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Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

Liver Research 2024年第1期8卷 46-53页

作者： Joshua hefler Rena Pawlick Braulio A.Marfil-Garza Aducio Thiesen Nerea Cuesta-Gomez Sanaz hatami darren h.freed Constantine Karvellas David L.Bigam A.M.James Shapiro Department of Surgery Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada Department of Medicine Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada ChRISTUS-LatAm hub Excellence&Innovation Center MonterreyMexico Alberta Diabetes Institute University of AlbertaEdmontonABCanada Clinical Islet Transplant Program University of AlbertaEdmontonABCanada Department of Laboratory Medicine&Pathology Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada

Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of *** hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or ***(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and ***-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the *** this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine *** and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/***,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after *** alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory ***:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(Phe liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,h CsA at all doses(P=0.012,0.007,andhe pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control ***

关键词： Cyclosporine(CsA) Cyclosporine analogue Liver surgery Ischemia-reperfusion injury(IRI) Animal model NIM-811

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hypoxia Enhances the Therapeutic Potential of Superparamagnetic Iron Oxide-labeled Adipose-derived Stem Cells for Myocardial Infarction

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Journal of huazhong University of Science and Technology(Medical Sciences) 2017年第4期37卷 516-522页

作者：王剑向波邓继先林宏宇 darren h.freed Rakesh C.Arora 田钢虹 Department of Vascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China National Research Council of Canada Winnipeg R3B 1Y6Canada Department of Physiology Faculty of MedicineUniversity of ManitobaWinnipeg R3E 3P5Canada Department of Pharmacology and Therapeutics Faculty of MedicineUniversity of ManitobaWinnipeg R3E OT6Canada Division of Cardiac Surgery University of Alberta Hospital Edmonton T6G 2B7Canada Cardiac Science Program Institute of Cardiovascular ScienceSt.Boniface General Hospital Winnipeg R2H 2A6Canada

Adipose-derived stem cells（ASCs） induce therapeutic angiogenesis due to pro-angiogenic cytokines secretion. Superparamagnetic iron oxide（SPIO） nanoparticles are critical for magnetic resonance（MR） tracking of implanted cells. hypoxia is a powerful stimulus for angiogenic activity of ASCs. In this study, we investigated whether therapeutic potency could be enhanced by implantation of hypoxia-preconditioned SPIO-labeled ASCs（SPIOASCs） into the infarcted myocardium. ASCs and SPIOASCs were cultured under 2% O_2（hypoxia） or 95% air（normoxia）. Cells were intramyocardially injected into the infarcted myocardium after 48-h culture. We found that hypoxia culture increased the m RNA expression of hypoxia-inducible factor-1 alpha（hIF-1α） and vascular endothelial growth factor（VEGF） in ASCs and SPIOASCs. The VEGF protein in the conditioned medium was significantly higher in hypoxic ASCs and SPIOASCs than in normoxic ASCs and SPIOASCs. The capillary density and left ventricular contractile function in the infarcted myocardium were significantly higher 4 weeks after implantation with hypoxic ASCs and SPIOASCs than with normoxic ASCs and SPIOASCs. Improvement in the capillary density and left ventricle function didn＇t differ between hypoxic ASCs-transplanted rats and hypoxic SPIOASCs-transplanted rats. hypoxic culture enhanced the angiogenic efficiency of ASCs. It was concluded that implantation of hypoxic ASCs or SPIOASCs promotes therapeutic angiogenesis and cardiac function recovery in the infarcted myocardium. SPIO labeling does not impact the beneficial effect of hypoxic ASCs.

关键词： hypoxia adipose-derived stem cells superparamagnetic iron oxide myocardial infarction

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The growing threat of non-alcoholic fatty liver disease-related hepatocellular carcinoma

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hepatobiliary Surgery and Nutrition 2022年第5期11卷 735-737页

作者： Margaret L.P.Teng Kai En Chan darren J.h.Tan Daniel Q.huang Division of Gastroenterology and hepatology Department of MedicineNational University Health SystemSingaporeSingapore Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore

Non-alcoholic fatty liver disease(NAFLD)is the fastest growing cause of hepatocellular carcinoma(hCC)worldwide(1).It is anticipated that the burden of NAFLD-related hCC will continue to increase in tandem with the global obesity epidemic(2,3).This has become a global issue of concern,as liver cancer is associated with significant morbidity and mortality,and is currently the third leading cause of cancer death(4).

关键词： hepatocellular NAFLD liver

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Identification of QTL and underlying genes for root system architecture associated with nitrate nutrition in hexaploid wheat

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Journal of Integrative Agriculture 2022年第4期21卷 917-932页

作者： Marcus GRIFFIThS Jonathan A.ATKINSON Laura-Jayne GARDINER Ranjan SWARUP Michael P.POUND Michael h.WILSON Malcolm J.BENNETT darren M.WELLS School of Biosciences University of NottinghamSutton Bonington CampusLE125RDUK Future Food Beacon of Excellence University of NottinghamSutton Bonington CampusLE125RDUK Integrative Phenomics Group School of BiosciencesUniversity of NottinghamSutton Bonington CampusLE125RDUK IBM Research The Hartree CentreWarringtonWA44ADUK School of Computer Science University of NottinghamNottinghamNG81BBUK

The root system architecture(RSA) of a crop has a profound effect on the uptake of nutrients and consequently the potential yield. however, little is known about the genetic basis of RSA and resource adaptive responses in wheat(Triticum aestivum L.). here, a high-throughput germination paper-based plant phenotyping system was used to identify seedling traits in a wheat doubled haploid mapping population, Savannah×Rialto. Significant genotypic and nitrate-N treatment variation was found across the population for seedling traits with distinct trait grouping for root size-related traits and root distribution-related traits. Quantitative trait locus(QTL) analysis identified a total of 59 seedling trait QTLs. Across two nitrate treatments, 27 root QTLs were specific to the nitrate treatment. Transcriptomic analyses for one of the QTLs on chromosome 2 D, which was found under low nitrate conditions, revealed gene enrichment in N-related biological processes and 28 differentially expressed genes with possible involvement in a root angle response. Together, these findings provide genetic insight into root system architecture and plant adaptive responses to nitrate, as well as targets that could help improve N capture in wheat.

关键词： doubled-haploid population nitrate RNA-seq quantitative trait loci root system architecture Triticum aestivum L.(wheat)

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Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

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World Journal of Nephrology 2023年第5期12卷 168-181页

作者： Rajkumar Chinnadurai henry h L Wu Jones Abuomar Sharmilee Rengarajan David I New darren Green Philip A Kalra Donal O’Donoghue Renal Research Centre&Department of Renal Medicine Northern Care Alliance NHS Foundation TrustSalford M68HDUnited Kingdom Department of Renal Research Kolling Institute of Medical ResearchRoyal North Shore Hospital&The University of SydneySt.Leonards(Sydney)2065New South WalesAustralia Faculty of Biology Medicine&HealthThe University of ManchesterManchester M17HRUnited Kingdom

BACKGROUND hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and *** remains variability in antihypertensive treatment *** To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD *** The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since *** patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were *** between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression ***-Meier analysis demonstrated differences in survival *** Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were *** median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,Phypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,Ph the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system *** pr

关键词： hypertension Chronic kidney disease Antihypertensive agents Prescribing patterns Cardiovascular complications Renin angiotensin system blockers

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Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams

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Light(Science & Applications) 2022年第11期11卷 2790-2804页

作者： Philip Wijesinghe Stella Corsetti darren J.X.Chow Shuzo Sakata Kylie R.Dunning Kishan Dholakia SUPA School of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsFife KY169SSUK Robinson Research Institute Adelaide Medical SchoolThe University of AdelaideAdelaideSAAustralia Australian Research Council Centre of Excellence for Nanoscale BioPhotonics The University of AdelaideAdelaideSAAustralia Institute for Photonics and Advanced Sensing The University of AdelaideAdelaideSAAustralia Strathclyde Institute of Pharmacy and Biomedical Sciences University of StrathclydeGlasgow G4 OREUK School of Biological Sciences The University of AdelaideAdelaideSAAustralia Department of Physics College of ScienceYonsei UniversitySeoul 03722South Korea

Deconvolution is a challenging inverse problem,particularly in techniques that employ complex engineered pointspread functions,such as microscopy with propagation-invariant ***,we present a deep-learning method for deconvolution that,in lieu of end-to-end training with ground truths,is trained using known physics of the imaging ***,we train a generative adversarial network with images generated with the known point-spread function of the system,and combine this with unpaired experimental data that preserve perceptual *** method rapidly and robustly deconvolves and super-resolves microscopy images,demonstrating a two-fold improvement in image contrast to conventional deconvolution *** contrast to common end-to-end networks that often require 1000-10,000s paired images,our method is experimentally unsupervised and can be trained solely on a few hundred regions of *** demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes,preimplantation embryos and excised brain tissue,as well as illustrate its utility for Bessel-beam *** method aims to democratise learned methods for deconvolution,as it does not require data acquisition outwith the conventional imaging protocol.

关键词： invariant propagation implantation

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Clinical utility of non-invasive tests to predict clinical outcomes in non-alcoholic fatty liver disease

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hepatobiliary Surgery and Nutrition 2023年第6期12卷 916-918页

作者： Shi Yan Lee darren J.h.Tan Wen hui Lim Cheng han Ng Mark Muthiah Daniel Q.huang Division of Gastroenterology and hepatology Department of MedicineNational University HospitalSingaporeSingapore Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore National University Centre for Organ Transplantation National University Health SystemSingaporeSingapore

Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease,and the fastest-growing cause of hepatocellular carcinoma(hCC)worldwide(1,2).As the number of people with NAFLD is too great to perform surveillance in all,risk-stratification strategies are increasingly important to identify those at the highest risk of decompensation and hCC(3,4).

关键词： Non-alcoholic fatty liver disease(NAFLD) non-invasive tests fibrosis-4(FIB-4) vibration-controlled transient elastography(VCTE) clinical outcomes

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A mixed acid methodology to produce thermally stable cellulose nanocrystal at high yield using phosphoric acid

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Journal of Bioresources and Bioproducts 2022年第2期7卷 17-26页

作者： Khairatun Najwa Mohd Amin Alireza hosseinmardi darren J.Martin Pratheep K.Annamalai Australian Institute for Bioengineering and Nanotechnology(AIBN) the University of QueenslandBrisbaneQLD 4072 Australia Faculty of Chemical and Process Engineering Technology College of Engineering TechnologyUniversiti Malaysia PahangLebuhraya Tun Razak26300 Gambang KuantanPahang D.M.Malaysia

Cellulose nanocrystal(CNC)with distinctive shape-morphology,enhanced thermal stability and dispersibility is essential for overcoming the challenges in processing polymer/CNC nanocom-posites through melt compounding at elevated *** study shows a mixed acid hy-drolysis method to produce CNC with improved thermal stability and high *** use of phosphoric acid(h_(3)PO_(4)),as a mild acid,in combination with a strong acid either sulphuric acid(h_(2)SO_(4))or hydrochloric acid(hCl)leads to reduced use of strong acids and low impact on our *** influences of acid combination and sequence of addition on the production yield were investigated by retaining the proportion of h_(3)PO_(4)to corrosive acid(h_(2)SO_(4)and hCl)4 to 1,and solid to liquid ratio 1꞉*** methodology has enabled to isolate CNC with higher thermal stability,dispersibility and productivity in terms of amount acid used 1 g of CNC,as compared with single acid *** CNC produced using the combination of h_(3)PO_(4)and hCl exhibits high thermal stability,dispersibility and rod-like shape morphology with length and width of(424±86)and(22±3)nm,***,this approach has reduced h_(3)PO_(4)consumption by 54%as compared with single acid hydrolysis method for the production of same amount of CNC.

关键词： Cellulose nanocrystal(CNC) Acid hydrolysis Thermal stability Mixed acid Crystallinity Production yield

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Robust nonlinear control strategy to maximize energy capture in a variable speed wind turbine with an internal induction generator

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控制理论与应用（英文版） 2012年第2期10卷 184-194页

作者： Erhun IYASERE Mohammed h. SALAh darren M. DAWSON John R. WAGNER Enver TATLICIOGLU Jacobsen a Textron CompanyCharlotteNCU.S.A. Department of Mechatronics Engineering Hashemite UniversityZarqaJordan Department of Electrical & Computer Engineering Clemson UniversityClemsonSCU.S.A. Department of Mechanical Engineering Clemson UniversityClemsonSCU.S.A. Department of Electrical & Electronics Engineering Izmir Institute of TechnologyIzmirTurkey

This paper proposes a control strategy to maximize the wind energy captured in a variable speed wind turbine, with an internal induction generator, at low to medium wind speeds. The proposed strategy controls the tipspeed ratio, via the rotor angular speed, to an optimum point at which the efficiency constant （or power coefficient） is maximum for a particular blade pitch angle and wind speed. This control method allows for aerodynan^c rotor power maximization without exact wind turbine model knowledge. Representative numerical results demonstrate that the wind turbine can be controlled to achieve near maximum energy capture.

关键词： Robust nonlinear control Maximum energy capture Wind turbine

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Scoring of sperm chromosomal abnormalities by manual and automated approaches：qualitative and quantitative comparisons

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Asian Journal of Andrology 2010年第2期12卷 257-262页

作者： helen G. Tempest Siu Yan Cheng David J. Gillott Alan h. handyside Alan R. Thomhill darren K. Griffin London Bridge Fertility Gynaecology and Genetics Centre London SEI 9RY UK Bridge Genoma London SE1 9RY UK Department of Biosciences University of Kent Canterbury Kent CT2 7N J UK

It is now well known that levels of sperm disomy correlate to levels of infertility （as well as other factors）.The risk of perpetuating aneuploidy to the offspring of infertile males undergoing intracytoplasmic sperm injection （ICSI） has become a hotly debated issue in assisted reproduction;however,there remain barriers to the practical implementation of offering sperm disomy screening in a clinical setting. The major barrier is the operator time taken to analyze a statistically meaningful （sufficient） number of cells. The introduction of automated ＇spot counting＇software-hardware combinations presents a potential solution to this problem. In this preliminary validation study,we analyzed 10 patients,both manually and using a commercially available spot counter. Results show a statistically significant correlation between both approaches for scoring of sperm disomy,but no correlation is found when scoring for diploid sperm. The most likely explanation for the latter is an apparent overscoring of two closely associated sperm heads as a single diploid cell. These results,and similar further studies that will ensue,help to inform cost-benefit analyses that individual clinics need to carry out in order to decide whether to adopt sperm aneuploidy screening as a routine tool for the assessment of sperm from men requiring ICSI treatment.

关键词： aneuploidy assisted reproductive technologies automation fluorescent in situ hybridization methods scoring spermatozoa

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