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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao jie tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen–Hong Kong Institute of Brain Science Shenzhen Institute of Advanced Technology Chinese Academy of Sciences CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced Technology Chinese Academy of Sciences University of Chinese of Academy of Sciences Faculty of Life and Health Sciences Shenzhen Institute of Advanced Technology Chinese Academy of Sciences

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration

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Controlling antifungal activity with light:Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

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药学学报:英文版 2023年第7期13卷 3080-3092页

作者： Zhuang Li Na Liu Wanzhen Yang jie tu Yahui Huang Wei Wang Chunquan Sheng State Key Laboratory of Bioengineering Reactor And Shanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science&TechnologyShanghai 200237China School of Pharmacy Second Military Medical University(Naval Medical University)Shanghai 200433China Department of Pharmacology and Toxicology College of PharmacyAnd BIO5 InstituteUniversity of ArizonaTucsonAZ 85721USA

Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

关键词： Antifungal agents Ergosterol biosynthesis Triazoles Photocaged Optical control

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Small molecules for combating multidrug-resistant superbug Candida auris infections

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4056-4074页

作者： jie tu Na Liu Yahui Huang Wanzhen Yang Chunquan Sheng School of Pharmacy Second Military Medical UniversityShanghai 200433China

Candida auris is emerging as a major global threat to human health. C. auris infections are associated with high mortality due to intrinsic multi-drug resistance. Currently, therapeutic options for the treatment of C. auris infections are rather limited. We aim to provide a comprehensive review of current strategies, drug candidates, and lead compounds in the discovery and development of novel therapeutic agents against C. auris. The drug resistance profiles and mechanisms are briefly summarized. The structures and activities of clinical candidates, drug combinations, antifungal chemosensitizers, repositioned drugs, new targets, and new types of compounds will be illustrated in detail, and perspectives for guiding future research will be provided. We hope that this review will be helpful to prompting the drug development process to combat this fungal pathogen.

关键词： Candidaauris Antifungal agents Drug resistance Virulence factors Antifungal targets

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Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice

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Neuroscience Bulletin 2021年第9期37卷 1325-1338页

作者： Xinyi Zhou Bifeng Wu Wenhao Liu Qian Xiao Wei He Ying Zhou Pengfei Wei Xu Zhang Yue Liu jie Wang Jufang He Zhigang Zhang Weidong Li Liping Wang jie tu Guangdong Provincial Key Laboratory of Brain Connectome and Behavior CAS Key Laboratory of Brain Connectome and Manipulationthe Brain Cognition and Brain Disease InstituteShenzhen-Hong Kong Institute of Brain ScienceShenzhen Fundamental Research InstitutionsShenzhen Institute of Advanced TechnologyChinese Academy of Sciences518055 ShenzhenChina University of Chinese of Academy of Sciences Beijing 100049China Department of Information Technology and Electrical Engineering Zurich Swiss Federal Institute of Technology Zurich8092 ZurichSwitzerland Department of Biomedical Sciences City University of Hong KongKowloon TongHong Kong Virginia Polytechnic Institute and State University BlacksburgVirginia 24061USA Department of Psychiatry and Behavioral Sciences Emory University School of MedicineAtlanta 30322USA Bio-X Institutes Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders(Ministry of Education)Shanghai Key Laboratory of Psychotic Disordersand Brain Science and Technology Research CenterShanghai Jiao Tong UniversityShanghai 200240China Center of Brain Science State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsInnovation Academy for Precision Measurement Science and TechnologyNational Center for Magnetic Resonance in WuhanKey Laboratory of Magnetic Resonance in Biological SystemsWuhan Institute of Physics and MathematicsChinese Academy of Sciences430071 WuhanChina Department of Neuroscience City University of Hong KongKowloon TongHong Kong City University of Hong Kong Shenzhen Research Institute Shenzhen 518057China

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.

关键词： DISC1 Risk avoidance Parvalbumin Nucleus accumbens

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基于压力相关的城市供水管网漏失预警研究

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水电能源科学 2024年第1期42卷 139-143页

作者：涂杰刘文睿丁祥吴芬芬中冶南方工程技术有限公司湖北武汉430223 中国市政工程华北设计研究总院有限公司天津300074 长安大学基建处陕西西安710064 中国市政工程西北设计研究院有限公司甘肃兰州730099

近年来极端天气频发,加之我国大部分城市长期存在严重的缺水问题,因此为节约有限的淡水资源,及时发现城市供水管网漏失事故十分必要。首先通过某市供水管网历史压力数据分析了正常运行工况下的压力数据特征;然后探讨了当供水管网发生漏... 详细信息

近年来极端天气频发,加之我国大部分城市长期存在严重的缺水问题,因此为节约有限的淡水资源,及时发现城市供水管网漏失事故十分必要。首先通过某市供水管网历史压力数据分析了正常运行工况下的压力数据特征;然后探讨了当供水管网发生漏失事故时影响漏失点压力变化的因素,并利用FLUENT流体模拟软件进行仿真模拟验证;最后在各种工况压力变化规律的基础上建立了供水管网压力波动阈,当监测压力值超出压力波动阈,综合考虑压力监测点单一时刻的压力波动程度及一个时间周期内的压力变化趋势等多方面的因素,来预警供水管网是否发生漏失事故,并以某市供水管网为例,验证了所提漏失预警方法有效、可行。

关键词：仿真模拟供水管网压力波动漏失预警

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苯并[a]芘和慢性压力应激暴露对小鼠肝脏代谢的影响

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环境化学 2024年第1期43卷 60-68页

作者：于景娜谢丽陈志宇钟慧芳屠洁李芳杨甲甲罗茜河北工程大学材料科学与工程学院邯郸056038 中国科学院深圳先进技术研究院深圳518055 中国科学院大学北京100049

环境污染和慢性压力是影响人类健康的两大类常见风险因子,本研究通过表征苯[a]并芘(benzo[a]pyrene,B[a]P)与慢性压力应激(chronic unpredictable mild stimulation,CUMS刺激)暴露对小鼠肝脏代谢的影响,并探讨了同时暴露时两大风险因子... 详细信息

环境污染和慢性压力是影响人类健康的两大类常见风险因子,本研究通过表征苯[a]并芘(benzo[a]pyrene,B[a]P)与慢性压力应激(chronic unpredictable mild stimulation,CUMS刺激)暴露对小鼠肝脏代谢的影响,并探讨了同时暴露时两大风险因子之间潜在的相互作用.采用靶向代谢组学结合多元统计学方法分析了两个剂量B[a]P(2.0 mg·kg^(-1)·d^(-1)和20.0 mg·kg^(-1)·d^(-1))与CUMS刺激单独或联合暴露21 d后,雄性C57BL/6J小鼠肝脏中氨基酸代谢、TCA循环和胆汁酸代谢的变化.研究发现,2.0 mg·kg^(-1)·d^(-1)B[a]P可使小鼠肝脏中精氨琥珀酸、精氨酸和丙氨酸显著升高,谷氨酰胺显著降低;20.0 mg·kg^(-1)·d^(-1)B[a]P则主要导致丙氨酸显著上升,谷氨酰胺下降.慢性压力应激使小鼠肝脏同型半胱氨酸的含量显著下降. B[a]P与慢性压力应激同时暴露时,小鼠肝脏氨基酸和胆汁酸代谢会发生显著变化.进一步采用代谢扰乱度(metabolic effect level index,MELI)评估了两个风险因子的联合作用效果,发现2.0 mg·kg^(-1)·d^(-1)B[a]P和慢性压力应激同时暴露对小鼠氨基酸代谢、TCA循环和胆汁酸代谢的影响分别为拮抗、协同和加和作用;而20 mg·kg^(-1)·d^(-1) B[a]P和慢性压力应激同时暴露的小鼠氨基酸代谢和胆汁酸代谢的影响均为加和作用,TCA循环为拮抗作用.结果表明,不同剂量的B[a]P和CUMS暴露造成小鼠肝脏氨基酸代谢和胆汁酸代谢紊乱,差异的代谢物与两者单独暴露时明显不同,且代谢的变化与B[a]P暴露剂量密切相关.

关键词：苯并[a]芘慢性压力应激暴露组学小鼠肝脏代谢组学

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液压劈裂静态爆破在石方破碎施工中的应用研究

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价值工程 2024年第1期43卷 122-124页

作者：黄图杰曾云峰王鑫潘富远广西路建工程集团有限公司南宁530001

文章以钦州市灵山县某段在建高速公路为工程实例,通过对花岗岩球形风化体分布特点的路基石方段开挖比选不同的爆破施工工艺,然后采用液压劈裂静态爆破施工工艺进行应用研究,并对其设计了施工参数,最后通过现场施工验证了液压劈裂静态爆... 详细信息

文章以钦州市灵山县某段在建高速公路为工程实例,通过对花岗岩球形风化体分布特点的路基石方段开挖比选不同的爆破施工工艺,然后采用液压劈裂静态爆破施工工艺进行应用研究,并对其设计了施工参数,最后通过现场施工验证了液压劈裂静态爆破施工工艺的合理性。

关键词：花岗岩液压劈裂静态爆破

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Assessment of the Characteristics of Demersal Fish Communities Using Species-and Trait-Based Approaches in the Coastal Habitats Along Rongcheng Bay,Shandong Peninsula,China

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Journal of Ocean University of China 2024年第3期23卷 786-796页

作者： YUAN Shunjie SUN Xin tu Zhong SUN jie WANG Xianning ZHANG Peidong Key Laboratory of Mariculture(Ocean University of China Ministry of EducationQingdao 266003China Shandong Fisheries Development and Resource Conservation Center Yantai 264003China

Biodiversity declines have motivated many studies on the relationship between species diversity and ecosystem functioning.In this study,we described the spatial-temporal characteristics of demersal fish communities along a coastal habitat in Rongcheng Bay,Shandong Peninsula,China with both species-based and biological trait-based approaches.The field survey was carried out monthly using traps from April to October of 2018,and divided into three seasons(spring:April and May;summer:June,July and August;autumn:September,October and November).The study area included five distinct habitats:seagrass bed,natural rocky reef,bare sand,artificial reef together with natural rocky reef,and artificial reef together with bare sand.We analyzed the fish communities with three taxonomic diversity indices,including Shannon-Wiener,Simpson,and Pielou Evenness,as well as four functional diversity indices,including FRic,FEve,FDiv,and FDis,based on 7 functional groups which are categorized into 27 traits.The results showed that there were no significant differences in taxonomic diversity indices among different habitats in the three seasons.However,significant differences were found in the functional richness of fish communities among different habitats in three seasons.Seagrass bed represented the highest functional richness in spring and autumn.This study demonstrates that seagrass bed is very important in enhancing the functional diversity of fish communities in a complex habitat.The study also indicates that the combination of taxonomic diversity and functional diversity will provide a more detailed description of the characteristics of fish communities.

关键词： complex habitat biological traits biodiversity fish communities

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Antioxidant and Anti-aging Activities of Silybum Marianum Protein Hydrolysate in Mice Treated with D-galactose

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Biomedical and Environmental Sciences 2017年第9期30卷 623-631页

作者： ZHU Shu Yun JIANG Ning tu jie YANG Jing ZHOU Yue School of Food and Biological Engineering Jiangsu UniversityZhenjiang 212013JiangsuChina JiangsuHengshun Group Co.Ltd. Zhenjiang 212000JiangsuChina Institute of Vegetables Jiangsu Academy ofAgricultural SciencesNanjing 210014JiangsuChina College of Biotechnology Jiangsu University of Scienceand TechnologyZhenjiang 212018JiangsuChina

Objective In the present study, we investigated the antioxidant and anti‐aging effects of Silybum marianum protein hydrolysate（SMPH） in D‐galactose‐treated mice. Methods D‐galactose（500 mg/kg body weight） was intraperitoneally injected daily for 7 weeks to accelerate aging, and SMPH（400, 800, 1,200 mg/kg body weight, respectively） was simultaneously administered orally. The antioxidant and anti‐aging effects of SMPH in the liver and brain were measured by biochemical assays. Transmission electron microscopy（TEM） was performed to study the ultrastructure of liver mitochondria. Results SMPH decreased triglyceride and cholesterol levels in the D‐galactose‐treated mice. It significantly elevated the activities of superoxide dismutase（SOD） and glutathione peroxidase（GSH‐Px）, and total antioxidant capacity（T‐AOC）, which were suppressed by D‐galactose. Monoamine oxidase（MAO） and malondialdehyde（MDA） levels as well as the concentrations of caspase‐3 and 8‐OHd G in the liver and brain were significantly reduced by SMPH. Moreover, it increased Bcl‐2 levels in the liver and brain. Furthermore, SMPH significantly attenuated D‐galactose‐induced liver mitochondrial dysfunction by improving the activities of Na＋‐K＋‐ATPase and Ca2＋‐Mg2＋‐ATPase as well as mitochondrial membrane potential（ΔΨm） and fluidity. TEM showed that the degree of liver mitochondrial damage was significantly decreased by SMPH. Conclusion The results indicated that SMPH protects against D‐galactose‐induced accelerated aging in mice through its antioxidant and anti‐aging activities.

关键词： Silybum marianum protein hydrolysate Antioxidant Anti‐aging D‐galactose

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食醋中γ-氨基丁酸的检测及变化规律研究

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食品安全质量检测学报 2024年第9期15卷 197-204页

作者：张芳耿思奕韩华凤刘嘉慧刘冠卉郑博强屠洁江苏科技大学粮食学院镇江212100 广西农业职业技术大学食品药品研究院南宁530007 江苏科技大学生物技术学院镇江212100

目的建立快速准确检测高酸度食醋中γ-氨基丁酸(γ-aminobutyric acid,GABA)含量的方法。方法建立高效液相色谱法检测食醋中GABA含量的方法并进行方法学验证,通过检测不同原料、酿造方法、发酵阶段、贮藏时间的32种食醋样品,分析GABA变... 详细信息

目的建立快速准确检测高酸度食醋中γ-氨基丁酸(γ-aminobutyric acid,GABA)含量的方法。方法建立高效液相色谱法检测食醋中GABA含量的方法并进行方法学验证,通过检测不同原料、酿造方法、发酵阶段、贮藏时间的32种食醋样品,分析GABA变化规律。结果该方法在0.01~1.00mg/m L范围内线性关系良好,R2为0.9992,精密度试验相对标准偏差小于2.0%,回收率在96.4%~103.0%之间,精密度和准确性均符合方法学要求。不同原料食醋的GABA含量差异显著(P<0.05),谷物醋含量最高;传统发酵工艺和菌种酿造的食醋GABA高于液体发酵、纯菌种发酵食醋(P<0.05);秋季醋GABA含量高于冬季醋(P<0.05);醋酸发酵阶段的GABA累积量高于酒精发酵(P<0.05),适当陈酿可提高产品中GABA含量;商品醋中GABA的衰减符合一级动力学反应;发芽糙米醋的GABA含量是未发芽糙米醋的2.29倍,是精米醋的4.73倍。结论所建立的检测方法GABA出峰时间为12min,分离度大于2,可快速、准确分析食醋中GABA。食醋中GABA含量与食醋原料、工艺、菌种、生产季节、贮藏时间等相关。以多种谷物或发芽谷物为原料,采用传统固态发酵工艺,秋季酿制,并适当延长陈酿时间有利于食醋中GABA的生成。

关键词： γ-氨基丁酸醋高效液相色谱法变化规律

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