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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative Medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-d-aspartate *** N-methyl-d-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-d-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-d-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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GAJA:3d CAd methodology for developing a parametric system for the automatic(re)modeling of the cutting components of compound washer dies

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2013年第5期14卷 327-340页

作者： david POTONIK Bojan dOLAK miran ULBIN Emo-orodjarna d.o.o. Bezigrajska 10SI-3000CeljeSlovenia Faculty of Mechanical Engineering University of MariborSmetanova 17SI-2000MariborSlovenia

For the designing of cutting-dies is a complex and experience-based process,it is poorly supported by conventional 3d CAd ***,the majority of design activities,including the(re)modeling of those cutting die-components that are directly responsible for performing shaping operations on a sheet-metal stamping part,traditionally still need to be carried-out repetitively,separately,and manually by the *** eliminate some of these drawbacks and upgrade the capabilities of conventional 3d CAd software,this paper proposes a new methodology for the development of a parametric system capable of automatically performing a(re)modeling process of compound washer dies' *** presented methodology integrates CATIA V5 built-in modules,including Part design,Assembly design and Knowledge Advisor,publication mechanism,and compound cutting die-design *** system developed by this methodology represents an 'intelligent' assembly template composed of two modules GAJA1 and GAJA2,***1 is responsible for the direct input of the die-design problem regarding the shape,dimensions and material of the stamping part,its extraction in the form of geometric features,and the transferring of relevant design parameters and features to the module ***2 interprets the current values for the input parameters and automatically performs the modeling process of cutting die-components,using die-design knowledge and the company's internal design and manufacturing *** results show that this system significantly shortens the modeling-time for cutting the die-components,improves the modeling-quality,and enables the training of inexperienced designers.

关键词： Parametric modeling Cutting dies Computer-aided systems Knowledge-based design

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera jorge.d.miran.a department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko Jeremic Lydia Jiménez-díaz Juan d.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

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Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： diogo Tomé Ramiro d.Almeida iBiMEd-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

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Efficient desulfurization of gasoline fuel using ionic liquid extraction as a complementary process to adsorptive desulfurization

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Petroleum Science 2015年第2期12卷 330-339页

作者： N.Farzin Nejad A.A.miran Beigi Petroleum Refining Technology development division Research Institute of Petroleum Industry

The extractive desulfurization of a model gaso- line containing several alkyl thiols and aromatic thiophenic compounds was investigated using two imidazolium-based ionic liquids （ILs）, 1-butyl-3-methylimidazolium tetrachloroaluminate, and 1-octyl-3-methylimidazolium te- trafluoroborate, as extractants. A fractional factorial design of experiments was employed to evaluate the effects and possible interactions of several process variables. Analysis of variance tests indicated that the number of extraction steps and the IL/gasoline volume ratio were of statistically highly significant, but none of the interactions were significant. The results showed that the desulfurization efficiency of the model gasoline by the ILs could reach 95.2 % under the optimal conditions. The optimized conditions were applied to study the extraction of thiophenic compounds in model gasoline and several real gasoline samples; the following order was observed in their separation： benzothio- phenc 〉 thiophcne 〉 3-methylthiophene 〉 2-methylthiophene, with 96.1% removal efficiency for benzothiophene. The IL extraction was successfully applied as a complementary process to the adsorptive desulfurization with acti- vated Raney nickel and acetonitrile solvent. The results indicated that the adsorptive process combined with IL extraction could provide high efficiency and selectivity, which can be regarded as a promising energy efficient desulfurization strategy for production of low-sulfur gasoline.

关键词： Liquid-liquid extraction Experimentaldesign Adsorptive desulfurization Gasoline Thiopheniccompounds

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi James d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3229-3230页

作者： Savina Apolloni Nadia d’Ambrosi department of Biology University of Rome Tor VergataRomeItaly

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and *** the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 *** is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.

关键词： STAT3 dissection sclerosis

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Combination of hydrotreating and delayed coking technologies for conversion of residue

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Chinese Journal of Chemical Engineering 2023年第11期63卷 209-219页

作者： José A.d.Munoz Gabriel Páez jorge Ancheyta Instituto Mexicano del Petróleo Eje Central Lázaro Cárdenas Norte 152Col.San Bartolo AtepehuacanMéxico City 07730México

Residue conversion by combining catalytic hydrotreating and delayed coking has been evaluated comparatively with both processes *** operating conditions are defined to achieve the greatest economic benefit for upgrading an atmospheric residue from a heavy crude oil.A literature model was adapted to simulate the hydrotreating reactor,and for delayed coking,correlations reported in the literature were *** results with both approaches were employed to calculate the techno-economic feasibility of the combined process *** combination of hydrotreating and delayed coking presented an increase in light fractions of 29% and a reduction in coke production of 47.8%.Based on the calculated net benefit values,it was demonstrated that the combination of hydrotreating and delayed coking is technically and economically better than using each process alone,with highest benefit of 57.7 USd·m^(-3).

关键词： Economic benefit Heavy oil Hydrotreating delayed coking

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Corneal collagen cross‑linking epithelium‑on ***‑off:a systematic review and meta‑analysis

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Eye and Vision 2021年第6期8卷 338-352页

作者： Francesco d’Oria Antonio Palazón jorge L.Alio Vissum Innovation c/Cabañal103016 AlicanteSpain division of Ophthalmology Universidad Miguel HernándezAlicanteSpain Section of Ophthalmology Department of Basic Medical ScienceNeuroscience and Sense OrgansUniversity of BariBariItaly department of Clinical Medicine Miguel Hernández UniversitySan Juan de AlicanteSpain

Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off ***:We searched MEdLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias *** considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UdVA and CdVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECd).We also investigated adverse events related to the treatments and treatment ***-analysis was conducted with a fixed or random-effects model using weighted mean difference(Md)with 95%confidence interval(CI)as the effect ***:A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this *** analysis revealed significant postoperative differences in CdVA(Md=0.07;95%CI 0.04 to 0.10;Pd no significative differences in UdVA,Kmax,central corneal thickness(CCT)and ECd(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion:Epi-on CXL is as effective as epi-off *** for a higher significant improvement in CdVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial ***-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.

关键词： Corneal collagen cross-linking Keratoconus Transepithelial CXL Epithelium-off CXL Epithelium-on CXL Iontophoresis

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