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Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells

The Innovation 2024年第3期5卷 138-145页

作者： Alfred Akinlalu Zachariah Flaten Komila Rasuleva Md Saimon Mia Aaron Bauer Santhalingam Elamurugan Nega Ejjigu Sudipa Maity Amara Arshad Min Wu Wenjie Xia jia Fan Ang guo Sijo Mathew Dali Sun Department of Electrical and Computer Engineering University of Denver2155 E Wesley AvenueDenverCO 80210USA Biomedical Engineering Program North Dakota State University1401 Centennial BoulevardEngineering AdministrationRoom 203FargoND 58102USA Department of Pharmaceutical Sciences School of PharmacyNorth Dakota State University1001 S.1401 Albrecht Boulevard Sudro HallFargoND 58102USA Materials and Nanotechnology Program North Dakota State University1410 North 14th AvenueCIE 201FargoND 58102USA Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325000China Department of Aerospace Engineering Iowa State UniversityAmesIA 50011USA Center for Cellular and Molecular Diagnostics Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Department of Biochemistry and Molecular Biology Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Knoebel Institute for Healthy Aging University of Denver2155 E Wesley AvenueDenverCO 80210USA

Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease *** and selective treatments are urgently needed,since current therapies have limited efficacy and significant side *** proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor *** findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular *** amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor *** in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC ***,we also identified XRN1 as a potential target for these amino *** high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal ***,we found this treatment approach is easy-to-administer and with sustained tumor-killing ***,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.

关键词： finding identif selectivity

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Electroacupuncture activates AMPKa1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics

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journal of Integrative Medicine 2024年第5期22卷 588-599页

作者： Wei-wei jia Hua-wei Lin Min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao Sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of Rehabilitation Medicine Fujian University of Traditional Chinese Medicine The Institute of Rehabilitation Industry Fujian University of Traditional Chinese Medicine National-Local joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese Medicine Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese Medicine

Objective: Studies have shown that electroacupuncture(EA) can alleviate cognitive impairments from Alzheimer's disease(AD) by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial ***: The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKa1-subunit conditional knockout(AMPKa1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition,chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 ***: Both APP/PS1 mice and AMPKa1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferatoractivated receptor-γ coactivator-1a(PgC-1a) pathway increased pathological amyloid-β(Aβ) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PgC-1a pathway, specifically by reducing pathological Aβ deposition, normalizing energy metabolism, protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by ***: The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PgC-1a pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

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压缩空气储能人工硐库热力耦合解析方法研究

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岩土力学 2024年第8期45卷 2263-2278,2289页

作者：贾宁刘顺王洪播中国电力工程顾问集团华北电力设计院有限公司北京100120

压缩空气储能人工硐库在充气和抽气循环过程中,空气温度、压力,以及硐壁密封层、混凝土衬砌和围岩的温度、应力和应变一直处于变化之中。联合求解这些变量是工程设计中的关键技术,也是理论分析的难点。在一维热传导基本解和人工硐库空... 详细信息

压缩空气储能人工硐库在充气和抽气循环过程中,空气温度、压力,以及硐壁密封层、混凝土衬砌和围岩的温度、应力和应变一直处于变化之中。联合求解这些变量是工程设计中的关键技术,也是理论分析的难点。在一维热传导基本解和人工硐库空气温度基本解的基础上,基于硐壁对流换热和热传导能量守恒,提出人工硐库内空气热力学计算与硐壁热传导的耦合解析方法。与数值模拟结果进行了对比,验证了所提方法的正确性。对一个钢质密封层人工硐库实例进行了分析。结果表明,充抽气过程引起硐库内空气温度的剧烈变化,空气压力变幅明显大于基于恒温假定得到的压力变化结果。硐壁温度周期波动影响深度有限,当混凝土衬砌厚度大于周期波动影响范围后,围岩温度以持续升高直至稳定为特征,围岩强度和稳定性分析可以不考虑周期循环温度的影响。密封层受温度和空气内压双重作用明显,密封层设计需考虑材料的热机械疲劳问题。混凝土衬砌内外表面环向应力和法向应变特征差异巨大,不同工况下内外表面环向应力可能接近混凝土材料的抗压和抗拉强度,混凝土材料的抗压和抗拉强度同为设计的控制因素。混凝土衬砌可以减小围岩压力,但作用有限。在适当的埋深条件下,选择适当的充气压力,可以保证围岩处于弹性状态。

关键词：压缩空气储能内衬硐库解析方法温度气体内压应力应变

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Association between composite dietary antioxidant index and stroke among individuals with diabetes

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World journal of Diabetes 2024年第8期15卷 1742-1752页

作者： Hong-Qiang Zhang jie Shi Tong Yue jia-Hao Weng Xu-Lin Wang Hao Wang Xiao-Yu Su Xue-Ying Zheng Si-Hui Luo Yu Ding Chao-Fan Wang Department of Cardiology Centre for Leading Medicine and Advanced Technologies of IHMThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Endocrinology Centre for Leading Medicine and Advanced Technologies of IHMThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina graduate School Bengbu Medical CollegeBengbu 233030Anhui ProvinceChina Department of Endocrinology and Metabolism The Third Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of DiabetologyGuangzhou 510630Guangdong ProvinceChina

BACKgROUND Recent research has underscored the potentially protective role of dietary antioxidants against chronic conditions,such as cardiovascular diseases and *** composite dietary antioxidant index(CDAI),which reflects the overall intake of key dietary antioxidants,has been identified as a crucial metric for exploring this *** previous research has shown a negative correlation between CDAI levels and stroke risk in prediabetic individuals,there remains a substantial gap in understanding this association among individuals with diabetes,who are at an inherently greater risk for cerebrovascular *** To investigate the association between CDAI and stroke risk in individuals with *** Using a cross-sectional study design,this investigation analyzed data from the National Health and Nutrition Examination Survey spanning from 2003 to 2018 that included 6735 participants aged over 20 years with *** CDAI was calculated from 24-h dietary recalls to assess intake of key antioxidants:Vitamins A,C,and E;carotenoids;selenium;and *** logistic regression and restricted cubic spline analysis were used to rigorously examine the relationship between CDAI and stroke *** The participant cohort,with an average age of 59.5 years and a slight male majority,reflected the broader demographic characteristics of individuals with *** analysis revealed a strong inverse relationship between CDAI levels and stroke ***,those in the highest quintile of CDAI demonstrated a 43%lower prevalence of stroke compared to those in the lowest quintile,even after adjustments for various *** finding not only highlights the negative association between CDAI and stroke risk but also underscores the significant potential of antioxidant-rich diets in reducing stroke prevalence among patients with *** Our findings suggested that CDAI was inversely associated with stroke prevalence among pa

关键词： Stroke Diabetes Composite dietary antioxidant index National Health and Nutrition Examination Survey Crosssectional study

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Visualization of the protective role of estrogen against female liver fibrosis via an ER viscosity NIR fluorescent probe

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Science China Chemistry 2024年

作者： Zheng Liu Changyu Zhang Zipeng Li Wanying Ma jia Liu Xiang Xia Ning Xu Wen Sun jianjun Du jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Dalian University of Technology Ningbo Institute of Dalian University of Technology

Endoplasmic reticulum(ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared(NIR) fluorescent probe HBT-PP for investigations of HF *** twisted intramolecular charge transfer(TICT) and the excited state intramolecular proton transfer(ESIPT) are combined to endow HBT-PP with the selective response towards viscosity(～62-fold) and a super large stokes shift(～320 nm). HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells. Significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.

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中美民用航空器水上救援体系建设现状分析与探讨

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消防科学与技术 2024年第2期43卷 282-287页

作者：贾井运陈现涛中国民用航空飞行学院四川广汉618300

航空应急管理体系是民航发展的生命线,而航空器水上救援体系建设则是航空应急管理体系的重要内容。本文从中美民用航空器水上救援体系建设现状出发,客观分析我国民用航空器水上救援体系在标准建设、应急处置、救援装备、专业培训等方面... 详细信息

航空应急管理体系是民航发展的生命线,而航空器水上救援体系建设则是航空应急管理体系的重要内容。本文从中美民用航空器水上救援体系建设现状出发,客观分析我国民用航空器水上救援体系在标准建设、应急处置、救援装备、专业培训等方面存在的问题。认为可以通过完善民航水上救援标准体系、构建区域部门救援协调机制、加大专项救援设备研发力度、建立国家综合信息保障平台、合理布局水上救援培训基地等途径,进一步完善我国民用航空器水上救援体系的建设和发展。

关键词：航空应急管理水上救援标准体系应急处置救援装备专业培训

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Evolution of treatment options for juvenile idiopathic arthritis

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World journal of Orthopedics 2024年第9期15卷 831-835页

作者： Tao Ren jia-Hui guan Yu Li Nan-Nan Li Zheng Li Department of Colorectal Surgery Taihe County People’s Hospital of Anhui ProvinceFuyang 236600Anhui ProvinceChina Department of Pharmacy Taihe County People’s Hospital of Anhui ProvinceFuyang 236600Anhui ProvinceChina University of Science and Technology of China The First Affiliated Hospital of University of Science and Technology of ChinaHefei 230001Anhui ProvinceChina jiangsu Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells College of Health SciencesSchool of Life SciencesJiangsu Normal UniversityXuzhou 221116Jiangsu ProvinceChina

A recent study published in World j Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(jia).Herein,we outline the progress in drug therapy of *** have traditionally been the primary treatment for all forms of *** are symptom-relief medications,and well tolerated by ***,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional *** is another kind of symptom-relief medications with potent anti-inflammatory ***,the frequent adverse events limit the clinical *** NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint ***,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of jia,compared with conventional synthetic *** a newly developed class of drugs,the places of most bDMARDs in the management of jia remain to be well ***,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for jia.

关键词： juvenile idiopathic arthritis Treatment Non-steroidal anti-inflammatory drug Disease-modifying antirheumatic drug Evolution

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Lysophosphatidylcholine binds α-synuclein and prevents its pathological aggregation

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National Science Review 2024年第06期 119-128页

作者： Chunyu Zhao jia Tu Chuchu Wang Wenbin Liu jinge gu Yandong Yin Shengnan Zhang Dan Li jiajie Diao Zheng-jiang Zhu Cong Liu Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education Shanghai Jiao Tong University Zhangjiang Institute for Advanced Study Shanghai Jiao Tong University Department of Cancer Biology University of Cincinnati College of Medicine

Accumulation of aggregated α-synuclein(α-syn) in Lewy bodies is the pathological hallmark of Parkinson's disease(PD). genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism. The role of α-syn's lipid interactions in its function and aggregation is recognized, yet the specific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegeneration remain unclear. Here, we found that α-syn shows a preference for binding to lysophospholipids(LPLs),particularly targeting lysophosphatidylcholine(LPC) without relying on electrostatic interactions. LPC is capable of maintaining α-syn in a compact conformation, significantly reducing its propensity to aggregate both in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs is associated with an increase in α-syn accumulation. Our work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and α-syn aggregation in PD.

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叶片破损对压气机性能的影响

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哈尔滨工程大学学报 2024年第4期45卷 722-729页

作者：王忠义赵佳张晶王萌哈尔滨工程大学动力与能源工程学院黑龙江哈尔滨150001 中船黄埔文冲船舶有限公司广东广州510715

为了研究叶片破损对压气机内部流场的影响机理,本文针对带有破损的跨音速压气机叶片进行气动性能变化规律和机理研究。通过NASA rotor 37实验结果验证了计算方法的准确性,利用数值仿真研究了叶片破损对压气性能的影响规律,并对2种典型... 详细信息

为了研究叶片破损对压气机内部流场的影响机理,本文针对带有破损的跨音速压气机叶片进行气动性能变化规律和机理研究。通过NASA rotor 37实验结果验证了计算方法的准确性,利用数值仿真研究了叶片破损对压气性能的影响规律,并对2种典型工况下叶片破损前后的流场结构进行对比分析,探讨引起性能变化的具体原因。研究表明:叶片破损会导致压气机的压比降低0.6631%、绝热效率降低0.7877%,且压气机的稳定裕度降低更为明显。叶尖破损主要对叶顶流场结构产生影响,使叶顶区域泄漏流增强,当其与激波相互作用时,通道内产生了流动堵塞和流动损失。本文研究成果可为实际服役中的航空发动机特性评定提供理论参考。

关键词：跨音速压气机叶片破损数值模拟气动性能压比效率稳定裕度叶顶泄漏流

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从“身体图绘”看光学战争表征中的身体

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外语导刊 2024年第4期47卷 56-63,159页

作者：叶家春中国民用航空飞行学院四川广汉618307

人文地理学家德里克·格雷戈里的“身体图绘”从现代光学战争中的身体入手,分析了被认定为“他者”的群体在当代战争文化中被呈现的方式,强调身体感触即使在当代远程战争中也不可或缺。“身体图绘”的落脚点是光学战争中“被消失”的身... 详细信息

人文地理学家德里克·格雷戈里的“身体图绘”从现代光学战争中的身体入手,分析了被认定为“他者”的群体在当代战争文化中被呈现的方式,强调身体感触即使在当代远程战争中也不可或缺。“身体图绘”的落脚点是光学战争中“被消失”的身体,这些身体被一种地理划分的“敌意结构”认定具有暴力倾向,因而可以被随意处置。然而,正是这些被忽略的身体测绘着权力和空间性的交织。重申“他者”身体对战争文学的重要性,一方面是对殖民化身体研究的补充。另一方面,把被监控的身体放置在光学战争中,从视觉文化的角度来研究身体的“他者化”过程,是把身体放置在多元的社会因素中考量,展现了身体研究的跨学科性。把“身体图绘”应用于战争文学批评,是对传统后殖民研究依赖文本分析的跨越,并进一步拓宽了文学中的身体研究。

关键词：身体图绘德里克·格雷戈里光学战争战争文学身体研究

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