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Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction

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World Journal of Gastroenterology 2018年第16期24卷 1748-1765页

作者： Michelle l Boland Stephanie Oldham Brandon B Boland Sarah Will Jean-Martin lapointe Silvia Guionaud Christopher J Rhodes james l trevaskis Cardiovascular and Metabolic Diseases MedImmune LLC Pathology MedImmune Ltd. Pathology Drug Safety and MetabolismIMED Biotech UnitAstraZeneca

AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFlD) with or without progressive fibrosis: lep^(ob)/lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMlN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESUlTS When challenged with AMlN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMlN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMlN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMlN mice compared to FATZO AMlN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 Bl6 J control mice, but significantly perturbed in ob/ob mice. CONClUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is a key factor for development of hepatic injury

关键词： Nonalcoholic steatohepatitis Steatosis Fibrosis Mitochondrial function Oxidative stress

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Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source

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World Journal of Gastroenterology 2019年第33期25卷 4904-4920页

作者： Michelle l Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang james l trevaskis Henrik H Hansen Cardiovascular Renal and Metabolic DiseasesMedImmuneGaithersburgMD 20878United States Pharmacology GubraH■rsholm DK-2970Denmark

BACKGROUND The trans-fat containing AMlN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57Bl/6J mice with or without the lep^ob/lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57Bl/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMlN diet or a modified AMlN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57Bl/6J mice were fed the same diets for 28 wk.AMlN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESUlTS The GAN diet was more obesogenic compared to the AMlN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMlN diet.C57Bl/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONClUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57Bl/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

关键词： Non-alcoholic steatohepatitis High-fat diet Mouse model Histopathology Fibrosis liver biopsy liver transcriptome

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Competitive interactions and coexistence of sympatric flagship carnivores in Asia

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Integrative Zoology 2024年第2期19卷 183-199页

作者： Zhilin lI Jiayu lU Xiaoyi SHI li’an DUO james l.D.SMITH Tianming WANG Tianjin Key laboratory of Conservation and Utilization of Animal Diversity College of Life SciencesTianjin Normal UniversityTianjinChina Department of Fisheries Wildlife and Conservation BiologyUniversity of MinnesotaSt.PaulMinnesotaUSA Ministry of Education Key laboratory for Biodiversity Science and Engineering College of Life SciencesBeijing Normal UniversityBeijingChina National Forestry and Grassland Administration Key laboratory for Conservation Ecology of Northeast Tiger and leopard BeijingChina

Understanding the competition and coexistence of flagship carnivores is key to creating strategies for their conservation in the face of global carnivore declines.Although studies exploring the dynamics and competition between tigers(Panthera tigris)and leopards(P.pardus)span decades,there is a lack of understanding regarding the factors that influence their coexistence mechanisms on a broad scale,as well as the drivers determining their exploitative and interference competition.We gathered a comprehensive list of research papers among which 36 papers explored the interspecific interactions between tigers and leopards and tested the influence of biotic and abiotic factors on the coexistence mechanisms along three dimensions using multiple response variables regression models;we also tested the influence of ecological drivers determining the exploitative or interference competition between tigers and leopards.Elevation and ungulate density were the most important predictors in regulating the coexistence mechanisms.Tigers and leopards exhibited more positive relations/higher overlaps as elevation increased in the spatial niche.In addition,they showed a higher dietary overlap in the prey-rich regions.We determined that interference competition between tigers and leopards was less frequently observed in habitats with dense tree cover and homogeneous vegetation structures.Meanwhile,studies with multiple metrics would promote the detection of interference competition.Our study provides new insight into the competitive interactions and coexistence mechanisms of tigers and leopards on a broad scale.Policy-makers and managers should pay more attention to the factors of elevation,prey abundance,and habitat structures for the conservation of tigers and leopards.

关键词： carnivores coexistence mechanisms competitive interactions exploitative competition interference competition

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The Making of a Health Profession:How Chinese Medicine Became a Nationally Registered Allied Health Profession in Australia

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Chinese Medicine and Culture 2024年第1期7卷 51-62页

作者： John l McDonald Judy B james School of Chinese Medicine Endeavour College of Natural HealthSouthport 4215Australia Acupuncture Now Australia Brisbane 4120Australia

In 2012, traditional Chinese medicine(TCM) practitioners in Australia became nationally-registered allied health professionals in three categories: acupuncturist, Chinese herbal medicine practitioner, and Chinese herbal medicine dispenser. Australia was the first Western country to introduce national registration for Chinese medicine, followed by Portugal and, recently, New Zealand. The practice of TCM in Australia can be traced back to the beginning of Chinese immigration to Australia during the Victorian Gold Rush which began in the 1850s. The process which led to national registration commenced in the early 1970s with the establishment of the first acupuncture courses. Decades of gradual development of courses from unaccredited part-time diplomas to accredited bachelor degrees, and the development, by the profession, of national consensus on educational standards were essential elements in the process which led to registration. Professional associations, such as the Australian Acupuncture and Chinese Medicine Association ltd.(AACMA), also developed a framework of professional selfregulation, including Codes of Ethics, Codes of Conduct, ongoing professional development requirements and Infection Control Guidelines, and provided leadership in the development of the profession. After decades of tribalism and division within the TCM profession, the National Academic Standards Committee brought almost all stakeholders together to reach a consensus on the Australian Guidelines for Traditional Chinese Medicine Education which were published by AACMA in 2001. Professional associations also collaborated on joint submissions to the government in support of registration, which was introduced first in the state of Victoria in 2000, and subsequently became national in 2012. Despite national registration, some barriers still remain, and professional associations continue to lobby the federal government for inclusion in Medicare, chronic disease management scheme, and Veterans Affairs.

关键词： Acupuncture Chinese medicine Registration Regulation Education Standards Australia TCM

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Nickel sulfate solution fluoride separation with hydrous zirconium oxide

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Tungsten 2024年第2期6卷 367-381页

作者： Elbert M.Nigri Ummul K.Sultana André l.A.Santos james W.Vaughan Sonia D.F.Rocha Department of Mining Engineering Federal University of Minas GeraisBelo Horizonte 31270-901Brazil School of Chemical Engineering University of QueenslandSt Lucia 4072Australia

Fluoride is an impurity in nickel sulfate production,which is required for electric vehicle batteries.Hydrous zirconium oxide(HZO)was evaluated for removing fl uoride from nickel sulfate solution.Maximum fluoride removal occurred at pH value 4 and optimal pH value is 4–5,considering Zr solubility.Fluoride availability decreases with pH due to hydrogen fluoride and zirconium fluoride aqueous species.Fluoride removal is initially rapid,with 50 wt.%removal in 7 min,followed by slow removal up to 68 wt.%after 72 h and follows second order rate kinetics.Fluoride removal was dominated by an ion exchange mechanism and resulting Zr–F bonds were observed using Fourier-transform infrared spectroscopy.The presence of nickel sulfate decreased loading capacity compared to a salt-free solution.HZO maintained adsorption capacity through five cycles of loading and regeneration.

关键词： Hydrous zirconium oxide Nickel sulfate Fluoride Adsorption Anion exchange

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Colorful facial markings are associated with foraging rates and affiliative relationships in a wild group-living cichlid fish

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Current Zoology 2024年第1期70卷 70-78页

作者： Brett M.Culbert james B.Barnett Isaac Y.ligocki Matthew G.Salena Marian Y.l.Wong Ian M.Hamilton Sigal Balshine Department of Integrative Biology University of GuelphGuelphOntarioCanada Department of Psychology Neuroscience&BehaviourMcMaster UniversityHamiltonOntarioCanada Department of Evolution Ecologyand Organismal BiologyThe Ohio State UniversityColumbusOHUSA Department of Biology Millersville UniversityMillersvillePAUSA School of Earth Atmospheric and Life SciencesUniversity of WollongongWollongongNew South WalesAustralia Department of Mathematics The Ohio State UniversityColumbusOHUSA

Many animals use color to signal their quality and/or behavioral motivations.Colorful signals have been well studied in the contexts of competi-tion and mate choice;however,the role of these signals in nonsexual,affiliative relationships is not as well understood.Here,we used wild social groups of the cichlid fish Neolamprologus pulcher to investigate whether the size of a brightly colored facial patch was related to 1)individual quality,2)social dominance,and/or 3)affiliative relationships.Individuals with larger patches spent more time foraging and tended to perform more aggressive acts against conspecific territory intruders.We did not find any evidence that the size of these yellow patches was related to social rank or body size,but dominant males tended to have larger patches than dominant females.Additionally,patch size had a rank-specific relationship with the number of affiliative interactions that individuals engaged in.Dominant males with large patches received fewer affiliative acts from their groupmates compared to dominant males with small patches.However,subordinates with large patches tended to receive more affiliative acts from their groupmates while performing fewer affiliative acts themselves.Taken together,our results suggest that patch size reflects interindividual variation in foraging effort in this cichlid fish and offer some of the first evidence that colorful signals may shape affiliative relationships withinwildsocialgroups.

关键词： affiliation foraging lake Tanganyika Neolamprologus pulcher visual signals

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Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： Joseph Rich Brian Cole Teng li Brandon lu Hanyu Fu Brittany N.Smith Jianping Xia Shujie Yang Ruoyu Zhong james l.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony Jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid actuation.However,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing.To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet printing.We successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler vibrometry.Finally,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration experiments.Overall,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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

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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 ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(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 injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials 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/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(AlT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower AlT levels(Ply).Moreover,the 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,ly)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,andly).levels of the 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 mice.Conclusions:Premedication with CsA or NIM-811 mitig

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

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An Automated,Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

Precision Chemistry

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Precision Chemistry 2024年第2期2卷 57-62页

作者： Ann Adele Byars Khushi R.Kompally Emily Mechnick Reilly E.Sonstrom Alexander Mikhonin Justin l.Neill Ruth Boetzel james MacGregor Courtney Talicska Jian li Yizhou liu BrightSpec Inc.CharlottesvilleVirginia 22903United States Pfizer R&D UK limited Sandwich CT139NJUnited Kingdom Analytical Research and Development Pfizer Research and DevelopmentGrotonConnecticut 06340United States

Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these processes.In this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring measurements.An interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and tested.Two reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol tautomerization.The spectrometer was able to provide kinetic information about the reaction and determine reaction completion.In the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.

关键词： molecular rotational resonance spectroscopy reaction monitoring reaction kinetics isotopes process analytical technology

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Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

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Acta Pharmaceutica Sinica B 2024年第2期14卷 653-666页

作者： Shining loo Antony Kam Bamaprasad Dutta Xiaohong Zhang Nan Feng Siu Kwan Sze Chuan-Fa liu Xiaoliang Wang james P.Tam School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Department of Biological Sciences Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Institute of Materia Medica Chinese Academy of Medical SciencesBeijing 100050China Department of Health Sciences Brock UniversityNiagara RegionON L2S 3A1Canada

Stress and illness connection is complex and involves multiple physiological systems.Panax ginsengs,reputed for their broad-spectrum“cure-all”effect,are widely prescribed to treat stress and related illnesses.However,the identity of ginseng’s“cure-all”medicinal compounds that relieve stress remains unresolved.Here,we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress.Ginsentides are disulfide-rich,cell-penetrating and proteolytic-stable microproteins.Using affinity-enrichment mass spectrometry target identification together with in vitro,ex vivo and in vivo validations,we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway,alleviate a1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta,decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation.Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation,to prevent collagen and adrenalineinduced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice.Together,these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra-and intra-cellular proteins to reverse stress-induced damages.

关键词： Ginseng Cysteine-rich peptides Microproteins Cure-all Stress Homeostasis

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