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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and department of pharmacology University of North Carolina–Chapel HillChapel HillNCUSA department of medicinal chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

A low redox potential and long life organic anode material for sodium-ion batteries

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Journal of Energy chemistry 2025年第1期100卷 557-564页

作者： Zhi Li Yang Wei Kang Zhou Xin Huang Xing Zhou Jie Xu Taoyi Kong Junwei Lucas Bao Xiaoli Dong Yonggang Wang department of chemistry and Shanghai Key Laboratory of molecular Catalysis and Innovative Materials Institute of New Energy Collaborative Innovation Center of Chemistry for Energy Materials (iChEM) Fudan University department of chemistry Boston College School of Materials Science and Engineering Anhui University of Technology

Sodium-ion batteries （SIBs） with organic electrodes are an emerging research direction due to the sustainability of organic materials based on elements like C,H,O,and sodium ***,organic electrode materials for SIBs are mainly used as cathodes because of their relatively high redox potentials（>1 V）.Organic electrodes with low redox potential that can be used as anode are ***,a novel organic anode material （tetrasodium 1,4,5,8-naphthalenetetracarboxylate,Na4TDC） has been developed with low redox potential （<0.7 V） and excellent cyclic *** three-sodium storage mechanism was demonstrated with various in-situ/ex-situ spectroscopy and theoretical calculations,showing a high capacity of 208 mAh/g and an average decay rate of merely 0.022%per ***,the Na4TDC-hard carbon composite can further acquire improved capacity and cycling stability for 1200 cycles even with a high mass loading of up to 20 mg *** pairing with a thick Na3V2（PO4）3cathode (20.6 mg cm-2),the as-fabricated full cell exhibited high operating voltage （2.8 V）,excellent rate performance and cycling stability with a high capacity retention of 88.7% after 200 cycles,well highlighting the Na4TDC anode material for SIBs.

关键词： Organic anode material Low redox potential Composite anode Sodium-ion batteries

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina department of medicinal chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

CO2-mediated bicarbonate conversion to concentrated formate in a CEM-based electrolyzer

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Journal of Energy chemistry 2025年第1期100卷 605-611页

作者： Haocheng Xiong Donghuan Wu Haonan Li Andrew Li Qikun Hu Siyao Song Bingjun Xu Qi Lu State Key Laboratory of Chemical Engineering Department of Chemical Engineering Tsinghua University College of chemistry and molecular Engineering Peking University Ordos Laboratory

Renewable energy-driven bicarbonate conversion to valuable chemicals presents an attractive strategy for mitigating CO2emissions,as bicarbonate can be efficiently generated from the capture of atmospheric CO2using alkaline solutions with reactive *** this work,we present a CO2-mediated bicarbonate conversion to pure formate using a cation exchange membrane-based electrolyzer with a 25 cm2electrode *** electrolysis achieved selectivities exceeding 75%for formate at a total current of 2.5 A,achieving formate concentrations up to 1.2 M and yields as high as 95%over extended *** techno-economic assessment confirmed the economic viability of the process,highlighting the potential for bicarbonate electrolysis as a sustainable method for producing valuable chemicals.

关键词： Electrocatalysis Techno-economic assessments Electrochemistry Flow electrolyzer

Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina Schmidt department of molecular pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

Efficient photocatalytic reduction of CO2 to formate by a molecular noble metal-free system

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Science China chemistry 2025年第1期68卷 152-156页

作者： Lihua Zhang Lingjing Chen Huatian Shi Yue Wei Gui Chen Tai-Chu Lau School of Environment and Civil Engineering Research Center for Eco-environmental Engineering Dongguan University of Technology department of chemistry and Institute of molecular Functional Materials City University of Hong Kong

Reducing CO2to carbon-neutral solar fuels can not only alleviate the energy demand but also mitigate the greenhouse *** present,developing an efficient non-noble metal photo/electrocatalytic system for converting CO2to a specific product beyond CO is still a big ***,we report a new cobalt complex bearing 2,2′-bi-1,10-phenanthroline ligand that can photocatalytically reduce CO2to formate （HCOO-）.Turnover number （TON） for HCOO-up to 677 with 99%selectivity can be achieved using organic dyes purpurin as photosensitizer and 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole （BIH） as sacrificial reductant in a CO2-saturated NMP/TEA （v/v,3:1） solution under visible light *** potential electrolysis at-1.41 V （***/Ag Cl） in the presence of 12 m M Et3NHBF4also produced HCOO-with Faradaic efficiency of 39%.Spectroscopic and electrochemical studies suggest that a[CoI-H]species is the key intermediate for CO2reduction.

关键词： photocatalysis noble metal-free CO2 reduction formate cobalt hydride

Stepwise assembly to construct stable copper(I) cluster-based circularly polarized luminescent MOFs

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Science China chemistry 2025年

作者： Jing-Wen Xie Meng-Ting Wang Yan Jin Si Li Jian-Hua Qin Shuang-Quan Zang Tomas C.W.Mak College of chemistry Henan Key Laboratory of Crystalline Molecular Functional Materials Zhengzhou University College of chemistry and Chemical Engineering Luoyang Normal University department of chemistry The Chinese University of Hong Kong

Circularly polarized luminescence （CPL） materials have been extensively studied in recent years owing to their widespread applications in 3D display,optical storage,optical anti-counterfeiting,and biological imaging,***（I） clusters have emerged as a promising candidate for CPL materials,driven by their cost-effectiveness,superior luminescent properties,precise structure,and low ***,the poor environmental stability of copper（I） clusters renders their synthesis and preservation challenging,thereby significantly impeding their ***,we have designed and synthesised a chiral double-coordinated ligand in order to construct copper（I） cluster nodes that can be further *** anticipated,by utilizing stepwise assembly strategy,a Cu4cluster node co-modified by chiral alkynyl ligands and triphenylphosphine was further assembled with Cd2+ions to obtain 2D layers structure,L/*** L/D-Cu4-Cd exhibits excellent stability and optical properties,including bright yellow emission,solvent-responsive luminescence,and CPL activity with a maximum glumup to 2.0×10-3,which shows potential applications in the WLED and *** interestingly,the material also exhibits deflection ability towards different wavelengths of linearly polarized light,showing certain potential in the preparation of circular polarizer.

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Design of multifunctional interfaces on ceramic solid electrolytes for high-performance lithium-air batteries

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Green Energy & Environment 2025年第1期10卷 183-192页

作者： Yunxin Shi Ziyang Guo Changhong Wang Mingze Gao Xiaoting Lin Hui Duan Yonggang Wang Xueliang Sun College of Energy Material and chemistry College of Chemistry and Chemical EngineeringInner Mongolia UniversityHohhot010021China department of Mechanical and Materials Engineering Western UniversityLondonONN6A 5B9Canada department of chemistry and Shanghai Key Laboratory of molecular Catalysis and Innovative Materials Institute of New EnergyiChEM(Collaborative Innovation Center of Chemistry for Energy Materials)Fudan UniversityShanghai200433China Eastern Institute for Advanced Study Eastern Institute of TechnologyNingboZhejiang315100China

High-energy-density lithium(Li)–air cells have been considered a promising energy-storage system,but the liquid electrolyte-related safety and side-reaction problems seriously hinder their *** address these above issues,solid-state Li–air batteries have been widely ***,many commonly-used solid electrolytes generally face huge interface impedance inLi–air cells and also showpoor stability towards ambient air/Li ***,we fabricate a differentiating surface-regulated ceramic-based composite electrolyte(DSCCE)by constructing disparately LiI-containing polymethyl methacrylate(PMMA)coating and Poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP)layer on both sides of Li_(1.5)Al_(0.5)Ge_(1.5)(PO_(4))_(3)(LAGP).The cathode-friendly LiI/PMMA layer displays excellent stability towards superoxide intermediates and also greatly reduces the decomposition voltage of discharge products in Li–air ***,the anode-friendly PVDF-HFP coating shows low-resistance properties towards ***,Li dendrite/passivation derived from liquid electrolyte-induced side reactions and air/I-attacking can be obviously suppressed by the uniformand compact composite *** a result,the DSCCE-based Li–air batteries possess high capacity/low voltage polarization(11,836mAh g^(-1)/1.45Vunder 500mAg^(-1)),good rate performance(capacity ratio under 1000mAg^(-1)/250mAg^(-1) is 68.2%)and longterm stable cell operation(~300 cycles at 750 mA g^(-1) with 750 mAh g^(-1))in ambient air.

关键词： Li-air batteries Li_(1.5)Al_(0.5)Ge_(1.5)(PO_(4))_(3) Polymers Composite electrolyte Ambient air