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A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： Yaqin Wei Xiangqing Xu Qiang Guo Song zhao Yinli Qiu Dongli Wang wenwen Yu Yani Liu KeWei Wang School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition.In this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion.Intragastric administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like behavior.Additionally,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not fluoxetine.Furthermore,D01 reverses the long-term potentiation(LTP)inhibition induced by scopolamine.Taken together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： SERT 5-HT Kv7/KCNQ/M current D01 Depression Cognition

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Neurotrophins and neural stem cells in posttraumatic brain injury repair

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Animal Models and Experimental Medicine 2024年第1期7卷 12-23页

作者： wenwen Guo Ke Liu Yinghua Wang Xu Ge Yifan Ma Jing Qin Caiqin Zhang Ya zhao Changhong Shi Laboratory Animal Center Fourth Military Medical UniversityXi'anP.R.China Gansu University of Traditional Chinese Medicine LanzhouP.R.China Medical College of Yan'an University Yan'anP.R.China

Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.

关键词： mutual effect neural stem cells neurological function neurotrophins traumatic brain injury

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Numerical simulation of hypersonic thermochemical nonequilibrium flows using nonlinear coupled constitutive relations

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Chinese Journal of Aeronautics 2023年第3期36卷 63-79页

作者： Shuhua ZENG Zhenyu YUAN wenwen zhao Weifang CHEN School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310027China School of Energy and Power Engineering Nanjing University of Science and TechnologyNanjing 210094China

To predict aeroheating performance of hypersonic vehicles accurately in thermochemical nonequilibrium flows accompanied by rarefaction effect,a Nonlinear Coupled Constitutive Relations(NCCR)model coupled with Gupta’s chemical models and Park’s two-temperature model is firstly proposed in this paper.Three typical cases are intensively investigated for further validation,including hypersonic flows over a two-dimensional cylinder,a RAM-C II flight vehicle and a type HTV-2 flight vehicle.The results predicted by NCCR solution,such as heat flux coefficient and electron number densities,are in better agreement with those of direct simulation Monte Carlo or flight data than Navier-Stokes equations,especially in the extremely nonequilibrium regions,which indicates the potential of the newly-developed solution to capture both thermochemical and rarefied nonequilibrium effects.The comparisons between the present solver and NCCR model without a two-temperature model are also conducted to demonstrate the significance of vibrational energy source term in the accurate simulation of high-Mach flows.

关键词： Hypersonic flow Nonlinear coupled constitutive relations Rarefied gas Thermochemical nonequilibrium effect Vibrational excitation

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Development of a single transcript CRISPR/Cas9 toolkit for efficient genome editing in autotetraploid alfalfa

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The Crop Journal 2024年第3期12卷 788-795页

作者： Haixia zhao Siyi zhao Yingping Cao Xiping Jiang Lijuan zhao Zhimeng Li Mengqi Wang Ruijuan Yang Chuanen Zhou zhaoming Wang Feng Yuan Dongmei Ma Hao Lin wenwen Liu Chunxiang Fu CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Energy GeneticsQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdao 266101ShandongChina Shandong Energy Institute Qingdao 266101ShandongChina Qingdao New Energy Shandong Laboratory Qingdao 266101ShandongChina University of Chinese Academy of Sciences Beijing 100049China The Key Laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdao 266101ShandongChina Key Laboratory of Forage Breeding and Seed Production of Inner Mongolia Inner Mongolia M-Grass Ecology and Environment(Group)Co.Ltd.Hohhot 010016Inner MongoliaChina School of Ecology Environment Ningxia UniversityYinchuan 750021NingxiaChina Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China

Alfalfa(Medicago sativa.L.)is a globally significant autotetraploid legume forage crop.However,despite its importance,establishing efficient gene editing systems for cultivated alfalfa remains a formidable challenge.In this study,we pioneered the development of a highly effective ultrasonic-assisted leaf disc transformation system for Gongnong 1 alfalfa,a variety widely cultivated in Northeast China.Subsequently,we created a single transcript CRISPR/Cas9(CRISPR_2.0)toolkit,incorporating multiplex gRNAs,designed for gene editing in Gongnong 1.Both Cas9 and gRNA scaffolds were under the control of the Arabidopsis ubiquitin-10 promoter,a widely employed polymeraseⅡconstitutive promoter known for strong transgene expression in dicots.To assess the toolkit’s efficiency,we targeted PALM1,a gene associated with a recognizable multifoliate phenotype.Utilizing the CRISPR_2.0 toolkit,we directed PALM1 editing at two sites in the wild-type Gongnong 1.Results indicated a 35.1%occurrence of editing events all in target 2 alleles,while no mutations were detected at target 1 in the transgenic-positive lines.To explore more efficient sgRNAs,we developed a rapid,reliable screening system based on Agrobacterium rhizogenes-mediated hairy root transformation,incorporating the visible reporter MtLAP1.This screening system demonstrated that most purple visible hairy roots underwent gene editing.Notably,sgRNA3,with an 83.0%editing efficiency,was selected using the visible hairy root system.As anticipated,tetra-allelic homozygous palm1 mutations exhibited a clear multifoliate phenotype.These palm1 lines demonstrated an average crude protein yield increase of 21.5%compared to trifoliolate alfalfa.Our findings highlight the modified CRISPR_2.0 system as a highly efficient and robust gene editing tool for autotetraploid alfalfa.

关键词： Alfalfa Gene editing CRISPR_2.0 toolkit Hairy root system Tetra-allelic homozygous mutants

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Research on Detection of Food additives Based on Terahertz Spectroscopy and Analytic Hierarchy Process

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Instrumentation 2024年第1期11卷 30-37页

作者： Miaoyu zhao Fang Yan wenwen Li Yangshuo Liu Inner Mongolia University of Science and Technology School of Automation and Electrical Engineering BaotouInner Mongolia 014010China

Terahertz time-domain spectroscopy is a kind of far-infrared spectroscopy technology,and its spectrum reflects the internal properties of substances with rich physical and chemical information,so the use of terahertz waves can be used to qualitatively identify food additives containing nitrogen elements.Analytic hierarchy process(AHP)was originally used to solve evaluation-type problems,and this paper introduces it into the field of terahertz spectral qualitative analysis,proposes a terahertz time-domain spectral qualitative identification method combined with analytic hierarchy process,and verifies the feasibility of the method by taking four common food additives(xylitol,L-alanine,sorbic acid,and benzoic acid)and two illegal additives(melamine,and Sudan Red No.I)as the objects of study.Firstly,the collected terahertz time-domain spectral data were pre-processed and transformed into a data set consisting of peaks,peak positions,peak numbers and overall trends;then,the data were divided into comparison and test sets,and a qualitative additive identification model incorporating analytic hierarchy process was constructed and parameter optimisation was performed.The results showed that the qualitative identification accuracies of additives based on single factors,i.e.,overall trend,peak value,peak position,and peak number,were 80.23%,70.93%,67.44%,and 40.70%,respectively,whereas the identification accuracy of the analytic hierarchy process qualitative identification method based on multi-factors could be improved to 92.44%.In addition,the fuzzy characterisation of the absorption spectrum data was binarised in the data pre-processing stage and used as the base data for the overall trend,and the recognition accuracy was improved to 94.19%by combining the fuzzy characterisation method of such data with the hierarchical analysis qualitative recognition model.The results show that it is feasible to use terahertz technology to identify different varieties of additives,and this paper constructs a hierarchical analytical qu

关键词： terahertz time-domain spectroscopy analytic hierarchy process qualitative identification food additives

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Effects of Dietary Changes on the Gut Microbiota of Cynops orientalis

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Asian Herpetological Research 2024年第2期15卷 63-72页

作者： Yuting WANG Yuning XIE Siyu WU wenwen ZHANG Xiner CHENG Zixuan LI Fangfei HAN Jiayi SHI Yingying SHI Zhirong HE Chunna ZHANG Yixin JIANG Na zhao Jiaqi LI Supen WANG College of Life Sciences Anhui Normal UniversityWuhu 241000AnhuiChina Nanjing Institute of Environmental Sciences Ministry of Ecology and Environment of ChinaNanjing 210042JiangsuChina School of Ecology and Environment Anhui Normal UniversityWuhu 241002AnhuiChina Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing 100101China

The gut microbiota plays a pivotal role in the maintenance of health for amphibians,and it has been fully recognized,but the effectiveness of various influencing factors has not yet been fully clarified.Although this association should be considered while the amphibian order Caudata is facing a severe situation of population decline and extinction,there is little understanding of the association between diets and the diversity of gut microbiota in the amphibian order Caudata.Here,we conducted an extensive analysis of the gut microbiota of Cynops orientalis fed different diets using functional prediction and 16S rRNA amplicon sequencing techniques.First,we found that wild individuals had greater gut microbial diversity and richness in comparison to captive individuals.Second,we identified the bacterial taxa associated with diets and observed differences in the relative abundance of gut microbiota among people on various diets.Finally,we have a predictive comprehension of the selection and adaptative significance of shared core ASVs in the gut microbiota in maintaining the healthy survival of C.orientalis in a large-scale spatiotemporal map.Our study emphasizes how diets alter the gut microbiota of Caudata and offers fresh perspectives on the conservation and captive management of species in Caudata.

关键词： 16S rRNA Caudata core microbiota diet gut microbiota

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Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents

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General Psychiatry 2024年第2期37卷 216-223页

作者： Shuyin Xu Yumeng Ju Xiyu Wei wenwen Ou Mohan Ma Guanyi Lv Xiaotian zhao Yaqi Qin Yunjing Li Liang Li Mei Huang Siqi Yang Yimei Lu Yafei Chen Junwu Liu Jin Liu Bangshan Liu Yan Zhang Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Mental Health Institute of Central South University China National Technology Institute on Mental DisordersHunan Technology Institute of PsychiatryHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation.Aims The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety.Methods 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder Scale,and 716 adolescents who scored≥5 on both scales were selected as participants.Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms.Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9.A comparison was made between the depression-anxiety symptom networks of the two groups.Results‘Restlessness’,‘sad mood’and‘trouble relaxing’were the most prominent central symptoms in the depression-anxiety symptom network,and‘restlessness’,‘nervousness’and‘reduced movement’were the bridge symptoms in this network.‘Sad mood’was found to be directly related to‘suicide ideation’with the highest variance.The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group,with‘restlessness’and‘sad mood’exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group.Conclusion Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

关键词： symptoms adolescent assessed

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Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways

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Acta Pharmaceutica Sinica B 2015年第4期5卷 323-329页

作者： Chuanhong Wu wenwen zhao Xuenong Zhang Xiuping Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macao

Neocryptotanshinone(NCTS) is a natural product isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. In this study, we investigated its anti-inflammatory effects in lipopolysaccharide(LPS)-stimulated mouse macrophage(RAW264.7) cells. MTT results showed that NCTS partly reversed LPS-induced cytotoxicity. Real-time PCR results showed that NCTS suppressed LPS-induced mRNA expression of inflammatory cytokines, including tumor necrosis factor α(TNFα), interleukin-6(IL-6) and interleukin-1β(IL-1β). Moreover, NCTS could decrease LPS-induced nitric oxide(NO)production. Western blotting results showed that NCTS could down-regulate LPS-induced expression of inducible nitric oxide synthase(iNOS), p-IκBα, p-IKKβ and p-NF-κB p65 without affecting cyclooxygenase-2(COX-2). In addition, NCTS inhibited LPS-induced p-NF-κB p65 nuclear translocation.In conclusion, these data demonstrated that NCTS showed anti-inflammatory effect by suppression of NF-κB and iNOS signaling pathways.

关键词： Neocryptotanshinone Inflammation NF-κB Inducible nitric oxide synthase

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Tobacco control challenges in China: Big data analysis of online tobacco marketing information

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International Journal of Nursing Sciences 2020年第S1期7卷 52-60页

作者： Xiuli Wang Ying Xiong wenwen zhao School of New Media Peking UniversityDirector of Center for Social Media ResearchBeijingChina

Objective:To develop tobacco control strategies by analyzing online tobacco marketing information in China.Methods:Using web-crawler software,this study acquired 106,485 pieces of online tobacco marketing information published on 11 different Internet platforms including Weibo,WeChat,Baidu,etc.,from January-June 2018.The data were used to investigate the characteristics and social networks of online tobacco marketing via content and social network analysis.Results:The total volume of online tobacco marketing during the study period was high,showing a positive trend.Of all the marketing subjects,those involving"flavor capsule","Marlboro",and"Esse"were the most popular.The Weibo platform had the highest volume of online tobacco marketing information as well as the largest proportion of explicit marketing information.This was followed by other social media platforms such as Baidu Search,Baidu Tieba,and Xiaohongshu,where implicit marketing information predominated.The overall network structure of tobacco websites exhibited a significant centralization feature,where traditional and novel tobacco websites formed two clusters with almost no intersections.The China Tobacco Science and Education Website(http://***/)and E-Cigarette Home(http://***/)were the two nodes of the highest degree centrality within the respective"circle",while the China Tobacco Monopoly Bureau Website(http://***/)was the node with the highest closeness centrality.By contrast,Baidu Tieba's overall network structure was more decentralized,and the degree of correlation between different nodes was relatively low.Conclusion:Online tobacco marketing demonstrated high volumes and wide coverage,and an intertwined network,thereby creating major obstacles for tobacco control.To address this issue,the government should strengthen network supervision of tobacco marketing and revise its current regulations.Meanwhile,Internet platforms should improve self-regulation by comprehensively removing and blocking tobacco-related information.Lastly,the media and public

关键词： Big data China Internet Marketing Social media Social networking Tobacco Tobacco products

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节能减碳政策对企业金融化的影响研究

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经济经纬 2024年第2期41卷 88-99页

作者：赵雯雯王书华山西财经大学金融学院山西太原030006 山西财经大学晋商研究院山西太原030006

以2008—2021年上市实体企业为研究样本,运用双重差分模型探讨节能减碳政策对企业金融化的影响效应和作用机理。实证结果表明:节能减碳政策显著降低了政策试点企业金融化水平,该结论通过了平行趋势检验、替换变量和PSM-DID等一系列稳健... 详细信息

以2008—2021年上市实体企业为研究样本,运用双重差分模型探讨节能减碳政策对企业金融化的影响效应和作用机理。实证结果表明:节能减碳政策显著降低了政策试点企业金融化水平,该结论通过了平行趋势检验、替换变量和PSM-DID等一系列稳健性和内生性检验。机制检验显示,节能减碳政策通过提高技术创新能力和缓解管理者短视来抑制企业金融化。异质性分析表明,节能减碳政策的脱虚向实效应存在异质性,在高管有金融背景的企业、竞争度高行业以及经济政策较稳定时更为显著。拓展分析表明,节能减碳政策改变了企业投资偏向,促进脱虚向实。基于此,政府应不断优化环境规制体系建设,实现环境保护和经济发展的双赢目标。

关键词：环境规制节能减碳政策企业金融化脱虚向实

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