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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： John Mitrofanis jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Wilson's disease in two siblings from Ecuador:Two case reports

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World Journal of Clinical Cases 2025年第3期13卷 50-60页

作者： Enrique Carrera jonathan Alvarado Martina Astudillo Galo Pillajo Department of Gastroenterology and Hepatology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador Faculty of Medicine Pontificia Universidad Catolica del EcuadorQuito 170143PichinchaEcuador Department of Radiology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador

BACKGRoUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and *** and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are *** diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life *** clinical presentations and outcomes of WD can vary within a single *** SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family *** male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer *** developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication *** condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of *** female patient,diagnosed at age 10,exhibited only biochemical *** treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up *** discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic *** our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.

关键词： Wilson disease Kayser-Fleischer rings Copper chelator D-penicillamine Trientine tetrahydrochloride Case report

The effect of platform switching on the levels of metal ion release from different implant–abutment couples

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International Journal of oral Science 2016年第2期8卷 117-125页

作者： Ghada o Alrabeah jonathan C Knowles Haralampos Petridis Division of Biomaterials and Tissue Engineering UCL Eastman Dental Institute University College London London UK Prosthodontic Unit Department of Restorative Dentistry UCL Eastman Dental Institute University College London London UK

The improved peri-implant bone response demonstrated by platform switching may be the result of reduced amounts of metal ions released to the surrounding tissues. The aim of this study was to compare the levels of metal ions released from platform-matched and platform-switched implant-abutment couples as a result of accelerated corrosion. Thirty-six titanium alloy （Ti-6AI-4V） and cobalt-chrome alloy abutments were coupled with titanium cylinders forming either platform-switched or platform-matched groups （n = 6）. In addition, 18 unconnected samples served as controls. The specimens were subjected to accelerated corrosion by static immersion in 1% lactic acid for 1 week. The amount of metal ions ion of each test tube was measured using inductively coupled plasma mass spectrometry. Scanning electron microscope （SEM） images and energy dispersive spectroscopy X-ray analyses were performed pre- and post-immersion to assess corrosion at the interface. The platform-matched groups demonstrated higher ion release for vanadium, aluminium, cobalt, chrome, and molybdenum compared with the platform-switched groups （P〈 0.05）. Titanium was the highest element to be released regardless of abutment size or connection （P〈0.05）. SEM images showed pitting corrosion prominent on the outer borders of the implant and abutment platform surfaces. In conclusion, implant-abutment couples underwent an active corrosion process resulting in metal ions release into the surrounding environment. The highest amount of metal ions released was recorded for the platform-matched groups, suggesting that platform-switching concept has a positive effect in reducing the levels of metal ion release from the implant-abutment couples.

关键词： corrosion dental implants ion release peri-implant bone loss platform-switching titanium

Effects of larval size and hydrodynamics on the growth rates of the black fly Simulium tribulatum

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Integrative Zoology 2014年第1期9卷 61-69页

作者： Michelle T.BRANNIN Mary Kate o’DoNNELL jonathan FINGERUT Patrick Center for Environmental Research Academy of Natural Sciences of PhiladelphiaPhiladelphiaPennsylvaniaUSA Department of Biology Saint Joseph’s University PhiladelphiaPennsylvaniaUSA

Black flies are ubiquitous and important members of lotic *** is known to affect many aspects of their life in the aquatic larval stage,including intraspecific competition for feeding *** filter feeders,flow affects their ability to feed and reach sufficiently fast ***,in turn,can lead to risky fluid-mediated disper-sal behavior in search of better *** is surprising,therefore,that little information is available regard-ing how physiological and environmental factors combine to affect larval growth *** present study deter-mines the relative growth rates of small(0.6 mm)and large(approximately 4 mm)larvae in laboratory flumes designed to produce spatially homogeneous and temporally consistent flow regimes at ecologically relevant ve-locities(44 and 64 cm/s).our results indicate that size and flow both influence growth rates and that the 2 in-teract *** larvae exhibit faster growth rates and a greater positive response to increased flow *** result might help explain why smaller larvae have a greater propensity to disperse than larger lar-vae:the benefit of increased growth rate that they receive from relocating to faster flow might balance the risks inherent in dispersal.

关键词： black fly larvae flow rate growth rate larval size

origin and diversification of maize: Two teosintes but different contributions

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Molecular Plant 2024年第2期17卷 233-235页

作者： jonathan Acosta-Bayona Gloria Leon-martinez Jean-Philippe Vielle-Calzada Grupo de Desarrollo Reproductivo y Apomixis UGA Laboratorio Nacional de Genomica para la BiodiversidadCinvestav IrapuatoIrapuato Gto CP36825Mexico

The unique topographic,climatic,and latitudinal heterogeneity of Mesoamerica is crucial to understanding the evolutionary emergence of one of the richest cultural and biological regions in the planet and its impact on food *** divided between two regions of large biodiversity-lowland tropical or coastal zones and temperate or subtropical highlands sculpted by parallel sierras and their central plateau-the Mexican territory harbors more than 2000 endemic monocotyledonous species,including several hundred grasses(Poaceae),particularly those belonging to the genus Zea,composed of maize(Zea mays ***)and its wild relatives,collectively referred as teosintes.

关键词： collective planet harbor

Involvement of ethylene receptors in the salt tolerance response of Cucurbita pepo

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Horticulture Research 2021年第1期8卷 1058-1071页

作者： Gustavo Cebrian Jessica Iglesias-Moya Alicia Garcia Javier martinez jonathan Romero Jose Javier Regalado Cecilia martinez Juan Luis Valenzuela Manuel Jamilena Department of Biology and Geology Agri-food Campus of International Excellence(CeiA3)and Research Center CIAMBITALUniversity of Almeria04120 AlmeriaSpain

Abiotic stresses have a negative effect on crop production,affecting both vegetative and reproductive *** plays a relevant role in plant response to environmental stresses,but the specific contribution of ethylene biosynthesis and signalling components in the salt stress response differs between Arabidopsis and rice,the two most studied model *** this paper,we study the effect of three gain-of-function mutations affecting the ethylene receptors CpETR1B,CpETR1A,and CpETR2B of Cucurbita pepo on salt stress response during germination,seedling establishment,and subsequent vegetative growth of *** mutations all reduced ethylene sensitivity,but enhanced salt tolerance,during both germination and vegetative growth,demonstrating that the three ethylene receptors play a positive role in salt *** salt stress,etr1b,etr1a,and etr2b germinate earlier than WT,and the root and shoot growth rates of both seedlings and plants were less affected in mutant than in *** enhanced salt tolerance response of the etr2b plants was associated with a reduced accumulation of Na^(+)in shoots and leaves,as well as with a higher accumulation of compatible solutes,including proline and total carbohydrates,and antioxidant compounds,such as *** membrane monovalent cation transporters,including Na^(+)/H^(+)and K^(+)/H^(+)exchangers(NHXs),K^(+)efflux antiporters(KEAs),high-affinity K^(+)transporters(HKTs),and K^(+)uptake transporters(KUPs)were also highly upregulated by salt in etr2b in comparison with *** aggregate,these data indicate that the enhanced salt tolerance of the mutant is led by the induction of genes that exclude Na+in photosynthetic organs,while maintaining K^(+)/Na^(+)homoeostasis and osmotic *** the salt response of etr mutants occurs via the ethylene signalling pathway,our data show that ethylene is a negative regulator of salt tolerance during germination and vegetative ***,the higher upregulation

关键词： subsequent aggregate likely

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

occurrence,distribution and ecological risk assessment of organophosphorus flame retardants and plasticizers in sediment samples along the Vaal River catchment,South Africa

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Emerging Contaminants 2019年第1期5卷 173-178页

作者： Tlou B.Chokwe jonathan o.okonkwo Scientific Services Rand WaterP.O.Box 3526Vereeniging1930South Africa Department of Water Environmental and Earth SciencesTshwane University of Technology175 Mandela RoadPretoria0001South Africa

The occurrence,distribution and ecological risk assessment of twelve(12)organophosphorus flame retardants(oPFRs)were investigated in sediments from the Vaal River,South *** halogenated oPFRs[tris-(2-chloroethyl)phosphate(TCEP),three isomers of tris-(chloropropyl)phosphate(TCiPPs),tris-(1,3-dichloro-2-propyl)phosphate(TDCiPP)and tris-(2,3 dibromopropyl)phosphate(TDBPP)]and six non-halogenated oPFRs[tris-(n-butyl)phosphate(TBP),tris-(phenyl)phosphate(TPhP),tris-(butyl ethoxy)phosphate(TBoEP),tris-(2-ethylhexyl)phosphate(TEHP),diphenyl-2-ethylhexyl phosphate(DPEHP)and tris-(m-cresyl)phosphate(m-TCP)]were detected in this *** concentrations of twelve oPFRs in total(S12oPFRs)ranged from 68 to 278 ng g^-1 dry weight(dw)with the mean and median of 138 and 120 ng g^-1;*** non-halogenated oPFRs showed more abundances than the halogenated oPFRs with TDBPP,TBP,and TBoEP the most abundant ***,concentrations of oPFRs in more urbanized region were higher than those in less urbanized *** the concentrations of oPFRs and total organic carbon(ToC)were correlated,a moderate and significant correlation(pour results showed that m-TCP poses high risk(HQ>1)while TBoEP,TPhP,and TBP posed medium risk(0.1osing negligible risk(HQobtained in this study provides valuable information on the occurrence and risks of the investigated oPFRs within Vaal River.

关键词： oPFRs Concentrations Risk assessment Sediments Vaal river

The Need for Fuzzy AI

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IEEE/CAA Journal of Automatica Sinica 2019年第3期6卷 610-622页

作者： jonathan M.Garibaldi IEEE the School of Computer Science University of Nottingham

Artificial intelligence(AI) is once again a topic of huge interest for computer scientists around the world. Whilst advances in the capability of machines are being made all around the world at an incredible rate, there is also increasing focus on the need for computerised systems to be able to explain their decisions, at least to some degree. It is also clear that data and knowledge in the real world are characterised by *** systems can provide decision support, which both handle uncertainty and have explicit representations of uncertain knowledge and inference processes. However, it is not yet clear how any decision support systems, including those featuring fuzzy methods, should be evaluated as to whether their use is *** paper presents a conceptual framework of indistinguishability as the key component of the evaluation of computerised decision support systems. Case studies are presented in which it has been clearly demonstrated that human expert performance is less than perfect, together with techniques that may enable fuzzy systems to emulate human-level performance including *** conclusion, this paper argues for the need for "fuzzy AI" in two senses:(i) the need for fuzzy methodologies(in the technical sense of Zadeh's fuzzy sets and systems) as knowledge-based systems to represent and reason with uncertainty; and(ii) the need for fuzziness(in the non-technical sense) with an acceptance of imperfect performance in evaluating AI systems.

关键词： Artificial intelligence approximate reasoning fuzzy inference systems fuzzy sets human reasoning