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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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Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： Jeremy P.Tervo Patricia T.Jacobson brandon J.Vilarello Tiana M.Saak Francesco F.Caruana Liam W.Gallagher Joseph b.Gary David A.Gudis Paule V.Joseph D.P.Devanand Terry E.Goldberg Jonathan b.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID.Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function.Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery.Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell.This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.Methods:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time points.Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.Results:baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up assessment.Among participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year follow-up.Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points.The total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at 1-year.Improvements in threshold,but not discrimination or identification,most significantly mediate improvement of total TDI score at follow-up.

关键词： long COVID olfaction post-COVID condition smell dysfunction

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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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Advances in acute and chronic pancreatitis

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World Journal of Gastroenterology 2023年第7期29卷 1194-1201页

作者： Williamson b Strum Clement Richard boland Department of Gastroenterology Scripps ClinicLa JollaCA 92037United States Department of Medicine University of California San DiegoLa JollaCA 92037United States

Acute pancreatitis(AP)and chronic pancreatitis are the third leading gastrointestinal causes for admissions and readmissions to hospitals in the United States.This review of articles published between 2019-2022(December)from international sources identified four categories of crucial new findings:The report includes(1)New genetic pathogenic mutations(TRPV6);expected genetic outcomes in a Northern European population;(2)a new serum diagnostic marker for AP-fatty acid ethyl esters-distinguishing acute pancreatitis associated with alcohol;explanations of the impact of monocytes/macrophages on the inflammatory process that defines their future in diagnosis,staging,and treatment;(3)innovations in timing of per os low-fat,solid food intake immediately on admission;resolution of concepts of aggressive parenteral fluid intake;dramatic shifts to nonoperative from operative treatment of infected pancreatic necrosis.Each modification reduced interventions,complications,and lengths-of-stay;and(4)authoritarian recommendations for medical treatment of chronic pain.These advances offer opportunities to initiate newly proven treatments to enhance outcomes,alter the natural history,and envision the future of two diseases that have no known cure.

关键词： Genetics New diagnostics Macrophage regulation New approaches to early feeding Fluid management

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A reproducible and sensitive method for generating high-quality transcriptomes from single whitefly salivary glands and other low-input tissues

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Insect Science 2022年第5期29卷 1318-1328页

作者： Marco Gebiola brandon H.Le Kerry EMauck Department of Entomology University of California RiversideRiversideCalifornia Department of botany and Plant Sciences University of California RiversideRiversideCalifornia Institute of Integrative Genome biology University of California RiversideRiversideCaliforniaUSA

Transcriptomic studies are an important tool for understanding the molecular pathways underlying host plant use by agricultural pests,including vectors of damaging plant pathogens.Thus far,bulk RNA-Seq has been the main approach for non-model insects.This method relies on pooling large numbers of whole organisms or hundreds of individually dissected organs.The latter approach is logistically challenging,may introduce artifacts of handling and storage,and is not compatible with biological replication.Here,we tested an approach to generate transcriptomes of individual salivary glands and other low-input body tissues from whiteflies(bemisia tabaci MEAM1),which are major vectors of plant viruses.by comparing our outputs to published bulk RNA-Seq datasets for whole whitefly bodies and pools of salivary glands,we demonstrate that this approach recovers similar numbers of transcripts relative to bulk RNA-Seq in a tissue-specific manner,and for some metrics,exceeds performance of bulk tissue RNA-Seq.Libraries generated from individual salivary glands also yielded additional novel transcripts not identified in pooled salivary gland datasets,and had hundreds of enriched transcripts when compared with whole head tissues.Overall,our study demonstrates that it is feasible to produce high quality,replicated transcriptomes of whitefly salivary glands and other low-input tissues.We anticipate that our approach will expand hypothesis-driven research on salivary glands of whiteflies and other Hemiptera,thus enabling novel control strategies to disrupt feeding and virus transmission.

关键词： Aleyrodidae bemisia tabaci bulk RNA-Seq insect vectors low-input RNA-Seq plant pathogens

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Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation

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Acta Pharmaceutica Sinica b 2022年第2期12卷 907-923页

作者： Qiubing Chen Qian Li Yuqi Liang Menghang Zu Nanxi Chen brandon S.b.Canup Liyong Luo Chenhui Wang Liang Zeng bo Xiao State Key Laboratory of Silkworm Genome biology College of SericultureTextileand Biomass SciencesSouthwest UniversityChongqing 400715China Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing School of Materials and EnergySouthwest UniversityChongqing 400715China Department of Chemistry Center for Diagnostics and TherapeuticsGeorgia State UniversityAtlantaGA 30303USA College of Food Science Southwest UniversityChongqing 400715China Chongqing Key Laboratory of Natural Product Synthesis and Drug Research School of Pharmaceutical SciencesChongqing UniversityChongqing 401331China

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer,their inefficient therapeutic outcomes,serious adverse effects,and high cost of mass production remain crucial challenges.Herein,we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers(TFENs).These nanovehicles had desirable particle sizes(131 nm),exosome-like morphology,and negative zeta potentials.Furthermore,TFENs were found to contain large amounts of polyphenols,flavonoids,functional proteins,and lipids.Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species(ROS)amplification.The increased intracellular ROS amounts could not only trigger mitochondrial damage,but also arrest cell cycle,resulting in the in vitro anti-proliferation,anti-migration,and anti-invasion activities against breast cancer cells.Further mice investigations demonstrated that TFENs after intravenous(i.v.)injection or oral administration could accumulate in breast tumors and lung metastatic sites,inhibit the growth and metastasis of breast cancer,and modulate gut microbiota.This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.***.and oral routes.

关键词： Tea flower Exosome-like nanoparticle breast cancer Metastasis ROS generation Microbiota modulation Intravenous injection Oral administration

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Clinical outcomes of cemented distal femur replacements with allpolyethylene tibial components for oncologic indications

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World Journal of Orthopedics 2023年第4期14卷 218-230页

作者： Alexander b Christ brian C Chung Matthew Urness Lucas W Mayer brandon S Gettleman Nathanael DHeckmann Lawrence R Menendez Department of Orthopedic Surgery Keck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033United States University of South Carolina School of Medicine ColumbiaSC 29209United States

bACKGROUND Endoprosthetic distal femoral replacement(DFR)is a well-established salvage procedure following resection of malignant tumors within the distal femur.Use of an all-polyethylene tibial(APT)component is cost-effective and avoids failure due to locking-mechanism issues and backside wear,but limits modularity and the option for late liner exchange.Due to a paucity of literature we sought to answer three questions:(1)What are the most common modes of implant failure for patients undergoing cemented DFR with APT for oncologic indications?(2)What is the survivorship,rate of all-cause reoperation,and rate of revision for aseptic loosening of these implants?And(3)Is there a difference in implant survivorship or patient demographics between cemented DFRs with APT performed as a primary reconstruction vs those performed as a revision procedure?AIM To assess outcomes of cemented DFRs with APT components used for oncologic indications.METHODS After Institutional Review board approval,a retrospective review of consecutive patients who underwent DFR between December 2000 to September 2020 was performed using a single-institutional database.Inclusion criteria consisted of all patients who underwent DFR with a GMRS®(Global Modular Replacement System,Stryker,Kalamazoo,MI,United States)cemented distal femoral endoprosthesis and APT component for an oncologic indication.Patients undergoing DFR for non-oncologic indications and patients with metal-backed tibial components were excluded.Implant failure was recorded using Henderson's classification and survivorship was reported using a competing risks analysis.RESULTS 55 DFRs(55 patients)with an average age of 50.9±20.7 years and average body mass index of 29.7±8.3 kg/m2 were followed for 38.8±54.9 mo(range 0.2-208.4).Of these,60.0%were female and 52.7%were white.The majority of DFRs with APT in this cohort were indicated for oncologic diagnoses of osteogenic sarcoma(n=22,40.0%),giant cell tumor(n=9,16.4%),and metastatic carcinoma(n=8,14.6%).DFR with APT implantation was per

关键词： Distal femoral replacement Modular Revision Dislocation Oncologic

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Look into my eyes:What can eye-based measures tell us about the relationship between physical activity and cognitive performance?

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Journal of Sport and Health Science 2023年第5期12卷 568-591页

作者： Liye Zou Fabian Herold Sebastian Ludyga Keita Kamijo Notger G.Muller Matthew b.Pontifex Matthew Heath Ryuta Kuwamizu Hideaki Soya Charles H.Hillman Soichi Ando brandon L.Alderman boris Cheval Arthur F.Kramer body-brain-Mind Laboratory School of PsychologyShenzhen UniversityShenzhen 518060China Research Group Degenerative and Chronic Diseases MovementFaculty of Health Sciences BrandenburgUniversity of PotsdamPotsdam 14476Germany Department of Sport Exerciseand HealthUniversity of BaselBasel 4052Switzerland Faculty of Liberal Arts and Sciences Chukyo UniversityNagoya 466-8666Japan Department of Kinesiology Michigan State UniversityEast LansingMI 48824USA School of Kinesiology Faculty of Health SciencesUniversity of Western OntarioLondon ON N6A 3K7Canada Canadian Centre for Activity and Aging University of Western OntarioLondon ONN6A 3K7Canada Graduate Program in Neuroscience University of Western OntarioLondon ONN6A 3K7Canada Laboratory of Exercise biochemistry and Neuroendocrinology Faculty of Health and Sport SciencesUniversity of TsukubaTsukuba 305-0006Japan Sport Neuroscience Division Advanced Research Initiative for Human High Performance(ARIHHP)Faculty of Health and Sport SciencesUniversity of TsukubaTsukuba 305-0006Japan Center for Cognitive and brain Health Department of PsychologyDepartment of Physical TherapyMovementand Rehabilitation SciencesNortheastern UniversityBostonMA 02115USA Graduate School of Informatics and Engineering The University of Electro-CommunicationsTokyo 182-8585Japan Department of Kinesiology and Health Rutgers UniversityNew BrunswickNew BrunswickNJ 08854USA Swiss Center for Affective Sciences University of GenevaGeneva 1205Switzerland Laboratory for the Study of Emotion Elicitation and Expression(E3Lab) Department of PsychologyUniversity of GenevaGeneva 1205Switzerland Department of Psychology Center for Cognitive and Brain HealthNortheastern UniversityBostonMA 02115USA beckman Institute University of Illinois at Urbana-ChampaignChampaignIL 61820USA

background:There is a growing interest to understand the neurobiological mechanisms that drive the positive associations of physical activity and fitness with measures of cognitive performance.To better understand those mechanisms,several studies have employed eye-based measures(e.g., eye movement measures such as saccades,pupillary measures such as pupil dilation,and vascular measures such as retinal vessel diameter)deemed to be proxies for specific neurobiological mechanisms.However,there is currently no systematic review providing a comprehensive overview of these studies in the field of exercise-cognition science.Thus,this review aimed to address that gap in the literature.Methods:To identify eligible studies,we searched 5 electronic databases on October 23,2022.Two researchers independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale,for interventional studies) and the critical appraisal tool from the Joanna briggs Institute(for cross-sectional studies).Results:Our systematic review(n=35 studies) offers the following main findings:(a) there is insufficient evidence available to draw solid conclusions concerning gaze-fixation-based measures;(b) the evidence that pupillometric measures,which are a proxy for the noradrenergic system,can explain the positive effect of acute exercise and cardiorespiratory fitness on cognitive performance is mixed;(c) physical training-or fitness-related changes of the cerebrovascular system(operationalized via changes in retinal vasculature) are,in general,positively associated with cognitive performance improvements;(d) acute and chronic physical exercises show a positive effect based on an oculomotor-based measure function(operationalized via antisaccade tasks);and(e) the positive association between cardiorespiratory fitness and cognitive performance is partly mediated by the dopaminergic system(operationalized via spontaneous eye-blink rate).Conclusion:This systema

关键词： Cognition Exercise Fitness Pupil size RetinaTagedAPTARAEnd

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Computational discovery of ultra-strong, stable, and lightweight refractory multi-principal element alloys. Part II: comprehensive ternary design and validation

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npj Computational Materials 2023年第1期9卷 1469-1481页

作者： Kate L.M.Elder Joel berry Aurélien Perron brandon bocklund Jibril Shittu Connor J.Rietema Hunter b.Henderson Scott K.McCall Joseph T.McKeown Materials Science Division Lawrence Livermore National LaboratoryLivermoreCA 94550USA.✉

Here the discovery of refractory multi-principal element alloys(MPEAs)with high-temperature strength and stability is pursued within a constrained and application-relevant design space.A comprehensive approach is developed and applied to explore all 165 ternary systems in the Al-Ce-Fe-Hf-Mo-Nb-Ta-Ti-V-W-Zr family.A subset of ternary systems that contain large areas in composition–temperature space with high strength and robust bCC phase stability is found.Twelve sets of high-performing alloys are identified,each set optimized for one combination of phase constraint,optimization target,and temperature range.Preliminary mechanical tests support the viability of the method.This work highlights the importance of considering phase stability,exploring non-equiatomic regions of composition space,and applying application-relevant constraints.Parts I and II provide three down-selection techniques for identifying high-performing bCC refractory MPEAs,design guidelines,and many candidates predicted to have bCC phase stability and strengths 2–3 times higher than any reported to date.

关键词： alloys element ternary

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Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies

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Acta Pharmaceutica Sinica b 2018年第4期8卷 518-529页

作者： brandon bumbaca Wei Li Department of Pharmaceutical Sciences College of Pharmacythe University of Tennessee Health Science Center

Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all patients.Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.

关键词： Castration-resistant prostate cancer Drug efflux transporters Taxane resistance Androgen receptor PI3K/AKT pathway Microtubules Cancer stem cells Efflux transporter

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