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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural regeneration research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown rafael j.Yáñez-Muñoz Heidi r.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

The role of organic electron donors in the initiation of BHAS base-induced coupling reactions between haloarenes and arenes

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Science China Chemistry 2019年第11期62卷 1425-1438页

作者： Andrew j.Smith Darren L.poole john A.Murphy Department of Pure and Applied Chemistry University of StrathclydeStrathclydeGlasgow G11XLUnited Kingdom Flexible Discovery Unit GlaxoSmithKline Medicines Research CentreStevenageSG12NYUnited Kingdom

Coupling reactions between haloarenes and arenes(including heteroarenes)that are conducted without added transition metals but in the presence of KOtBu or NaOtBu,have been a topic of great interest since their discovery in *** organic structures act as additives that assist these *** additives are converted into organic electron donors by the butoxide base and this leads to initiation of the coupling reactions,which proceed by radical chain *** review provides an overview of the initiation stages of these reactions.

关键词： organic electron donor potassium tert-butoxide electron transfer base-promoted homolytic aromatic substitution(BHAS) coupling benzyne

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural regeneration research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural regeneration research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

Terahertz Generation Using Implanted InGaAs Photomixers and Multi-wavelength Quantum Dot Lasers

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Nano-Micro Letters 2012年第1期4卷 10-13页

作者： Y.Hou j.r.Liu M.Buchanan A.j.Spring Thorpe P.j.poole H.C.Liu Ke Wu Sjoerd roorda X.P.Zhang Institute for Microstructural Sciences National Research Council Also with Department of Electrical Engineering Concordia University Now with Key Laboratory of Artificial Structures and Quantum Control Department of Physics Shanghai Jiao Tong University Department of Electrical Engineering Ecole Polytechnique Département de physique Université de Montréal Department of Electrical Engineering Concordia University

We report on a study of terahertz(THz) generation using implanted In Ga As photomixers and multi-wavelength quantum dot lasers. We carry out In Ga As materials growth, optical characterization, device design and fabrication, and photomixing experiments. This approach is capable of generating a comb of electromagnetic radiation from microwave to terahertz. For shortening photomixer carrier lifetime, we employ proton implantation into an epitaxial layer of lattice matched In Ga As grown on InP. Under a 1.55 μm multimode In GaAs/In GaAsP quantum dot laser excitation, a frequency comb with a constant frequency spacing of 50 GHz generated on the photomixer is measured, which corresponds to the beats of the laser longitudinal modes. The measurement is performed with a Fourier transform infrared spectrometer. This approach affords a convenient method to achieve a broadband multi-peak coherent THz source.

关键词： Proton implanted In Ga As Trahertz Photomixer Multi-wavelength quantum dot laser Fourier transform infrared spectroscopy

Accommodating the bacterial decoding release factor as an alien protein among the rNAs at the active site of the ribosome

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Cell research 2007年第7期17卷 591-607页

作者： Elizabeth S poole David j Young Marjan E Askarian-Amiri Debbie-jane G Scarlett Warren P Tate Department of Biochemistry University of OtagoP.O.Box 56 DunedinNew Zealand

The decoding release factor (rF) triggers termination of protein synthesis by functionally mimicking a trNA to spanthe decoding centre and the peptidyl transferase centre (PTC) of the ribosome. Structurally, it must fit into a site craftedfor a trNA and surrounded by five other rNAs, namely the adjacent peptidyl trNA carrying the completed polypeptide,the mrNA and the three rrNAs. This is achieved by extending a structural domain from the body of the protein thatresults in a critical conformational change allowing it to contact the PTC. A structural model of the bacterial terminationcomplex with the accommodated rF shows that it makes close contact with the first, second and third bases of the stopcodon in the mrNA with two separate loops of structure: the anticodon loop and the loop at the tip of helix α5. Theanticodon loop also makes contact with the base following the stop codon that is known to strongly influence termina-tion efficiency. It confirms the close contact of domain 3 of the protein with the key rNA structures of the PTC. ThemrNA signal for termination includes sequences upstream as well as downstream of the stop codon, and this may reflectstructural restrictions for specific combinations of trNA and rF to be bound onto the ribosome together. An unbiasedSELEX approach has been investigated as a tool to identify potential rrNA-binding contacts of the bacterial rF in itsdifferent binding conformations within the active centre of the ribosome.

关键词： release factor protein synthesis termination trNA functional mimicry molecular mimicry SELEX ribosome

Women in visual neural regeneration research

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Neural regeneration research 2025年第2期20卷 489-490页

作者： Tonia S.rex David j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue ridge Institute for Medical research and data from the major professional organization for eye and vision research,the Association for research in Vision and Ophthalmology(ArVO).

关键词： neural visual Times

Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural regeneration research 2025年第7期20卷 2013-2014页

作者： Nathanael j.Lee ryota L.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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： Biorefinery Carbon mitigation Climate change Global warming Lignin utilization Bioeconomy