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Science China(Life Sciences) 2020年第1期63卷 59-67页

作者： Jia Li Hong-Yu Li shan-ye gu Hua-Xing Zi Lai Jiang Jiu-Lin Du Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyShanghai Research Center for Brain Science and Brain-Inspired IntelligenceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Department of Anesthesiology and Surgical Intensive Care Unit Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China School of Life Science and Technology Shanghai Tech UniversityShanghai 200031China

The zebrafish has become a popular vertebrate animal model in biomedical ***,it is still challenging to make conditional gene knockout(CKO)models in zebrafish due to the low efficiency of homologous recombination(HR).Here we report an efficient non-HR-based method for generating zebrafish carrying a CKO and knockin(KI)switch(zCKOIS)coupled with dual-color fluorescent *** this strategy,we generated hey2^zCKOIS which served as a hey2 KI reporter with EGFP *** Cre induction in targeted cells,the hey2^zCKOIS was switched to a non-functional CKO allele hey2^zCKOIS-inv associated with Tag RFP expression,enabling visualization of the CKO ***,simplification of the design,and the visibility and combination of both CKO and KI alleles make our z CKOIS strategy an applicable CKO approach for zebrafish.

关键词： NHEJ non-HR knockin conditional knockout visible switch zCKOIS zebrafish

Neuronal miR-132 regulates the integrity of brain vasculature via eEF2K in zebrafish

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Neuronal miR-132 regulates the integrity of brain vasculatur...

中国神经科学学会第十届全国学术会议

作者： Bing XU Yu ZHANG Xu-Fei DU shan-ye gu Jiu-Lin DU Institute of Neuroscience and State Key Laboratory of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences

The blood-brain barrier（BBB） maintains a stable microenvironment for neural *** disruption causes leakage of blood-borne factors and cells into the brain,leading to the damage of neural *** mechanisms underlying the BBB formation remain largely *** the present study,we find that microRNA-132（miR-132）,a neuron-enriched microRNA,is required for the integrity of zebrafish brain vasculature during *** of miR-132 in zebrafish with miR-132 morpholino results in severe intracranial hemorrhage,and a lot of blood cells are accumulated in the brain ventricles and even brain ***,the defects can be mimicked by specific knockdown of miR-132 in neurons with miR-132 sponge,indicating that neuronal miR-132 is necessary for brain vessel *** cell cultures,we further find that miR-132 can be transferred from neurons into endothelial cells via ***,miR-132 targets eukaryotic elongation factor 2 kinase（eEF2k） to regulate the expression of VE-cadherin,which is important for blood vessel ***,our findings demonstrate that neuronal miR-132 can regulate the development of brain vessel integrity via a cell-cell communication process.

关键词： microRNA-132 blood-brain barrier integrity vessel VE-cadherin zebrafish

Neuronal NMDA receptors regulate brain vascular development in zebrafish

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Neuronal NMDA receptors regulate brain vascular development ...

中国神经科学学会第十届全国学术会议

作者： shan-ye gu Ting-Ting LIU Rong-Wei ZHANG Qi CHEN Bing XU Jiu-Lin DU Institute of Neuroscience and State Key Laboratory of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences

Brain blood vasculature is critical for brain development and *** embryogenesis and early hfe,the nervous and vascular systems simultaneously develop and *** and how the nervous system regulates brain angiogenesis during development remain largely *** we reveal that neuronal NMDA receptors（NRs）can regulate brain vascular development via controlling VEGFA release in *** genetic downregulation or pharmacological blockade of NRs dramatically decreases brain angiogenesis during 4-7 days post-fertilization,meanwhile NR activation increases the *** effect requires neuronal NRs,because specific impairment of NRs in neurons but not endothelial cells leads to brain angiogenic defects,and the effect of global downregulation of NRs can be rescued by NR overexpression in *** neuronal NR action is mainly mediated by VEGFA,because NR downregulation reduces VEGFA synthesis and VEGFA overexpression in neurons can rescue the effect of NR ***,we find that neural activity can efficiently regulate brain angiogenesis mainly through ***,being detectors of neural activity,neuronal NRs can regulate brain vascular development via VEGFA signaling.

关键词： brain angiogenesis NMDA receptor VEGFA neural activity zebrafish

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu shan ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Long-term synaptic potentiation in developing zebrafish retinae in vivo

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Long-term synaptic potentiation in developing zebrafish reti...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Hong-Ping WEI Yuan-Yuan YAO Xu-Fei DU shan-ye gu Jiu-Lin DU~* Laboratory of Sensory Integration and Behavior Institute of Neuroscience Chinese Academy of Science shanghai 200031 China

＜正＞Neural activity-dependent long-term potentiation（LTP） of synaptic transmission is believed to be a cellular basis of learning/memory and experience-dependent refinement of neural *** LTP has been reported in nearly all brain regions examined,it is unknown whether it also exists in peripheral sensory *** here report that electrical activity can induce LTP of ribbon synapses formed by bipolar cells（BCs） on retinal ganglion cells（RGCs） in intact retinae of zebrafish *** in vivo whole-cell perforated-patch recording from RGCs,we found that brief theta burst stimulation（TBS） of the inner nuclear layer resulted in persistent increase in the amplitude of excitatory postsynaptic currents（EPSCs） for up to 45 min,an effect that required the depolarization but not spiking of RGCs and the activation of postsynaptic N-methyl-D-aspartate subtype of the glutamate receptors（NMDARs）.Furthermore,repetitive light stimulation of the retina also resulted in a persistent increase in light-induced RGC ***,TBS-induced LTP of these synapses is functionally important because it enhances light-evoked synaptic responses in ***,activity-dependent long-term synaptic plasticity exists in the developing retina and may contribute to sensory experience-dependent refinement of neural circuits.

关键词： LTP EPSC retinal ganglion cell zebrafish

Characterization of brain angiogenesis in zebrafish larvae

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Characterization of brain angiogenesis in zebrafish larvae

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： shan-ye gu,Bing XU,Yu-Han guO,Jiu-Lin DU~* Institute of Neuroscience and State Key Laboratory of Neuroscience,shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,shanghai 200031,China

＜正＞Objective Brain development is supported by concomitant development of brain *** notions of CNS vascularization suggest that blood vessels penetrate passively into brain parenchyma from pial vascular plexuses for meeting metabolic needs of growing neural *** still remains elusive how the brain vasculature forms. Methods In the present study,we characterized the 3-D midbrain vasculature pattern formation during development using in vivo time-lapse confocal imaging of transgenic zebrafish larvae,of which blood endothelial cells express *** We found that midbrain angiogenic sprouts emanated from the bilateral choroidal vascular plexuses, elongated dorsally,and targeted to the mesencephalic central artery at the midline during 2-5 days post-fertilization （dpf）.During later stages,some vessels sprouted from the pial vessels,grew ventrally and anatomosed with the mesencephalic central ***,stereotyped expression patterns of semaphrin 3E and wnt3 were required for this pattern formation of brain *** experiments are being performed to examine its detailed molecular mechanisms.

关键词： brain angiogenesis vasculature semaphrin 3E wnt 3

Synthesis and Characterization ofN-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-thiocarbamic-4-hydroxy-benzoyl Hydrazine Dihydrate

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Chemical Research in Chinese Universities 2005年第5期21卷 545-548页

作者： ZHANG Shu-sheng ye Su-juan LI Xue-mei gu shan-shan LIU Qing College of Chemistry and Molecular Engineering Qingdao University of Science and Technology Qingdao 266042 P. R. China

A new complex of N-（ 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl ） -thiocarbamic 4-hydroxy-benzoyl hydrazine dihydrate, C22 H27 N3 O10S · 2H2 O, was synthesized and its structure was determined by X-ray crystallography and TG/DTG methods. The compound belongs to the orthorhombic system, which crystallizes in space group P212121 , with a = 1. 0275 （ 3 ）, b = 1. 3419 （4）, c = 2. 0234 （ 6 ）, V = 2. 7899 （ 16 ） nm^3, and Z = 4. The hexopyranosyl ring adopts a ^4C1 conformation. All the substituents are at equatorial positions. The molecules are linked into a three-dimensional framework via intermolecular interactions. Atoms O5 and O9 show oositional disorders.

关键词： N-(2,3,4,6-Tetra-O-aeetyl-β-D-glueopyranose Synthesis Crystal structure Characterization

A Three-Dimensional DEM Method for Trajectory Simulations of Rockfall under Irregular-Shaped Slope Surface and Rock Blocks

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Journal of Earth Science 2024年第1期35卷 306-312页

作者： Liang Chen Weiqian Zeng Xianbiao Wang Yang ye Yunfeng Ge Dongming gu shan Dong Huadong Engineering Corporation Limited Fuzhou 350003China Faculty of Engineering China University of GeosciencesWuhan 430074China Badong National Observation and Research Station of Geohazards China University of GeosciencesWuhan 430074China

0 *** is a common geological hazard that poses a serious threat to residents and infrastructures(Gao et al.,2022;ye et al.,2022).The precise prediction of rockfall trajectories is essential to the design of protection engineering structures of rockfall(Ma et al.,2021).The discrete element modelling(DEM)is increasingly used to analyse rockfall movement *** et al.(2022)used Rockyfor3D software to obtain the possible trajectory of falling rock blocks.

关键词： rock prediction hazard

Synthesis of Iminosugar-Containing KRN7000 Analogues

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Chinese Journal of Chemistry 2017年第6期35卷 1001-1008页

作者： LeiZhang Xin-shan ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Xue Yuan Road No. 38 Beijing 100191 China

Three new iminosugar-containing KRN7000 （also referred to as α-GalCer） analogues were designed and syn- thesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar struc- tures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifica- tions. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRNT000 derivatives.

关键词： KRN7000 analogue glycolipid a-GalCer iminosugar synthesis

Donor Preactivation-Based Glycosylation:An Efficient Strategy for Glycan Synthesis

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Chinese Journal of Chemistry 2021年第3期39卷 531-542页

作者： Xianjin Qin Xin-shan ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityXue Yuan Road No.38Beijing 100191China

Carbohydrates have gained a lot of appreciation in the past few decades due to their important roles in numerous biological *** a structurally well-defined carbohydrate compound is essential for the understanding of its *** some innovative methods have been developed for the synthesis of complex oligosaccharides,glycan synthesis is in general still a time-consuming and difficult ***,we will introduce the preactivation-based glycosylation strategy,which is an efficient protocol independent of the reactivity of glycosyl *** review will focus on summarizing the versatile applications of preactivation strategy in stereoselective glycosylation and one-pot assembly of biologically important oligosaccharides and even polysaccharides。

关键词： Preactivation Chemoselectivity Glycosylation Carbohydrates Solvent effect Oligosaccharide synthesis