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Activation of parvalbumin interneurons in anterior cingulate cortex impairs observational fear

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

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Characterization of glutamatergic VTA neural population responses to aversive and rewarding conditioning in freely-moving mice

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Science Bulletin 2019年第16期64卷 1167-1178页

作者： Quentin Montardy Zheng Zhou Zhuogui Lei Xuemei Liu Pengyu Zeng Chen Chen Yuanming Liu Paula Sanz-Leon Kang Huang Liping Wang shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science Guangdong Provincial Key Laboratory of Brain Connectome and BehaviorCAS Center for Excellence in Brain Science and Intelligence TechnologyThe Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China School of Physics the University of SydneySydney 2006Australia Centre for Integrative Brain Function the University of SydneySydney 2006Australia Department of Biomedical Sciences City University of Hong KongTat Chee AvenueKowloonHong KongSAR 999077China

The Ventral Tegmental Area(VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic(VGluT2) neurons in these *** activation of VGluT2 soma evokes rewarding behaviors, while activation of their downstream projections evokes aversive behaviors. To facilitate our understanding of these conflicting properties, we recorded calcium signals from VTAVGluT2+ neurons using fiber photometry in VGluT2-cre mice to investigate how this population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. To help understand these differences based on VTAVGluT2+ neuronal networks, the inputs and outputs of VTAVGluT2+ neurons were investigated using Cholera Toxin B(CTB) and rabies virus. Based on our results, we propose that the divergent VTAVGluT2+ neuronal responses to aversion and reward conditioning may be partly due to the existence of VTAVGluT2+ subpopulations that are characterized by their connectivity.

关键词： Ventral Tegmental Area Aversion Reward Conditioning Behavior

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Chemical proteomic profiling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin

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Chinese Chemical Letters 2023年第12期34卷 486-491页

作者： Peng Gao Jiayun Chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang Chen Wang Yin Kwan Wong Yinhua Zhu Chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Pharmaceutical College Henan University Shandong Academy of Chinese Medicine Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and Technology

Present research on the antimalarial mechanisms of artemisinin(ART) is mainly focused on covalent drug binding targets alkylated by free radicals, while non-covalent binding targets have rarely been ***, we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics. The results demonstrated that ART can bind to parasite proteins by both covalent and non-covalent modification, and these may jointly contribute to the antimalarial effects. Our work enriches the research on the antimalarial targets of ART, and provides a new perspective for further exploring the antimalarial mechanism of ART.

关键词： Artemisinin Antimalarial Chemical proteomic Target identification Photoaffinity probe

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Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma

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Asian Journal of Pharmaceutical Sciences 2023年第6期18卷 157-174页

作者： Piao Luo Qian Zhang Shuo Shen Yehai An Lixia Yuan Yin-Kwan Wong Sizhe Huang Shaohui Huang Jingnan Huang Guangqing Cheng Jiahang Tian Yu Chena Xiaoyong Zhang Weiguang Li Songqi He Jigang Wang Qingfeng Du School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Biological Sciences National University of SingaporeSingapore 117543Singapore Department of Nephrology Shenzhen key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People’s HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Health Technology and Informatics The Hong Kong Polytechnic UniversityHong Kong 100872China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China

Hepatocellular carcinoma(HCC)is one of most common and deadliest ***(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting ***,its clinical application has been hindered by the unclear mechanism of ***,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in *** demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)*** further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC ***,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side *** has been shown to effectively suppress the proliferation of tumor *** a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted *** findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side ***,Cel shows promise as a therapeutic agent for HCC.

关键词： Celastrol VDAC2 Ferroptosis Apoptosis Hepatocellular carcinoma Liposomes

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Bimeron clusters in chiral antiferromagnets

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npj Computational Materials 2020年第1期6卷 270-278页

作者： Xiaoguang Li Laichuan Shen Yuhao Bai Junlin Wang Xichao Zhang Jing Xia Motohiko Ezawa Oleg A.Tretiakov Xiaohong Xu Michal Mruczkiewicz Maciej Krawczyk Yongbing Xu Richard F.L.Evans Roy W.C.hantrell Yan Zhou School of Science and Engineering The Chinese University of Hong Kong518172 ShenzhenChina Hefei National Laboratory for Physical Sciences at the Microscale Department of PhysicsUniversity of Science and Technology of China230026 HefeiChina Research Institute of Materials Science of Shanxi Normal University&Collaborative Innovation Center for Shanxi Advanced Permanent Magnetic Materials and Technology 041004 LinfenChina School of Physics and Electronic Information Shanxi Normal University041004 LinfenChina Department of Physics University of YorkYork YO105DDUK York-Nanjing International Center of Spintronics(YNICS) Nanjing University210093 NanjingChina Department of Applied Physics The University of Tokyo7-3-1 HongoTokyo 113-8656Japan School of Physics The University of New South WalesSydney 2052Australia National University of Science and Technology‘MISiS’ Moscow 119049Russia School of Chemistry and Materials Science of Shanxi Normal University&Key Laboratory of Magnetic Molecules and Magnetic Information Materials of Ministry of Education 041004 LinfenChina Institute of Electrical Engineering Slovak Academy of SciencesDúbravskácesta 984104 BratislavaSlovakia Centre for Advanced Materials Application CEMEA Slovak Academy of SciencesDúbravskácesta 5807/984511 BratislavaSlovakia Faculty of Physics Adam Mickiewicz University in PoznanUniwersytetu Poznanskiego 261-614 PoznanPoland

A magnetic bimeron is an in-plane topological counterpart of a magnetic *** the topological equivalence,their statics and dynamics could be distinct,making them attractive from the perspectives of both physics and spintronic *** this work,we demonstrate the stabilization of bimeron solitons and clusters in the antiferromagnetic(AFM)thin film with interfacial Dzyaloshinskii–Moriya interaction(DMI).Bimerons demonstrate high current-driven mobility as generic AFM solitons,while featuring anisotropic and relativistic dynamics excited by currents with in-plane and out-ofplane polarizations,***,these spin textures can absorb other bimeron solitons or clusters along the translational direction to acquire a wide range of Néel topological *** clustering involves the rearrangement of topological structures,and gives rise to remarkable changes in static and dynamical *** merits of AFM bimeron clusters reveal a potential path to unify multibit data creation,transmission,storage,and even topology-based computation within the same material system,and may stimulate spintronic devices enabling innovative paradigms of data manipulations.

关键词： properties topological clusters

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Chemical proteomic profling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin

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Chinese Chemical Letters 2023年第12期34卷 460-465页

作者： Peng Gao Jiayun Chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang Chen Wang Yin Kwan Wong Yinhua Zhu Chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Pharmaceutical College Henan UniversityKaifeng 475004China Shandong Academy of Chinese Medicine Ji'nan 250014China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Afiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China

Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been ***,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical *** results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial *** work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART.

关键词： Artemisinin Antimalarial Chemical proteomic Target identification Photoaffinity probe

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