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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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Portal vein embolization combined with ex vivo liver resection and autotransplantation: A novel treatment strategy for end-stage and metastatic hepatic alveolar echinococcosis

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 210-216页

作者： Qiang GUO Mao-Lin Wang Kai Zhong Jia-Long Li Tie-Min Jiang Hao Wen Tuerganaili Aji Ying-Mei Shao Department of Hepatobiliary and Echinococcosis Surgery Digestive and Vascular Surgery CenterFirst Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054China Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region Urumqi 830054China State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Medical UniversityUrumqi 830054China

Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the liver.Most of the affected individ-uals remain asymptomatic and the disease is often diagnosed at an advanced stage.The infection may spread to organs adjacent to the liver or distant locations,eventually causing end-stage multi-ple organ AE.Brain metastasis of AE is the most fatal with an inci-dence rate of 0.2%[1].

关键词： organs echinococcosis metastasis

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Moisture‑Electric–Moisture‑Sensitive Heterostructure Triggered Proton Hopping for Quality‑Enhancing Moist‑Electric Generator

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Nano-Micro Letters 2024年第3期16卷 351-366页

作者： Ya’nan Yang Jiaqi Wang Zhe Wang Changxiang Shao Yuyang Han Ying Wang Xiaoting Liu Xiaotong Sun Liru Wang Yuanyuan Li Qiang GUO Wenpeng Wu Nan Chen Liangti Qu Key Laboratory of Cluster Science Ministry of Education of ChinaKey Laboratory of Photoelectronic/Electrophotonic Conversion MaterialsSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081People’s Republic of China Yangtze Delta Region Academy of Beijing Institute of Technology Jiaxing 314019People’s Republic of China Department of Chemistry Key Laboratory of Organic Optoelectronics&Molecular EngineeringMinistry of EducationTsinghua UniversityBeijing 100084People’s Republic of China

Moisture-enabled electricity(ME)is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can be directly applied to energy harvesting and signal expression.However,ME can be unreliable in numerous applications due to its sluggish response to moisture,thus sacrificing the value of fast energy harvesting and highly accurate information representation.Here,by constructing a moisture-electric-moisture-sensitive(ME-MS)heterostructure,we develop an efficient ME generator with ultra-fast electric response to moisture achieved by triggering Grotthuss protons hopping in the sensitized ZnO,which modulates the heterostructure built-in interfacial potential,enables quick response(0.435 s),an unprecedented ultra-fast response rate of 972.4 mV s^(−1),and a durable electrical signal output for 8 h without any attenuation.Our research provides an efficient way to generate electricity and important insight for a deeper understanding of the mechanisms of moisture-generated carrier migration in ME generator,which has a more comprehensive working scene and can serve as a typical model for human health monitoring and smart medical electronics design.

关键词： Moist-electric generators Grotthuss proton hopping Fast response Durable electrical output Personal health monitoring

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Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

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BIOCELL 2024年第1期48卷 123-138页

作者： ZHENHUA LI HUILAI LV FAN ZHANG ZIMING ZHU Qiang GUO MINGBO WANG CHAO HUANG LIJUAN CHEN WENPAN ZHANG YUN LI ZIqiang TIAN Department of Thoracic Surgery Fourth Hospital of Hebei Medical UniversityShijiazhuang050011China Department of Thoracic Surgery The First Hospital of XingtaiXingtai054001China Department of Thoracic Surgery Affiliated Hospital of Hebei UniversityBaoding050017China Shanghai OrigiMed Co. Ltd.Shanghai200000China Department of Thoracic Surgery The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer type

关键词： DNA polymerases(POLYs) Prognostic biomarker The Cancer Genome Atlas(TCGA) Ubiquitination network

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Single-center retrospective study of the diagnostic value of doubleballoon enteroscopy in Meckel’s diverticulum with bleeding

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1043-1054页

作者： Tian He Chao Yang Jing Wang Ji-Sheng Zhong Ai-Hua Li Ya-Jing Yin Li-Ling Luo Chun-Mei Rao Nian-Fen Mao Qiang GUO Zan Zuo Wen Zhang Ping Wan Yunnan Digestive Endoscopy Clinical Medical Center Department of GastroenterologyThe First People’s Hospital of Yunnan ProvinceThe Affiliated Hospital of Kunming University of Science and TechnologyKunming 650032Yunnan ProvinceChina Department of Medicine Kunming University of Science and TechnologyKunming 650093Yunnan ProvinceChina School of Medicine Yunnan University of Traditional Chinese MedicineKunming 650011Yunnan ProvinceChina Department of Gastroenterology Qujing Hospital of Traditional Chinese MedicineQujing 655000Yunnan ProvinceChina Department of Gastroenterology Yunnan University of Traditional Chinese MedicineKunming 650011Yunnan ProvinceChina

BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate the value of double-balloon enteroscopy(DBE)in MD diagnosis and the prognosis after laparoscopic diverticula resection.AIM To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding.METHODS The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations,auxiliary examination,and follow-up after laparoscopic resection of diverticula.RESULTS(1)Among 84 MD patients complicated with hemorrhage,77 were male,and 7 were female with an average age of 31.31±10.75 years.The incidence was higher in men than in women of different ages;(2)Among the 84 MD patients,65(78.40%)had defecated dark red stools,and 50(58.80%)had no accompanying symptoms during bleeding,indicating that most MD bleeding appeared a dark red stool without accompanying symptoms;(3)The shock index of 71 patients(85.20%)was30%;(4)The DBE-positive rate was 100%(54/54),99mTcpertechnetate-positive scanning rate was 78%(35/45)compared with capsule endoscopy(36%)and small intestine computed tomography(19%).These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding,especially DBE was a highly precise examination method in MD diagnosis;(5)A total of 54 MD patients with hemorrhage underwent DBE examination before surgery.DBE endoscopy revealed many mucosal manifestations including normal appearance,inflammatory changes,ulcerative changes,diverticulum inversion,and nodular hyperplasia,with ulcerative changes being the most common(53.70%).This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding;and(6

关键词： Meckel’s diverticulum with bleeding Double-balloon colonoscopy 99mTc-pertechnetate scanning Capsule endoscopy Ectopic gastric mucosa

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Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction:A randomized non-inferiority trial

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Chinese Medical Journal 2024年第3期137卷 312-319页

作者： Xingshan Zhao Yidan Zhu Zheng Zhang Guizhou Tao Haiyan Xu Guanchang Cheng Wen Gao Liping Ma Liping Qi Xiaoyan Yan Haibo Wang Qingde Xia Yuwang Yang Wanke Li Juwen Rong Limei Wang Yutian Ding Qiang GUO Wanjun Dang Chen Yao Qin Yang Runlin Gao Yangfeng Wu Shubin Qiao Department of Cardiology Beijing Jishuitan HospitalCapital Medical UniversityThe Fourth Clinical Medical College of Peking UniversityBeijing 100035China Peking University Clinical Research Institute Peking University First HospitalBeijing 100191China Department of Cardiology The First Hospital of Lanzhou UniversityLanzhouGansu 730013China Department of Cardiology The First Affiliated Hospital of Liaoning Medical UniversityJinzhouLiaoning 110002China Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China Department of Cardiology Huaihe Hospital of Henan UniversityKaifengHenan 450001China Department of Cardiology Bayannur HospitalBayannurInner Mongolia 015208China Department of Cardiology Puyang People’s HospitalPuyangHenan 457099China Department of Cardiology Xingtai Third HospitalXingtaiHebei 054099China Department of Cardiology Lintao County People’s HospitalDingxiGansu 730599China Department of Cardiology Dancheng County People’s HospitalZhoukouHenan 477150China Department of Cardiology The First People’s Hospital of LingbaoSanmenxiaHenan 472500China Department of Cardiology Shanyin County People’s HospitalShuozhouShanxi 036999China Department of Cardiology Uxin Banner People’s HospitalOrdosInner Mongolia 017399China Department of Cardiology Lingqiu County People’s HospitalDatongShanxi 034499China Department of Cardiology Huaibin County People’s HospitalXinyangHenan 464411China Department of Cardiology Tianzhu County People’s HospitalWuweiGansu 733200China Guangzhou Recomgen Biotech Co. LtdGuangzhouGuangdong 510530China

Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No.NCT028355

关键词： Thrombolytic therapy rhTNK-tPA Randomized controlled trial ST elevation myocardial infarction

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Spontaneous Infection and Periodic Evolving of Domain in a Diffusive SIS Epidemic Model

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 164-191页

作者： qiang Wen guo-qiang Ren Bin Liu School of Mathematics and Statistics Huazhong University of Science and TechnologyWuhan430074China Hubei Key Laboratory of Engineering Modeling and Scientific Computing Huazhong University of Science and TechnologyWuhan430074China

In this paper, we consider a susceptible-infective-susceptible(SIS) reaction-diffusion epidemic model with spontaneous infection and logistic source in a periodically evolving domain. Using the iterative technique,the uniform boundedness of solution is established. In addition, the spatial-temporal risk index R0(ρ) depending on the domain evolution rate ρ(t) as well as its analytical properties are discussed. The monotonicity of R0(ρ)with respect to the diffusion coefficients of the infected dI, the spontaneous infection rate η(ρ(t)y) and interval length L is investigated under appropriate conditions. Further, the existence and asymptotic behavior of periodic endemic equilibria are explored by upper and lower solution method. Finally, some numerical simulations are presented to illustrate our analytical results. Our results provide valuable information for disease control and prevention.

关键词： diffusive SIS model spontaneous infection periodically evolving domain periodic endemic equilibrium

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Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

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Chinese Journal of Chemistry 2024年第5期42卷 533-542页

作者： Dong Wei guo-qiang Lin State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteShanghai Key Laboratory of Systems Regulation and Clinical Translation for CancerRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai200127 China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032 China

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic transformations.This mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late 2023.These reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization reactions.By showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical industry.Key Scientists In 1980,a seminal work by Breslow et al.showed an acceleration of reaction rate in the Diels-Alder reaction.Sharpless and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic solvents.The term "on-water" was then coined to describe this phenomenon.This strategy was further expanded to transition-metal catalyzed transformations by Ackermann in 2011.Later,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou group.Later on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst loading.Very recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck reactions.This mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

关键词： Pd-catalyzed “On-water” Green chemistry Aqueous reactions Mechanism Methodology and reactions Mizoroki-Heck reaction Cross-coupling

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Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating Osteoporosis and Osteoarthritis

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Chinese Journal of Integrative Medicine 2024年第4期30卷 379-384页

作者： XIN Li TAN guo-yao ZHANG qiang ZHANG Qun Good Clinical Practice Development Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhou(510630)China Department of Pharmacy Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou(510120)China

Phellodendron(PN)species,traditionally used in Chinese medicine for centuries,hold promise as a potential treatment for osteoporosis(OP)and osteoarthritis(OA)due to their bioactive compounds.The bioactive compounds,including berberine and palmatine,exhibit anti-inflammatory,antioxidant,and bone-protective properties,contributing to their potential therapeutic benefits in promoting bone health and preventing bone loss.However,challenges such as the need for standardized preparation and dosing,limited clinical studies,and potential interactions with other medications hinder their clinical use.Nonetheless,the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and OA.Further research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

关键词： Phellodendron species bone health osteoporosis osteoarthritis review

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Bald Eagle Search Optimization Algorithm Combined with Spherical Random Shrinkage Mechanism and Its Application

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Journal of Bionic Engineering 2024年第1期21卷 572-605页

作者： Wenyan guo Zhuolin Hou Fang Dai Xiaoxia Wang Yufan qiang Department of Applied Mathematics School of ScienceXi'an University of TechnologyXian 710054ShaanxiChina

Over the last two decades,stochastic optimization algorithms have proved to be a very promising approach to solving a variety of complex optimization problems.Bald eagle search optimization(BES)as a new stochastic optimization algorithm with fast convergence speed has the ability of prominent optimization and the defect of collapsing in the local best.To avoid BES collapse at local optima,inspired by the fact that the volume of the sphere is the largest when the surface area is certain,an improved bald eagle search optimization algorithm(INMBES)integrating the random shrinkage mechanism of the sphere is proposed.Firstly,the INMBES embeds spherical coordinates to design a more accurate parameter update method to modify the coverage and dispersion of the population.Secondly,the population splits into elite and non-elite groups and the Bernoulli chaos is applied to elite group to tap around potential solutions of the INMBES.The non-elite group is redistributed again and the Nelder-Mead simplex strategy is applied to each group to accelerate the evolution of the worst individual and the convergence process of the INMBES.The results of Friedman and Wilcoxon rank sum tests of CEC2017 in 10,30,50,and 100 dimensions numerical optimization confirm that the INMBES has superior performance in convergence accuracy and avoiding falling into local optimization compared with other potential improved algorithms but inferior to the champion algorithm and ranking third.The three engineering constraint optimization problems and 26 real world problems and the problem of extracting the best feature subset by encapsulated feature selection method verify that the INMBES’s performance ranks first and has achieved satisfactory accuracy in solving practical problems.

关键词： Bald eagle search optimization algorithm Spherical coordinates Chaotic variation Simplex method Encapsulated feature selection

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