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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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A new unequal-weighted triple-frequency first order ionosphere correction algorithm and its application in COMPASS

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Science China(Physics,Mechanics & Astronomy) 2012年第3期55卷 546-552页

作者： WenXiang Liu WeiHua mou FeiXue wang Natl Univ Def Technol Satellite Nav Res & Dev Ctr Sch Elect Sci & Engn Changsha 410073 Hunan Peoples R China

As the introduction of triple-frequency signals in GNSS,the multi-frequency ionosphere correction technology has been fast *** indicate that the triple-frequency second order ionosphere correction is worse than the dual-frequency first order ionosphere correction because of the larger noise amplification *** the assumption that the variances of three frequency pseudoranges were equal,other references presented the triple-frequency first order ionosphere correction,which proved worse or better than the dual-frequency first order correction in different *** practice,the PN code rate,carrier-to-noise ratio,parameters of DLL and multipath effect of each frequency are not the same,so three frequency pseudorange variances are *** this consideration,a new unequal-weighted triple-frequency first order ionosphere correction algorithm,which minimizes the variance of the pseudorange ionosphere-free combination,is proposed in this *** is found that conventional dual-frequency first-order correction algorithms and the equal-weighted triple-frequency first order correction algorithm are special cases of the new algorithm.A new pseudorange variance estimation method based on the three carrier combination is also *** analysis shows that the new algorithm is *** experiment with COMPASS G3 satellite observations demonstrates that the ionosphere-free pseudorange combination variance of the new algorithm is smaller than traditional multi-frequency correction algorithms.

关键词： GNSS ionospheric delay ionosphere-free combination COMPASS

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Quickly obtaining densely dispersed coherent particles in steel matrix and its related mechanical property

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 111-118页

作者： Xiaoxiao wang Qingsong Huang School of Chemical Engineering Sichuan UniversityChengdu 610065China

Densely distributed coherent nanoparticles(DCN)in steel matrix can enhance the work-hardening ability and ductility of steel *** the routes to this end can be generally classified into the liquid-solid route and the solid-solid ***,the formation of DCN structures in steel requires long processes and complex *** far,obtaining steel with coherent particle enhancement in a short time remains a bottleneck,and some necessary steps remain ***,we show a high-efficiency liquid-phase refining process reinforced by a dynamic magnetic ***-Y-Mn-O particles had an average size of around(3.53±1.21)nm and can be obtained in just around 180 *** small nanoparticles were coherent with the matrix,implying no accumulated dislocations between the particles and the steel *** findings have a potential application for improving material machining capacity,creep resistance,and radiation resistance.

关键词： ferritic steels coherent particles microstructure compression test work hardening

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A Physics-Based Dual-Frequency Approach for Altimeter Wind Speed Retrieval

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Journal of Ocean University of China 2014年第4期13卷 579-583页

作者： LI Shuiqing zhou Liangming LI Zhanbin MIAO Qingsheng mou Lin wang Aifang Institute of Oceanology Chinese Academy of Sciences Physical Oceanography Laboratory Ocean University of China National Marine Data and Information Service State Oceanic Administration of People’s Republic of China Engineering Reconnaissance and Design Institute Ocean University of China

The altimeter normalized radar cross section(NRCS) has been used to retrieve the sea surface wind speed for decades, and more than a dozen of wind speed retrieval algorithms have been proposed. Despite the continuing efforts to improve the wind speed measurements, a bias dependence on wave state persists in all wind algorithms. On the basis of recent evidence that short waves are essentially modulated by local winds and much less affected by wave state, we proposed a physics-based approach to retrieve the wind speed from the dual-frequency difference in terms of the mean square slope of short waves. A collocated dataset of coincident altimeter/buoy measurements were used to develop and validate the approach. Validation against buoy measurements indicates that the approach is almost unbiased and has an overall root mean square error of 1.24 m s-1, which is 5.3% lower than the single-parameter algorithm in operational use(Witter and Chelton, 1991) and 2.4% lower than another dual-frequency approach(Chen et al., 2002). Furthermore, the results indicate that the new approach significantly improves the wave-dependent bias compared to the single-parameter algorithm. The capacity of altimeter to retrieve sea surface wind speed appears to be limited for the case of winds below 3 m s-1. The validity of the approach at high winds needs to be further examined in the future study.

关键词： altimeter mean square slope dual-frequency wind speed retrieval

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Stabilities and Dynamics of Protein Folding Nuclei by Molecular Dynamics Simulation

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Communications in Theoretical Physics 2017年第7期67卷 137-148页

作者： Yong-Shun Song Xin zhou Wei-mou Zheng Yan-Ting wang School of Physical Sciences University of Chinese Academy of Sciences Beijing 100049 China Key Laboratory of Theoretical Physics Institute of Theoretical Physics Chinese Academy of Sciences Beijing 100190 China

To understand how the stabilities of key nuclei fragments affect protein folding dynamics, we simulate by molecular dynamics （MD） simulation in aqueous solution four fragments cut out of a protein G, including one a-helix （seqB： KVFKQYAN）, two -turns （seqA： LNGKTLKG and seqC： YDDATKTF）, and one -strand （seqD： DGEWTYDD）. The Markov State Model clustering method combined with the coarse-grained conformation letters method are employed to analyze the data sampled from 2-#s equilibrium MD simulation trajectories. We find that seqA and seqB have more stable structures than their native structures which become metastable when cut out of the protein structure. As expected, seqD alone is flexible and does not have a stable structure. Throughout our simulations, the native structure of seqC is stable but cannot be reached if starting from a structure other than the native one, implying a funnel-shape free energy landscape of seqC in aqueous solution. All the above results suggest that different nuclei have different formation dynamics during protein folding, which may have a major contribution to the hierarchy of protein folding dynamics.

关键词： protein folding molecular dynamics simulation structure prediction

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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3124-3143页

作者： Yuanyuan wang Daidi Li Kaifei Xu Guoqing wang Feng Zhang International Research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi wang Mengke Zhao Dong Fu Meina wang Chao Han Zhongyue Lv Liang wang Jing Liu Stem Cell Clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem Cell and Precision Medicine DalianLiaoning ProvinceChina Institute(College)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo wang Tingli Yuan Tianjie Lyu Ling Zhang Meng wang Zhiying He Yongjun wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Relaxor behavior and superior ferroelectricity of Y_(2)O_(3)-doped(Ba_(0.98)Ca_(0.02))(Ti_(0.94)Sn_(0.04)Zr_(0.02))O_(3) lead-free ceramics

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Journal of Rare Earths 2022年第6期40卷 942-951,I0004页

作者： Sifan wang Qibin Liu Enpei Cai Fanghui mou An Xue College of Material and Metallurgy Guizhou UniversityGuiyang 550025China Key Laboratory for Modern Manufacturing Technology of Educational Ministry Guiyang 550025China

To upgrade the electric properties of lead-free piezoceramics,(1-x)(Ba_(0.98)Ca_(0.02)Ti_(0.94)Sn_(0.04)Zr_(0.02))O_(3)-xY_(2)O_(3)(abbreviated as(1-x)BCTSZ-xY,x=0 mol%,0.02 mol%,0.04 mol%,0.06 mol%,0.08 mol%and 0.1 mol%)ceramics were successfully synthesized by traditional solid-state sintering *** phase structure and microstructure of ceramics were investigated by X-ray diffraction(XRD),scanning electron microscopy(SEM)and piezoresponse force microscopyeramics(PFM).The electric properties of ceramics were researched through piezoelectric,dielectric and ferroelectric test *** results show that all samples have pure perovskite structure and favorable electric *** optimal electric properties which especially include superior ferroelectric properties are gained when Y_(2)O_(3)content is 0.06 mol%(d_(33)=419 pC/N,k_(p)=52%,T_(c)=89.5℃,ε_(r)=26900,tanδ=2.86%,P_(r)=14.41μC/cm^(2),Ec=1.8 kV/cm).Moreover,the temperature-dependent dielectricity of samples shows apparent relaxor behavior under different *** Curie-Weiss law further proves that all samples are typical relaxor ferroelectrics,and the relaxor degree of samples decreases with increase of Y_(2)O_(3)*** conclusion,Y_(2)O_(3)plays a significant role in enhancing electric properties of BCTSZ ceramics.

关键词： Lead-free ceramics Y2O_(3)doping Relaxor behavior Ferroelectric properties Rare earths

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Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda Zhang Weimin Yuan Zhixing Ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng wang Lei Yang Bing Zhang Chen Zhang Shuang-Nan Zhang Yonghe Zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong Li Bifang Liu Mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng wang Song wang Tinggui wang Zhongxiang wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian Zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai Dongwei Fan Ju Guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen Jiang Ge Jin Chengkui Li Junfei Li Longhui Li Maoshun Li Wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu Fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao wang Juan wang Lei wang Wenxin wang Yilong wang Yusa wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang Juan Zhang Mo Zhang Wenjie Zhang Zhen Zhang Zhen Zhang Ziliang Zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan zhou Yilin zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Sciences University of Chinese Academy of Sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Institute of Space Sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of Sciences Department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University Department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of Sciences Physics Department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas Department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory Department of Astronomy University of Cape Town Department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM Department of Astronomy Guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen Department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC Department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney Department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University Department of Astronomy University of Science and Technology School of Astronomy and Space Sciences University of Science and Technology of China Institute of Deep Space Sciences Deep Space Exploration Laboratory Department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

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