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Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla Eng-King Tan Department of Neurology National Neuroscience InstituteSingaporeSingapore neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune responses.Nelson et al.and Chen et al.have provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura Department of Neurosurgery Hokkaido University Graduate School of Medicine

Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including antiapoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

Building the toolbox for in vivo glia-to-neuron reprogramming

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Neural Regeneration Research 2024年第6期19卷 1171-1172页

作者： Ye Xie Bo Chen Departments of Ophthalmology and neuroscience Icahn School of Medicine at Mount Sinai

Unlike regenerative-competent species that possess a remarkable intrinsic capacity to replenish lost neurons and restore neurocircuits spontaneously, the central nervous system in adult mammals lacks the ability to compensate for the neuronal loss caused by neurodegenerative diseases or traumatic injuries resulting in permanent loss of functionality. Inspired by earlier discoveries that radial glia or astrocytes isolated from the postnatal cortex can generate neurons,

关键词： CONVERSION DISEASE

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration Research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of Brain and Cognitive neuroscience Guilin Medical University Department of Genetic Disease Research Osaka Metropolitan University Graduate School of Medicine Department of Scientific Research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim F.Trakhtenberg Department of neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

Characterization of size-resolved effective density of atmospheric particles in an urban atmosphere in Southern China

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Journal of Environmental Sciences 2024年第7期141卷 194-204页

作者： Tingting Xie Liming Cao Jinyi Zheng Peng Xuan Xiaofeng Huang Laboratory of Atmospheric Observation Supersite School of Environment and EnergyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Effective density(ρ_(eff))is one of the most important physical properties of atmospheric particles,providing important references in exploring the emissions and aging processes of fresh particles.In this study,a combined system of differential mobility analyzer,centrifugal particle mass analyzer,and condensation particle counter was used to periodically measure theρ_(eff)of atmospheric particles in Shenzhen from Oct.2021 to Jan.2022.Results showed that theρ_(eff)of particles with various size presented a bimodal distribution,which could be divided into main density(ρ_(m),main peak,corresponding to relatively dense particles after aging)and sub density(ρ_(s),sub peak,corresponding to fresh particles).The occurrence frequencies ofρ_(s)of particles with diameters of 50 and 80 nm were less than 20%,but were as high as about 40%of that with diameters from 120 to 350 nm.Theρ_(m)showed increasing trend with the size of particles,whileρ_(s)decreased as the increasing of the size of particles.Theρ_(eff)on pollution day varied significantly with chemical compositions.The increasing of the proportion of sulfate could promote the increasing ofρ_(eff),while black carbon and organic matter caused opposite effects,which may be related to various factors,including the difference of the material density and morphology of various chemical components.Theρ_(eff)of 50,80 and 120 nm particles decreased considerably during the new particle formation event,indicating that organic condensation was an important contributor to new particle growth.

关键词： DMA-CPMA-CPC Effective density Main/sub density Size distribution

Hyperspectral image super resolution using deep internal and self-supervised learning

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CAAI Transactions on Intelligence Technology 2024年第1期9卷 128-141页

作者： Zhe Liu Xian-Hua Han graduate school of Science and Technology for Innovation Yamaguchi UniversityYamaguchiJapan graduate school of Artificial Intelligence and Science Rikkyo UniversityTokyoJapan

By automatically learning the priors embedded in images with powerful modelling ca-pabilities,deep learning-based algorithms have recently made considerable progress in reconstructing the high-resolution hyperspectral(HR-HS)image.With previously collected large-amount of external data,these methods are intuitively realised under the full supervision of the ground-truth data.Thus,the database construction in merging the low-resolution(LR)HS(LR-HS)and HR multispectral(MS)or RGB image research paradigm,commonly named as HSI SR,requires collecting corresponding training triplets:HR-MS(RGB),LR-HS and HR-HS image simultaneously,and often faces dif-ficulties in reality.The learned models with the training datasets collected simultaneously under controlled conditions may significantly degrade the HSI super-resolved perfor-mance to the real images captured under diverse environments.To handle the above-mentioned limitations,the authors propose to leverage the deep internal and self-supervised learning to solve the HSI SR problem.The authors advocate that it is possible to train a specific CNN model at test time,called as deep internal learning(DIL),by on-line preparing the training triplet samples from the observed LR-HS/HR-MS(or RGB)images and the down-sampled LR-HS version.However,the number of the training triplets extracted solely from the transformed data of the observation itself is extremely few particularly for the HSI SR tasks with large spatial upscale factors,which would result in limited reconstruction performance.To solve this problem,the authors further exploit deep self-supervised learning(DSL)by considering the observations as the unlabelled training samples.Specifically,the degradation modules inside the network were elaborated to realise the spatial and spectral down-sampling procedures for transforming the generated HR-HS estimation to the high-resolution RGB/LR-HS approximation,and then the reconstruction errors of the observations were formulated for measuring the network modelling performance.By cons

关键词： computer vision deep learning deep neural networks hyperspectral image enhancement

Recent progress about transmission electron microscopy characterizations on lithium-ion batteries

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Journal of Energy Chemistry 2024年第8期95卷 39-56页

作者： Yihang Liu Qiuyun Li Ziqiang Wang Institute of Materials Research Shenzhen International Graduate School Tsinghua University

With the rapid development of portable electronics, new energy vehicles, and smart grids, ion batteries are becoming one of the most widely used energy storage devices, while the safety concern of ion batteries has always been an urgent problem to be solved. To develop a safety-guaranteed battery, the characterization of the internal structure is indispensable, where electron microscopy plays a crucial role. Based on this, this paper summarizes the application of transmission electron microscopy(TEM) in battery safety, further concludes and analyzes the aspects of dendrite growth and solid electrolyte interface(SEI) formation that affect the safety of ion batteries, and emphasizes the importance of electron microscopy in battery safety research and the potential of these techniques to promote the future development of this field. These advanced electron microscopy techniques and their prospects are also discussed.

关键词： Dendrites Electron microscopy characterizations Lithium-ion batteries SEI

Non-Kramers doublet ground state in a quaternary cubic compound PrRu_(2)In_(2)Zn_(18) investigated by ultrasonic measurements

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Chinese Physics B 2024年第6期33卷 405-411页

作者：张化远 Kazuhei Wakiya Mitsuteru Nakamura Masahito Yoshizawa Yoshiki Nakanish graduate school of Science and Engineering Iwate UniversityMorioka 020-8551Japan

We performed ultrasonic measurements on a quaternary cubic compound PrRu_(2)In_(2)Zn_(18) to explore the ground state properties derived from non-Kramers Γ_(3) doublet of Pr^(3+).PrRu_(2)In_(2)Zn_(18) is a quaternary derivative of the ternary compound PrRu_(2)Zn_(20) that exhibits a structural phase transition at T_S=138 K.In PrRu_(2)In_(2)Zn_(18),the Zn atoms at the 16c site in PrRu_(2)Zn_(20) are selectively replaced by In atoms.A monotonic increase was observed in the temperature dependence of elastic constants C_L=(C_(11)+2C_(12)+4C_(44))/3 and C_(T)=(C_(11)-C_(12)+C_(44))/3 in the temperature range around T_(S) to which an elastic softening was observed in(C_(11)-C_(12))/2 for PrRu_(2)Zn_(20).The disappearance of the softening indicates that the structural transition in PrRu_(2)Zn_(20) is suppressed by the substitution of Zn ions by In ones with a larger ionic radius.Alternatively,the C_(T) of PrRu_(2)In_(2)Zn_(18) exhibits a precursor Curie-type elastic softening toward low temperatures being responsible for the non-Kramers Γ_(3) ground state.We discuss the ground state and the evolution of the elastic properties of the different single-crystal samples of PrRu_(2)In_(2)Zn_(18) grown under different conditions.

关键词： ultrasonic measurements non-Kramers doublet structural phase transition crystalline electric field effect