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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon c.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Status and prospects for symmetric organic redox flow batteries

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journal of Energy chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan c.Adam Dyker Department of chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Leadless pacemakers： a contemporary review

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journal of Geriatric cardiology 2018年第4期15卷 249-253页

作者： neal Bhatia Mikhael El-chami Department of Medicine Division of Cardiology Section of Electrophysiology Emory University School of Medicine Atlanta USA

1 Introduction Over one million cardiac pacemakers are implanted every year worldwide,[11 of which approximately 200,000 are implanted in the United States alone.121 combined with an aging population and increasing pacing indications, these numbers are expected to grow. Since the first pacemaker implantation in 1950s, cardiac pacemaker technology has rapidly advanced. Reduction in generator size, increased battery longevity, quality of pacemaker leads, algorithmic and rate responsive programming-all have revolutionized and transformed the implantation and management of transvenous cardiac pacemaker （TV-PPM）.

关键词： Leadless pacemakers Micra Nanostim Perforation

Maximizing biomass utilization: An integrated strategy for coproducing multiple chemicals

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journal of Energy chemistry 2025年第1期100卷 180-191页

作者： Byeongchan Ahn Sua jo jonggeol Na j.jay Liu Young-ju Kim Wangyun Won Department of chemical and Biological Engineering Korea University Department of chemical Engineering (Integrated process) Kyung Hee University Department of chemical Engineering and Materials Science Ewha Womans University Department of chemical Engineering Pukyong National University Resources Engineering Plant Research Department Korea Institute of Geoscience and Mineral Resources

Lignocellulosic biomass is one of the viable solutions to alleviate the global warming. However, the limited utilization of biomass majorly focused on cellulose and hemicellulose restricts the economic and environmental feasibilities. To cope with this issue, we proposed an integrated process of co-producing 1,6-hexanediol（1,6-HDO） with tetrahydrofuran and adipic acid from biomass, referred to as Strategy A. To compare the impacts of lignin upgrading and feedstock, Strategy B, which co-produces tetrahydrofuran alone, and Strategy c, which is the traditional route to produce 1,6-HDO from fossil fuels, were used. Heat networks are also designed to reduce operating costs and indirect carbon emissions due to energy consumption, saving 87% and 83% of the heat and cooling requirements, respectively, in Strategy A. The market competitiveness of Strategy A was evaluated by determining the minimum selling price through techno-economic analysis, and sustainability was thoroughly investigated by quantifying the environmental impacts through both midpoint and endpoint life-cycle assessments（LcAs）.Strategy A was found to be the most favorable both economically（USRDScHARDOLLAR3,402/ton） and environmentally（-26.9 kg cO2eq.）. This indicates that lignin valorization is not only economically but also environmentally preferred. Finally, changes in economic and environmental feasibilities depending on economic, process, and environmental parameters were investigated using sensitivity and uncertainty analyses. The results of these analyses provide valuable insight into bio-based chemical production.

关键词： carbon capture and utilization

Geochronology and Significance of Granites Associated with Gold Deposits in the jidong Area, china

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Acta Geologica Sinica(English Edition) 2000年第2期74卷 306-310页

作者： neal McNAUGHTON David GROVES Department of Geology University of West Australia AustraliaDepartment of Geology University of West Australia Australia

The jidong area is located on the north margin of the North china craton. It is a nucleus composed of the oldest rocks in china. Precambrian metarnorphic rocks with various Phanerozoic granitoids invaded are widespread. Gold deposits here have close spatial relations to granitoids. Some deposits occur within them and others in the outer zone of the contact belt of the intrusion, extending thousands of metres. There have been controversial views in regard to the relations of the deposits to the intrusions although traditional techniques have been used to date the intrusions. In order to solve such a problem, the SHRIMP technique was adopted to date the U-Pb ages of zircon collected from the Yuerya intrusion which hosts the large-sized Yuerya Au deposit and Qingshankou intrusion 2 km away from the jinchangyu (larger-sized) Au deposit. Analysis shows that the ages of 175±1 Ma and 174±3 Ma for Yuerya intrusion and the age of 199±2 Ma for Qingshankou granite indicate the Early Yanshanian stage of the Mesozoic. The Yuerya intrusion also contains inherited zircon aged at about 2500 Ma, indicating that part of its source materials are Archaean metamorphic rocks. In addition to the SHRIMP data of this study, a great deal of data related to the alteration of Au deposits indicate the formation of the deposits at the Yanshanian stage of the Mesozoic, so the ore formation of Au deposits is inferred to relate to granitic intrusion.

关键词： SHRIMP geochronology granite Yanshanian East china

combined U-Pb SHRIMP and Hf isotope study of the Late Paleozoic Yaminue complex,Rio Negro Province,Argentina:Implications for the origin and evolution of the Patagonia composite terrane

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Geoscience Frontiers 2013年第1期4卷 37-56页

作者： carlos j.chernicoff Eduardo O.Zappettini joao O.S.Santos neal j.McNaughton Elena Belousova National Scientific and Technical Research council(cONIcET) Argentina Argentine Geological-Mining Survey(SEGEMAR) Argentina Argentine Geological-Mining Survey(SEGEMAR).Argentina University of Western Australia PerthWA 6009Australia Redstone Resources.Perth.WA 6849.Australia john de Laeter centre Curtin UniversityPerthWA 6102Australia ARc National Key centre for Geochemical Evolution and Metallogeny of continents(GEMOc) Macquarie UniversitySydneyNSW 2109Australia

We have carried out zircon U-Pb SHRIMP dating and Hf isotope determinations on a biotite paraschist and on a tonalitic orthogneiss of the Yaminué complex, and re-evaluate this complex in the broader context of the tectonic evolution of the Patagonia composite terrane. In the metasedimentary unit （msuYc）, the youngest detrital zircon dated at 318 ± 5 Ma （Mississippian/Pennsylvanian boundary） indicates a Pennsylvanian （or younger） depositional age. The three main age populations peak at 474, 454 and 374 Ma. Preliminary Hf isotope data for two detrital zircons （447 and 655 Ma） yielded ε（Hf） values of -0.32 and 0.48, indicating that their primary sources contained small amounts of recycled crustal components （of calymmian age; TDM 1.56 Ga）. Zircons from the orthogneiss （miuYc; intrusive into msuYc） show a crystallization age of 261.3 - 2.7 Ma （capitanian; late middle Permian） which is broadly coeval with deformation, and Neoarchean-Paleoproterozoic inheritance. Meaningful core-rim relationship between Neoarchean zircon cores and late Permian rims is well defined, indicating the occurrence of Archean crust in this sector of Patagonia. Hf TDM of Permian zircons is mainly Meso-Paleoarchean （2.97-3.35 Ga）, with highly negative e（Hf） values （ca, -33）. Hf TDM of inherited Neoarchean zircon cores is also Meso-Paleoarchean （3.14-3.45 Ga） but more juvenile （ε（Hf） = -0.3）. Hf isotopes reinforce the presence of unexposed ancient crust in this area. combining geological and isotope data, as well as geophysical models, we identify the Yaminué complex within the La Esperanza-Yaminué crustal block flanked by two other, distinct crustal blocks： the Eastern block which forms part of the Patagonia terrane sensu stricto, located in the eastern Patagonian region, and the Western block forming part of the Southern Patagonia terrane. Their origins and timing of amalgamation to form the Patagonia composite terrane are also discussed.

关键词： Yaminue complex U-Pb SHRIMP geochronology Hf isotopes Tectonics North Patagonian Massif Argentina

NEcAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno Michael K.E.Schafer Sudena Wang Michael j.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NEcAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized c-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NEcAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NEcAB2 interacts with predominantly striatal G-protein-coupled receptors, while NEcAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NEcAB proteins exhibit distinct subcellular localizations: NEcAB1 is found in the nucleus and cytosol, NEcAB2 resides in endosomes and the plasma membrane, and NEcAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NEcAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NEcAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

Phylogenetic and sequence analyses of insect transferrins suggest that only transferrin 1 has a role in iron homeostasis

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Insect Science 2021年第2期28卷 495-508页

作者： Diana G.Najera neal T.Dittmer jacob j.Weber Michael R.Kanost Maureen j.Gorman Department of Biochemistry and Molecular Biophysics Kansas State UniversityManhattanKansasUSA

Iron is essential to life,but surprisingly little is known about how iron is managed in nonvertebrate *** mammals,the well-characterized transferrins bind iron and are involved in iron transport or immunity,whereas other members of the transferrin family do not have a role in iron *** insects,the functions of transferrins are still poorly *** goals of this project were to identify the transferrin genes in a diverse set of insect species,resolve the evolutionary relationships among these genes,and predict which of the transferrins are likely to have a role in iron *** phylogenetic analysis of transferrins from 16 orders of insects and two orders of noninsect hexapods demonstrated that there are four orthologous groups of insect *** analysis suggests that transferrin 2 arose prior to the origin of insects,and transferrins/,i,and 4 arose early in insect *** sequence analysis of each of the insect transferrins was used to predict signal peptides,carboxyl-terminal transmembrane regions,GPI-anchors,and iron *** on this analysis,we suggest that transferrins 2,and 4 are unlikely to play a major role in iron *** contrast,the transferrin 1 orthologs are predicted to be secreted,soluble,iron-binding *** conclude that transferrin 1 orthologs are the most likely to play an important role in iron ***,it appears that the louse,aphid,and thrips lineages have lost the transferrin 1 gene and,thus,have evolved to manage iron without transferrins.

关键词： hemolymph insect iron homeostasis melanotransferrin phylogeny transferrin