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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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Optimizing high-coordination shell of Co-based single-atom catalysts for efficient ORR and zinc-air batteries

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Journal of Energy Chemistry 2024年第8期95卷 306-314页

作者： Yugang Qi Qing Liang Kexin song Xinyan Zhou Meiqi Liu wenwen Li Fuxi Liu Zhou Jiang Xu Zou Zhongjun Chen Wei Zhang Weitao Zheng Key Laboratory of Automobile Materials MOE School of Materials Science & Engineering Electron Microscopy Center and International Center of Future Science Jilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy Materials Jilin University Institute of High Energy Physics Chinese Academy of Sciences

Atom-level modulation of the coordination environment for single-atom catalysts(SACs) is considered as an effective strategy for elevating the catalytic performance. For the MNxsite, breaking the symmetrical geometry and charge distribution by introducing relatively weak electronegative atoms into the first/second shell is an efficient way, but it remains challenging for elucidating the underlying mechanism of interaction. Herein, a practical strategy was reported to rationally design single cobalt atoms coordinated with both phosphorus and nitrogen atoms in a hierarchically porous carbon derived from metal-organic frameworks. X-ray absorption spectrum reveals that atomically dispersed Co sites are coordinated with four N atoms in the first shell and varying numbers of P atoms in the second shell(denoted as Co-N/P-C).The prepared catalyst exhibits excellent oxygen reduction reaction(ORR) activity as well as zinc-air battery performance. The introduction of P atoms in the Co-SACs weakens the interaction between Co and N,significantly promoting the adsorption process of *OOH, resulting in the acceleration of reaction kinetics and reduction of thermodynamic barrier, responsible for the increased intrinsic activity. Our discovery provides insights into an ultimate design of single-atom catalysts with adjustable electrocatalytic activities for efficient electrochemical energy conversion.

关键词： Electrocatalytic Oxygen reduction reaction Shell coordination optimization Single atom catalyst

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Transcriptome-wide N6-methyladenosine(m^(6)A)methylation in soybean under Meloidogyne incognita infection

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aBIOTECH 2022年第3期3卷 197-211页

作者： Xue Han Qianqian Shi Ziyi He wenwen song Qingshan Chen Zhaoming Qi College of Agriculture Northeast Agricultural UniversityHarbin150030China Shandong Engineering Research Center for Environment-Friendly Agricultural Pest Management College of Plant Health and MedicineQingdao Agricultural UniversityQingdao266109China

N^(6)-methyladenosine(m^(6)A)is a reversible epigenetic modification of mRNA and other RNAs that plays a significant role in regulating gene expression and biological processes.However,m^(6)A abundance,dynamics,and transcriptional regulatory mechanisms remain unexplored in the context of soybean resistance to Meloidogyne incognita.In this study,we performed a comparative analysis of transcriptome-wide m^(6)A and metabolome profiles of soybean root tissues with and without M.incognita infection.Global m^(6)A hypermethylation was widely induced in response to M.incognita infection and was enriched around the 3′end of coding sequences and in 3′UTR regions.There were 2069 significantly modified m^(6)A sites,594 differentially expressed genes,and 103 differentially accumulated metabolites between infected and uninfected roots,including coumestrol,psoralidin,and 2-hydroxyethylphosphonate.Among 101 m^(6)A-modified DEGs,34 genes were hypomethylated and upregulated,and 39 genes were hypermethylated and downregulated,indicating a highly negative correlation between m^(6)A methylation and gene transcript abundance.A number of these m^(6)A-modified DEGs,including WRKY70,ERF60,POD47 and LRR receptor-like serine/threonine-protein kinases,were involved in plant defense responses.Our study provides new insights into the critical role of m^(6)A modification in early soybean responses to M.incognita.

关键词： m^(6)A methylation Soybean Meloidogyne incognita m^(6)A-seq RNA-seq Metabolome

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Yielding behavior of triplex medium Mn steel alternated with cooling strategies altering martensite/ferrite interfacial feature

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Journal of Materials Science & Technology 2022年第31期126卷 60-70页

作者： Bin Hu Xiao Shen Qinyi Guo Qinghua Wen Xin Tu Cancan Ding Fanglin Ding wenwen song Haiwen Luo School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing 100083China Steel Institute RWTH Aachen UniversityIntzestraße 152072 AachenGermany

In this paper, we report the influence of cooling processes on the yielding behavior of a medium Mn steel(MMS) with triplex microstructure, i.e. austenite(γ), ferrite(α) and as-quenched martensite(α’). After the intercritical annealing(IA) at both 725℃ and 750℃, the steel was subjected to the two cooling processes, i.e. air cooling(AC) and water quenching(WQ). It exhibits the discontinuous yielding after the AC following the IA at 750℃ while the continuous yielding after the WQ. Compared with WQ process,both the dilatometry and the microstructural examinations show that the AC process leads to lower Ms temperature, larger retained austenite(RA) fraction and less martensite, the latter is always companied with geometry necessary dislocations(GNDs) generated near the α/α’ interfaces. Considering the complexity of nanosized tri-phases in this steel, the presence of martensite with key features in the resultant specimens was systematically examined by atom probe tomography(APT) on the samples prepared by the specific target lift-out method. The APT results directly revealed the C/Mn co-segregation at the α’/αinterfaces in the AC samples but not in WQ samples. The numerical simulation results further suggest that the segregation of C and Mn at the α’/α interfaces may be due to different mechanisms. We conclude that the yielding of triplex MMS is determined by both the quantity of GNDs generated near theα/α’ interfaces, which increases with martensite fraction, and the extent of their immobilization resulting from the interfacial segregation of solute atoms when the presence of martensite is sufficient. WQ tends to suppress the discontinuous yielding of MMS since the rapid cooling may promote more martensite formed with the increasing quantity of GNDs and prevent the interfacial segregation of both C and Mn.

关键词： Triplex medium Mn steel Phase boundary Segregation Discontinuous yielding

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建阳刻书创意研究

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学海 2024年第2期 205-212页

作者：宋文文南京师范大学美术学院南京师范大学紫金非遗管理与品牌传播研究中心南京210023

历史上建阳书坊以营利为目的,形式创新与广告宣传一直是建阳书商营销的惯用手段。建阳书坊主在书业广告设计方面下足了功夫,不断推陈出新,在刻书形式上,都展现出极高的创意,为读者提供方便,以新颖的形式吸引读者。因此,建阳书籍广告成... 详细信息

历史上建阳书坊以营利为目的,形式创新与广告宣传一直是建阳书商营销的惯用手段。建阳书坊主在书业广告设计方面下足了功夫,不断推陈出新,在刻书形式上,都展现出极高的创意,为读者提供方便,以新颖的形式吸引读者。因此,建阳书籍广告成为古代书业广告中最具代表性的典范。本文将此作为研究对象,探究宋元明时期建阳刻书的创意性,总结建阳书业对于今天的重要启示。

关键词：建阳刻书创意文化传播

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Control of Strain Hardening Behavior in High-Mn Austenitic Steels

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Acta Metallurgica Sinica(English Letters) 2014年第3期27卷 546-556页

作者： wenwen song Tobias Ingendahl Wolfgang Bleck Steel Institute RWTH Aachen University Intzestr.1 52072 AachenGermany

Austenitic high-Mn steels with Mn contents between approximately 15 and 30 wt% gain much interest because of their excellent mechanical properties and the option for adjusting strain hardening behavior due to different deformation mechanisms. 2D and 3D composition-dependent stacking fault energy （SFE） maps indicate the effect of chemical composition and temperature on SFE and consequently on the deformation mechanisms. Three steels with different chemical compositions and the same or different SFE are characterized in quasi-static tensile tests. The control parameters of strain hardening behavior in the high-Mn austenitic steels are described, and consequences for future developments are discussed.

关键词： High-Mn austenitic steels Stacking fault energy Strain hardening

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GmNMHC5 may promote nodulation via interaction with GmGAI in soybean

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The Crop Journal 2022年第1期10卷 273-279页

作者： Wenting Wang Zhili Wang Wensheng Hou Li Chen Bingjun Jiang Wenya Ma Lijuan Bai wenwen song Cailong Xu Tianfu Han Yongjun Feng Cunxiang Wu School of Life Science Beijing Institute of TechnologyBeijing 100081China MARA Key Laboratory of Soybean Biology(Beijing) Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China

Soybean(Glycine max[L.]Merr.)is a food and oil crop whose growth and yield are influenced by root and nodule development.In the present study,Gm NMHC5 was found to promote the formation of nodules in overexpressing mutants.In contrast,the number of nodules in Gmnmhc5 edited with CRISPR/Cas9 decreased sharply.In 35 S:Gm NMHC5 mutants,expression levels of genes involved in nodulation were significantly up-regulated.Both in vitro and in vivo biochemical analyses showed that Gm NMHC5 directly interacted with Gm GAI(a DELLA protein),and the content of gibberellin 3(GA_(3))in overexpressing mutants was lower than that in the wild type.These results revealed that Gm NMHC5 participates in the classical GA signaling pathway,and may regulate the content of GA_3 to match the optimal concentration required for nodule formation,thereby promoting nodulation by directly interacting with Gm GAI.A model illustrating the mechanism by which Gm NMHC5 promotes soybean nodulation is presented.

关键词： Glycine max GmNMHC5 GmGAI Nodulation GA pathway

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Pharmacokinetics and enterohepatic circulation of jervine,an antitumor steroidal alkaloid from Veratrum nigrum in rats

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Journal of Pharmaceutical Analysis 2019年第5期9卷 367-372页

作者： Bingjing Zheng Caihong Wang wenwen song Xiaoxia Ye Zheng Xiang School of Pharmaceutical Sciences Wenzhou Medical University

Jervine,a novel steroidal alkaloid from Veratrum nigrum L.,exhibits both antitumor effect and potential toxicity.The aim of study was to characterize the pharmacokinetic behaviors and enterohepatic circulation of jervine in rats.A rapid and simple ultra-high performance liquid chromatography-tandem mass spectrometric method was developed and validated for quantification of jervine and alpinetin (internal standard) in rat plasma.After extraction from rat plasma by a simple protein-precipitation method,the analyte was separated on a C18 column (2.1 mm×50 mm,1.7μm) using water with 0.1%formic acid and acetonitrile as the mobile phase delivered at a flow rate of 0.4mL/min.Jervine and alpinetin were determined in the positive mode with multiple reaction monitoring (MRM) of the ion transitions at m/z426.3→108.8 and m/z 271.0 166.9,respectively.Molecular docking method was used to investigate the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase.The method was well validated within acceptance limits including specificity,matrix effect,recovery,precision,accuracy,and stability,and was successfully applied to the pharmacokinetic study of jervine after oral and intravenous administration to rats.Jervine presented a small volume of distribution,fast absorption,high oral bioavailability,and enterohepatic circulation.The enterohepatic circulation was first observed in veratrum alkaloids,and was further investigated by molecular docking studies,which was related to the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase.The pharmacokinetic properties and enterohepatic circulation of jervine in rats provided a significant basis for the drug-drug interaction and toxicity study in the future.

关键词： Jervine UPLC-MS/MS Pharmacokinetics Enterohepatic circulation

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Surface modification of plasma nitriding on AlxCoCrFeNi high-entropy alloys

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Journal of Materials Science & Technology 2020年第13期47卷 140-145页

作者： Jinxiong Hou wenwen song Liwei Lan Junwei Qiao College of Materials Science and Engineering Taiyuan University of TechnologyTaiyuan030024China Steel Institute RWTH Aachen UniversityAachen52072Germany Key Laboratory of Interface Science and Engineering in Advanced Materials Ministry of EducationTaiyuan University of TechnologyTaiyuan030024China

Plasma nitriding is successfully employed in treating AlxCoCrFeNi high-entropy alloys(HEAs)with finelydivided Al content(i.e.,x values in molar ratio,x=0.1-0.8)to develop wear-resistant structural materials.Nitridation greatly removes the Al from the matrix that completely deplete the Ni-Al enriched phase,forming nanoscaled nitrides(AIN and CrN)precipitations near the surface.Nitriding promotes the hardness of present alloys with values widely ranging from 276 HV to 722 HV.Interestingly,the higher content the Al,the smaller thickness the nitrides layer,but the higher hardness due to the increased amount of hard nitrides phases and volume fraction of BCC phase.Significantly,plasma nitriding considerably improves the wear re sistance of AlxCoCrFeNi HEAs by 4-18 times.

关键词： Plasma nitriding High-entropy alloy Microstructure Hardness Wear and tribology

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教育家精神的概念阐释、逻辑基点及其理论争鸣

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中国教育科学（中英文） 2024年第1期7卷 32-45页

作者：宋文文张广君华南师范大学教育科学学院广州510631

当代教育家精神具有爱国情怀、道德意志、职业态度、创新品质、奉献意识和人文关怀等含义。作为当代教育家精神的重要内涵,“蜡烛精神”对我国教师职业道德取向、教育教学实践、教师职业伦理研究等均有着深刻影响,是深入阐释我国当代“... 详细信息

当代教育家精神具有爱国情怀、道德意志、职业态度、创新品质、奉献意识和人文关怀等含义。作为当代教育家精神的重要内涵,“蜡烛精神”对我国教师职业道德取向、教育教学实践、教师职业伦理研究等均有着深刻影响,是深入阐释我国当代“教育家精神”的逻辑基点。“蜡烛精神”发展至今,在评价上经历了肯定、否定再到否定之否定的历史过程,在不同阶段有着不同的理论观点、实践意义以及不足之处。从生成教育理论的视角看,面对“蜡烛精神”的当代可能性及未来发展问题,有必要从文化历史、时代状况、教育现实诸维度澄清其存在的必要性与价值,进而从历史意义、伦理意涵、行为意向和基础意求等角度,即从“薪火相传”的文化意象、“历史担当”的责任伦理、“深沉热爱”的教育情怀、“自我实现”的职业底线等方面,理解和描绘当代教师“蜡烛精神”的整体意象,以求深入理解、阐释和弘扬当代教育家精神。

关键词：教育家精神蜡烛精神生成教育理论

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