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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

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Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and Notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Simulation of plastic deformation induced texture evolution using the crystallographic homogenization finite element method

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Acta Mechanica Solida Sinica 2017年第1期30卷 51-63页

作者： y.p.Chen y.y.Cai Department of Mechanics Huazhong University of Science and Technology

A semi-implicit elastic/crystalline viscoplastic finite element（FE） method based on a ＂crystallographic homogenization＂ approach is formulated for a multi-scale analysis. In the formulation, the asymptotic series expansion is introduced to define the displacement in the micro-continuum. This homogenization FE analysis is aimed at predicting the plastic deformation induced texture evolution of polycrystalline materials, the constituent microstructure of which is represented by an assembly of single crystal grains. The rate dependent crystal plasticity model is adopted for the description of microstructures. Their displacements are decomposed into two parts： the homogenized deformation defined in the macrocontinuum and the perturbed one in the micro-continuum. This multi-scale formulation makes it possible to carry out an alternative transition from a representative micro-structure to the macro-continuum. This homogenization procedure satisfies both the compatibility and the equilibrium in the micro-structure. This developed code is applied to predict the texture evolution, and its performance is demonstrated by the numerical examples of texture evolution of FCC polycrystalline metals.

关键词： Homogenization Local periodicity Crystalline plasticity Texture Finite element

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A novel supercapacitor-fuel cell hybrid cell

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Rare Metals 2006年第z1期25卷 12-18页

作者： WANG y ZHENG Jim p Department of Electrical and Computer Engineering Florida A&M University and Florida State University Tallahassee FL 32310 USA Department of Electrical and Computer Engineering Florida A&M University and Florida State University Tallahassee FL 32310 USA

A monolithic hybrid fuel cell (MHFC) with a novel configuration was proposed in an effort to improve the fuel cell performance during instantaneous power changes. A modified direct methanol fuel cell (DMFC) with a layer of hydrous ruthenium dioxide (RuO2·xH2O) sandwiched between the anode catalyst layer and membrane was used to demonstrate the principle of the MHFC. Experimental results indicate that the RuO2·xH2O layer is equivalent to a resistor-capacitor transmission line and functions similar to a capacitor in parallel with the anode electrode. The improvement in dynamic response of the MHFC was experimentally confirmed under step current change and square current pulse operating. The ionic conductivity of the RuO2·xH2O layer was also obtained.

关键词： hybrid devices direct methanol fuel cells hydrous ruthenium dioxide dynamic response

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Multi-relaxation-time lattice Boltzmann simulations of lid driven flows using graphics processing unit

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Applied Mathematics and Mechanics(English Edition) 2017年第5期38卷 707-722页

作者： Chenggong LI J.p.y.MAA National Engineering Laboratory for Methanol to Olefins Dalian National Laboratory for Clean EnergyDalian Institute of Chemical PhysicsChinese Academy of Sciences College of William and Mary Virginia Institute of Marine Science

Large eddy simulation （LES） using the Smagorinsky eddy viscosity model is added to the two-dimensional nine velocity components （D2Q9） lattice Boltzmann equation （LBE） with multi-relaxation-time （MRT） to simulate incompressible turbulent cavity flows with the Reynolds numbers up to 1 × 10^7. To improve the computation efficiency of LBM on the numerical simulations of turbulent flows, the massively parallel computing power from a graphic processing unit （GpU） with a computing unified device architecture （CUDA） is introduced into the MRT-LBE-LES model. The model performs well, compared with the results from others, with an increase of 76 times in computation efficiency. It appears that the higher the Reynolds numbers is, the smaller the Smagorinsky constant should be, if the lattice number is fixed. Also, for a selected high Reynolds number and a selected proper Smagorinsky constant, there is a minimum requirement for the lattice number so that the Smagorinsky eddy viscosity will not be excessively large.

关键词： large eddy simulation (LES) multi-relaxation-time (MRT) lattice Boltzmann equation (LBE) two-dimensional nine velocity components (D2Q9) Smagorinskymodel graphic processing unit (GpU) computing unified device architecture (CUDA)

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Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros p papadakos Research Unit of Radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Department of Radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical practice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

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Nanotexturing and Wettability Ageing of polypropylene Surfaces Modified by Oxygen Capacitively Coupled Radio Frequency plasma

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Journal of Materials Science & Technology 2014年第10期30卷 965-972页

作者： y.p.Li M.K.Lei Surface Engineering Laboratory School of Materials Science and EngineeringDalian University of Technology

polypropylene （pp） was treated by an oxygen capacitively coupled radio frequency plasma （CCp） under a radio frequency （RF） power of 200 W for exposure time of 1, 5, and 10 rain. The ageing process of the plasma- treated pp was studied at an ageing temperature of 90 ~C during an ageing time up to 25 h. The formation of the nanotextures with different geometry and aspect ratio and the grafting of large number of oxygen- containing groups were achieved on as-treated pp surfaces under the oxygen CCp treatment for the increased exposure time. The hydrophilicity on the as-treated pp surfaces with the stable nanotextures was rapidly depressed during the ageing process at 90 ℃ due to the restructuring of chemical composition. The surface restructuring rate was dependent on the aspect ratio and the oxygen-containing groups on the nanotextured pp with increasing exposure time. The hydrophobic over-recovery to high hydrophobicity and superhydrophobicity were observed on the post-aged surfaces with the stable nanofibrils from as-treated hydrophilic surfaces. The superhydrophobicity with the low water adhesion was achieved on the post-aged surfaces preserving the nanofibrils with high aspect ratio and large distance due to the decrease of the oxygen-containing groups after the surface restructuring.

关键词： polypropylene plasma nanotexturing Ageing Surface restructuring Superhydrophobicity

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performance of LIDAR- and radar-based turbulence intensity measurement in comparison with anemometer-based turbulence intensity estimation based on aircraft data for a typical case of terrain-induced turbulence in association with a typhoon

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Journal of Zhejiang University-Science A(Applied physics & Engineering) 2013年第7期14卷 469-481页

作者： p.W.CHAN y.F.LEE Hong Kong Observatory

The Hong Kong Observatory (HKO) provides low-level turbulence alerting service for the Hong Kong International Airport (HKIA) through the windshear and turbulence warning system (WTWS). In the WTWS, turbulence intensities along the flight paths of the airport are estimated based upon correlation equations established between the surface anemometer data and the turbulence data from research aircraft before the opening of the airport. The research aircraft data are not available on day-to-day basis. The remote sensing meteorological instruments, such as the Doppler light detection and ranging (LIDAR) and radar, may be used to provide direct measurements of turbulence intensities over the runway corridors. The performances of LIDAR- and radar-based turbulence intensity data are studied in this paper based on actual turbulence intensity measurements made on 423 commercial jets for a typical case of terrain-induced turbulence in association with a typhoon. It turns out that, with the tuning of the relative operating characteristic (ROC) curve between hit rate and false alarm rate, the LIDAR-based turbulence intensity measurement performs better than the anemometer-based estimation of WTWS for turbulence intensity at moderate level or above. On the other hand, the radar-based measurement does not perform as well when compared with WTWS. By combining LIDAR- and radar-based measurements, the performance is slightly better than WTWS, mainly as a result of contribution from LIDAR-based measurement. As a result, the LIDAR-based turbulence intensity measurement could be used to replace anemometer-based estimate for non-rainy weather conditions. Further enhancements of radar-based turbulence intensity measurement in rain would be necessary.

关键词： Fault tolerant High availability quadruple vital computer (HAQVC) Reliability availability maintainability and safety (RAMS)

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Microstructure and mechanical properties of TiAl/TiAl joints brazed with a newly developed Ti–Ni–Nb–Zr quaternary filler alloy

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progress in Natural Science:Materials International 2022年第6期32卷 758-768页

作者： H.S.Ren y.L.Shang X.y.Ren y.J.Jing H.p.Xiong y.y.Cheng Welding and plastic Forming Division Beijing Institute of Aeronautical Materials

A novel Ti-Ni-Nb-Zr quaternary filler alloy with the composition of Ti-(19～25)Ni-(15～25)(Nb+Zr)(wt.%) was *** filler alloy was composed of(Ti,Nb)ss,(Ti,Zr,Nb)ss+(Ti,Zr)2Ni,α-Ti and Ti2Ni *** was fabricated into filler foil with a thickness of about 45 μm by a rapid solidification *** results indicate that the liquidus temperature of the Ti-Ni-Nb-Zr brazing alloy was about 978℃,and the brazing alloy presented excellent wettability on TiAl *** TiAl joint mainly consisted of β/B2 phase,Ti2Al,Ti2AlNi and α2-Ti3Al *** diffusion of Al atom from base metal to brazed seam led to the formation of Ti2Al and *** that no previously references on XRD pattern of Ti2AlNi compound can be found,Ti2AlNi cast alloy specimen was specially prepared and XRD peaks were specially *** micro-hardness and bending strength tests of the Ti2AlNi phase were carried out,and the results were 761 HV and 192 Mpa,*** brazing parameters of 1010 ℃/10 min offered the joint shear strength of 280 Mpa at room temperature,and the joints exhibited tensile strength of 372 Mpa at room temperature and 340 Mpa at 750 ℃,indicating that the newly developed filler alloy could offer a stable high-temperature strength.

关键词： TiAl Brazing Filler alloy Microstructure Mechanical properties

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