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The plasminogen activating system in the pathogenesis of Alzheimer’s disease

Neural Regeneration Research 2021年第10期16卷 1973-1977页

作者： manuel Yepes Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published t

关键词： Alzheimer’s disease amyloid precursor protein amyloidβ neuroserpin plasmin plasminogen activating system plasminogen activator inhibitor-1 synapse tissue-type plasminogen activator urokinase-type plasminogen activator

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Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system:implications for neurorepair in the ischemic brain

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Neural Regeneration Research 2020年第4期15卷 620-624页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research Center Department of Neurology Emory University School of Medicine Department of Neurology Veterans Affairs Medical Center

The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of disability.Unfortunately,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled patients.Thus,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic implications.Cerebral ischemia has a harmful effect on synaptic structure associated with the development of functional impairment.In agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic stroke.Furthermore,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic insult.The plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of plasmin.However,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin generation.Urokinase-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and survival.The role of uPA is the brain is not fully understood.However,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of cells.Remarkably,following an ischemic injury to the mature brain the expression of uPA and uPAR increases to levels comparable

关键词： cerebral ischemia neurorepair plasminogen plasticity stoke synapse urokinase urokinase receptor

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New sciences&technologies in soil conservation and eco-sustainability

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International Soil and Water Conservation Research 2023年第2期11卷 412-414页

作者： Paolo Tarolli manuel EstebanLucas-Borja Guoqiang Yu Xiangzhou Xu Department of Land EnvironmentAgriculture and ForestryUniversity of PadovaAgripolisViale Dell'Universita 16LegnaroPD35020Italy School of Advanced Agricultural and Forestry Engineering Castilla La Mancha UniversityCampus Universitario s/nE-02071AlbaceteSpain Xi'an Center of Geological Survey China Geological SurveyXi'an710499China School of Hydraulic Engineering Dalian University of TechnologyDalian116024China

Soil conservation is necessary to achieve a sustainable world because soils play a crucial role in the Earth's system.At the same time,the applicable and precise methods are vital to obtaining credible data in soil studies.A collection of 10 articles have been organized to focus on the new technologies regarding soil conservation and eco-sustainability and the results related to the novel approaches.The articles put effort into the innovative works of field investigations,field experiments,model experiments,and nu-merical simulations.Pivotal questions baffling soil scientists have been clarified and solved,and many valuable insights have been aroused.

关键词： Development Soil loss Soil conservation Eco-sustainability

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A Simulation of Market-based Non-frequency Ancillary Service Procurement Based on Demand Flexibility

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Journal of Modern Power Systems and Clean Energy 2023年第3期11卷 781-792页

作者： Ricardo Faia Fernando Lezama Tiago Pinto Pedro Faria Zita Vale José manuel Terras Susete Albuquerque Research Group on Intelligent Engineering and Computing for Advanced Innovation and Development(GECAD) R.Dr.António Bernardino de Almeida4314249-015PortoPortugal E-REDES Distribuição de Eletricidade S.A.R.Camilo Castelo Branco43LisboaPortugal

This paper proposes a novel approach for the provision of non-frequency ancillary service(AS)by consumers connected to low-voltage distribution networks.The proposed approach considers an asymmetric pool-based local market for AS negotiation,allowing consumers to set a flexibility quantity and desired price to trade.A case study with 98 consumers illustrates the proposed market-based non-frequency AS provision approach.Also,three different strategies of consumers’participation are implemented and tested in a real low-voltage distribution network with radial topology.It is shown that consumers can make a profit from the sale of their flexibility while contributing to keeping the network power losses,voltage,and current within pre-defined limits.Ultimately,the results demonstrate the value of AS coming directly from end-users.

关键词： Demand flexibility local electricity market ancillary service low-volatge distribution network

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A High-Speed Launching Mechanism Inspired by a Slingshot Spider’s Web

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Journal of Bionic Engineering 2022年第2期19卷 440-447页

作者： Tom Bates John Gerig manuel Avitia Gunnar Waldvogel Tesfay Legesse Justin Washington Pranav A.Bhounsule Robotics and Motion Laboratory Department of Mechanical and Industrial EngineeringUniversity of Illinois at Chicago842 W.Taylor St.ChicagoIL 60607USA

Slingshot spiders use their conical webs to launch themselves at high speeds to catch prey.We built a launching mechanism inspired by the slingshot spider.Our launch mechanisms comprise a steel structure with eye bolts to hold a conical web made from latex rubber tubing.We pull the web by a winch using a lever arm.A quick-release mechanism connects the web to the winch using a tough-grid paracord.When we release the quick-return mechanism,the projectile material consisting of a steel ball achieved an acceleration of 5107 m s^(-2) or 521 times gravity,and a speed of 66.41 m s^(-1).The power per unit mass and energy per unit mass of our prototype was one tenth and one fifth that of the spider’s web respectively.In particular,we found that web structure consisting multiple radial web elements reinforced with circumferential web elements provide enhanced stiffness;as a comparison our web had a stiffness of about eight times that of traditional slingshot with a single radial web element.Our results suggest that adapting designs from nature can lead to potentially superior performance of man-made contraptions.

关键词： Slingshot spider Launching mechanisms Catapult Bioinspiration

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Short-term outcomes of robotic liver resection: An initial singleinstitution experience

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World Journal of Hepatology 2022年第1期14卷 224-233页

作者： manuel Durán Javier Briceño Ana Padial Ferdinando Massimiliano Anelli Juan manuel Sánchez-Hidalgo María Dolores Ayllón Rafael Calleja-Lozano Carmen García-Gaitan Unit of Hepatobiliary Surgery and Liver Transplantation General and Digestive Surgery DepartmentReina Sofia University HospitalCordoba 14004Spain GC18 Translational Research in Surgery of Solid Organ Transplantation Maimonides Biomedical Research InstituteCórdoba 14004Spain GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery Maimonides Biomedical Research InstituteCórdoba 14004Spain Department of Anesthesiology and Resuscitation Reina Sofia University HospitalCordoba 14004Spain

BACKGROUND Liver surgery has traditionally been characterized by the complexity of its procedures and potentially high rates of morbidity and mortality in inexperienced hands.The robotic approach has gradually been introduced in liver surgery and has increased notably in recent years.However,few centers currently perform robotic liver surgery and experiences in robot-assisted surgical procedures continue to be limited compared to the laparoscopic approach.AIM To analyze the outcomes and feasibility of an initial robotic liver program implemented in an experienced laparoscopic hepatobiliary center.METHODS A total of forty consecutive patients underwent robotic liver resection(da Vinci Xi,***,United States)between June 2019 and January 2021.Patients were prospectively followed and retrospectively reviewed.Clinicopathological characteristics and perioperative and short-term outcomes were analyzed.Data are expressed as mean and standard deviation.The study was approved by the Institutional Review Board.RESULTS The mean age of patients was 59.55 years,of which 18(45%)were female.The mean body mass index was 29.41 kg/m^(2).Nine patients(22.5%)were cirrhotic.Patients were divided by type of resection as follows:Ten segmentectomies,three wedge resections,ten left lateral sectionectomies,six bisegmentectomies(two VVI bisegmentectomies and four IVb-V bisegmentectomies),two right anterior sectionectomies,five left hepatectomies and two right hepatectomies.Malignant lesions occurred in twenty-nine(72.5%)of the patients.The mean operative time was 258.11 min and two patients were transfused intraoperatively(5%).Inflow occlusion was used in thirty cases(75%)and the mean total clamping time was 32.62 min.There was a single conversion due to uncontrollable hemorrhage.Major postoperative complications(Clavien–Dindo>Ⅲb)occurred in three patients(7.5%)and mortality in one(2.5%).No patient required readmission to the hospital.The mean hospital stay was 5.6 d.CONCLUSION Although robotic hepatectomy is a safe and feasible procedure wi

关键词： Robotics Hepatectomy Minimally invasive surgery Liver surgery Da vinci

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Anti-lipid droplets accumulation effect of Annona montana(mountain soursop)leaves extract on differentiation of preadipocytes

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BIOCELL 2022年第3期46卷 567-578页

作者： IVY LEUNG MARIA-LUISA VEISAGA MARGARITA ESPINAL WEI ZHANG ROBERT BARNUM manuel ALEJANDRO BARBIERI Department of Biological Sciences Florida International UniversityMiami33199USA Biomolecular Sciences Institute Florida International UniversityMiami33199USA Fairchild Tropical Botanic Garden Coral Gables33156USA International Center of Tropical Botany Florida International UniversityMiami33199USA

The Annona genus is a member of Annonaceae,one of the largest families of plants across tropical and subtropical regions.This family has been used in several ethnomedicinal practices to treat a multitude of human diseases.However,the molecular mechanism underlying its effect on the lipid droplet formation and on the expression of adipogenic markers of this plant remain to be investigated.In this study,we examined whether the extracts from the aerial part of Annona montana affect in vitro differentiation of preadipocytes.For our investigations,both mouse embryo fibroblast 3T3-L1 and normal human primary subcutaneous preadipocytes were incubated with Annona montana extracts(-and its subfractions-)and then analyzed on preadipocyte differentiation,lipid content,lipid droplet size and number,the expression of adipogenic-specific transcriptional factors,as well as cell survival.From our examinations,we found the Annona montana ethyl acetate extract to exhibit a potent inhibitory effect on adipogenesis,without affecting cell survival,in a dose-dependent manner.Such inhibitory effects included a significant decrease in the accumulation of lipid content by both a dramatic reduction of size and number of lipid droplets.This extract strongly attenuated the expression of PPARγand HMGB2.It also inhibited the expression of CEBPα,FAS,and Akt without influencing Erk1/2 activities.Our findings suggest that specifically,the Annona montana ethyl acetate extract has a prominent inhibitory effect in cellular pathways of adipocyte differentiation by modulating specific gene expression,which is known to perform a pivotal role during adipogenesis.

关键词： Annona montana extracts Phytochemical analysis Adipogenesis Lipid droplets Adipogenic-specific markers

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A summary of Copepoda:synthesis,trends,and ecological impacts

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Journal of Oceanology and Limnology 2023年第3期41卷 1050-1072页

作者： Vinod VAKATI Juan manuel FUENTES-REINÉS Pengbin WANG Jun WANG Steven DODSWORTH Key Laboratory of Conservation and Utilization of Fish Resources College of Life SciencesNeijiang Normal UniversityNeijiang 641100China Universidad del Magdalena Grupo de Investigación en Biodiversidad y Ecología AplicadaSanta Marta AA 731Colombia Key Laboratory of Marine Ecosystem Dynamics the Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China Fourth Institute of Oceanography Ministry of Natural ResourcesBeihai 536000China Department of Life Science College of Natural SciencesHanyang UniversitySeoul 04763Republic of Korea School of Biological Sciences University of PortsmouthPortsmouth PO12DYUnited Kingdom

Copepoda are one of the most significant animal groups present in aquatic ecosystems.Ecologists,evolutionary biologists,and biotechnologists continue to test new methods to study the application of Copepoda as model organisms in various fields of pure and applied science,from evolution and ecology to aquaculture as live feed,as biological control of mosquito larvae,as biological indicators of water and sediment quality,in environmental monitoring and as a source of protein in the food industry.This paper reviews the current progress and trends within copepod research from a number of different perspectives.We emphasize the importance of Copepoda and the necessity of strengthening research on various topics related to copepod biology,some of which are of great significance to local sustainable development.

关键词： bioindicators aquaculture pollutants eutrophication nutrition halotolerance

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Stochastic Earned Duration Analysis for Project Schedule Management

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Engineering 2022年第2期8卷 148-161页

作者： Fernando Acebes David Poza Josémanuel González-Varona Adolfo López-Paredes GIR INSISOC-Department of Business Organization and CIM School of Industrial EngineeringUniversity of ValladolidValladolid 47011Spain

Earned duration management(EDM)is a methodology for project schedule management(PSM)that can be considered an alternative to earned value management(EVM).EDM provides an estimation of devia-tions in schedule and a final project duration estimation.There is a key difference between EDM and EVM:In EDM,the value of activities is expressed as work periods;whereas in EVM,value is expressed in terms of cost.In this paper,we present how EDM can be applied to monitor and control stochastic pro-jects.To explain the methodology,we use a real case study with a project that presents a high level of uncertainty and activities with random durations.We analyze the usability of this approach according to the activities network topology and compare the EVM and earned schedule methodology(ESM)for PSM.

关键词： Earned duration management Earned value management Stochastic project control Duration forecasting Uncertainty

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Patterns of species richness and beta diversity of vascular plants along elevation gradient in Brazilian páramo

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山地科学学报(英文) 2023年第7期20卷 1911-1920页

作者： CORDEIRO Anais de Almeida Campos KLANDERUD Kari VILLA Pedro manuel NERI Andreza Viana Federal University of Viçosa Department of Plant BiologyLaboratory of Ecology and Evolution of PlantsCampus Viçosa36570-900Viçosa-MGBrazil Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesP.O.Box 5003N-1432ÅsNorway Biodiversity Conservation Association 7101Puerto AyacuchoEstado AmazonasVenezuela

Understanding the relationships between plant diversity and the environment is an important step towards conservation of species and ecosystems.In this study,we hypothesize that community species richness decreases and species composition change along the elevation gradient,with a greater contribution of species turnover than nestedness to beta diversity.We surveyed plant species in 300 plots(1 m×1 m)in four elevational bands(2100 m,2300m,2500 m,and 2700 m)in the CaparaóNational Park,Southeastern Brazil.The samples presented a great number of species(97 spp.,59 genera,27families),however,74%of the species were considered rare with their relative abundance being<1%.Among the four bands along the gradient,we detected two distinct communities with few species in common.The transition between the two communities occurred at 2500 m,and this elevation band also had the highest species richness in total.A non-metric multidimensional scaling(NMDS)showed floristic differences between the bands even though they had similar richness.In 89%of the plot pairs,using pairwise comparison of species composition,only half of the species that occurred in one did occur in the other plot.The dissimilarity among the plots and elevational band reflects a significant contribution of spatial species turnover to the species richness and beta diversity on the Caparaómountain.Beta diversity increased with spatial scale(from plot to elevational-band).The dissimilarity(βSOR=0.907)in the area was due almost exclusively to spatial species turnover(βSIM=0.879),with very low contribution of species nestedness(βSNE=0.028).Our research showed that species richness does not decrease with elevation in the study area,but the floristic composition changes.The clear distinction of species along the gradient show that spatial species turnover is the major diversitygenerating process in the studied area.

关键词： High altitude grassland Species turnover Partitioning diversity Campo de altitude Tropical mountains

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