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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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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang guo Yi guo Yongming Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Tianjin 301617China Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital)Qingdao 266033China School of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China School of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE:To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese Medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3)receptor signaling system as an indicator of the body's energy state,commonly referred to as"Qi".METHODS:The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice,while also assessing adenosine(ADO)levels and adenylate energy charge(EC)at Zusanli(ST36).The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects,the study examined the impact of ATP,a P2X3 receptor antagonist,and adenosine disodium on PTT following acupuncture ***:Acupuncture at Zusanli(ST36)led to significant improvements in PTT in mice,with the most effective interventions being twirling for 2 min and needle retention for 28 *** interventions also resulted in significant increases in ATP *** effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36),and pretreatment with a P2X3 receptor antagonist decreased *** EC peaked at 30 min after intraperitoneal injection of ATP,and pretreatment with various doses of *** 30 min prior to acupuncture increased PTT in a dose-dependent ***,pretreatment with an *** intramuscular injection of adenosine disodium enhanced the effects of ***:This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture,revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture point ST36(Zusanli) adenosine triphosphate receptors,purinergic P2X3 energy state

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p38 Signaling Mediates Naringin-Induced Osteogenic Differentiation of Porcine Metanephric Mesenchymal Cells

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Chinese Journal of Integrative Medicine 2024年第9期30卷 818-825页

作者： JI Peng-cheng XIE Yuan-sheng guo Wen-kai FU Bo CHEN Xiang-mei Chinese PLA Medical School Beijing100853China Department of Nephrology First Medical Center of Chinese PLA General HospitalChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney DiseasesBeijing100853China School of Medicine Nankai UniversityTianjin300071China

Objective:To explore the potential of metanephric mesenchymal cells(MMCs)for osteogenesis and naringin’s ability to enhance this process and its molecular ***:Porcine MMCs at 70 days of gestation were used as tool cells,cultured in osteogenic induction medium,identified by immunocytochemistry *** potential of porcine MMCs and naringin’s ability to enhance this process was tested by detecting changes in cell viability,alkaline phosphatase(ALP)activity,the expression of runt-related transcription factor 2(Runx2),osteopontin(OPN)and osteocalcin(OCN),and the formation of mineralized nodules,and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of ***:Immunocytochemical staining showed that the cells were Vimentin and Six2(+),E-cadherin and CK-18(−).Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability,ALP activity,the expressions of Runx2,OPN and OCN,and the formation of mineralized nodules(P<0.05).The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin,manifested by decreased ALP activity,the expressions of Runx2,OPN and OCN,and the formation of mineralized nodules(P<0.05).Conclusion:Naringin,the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen(Kidney)and strengthening bone,enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.

关键词： metanephric mesenchymal cells naringin osteogenesis differentiation

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Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1525-1541页

作者： Qi Shang Wandong Liu Faith Leslie Jiapei Yang Mingmei guo Mingjiao Sun Guangji Zhang qiang Zhang Feihu Wang School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province Hangzhou 310053China Department of Chemical and Biomolecular Engineering Whiting School of Engineeringthe Johns Hopkins UniversityBaltimoreMD 21218USA Traditional Chinese Medicine“Preventing Disease”Wisdom Health Project Research Center of Zhejiang Hangzhou 310053China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

关键词： Chinese herbal medicines Nano-formulation Activeingredients Drug delivery Cancer immunotherapy Innate immune system Adaptive immune system

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Low-fat microwaved peanut snacks production:Effect of defatting treatment on structural characteristics,texture,color,and nutrition

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Journal of Integrative Agriculture 2024年第7期23卷 2491-2502页

作者： Bo Jiao Xin guo Yiying Chen Shah Faisal Wenchao Liu Xiaojie Ma Bicong Wu Guangyue Ren qiang Wang Institute of Food Science and Technology Chinese Academy of Agricultural Sciences/Key Laboratory of Agro-Products ProcessingMinistry of Agriculture and Rural AffairsBeijing 100193China College of Food and Bioengineering Henan University of Science and TechnologyLuoyang 471000China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China

This study develops low-fat microwaved peanut snacks(LMPS)using partially defatted peanuts(PDP)with different defatting ratios,catering to people’s pursuit of healthy,low-fat *** effects of defatting treatment on the structural characteristics,texture,color,and nutrient composition of LMPS were comprehensively *** structural characteristics of LMPS were characterized using X-ray micro-computed tomography(Micro-CT)and scanning electron microscope(SEM).The results demonstrated that the porosity,pore number,pore volume,brightness,brittleness,protein content,and total sugar content of LMPS all significantly increased(P<0.05)with the increase in the defatting *** the micro level,porous structure,cell wall rupture,and loss of intracellular material could be observed in LMPS after defatting *** made from PDP with a defatting ratio of 64.44%had the highest internal pore structural parameters(porosity 59%,pore number 85.3×10^(5),pore volume 68.23 mm3),the brightest color(L^(*) 78.39±0.39),the best brittleness(3.64±0.21)mm^(–1)),and the best nutrition(high protein content,(34.02±0.38)%;high total sugar content,(17.45±0.59)%;low-fat content,(27.58±0.85)%).The study provides a theoretical basis for the quality improvement of LMPS.

关键词： low-fat microwaved peanut snacks(LMPS) X-ray micro-computed tomography(Micro-CT) porosity texture color nutrition

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Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu qiang Xu Jianjun Zou Yang Sun Wenjie guo State Key Laboratory of Pharmaceutical Biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of Clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th17 Colitis Allosteric activator

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Numerical Analysis of Cold-Formed Thin-Walled Steel Short Columns with Pitting Corrosion during Bridge Construction

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Structural Durability & Health Monitoring 2024年第2期18卷 181-196页

作者： Hongzhang Wang Jing guo Shanjun Yang Chaoheng cheng Jing Chen Zhihao Chen CCCC Second Harbor Engineering Third Engineering Co. Ltd.Zhenjiang212000China Suqian Highway Development Center Suqian223800China School of Mechanics and Civil Engineering China University of Mining and TechnologyXuzhou221116China

Pitting corrosion is harmful during bridge construction,which will lead to uneven roughness of steel surfaces and reduce the thickness of ***,the effect of pitting corrosion on the mechanical properties of cold-formed thin-walled steel stub columns is studied,and the empirical formulas are established through regression fitting to predict the ultimate load of web and flange under pitting *** detail,the failure modes and load-displacement curves of specimens with different locations,area ratios,and depths are obtained through a large number of non-linear finite element *** for the specimens with pitting corrosion on the web,all the specimens are subject to local buckling failure,and the failure mode will not change with pitting corrosion,but the failure location will change with pitting corrosion location;the size,location,and area ratio of pitting corrosion have little influence on the ultimate load of cold-formed thin-walled steel short columns,but the loss rate of pitting corrosion section area has a greater impact on the ultimate bearing *** for the specimen with flange pitting corrosion,the location and area ratio of pitting corrosion have less influence on the ultimate load of cold-formed thin-walled steel short columns,and the section area loss rate has greater influence on the ultimate bearing capacity;the impact of web pitting corrosion on the ultimate load is greater than that of flange pitting corrosion under the same condition of pitting corrosion section *** prediction formulas of limit load which are suitable for pitting corrosion of web and flange are established,which can provide a reference for performance evaluation of corroded cold-formed thin-walled steel.

关键词： Pitting corrosion cold-formed thin-walled steel ultimate load prediction formula short columns

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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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Enhancing the electrochemical performance of Na metal anodes via local eutectic melting in porous Al-Cu alloy hosts

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Nano Research 2024年第7期17卷 6111-6118页

作者： Tao Hu qiang Wu cheng Wang Jialu Chen Fu Su Zibo Chen Yizhou Wang Jianyu Chen Yanwen Ma Jin Zhao State Key Laboratory of Organic Electronics and Information Displays&Institute of Advanced Materials(IAM) Nanjing University of Posts&Telecommunications9 Wenyuan RoadNanjing 210023China Materials Science and Engineering King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia Suzhou Vocational Institute of Industrial Technology 1 Zhineng AvenueSuzhou International Education ParkSuzhou 215104China

Sodium(Na)metal batteries(SMBs)have emerged as promising alternatives to lithium metal batteries for large-scale energy storage applications,owing to their cost-effectiveness,abundance,and favorable redox ***,the practical implementation of SMBs faces several challenges associated with the Na metal anode,including the formation of dendrites,low Coulombic efficiency,and capacity ***,we propose a novel approach to enhance the electrochemical performance of Na metal anodes through a porous Al-Cu alloy host(PAC)fabricated by a local eutectic melting *** local eutectic melting facilitates the development of a conductive network,offering mechanical support,and the porous structure provides abundant channels for the diffusion of Na ions and accommodates volume fluctuations in the Na metal during charge–discharge ***,the PAC exhibits a high average Coulombic efficiency of 99.8%at 1 mA·cm^(−2)for 1 mAh·cm^(−2)and a low voltage polarization of 19 mV during 500 *** study provides valuable insight into the design and fabrication of highperformance Na metal anodes,which hold significant promise for the advancements of next-generation energy storage systems.

关键词： Na metal anode porous Al-Cu alloy porous current collector local eutectic melting

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An improved ASM-HEMT model for kink effect on GaN devices

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JOURNAL OF INFRARED AND MILLIMETER WAVES 2024年第4期43卷 520-525页

作者： Wang, Shuai cheng, Ai-qiang Ge, Chen Chen, Dun-Jun Liu, Jun Ding, Da-Zhi Nanjing Univ Dept Elect Sci & Engn Nanjing 210033 Peoples R China Nanjing Elect Devices Inst Nanjing 210016 Peoples R China Hangzhou Dianzi Univ Dept Elect Informat Hangzhou 310018 Peoples R China Nanjing Univ Sci & Technol Dept Microelect Nanjing 210094 Peoples R China

With the analysis of experiment and theory on GaN HEMT devices under DC sweep, an improved model for kink effect based on advanced SPICE model for high electron mobility transistors (ASM-HEMT) is proposed, considering the relationship between the drain/gate-source voltage and kink effect. The improved model can not only accurately describe the trend of the drain-source current with the current collapse and kink effect, but also precisely fit different values of drain-source voltages at which the kink effect occurs under different gatesource voltages. Furthermore, it well characterizes the DC characteristics of GaN devices in the full operating range, with the fitting error less than 3%. To further verify the accuracy and convergence of the improved model, a load-pull system is built in ADS. The simulated result shows that although both the original ASM-HEMT and the improved model predict the output power for the maximum power matching of GaN devices well, the improved model predicts the power-added efficiency for the maximum efficiency matching more accurately, with 4% improved.

关键词： ASM-HEMT DC current collapse kink effect

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