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Axonal regeneration after spinal cord injury in zebrafish and mammals: differences, similarities, translation

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Neuroscience Bulletin 2013年第4期29卷 402-410页

作者： Katarina Vajn Jeffery A Plunkett Alexis Tapanes-Castillo martin oudega Departments of Physical Medicine & Rehabilitation University of Pittsburgh School of Science Technology and Engineering Management St. Thomas University Departments of Neurobiology University of Pittsburgh Departments of Bioengineering University of Pittsburgh

Spinal cord injury （SCl） in mammals results in functional deficits that are mostly permanent due in part to the inability of severed axons to regenerate. Several types of growth-inhibitory molecules expressed at the injury site contribute to this regeneration failure. The responses of axons to these inhibitors vary greatly within and between organisms, reflecting axons＇ characteristic intrinsic propensity for regeneration. In the zebrafish （Danio rerio） many but not all axons exhibit successful regeneration after SCI. This review presents and compares the intrinsic and extrinsic determinants of axonal regeneration in the injured spinal cord in mammals and zebrafish. A better understanding of the molecules and molecular pathways underlying the remarkable individualism among neurons in mature zebrafish may support the development of therapies for SCI and their translation to the clinic.

关键词： spinal cord injury axonal regeneration growth inhibition functional recovery zebrafish

Survival of transplanted neurotrophin-3 expressing human neural stem cells and motor function in a rat model of spinal cord injury

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Neural Regeneration Research 2009年第7期4卷 485-491页

作者： Peiqiang Cai Guangyun Sun Peishu Cai martin oudega Rui Xiao Xuewen Wang Wei Li Yunbing Shu Cheng Cai Haihao Yang Xuebing Shan Wuhua Luo Department of Orthopaedics First People's Hospital of Yibin Yibin 644000 Sichuan Province China International Center for Spinal Cord Injury Kennedy Krieger Institute Department of Neurology Johns Hopkins University School of MedicineBaltimore MD 21205 USA

BACKGROUND： Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes. OBJECTIVE： To investigate the repair feasibility for rat spinal cord injury using human neural stem cells （hNSCs） genetically modified by lentivirus to express neurotrophin-3. DESIGN, TIME AND SETTING： In vitro cell biological experiment and in vivo randomized, controlled genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People＇s Hospital of Yibin, China from March 2006 to December 2007. MATERIALS： A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls. METHODS： hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension （5 × 10^5） was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco＇s-modified Eagle＇s medium was infused into the rat spinal cord in the model grop. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluated using the Basso, Beattie, and Bresnahan （BBB） scale. MAIN OUTCOME MEASURES： The following parameters were measured： expression of neurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival of hNSCs in rats, motor function in rats. RESULTS： hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The transplanted hNSCs primarily gathere

关键词： lentivirus spinal cord injuryi human neural stem cells genetic engineering neurotrophin-3 clreen fluorescence protein

Lentivirus介导分泌神经营养因子-3的基因工程神经干细胞移植治疗脊髓损伤的实验研究

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中华外科杂志 2005年第16期43卷 1091-1093页

作者：蔡培强汤逊林月秋 martin oudega Bas Blits 徐林阳运康成都军区昆明总医院骨科昆明650032 美国迈阿密大学医学院荷兰阿姆斯特丹神经科学研究院中国科学院昆明动物研究所

神经干细胞(NSC)是中枢神经系统中具有自我更新能力和多种分化潜能的细胞,是脊髓损伤(SCI)后再生修复的理想材料和基因载体.我们探讨了Lentivirus介导分泌神经营养因子-3(NT-3)的基因工程NSC移植治疗SCI的可行性,以期为SCI后功能恢复的... 详细信息

神经干细胞(NSC)是中枢神经系统中具有自我更新能力和多种分化潜能的细胞,是脊髓损伤(SCI)后再生修复的理想材料和基因载体.我们探讨了Lentivirus介导分泌神经营养因子-3(NT-3)的基因工程NSC移植治疗SCI的可行性,以期为SCI后功能恢复的实验研究以及进一步临床研究提供基础资料。

关键词：脊髓损伤(SCI) 神经干细胞移植治疗神经营养因子-3 实验研究基因工程神经干细胞(NSC) 分泌介导自我更新能力

GENETIC ENGINEERING NEURAL STEM CELL MODIFIED BY LENTIVIRUS FOR REPAIR OF SPINAL CORD INJURY IN RATS

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Chinese Medical Sciences Journal 2006年第2期21卷 120-124页

作者： Xun Tang Pei-qiang Cai Yue-qiu Lin martin oudega Bas Blits Ling Xu Yun-kang Yang Tian-hua Zhou Department of Orthopaedics Kunming General Hospital of Chengdu Military Command Kunming 650032 The Miami Project to Cure Paralysis University of Miami School of Medicine Miami FL 33101 USA Graduate School for Neurosciences Amsterdam Netherlands Institute for Brain Research Amsterdam Postbus 7057 1007 MB the Netherlands Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650000

Objective To explore the feasibility for therapy of spinal cord injury (SCI) by genetic engineering neural stem cell (NSC) modified by lentiviral vector. Methods Following the construction of the genetic engineering NSC modified by lentivirus to secrete both neurotrophic factor-3 (NT-3) and green fluorescence protein (GFP), hemisection of spinal cord at the level of T_ 10 was performed in 56 adult Wistar rats that were randomly divided into 4 groups (n=14), namely 3 therapeutic groups and 1 control group. The therapeutic groups were dealed with NSC, genetic engineering NSC, and concentrated lentiviral supernatant which carries both GFP and NT-3, respectively. Then used fluorescence microscope to detect the transgenic expression in vitro and in vivo, migration of the grafted cells in vivo, and used the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test to assess the recovery of function. Results The transplanted cells could survive for long time in vivo and migrate for long distance. The stable transgenic expression could be detected in vivo. The hindlimb function of the injured rats in 3 therapeutic groups, especially those dealed with genetic engineering NSC, improved obviously. Conclusion It is feasible to combine NSC with lentivirus for the repair of SCI. NSC modified by lentivirus to deliver NT-3, acting as a source of neurotrophic factors and function cell in vivo, has the potential to participate in spinal cord repair.

关键词：神经干细胞遗传技术脊椎损伤神经营养

Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration Research 2024年第1期19卷 29-34页

作者： Marta Zagrebelsky martin Korte Division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for Infection Research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin rec

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

Comprehensive Euler/Lagrange modelling including particle erosion for confined gas-solid flows

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Particuology 2024年第1期84卷 209-235页

作者： Guiherme A.Novelletto Ricardo martin Sommerfeld Multiphase Flow Systems Institute of Process EngineeringOtto-von-Guericke-University MagdeburgHoher Weg 7b06120Halle(Saale)Germany

The present research aims to assess the capability of a comprehensive Euler/Lagrange approach for predicting gas-solid flows and the associated solid particle erosion.The open-source code OpenFOAM®4.1 was used to carry out the numerical simulations,where the standard Lagrangian libraries were substantially extended to account for all necessary models.Particles are tracked considering both translational and rotational motion as well as all relevant forces,such as gravity/buoyancy,drag and transverse lift due to shear and particle rotation.The tracking time step was dynamically adapted ac-cording to the locally relevant time scales,which drastically reduces computational times.Stochastic approaches are adopted to model particle turbulent dispersion,particle collisions with rough walls and particle-particle interactions.Five solid particle erosion models,available in the literature,were considered to estimate pipe bend erosion.Three study cases are provided to validate the adopted nu-merical approach and erosion models extensively.The first case intends to evaluate the ability of the extended CFD code to predict the behaviour of gas-solid flows in pneumatic conveying systems.This goal is achieved by comparing the numerical results with the experimental data obtained by Huber(1997)and Huber and Sommerfeld(1994,1998)in a pneumatic conveying system.Here,the importance of considering inter-particle collisions and surface roughness for predicting particle velocity,mass flux and mean diameter distributions in gas-solid flows is highlighted.The second and third case intend to evaluate the ability of the erosion models in estimating bend erosion in diluted gas-solid flows.The erosion data obtained experimentally by Mazumder et al.(2008)and Solnordal et al.(2015)in very dilut pneumatic conveying systems is used for validating the numerical results,neglecting now inter-particle collisions and two-way coupling.Besides a comprehensive analysis of the different influential properties on erosion,the innovation of the present stud

关键词： Pneumatic conveying Pipe bend Numerical calculation(CFD) Euler/Lagrange approach Erosion models Wall roughness

Differential roles of seed and sprout regeneration in forest diversity and productivity after disturbance

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Forest Ecosystems 2024年第3期11卷 371-380页

作者： Marek Mejstrík martin Svatek martina Pollastrini martin Sramek Radim Matula Department of Forest Ecology Faculty of Forestry and Wood SciencesCzech University of Life Sciences PragueKamýcka 12916500PragueCzech Republic Department of Forest Botany Dendrology and GeobiocoenologyFaculty of Forestry and Wood TechnologyMendel University in BrnoZemedelska 361300BrnoCzech Republic Department of Agriculture FoodEnvironment and ForestryUniversity of FirenzePiazzale Delle Cascine 2850144FirenzeItaly

Natural regeneration after disturbances is a key phase of forest development,which determines the trajectory of successional changes in tree species composition and diversity.Regenerating trees can originate from either seeds or sprouts produced by disturbed trees with sprouting ability.Although both regeneration strategies often develop and co-occur after a disturbance,they tend to affect forest development differently due to significant functional differences.However,the origin of tree regeneration is rarely distinguished in post-disturbance forest surveys and ecological studies,and the differential roles of seed and sprout regeneration in forest productivity and diversity remain poorly understood.To address these research gaps,we explored the role of sprout and seed regeneration in the formation of woody species diversity and above-ground biomass(AGB)productivity in early-stage forest development.Data were collected in two experimental forest stands in the Czech Republic,where trees were cut with varying intensities with the density of residual(uncut)trees ranging from 0 to 275 trees per hectare.All trees were mapped and their sizes were measured before cutting and then,either as a stump with sprouts or a residual tree,remeasured 11 years later.In addition,all tree saplings were mapped and measured 11 years after logging,and their origin(sprout or seed)was identified.To assess abundances and productivity,we estimated AGB of all2,685 sprouting stumps of 19 woody species and 504 generative(i.e.,seed origin)individuals of 16 woody species,using allometric equations.Mixed-effects models were used to analyze the effects of each regeneration strategy on woody species diversity and the total AGB under varying densities of residual trees.Nonmetric multidimensional scaling was used to evaluate the effect of regeneration strategies on species composition.AGB and diversity of sprouts were significantly higher than those of seed regeneration.Sprouts formed on average97.1%of the total regeneration AGB in H ady and 98.6%in

关键词： Resprouting Seeding Residual trees Tree diversity Above-ground biomass

Increased number of symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged time to return to full sports performance—AWAREⅧ

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Journal of Sport and Health Science 2024年第3期13卷 280-287,I0001页

作者： Carolette Snyders Marlise Dyer Nicola Sewry Esme Jordaan martin Schwellnus Sport Exercise Medicine and Lifestyle Institute(SEMLI)Faculty of Health SciencesUniversity of PretoriaPretoria 0083South Africa Section Sports Medicine Faculty of Health SciencesUniversity of PretoriaPretoria 0083South Africa IOC Research Centre of South Africa Pretoria 0083South Africa Biostatistics Unit South African Medical Research CouncilTygerberg 7505South Africa Statistics and Population Studies Department University of the Western CapeCape Town 7535South Africa

Purpose The aim of the study was to identify factors associated with prolonged time to return to full performance(RTFP)in athletes with recent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Methods Prospective cohort study with cross sectional analysis.A total of 84 athletes with confirmed SARS-CoV-2 infection assessed at a coronavirus disease 2019 recovery clinic gave a history of age,sex,type/level of sport,co-morbidities,pre-infection training hours,and 26 acute SARS-CoV-2 symptoms from 3 categories(“nose and throat”,“chest and neck”,and“whole body”/systemic).Data on days to RTFP were obtained by structured interviews.Factors associated with RTFP were demographics,sport participation,history of co-morbidities,pre-infection training history,and acute symptoms(type,number).Outcomes were:(a)days to RTFP(median,interquartile range(IQR))in asymptomatic(n=7)and symptomatic athletes(n=77),and(b)hazard ratios(HRs;95%confidence interval)for symptomatic athletes with vs.without a factor(univariate,multiple models).HR0.05).Factors associated with prolonged RTFP(univariate models)were:females(HR=0.57;p=0.014),endurance athletes(HR=0.41;p<0.0001),co-morbidity number(HR=0.75;p=0.001),and respiratory disease history(HR=0.54;p=0.026).In symptomatic athletes,prolonged RTFP(multiple models)was significantly associated with increased“chest and neck”(HR=0.85;p=0.017)and“nose and throat”(HR=0.84;p=0.013)symptoms,but the association was more profound between prolonged RFTP and increased total number of“all symptoms”(HR=0.91;p=0.001)and“whole body”/systemic(HR=0.82;p=0.007)symptoms.Conclusion A larger number of total symptoms and specifically“whole body”/systemic symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged RTFP.

关键词： Athletes COVID-19 Performance Recovery Return to play

Time trends and outcomes of gastrostomy placement in a Swedish national cohort over two decades

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World Journal of Gastroenterology 2024年第10期30卷 1358-1367页

作者： martin Löfling Skogar Magnus Sundbom Department of Surgical Sciences Uppsala UniversityUppsala 75185Sweden

BACKGROUND Percutaneous endoscopic gastrostomy(PEG)and laparoscopically inserted gastrostomy have become the gold standard for adult patients and children,respectively,requiring long-term enteral nutrition support.Procedure-related mortality is a rare event,often reported to be zero in smaller studies.National data on 30-d mortality and long-term survival rates after gastrostomy placement are scarce in the literature.AIM To study the use of gastrostomies in Sweden from 1998-2019 and to analyze procedure-related mortality and short-term(<30 d)and long-term survival.METHODS In this retrospective,population-based cohort study,individuals that had received a gastrostomy between 1998-2019 in Sweden were included.Individuals were identified in the Swedish National Patient Register,and survival analysis was possible by cross-referencing the Swedish Death Register.The cohort was divided into three age groups:Children(0-18 years);adults(19-64 years);and elderly(≥65 years).Kaplan-Meier with log-rank test and Cox regression were used for survival analysis.RESULTS In total 48682 individuals(52%males,average age 60.9±25.3 years)were identified.The cohort consisted of 12.0%children,29.5%adults,and 58.5%elderly.An increased use of gastrostomies was observed during the study period,from 13.7/100000 to 22.3/100000 individuals(P<0.001).The use of PEG more than doubled(about 800 to 1800/year),with a corresponding decrease in open gastrostomy(about 700 to 340/year).Laparoscopic gastrostomy increased more than ten-fold(about 20 to 240/year).Overall,PEG,open gastrostomy,and laparoscopic gastrostomy constituted 70.0%(n=34060),23.3%(n=11336),and 4.9%(n=2404),respectively.Procedure-related mortality was 0.1%(n=44)overall(PEG:0.05%,open:0.24%,laparoscopic:0.04%).The overall 30-d mortality rate was 10.0%(PEG:9.8%,open:12.4%,laparoscopic:1.7%)and decreased from 11.6%in 1998-2009 vs 8.5%in 2010-2019(P<0.001).One-year and ten-year survival rates for children,adults,and elderly were 93.7%,67.5%,and 42.1%and 79.9%,39.2%,and 6.8%,respectively.Th

关键词： Gastrostomy Percutaneous endoscopic gastrostomy Dysphagia Enteral nutrition Long-term Survival Complication