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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang li Xingping Quan Jinfen Chen Yan Han li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina Department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua li Xiaojiang li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Manufacture the conducting polymer with light

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Science China Chemistry 2025年第01期 8-9页

作者： Yang li Tianyu li Yan Ji Baoguang liu College of Electronic and Optical Engineering & College of Flexible Electronics (Future Technology) Nanjing University of Posts & Telecommunications

Poly(3,4-ethylenedioxythiophene) (PEDOT), heralded as the “king” of conducting polymers, is esteemed in bioelectronics for its mixed electronic and ionic conductivity, mechanical properties compatible with biological tissues, tunable healing ability and stability in diverse environments [1]. Based on additive manufacturing of three-dimensional structures,PEDOT realizes the implementation in the efficient production of flexible bioelectronics, the construction of intricate electrode-neural implantations, and the development of smart brain-computer-interfaces [2].

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Precursor Role of Winter Sea-Ice in the Labrador Sea for Following-Spring Precipitation over Southeastern North America and Western Europe

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Advances in Atmospheric Sciences 2018年第1期35卷 65-74页

作者： zhe HAN Shuanglin li CAS Key Laboratory of Regional Climate-Environment for Temperate East Asia Institute of Atmospheric Physics Chinese Academy of Sciences Beijing 100029 China Climate Change Research Center Institute of Atmospheric Physics Chinese Academy of Sciences Beijing 100029 China China University of Geosciences Wuhan 430074 China

The role of winter sea-ice in the Labrador Sea as a precursor for precipitation anomalies over southeastern North America and Western Europe in the following spring is investigated. In general terms, as the sea ice increases, the precipitation also increases. In more detail, however, analyses indicate that both the winter sea-ice and the sea surface temperature(SST)anomalies related to increases in winter sea-ice in the Labrador Sea can persist into the following spring. These features play a forcing role in the spring atmosphere, which may be the physical mechanism behind the observational relationship between the winter sea-ice and spring precipitation anomalies. The oceanic forcings in spring include Arctic sea-ice anomalies and SST anomalies in the tropical Pacific and high-latitude North Atlantic. Multi-model Coupled Model Intercomparison Project Phase 5 and Atmospheric Model Intercomparison Project simulation results show that the atmospheric circulation response to the combination of sea-ice and SST is similar to that observed, which suggests that the oceanic forcings are indeed the physical reason for the enhanced spring precipitation. Sensitivity experiments conducted using an atmospheric general circulation model indicate that the increases in precipitation over southeastern North America are mainly attributable to the effect of the SST anomalies, while the increases over Western Europe are mainly due to the sea-ice anomalies. Although model simulations reveal that the SST anomalies play the primary role in the precipitation anomalies over southeastern North America, the observational statistical analyses indicate that the area of sea-ice in the Labrador Sea seems to be the precursor that best predicts the spring precipitation anomaly.

关键词： winter Labrador sea ice spring precipitation air-sea interaction

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Adaptive-basis decomposition-based low-rank network for efficient non-uniform motion deblurring

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Optoelectronics Letters 2025年第1期21卷 43-50页

作者： CHEN Lei XIONG Qingbo ZHANG Wei li Runde School of Software Henan University School of Applied Technology China University of Labor Relations

In this study, we present a unified sparsity-driven framework that significantly enhances motion deblurring performance by integrating two key components: a custom-designed dataset and a low-rank module(LRM). This framework leverages the inherent sparsity of per-pixel blur kernels to bolster both deblurring accuracy and model interpretability. Firstly, we propose an adaptive-basis decomposition-based deblurring(ADD) approach, which constructs a tailored training dataset to enhance the generalization capacity of the deblurring network. The ADD framework adaptively decomposes motion blur into sparse basis elements, effectively addressing the intricacies associated with non-uniform blurs. Secondly, an LRM is proposed to improve the interpretability of deblurring models as a plug-and-play module, primarily designed to identify and harness the intrinsic sparse features in sharp images. A series of ablation studies have been conducted to substantiate the synergistic advantages of combining the proposed ADD with the LRM for overall improvement in deblurring efficacy. Subsequently, we empirically demonstrate through rigorous experimentation that incorporating the LRM into an existing Uformer network leads to substantial enhancement in reconstruction performance. This integration yields a sparsity-guided low-rank network(SGLRN). Operating under the overarching principle of sparsity, SGLRN consistently outperforms state-of-the-art methods across multiple standard deblurring benchmarks. Comprehensive experimental results, assessed through quantitative metrics and qualitative visual evaluations, provide compelling evidence of its effectiveness. The overall deblurring results are available at Google Drive.

关键词： Image enhancement

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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

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Neural Regeneration Research 2025年第2期20卷 533-547页

作者： Yanli Zhang Tian li Jie Miao Zhina Zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei Zhang Haiting li Qiang Su Junhong Guo Department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina Department of Physiology Key Laboratory of Cellular PhysiologyMinistry of EducationShanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Hernia and Abdominal Wall Surgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Laboratory Medicine of Fenyang College Shanxi Medical UniversityFenyangShanxi ProvinceChina

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial ***,the functional role of GGT5 in the development of Alzheimer’s disease remains *** study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying *** observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse ***,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive ***,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 *** effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa *** findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 *** findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1

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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

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Neural Regeneration Research 2025年第10期20卷 2741-2757页

作者： Qianzi Jin Suyu Wang Yujia Yao Qin Jiang Keran li Department of Ophthalmology The Affiliated Eye Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina The Fourth School of Clinical Medicine Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts ***,the specific pathogenesis remains unclear,and effective early treatment options are consequently *** microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a *** intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other *** dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many *** recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the ***,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s ***,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular ***,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable *** such,the intestinal flora may play an important role in age-related macular *** the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic ***,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular ***-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the inte

关键词： age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora metabolite microecology neurodegenerative disease

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Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

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Science China Chemistry 2025年

作者： Wen Zhang Jiaxin li Nan Wang Muzi li Chen Peng Xinyue Zhang Guanghui Ouyang Yan li Beijing Key Laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering University of Science and Technology Beijing CAS Key Laboratory of Colloid Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences

lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

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Investigation of bubbles escape behavior from low basicity mold flux for high-Mn high-Al steels using 3D X-ray microscope

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 102-110页

作者： Qiang liu Xiang li Shen Du Ming Gao Yanbin Yin Jiongming Zhang State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

During the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the *** which,the behavior of bubbles traversing the liquid slag serves as a restrictive link,closely associated with viscosity and the thickness of liquid *** contrast to two-dimensional surface observation,three-dimensional(3D)analysis method can offer a more intuitive,accurate,and comprehensive ***,this study employs a 3D X-ray microscope(3D-XRM)to obtained spatial distribution and 3D morphological characteristics of residual bubbles in mold flux under different basicity of liquid slag,different temperatures,and different holding *** results indicate that as basicity of slag increases from 0.52 to 1.03,temperature increases from 1423 to 1573 K,the viscosity of slag decreases,the floating rate of bubbles *** addition,when holding time increases from 10 to 30 s,the bubbles floating distance increases,and the volume fraction and average equivalent sphere diameter of the bubbles solidified in the mold flux gradually *** one word,increasing the basicity,temperature,and holding time leading to an increase in the removal rate of bubbles especially for the *** findings of bubbles escape behavior provide valuable insights into optimizing low basicity mold flux for high-Mn high-Al steels.

关键词： mold flux low basicity bubbles three-dimensional X-ray microscope viscosity

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Reveal the nematic topological superconductivity from the anisotropic unconventional Josephson effect:Theory and application to doped Bi_(2)Se_(3)

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Science China(Physics,Mechanics & Astronomy) 2021年第9期64卷 112-122页

作者： Han-Bing Leng chuang li Xin liu School of Physics and Institute of Quantum Science and Engineering Huazhong University of Science and TechnologyWuhan 430074China Wuhan National High Magnetic Field Center and Hubei Key Laboratory of Gravitation and Quantum Physics Wuhan 430074China

We propose a scheme to reveal the possible nematic superconducting order parameter in the doped Bi2Se3 by observing the anisotropic unconventional Josephson effect without an external magnetic *** find the presence of an intrinsicπ-phase in the spin-triplet channel of Andreev *** competition with the odd-parity superconducting gap phase can lead to unconventional Josephson effect in the Josephson junction,whose normal region is connected to the same side of the superconductor,called the U-shaped junction according to its *** Josephson junctions with the interfaces perpendicular to the nematic direction,the competition will lead to a Josephsonπ-*** the case where the interface is parallel to the nematic direction,it will lead to a Josephson ***,this can directly reflect the nematic *** is worth noting that Josephson coupling with the 4πperiod appears only in the normal injected ***,if the Josephson junction adopts a conventional geometry,it always exhibits a normal Josephson 0-junction regardless of the gap function taken by the doped Bi2Se3 and therefore cannot distinguish the pairing *** thus propose a superconducting quantum interference device containing a U-shaped Josephson junction to detect nematic *** proposal not only can be applied to detect nematic superconductivity but also provides a feasible platform for topological quantum computation.

关键词： topological superconductors spin-triplet pairings odd parity unconventional Josephson effect

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