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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

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

Geographic variation in larval cold tolerance and exposure across the invasion front of a widely established forest insect

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Insect Science 2024年第6期31卷 1930-1942页

作者： Petra Hafker Lily M.thompson jonathan A.Walter Dylan Parry Kristine L.Grayson Department of Biology University of RichmondRichmondVAUSA Department of Entomology Cornell UniversityIthacaNYUSA Department of Forestry and Environmental Conservation Clemson UniversityClemsonSCUSA Department of Environmental Sciences University of VirginiaCharlottesvilleVAUSA Department of Environmental Biology State University of New YorkCollege of Environmental Science and ForestrySyracuseNYUSA

Under global climate change,high and low temperature extremes can drive shifts in species *** the range of a species,thermal tolerance is based on acclimatization,plasticity,and may undergo selection,shaping resilience to temperature *** this study,we measured variation in cold temperature tolerance of early instar larvae of an invasive forest insect,Lymantria dispar dispar L.(Lepidoptera:Erebidae),using populations sourced from a range of climates within the current introduced range in the Eastern United *** tested for population differences in chill coma recovery(CCR)by measuring recovery time following a period of exposure to a nonlethal cold temperature in 2 cold exposure experiments.A 3rd experiment quantified growth responses after CCR to evaluate sublethal *** results indicate that cold tolerance is linked to regional climate,with individuals from populations sourced from colder climates recovering faster from chill *** this geographic gradient is seen in many species,detecting this pattern is notable for an introduced species founded from a single point-source *** demonstrate that the cold temperatures used in our experiments occur in nature during cold spells after spring egg hatch,but impacts to growth and survival appear *** expect that population differences in cold temperature performance manifest more from differences in temperature-dependent growth than acute *** intraspecific variation in cold tolerance increases our understanding of the role of climatic gradients on the physiology of an invasive species,and contributes to tools for predicting further expansion.

关键词： chill coma recovery forest insect geographic gradient Lymantria dispar spring cold spell thermal performance

Hydrogen peroxide ingestion with injury to upper gastrointestinal tract

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World Journal of Clinical Cases 2017年第10期5卷 378-380页

作者： jonathan v Martin Choichi Sugawa Michael and Marian Ilitch Department of Surgery 6-C University Health Center

Hydrogen peroxide is a common over-the-counter solution that has developed a growing body of literature regarding toxic ingestion. Intentional ingestion of high concentration hydrogen peroxide for health purposes has gained popularity in certain patient populations; purported benefits are due to the increased oxygen released into the blood stream. We present for evaluation one such case with associated imaging that presented to our urban medical center. A brief review of the literature was also performed noting current recommendations regarding both outcomes and indications for endoscopy as well as hyperbaric oxygen therapy following ingestion of hydrogen peroxide. Our patient was a 51-year-old white female who presented with foamy hematemesis after ingesting 10 drops of 35% hydrogen peroxide as part of a home remedy to cleanse her colon and improve blood oxygenation. In addition to hematemesis,she also reported diffuse abdominal pain with sore throat and hoarse voice. Her imaging demonstrated portal venous gas and gastric edema. She was admitted for hyperbaric oxygen therapy and underwent upper endoscopy demonstrating diffuse esophagitis and gastritis with white exudate and multiple petechiae. She was later discharged home in stable condition and was lost to follow-up.

关键词： Hydrogen peroxide Caustic injury Hyperbaric oxygen therapy Ingestion of hydrogen peroxide Arterial gas emboli

Celiac plexus neurolysis in the management of unresectable pancreatic cancer:When and how?

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World Journal of Gastroenterology 2014年第9期20卷 2186-2192页

作者： jonathan M Wyse Yen-I Chen Anand v Sahai Division of Gastroenterology Jewish General Hospital McGill University Montreal H3T 1E2 QuebecCanada McGill University Health Center McGill University Montreal H3A 1A1 Quebec Canada Division of Gastroenterology Hopital Saint Luc Centre Hospitaliér de l’Universite de Montréal Montreal H2X 1P1 Quebec Canada

Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20%resectability at diagnosis,and overall 5-year survival of 5%.Pain is common in pancreatic cancer patients with 70%-80%suffering substantial *** plexus neurolysis(CPN)is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid *** is performed by injecting absolute alcohol into the celiac plexus neural network of *** review sets out to explore the current status of CPN in non-resectable pancreatic *** will examine:(1)the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN;(2)specific technique modifications including bilateral(vs central)injections and celiac ganglia neurolysis;and(3)the issue of CPN timing,early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.

关键词： Celiac plexus neurolysis Endoscopic ultrasound Pancreatic cancer Pain Opioid Gastrointestinal endoscopy

Light-Absorbing Products Form during the Aqueous Phase Reaction of Phenolic Compounds in the Presence of Nitrate and Nitrite with Uv Illumination

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Open Journal of Air Pollution 2012年第2期1卷 13-21页

作者： Hao Tang jonathan E. thompson Department of Chemistry & Biochemistry Texas Tech University Lubbock TX 79409-1061

Phenolic compounds are emitted into earth’s atmosphere through industry and biomass burning events. These compounds may react in the gas or particle phase to form additional airborne pollutants. In this work, the aqueous phase chemical reactions of syringol, guaiacol, and catechol were studied in the presence of nitrate (NO-3 ) or nitrite ( NO-2) with and without Uv illumination. The reactions were found to yield light absorbing products and electrospray ionization mass spectrometry (ESI-MS) experiments indicate some of the compounds formed may be the nitrated analogues of the starting organic compounds. However, infrared absorption data suggests the reaction products are composed of a complicated mixture. This suggests additional reactions occur simultaneously in solution. Treatment of the isolated reaction products with ozone (O3) suggest they are unstable and will eventually chemically decompose if/when formed in the atmosphere.

关键词： Air Pollution Biomass Burning Nitration Aerosol Airborne Particulate Matter Secondary Organic Aerosol

Curvature-induced lipid segregation

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Chinese Physics B 2015年第6期24卷 95-99页

作者：郑斌孟庆田 Robin L.B.Selinger jonathan v.Selinger 叶方富 College of Physics and Electronics Shandong Normal University Beijing National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics of Chinese Academy of Sciences Institute of PhysicsChinese Academy of Sciences Liquid Crystal Institute Kent State University

We investigate how an externally imposed curvature influences lipid segregation on two-phase-coexistent membranes. We show that the bending-modulus contrast of the two phases and the curvature act together to yield a reduced effective line tension. On largely curved membranes, a state of multiple domains （or rafts） forms due to a mechanism analogous to that causing magnetic-vortex formation in type-II superconductors. We determine the criterion for such a multi-domain state to occur; we then calculate respectively the size of the domains formed on cylindrically and spherically curved membranes.

关键词： curvature phase separation lipid membrane rafts

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