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Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Acta Pharmaceutica Sinica B 2024年第2期14卷 667-681页

作者： Yue Zhang jingwen Gao Na Li Peng xu Shimeng Qu Jinqian Cheng Mingrui Wang xueru Li Yaheng Song Fan Xiao Xinyu Yang Jihong Liu Hao Hong Ronghao Mu Xiaotian Li Youmei Wang Hui xu Yuan Xie Tianming Gao Guangji Wang Jiye Aa Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural MedicinesResearch Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical SciencesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Monitoring and Control Drug Intelligence and Forensic CenterMinistry of Public SecurityBeijing 100193China School of Pharmacy China Pharmaceutical UniversityNanjing 211198China School of Foreign Languages China Pharmaceutical UniversityNanjing 211198China Department of Neurobiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pharmacology China Pharmaceutical UniversityNanjing 211198China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China

Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated.Here,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1 receptor medium spiny neurons(D1-MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors.Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons(D2-MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs.We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration,but not a lower dose.The fast onset property of crocin was verified through multicenter studies.Moreover,crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN.These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.

关键词： CAMP Nucleus accumbens Depression D1-MSN D2-MSN

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Engineering large-scaled electrochromic semiconductor films as reproductive SERS substrates for operando investigation at the solid/liquid interfaces

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Chinese Chemical Letters 2022年第12期33卷 5169-5173页

作者： Lingling Yang Jiuju Feng Jia-Ning Wang Zhida Gao jingwen xu Ye Mei Yan-Yan Song College of Sciences Northeastern UniversityShenyang 110004China State Key Laboratory of Precision Spectroscopy School of Physics and Electronic ScienceEast China Normal UniversityShanghai 200062China NYU-ECNU Center for Computational Chemistry at NYU Shanghai Shanghai 200062China Collaborative Innovation Center of Extreme Optics Shanxi UniversityTaiyuan 030006China College of Chemistry and Life Sciences Zhejiang Normal UniversityJinhua 321004China

Although surface-enhanced Raman spectroscopy(SERS)has been applied for gathering fingerprint information,even in single molecule analysis,the decayed Raman signals in aqueous solutions largely obstruct the on-site insight reaction process.In this study,large-scaled semiconductor films with multi-walled(TiO_(2)/WO_(3)/TiO_(2))nanopore distribution are fabricated by combining electrochemical anodization and sputtering technique,and then employed as the SERS substrates for detection of molecules at the solid/liquid interfaces.Given the remarkably improved electrochromic property of the multi-walled film,such SERS substrates were endowed with tunable oxygen vacancy(VO)density and distribution via simply applying electrochemical bias voltage,which enabled one to achieve an enhanced charge transfer efficiency and thus a remarkably increased Raman signal even in solution.The VO-rich SERS substrate is highly repeatable,thus providing a reliable platform for in-situ monitoring of the target molecules or intermediates at the solid/liquid interfaces.

关键词： Charge transfer Electrochromism Oxygen vacancies SERS substrate Solid liquid interface

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ADVISING score:a reliable grading scale based on injury and response for intracerebral haemorrhage

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Stroke & Vascular Neurology 2023年第2期8卷 111-118页

作者： Yan Wan Hongxiu Guo Shaoli Chen Jiang Chang David Wang Rentang Bi Man Li Ke Shi Zhaowei Wang Daokai Gong jingwen xu Quanwei He Bo Hu Department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina School of Public Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Neurovascular Division Department of NeurologyBarrow Neurological Institute/Saint Joseph Hospital Medical CenterPhoenixArizonaUSA Department of Neurology Qianjiang Central HospitalQianjiangHubeiChina Department of Neurology Jingzhou Central HospitalJingzhouHubeiChina Department of Neurology Honghu People's HospitalHonghuHubeiChina

Background Intracerebral haemorrhage(ICH)is the most devastating form of stroke causing high morbidity and mortality.We aimed to develop a novel clinical score incorporating multisystem markers to predict functional dependence at 90 days after ICH.Methods We analysed data from Chinese Cerebral Hemorrhage:Mechanism and Intervention study.Multivariable logistic regression analysis was used to identify the factors associated with 90-day functional dependency(the modified Rankin Scale≥3)after ICH and develop the ADVISING scoring system.To test the scoring system,a total of 2111 patients from Hubei province were included as the training cohort,and 733 patients from other three provinces in China were included as an external validation cohort.Results We found nine variables to be significantly associated with functional dependency and included in the ADVISING score system:age,deep location of haematoma,volume of haematoma,National Institutes of Health Stroke Scale,aspartate transaminase,international normalised ratio,neutrophil-lymphocyte ratio,fasting blood glucose and glomerular filtration rate.Individuals were divided into 12 different categories by using these nine potential predictors.The proportion of patients who were functionally dependent increased with higher ADVISING scores,which showed good discrimination and calibration in both the training cohort(C-statistic,0.866;p value of Hosmer-Lemeshow test,0.195)and validation cohort(C-statistic,0.884;p value of Hosmer-Lemeshow test,0.853).The ADVISING score also showed better discriminative performance compared with the other five existing ICH scores(p<0.001).Conclusions ADVISING score is a reliable tool to predict functional dependency at 90 days after ICH.

关键词： score statistic reliable

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A Multi-Agent Spatial Logic for Scenario-Based Decision Modeling and Verification in Platoon Systems

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Journal of Computer Science & Technology 2021年第6期36卷 1231-1247页

作者： jingwen xu Yanhong Huang Jianqi Shi Shengchao Qin National Trusted Embedded Software Engineering Technology Research Center East China Normal University Shanghai 200062China College of Computer Science and Software Engineering Shenzhen UniversityShenzhen 518061China

To cater for the scenario of coordinated transportation of multiple trucks on the highway,a platoon system for autonomous driving has been extensively explored in the industry.Before such a platoon is deployed,it is necessary to ensure the safety of its driving behavior,whereby each vehicle’s behavior is commanded by the decision-making function whose decision is based on the observed driving scenario.However,there is currently a lack of verification methods to ensure the reliability of the scenario-based decision-making process in the platoon system.In this paper,we focus on the platoon driving scenario,whereby the platoon is composed of intelligent heavy trucks driving on cross-sea highways.We propose a formal modeling and verification approach to provide safety assurance for platoon vehicles’cooperative driving behaviors.The existing Multi-Lane Spatial Logic(MLSL)with a dedicated abstract model can express driving scene spatial properties and prove the safety of multi-lane traffic maneuvers under the single-vehicle perspective.To cater for the platoon system’s multi-vehicle perspective,we modify the existing abstract model and propose a Multi-Agent Spatial Logic(MASL)that extends MLSL by relative orientation and multi-agent observation.We then utilize a timed automata type supporting MASL formulas to model vehicles’decision controllers for platoon driving.Taking the behavior of a human-driven vehicle(HDV)joining the platoon as a case study,we have implemented the model and verified safety properties on the UPPAAL tool to illustrate the viability of our framework.

关键词： autonomous driving decision-making model platoon system safety verification timed automaton

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具有发酵工程学科特色的合成生物学研究生教学改革

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生物工程学报 2024年第6期40卷 1963-1971页

作者：徐国强余世琴周景文江南大学生物工程学院江苏无锡214122 江南大学粮食发酵与食品生物制造国家工程研究中心江苏无锡214122 江南大学未来食品科学中心江苏无锡214122

工业生物技术被认为是推动工业可持续发展最有希望的技术。合成生物学的发展为工业生物技术的进步带来了新的机遇同时创造了无限可能。发酵工程是所有生物技术产业化实现的抓手和落脚点。为进一步建立与发酵工程学科相匹配的合成生物学... 详细信息

工业生物技术被认为是推动工业可持续发展最有希望的技术。合成生物学的发展为工业生物技术的进步带来了新的机遇同时创造了无限可能。发酵工程是所有生物技术产业化实现的抓手和落脚点。为进一步建立与发酵工程学科相匹配的合成生物学教学体系,教学团队优化了教学内容,创新了教学模式,突出了教学特色(发酵故事讲述培养工匠精神、生物经济教育强化工程化思维和生物伦理与安全教育培育担当精神),并对本课程教学改革进行了总结和展望。通过教学改革,合成生物学的研究生教学工作有望取得新的进展,为相关领域的合成生物学教学提供参考,同时为工业生物技术的发展(加强生物制造创新能力,培育生物经济新动能)提供人才培养的保障。

关键词：工业生物技术合成生物学发酵工程教学改革

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代谢工程改造酿酒酵母合成玉米黄质

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食品与发酵工业 2024年第5期50卷 1-6页

作者：赵崇屹周景文徐沙江南大学粮食发酵工艺与技术国家工程实验室江苏无锡214122 江南大学生物工程学院江苏无锡214122 江南大学未来食品科学中心江苏无锡214122

玉米黄质是一种类胡萝卜素,在很多领域都有一定的应用。该研究在前期构建的脂质体积累酿酒酵母的基础上,表达玉米黄质合成酶,初步得到一株能够积累玉米黄质的酿酒酵母工程菌。进一步优化补料碳源、补料时间和补料方式,最终在5 L的发酵罐... 详细信息

玉米黄质是一种类胡萝卜素,在很多领域都有一定的应用。该研究在前期构建的脂质体积累酿酒酵母的基础上,表达玉米黄质合成酶,初步得到一株能够积累玉米黄质的酿酒酵母工程菌。进一步优化补料碳源、补料时间和补料方式,最终在5 L的发酵罐从48 h开始以指数流加的方式流加葡萄糖,得到玉米黄质的产量为47.7 mg/L。综上,该研究构建了一株高产玉米黄质重组菌并对其进行了发酵验证,研究结果为后续进行发酵优化提供了基础以及改进的方向。

关键词：玉米黄质指数流加酿酒酵母脂质载体补加葡萄糖

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Enhanced removal of Cr(Ⅵ) by biochar with Fe as electron shuttles

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Journal of Environmental Sciences 2019年第4期31卷 109-117页

作者： jingwen xu Yongguang Yin Zhiqiang Tan Bowen Wang Xiaoru Guo Xia Li Jingfu Liu School of Environmental Sciences Liaoning University State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of Sciences University of Chinese Academy of Sciences

Biochar is extensively used as an effective soil amendment for environmental remediation.In addition to its strong contaminant sorption capability, biochar also plays an important role in chemical transformation of contaminant due to its inherent redox-active moieties.However, the transformation efficiency of inorganic contaminants is generally very limited when the direct adsorption of contaminants on biochar is inefficient. The present study demonstrates the role of Fe ion as an electron shuttle to enhance Cr(Ⅵ) reduction by biochars. Batch experiments were conducted to examine the effects of Fe(Ⅲ) levels,pyrolysis temperature of biochar, initial solution pH, and biochar dosage on the efficiency of Cr(Ⅵ) removal. Results showed a significant enhancement in Cr(Ⅵ) reduction with an increase in Fe(Ⅲ) concentration and a decrease of initial pH. Biochar produced at higher pyrolysis temperatures(e.g., 700°C) favored Cr(Ⅵ) removal, especially in the presence of Fe(Ⅲ), while a higher biochar dosage proved unfavorable likely due to the agglomeration or precipitation of biochar. Speciation analysis of Fe and Cr elements on the surface of biochar and in the solution further confirmed the role of Fe ion as an electron shuttle between biochar and Cr(Ⅵ). The present findings provide a potential strategy for the advanced treatment of Cr(Ⅵ) at low concentrations as well as an insight into the environmental fate of Cr(Ⅵ) and other micro-pollutants in soil or aqueous compartments containing Fe and natural or engineered carbonaceous materials.

关键词： Biochar Electron shuttle Fe(Ⅲ) Reduction Cr(Ⅵ)

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数字普惠金融对共同富裕的空间动态影响分析

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中国软科学 2024年第5期 163-172页

作者：邹洋徐靖文姜沐汐南开大学经济学院天津300071 南开大学经济行为与政策模拟实验室天津300071 国家税务总局税收科学研究所北京100053

基于中国城市层面数据和北京大学数字普惠金融指数,构建空间动态杜宾模型,从增收和改善收入分配的视角实证分析数字普惠金融对共同富裕的影响。研究结果显示:数字普惠金融对农村居民人均纯收入影响的短期直接效应显著为正;无论短期还是... 详细信息

基于中国城市层面数据和北京大学数字普惠金融指数,构建空间动态杜宾模型,从增收和改善收入分配的视角实证分析数字普惠金融对共同富裕的影响。研究结果显示:数字普惠金融对农村居民人均纯收入影响的短期直接效应显著为正;无论短期还是长期,数字普惠金融对城乡居民收入分配差距影响的间接效应均显著为负;相较于拓宽数字普惠金融覆盖广度和加深数字普惠金融使用深度,数字化程度的提高能同时达到增收和改善收入分配的目的,更有利于促进共同富裕。

关键词：共同富裕数字普惠金融空间动态杜宾模型

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旧石器时代遗址中出土的赭石及相关遗物的研究方法

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人类学学报 2024年第2期43卷 331-343页

作者：许竞文浣发祥杨石霞中国科学院脊椎动物演化与人类起源重点实验室中国科学院古脊椎动物与古人类研究所中国科学院生物演化与环境卓越创新中心中国科学院大学

赭石是考古发现中一类较为常见的矿物颜料。遗址中的矿物颜料研究对于解读中更新世以来人类行为的演化与发展以及人群的迁徙和交流互动具有重要意义。目前，我国出土和被识别的赭石相关考古发现日益增多，但研究程度还有待深入，旧石器... 详细信息

赭石是考古发现中一类较为常见的矿物颜料。遗址中的矿物颜料研究对于解读中更新世以来人类行为的演化与发展以及人群的迁徙和交流互动具有重要意义。目前，我国出土和被识别的赭石相关考古发现日益增多，但研究程度还有待深入，旧石器时代考古发现中相关材料的识别和解读较为有限。如何综合利用多学科测试分析方法建立起完善的研究方案，深度挖掘赭石颜料利用所指示的人类行为发展模式和民族学意义，还需要我们进行系统性地总结和思考。因此，本文通过梳理现有的考古学、地球物理、地球化学和民族学等各领域的国内外研究成果，归纳了旧石器时代考古遗址中出土的赭石及相关遗物的主要研究内容——成分定性、产地溯源和加工技术分析，以及各自适用的分析方法。综合多项研究案例，我们认为在性质、产地和技术分析的基础上，需要结合民族学方法、生态环境背景才能更有效地解读和复原史前人类的行为模式及社会学、民族学意义。

关键词：旧石器时代赭石理化分析人类学

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人乳低聚糖与肠道菌群互作及其调节婴儿免疫功能的研究进展

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食品工业科技 2024年第3期45卷 363-371页

作者：徐颢轩刘婧雯尚佳萃孟祥晨东北农业大学食品学院乳品科学教育部重点实验室黑龙江哈尔滨150030

人乳低聚糖(human milk oligosaccharides,HMOs)是母乳中的一类重要组分,迄今为止已经确定了200多种结构不同的HMOs。HMOs能在肠道微生物的作用下产生短链脂肪酸,对婴儿健康产生有益影响,这是母乳与配方粉的主要区别之一。研究表明,不... 详细信息

人乳低聚糖(human milk oligosaccharides,HMOs)是母乳中的一类重要组分,迄今为止已经确定了200多种结构不同的HMOs。HMOs能在肠道微生物的作用下产生短链脂肪酸,对婴儿健康产生有益影响,这是母乳与配方粉的主要区别之一。研究表明,不同种类的肠道微生物利用不同机制来识别和消化不同结构的HMOs,维持肠道菌群平衡。同时,HMOs还具有缓解过敏症状,预防坏死性小肠结肠炎等多种功能。本文对HMOs的结构、种类与含量、与婴儿肠道菌群的互作及其免疫调节功能进行了综述。HMOs可促进婴儿肠道菌群的定植与生长,并通过多种方式直接或间接调节婴儿免疫功能。本文为HMOs在婴幼儿食品中的应用提供理论支持,对其未来研发方向提供新思路。

关键词：母乳低聚糖岩藻糖基化肠道菌群免疫抵抗病原体粘附

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