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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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Remote stereocontrol in the(4+2)cycloadditions of 1,7-zwitterions:Asymmetric synthesis of multifunctionalized tetrahydroquinoline derivatives

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Chinese Chemical Letters 2024年第1期35卷 222-226页

作者： Chen Chen Jin Zhou Jing Jiang Yang Li Ting Mao Cheng Peng gu zhan Wei Huang State Key Laboratory of Southwestern Chinese Medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China

The scope of stereochemistry recognition usually occurs near the chiral scaffold of a ligand or *** stereocontrol,which can surpass the limits of stereorecognition of remote prochiral centers,has long been a challenging object of great interest in asymmetric *** current work realized the remote stereocontrol of 1,7-zwitterion intermediates formed from Huang's o-amino aryl MBH *** simple and easily accessibleβ-ICD as the bifunctional catalyst,multifunctionalized tetrahydroquinoline derivatives could be synthesized via(4+2)cycloadditions with excellent enantioselectivity and diastereoselectivity under mild *** strategy possesses broad substrate scope,and three types of electron-deficient enones are successfully *** studies disclosed the Lewis base-catalyzed reaction pathway,and H-bonding between the catalyst and enones is crucial for long-range ***-up reaction and transformations of the tetrahydroquinoline products demonstrated the potential of this strategy.

关键词： Asymmetric synthesis Tetrahydroquinoline Remote stereocontrol Pyrazolone Lewis base catalysis 1,7-Zwitterion

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硫醇加成/氧化构建具稳定阻转异构体的萘醌化合物

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合成化学 2024年第1期32卷 31-38页

作者：吴玉玲詹固黄维成都中医药大学药学院西南特色中药资源国家重点实验室四川成都611137

轴手性是自然界的本征特性之一,在有机化学和药物化学研究中具有重要意义。醌类化合物广泛存在于天然产物、药物和其他功能性分子中,对构建含稳定阻转异构体的醌类化合物有重要研究价值。(1,2′-联萘)-1′,4′-二酮为一类含有C—C手性... 详细信息

轴手性是自然界的本征特性之一,在有机化学和药物化学研究中具有重要意义。醌类化合物广泛存在于天然产物、药物和其他功能性分子中,对构建含稳定阻转异构体的醌类化合物有重要研究价值。(1,2′-联萘)-1′,4′-二酮为一类含有C—C手性轴的化合物,但与常见的2,2′-双取代的1,1′-联萘不同,其手性轴的旋转能垒较小,室温下构型不稳定,故通过简单高效反应构建具稳定阻转异构体的1,2′-联萘醌是一项有吸引力的课题。本文以不同位阻取代的(1,2′-联萘)-1′,4′-二酮为底物,Cu(OAc)_(2)为助氧剂,EtOH为溶剂,在Et_(3)N的作用下,通过硫醇的加成/氧化反应直接构建了一系列具有稳定阻转异构体的联萘醌衍生物,共经^(1)H NMR,^(13)C NMR和HR-MS表征。

关键词：有机合成醌类联萘硫醇阻转异构

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[3＋3] Formal Cycloadditions of Nitrones from Isatins and Azaoxyallyl Cations for Construction of Spirooxindoles

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Chinese Journal of Chemistry 2017年第6期35卷 857-860页

作者： Weijia Lin gu zhan Minglin Shi Wei Du Yingchun Chen Department of Medicinal Chemistry West China School of Pharmacy Sichuan University Chengdu Sichuan 610041 China College of Pharmacy Third Military Medical University Shapingba Chongqing 400038 China

A [3＋3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxin- doles incorporating a six-membered heterocyclic scaffold.

关键词： cycloaddition spirooxindoles azaoxyallyl cations nitrones 1,3-dipoles

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Environmental Conditions Conducive to the Formation of Multiple Tropical Cyclones over the Western North Pacific

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Advances in Atmospheric Sciences 2024年第10期41卷 2027-2042页

作者： Yining gu Ruifen zhan Xiaomeng LI Department of Atmospheric and Oceanic Sciences/Institute of Atmospheric Sciences Fudan University CMA-FDU Joint Laboratory of Marine Meteorology Institute of Desert and Meteorology China Meteorological Administration

There is limited understanding regarding the formation of multiple tropical cyclones(MTCs). This study explores the environmental conditions conducive to MTC formation by objectively determining the atmospheric circulation patterns favorable for MTC formation over the western North Pacific. Based on 199 MTC events occurring from June to October 1980–2020, four distinct circulation patterns are identified: the monsoon trough(MT) pattern, accounting for 40.3% of occurrences, the confluence zone(CON) pattern at 26.2%, the easterly wave(EW) pattern at 17.8%, and the monsoon gyre(MG) pattern at 15.7%. The MT pattern mainly arises from the interaction between the subtropical high and the monsoon trough, with MTCs forming along the monsoon trough and its flanks. The CON pattern is affected by the subtropical high,the South Asian high, and the monsoon trough, with MTCs emerging at the confluence zone where the prevailing southwesterly and southeasterly flows converge. The EW pattern is dominated by easterly flows, with MTCs developing along the easterly wave train. MTCs in the MG pattern arise within a monsoon vortex characterized by strong southwesterly flows. A quantitative analysis further indicates that MTC formation in the MT pattern is primarily governed by mid-level vertical velocity and low-level vorticity, while mid-level humidity and vertical velocity are significantly important in the other patterns. The meridional shear and convergence of zonal winds are essential in converting barotropic energy from the basic flows to disturbance kinetic energy, acting as the primary source for eddy kinetic energy growth.

关键词： barotropic energy conversion circulation pattern monsoon trough multiple tropical cyclones western North Pacific

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Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells

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Organic Chemistry Frontiers 2022年第4期9卷 1048-1055页

作者： Xiang-Hong He Xue-Ju Fu gu zhan Nan zhang Xiang Li Hong-Ping Zhu Cheng Peng gu He Bo Han State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China State Key Laboratory of Biotherapy and Department of Pharmacy West China HospitalSichuan UniversityChengdu610041China Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province Sichuan Industrial Institute of AntibioticsChengdu UniversityChengdu 610052China

Organocatalytic asymmetric[3+3]annulations of isatin-derived MBH carbonates and indolin-2-imines were efficiently *** appears to be the first enantioselective approach for using isatin-derived MBH carbonates as 3C synthons to react with indole-derived C,N-dinucleophiles,yielding a series of multifunctionalized α-carboline-spirooxindole hybrids in good to high yields with high stereoselectivities.

关键词： asymmetric indole catalytic

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NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

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Chinese Chemical Letters 2021年第8期32卷 2567-2571页

作者： Haijun Leng Qian Zhao Qing Mao Shuaijiang Liu Menglan Luo Rui Qin Wei Huang gu zhan State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and School of Basic Medical SciencesChengdu University of Traditional Chinese MedicineChengdu 611137China Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province Sichuan Industrial Institute of AntibioticsSchool of PharmacyChengdu UniversityChengdu 610052China

An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been *** ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents(THF or DCE).The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole andα,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC ***,four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.

关键词： Asymmetric synthesis Solvent-controlled diastereodivergence Retro-aldol/aldol Cascade reaction Spirooxindole N-Heterocyclic carbene catalysis

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不同品种苦荞UPLC-DAD-CAD指纹图谱和有效成分含量比较

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中药与临床 2024年第1期15卷 9-14页

作者：王迪杨汉梅李维詹固李阳倩杨帆成都中医药大学药学院西南特色中药资源国家重点实验室四川成都611137 四川大学生物治疗国家重点实验室四川成都610041 成都大学基础医学院四川成都610106 成都中医药大学资产与实验室管理处四川成都611137 成都中医药大学教务处四川成都611137

建立13个不同品种苦荞麦的超高效液相-二极管阵列检测器-电雾式检测器(UPLC-DAD-CAD)指纹图谱,并测定4种主要成分含量,为科学评价和控制其质量提供可靠依据。采用ThermoFisher AccucoreTMC18色谱柱(3.0 mm×100mm,2.6μm);流动相为乙腈-... 详细信息

建立13个不同品种苦荞麦的超高效液相-二极管阵列检测器-电雾式检测器(UPLC-DAD-CAD)指纹图谱,并测定4种主要成分含量,为科学评价和控制其质量提供可靠依据。采用ThermoFisher AccucoreTMC18色谱柱(3.0 mm×100mm,2.6μm);流动相为乙腈-0.1%甲酸水溶液,梯度洗脱;检测波长为285nm;CAD检测器雾化温度为50℃,采集频率和过滤常数分别为10 Hz和5 s;采用夹角余弦法进行相似度评价,建立了苦荞麦UPLC-DAD-CAD特征指纹图谱共有模式。标定了20个电雾式检测共有峰与7个紫外检测共有峰,在CAD检测器中各品种间相似度均大于0.999,DAD检测器中各品种间相似度均大于0.948;同时指认了芦丁、山奈酚-3-O-芸香糖苷、槲皮素和山奈酚4种主要成分,并以芦丁的峰面积为标准,计算了13个品种苦荞麦中山奈酚-3-O-芸香糖苷、槲皮素和山奈酚3种待测成分的响应比例值,结果信号响应均以CAD检测器较优。分析比较了4种成分在不同品种苦荞麦中的含量差异,结果表明生长在四川盆地的川荞1号、川荞2号、西荞1号和西荞2号4种黄酮含量相对较低,与其他大部分品种苦荞麦相比,皆存在统计学差异,而生长在海拔高光照强的云贵高原和川西高原的迪苦、黔荞和米荞4种黄酮含量相对较高。本研究首次使用UPLC-DAD-CAD方法建立了不同品种苦荞麦的指纹图谱并对其有效成分含量进行了测定,为苦荞麦的质量控制和资源评价奠定了基础。

关键词：苦荞麦超高效液相-二极管阵列检测器-电雾式检测器(UPLC-DAD-CAD) 指纹图谱共有峰相似度评价含量差异

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“K_(2)O-Na_(2)O-CaO-BaO-SrO”复合熔剂熔融特性及对陶瓷岩板釉面性能的影响

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中国陶瓷 2024年第3期60卷 45-51页

作者：古战文陈志川李勇进吕正平洪庆复胡克艳江西和美陶瓷有限公司丰城331132 东莞市唯美陶瓷工业园有限公司东莞523281 江西唯美陶瓷有限公司丰城331131 景德镇陶瓷大学景德镇333403

以“BaO-Al_(2)O_(3)-SiO_(2)”三元系统相图为基础,选取烧氧化锌、碳酸钡、超细石英和S17#高锶熔块为变量原料,采用正交试验方法系统研制出复合溶剂型亚光釉料并制备出相应的釉饰陶瓷岩板产品;借助灰熔点测定了复合溶剂釉的熔融温度范... 详细信息

以“BaO-Al_(2)O_(3)-SiO_(2)”三元系统相图为基础,选取烧氧化锌、碳酸钡、超细石英和S17#高锶熔块为变量原料,采用正交试验方法系统研制出复合溶剂型亚光釉料并制备出相应的釉饰陶瓷岩板产品;借助灰熔点测定了复合溶剂釉的熔融温度范围,采用X射线衍射仪、扫描电子显微镜和原子力显微镜等研究了釉面的组成,结构和表面平整度;研究结果表明:当釉料配方中烧氧化锌为5%、碳酸钡为6%、超细石英为3%和S17#熔块为45%时,其所制备出对应的产品釉层可在1169~1185℃烧成温度范围内出现不同形状的(K,Na,Sr,Ba)Al_(x)Si_(x)O_(8)长石晶体,从而产生了漫反射,达到釉面的亚光效果;其釉层表面粗糙度Ra为0.91μm、Rz为8.12μm,轮廓显微形貌相对比较完整且平缓,有利于提升陶瓷岩板产品釉面的细腻平滑、易清洁性能。

关键词： K_(2)O-Na_(2)O-CaO-BaO-SrO 亚光釉熔融特性表面粗糙度表面形貌

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“(K,Na)_(2)O-Al_(2)O_(3)-(Ba,Sr)O-SiO_(2)”系亚光微晶釉显微结构及光学性能分析

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中国陶瓷 2024年第10期60卷 61-67页

作者：古战文余海龙刘任松王永强邓江文潘超宪刘学斌马可波罗控股股份有限公司东莞523055 江西和美陶瓷有限公司丰城331132 东莞市唯美陶瓷工业园有限公司东莞523281 广东家美陶瓷有限公司清远511500 江西唯美陶瓷有限公司丰城331131

以“钡、锌、锶”为主要复合熔剂,在1169~1185℃烧成温度范围内制备了应用于高端陶瓷岩板产品表面装饰的“(K,Na)_(2)O-Al_(2)O_(3)-(Ba,Sr)O-SiO_(2)”系亚光微晶釉玻璃,并对样品表面的亚光微晶釉玻璃进行了XRD、SEM和EDS表征。结果表... 详细信息

以“钡、锌、锶”为主要复合熔剂,在1169~1185℃烧成温度范围内制备了应用于高端陶瓷岩板产品表面装饰的“(K,Na)_(2)O-Al_(2)O_(3)-(Ba,Sr)O-SiO_(2)”系亚光微晶釉玻璃,并对样品表面的亚光微晶釉玻璃进行了XRD、SEM和EDS表征。结果表明:该亚光微晶釉玻璃表面存在数量众多且极其细小尺寸的柱状、棒状、颗粒状等多种形态的长石系晶体,晶体尺寸为10μm左右,呈现相对分散的状态,易使入射光线呈现漫反射效果。此外,发现在这些晶相周围呈现着相对均一的亮光点,这是在烧成急冷过程中局部没有析出晶粒的透明釉玻璃产生镜面反射形成的;可通过微晶釉玻璃表面的结晶度来调控产品釉面的光学性能,从而可指导项目亚光微晶陶瓷岩板产品表面的质感控制方向。

关键词：亚光釉微晶玻璃显微结构光学性能陶瓷岩板

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