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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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Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

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Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang Stephen Temitayo Bello department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator

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A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health Sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain Sciences University of MacaoMacao Special Administrative RegionChina department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina department of Emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging

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Efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases

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World Journal of Clinical Cases 2025年第6期13卷 14-23页

作者： Hang Shu Xiao-Yu Chen Jie Zhao Pin Li Zhen Sun department of Traditional Chinese Medicine Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air ForceNanjing 210000Jiangsu ProvinceChina department of Convalescence Hangzhou Special Service Recuperation Center of Chinese People's Liberation Army Air ForceNanjing 210000Jiangsu ProvinceChina

BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s syndrome,among *** pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune *** prevalence and morbidity of rheumatic immune diseases are high,imposing a significant burden on patients'quality of life and socio-economic ***,the treatment of rheumatic immune diseases mainly relies on Western medicine,such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,and ***,the therapeutic effects of Western medicine are not ideal,some patients poorly respond or are resistant to Western medicine,and long-term use often causes various adverse *** To systematically evaluate the efficacy and safety of Tripterygium wilfordii gly-cosides tablets combined with Western medicine in the treatment of patients with rheumatic immune *** This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune *** and English databases were searched for randomized controlled trials(RCTs)on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western *** quality of the included studies was assessed using the Cochrane risk of bias assessment ***-analysis was performed using RevMan 5.4 *** The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune *** combined treatment significantly reduced the risk of disease recurrence(relative risk=1.07,95%confidence interval:1.01-1.15,P<0.05)and showed no significant heterogeneity(I2=0%,P=0.53),indicating that Tripterygium wilfordii glycosides

关键词： Rheumatic immune diseases Tripterygium wilfordii polyglycosides tablets Western medicine treatment Systematic review Meta-analysis

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Curcumin in gastric cancer treatment:A commentary on mechanistic insights and future directions

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 265-267页

作者： Xin-Yue Wei Wen-Bo Cao Sai-Jun Mo Zhi-Yan Sun department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina School of Basic Medical Science Zhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of Basic Science of Oncology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina department of special Service No.988 Hospital of the Joint Service Support Force of PLAZhengzhou 450042Henan ProvinceChina

The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC *** genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC *** docking con-firmed strong binding affinity of curcumin to these *** vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.

关键词： Curcumin Gastric cancer Network pharmacology Mechanism of action In vitro experiments

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Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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Neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin Li Xiaolei Chu Qi Li Ruihua Li Qingwen Li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Haihe Laboratory of Brain-Machine Interface and Human-Machine Fusion TianjinChina department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina department of Biomedical Engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So Li Zhang Haining Ou department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Exact Computation of the Topology and Geometric Invariants of the Voronoi Diagram of Spheres in 3D

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Journal of Computer Science & Technology 2013年第2期28卷 255-266页

作者： Franois Anton Darka Mioc Marcelo Santos Research Division of geodesy National Space Institute Technical University of Denmark department of geodesy and Geomatics Engineering University of New Brunswick

In this paper, we are addressing the exact the Voronoi diagram of spheres using Wu＇s algorithm. computation of the Delaunay graph （or quasi-triangulation） and Our main contributions are first a methodology for automated derivation of invariants of the Delaunay empty circumsphere predicate for spheres and the Voronoi vertex of four spheres, then the application of this methodology to get all geometrical invariants that intervene in this problem and the exact computation of the Delaunay graph and the Voronoi diagram of spheres. To the best of our knowledge, there does not exist a comprehensive treatment of the exact computation with geometrical invariants of the Delaunay graph and the Voronoi diagram of spheres. Starting from the system of equations defining the zero-dimensional algebraic set of the problem, we are applying Wu＇s algorithm to transform the initial system into an equivalent Wu characteristic （triangular） set. In the corresponding system of algebraic equations, in each polynomial （except the first one）, the variable with higher order from the preceding polynomial has been eliminated （by pseudo-remainder computations） and the last polynomial we obtain is a polynomial of a single variable. By regrouping all the formal coefficients for each monomial in each polynomial, we get polynomials that are invariants for the given problem. We rewrite the original system by replacing the invariant polynomials by new formal coefficients. We repeat the process until all the algebraic relationships （syzygies） between the invariants have been found by applying Wu＇s algorithm on the invariants. Finally, we present an incremental algorithm for the construction of Voronoi diagrams and Delaunay graphs of spheres in 3D and its application to geodesy.

关键词： Voronoi diagram of spheres Delaunay graph of spheres Wu's method invariant characteristic set

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Investigation of the Co-seismic Gravity Field Variations Caused by the 2004 Sumatra-Andaman Earthquake Using Monthly GRACE Data

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Journal of Earth Science 2011年第2期22卷 280-291页

作者：李进申文斌 department of Geophysics School of Geodesy and GeomaticsWuhan University Key Laboratory of Geodynamic geodesy Chinese Academy of Sciences department of Geophysics School of Geodesy and Geomatics/Key Laboratory of Geospace Environment and GeodesyWuhan University State Key Laboratory of Information Engineering in Surveying Mapping and Remote Sensing

Gravity Recovery and Climate Experiment（GRACE） observations have been used to de-tect the co-seismic and post-seismic gravity field variations due to the Mw=9.3 Sumatra-Andaman earthquake that occurred on December 26,*** article focuses on investigating some gravita-tional effects caused by this huge *** computed the geoid height changes,the equivalent water height（EWH） changes,and the gravity changes using the GRACE Level-2 monthly spherical harmonic（SH） solutions released by University of Texas Center for Space Research（UTCSR）.The GRACE results agree well with the prediction by a dislocation model and are consistent with the results obtained by some previous *** particular,we calculated the three components of the gravity gradient variations and found that they can recover the seismic-related signature more sensitively due to a certain degree of amplification of the signals.A positive-negative-positive mode predominates in the spatial distribution of the horizontal components of the gravity gradient variations,which is possibly attributed to the anomalies in the crustal density distribution caused by the uplift-subduction effect of the dip-slip ***,the latitude components of the gravity gradient changes show strong suppression of the north-south stripes,which is due to the along-orbit measurements of the two GRACE *** conclude that the posi-tive-negative-positive mode in latitude gravity gradient changes would be a more sensitive fea-ture to detect the deformations of some major dip-slip earthquakes by GRACE data.

关键词： satellite geodesy time-variablegravity gravity gradient change dislocation model Sumatra-Andaman earthquake.

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Precise orbit determination for LEO satellites:single-receiver ambiguity resolution using GREAT products

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Geo-Spatial Information Science 2022年第1期25卷 63-73页

作者： Xingxing Li Yujie Qin Keke Zhang Jiaqi Wu Wei Zhang Qian Zhang Hongmin Zhang School of geodesy and Geomatics Wuhan UniversityWuhanHubeiChina department of geodesy and Remote Sensing of the German Research Centre for Geosciences(GFZ) PotsdamGermany

In recent years,the large Low Earth Orbit(LEO)constellations have become a hot topic due to their great potential to improve the Global Navigation Satellite Systems(GNSS)positioning *** of the important focus is how to obtain the accurate and reliable orbits for these constellations with dozens of LEO *** GNSS-based Precise Orbit Determination(POD)will be exclusively performed to achieve this goal,where the Integer Ambiguity Resolution(IAR)plays a key role in acquiring high-quality *** this study,we present a comprehensive analysis of the benefit of the single-receiver IAR in LEO POD and discuss its implication for the future LEO *** perform ambiguity-fixed LEO POD for four typical missions,including Gravity Recovery and Climate Experiment(GRACE)Follow-On(GRACE-FO),Swarm,Jason-3 and Sentinel-3,using the Uncalibrated Phase Delay(UPD)products generated by our GREAT(GNSS+REsearch,Application and Teaching)*** results show that the ambiguity fixing processing can significantly improve the accuracy of LEO *** are negligible differences between our UPD-based ambiguity-fixed orbits and those based on the Observable Signal Bias(OSB)and Integer Recovery Clock(IRC)products,indicating the good-quality of UPD products we *** to the float solution,the fixed solution presents a better consistency with the external precise science orbits and the largest accuracy improvement of 5 mm is achieved for GRACE-FO ***,the benefit can be observed in laser ranging residuals as well,with a Standard Deviation(STD)reduction of 3–4 mm on average for the fixed *** from the absolute orbits,the relative accuracy of the space baseline is also improved by 20–30%in the fixed *** result demonstrates the superior performance of the ambiguity-fixed LEO POD,which appears as a particularly promising technique for POD of future LEO constellations.

关键词： Precise orbit determination single-receiver ambiguity resolution onboard GPS observation LEO

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