannanase supplementation did not affect immune status, nutrient digestibility, growth performance,energy balance, or MEm. The ISS treatment induced fever, elevated proinflammatory cytokines and decreased leukocyte concentrations(P 0.10),but increased total HP(21%) and MEm(23%), resulting in decreased lipid deposition(-30%) and average daily gain(-18%)(P ffects on immune parameters and energy balance i

关键词： Acute phase proteins β-Mannan Cytokines Digestibility feed induced immune response Heat production Inflammation Lipopolysaccharide Nitrogen balance Swine