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Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats

Neuroscience Bulletin 2016年第6期32卷 523-530页

作者： Xiao-Fei Wang Tai-Yun Zhao Rui-Bin Su Ning Wu Jin Li State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of NeuropsychopharmacologyBeijing Institute of Pharmacology and Toxicology

Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

关键词： Keywords Agmatine Opioid addiction HippocampusExtracellular glutamate NMDA receptors

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Mechanism and impact of a novel allosteric AMPA receptor modulator on protection against respiratory depression

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中国药理学与毒理学杂志 2018年第4期32卷 276-277页

作者： Wei DAI Xiang GAO Yu-lei LI Zheng YONG Rui-Bin Su State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hyp.notics.To explore the mechanism of LCX001 on protection against respiratory depression,a novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration.METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid(fentanyl and TH-030418),propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate analgesic effect of LCX001.binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation.The function of AMPA receptors were determined by location of receptors in the membrane and state of channel opening,and both processes were impressed by AMPA receptor regulatory proteins.Ac.cording to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by west.ern blotting.The variation of receptor surface location was observed by live cell imaging.The regula.tion on neuronal Ca^(2+) and cell function was investigated intensively by Ca^(2+) imaging to clarify mecha.nism of LCX001.REsuLTS LCX001 effectively rescued and prevented opioid(fentanyl and TH-030418),propofol,and pentobarbital-induced respiratory depression by strengthening respiratory fre.quency and minute ventilation in rats.The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001,in contrast to some ampakines that did not affect analgesia.Fur.thermore,LCX001 potentiated [3 H]AMPA and L-glutamate binding affinity to AMPA receptors,and facili.tated glutamate-evoked inward currents in HEK293 cells stably expressing GluA2(R).Importantly,appli.cation of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioid-induced abnormal intracellular Ca^(2+) load,which might par.ticipate in breathing modulation.CONCLUSION The novel pharmacological effe

关键词：麻醉药镇静催眠药临床分析治疗方法

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Efficacy and Mechanism of Buxue Yimu Pillson Gynecological Anemia:A Combination of Clinical and Network Pharmacology Study

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Chinese Journal of Integrative Medicine 2022年第12期28卷 1072-1080页

作者： WANG Yan-fang DENG Yan ZHANG su-ying LIU Dong LUO bin WANG Xue DENG Miao MA rui-lin suN Ai-jun Department of Obstetrics and Gynecology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Obstetrics and Gynecology the Second Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410001China West China Second Hospital Key Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityMinistry of EducationSichuan UniversityChengdu 610041China Department of Obstetrics and Gynecology Hangzhou Women's Hospital(Hangzhou Maternity and Child Health Care Hospital)Hangzhou 310008China

Objective:Tocompare the clinical efficacyand safety of oral administration of BuxueYimuPills(BYP),ferrous sulfate(FS),and the combination of BYP and FS on gynecological anemia,and investigate the mechanisms using network pharmacology.Methods:A randomized,controlled,multi-center clinical trial was conducted.Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized(using the block randomization method)into Buxue Yimu Pills group(24 g/d),oral iron group(FS Tablets,0.9 g/d),and combined treatment group(BYP,24g/d plus FS Tablets,0.9 g/d),50 patients in each group.At the enrollment and 4-week treatment,complete blood count,serum iron indexes were evaluated.Adverse events,liver and renal functions,as well as blood coagulation were observed.Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.Results:Ten(20%)and 7(14%)participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups.All 3 groups showed elevated hemoglobin.The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity.No change in iron indexes was observed in BYP group.The patients in the combination treatment group neither showed significant changes in serum ferritin nortotal iron-binding capacity.No significant adverse reactions were observed in the BYP group.The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia.Biological processes and pathways including regulation of inflammation,hormone,angiogenesis and hemostasis,responsetodecreased oxygen levels,effects on myeloma cell,and responseto metal ions were identified.Conclusion:BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution.

关键词： Chinese medicine Buxue Yimu Pills gynecological anemia network pharmacology multi-target mechanism

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Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

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Zoological Research 2023年第3期44卷 620-635页

作者： rui-Can Cao Yue Lv Gang Lu Hong-bin Liu Wuming Wang Chunlai Tan Xian-Wei su Zhiqiang Xiong Jin-Long Ma Wai-Yee Chan Center for Reproductive Medicine Shandong UniversityJinanShandong 250012China Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics The Chinese University of Hong KongHong Kong SARChina CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinanShandong 250012China Shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250012China SDIVF R&D Centre 12WHKSTPHong Kong SARChina Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

关键词： Extracellular vesicles Premature ovarian insufficiency Human induced pluripotent stem cell-derived mesenchymal stem cells ILK-PI3K/AKT pathway

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Carbon dots embedded nanofiber films:Large-scale fabrication and enhanced mechanical properties

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Chinese Chemical Letters 2022年第1期33卷 304-307页

作者： Chang Liu rui Cheng Jiazhuang Guo Ge Li He Li Hong-Gang Ye Zhi-bin Liang Cai-Feng Wang su Chen State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical Engineeringand Jiangsu Key Laboratory of Fine Chemicals and Functional Polymer MaterialsNanjing Tech UniversityNanjing 210009China

Valuable application prospects and large-scale production technologies are powerful driving forces for the development of materials science.Carbon dots(CDs)are a kind of promising carbon-based fluorescent nanomaterials,which possess wide application prospects based and even beyond the fluorescence properties.Herein,we report the fast and high-yield synthesis of CDs and the large-scale preparation of fluorescent nanofiber films with enhanced mechanical properties.CDs were prepared from magnetic hyperthermia treatment of citric acid and carbamide,with the output of 25.37 g in a single batch.The asprepared CDs exhibit a high absolute photoluminescence(PL)quantum yield(QY)of 67%and wonderful dispersibility in polar solvents.Then,solution blow spinning of CDs and polymer matrixes of alcohol soluble polyurethane(APU)and polyacrylonitrile(PAN)led to large-area fluorescent CDs-embedded nanofiber films,APU/CDs(size:120 cm×18 cm)and PAN/CDs(size:120 cm×22 cm),respectively.The resultant large-area APU/CDs and PAN/CDs nanofiber films have dramatically enhanced mechanical properties,to show integrated improvement of tensile strength and elongation.

关键词： Carbon dots Mass production Solution blow spinning Nanofiber Mechanical properties

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Involvement of VGLUT2 in Neuropathic Pain and Its Regulation by Wnt1/β-Catenin Signaling

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神经药理学报 2019年第Z1期 52-53页

作者： YU Gang su rui-bin State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of NeuropsychopharmacologyBeijing Institute of Pharmacology and Toxicology

Backgrounds:Vesicular glutamate transporters(VGLUTs),which transport glutamate into presynaptic vesicles selectively,are fundamental in glutamate storage and release. The distribution of VGLUT2 isoform in CNS suggests a possible involvement of VGLUT2 in pain signaling. Objective:The present study was aimed to investigate the involvement of VGLUT2 in neuropathic pain and to elucidate the regulatory mechanism of VGLUT2,in a mouse spared nerve injury(SNI) model. Methods:The temporal changes in VGLUT2 expression were determined by western blot and immunohistochemistry in the spinal cord and pain-related brain regions of SNI mice. The cell distribution characteristics of VGLUT2 in the pathological condition were observed by immunofluorescent staining. Then,we regulated the expression and function of VGLUT2 by shRNA interference and VGLUT inhibitors respectively,and the behavioral consequences were observed. We also investigated the effects of VGLUT2 down-regulation or inhibition on glutamate release. Finally,the effects of Wnt/β-catenin signaling on VGLUT2 expression and pain behavior were investigated by using Wnt agonist,Wnt1,and Wnt/β-catenin pathway inhibitor XAV939 in SNI mice. Results:SNI surgery induced significant up-regulation of VGLUT2 in the spinal cord and supraspinal regions. In SNI mice,VGLUT2 is mainly co-locolized with NeuN and MAP2,but not Iba-1 and GFAP. Intrathecal or intracerebral administration of VGLUT2 shRNAs or CSB6 B significantly attenuated mechanical allodynia and decreased glutamate release. Meanwhile,Wnt1/β-catenin signaling was also activated in SNI mice. Wnt agonist or Wnt1 significantly increased VGLUT2 expression,while Wnt/β-catenin pathway inhibitor XAV939 decreased VGLUT2 expression. Additionally,XAV939 attenuated mechanical allodynia in mice,and this effect was in accordance with down-regulation of VGLUT2 protein levels. VGLUT2 shRNAs significantly attenuated mechanical allodynia induced by Wnt agonist or Wnt1. Conclusion:The changes in VGLUT2 expression and function are involved in

关键词： VGLUT2 neuropathic pain RNA interference Glutamate release Wnt1 β-catenin

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Inverse Calculation and Regularization Process for the Solar Aspect System(SAS) of HXI Payload on ASO-S Spacecraft

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Research in Astronomy and Astrophysics 2024年第4期24卷 13-34页

作者： Ji-rui Yu Ping Ruan Yang su Ying-Hong He Jin-You Tao Zhe Zhang Song Guo bin Xue Jian-Feng Yang Xi'an Institute of Optics and Precision Mechanics of Chinese Academy of Sciences Xi'an 710119China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Dark Mater and Space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjing 20034China School ofAstronomy and Space Science Universityof Science andTechnologyof ChinaHefei 230026China

For the ASO-S/HXI payload, the accuracy of the flare reconstruction is reliant on important factors such as the alignment of the dual grating and the precise measurement of observation orientation. To guarantee optimal functionality of the instrument throughout its life cycle, the Solar Aspect System (SAS) is imperative to ensure that measurements are accurate and reliable. This is achieved by capturing the target motion and utilizing a physical model-based inversion algorithm. However, the SAS optical system’s inversion model is a typical ill-posed inverse problem due to its optical parameters, which results in small target sampling errors triggering unacceptable shifts in the solution. To enhance inversion accuracy and make it more robust against observation errors, we suggest dividing the inversion operation into two stages based on the SAS spot motion model. First, the as-rigid-aspossible (ARAP) transformation algorithm calculates the relative rotations and an intermediate variable between the substrates. Second, we solve an inversion linear equation for the relative translation of the substrates, the offset of the optical axes, and the observation orientation. To address the ill-posed challenge, the Tikhonov method grounded on the discrepancy criterion and the maximum a posteriori (MAP) method founded on the Bayesian framework are utilized. The simulation results exhibit that the ARAP method achieves a solution with a rotational error of roughly±3 5 (1/2-quantile);both regularization techniques are successful in enhancing the stability of the solution, the variance of error in the MAP method is even smaller—it achieves a translational error of approximately±18μm (1/2-quantile) in comparison to the Tikhonov method’s error of around±24μm (1/2-quantile). Furthermore, the SAS practical application data indicates the method’s usability in this study. Lastly, this paper discusses the intrinsic interconnections between the regularization methods.

关键词： methods:data analysis sun:flares sun:X-rays gamma rays

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In-situ synthesis of stable perovskite quantum dots in core-shell nanofibers via microfluidic electrospinning

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Chinese Chemical Letters 2023年第3期34卷 518-521页

作者： rui Cheng Zhi-bin Liang Haixia Shen Jiazhuang Guo Cai-Feng Wang su Chen State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical Engineeringand Jiangsu Key Laboratory of Fine Chemicals and Functional Polymer MaterialsNanjing Tech UniversityNanjing 210009China

Perovskite quantum dots(PQDs) possess remarkable optical properties, such as tunable photoluminescence(PL) emission spectra, narrow full width at half maximum(FWHM) and high PL quantum yield(QY), endowing the PQDs great application prospects. However, the inherent structural instability of PQDs has seriously hindered the application of PQDs in various photoelectric devices. In this work, a microfluidic electrospinning method was used to fabricate color-tunable fluorescent formamidinium lead halogen(FAPbX_(3), X = Cl, Br, I) PQDs/polymer core-shell nanofiber films. The core-shell spinning nanofiber not only supplies the interspace for the in-situ formation of PQDs, but also significantly reduces the permeability of moisture and oxygen in the air, which greatly improves the stability of PQDs. After adjusting the composition of precursors, the blue-emissive polystyrene(core) and polymethyl methacrylate(shell) coated FAPbCl_(3) QDs(abbreviated as PS/FAPbCl_(3)/PMMA, hereinafter), green-emissive PS/FAPbBr_(3)/PMMA and redemissive PS/FAPbI_(3)/PMMA nanofiber films were fabricated with the highest PL QY of 82.3%. Moreover,the PS/FAPbBr_(3)/PMMA nanofiber film exhibits great PL stability under blue light irradiation, long-term storage in the air and water resistance test. Finally, the green-and red-emissive nanofiber films were directly applied as light conversion films to fabricate wide-color-gamut display with the color gamut of 125%, indicating their tremendous potentials in optoelectronic applications.

关键词： Perovskite quantum dots Microfluidic electrospinning Nanofiber PL stability Display

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致幻剂的药理作用及其机制研究进展

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中国药理学与毒理学杂志 2021年第4期35卷 241-250页

作者：孙毅苏瑞斌军事科学院军事医学研究院毒物药物研究所北京100850 抗毒药物与毒理学国家重点实验室北京100850 神经精神药理学北京市重点实验室北京100850

致幻剂是一类使人产生幻觉、发生意识改变的5-羟色胺(5-HT)受体激动剂,是新型毒品"邮票"的主要成分。除独特的致幻作用,致幻剂也会引起眩晕、嗜睡、血压和心率升高等可恢复性躯体症状。致幻剂滥用会导致精神紊乱、持续性感觉障碍等精神... 详细信息

致幻剂是一类使人产生幻觉、发生意识改变的5-羟色胺(5-HT)受体激动剂,是新型毒品"邮票"的主要成分。除独特的致幻作用,致幻剂也会引起眩晕、嗜睡、血压和心率升高等可恢复性躯体症状。致幻剂滥用会导致精神紊乱、持续性感觉障碍等精神性副作用,重复使用会使机体产生耐受。尽管尚未有致幻剂直接致人死亡的确切证据,但其使用有间接导致死亡的风险。近年来,诸多临床应用研究表明,致幻剂具有镇痛、治疗成瘾、治疗自身免疫性疾病、改善抑郁和焦虑等精神类疾病的潜能。目前普遍认为致幻剂主要通过5-HT2A受体发挥作用,但具体机制尚不明确。本文对致幻剂的概念、药理效应、主要作用机制和临床应用潜能进行综述,为致幻剂作用机制研究、防治药物开发及临床应用提供参考。

关键词：致幻剂 5-羟色胺受体物质滥用

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Effect of China's industrial structure adjustment on carbon emissions

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Ecological Economy 2017年第2期10卷 117-124页

作者： FENG rui DAI bin-zheng su Hui School of Economics and Statistics Guangzhou University China Lounge Investments Limited

Confronting the contradiction between the rapid development of economy and the effective protection of environment, and developing low carbon economy by optimizing the industrial structure have become one of the effective way to attract more attention. In the paper, we made a research on the correlation between china's three main industries and carbon emission intensity to find out the main factors which affect the intensity of carbon emission in China by measuring the gross emission in china's 28 main provinces in 2003-2013 and using Grey correlation analysis based on the change tendency. The results indicate that the second industry has the largest correlation with carbon emission intensity; the tertiary industry helps reduce the intensity of carbon emission, but it is not very obvious; the first industry has the least impact on carbon emission intensity. In the last part, according to the characteristics of industrial structure and carbon emission, we put forward the suggestions and strategies on the adjustment of china's industrial structure in future with the results analysis.

关键词： industrial structure carbon emission intensity grey correlation analysis

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