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2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li Zhichao Fan Ling Zou Siwei Chen lingjuan zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

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血清CRP/ALB与PCT/ALB对急性胰腺炎严重程度的早期预测价值

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中国临床研究 2024年第5期37卷 760-763页

作者：朱令娟崔静郑州大学第二附属医院消化内科河南郑州450053

目的探讨C反应蛋白与白蛋白比值(CRP/ALB)、降钙素原与白蛋白比值(PCT/ALB)对急性胰腺炎(AP)严重程度的早期预测价值。方法回顾性分析2020年1月至2022年12月郑州大学第二附属医院住院治疗的133例AP患者的临床资料。其中,非重症急性胰腺... 详细信息

目的探讨C反应蛋白与白蛋白比值(CRP/ALB)、降钙素原与白蛋白比值(PCT/ALB)对急性胰腺炎(AP)严重程度的早期预测价值。方法回顾性分析2020年1月至2022年12月郑州大学第二附属医院住院治疗的133例AP患者的临床资料。其中,非重症急性胰腺炎(NSAP)组85例,重症急性胰腺炎(SAP)组48例。对两组患者的年龄、住院总天数、转入ICU率、血淀粉酶、白细胞(WBC)、红细胞比容(HCT)、Ca^(2+)、血清肌酐(Cr)、血清尿素氮(BUN)、D-二聚体、PCT、CRP、ALB、PCT/ALB、CRP/ALB等进行单因素方差分析,筛选出与AP严重程度相关的指标,并对筛选出的指标进行ROC曲线分析和二元logistic回归分析。结果ROC曲线分析结果显示,CRP、CRP/ALB、PCT、PCT/ALB预测AP严重程度的曲线下面积分别为0.793、0.804、0.869、0.881;logistic回归分析结果显示,CRP/ALB[OR=1.685,95%CI(1.293,2.195)]、PCT/ALB[OR=1.255,95%CI(1.052,1.497)]是早期预测AP严重程度的独立危险因素。结论CRP/ALB、PCT/ALB比值越高,AP患者发展为重症的可能性越大,二者与AP患者的疾病严重程度呈正相关。

关键词：急性胰腺炎,重症严重程度 C反应蛋白与白蛋白比值降钙素原与白蛋白比值

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Free-cell therapeutics and mechanism of exosomes from adipose-derived stem cells in promoting wound healing: current understanding and future applications

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Chinese Medical Journal 2022年第15期135卷 1803-1805页

作者： Na Liu Yun Xie Yonghuan Zhen Yujia Shang GuanhuiEr Wang lingjuan zhu Yang An Department of Plastic Surgery Peking University Third HospitalBeijing 100191China College of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyangLiaoning 110016China Department of Plastic and Reconstructive Surgery Shanghai Ninth People's HospitalShanghai Jjao Tong University School of MedicineShanghai 200011China

Adipose stem cells(ADSCs)have been reported to have multidirectional differentiation potential,and can promote cell proliferation and growth,and nerve regeneration function,which has become a promising treatment regimen forwound *** derived from ADSCs(ADSCs-Exos)have excellenttissuerepairfunctions,including high vascular endothelial growth factor A,fibroblast growth factor_2,hepatocyte growth factor,platelet-derived growth factor subunit BB,and other importantwoundhealingfactors.l Supplementary Figure1,http:/***/CM9/A828 is a simplified diagram of the exosome formation and release model.

关键词： wound healing Figure

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Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

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Acta Pharmaceutica Sinica B 2022年第2期12卷 532-557页

作者： Leilei Fu Wenke Jin Jiahui Zhang lingjuan zhu Jia Lu Yongqi Zhen Lan Zhang Liang Ouyang Bo Liu Haiyang Yu Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China College of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110064China State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved *** non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy,with potentially lower overall costs and shorter *** non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers,with the aid of some new emerging technologies,such as omics sequencing and artificial intelligence to overcome the bottleneck of drug ***,in this review,we focus on summarizing the therapeutic potential of non-oncology drugs,including cardiovascular drugs,microbiological drugs,small-molecule antibiotics,anti-viral drugs,anti-inflammatory drugs,antineurodegenerative drugs,antipsychotic drugs,antidepressants,and other drugs in human *** also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer *** together,these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

关键词： Drug repurposing Non-oncology drug Cancer therapy Cardiovascular drug Microbiological drug Small-molecule antibiotics Anti-viral drug Anti-inflammatory drug

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Antimalarial and neuroprotective ent-abietane diterpenoids from the aerial parts of Phlogacanthus curviflorus

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中国天然药物:英文版 2023年第8期21卷 619-630页

作者： LI Jia MENG Xiao YIN Chengyue ZHANG Lixia LIN Bin LIU Peng zhu lingjuan WANG Haifeng LIU Hongwei ZHANG Xue YAO Xinsheng School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Institute of Traditional Chinese Medicine&Natural Products College of PharmacyJinan UniversityGuangzhou 510632China

Six new ent-abietane diterpenoids,abientaphlogatones A−F(1−6),along with two undescribed ent-abietane diterpenoid glucosides,abientaphlogasides A−B(7−8)and four known analogs were isolated from the aerial parts of Phlogacanthus curviflorus(***).The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),one-dimensional and two-dimensional nuclear magnetic resonance(NMR)spectroscopy,electronic circular dichroism(ECD)spectra,and quantum chemical ***,compounds 5 and 6 represented the first reported instances of entnorabietane diterpenoids from the genus *** theβ-hematin formation inhibition assay,compounds 2,4,7−10,and 12 displayed antimalarial activity,with IC_(50) values of 12.97−65.01μmol·L−***,compounds 4,5,8,and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H_(2)O_(2) and MPP+.

关键词： Phlogacanthus curviflorus Acathaceae ent-Abietane diterpenoids Antimalarial activity Neuroprotective effect

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Factors influencing myogenic differentiation of adipose-derived stem cells and their application in muscle regeneration

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Chinese Journal Of Plastic and Reconstructive Surgery 2022年第3期4卷 126-132页

作者： Na Liu Guanhuier Wang Yonghuan Zhen Yujia Shang Fangfei Nie lingjuan zhu Zhenmin Zhao Yang An Department of Plastic Surgery Peking University Third HospitalBeijing 100191China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Skeletal muscle regeneration mainly depends on muscle satellite cells;however,these cells are not sufficient for supporting repair and regeneration in volumetric muscle loss(VML),Duchenne muscular dystrophy,and other muscle injuries or muscle *** such,much work has been conducted in recent years to search for myogenic stem ***-derived stem cells(ADSCs)have a wide range of sources,rapid growth,and multi-directional differentiation potential,and have become vital candidates for muscle *** factors influence the myogenic differentiation capacity of *** paper reviews the regulatory aspects and possible factors that have been identified in recent years to affect myogenic differentiation of *** on these factors,gene editing,and perfusion concepts,a method was proposed to achieve maximal differentiation efficiency of *** study focused on the application of ADSCs in muscle regeneration and *** on the importance of myogenic differentiation of ADSCs for the repair and regeneration of muscle damage,this study provides a basis for future research surrounding the efficient induction of myogenic differentiation of ADSCs in vitro.

关键词： Adipose-derived stem cells Muscle regeneration Muscle diseases Myogenic differentiation Regulatory factors

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药学有机化合物波谱解析课程思政教学改革探讨

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药学教育 2024年第3期40卷 31-35页

作者：李玲芝高慧媛华会明朱玲娟刘庆博张艳沈阳药科大学中药学院沈阳110016

药学有机化合物波谱解析课程是面向中药学、药学等相关专业本科生的核心专业基础课程。目前教学中存在的主要问题为基础理论比较抽象,学习研究难度大;而且专业课程教学重点关注专业知识的传授,与思政教学融入度不高。教师要深度挖掘药... 详细信息

药学有机化合物波谱解析课程是面向中药学、药学等相关专业本科生的核心专业基础课程。目前教学中存在的主要问题为基础理论比较抽象,学习研究难度大;而且专业课程教学重点关注专业知识的传授,与思政教学融入度不高。教师要深度挖掘药学有机化合物波谱解析课程思政教育资源,根据不同专业人才培养目标制定相应的教学方案,采用多元化的教学方法,完善考核制度。

关键词：药学有机化合物波谱解析思政教学教学改革

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Stress-strain relationship for reactive powder concrete with recycled powder under uniaxial compression

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Frontiers of Structural and Civil Engineering 2024年第7期18卷 1015-1027页

作者： Peng zhu Yunming zhu Wenjun QU Liyu XIE College of Civil Engineering Tongji UniversityShanghai 200092China Key Laboratory of Performance Evolution and Control for Engineering Structures of Ministry of Education Tongji UniversityShanghai 200092China

The recycled powder(RP)from construction wastes can be used to partially replace cement in the preparation of reactive powder *** this paper,reactive powder concrete mixtures with RP partially replacing cement,and natural sand instead of quartz,are *** curing is used,instead of steam curing that is normally requested by standard for reactive powder *** influences of RP replacement ratio(0%,10%,20%,30%),silica fume proportion(10%,15%,20%),and steel fiber proportion(0%,1%,2%)are *** effects of RP,silica fume,and steel fiber proportion on compressive strength,elastic modulus,and relative absorption energy are analyzed,and theoretical models for compressive strength,elastic modulus,and relative absorption energy are established.A constitutive model for the uniaxial compressive stress-strain relationship of reactive powder concrete with RP is *** the increase of RP replacement ratio from 0% to 30%,the compressive strength decreases by 42% and elastic modulus decreases by 24%.

关键词： recycled powder reactive powder concrete elastic modulus relative absorbed energy stress-strain relationship

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Carbon Emission Effects Driven by Evolution of Chinese Dietary Structure from 1987 to 2020

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Chinese Geographical Science 2024年第1期34卷 181-194页

作者： zhu Yuanyuan ZHANG Yan zhu Xiaohua Key Laboratory of Geographic Process Analysis&Simulation Hubei Province Central China Normal UniversityWuhan430079China Institute of Geographic Sciences and Natural Resources Research Chinese Academy of SciencesBeijing100101China

Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important *** study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary *** results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption *** dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality *** the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing *** per capita food carbon emissions of residents in urban and rural showed an overall upward *** total food carbon emissions in urban increased significantly,while that in rural increased first and then *** influence of beef and mutton on carbon emissions is the highest in dietary *** with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.

关键词： dietary structure structural evolution carbon emission effects carbon neutrality China

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Synergistic catalysis of the N-hydroxyphthalimide on flower-like bimetallic metal-organic frameworks for boosting oxidative desulfurization

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Petroleum Science 2024年第1期21卷 674-682页

作者： Jing He Kun zhu Wei Jiang Dong-Ao zhu Lin-Hua zhu Hai-Yan Huang Wen-Shuai zhu Hua-Ming Li Institute for Energy Research Jiangsu UniversityZhenjiang212013JiangsuChina College of Chemistry and Chemical Engineering Hainan Normal UniversityKey Laboratory of Water Pollution Treatment and Resource Reuse of Hainan ProvinceHaikou571158HainanChina

Synergic catalytic effect between active sites and supports greatly determines the catalytic activity for the aerobic oxidative desulfurization of fuel *** this work,Ni-doped Co-based bimetallic metal-organic framework(CoNi-MOF)is fabricated to disperse N-hydroxyphthalimide(NHPI),in which the whole catalyst provides plentiful synergic catalytic effect to improve the performance of oxidative desulfurization(ODS).As a bimetallic MOF,the second metal Ni doping results in the flower-like morphology and the modification of electronic properties,which ensure the exposure of NHPI and strengthen the synergistic effect of the overall *** with the monometallic Co-MOF and naked NHPI,the NHPI@CoNi-MOF triggers the efficient activation of molecular oxygen and improves the ODS performance without an *** sulfur removal of dibenzothiophene-based model oil reaches 96.4%over the NHPI@CoNi-MOF catalyst in 8 h of ***,the catalytic product of this aerobic ODS reaction is sulfone,which is adsorbed on the catalyst surface due to the difference in *** work provides new insight and strategy for the design of a strong synergic catalytic effect between NHPI and bimetallic supports toward high-activity aerobic ODS materials.

关键词： Metal-organic frameworks Doped Bimetallic N-hydroxyphthalimide Aerobic processes Oxidative desulfurization

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