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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 *** 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 *** 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 ***,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 ***,D01 reverses the long-term potentiation(LTP)inhibition induced by *** 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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Highly Thermally Conductive Polydimethylsiloxane Composites with Controllable 3D GO@f-CNTs Networks via Self-sacrificing Template Method

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Chinese Journal of Polymer Science 2024年第7期42卷 897-906,I0005页

作者： Shuang-Shuang Wang Dian-Ying Feng Zhi-Ming Zhang Xia Liu Kun-Peng Ruan Yong-qiang guo Jun-wei Gu Shaanxi Key Laboratory of Macromolecular Science and Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an710072China Shandong Institute of Nonmetallic Materials Jinan250031China Queen Mary University of London Engineering School Northwestern Polytechnical UniversityXi’an710072China

Constructing controllable thermal conduction networks is the key to efficiently improve thermal conductivities of polymer *** this work,graphite oxide(GO)and functionalized carbon nanotubes(f-CNTs)are combined to prepare“Line-Plane”-like hetero-structured thermally conductive GO@f-CNTs fillers,which are then performed to construct controllable 3D GO@f-CNTs thermal conduction networks via selfsacrificing template method based on oxalic ***,thermally conductive GO@f-CNTs/polydimethylsiloxane(PDMS)composites are fabricated via casting *** the size of oxalic acid is 0.24 mm and the volume fraction of GO@f-CNTs is 60 vol%,GO@f-CNTs/PDMS composites present the optimal thermal conductivity coefficient(λ,4.00 W·m^(-1)·K^(-1)),about 20 times that of theλof neat PDMS(0.20 W·m^(-1)·K^(-1)),also much higher than theλ(2.44 W·m^(-1)·K^(-1))of GO/f-CNTs/PDMS composites with the same amount of randomly dispersed ***,the obtained GO@f-CNTs/PDMS composites have excellent thermal stability,whoseλdeviation is only about 3%after 500 thermal cycles(20-200℃).

关键词： Polydimethylsiloxane Hetero-structured thermally conductive fillers Self-sacrificing template Thermal conduction networks

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CLAIR: An integrated lipid database across multiple crop species

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Plant Communications 2024年第7期5卷 5-7页

作者： Bing He Mengjia Bu qiang Lin Zhengwei Fu Junhua Xie wei fan Jianyang Li Ruonan Li wei Hua Wanfei Liu Peng Cui Guangdong Laboratory for Lingnan Modern Agriculture Genome Analysis Laboratory of the Ministry of Agriculture and Rural AreaAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China Key Laboratory of Biology and Genetic Improvement of Oil Crops Ministry of Agriculture and Rural AffairsOil Crops Research Institute of the Chinese Academy of Agricultural SciencesWuhan 430062China State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China College of Agronomy Qingdao Agricultural UniversityQingdao 266109China These authors contributed equally to this article

Lipids are an important global commodity and industrial raw *** of the lipids consumed worldwide are derived from *** 2017,the total production of vegetable oils and animal fats was estimated at 206.1 million tons per year,with vegetable oils accounting for∼87%of this total(Mielke,2017).Oilseed crops,a major source of vegetable oils,store triglycerides primarily in seeds and fruits,with variation in the specific types of oils produced(Zanetti et al.,2013).A comprehensive understanding of the genes and mechanisms associated with lipid biosynthesis in various oilseed crops is essential for improving oil content traits in these crops through molecular biology and breeding(Xu and Shanklin,2016).

关键词： crops commodity breeding

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Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

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World Journal of Psychiatry 2024年第1期14卷 26-35页

作者： Qi-fan Huo Li-Juan Zhu Jian-wei guo Yan-An Jiang Jing Zhao Department of Anesthesiology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture *** fracture is a common type of fracture in older *** hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint *** To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent *** A total of 397 patients who underwent THA from February 2019 to August *** conducted a three-year retrospective cohort study in Shaanxi Provincial People’s *** demographic data were obtained from the electronic medical record *** collected preoperative,intraoperative,and postoperative *** hundred twenty-nine patients who were administered Dex during the operation were included in the Dex *** hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin *** hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin *** patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were *** There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of th

关键词： Ulinastatin Dexmedetomidine Postoperative cognitive dysfunction Inflammatory cytokines Total hip arthroplasty

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Functional nanoemulsions: Controllable low-energy nanoemulsification and advanced biomedical application

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Chinese Chemical Letters 2024年第2期35卷 57-69页

作者： Maojie Zhang qiang Cao Yuming Yuan Xiaohan guo Dawei Pan Rui Xie Xiaojie Ju Zhuang Liu wei Wang Liangyin Chu College of Engineering Sichuan Normal UniversityChengdu 610101China School of Chemical Engineering Sichuan UniversityChengdu 610065China State Key Laboratory of Polymer Materials Engineering Sichuan UniversityChengdu 610065China

Nanoemulsions are widely used as advanced pharmaceutical delivery systems in biomedical field, due to their high encapsulation efficiency and good therapy *** techniques that produce nanoemulsions with controllable sizes and compositions are promising for creating advanced nanoemulsion systems for pharmaceutical *** review summarizes recent advances on low-energy emulsification techniques for producing nanoemulsions, and the use of these nanoemulsions as advanced pharmaceutical delivery systems and as templates to create drug-loaded functional particles for biomedical ***, nanoemulsification techniques that utilize elaborate interfacial physics/chemistry and micro-/nano-fluidics, featured with relatively-low energy input, to produce nanoemulsions with controllable sizes and compositions, are *** of these nanoemulsions to create nanoemulsionincorporated milli-particles, drug-loaded nanoparticles and nanoparticle-incorporated microparticles with sizes ranging from several millimeters to sub-10 nm are *** and efficient use of the nanoemulsions, functional nanoparticles and milli-/micro-particles integrated with nanoemulsions or nanoparticles for advanced pharmaceutical delivery in biomedical field are highlighted, with focus on how the interplay between their sizes and compositions achieve desired pharmaceutical-delivery ***, perspectives on further advances on the controllable production of nanoemulsions are provided.

关键词： Nanoemulsions Interfaces Drug delivery Template synthesis Nanoparticles

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In-situ SEM characterization of fracture mechanism of TiB/Ti-2Al-6Sn titanium matrix composites after electroshocking treatment

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Rare Metals 2024年第6期43卷 2805-2818页

作者： Ya-Ya Wu Jian Zhou guo-Lei Han Yan Wen Zhou Wang Li-qiang Wang wei-Jie Lv Le-Chun Xie Lin Hua Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China Hubei Collaborative Innovation Center for Automotive Components Technology Wuhan 430070China Faculty of Materials and Manufacturing Beijing University of TechnologyBeijing 100124China State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

In this article,in-situ scanning electron microscope characterization of the tensile properties of TiB/Ti-2Al-6Sn titanium matrix composite(TMC)was conducted before and after electroshocking treatment(EST).After EST,the tensile strength increased by 113.2 *** effect of EST on the tensile strength and fracture behavior of TiB was investigated using in-situ characterization of the fracture morphology and crack propagation path of the matrix and *** EST,TiB fracture introduced cracks that extended into the matrix,resulting in material *** EST,the refined TiB improved the bearing capacity of the matrix,thereby improving TMC ***,after EST,the cracks were introduced into the matrix,and resulting the fracture of matrix *** an increase in the external load,cracks in the matrix were observed to propagate to TiB,and the refined TiB was fractured,detached,and pulled out,resulting in the formation of *** the propagation path of the main crack after EST showed that the deflection angle of the main crack *** micro structure of the fracture surface indicated that the fracture of the matrix was plastic,whereas that of TiB was *** EST,the size and area of the dimples increased,confirming the increase in *** results revealed that the comprehensive mechanical properties of TiB/Ti-2Al-6Sn improved after ***,EST is an efficient method for tailoring the micro structures and mechanical properties of TMCs.

关键词： TiB/Ti-2Al-6Sn In-situ microstructure characterization Tensile properties Reinforcement Electroshocking treatment(EST)

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Carbendazim residue in plant-based foods in China:Consecutive surveys from 2011 to 2020

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Environmental Science and Ecotechnology 2024年第1期17卷 109-118页

作者： Dou Wang Guiling yang Xiao Yun Ting Luo Hao guo Liying Pan wei Du Yanhua Wang qiang Wang Pu Wang Qinghua Zhang Yun Li Nan Lin State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Laboratory(Hangzhou)for Risk Assessment of Agricultural Products of Ministry of AgricultureInstitute of Agro-product Safety and NutritionZhejiang Academy of Agricultural SciencesHangzhou310021ZhejiangChina College of Urban and Environmental Sciences Peking UniversityBeijing100871China Yunnan Provincial Key Laboratory of Soil Carbon Sequestration and Pollution Control Faculty of Environmental Science&EngineeringKunming University of Science&TechnologyKunming650500China Hubei Key Laboratory of Industrial Fume and Dust Pollution Control School of Environment and HealthJianghan UniversityWuhan430056China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing100085China Key Laboratory of Agro-Product Quality and Safety of Ministry of Agriculture Institute of Quality Standards and Testing Technology for Agro-ProductsChinese Academy of Agricultural SciencesBeijing100081China Department of Environmental Health School of Public HealthShanghai Jiao Tong UniversityShanghai200025China

Carbendazim,a widely used fungicide in China,has been found to have reproductive toxicity and mutagenic ***,information on the spatial-temporal variations of carbendazim residues in food in China is ***,we investigated the presence of carbendazim in China's plant-based foods from 2011 to 2020,evaluated the spatial-temporal characteristics,and assessed the associated exposure risks in the Chinese *** results revealed a high detection frequency of carbendazim in fruits(26.4%)and high concentrations in vegetables(~110 mg kg^(-1)),indicating widespread misuse of the *** acute risks of consuming certain vegetables and cereals exceeded the recommended limits by up to 12 and 5 times,*** there has been a decline in carbendazim residue levels in food since the implementation of the Chinese government's action plan for zero growth of pesticide use in 2015,some provinces still exhibited high levels of carbendazim in multiple food categories,which were positively correlated with annual pesticide *** highlight that carbendazim contamination reflects the broader issue of pesticide use in *** emphasizes the need for committed and targeted national policies to reduce carbendazim residues in food and suggests that such measures could also regulate the use of other pesticides,given that pesticide abuse in China is not limited to specific *** call for the re-evaluation of maximum residue limits of carbendazim,particularly in highly consumed foods such as cereals.

关键词： Carbendazim Plant-based foods China Spatial-temporal variations Exposure and risk assessment

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New roles of research data infrastructure in research paradigm evolution

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Journal of Data and Information Science 2024年第2期9卷 104-119页

作者： Yizhan Li Lu Dong Xiaoxiao fan Ren wei Shijie guo Wenzhen Ma Zexia Li National Library Science Chinese Academy of SciencesBeijing 100190China Department of Information Resources Management School of Economics and ManagementUniversity of Chinese Academy of SciencesBeijing100190China Bureau of Facility Support and Budget Chinese Academy of SciencesBeijing 100864China

Research data infrastructures form the cornerstone in both cyber and physical spaces,driving the progression of the data-intensive scientific research *** opinion paper presents an overview of global research data infrastructure,drawing insights from national roadmaps and strategic documents related to research data *** emphasizes the pivotal role of research data infrastructures by delineating four new missions aimed at positioning them at the core of the current scientific research and communication *** four new missions of research data infrastructures are:(1)as a pioneer,to transcend the disciplinary border and address complex,cutting-edge scientific and social challenges with problem-and data-oriented insights;(2)as an architect,to establish a digital,intelligent,flexible research and knowledge services environment;(3)as a platform,to foster the high-end academic communication;(4)as a coordinator,to balance scientific openness with ethics needs.

关键词： Research data infrastructure Landscape Data-centric Problem-oriented

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To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 529-538页

作者： Ling-Hou Meng Xian-wei Mo Bing-Yu yang Hai-Quan Qin Qing-Zhou Song Xin-Xin He qiang Li Zheng Wang Chang-Lin Mo guo-Hai yang Department of Gastrointestinal Surgery Guangxi Clinical Research Center for Colorectal CancerGuangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Colorectal and Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Radiology Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina First Department of Chemotherapy Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Over 90%of rectal cancer patients develop low anterior resection syndrome(LARS)after sphincter-preserving *** current globally recognized evaluation method has many drawbacks and its subjectivity is too strong,which hinders the research and treatment of *** To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging(MRI)defecography,and pathogenesis of *** We evaluated 34 patients using the standard LARS score,and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS *** In the LARS score model,there were 10(29.41%)mild and 24(70.58%)severe cases of *** comparison of defecation rate between the two groups was 29.36±14.17%versus 46.83±18.62%(P=0.004);and MRI-rectal compliance(MRI-RC)score was 3.63±1.96 versus 7.0±3.21(P=0.001).Severe and mild LARS had significant differences using the two evaluation *** was a significant negative correlation between LARS and MRI-RC score(P<0.001),and they had a negative correlation with defecation rate(P=0.028).CONCLUSION MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

关键词： Anterior resection syndrome Colorectal cancer Diagnostic evaluation system Magnetic resonance imaging defecography Pathogenesis

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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan guo Pan Xiang Xiaojiao Sun wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin qiang Huiliang Li Pengcheng Shu Xiaozhong Peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina State Key Laboratory of Common Mechanism Research for Major Diseases Beijing 100005China Wolfson Institute for Biomedical Research University College LondonGower StreetLondon WC1E 6BTUK Chinese Institute for Brain Research Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream ***,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and ***,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal ***,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and ***6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and *** finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

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