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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological Research 2024年第3期45卷 663-678页

作者： Li-Rong Liang Bing Liu Shu-Hui Cao You-Yi Zhao Tian Zeng Mei-Ting Zhai Ze Fan Dan-Yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China Department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive ***,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive ***,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly *** this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal *** neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral *** indicated that ADNP was significantly down-regulated following developmental exposure to *** adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine ***,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane ***-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by *** analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic *** of Wnt signaling was restored in the davunetide-treated ***,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general *** study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

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Neural Regeneration Research 2024年第7期19卷 1608-1617页

作者： Yanan Dou Xiaowei Fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu Zhou Fei Xia Li Fei Fei Department of Neurosurgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual *** is repo rted to play a protective role in neuroinflammation in the ***,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain *** our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion *** in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller *** found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion ***,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte *** opposite results we re observed with Homerla ove ***,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion *** together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关键词： caspase-8 Homer1a interleukin-18 interleukin-1β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 retina

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi Department of Radiation Oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China Department of Oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China Department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China School of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug Development center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

Resource-saving scheduling scheme for centralized target tracking in multiple radar system under automatic blanket jamming

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Chinese Journal of Aeronautics 2024年第5期37卷 349-362页

作者： Zhengjie LI Yujie WEI Junwei XIE Haowei ZHANG Yu TIAN air and Missile Defense College Air Force Engineering UniversityXi’an 710051China air force Xi’an Flying College Xi’an 710300China air and Missile Defense Institute Air Force Research InstituteBeijing 100085China School of Economics and Management Beihang UniversityBeijing 100191China

This paper investigates the problem of Joint Radar Node Selection and Power Allocation(JRNSPA)in the Multiple Radar System(MRS)in the blanket jamming *** radar node independently tracks moving target and subsequently transmits the raw observation data to the fusion center,which formulates a centralized tracking network *** order to establish a practical blanket jamming environment,we suppose that each target carries the self-defense jammer which automatically implements blanket jamming to the radar nodes that exceed the preset interception ***,the Predicted Conditional Cramer-Rao Lower Bound(PC-CRLB)is derived and utilized as the tracking accuracy *** at ensuring both the tracking performance and the Low Probability of Intercept(LPI)performance,the resource-saving scheduling model is formulated to minimize the transmit power consumption while meeting the requirements of tracking ***,the Modified Zoutendijk Method Of Feasible Directions(MZMFD)-based two-stage solution technique is adopted to solve the formulated non-convex optimization *** results show the effectiveness of the proposed JRNSPA scheme.

关键词： Multiple Radar System(MRS) Centralized target tracking Resource scheduling Blanket jamming Low Probability of Intercept(LPI)

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

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Neural Regeneration Research 2025年第7期20卷 2116-2128页

作者： Yuxue Mu Ning Zhang Dongyu Wei Guoqing Yang Lilingxuan Yao Xinyue Xu Yang Li Junhui Xue Zuoming Zhang Tao Chen Aerospace Clinical medical center School of Aerospace MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Aviation Medicine Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Emergency Medicine Wuhan No.1 HospitalWuhanHubei ProvinceChina Third Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Fourth Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain ***,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under *** 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic *** investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail *** results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly *** addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated *** findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

关键词： glial fibrous acidic protein gliosis Müller cells nerve growth factor neural differentiation neurodegeneration proteomic retinal degeneration retinal outer nuclear layer simulated weightlessness

Reduced-complexity multiple parameters estimation via toeplitz matrix triple iteration reconstruction with bistatic MIMO radar

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Chinese Journal of Aeronautics 2024年第7期37卷 482-495页

作者： Chenghong ZHAN Guoping HU Junpeng SHI Fangzheng ZHAO Hao ZHOU Graduate College Air Force Engineering UniversityXi’an 710051China air and Missile Defense College Air Force Engineering UniversityXi’an 710051China College of Electronic Countermeasure National University of Defense TechnologyHefei 230037China dBeijing Aeronautical Technology Research center Beijing 100076China

On-machine tool setting is a pivotal approach in achieving intelligent manufacturing,and laser tool setters have become a crucial component of smart machine *** tool setters play a crucial role in precisely measuring the dimensions of cutting tools during the part machining process,focusing on tool length and *** a measuring instrument,the positions of the laser axis of the laser tool setter need to be accurately calibrated before ***,in actual calibration scenarios,traditional calibration methods face challenges due to installation errors in the tool setter and geometric errors in the measuring *** address this issue,this study proposes a novel calibration ***,the calibration mechanism of the laser beam axis is *** on the accurate mathematical model of the laser beam and the measuring rod,and using the polygon clipping algorithm,the mathematical mechanism of the laser tool setter’s work is ***,a novel method is introduced to calculate the compensation distance between the laser beam reference point and the rod bottom center point at each moment during ***,by utilizing the kinematic chain of the tool setter calibration system,a new calibration method is developed to accurately calibrate the position of the laser beam axis in the machine tool coordinate ***,the accuracy of the calibration method is verified through simulation experiments and calibration *** method improves the calibration accuracy of the tool setter,and the mathematical model of the laser tool setter can be extended to the measurement of tools,thereby improving the precision of tool *** research significantly improves the efficient production performance of smart machine tools.

关键词： On-machine tool setting Smart machine tools Mathematical model Calibration method Laser tool setter

Clinical treatment procedure and experience of six gene-edited pigrhesus monkey heterotopic heart xenotransplantation

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Chinese medical Journal 2024年第8期137卷 997-999页

作者： Bing Zhang Pengfei Ji Langang Peng Mengen Zhai Jiayou Tang Lin Zhao Yan Jin Baoling Xu Xiangni Lyu Linhe Lu Yenong Zhou Zhenxiao Jin Weixun Duan Xiuling Yang Wei Yi Jincheng Liu Department of Cardiovascular Surgery Xijing HospitalAir Force Medical UniversityXi’anShaanxi 710032China

Heart transplantation is an effective treatment for endstage heart failure;however,problems such as the severe shortage of donor hearts,rejection,the toxic effects of immunosuppressants,and serious postoperative complications remain.[1]Heart xenotransplantation is one of the most promising alternatives to address the shortage of allogeneic donor ***,the recipient survival rate and quality of life are affected by major obstacles,including immune rejection,complement and coagulation dysfunction,and infection.[2,3]Owing to the continuous improvement of gene editing strategies for donor pigs and anti-immune rejection strategies for non-human primate recipients.

关键词： donor treatment shortage