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Electrical stimulation and denervated muscles after spinal cord injury

Neural Regeneration Research 2020年第8期15卷 1397-1407页

作者： subhalakshmi Chandrasekaran John Davis Ines Bersch gary Goldberg Ashraf s.Gorgey spinal Cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA swiss Paraplegic Centre NottwilSwitzerland Institute of Clinical sciences Department of Orthopedics at the University of GothenburgGothenburgSweden Department of Physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA Electrodiagnostic Center Hunter Holmes McGuire VA Medical CenterRichmondVAUSA

spinal cord injury(sCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous tissue.These morphological changes may put individuals with sCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and osteoporosis.Currently,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in sCI individuals with lower motor neuron denervation.We,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following sCI.Long pulse width stimulation(LPWs)technique is an upcoming method of stimulating denervated muscles.Our primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated muscle.stimulation parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and contraction.The use of electrical stimulation in animal and human models induces muscle hypertrophy.Findings in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle function.Human studies have shown similar outcomes,identifying the use of LPWs as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle function.Therefore,displaying promise is an effective future stimulation intervention.In summary,LPWs is a novel stimulation technique for denervated muscles in humans with sCI.successful studies on LPWs of denervated muscles will help in translating this stimulation technique to the clinical leve

关键词： denervation DXA electrical stimulation LMN injury LPWs MRI spinal cord injury stimulation parameters

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Building a hybrid DEVs and GRAss model using a composable cellular automaton

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International Journal of Modeling, simulation, and scientific Computing 2016年第1期7卷 62-92页

作者： gary R.Mayer Hessam s.sarjoughian Department of Computer science southern Illinois University Edwardsville 61 Circle Drive EdwardsvilleIllinois 62026USA Arizona Center for Integrative Modeling&simulation school of Computing Informaticsand Decision Systems Engineering Arizona State University699 South Mill Avenue TempeArizona 85281USA

Modeling and simulation is pervasive throughout many different disciplines.As computing technology has provided more capability,the systems being modeled and simulated have grown larger and more complex.Often times,these large systems are managed as interacting subsystems.When it is necessary for the simulation to allow disparate subsystems to maintain their independence,then a hybrid model of the subsystems should be used.Furthermore,to ease the burden of verification and validation of simulation results,a proven system theoretical modeling specification should be used.However,many communities have already adopted nonsystem theoretical software solutions and established a group of domain experts familiar with these tools.This paper provides two things:a formal approach to building a hybrid model,and a discussion of how to incorporate a nonsystem theoretical software implementation into a proven framework.The first is done through the implementation of a Knowledge Interchange Broker(KIB)as an Interaction Model(IM).The second is accomplished by exemplifying the use of the IM in an agent-environment hybrid model.In the hybrid model,the agent is implemented in the Discrete-event system(DEVs)specification and the environment is implemented in the Geographical Resources Analysis support system(GRAss)using a Composable Cellular Automaton(CCA)specification.This concept has been successfully applied to both example models and an interdisciplinary research project where the interactions between human activities and landscape processes are studied.

关键词： Multi-formalism modeling hybrid simulation composability agent cellular automata

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Macrophages in immunoregulation and therapeutics

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signal Transduction and Targeted Therapy 2023年第6期8卷 I0002-I0002,2821-2854页

作者： shanze Chen Abdullah F.U.H.saeed Quan Liu Qiong Jiang Haizhao Xu gary Guishan Xiao Lang Rao Yanhong Duo Department of Respiratory Diseases and Critic Care Unit Shenzhen Institute of Respiratory DiseaseShenzhen Key Laboratory of Respiratory DiseaseShenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen518020China Department of Cancer Biology Beckman Research Institute of City of Hope National Medical CenterLos AngelesCA91010USA Department of Laboratory Medicine Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital)Shenzhen UniversityShenzhen518052China Department of Respiratory The First Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen518055China state Key Laboratory of Fine Chemicals Department of Pharmaceutical SciencesSchool of Chemical EngineeringDalian University of TechnologyDalianChina Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen518132China Department of Microbiology Tumor and Cell Biology(MTC)Karolinska InstitutetStockholmSweden

Macrophages exist in various tissues,several body cavities,and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers.Macrophages possess binary M1/M2 macrophage polarization settings,which perform a central role in an array of immune tasks via intrinsic signal cascades and,therefore,must be precisely regulated.Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered.In addition,the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology.Moreover,they are an integral part of the tumor microenvironment,playing a part in the regulation of a wide variety of processes including angiogenesis,extracellular matrix transformation,cancer cell proliferation,metastasis,immunosuppression,and resistance to chemotherapeutic and checkpoint blockade immunotherapies.Herein,we discuss immune regulation in macrophage polarization and signaling,mechanical stresses and modulation,metabolic signaling pathways,mitochondrial and transcriptional,and epigenetic regulation.Furthermore,we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions.Moreover,we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis.Lastly,we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.

关键词： becoming polarization Macrophages

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Association of electrocardiographic markers with myocardial fibrosis as assessed by cardiac magnetic resonance in different clinical settings

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World Journal of Cardiology 2022年第9期14卷 483-495页

作者： George Bazoukis sebastian Garcia-Zamora GökselÇinier sharen Lee Enes Elvin Gul JesúsÁlvarez-García Gabi Miana Mertİlker Hayıroğlu gary Tse Tong Liu Adrian Baranchuk Department of Cardiology Larnaca General HospitalLarnaca 6036Cyprus Department of Basic and Clinical sciences University of Nicosia Medical SchoolNicosia 2414Cyprus Department of Cardiology Delta ClinicSanta Fe 341Argentina Department of Cardiology Dr.Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research CenterIstanbul 34668Turkey Cardiovascular Analytics Group Laboratory of Cardiovascular PhysiologyHong Kong 999077China Division of Cardiac Electrophysiology Madinah Cardiac CentreMadinah 42351Saudi Arabia Department of Cardiology Ramon y Cajal University HospitalMadrid 28034Spain Telehealth Center of Hospital das Clínicas Hong Kong 999077China Kent and Medway Medical school CanterburyCanterbury CT27FSUnited Kingdom Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of TianjinTianjin Medical UniversityTianjin 300211China Department of Cardiology The Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Cardiology Queen's UniversityOntario K7L 3N6Canada

BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODs A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://***).REsULTs A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRs(fQRs)is related to the presence and extent of myocardial fibrosis.fQRs and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRs has also been related to fibrosis in myocarditis.selvester score,abnormal Q waves,and notched QRs have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRs and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUsION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.

关键词： Myocardial fibrosis Late gadolinium enhancement Electrocardiogram Cardiac magnetic resonance

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Origins of Ultrafast Pulse Laser-Induced Nano straight Lines with Potential Applications in Detecting subsurface Defects in silicon Carbide Wafers

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Nanomanufacturing and Metrology 2022年第2期5卷 167-178页

作者： Tan shu Feng Liu shuai Chen Xingtao Liu Chen Zhang gary J.Cheng The Institute of Technological sciences Wuhan UniversityWuhan430072People’s Republic of China school of Power and Mechanical Engineering Wuhan UniversityWuhan430072People’s Republic of China school of Industrial Engineering Purdue UniversityWest LafayetteIN47906USA

The inspection of silicon carbide(siC)wafer quality has attracted considerable attention because internal microstructure defects are challenging to detect in production lines.Expensive and destructive methods are usually employed to detect dislocations and stacking faults inside siC wafers.Fast optical methods to monitor internal defects are in demand.In this work,an ultrafast pulse laser was used to address this issue.The formation of surface nanostructures under the ultrafast laser processing of siC wafers was explored systematically.This study discovered the origins of a typical surface nanostructure to the subsurface dislocation structure,called low-energy laser-induced nano straight lines(LLINss),which forms under low-energy ultrafast pulse laser irradiation on a siC wafer.The specific laser fluence ranges to form grooves,laser-induced periodic surface structures,LLINss,and their hybrids were identified.The formation of LLINss required an ultrafast laser(pulse width 280 fs)energy density less than 0.224 J/mm2,whereas that of pure LLINss required a small range of 0.1–0.08 J/mm2 for siC.LLINss and their surrounding microstructures were observed using scanning transmission electron microscopy to identify their origin,which is related to the subsurface dislocation structure.Molecular dynamics analysis revealed that the subsurface defect area has a high energy level,which can facilitate amorphous transformation under the irradiation of an ultrafast laser,and the amorphous area had a tendency to evolve into LLINss.Thus,subsurface lattice defects can be detected optically.This work opens new ways to detect the subsurface quality of semiconductor wafers in a green and sustainable manner.

关键词： Ultrafast laser processing surface nanostructure siC wafer Dislocation Molecular dynamics

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Kinetics of Local Anesthetic Interactions with Model Membranes: Adsorption and Permeation

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Open Journal of Anesthesiology 2022年第1期12卷 55-75页

作者： gary strichartz Pain Research Center Department of Anesthesiology Perioperative and Pain Medicine Brigham & Women’s Hospital Harvard Medical School Boston MA USA

Introduction: Local anesthetics (LAs) must be adsorbed to and permeate through membranes to reach their sites of action. The rates of these processes critically affect drug actions at the cellular level and also the in vivo pharmacokinetics of perineurally injected drugs. Therefore, we measured the adsorption equilibria and permeation kinetics of two LAs local anesthetics with markedly different hydrophobicities: tetracaine (TTC, Psub>octanol:buffersub> = 3.6 × 10sup>3sup>) and procaine (PRO, Psub>octanol:buffersub> = 8.1 × 10sup>1sup>), in unilamellar membranes of different composition and fluidity. Methods: Interactions with unilamellar vesicles made of dipalmitoylphosphatidylcholine (DPPC), at 23°C (solid gel state) or 45°C (liquid crystal state), without or with cholesterol (Chol), were investigated by a combination of fluorescence and stopped-flow techniques. Membrane adsorption was monitored by the LA’s fluorescence. Membrane permeation was monitored by the decrease of fluorescence intensity of intra-vesicular pyranine, when quenched by neighboring TTC or PRO. Results: Ionized TTC (TTCHsup>+sup>) and procaine (PROHsup>+sup>) adsorb to membranes more slowly and weakly than their neutral counterparts (time constant τ ~ 0.1 sec). Fluidizing of membranes, at the higher temperature (45°C) or by Chol inclusion, accelerated LA adsorption (faster than the mixing time of the stopped-flow device, 0.008 s). Permeation of protonated TTCHsup>+sup> through the solid gel DPPC membranes (23°C) occurred far more slowly than adsorption, (τ = 36.7 ± 0.7 s, n = 9), and 3 times slower than neutral TTC (τ = 10.9 ± 0.7 s, n = 9);neutral PRO permeated these membranes at the same rate as TTC. Inclusion of Chol with DPPC, disordering the fatty acyl tails of membrane phospholipids while crowding their polar headgroups, slowed permeation of TTC and of PRO to an even greater degree. Conclusions: Local anesthetic permeation through membranes is limited by the t

关键词： Local Anesthetic Fluorescence Phospholipids Kinetics stop-Flow Technique Adsorption Permeation

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食物-能源-水钮带关系研究能否与农业创新保持同步?

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Engineering 2023年第4期23卷 24-28页

作者：庄杰, Tom Gill Frank E.Löffler 金明洲 gary s.sayler Department of Biosystems Engineering and soil science The University of TennesseeKnoxvilleTN 37996USA Center for Environmental Biotechnology The University of TennesseeKnoxvilleTN 37996USA Institute for a secure and sustainable Environment The University of TennesseeKnoxvilleTN 37996USA Department of Agricultural Leadership Education and CommunicationsThe University of TennesseeKnoxvilleTN 37996USA smith Center for International Agriculture The University of TennesseeKnoxvilleTN 37996USA Department of Microbiology The University of TennesseeKnoxvilleTN 37996USA Department of Civil and Environmental Engineering The University of TennesseeKnoxvilleTN 37996USA Biosciences Division Oak Ridge National LaboratoryOak RidgeTN 37831USA Department of Industrial and systems Engineering The University of TennesseeKnoxvilleTN 37996USA

1.Introduction,The interconnection among food-energy-water(FEW)systems in meeting societal demands is broadly acknowledged[1].similarly,competitive or synergistic allocations of water and energy resources for agricultural production,manufacturing,and human consumption are understood,and their economic impacts can be predicted[2].Far less appreciated and understood are the outcomes of the FEW nexus in response to operation changes in agricultural practices and the associated technological innovations for future generations[3,4].Also,the inter-scale and feedback effects of emerging technology-driven resource reallocation and decision-making on FEW systems are largely unknown.For example,how do the agroeconomic feedbacks of intelligent technologies influence the FEW nexus of agricultural production under environmental and demographic changes?How does the necessary water allocation for powering non-powered dams and pumped-storage hydropower generation influence agricultural production and municipal water supply maintenance?How do solar and wind energy farms influence land use for agriculture and the rural economy?

关键词： agricultural understood allocation

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Nitric oxide regulation of plant metabolism

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Molecular Plant 2022年第2期15卷 228-242页

作者： Kapuganti Jagadis Gupta Vemula Chandra Kaladhar Teresa B.Fitzpatrick Alisdair R.Fernie Ian Max Møller gary J.Loake National Institute of Plant Genome Research Aruna Asaf Ali MargNew DelhiDelhi 110067 India Vitamins and Environmental stress Responses in Plants Department of Botany and Plant BiologyUniversity of GenevaGeneva 1211 Switzerland Max-Planck-Institute of Molecular Plant Physiology Am Mühlenberg 1Potsdam-Golm 14476 Germany Department of Molecular Biology and Genetics Aarhus UniversityForsøgsvej 14200 SlagelseDenmark Institute of Molecular Plant sciences School of Biological SciencesUniversity of EdinburghEdinburgh EH93BFUK

Nitric oxide(NO)has emerged as an important signal molecule in plants,having myriad roles in plant devel-opment.In addition,NO also orchestrates both biotic and abiotic stress responses,during which intensive cellular metabolic reprogramming occurs.Integral to these responses is the location of NO biosynthetic and scavenging pathways in diverse cellular compartments,enabling plants to effectively organize signal transduction pathways.NO regulates plant metabolism and,in turn,metabolic pathways reciprocally regu-late NO accumulation and function.Thus,these diverse cellular processes are inextricably linked.This re-view addresses the numerous redox pathways,located in the various subcellular compartments that pro-duce NO,in addition to the mechanisms underpinning NO scavenging.We focus on how this molecular dance is integrated into the metabolic state of the cell.Within this context,a reciprocal relationship be-tween NO accumulation and metabolite production is often apparent.We also showcase cellular pathways,including those associated with nitrate reduction,that provide evidence for this integration of NO function and metabolism.Finally,we discuss the potential importance of the biochemical reactions governing NO levels in determining plant responses to a changing environment.

关键词： hypoxi amitochondria metabolism nitric oxide s-nitrosylation pyridoxine reactive nitrogen species reactive oxygen species

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Type Ⅰ interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential

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Zoological Research 2018年第1期39卷 3-14页

作者： gary Wong Xiang-Guo Qiu shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhen Guangzhou 518020China Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China special Pathogens Program National Microbiology LaboratoryPublic Health Agency of CanadaWinnipegManitoba R3E 3R2Canada Department of Medical Microbiology and Infectious Diseases University of ManitobaWinnipegManitoba R3E 0J9Canada

Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.

关键词： Ifnar Mice Animal model Flavivirus Filovirus Arenavirus Bunyavirus Henipavirus Togavirus

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Mechanism-driven strategies for prevention of rheumatoid arthritis

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Rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： V.Michael Holers Kristine A.Kuhn M.Kristen Demoruelle Jill M.Norris gary s.Firestein Eddie A.James William H.Robinson Jane H.Buckner Kevin D.Deane Division of Rheumatology University of Colorado School of MedicineAuroraColoradoUSA Department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA Division of Rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research Institute SeattleWashingtonUSA Division of Immunology and Rheumatology Stanford UniversityStanfordCaliforniaUSA Department of Medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

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