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Because of their low cost and easy production, silica nanoparticles (SiNPs) are widely used in multiple manufacturing applications as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about the toxicity of this nanomaterial. SiNPs affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of SiNPs on the responses of 16HBE14o- cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca2+ concentration. Upon stimulation with extracellular ATP, these cells displayed a concentration-dependent increase in intracellular Ca2+, which was mediated by release from intracellular stores. SiNPs inhibited the Ca2+ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. SiNPs-induced inhibition is independent from the increase in intracellular Ca2+ they produce, is largely irreversible and occurs via a non-competitive mechanism. These findings suggest that SiNPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses. 相似文献
115.
针对高灵敏度、宽响应范围及自动检测三磷酸腺苷(ATP)的需求,设计了一种基于生物发光原理的ATP检测系统.系统采用自动加样技术,在发光反应的同时开始记录光强,使仪表检测自动化,且提高检测灵敏度;在优化光电检测单元设计和减小杂散光及电磁干扰的同时,提高荧光检测效率;通过电路和数据处理算法优化提高仪表检测范围.以浓度为10-15~10-6 M范围内的标准ATP溶液进行了实验,结果表明仪表测量光强与ATP实际浓度相关系数为0.974,检测范围达9个数量级.与市场相关仪器相比,该系统具有自动化测试,性能和灵敏度高、响应范围宽的特点,在ATP测量以及相关领域如细菌测量、毒性测试及卫生状况检测等方面具有广泛的应用前景. 相似文献
116.
基于支付能力和支付意愿的农民灌溉水价承受能力研究 总被引:3,自引:0,他引:3
从支付能力和支付意愿的角度,分别应用扩展线性支出系统(ELES)模型和条件价值评估法(CVM),提出了农民灌溉水价支付能力和支付意愿的定量方法,研究农民灌溉水价承受能力.以江苏省五岸灌区为例,通过问卷调查,计算分析了农民灌溉水价的支付能力、支付意愿、综合承受能力和水价调整空间等.研究表明:部分贫困农户支付能力有限,是重点考虑的对象,以人均纯收入为指标的分类定价策略值得考虑;不同支付能力农民的支付意愿无显著性差异,支付意愿对水价改革具有重要意义. 相似文献
117.
Craig K. Docherty Anastasiya Strembitska Christa P. Baker Fiona F. Schmidt Kieran Reay John R. Mercer 《International journal of molecular sciences》2022,23(1)
The cardiovascular disease of atherosclerosis is characterised by aged vascular smooth muscle cells and compromised cell survival. Analysis of human and murine plaques highlights markers of DNA damage such as p53, Ataxia telangiectasia mutated (ATM), and defects in mitochondrial oxidative metabolism as significant observations. The antiageing protein Klotho could prolong VSMC survival in the atherosclerotic plaque and delay the consequences of plaque rupture by improving VSMC phenotype to delay heart attacks and stroke. Comparing wild-type VSMCs from an ApoE model of atherosclerosis with a flox’d Pink1 knockout of inducible mitochondrial dysfunction we show WT Pink1 is essential for normal cell viability, while Klotho mediates energetic switching which may preserve cell survival. Methods: Wild-type ApoE VSMCs were screened to identify potential drug candidates that could improve longevity without inducing cytotoxicity. The central regulator of cell metabolism AMP Kinase was used as a readout of energy homeostasis. Functional energetic switching between oxidative and glycolytic metabolism was assessed using XF24 technology. Live cell imaging was then used as a functional readout for the WT drug response, compared with Pink1 (phosphatase-and-tensin-homolog (PTEN)-induced kinase-1) knockout cells. Results: Candidate drugs were assessed to induce pACC, pAMPK, and pLKB1 before selecting Klotho for its improved ability to perform energetic switching. Klotho mediated an inverse dose-dependent effect and was able to switch between oxidative and glycolytic metabolism. Klotho mediated improved glycolytic energetics in wild-type cells which were not present in Pink1 knockout cells that model mitochondrial dysfunction. Klotho improved WT cell survival and migration, increasing proliferation and decreasing necrosis independent of effects on apoptosis. Conclusions: Klotho plays an important role in VSMC energetics which requires Pink1 to mediate energetic switching between oxidative and glycolytic metabolism. Klotho improved VSMC phenotype and, if targeted to the plaque early in the disease, could be a useful strategy to delay the effects of plaque ageing and improve VSMC survival. 相似文献
118.
Ya-Fei Zhao Wen-Jing Ren Ying Zhang Jin-Rong He Hai-Yan Yin Yang Liao Patrizia Rubini Jan M. Deussing Alexei Verkhratsky Zeng-Qiang Yuan Peter Illes Yong Tang 《International journal of molecular sciences》2022,23(3)
Extracellular adenosine 5′-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans. 相似文献
119.
自由空间光通信ATP系统中精瞄偏转镜的设计 总被引:13,自引:9,他引:4
二维精瞄偏转镜是自由空间光通信中捕获、跟踪和瞄准(ATP)系统的关键组成部分,对偏转镜进行了机构设计和有限元模态分析,偏转镜采用压电陶瓷驱动器驱动,采用柔性铰链传动。研制了集驱动、检测、主控模块为一体的数字式精密定位控制器,在实验室构建了两套测试系统,对偏转镜的频率和静态性能进行了测试,并着重介绍了频率的两种测量方法及其优缺点分析。仿真和测试结果表明,偏转镜的频率约为1.5 kHz,转角范围约为±2 mrad,精度约为1 μrad,分辨率约为0.1 μrad。 相似文献
120.
Afshan Ardalan Matthew D. Smith Masoud Jelokhani-Niaraki 《International journal of molecular sciences》2022,23(3)
Higher concentration of protons in the mitochondrial intermembrane space compared to the matrix results in an electrochemical potential causing the back flux of protons to the matrix. This proton transport can take place through ATP synthase complex (leading to formation of ATP) or can occur via proton transporters of the mitochondrial carrier superfamily and/or membrane lipids. Some mitochondrial proton transporters, such as uncoupling proteins (UCPs), transport protons as their general regulating function; while others are symporters or antiporters, which use the proton gradient as a driving force to co-transport other substrates across the mitochondrial inner membrane (such as phosphate carrier, a symporter; or aspartate/glutamate transporter, an antiporter). Passage (or leakage) of protons across the inner membrane to matrix from any route other than ATP synthase negatively impacts ATP synthesis. The focus of this review is on regulated proton transport by UCPs. Recent findings on the structure and function of UCPs, and the related research methodologies, are also critically reviewed. Due to structural similarity of members of the mitochondrial carrier superfamily, several of the known structural features are potentially expandable to all members. Overall, this report provides a brief, yet comprehensive, overview of the current knowledge in the field. 相似文献