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Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism

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genes & Diseases 2022年第4期9卷 1129-1142页

作者： Brendan P.Norman Andrew S.Davison Juliette H.Hughes Hazel Sutherland Peter J.M.Wilson neil g.berry Andrew T.Hughes Anna M.Milan Jonathan C.Jarvis Norman B.Roberts Lakshminarayan R.Ranganath george Bou-gharios James A.gallagher Institute of Life Course and Medical Sciences University of LiverpoolWilliam Henry Duncan Building6 West Derby StreetLiverpoolL78TXUK Department of Clinical Biochemistry&Metabolic Medicine Liverpool Clinical LaboratoriesRoyal Liverpool University HospitalPrescot StreetLiverpoolL78XPUK School of Sport&Exercise Sciences Liverpool John Moores UniversityTom Reilly BuildingByrom StreetLiverpoolL33AFUK Department of Chemistry University of LiverpoolCrown StreetLiverpoolL697ZDUK

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HgD). The primary consequence of HgD deficiency is increased circulating homogentisic acid (HgA), the main agent in the pathology of AKU disease. Here we report the first metabolomic analysis of AKU homozygous Hgd knockout (Hgd−/−) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd−/− AKU (n = 15) and Hgd+/− non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd−/− were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the HgA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of 13C-labelled HgA to Hgd−/−(n = 4) and Hgd+/−(n = 4) mice (Experiment 3) to confirm direct association with HgA. Hgd−/− mice showed the expected increase in HgA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in Hgd−/− were HgA and previously unreported sulfate and glucuronide HgA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from HgA by the 13C-labelled HgA tracer. Our findings reveal that increased HgA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism.

关键词： Alkaptonuria Biotransformation Metabolism Metabolomics Mice

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How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia galea Kirsten Holte Caroline Luszawski Elizabeth Jenkins Jennifer O’neil Carolyn A Emery Rebekah Mannix Kathryn Schneider Keith Owen Yeates Roger Zemek Children’s Hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The Centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research Centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta Children’s Hospital Research Institute University of Calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of Pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the Cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and CERT publication,but p

关键词： Concussion Intervention Randomized controlled trial Systematic review

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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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general Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes Jessica Rast Caichen Zhong Renee M gardner Christina Dalman Kristen Lyal cRAIg Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind neil M Davies Brian K Lee Cecilia Magnusson Dheeraj Rai Department of global Public Health Karolinska InstitutetStockholmSweden Medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community Medicine Region StockholmStockholmSweden K.g Jebsen Center for genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample Mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,pgs from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

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Multivariate Approach to Characterizing Soil Quality of gabonese’s Ferralitic Soils

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Open Journal of Soil Science 2024年第4期14卷 237-268页

作者： neil-Yohan Musadji Rolf gaël Mabicka Obame Michel Mbina Mounguengui Jean Aubin Ondo Lydie-Stella Koutika Eric Ravire Claude geffroy Laboratoire De Chimie Des Milieux et Des Mat&#233riaux Inorganiques Laboratoire D&#8217Analyse Des Sols et Environnement D&#233partement Des Sciences Fondamentales De L&#8217Ing&#233nieur Institut National D&#8217Agronomie et De Biotechnologies Universit&#233 Des Sciences et Techniques De Masuku Franceville Gabon Institut De Chimie Des Milieux et Maté riaux De Poitiers (IC2MP) Universit&#233 De Poitiers Poitiers France Laboratoire De Chimie Des Milieux et Des Mat&#233riaux Inorganiques Laboratoire D&#8217Analyse Des Sols et Environnement D&#233partement De Phytotechnologie Institut National D&#8217Agronomie et De Biotechnologies Universit&#233 Des Sciences et Techniques De Masuku Franceville Gabon Dé partement De G&#233ologie Facult&#233 Des Sciences Universit&#233 Des Sciences et Techniques De Masuku Franceville Gabon Laboratoire Pluridisciplinaire Des Sciences Ecole Normale Sup&#233rieure Libreville Gabon Centre De Recherche Sur La Productivité et La Durabilit&#233 Des Plantations Industrielles Pointe Noire Republic of Congo Sucaf gabon Somdiaa Franceville Gabon

Assessing soil quality is essential for crop management and soil temporal changes. The present study aims to evaluate soil quality in the Ferralitic soils context countrywide. This assessment was done using multivariate soil quality indice (SQI) models, such as additive quality index (AQI), weighted quality indexes (WQIadd and WQIcom) and Nemoro quality index (NQI), applied to two approaches of indicator selection: total data set (TDS) and minimum data set (MDS). Physical and chemical soil indicators were extracted from the ORSTOM’s reports resulting from a sampling campaign in different provinces of gabon. The TDS approach shows soil quality status according to eleven soil indicators extracted from the analysis of 1,059 samples from arable soil layer (0 - 30 cm depth). The results indicated that 87% of all provinces presented a very low soil quality (Q5) whatever the model. Among soil indicators, exchangeable K+ and Mg2+, bulk density and C/N ratio were retained in MDS, using principal component analysis (PCA). In the MDS approach, 50 to 63% of provinces had low soil quality grades with AQI, WQIadd and NQI, whereas the total was observed with WQIcom. Only 25% of provinces had medium soil quality grades with AQI and NQI models, while 12.5% (NQI) and 25% (AQI) presented high quality grades. Robust statistical analyses confirmed the accuracy and validation (0.80 r P ≤ 0.016) of AQI, WQIadd and NQI into the TDS and MDS approaches. The same sensitivity index value (1.53) was obtained with AQI and WQIadd. However, WQIadd was chosen as the best SQI model, according to its high linear regression value (R2 = 0.82) between TDS and MDS. This study has important implications in decision-making on monitoring, evaluation and sustainable management of gabonese soils in a pedoclimatic context unfavorable to plant growth.

关键词： gabon Ferralitic Soil Soil Indicators Standard Score Function Soil Quality Indices Sustainable Soil Soil Management

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Diffusion weighted MRI and tractography for evaluating peripheral nerve degeneration and regeneration

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Neural Regeneration Research 2014年第24期9卷 2122-2124页

作者： neil g.Simon Michel Kliot Prince of Wales Clinical School University of New South Wales Central Clinical School The University of Sydney Department of Neurological Surgery Northwestern Feinberg School of Medicine

Accurately documenting and quantifying peripheral nerve axonal degeneration and regeneration is critically important for clinical research in peripheral nerve disorders such as nerve trauma, peripheral neuropathy and amyotrophic lateral sclerosis （ALS）. Current strategies include clinical assessments and neurophysiological studies （including nerve conduction studies and electromyography （EMg））. However, the information provided by these strategies is limited in a number of ways.

关键词： DTI MRI Figure

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Protective effects of trilinolein extracted from Panax notoginseng against cardiovascular disease

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Acta Pharmacologica Sinica 2002年第12期23卷 104-109页

作者： Paul CHAN,g neil THOMAS,Brian TOMLINSON Division of Cardiovascular Medicine Taipei Medical College Affiliated Taipei Wan Fang Hospital Taipei China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong SAR China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong SAR China

Trilinolein is a triacylglycerol purified from a commonly used traditional Chinese medicine Panax notoginseng. Trilinolein has been reported to provide a number of beneficial effects including reducing thrombogenicity and arrhythmias and increasing erythrocyte deformability. Additionally, trilinolein has been reported to be an antioxidant, which can counteract free radical damage associated with atherogenesis, and myocardial damage seen with is-chaemia and reperfusion. These pharmacologic effects may explain the perceived benefits derived from treating circulatory disorders with the herb over the centuries.

关键词： antioxidants cardiovascular system Chinese traditional medicine trilinolein Panax notoginseng

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National Soil Organic Carbon Stocks Inventories under Different Mangrove Forest Types in gabon

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Open Journal of Forestry 2024年第2期14卷 127-140页

作者： Rolf gaël Mabicka Obame neil-Yohan Musadji Jean Hervé Mve Beh Lydie-Stella Koutika Jean Aubin Ondo Farrel Nzigou Boucka Michel Mbina Mounguengui Claude geffroy Dé partement de Phytotechnologie Institut National d&#8217Agronomie et de Biotechnologies Universit&#233 des Sciences et Techniques de Masuku Franceville Gabon Dé partement des Sciences Fondamentales de l&#8217Ing&#233nieur Institut National d&#8217Agronomie et de Biotechnologies Universit&#233 des Sciences et Techniques de Masuku Franceville Gabon Institut Agronomiques et Forestiè res Centre National des Recherches Scientifiques et Technologiques Libreville Gabon Research Centre on the Durability and the Productivity of Industrial Plantations (CRDPI) Pointe Noire Republic of Congo Laboratoire Pluridisciplinaire des Sciences &#201cole Normale Sup&#233rieure Libreville Gabon Agence gabonaise d’ &#201tude et d&#8217Observation Spatiale Immeuble les Arcades Libreville Gabon Dé partement de G&#233ologie Faculte des Sciences Universit&#233 des Sciences et Techniques de Masuku Franceville Gabon Institut de Chimie des Milieux et Maté riaux de Poitiers (IC2MP) Universit&#233 de Poitiers Poitiers France

gabonese’s estuary is an important coastal mangrove setting and soil plays a key role in mangrove carbon storage in mangrove forests. However, the spatial variation in soil organic carbon (SOC) storage remain unclear. To address this gap, determining the SOC spatial variation in gabonese’s estuarine is essential for better understanding the global carbon cycle. The present study compared soil organic carbon between northern and southern sites in different mangrove forest, Rhizophora racemosa and Avicennia germinans. The results showed that the mean SOC stocks at 1 m depth were 256.28 ± 127.29 MgC ha−1. Among the different regions, SOC in northern zone was significantly (p p gher SOC stocks (254.62 ± 128.09 MgC ha−1) than upper layers (55.42 ± 25.37 MgC ha−1). The study highlights that low deforestation rate have led to less CO2 (705.3 Mg CO2e ha−1 - 922.62 Mg CO2e ha−1) emissions than most sediment carbon-rich mangroves in the world. These results highlight the influence of soil texture and mangrove forest types on the mangrove SOC stocks. The first national comparison of soil organic carbon stocks between mangroves and upland tropical forests indicated SOC stocks were two times more in mangroves soils (51.21 ± 45.00 MgC ha−1) than primary (20.33 ± 12.7 MgC ha−1), savanna and cropland (21.71 ± 15.10 MgC ha−1). We find that mangroves in this study emit lower dioxide-carbon equivalent emissions. This study highlights the importance of national inventories of soil organic carbon and can be used as a baseline on the role of mangroves in carbon sequestration and climate change mitigation but the variation in SOC stocks indicates the need for further national data.

关键词： Mangroves Forest Soil Organic Carbon Stocks Rizophora Racemose Avicenia germinans gabon

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Controlling human platelet activation with calcium-binding nanoparticles

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Nano Research 2020年第10期13卷 2697-2705页

作者： David Cabrera Karen Walker Sandhya Moise neil D.Telling Alan g.S.Harper School of Pharmacy and Bioengineering Keele UniversityGuy Hilton Research CenireThormburrow DriveHartshill Stoke-on Trent ST47QBUK ?Central Electron Microscope Unit School of Life SciencesKeele UniversityNewcastle-under LIymeStaffordshireST55BGUK Department of Chemical Engineering University of BathBath BA27AYUK School of Medicine Keele UniversityNewcastle-under-LymeStaffordshireST55BGUK

Human platelets aggregate at sites of blood vessel damage in response to a rise in their cytosolic calcium *** these cytosolic calcium rises would provide a method to inhibit platelet activation and prevent the unwanted blood clots that causes heart attack and *** we have predicted that calcium accumulation within the lumen of an infolded portion of the platelet plasma membrane called the open canalicular system(OCS)is essential for maintaining this cytosolic calcium *** to its nanometer dimensions of the OCS,it has been difficult to measure or interfere with the predicted luminal calcium *** we utilise iron oxide magnetic nanoparticles coated with the known calcium chelator,citrate,to create calcium-binding *** were used to assess whether an OCS calcium store plays a role in controlling the dynamics of human platelet activation and *** demonstrate that citrate-coated nanoparticles are rapidly and selectively uptaken into the OCS of activated human platelets,where they act to buffer the accumulation of calcium *** with these calcium-binding nanoparticles reduced thrombin-evoked cytosolic calcium rises,and slowed platelet aggregation and clot retraction in human *** contrast,nanoparticles that cannot bind calcium have no *** study demonstrates that the OCS acts as a key source of calcium for maintaining cytosolic calcium rises and accelerating platelet aggregation,and that calcium-binding nanoparticles targeted to the OCS could provide an anti-platelet therapy to treat patients at risk of suffering heart attacks or strokes.

关键词： nanochelators human platelets open canalicular system calcium signaling nanoparticles

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Mainstreaming Disaster Risk Reduction and Climate Change Adaptation in Comprehensive Development Planning of the Cities in Nueva Ecija in the Philippines

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International Journal of Disaster Risk Science 2021年第3期12卷 367-380页

作者： Arneil g.gabriel Patrick neil M.Santiago Rosemarie R.Casimiro Department of Public Administration Nueva Ecija University of Science and Technology3100 Cabanatuan CityPhilippines

Recent scientific consensus suggests that climate-related disasters are becoming more frequent and ***,increasing importance is given to disaster risk reduction(DRR)and climate change adaptation(CCA)in global *** projected global warming at 1.5℃and the climate variability that the Philippine archipelago experiences make DRR-CCA the key priorities of both the national and local government *** this study,we assessed and measured the degree of mainstreaming of DRR-CCA in the comprehensive development plans(CDPs)of the five component cities in the province of Nueva Ecija in the *** are among the areas in Central Luzon that are susceptible to hydrometeorological and geologic *** distributed survey questionnaires to 25 employees of the local government units in the five component cities in Nueva Ecija who are directly involved in planning *** triangulated their responses using archival data(review of written policies and plans).The main findings of the study indicate that in spite the presence of laws and policies on DRR-CCA,their implementation is only in the preliminary *** results also provide insights to policymakers and future researchers on the challenges and opportunities influencing the systemic mainstreaming of DRR-CCA in the province.

关键词： Climate-related disasters global warming Local development planning Philippines Southeast Asia

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Recent progress in hydrocarbon biofuel synthesis:Pathways and enzymes

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Chinese Chemical Letters 2015年第4期26卷 431-434页

作者： Feng-Ming Lin E.neil g.Marsh Xiaoxia Nina Lin State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast University Department of Chemistry University of Michigan Department of Chemical Engineering University of Michigan Department of Biological Chemistry University of Michigan

Biofuels derived from hydrocarbon biosynthetic pathways have attracted increasing attention. Routes to hydrocarbon biofuels are emerging and mainly fall into two categories based on the metabolic pathways utilized： Fatty acid pathway-based alkanes/alkenes and isoprenoid biosynthetic pathway based terpenes. The primary focus of this review is on recent progress in the application of hydrocarbon biosynthetic pathways for hydrocarbon biofuel production, together with studies on enzymes, including efforts to engineering them for improved performance.

关键词： BiofuelFatty acid biosynthesis pathwaylsoprenoid biosynthesis pathwayMetabolic engineering

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