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Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy:Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits

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Current Medical Science 2024年第2期44卷 450-461页

作者： Xiao-yun ding Hao ZHANG Yu-mei QIU Meng-die XIE hu WANG Zheng-yu XIONG Ting-ting LI Chun-ni HE Wei DONG Xi-lan TANG School of Pharmacy Jiangxi Science&Technology Normal UniversityNanchang 330013China Key Laboratory of Modern Preparation of Chinese Medicine Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Jiangxi Provincial Key Laboratory of Drug Design and Evaluation Nanchang 330013China

Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive *** this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte ***:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass *** were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 *** hypertrophy-related indicators and NLRP3 inflammasome expression were ***,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying ***:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene ***,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated *** further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col ***:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

关键词： Cymbopogon citratus essential oil cardiac hypertrophy NLRP3 inflammasome oxidative phosphorylation complex subunits

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时效处理对Fe-12Mn-8Al-1C-3Cu轻质钢的组织演变和力学性能的影响

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材料研究学报 2024年第5期38卷 356-364页

作者：刘加晓胡晓丁桦东北大学材料科学与工程学院沈阳110819 东北大学辽宁省轻量化用关键金属结构材料重点实验室沈阳110819

对中锰轻质钢进行不同时间的时效处理,研究了时效时间对其微观组织演变和力学性能的影响。结果表明,时效处理时间对析出物有显著的影响。时效时间短于30 min时,在奥氏体基体内析出大量调幅分解生成的弥散分布的晶内κ’碳化物。随着时... 详细信息

对中锰轻质钢进行不同时间的时效处理,研究了时效时间对其微观组织演变和力学性能的影响。结果表明,时效处理时间对析出物有显著的影响。时效时间短于30 min时,在奥氏体基体内析出大量调幅分解生成的弥散分布的晶内κ’碳化物。随着时效时间的延长,除了在晶内析出κ’碳化物,在晶间也发生共析反应在晶界处形成κ-碳化物,构成(α-铁素体+晶间κ-碳化物)片层组织。晶内κ’碳化物的生成使钢的强度提高,但是晶间κ-碳化物的析出使其塑性显著降低。与长时时效相比,短时时效使钢的强度显著提高,还使其保持较高的伸长率,使其具有更优异的综合力学性能。时效30 min的钢,其抗拉强度为1031 MPa,屈服强度为784 MPa,伸长率为41.08%,强塑积为42.35 GPa·%。

关键词：金属材料轻质钢时效处理组织演变应变硬化位错滑移

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Organization of microtubule plus-end dynamics by phase separation in mitosis

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Journal of Molecular Cell Biology 2024年第2期16卷 24-35页

作者： Fengrui Yang mingrui ding Xiaoyu Song Fang Chen Tongtong Yang Chunyue Wang Chengcheng hu Qing hu Yihan Yao Shihao Du Phil YYao Peng Xia Gregory Adams Jr Chuanhai Fu Shengqi Xiang Dan Liu Zhikai Wang Kai Yuan Xing Liu MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics Hefei National Research Center for Cross-disciplinary SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science&Technology of ChinaHefei 230027China Anhui Key Laboratory for Cellular Dynamics and Chemical Biology University of Science&Technology of ChinaHefei 230027China Keck Center for Organoids Plasticity Morehouse School of MedicineAtlantaGA 30310USA hunan Key Laboratory of Molecular Precision Medicine Central South UniversityChangsha 410083China

In eukaryotes,microtubule polymers are essential for cellular plasticity and fate ***-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in ***,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in *** of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila ***220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome *** data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.

关键词： phase separation mitosis microtubule dynamics EB1 acetylation

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Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke

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Stroke & Vascular Neurology 2024年第4期9卷 367-379,I0022-I0031页

作者： Tianchi Tang Li-bin hu Chao ding Zhihua Zhang Ning Wang Tingting Wang Hang Zhou Siqi Xia Linfeng Fan Xiong-jie Fu Feng Yan Xiangnan Zhang Gao Chen Jianru Li Department of Neurosurgery Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 2NeurosurgeryZhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 3Zhejiang University School of MedicineHangzhouZhejiangChina 4Zhejiang University Department of PharmacologyHangzhouZhejiangChina

Background Ischaemic stroke triggers neuronal mitophagy,while the involvement of mitophagy receptors in ischaemia/reperfusion(I/R)injury-induced neuronal mitophagy remain not fully ***,we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1(FUNDC1)and its modulation in neuronal mitophagy induced by I/R *** Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I/R injury,including transient middle cerebral artery occlusion(tMCAO)in vivo and oxygen glucose deprivation/reperfusion in *** outcomes of mice with two genotypes were *** mitophagy was analysed both in vivo and in *** of FUNDC1 and its regulator Src were *** impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist *** To our surprise,FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type *** neuronal mitophagy could be activated by I/R injury,FUNDC1 deletion did not disrupt neuronal *** activation of FUNDC1,represented by dephosphorylation of Tyr18,was detected in the early stages(within 3hours)of neuronal I/R injury;however,phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages(after 6hours),accompanied by a decrease in FUNDC1-light chain 3 *** inactivation of FUNDC1 was associated with Src activation,represented by phosphorylation of Tyr416,which changed in parallel with the level of phosphorylated FUNDC1(Tyr18)during neuronal I/R ***,FUNDC1-mediated mitophagy in neurons under I/R conditions can be rescued by pharmacological inhibition of *** FUNDC1 is inactivated by Src during the later stage(after 6hours)of neuronal I/R injury,and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.

关键词： FUNDC1 involvement injury

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Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 136-152页

作者： Xiaoju Guo Xiaoxiao Chen Jiayi ding Feng Zhang Shunyang Chen Xin hu Shiji Fang Lin Shen Chenying Lu Zhongwei Zhao Jianfei Tu Gaofeng Shu Minjiang Chen Jiansong Ji Lishui Central Hospital Shaoxing UniversityShaoxing 312000China Zhejiang Key Laboratory of Imaging and Interventional Medicine Imaging Diagnosis and Interventional Minimally Invasive InstituteThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Clinical College of The Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000China Key Laboratory of Precision Medicine of Lishui Lishui 323000China

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

关键词： CaCO3-based nanoparticles Hypoxia attenuation Acidity neutralization Reversal of chemotherapy resistance Enhanced chemo-immunotherapy

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雪冰样品离子色谱分析对样品瓶选择及前处理的要求

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冰川冻土 2010年第5期32卷 948-953页

作者：王晓香效存德崔晓庆丁明虎中国科学院寒区旱区环境与工程研究所冰冻圈科学圉家重点实验室甘肃兰州730000

用离子色谱分析雪冰样品中痕量化学成分时,样品瓶的选择和前处理是确保实验结果的关键环节之一.痕量雪冰样品瓶在选择时需要注意两点:第一,瓶子的材质要根据所采样品的性状和所测组份的化学性质选取;测试常规的阴、阳离子,需选择易于运... 详细信息

用离子色谱分析雪冰样品中痕量化学成分时,样品瓶的选择和前处理是确保实验结果的关键环节之一.痕量雪冰样品瓶在选择时需要注意两点:第一,瓶子的材质要根据所采样品的性状和所测组份的化学性质选取;测试常规的阴、阳离子,需选择易于运输和保存的聚乙烯(PE)、聚丙烯(PP)等材质的塑料采样瓶;测试有机酸时,为避免瓶子本身对样品的污染,通常选择玻璃瓶;第二,要确保所选样品瓶的密闭性,为保证雪冰内痕量化学成分的准确测定,不同材质的样品瓶应采取不同的清洗流程.塑料瓶首先用洗涤剂浸泡6～8h后刷洗,再用蒸馏水浸泡24h后充分冲洗,最后采用18.2MΩ的超纯水浸泡12h并冲洗至空白检测合格;玻璃瓶则需首先用洗涤剂浸泡6～8h后自来水冲洗干净,接着在1%～2%盐酸溶液或铬酸洗液中浸泡48h后充分冲洗,再用蒸馏水冲洗浸泡24h,充分冲洗,最后用18.2MΩ的超纯水浸泡12h并冲洗至空白检测合格.此外,在样品的采集与运输过程中,一定要预留空白,以检验样品瓶从运出实验室至返回实验室的整个过程中是否受到系统性污染,做好整个过程的质量控制工作.

关键词：离子色谱雪冰样品样品瓶前处理

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang hua Sun Xujia hu hua Wang Li Zhang Ruili huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway

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Neural Regeneration Research 2024年第1期19卷 180-189页

作者： Zhihao Zhang Zhiwen Song Liang Luo Zhijie Zhu Xiaoshuang Zuo Cheng Ju Xuankang Wang Yangguang Ma Tingyu Wu Zhou Yao Jie Zhou Beiyu Chen Tan ding Zhe Wang Xueyu hu Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury *** cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous *** proteins are thus candidate targets for spinal cord injury *** previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model ***,the specific mechanism and potential targets involved remain to be *** this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive *** found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal *** analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed *** staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord *** expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve ***,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB *** suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulatio

关键词： chondroitin sulfate proteoglycans Erk MAPK P38 photobiomodulation principal component analysis Smad3 Sox9 spinal cord injury versican

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γ⁃TiAl与Ti_(2)AlNb线性摩擦焊接头微观组织

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航空学报 2024年第13期45卷 258-265页

作者：杜随更胡弘毅丁珂西北工业大学航空发动机高性能制造工业和信息化部重点实验室西安710072 西北工业大学航空发动机先进制造技术教育部工程研究中心西安710072 三花研究院有限公司杭州310018

为促进γ-TiAl叶片与Ti_(2)AlNb轮盘异种材料整体叶盘线性摩擦焊接制造技术的发展,进行了全片层γ-TiAl与Ti_(2)AlNb的线性摩擦焊接,采用扫描电镜(SEM)、EBSD及拉伸试验方法对焊态及焊后热处理态焊接接头的微观组织及力学性能进行了分... 详细信息

为促进γ-TiAl叶片与Ti_(2)AlNb轮盘异种材料整体叶盘线性摩擦焊接制造技术的发展,进行了全片层γ-TiAl与Ti_(2)AlNb的线性摩擦焊接,采用扫描电镜(SEM)、EBSD及拉伸试验方法对焊态及焊后热处理态焊接接头的微观组织及力学性能进行了分析。结果表明,焊合区及近区的相构成自TiAl侧至Ti_(2)AlNb侧在焊态下为γ相-α_(2)相-B2相;经过800℃/2 h AC焊后热处理后转变为γ相-α_(2)相+B2相-O+B2相;γ-TiAl侧热力影响区(TMAZ)发生了片层弯折变形,Ti_(2)AlNb侧TMAZ发生了晶粒细化及再结晶。经焊后热处理接头室温及650℃抗拉强度分别达到277 MPa和478 MPa。

关键词：摩擦焊 TiAl Ti_(2)AlNb 微观组织整体叶盘

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基于极值理论的地基增强系统完好性评估方法

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兵工学报 2024年第2期45卷 641-650页

作者：胡杰严勇杰丁辉中国电子科技集团公司第二十八研究所江苏南京210007 空中交通管理系统全国重点实验室江苏南京210007

针对地基增强系统(Ground Based Augmentation System,GBAS)完好性风险事件的极端性而导致的无法通过风险事件发生频率评估系统性能的问题,提出一种基于极值理论的GBAS完好性评估方法。根据机载端(位置域)输出的位置误差和保护级计算安... 详细信息

针对地基增强系统(Ground Based Augmentation System,GBAS)完好性风险事件的极端性而导致的无法通过风险事件发生频率评估系统性能的问题,提出一种基于极值理论的GBAS完好性评估方法。根据机载端(位置域)输出的位置误差和保护级计算安全系数,并利用区间极大值模型对安全系数进行建模描述以获得其分布模型;利用极大似然法估计安全系数模型参数,进而利用模型外推法计算GBAS完好性风险值。给出GBAS完好性评估流程,并利用GBAS系统进行了验证实验。研究结果表明:对于C类GBAS进近服务而言,基于全球定位系统(Global Position System,GPS)增强GBAS和基于北斗卫星导航系统(Beidou Navigation Satellite System,BDS)增强GBAS可用性均大于99.9999%;对于F类GBAS进近服务而言,BDS GBAS可用性能要优于GPS GBAS;根据7 d观测数据外推得到的GPS GBAS垂直和侧向完好性风险值分别为4.557×10^(-8)/进近和5.152×10^(-8)/进近,BDS GBAS垂直和侧向完好性风险值分别为1.612×10^(-7)/进近和1.823×10^(-7)/进近,满足航空器终端区I类进近与着陆导航性能需求。

关键词：地基增强系统完好性风险极值理论安全系数

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