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Activation of parvalbumin interneurons in anterior cingulate cortex impairs observational fear

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Science Bulletin 2018年第12期63卷 771-778页

作者： Chunran Zhou Zheng Zhou Yushui Han Zhuogui Lei Lei Li Quentin Montardy xuemei Liu fuqiang xu Liping Wang Shenzhen Key Laboratory of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science.Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Center for Excellence in Brain Science and Intelligence TechnologyThe Brain Cognition and Brain Disease Institute(BCBDI).Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049.China Southern Medical University Guangzhou 510168China Center for Brain Science Key Laboratory of Magnetic Resonance in Biological Systems and State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsWuhan institute of Physics and MathematicsCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesWuhan 430071China

The ability to detect conspecific＇s distress is crucial for animal survival. In rodent models, observational fear （OF） occurs when one animal perceives another fear related negative emotions, which may model certain behaviors caused by witnessing traumatic experiences in humans. Anterior cingulate cortex （ACC） has been showed to play a crucial role in OF. However, cellular and neural circuit basis relating to ACC governing OF is poorly understood. Here, we used Designer Receptor Exclusively Activated by a Designer Drug （DREADD） system to investigate the cell type specific circuit mechanism of ACC in OF. Firstly, inhibitory hM4D （Gi） designer receptor together with clozapine N-oxide （CNO） injection was applied to inactivate ACC neurons in the observer mice. We found that, chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice. Next, combining PV-ires-Cre mice and Cre-dependent DREADD system, we selectively targeted the ACC parvalbumin （PV） interneurons with the excitatory hM3D （Gq） designer receptor. Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice, while had no effect on freezing response in the demon- strator mice. Finally, monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus （MD） and the ventromedial thalamic nucleus （VM）, both known for their roles in OF. Taken together, these findings reveal that ACC activation is important for OF, during which PV interneurons in ACC play an important regulatory role. Abnormal function of ACC PV interneurons might contribute to the pathology of empathy- deficits related diseases, such as autism and schizoohrenia.

关键词： Observational fear learning Anterior cingulate cortex PV interneurons Empathy

脉冲等离子体射流摩尔质量对其扩展特性的影响

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沈阳理工大学学报 2024年第5期43卷 63-68,76页

作者：徐付强岳明凯车龙董朋超权康男沈阳理工大学装备工程学院沈阳110159

脉冲等离子体射流特性是电热化学发射技术研究的重要内容。依据实验研究结果,采用Fluent软件中的VOF多相流模型对脉冲等离子体射流在大气中的扩展过程进行模拟,研究脉冲等离子体射流在近流场中的扩展特性及摩尔质量对扩展特性的影响规... 详细信息

脉冲等离子体射流特性是电热化学发射技术研究的重要内容。依据实验研究结果,采用Fluent软件中的VOF多相流模型对脉冲等离子体射流在大气中的扩展过程进行模拟,研究脉冲等离子体射流在近流场中的扩展特性及摩尔质量对扩展特性的影响规律。结果表明:仿真结果与实验数值基本吻合,射流形态和激波结构与等离子体射流图像基本相符,建立的模型比较可靠;摩尔质量越大,等离子体射流发展越迟缓,头部压力峰轴向位移越滞后,扩展初期的高温聚集区宽高比越大,射流的轴向扩展位移、速度以及掺混程度越小。本文研究结果可为电热化学发射技术及毛细管消融控制的相关研究提供参考。

关键词：等离子体射流 VOF模型扩展特性摩尔质量

Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Science China Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong xu Qiaochu Jiang Hai-Dong xu fuqiang Wang Gaolin Liang State Key Laboratory of Digital Medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis Center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

Mutation inε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice

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Neuroscience Bulletin 2021年第3期37卷 311-322页

作者： Jiao Li Yiqiong Liu Qin Li Xiaolin Huang Dingxi Zhou Hanjian xu Feng Zhao Xiaoxiao Mi Ruoxu Wang Fan Jia fuqiang xu Jing Yang Dong Liu xuliang Deng Yan Zhang State Key Laboratory of Membrane Biology College of Life SciencesPKU-IDG/McGovern Institute for Brain ResearchDepartment of Geriatric DentistryPeking University School and Hospital of StomatologyPeking UniversityBeijing 100871China Wuhan Institute of Physics and Mathematics Chinese Academy of SciencesWuhan 430071China College of Life Sciences Wuhan UniversityWuhan 430027China

Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding *** generating SGCE-knockout(KO)and human 237 C>T mutation knock-in(KI)mice,we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS *** promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in *** of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS ***,using a zebrafish MDS model,we found that among 1700 screened chemical compounds,Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease *** study strengthens the notion that mutations of SGCE lead to MDS and most likely,SGCE functions to brake synaptogenesis in the CNS.

关键词： SGCE MDS Filopodia Synapse Excitability

Microstructure evolution and phase transformation of the mushy zone in a quenchedβ-solidifying TiAl alloy

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Journal of Materials Science & Technology 2024年第2期169卷 28-41页

作者： fuqiang Zhang Xianfei Ding Leming xu Xin Feng Hai Nan Jianping He Yongfeng Liang Junpin Lin State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China Cast Titanium Alloy R&D Center Beijing Institute of Aeronautical MaterialsBeijing 100095China

This study investigates the phase constitutions and transformations that occur in the mushy zone and in the adjacent phase fields of a directionally solidified Ti-44Al-8Nb-1Cr alloy via quenching *** results indicate that the mushy zone consists of unmeltedβdendrites and interdendritic liquid,whose formation can be attributed to the difference in melting point aroused by local heterogeneity in ***βdendrite is composed of numerous subgrains with various *** quenching,theβdendrite transforms into Widmanstättenαvia a precipitation reaction,owing to the decreasing cooling rate caused by heat transfer from the surrounding ***,after quenching,the interdendritic liquid is transformed intoγ*** the singleβphase field and the lower part of the mushy zone,a massive transformation ofβtoγ***,in theβ+αphase field,bothβandαphases are retained to ambient *** the heating process,the transformation ofα→βgives rise to the formation ofβvariants,which affects the orientation ofβdendrites in the mushy *** growth kinematics of theα→βtransformation was elucidated,revealing the preferential growth directions of111and112forβ***,this study presents an illustration of the formation process of the mushy zone and the microstructural evolution during the heating and quenching process.

关键词： Titanium aluminides Mushy zone Quenching Electron backscattering diffraction Phase transformation

A double-layer radiative cooling coating that utilizes the refractive index difference between layers to achieve extremely high solar reflectivity

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Science China Technological Sciences 2024年第10期67卷 3182-3189页

作者： WANG fuqiang LI ChunZhe YANG ZhenNing XIE WeiXin LI Xiang xu ZengHui YAN YuYing CHENG ZiMing School of Energy Science and Engineering Harbin Institute of Technology School of New Energy Harbin Institute of Technology at Weihai China Construction Eco-Environmental Protection Technology Co. Ltd. Faculty of Engineering University of Nottingham

Passive daytime radiative cooling（PDRC） technology has great potential in reducing cooling energy consumption. In order to further improve the spectral performance of PDRC coatings, current researchers mostly focus on the selection and size design of functional particles, while ignoring the optical properties enhancement effect caused by the interlayer binder. In this study, based on the principle that the refractive index difference between layers enhanced the backscattering performance of the solar spectrum, we proposed and manufactured a double-layer PDRC coating with polyvinylidene difluoride（PVDF） as the filmforming material in the upper layer and polydimethylsiloxane（PDMS） as the film-forming material in the lower layer, both filled with Al2O3and SiO2particles. The double-layer PDRC coating exhibited excellent spectral performance that a high solar reflectivity of 98% and an emissivity of 0.95 at the “atmospheric window” band. In comparison, the solar spectrum reflectivity of the single-layer PDRC coatings based on PVDF and PDMS of the same thickness was 95% and 94.7%, respectively. Outdoor tests showed that the PDRC coating achieved a temperature decrease of up to 7.1℃ under direct sunlight at noon time. In addition, the PDRC coating had excellent weather resistance, water resistance, and other basic properties. This article opens up a new idea and provides methodological guidance for the design of double-layer PDRC coatings.

关键词： double-layer radiative cooling coating spectral modulation interlayer refractive index solar energy radiative transfer

Divergent Projection Patterns Revealed by Reconstruction of Individual Neurons in Orbitofrontal Cortex

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Neuroscience Bulletin 2021年第4期37卷 461-477页

作者： Junjun Wang Pei Sun Xiaohua Lv Sen Jin Anan Li Jianxia Kuang Ning Li Yadong Gang Rui Guo Shaoqun Zeng fuqiang xu Yu-Hui Zhang Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and TechnologyWuhan430074China MoE Key Laboratory for Biomedical Photonics School of Engineering SciencesHuazhong University of Science and TechnologyWuhan430074China Centre for Brain Science State Key Laboratory of Magnetic Resonance and Atomic Molecular PhysicsKey Laboratory of Magnetic Resonance in Biological SystemsWuhan Institute of Physics and MathematicsCAS Centre for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesWuhan430071China

The orbitofrontal cortex(OFC)is involved in diverse brain functions via its extensive projections to multiple target *** is a growing understanding of the overall outputs of the OFC at the population level,but reports of the projection patterns of individual OFC neurons across different cortical layers remain ***,by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system(fMOST),we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal *** compared the wholebrain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical *** found cortical layer-dependent projections characterized by divergent patterns for information *** study not only provides a structural basis for understanding the principles of laminar organizations in the OFC,but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

关键词： Orbitofrontal cortex Whole-brain imaging Morphological reconstruction Output Projection pattern

Regional Metabolic Patterns of Abnormal Postoperative Behavioral Performance in Aged Mice Assessed by XH-NMR Dynamic Mapping Method

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Neuroscience Bulletin 2020年第5期36卷 25-38页

作者： Taotao Liu Zhengqian Li Jindan He Ning Yang Dengyang Han Yue Li xuebi Tian Huili Liu Anne Manyande Hongbing Xiang fuqiang xu Jie Wang Xiangyang Guo Department of Anesthesiology Peking University Third HospitalBeijing 100191China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsWuhan Institute of Physics and MathematicsChinese Academy of SciencesWuhan 430071China Department of Anesthesiology and Pain Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Human and Social Sciences University of West LondonMiddlesex TW89GAUK University of Chinese Academy of Sciences Beijing 100049China The Second Hospital of Shijiazhuang Shijiazhuang 050051China

Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative *** disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to *** dynamic changes of metabolites in different brain regions after anesthesia and surgery,as well as their potential association with APNP are still not well ***,we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice,and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance('H-NMR)*** abnormal neurobehavioral performance occurred at 6 h and/or 9 h,and recovered at 24 h after anesthesia/*** with the control group,the altered metabolite of the model group at 6 h was aspartate(Asp),and the difference was mainly displayed in the cortex;while significant changes at 9 h occurred predominantly in the cortex and hippocampus,and the corresponding metabolites were Asp and glutamate(Glu).All changes returned to baseline at 24 *** altered metabolic changes could have occurred as a result of the acute APNP,and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.

关键词： Abnormal postoperative neurobehavioral performance 1H-NMR Metabolite Aspartate Glutamate

Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 120-135页

作者： Xiaomei Wu Renxiang Yuan Yichong xu Kai Wang Hong Yuan Tingting Meng fuqiang Hu Department of Pharmacy Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

关键词： Blood-brain barrier Lipid nanoparticles Brain delivery facilitation α-Symuclein Parkinson's disease