首页 > 最新文献

Redox Biochemistry and Chemistry最新文献

英文 中文
NADPH oxidase 5: Where are we now and which way to proceed? NADPH 氧化酶 5:我们现在在哪里?
Pub Date : 2024-08-01 DOI: 10.1016/j.rbc.2024.100036
Gábor L. Petheő, Zsolt Szeles, Miklós Geiszt

Since the incorporation of mitochondria in early eukaryotes cells struggle to keep the deleterious effects of reactive oxygen species (ROS), mainly originating from the respiratory chain, at bay. Evolutionary adaptation to ROS burden went so far that by acting as messenger and effector molecules, ROS became important in maintaining homeostasis. The evolutionary success of this phenomenon is underscored by the arising of professional ROS-generating enzymes, namely the family of NADPH oxidases (NOXes). NOXes, by shaping ROS levels at different subcellular locations and in extracellular space, are involved in such fundamental functions as proliferation, differentiation, apoptosis, host defense, fertilization, and hormone biosynthesis. NOX5, being a calcium-regulated professional ROS source exerts its function at the crossroad of these two fundamental but potentially deleterious intracellular signaling pathways (i.e. Ca2+ and ROS). The expression of NOX5 in the adult human body under unchallenged conditions is restricted to very few sites, among which the two major tissue groups are genital organs (mainly testis) and immune tissues (mainly spleen). In cases of increased cellular proliferation and protein synthesis (e.g., diverse tumors, cultured primary cells, or sites of tissue damage) the expression and activity of NOX5 is often upregulated in various tissues. This and the evolutionary conserved nature of NOX5 would imply a very fundamental role for this enzyme, but intriguingly the genomes of rodents essentially lack the NOX5 gene. The latter fact had been a major obstacle in determining the physiological roles of NOX5 in normal tissues until the very recent generation of a NOX5-deficient rabbit model.

自从线粒体在早期真核生物中出现以来,细胞就一直在努力抵御主要来自呼吸链的活性氧(ROS)的有害影响。进化过程中对 ROS 负担的适应发展到如此地步,ROS 通过充当信使和效应分子,成为维持体内平衡的重要物质。专业的 ROS 生成酶,即 NADPH 氧化酶(NOXes)家族的出现,凸显了这一现象在进化上的成功。NOXes 通过调节不同亚细胞位置和细胞外空间的 ROS 水平,参与增殖、分化、凋亡、宿主防御、受精和激素生物合成等基本功能。NOX5 是受钙调控的专业 ROS 源,在这两种基本但可能有害的细胞内信号通路(即 Ca2+ 和 ROS)的交叉路口发挥其功能。NOX5 在成人人体中的表达仅限于极少数部位,其中两个主要组织群是生殖器官(主要是睾丸)和免疫组织(主要是脾脏)。在细胞增殖和蛋白质合成增加的情况下(如各种肿瘤、培养的原代细胞或组织损伤部位),NOX5 的表达和活性往往在各种组织中上调。这一点以及 NOX5 的进化保守性意味着这种酶具有非常重要的作用,但有趣的是,啮齿类动物的基因组中基本上没有 NOX5 基因。这一事实一直是确定 NOX5 在正常组织中的生理作用的主要障碍,直到最近产生了一种 NOX5 缺陷兔模型。
{"title":"NADPH oxidase 5: Where are we now and which way to proceed?","authors":"Gábor L. Petheő,&nbsp;Zsolt Szeles,&nbsp;Miklós Geiszt","doi":"10.1016/j.rbc.2024.100036","DOIUrl":"10.1016/j.rbc.2024.100036","url":null,"abstract":"<div><p>Since the incorporation of mitochondria in early eukaryotes cells struggle to keep the deleterious effects of reactive oxygen species (ROS), mainly originating from the respiratory chain, at bay. Evolutionary adaptation to ROS burden went so far that by acting as messenger and effector molecules, ROS became important in maintaining homeostasis. The evolutionary success of this phenomenon is underscored by the arising of professional ROS-generating enzymes, namely the family of NADPH oxidases (NOXes). NOXes, by shaping ROS levels at different subcellular locations and in extracellular space, are involved in such fundamental functions as proliferation, differentiation, apoptosis, host defense, fertilization, and hormone biosynthesis. NOX5, being a calcium-regulated professional ROS source exerts its function at the crossroad of these two fundamental but potentially deleterious intracellular signaling pathways (i.e. Ca<sup>2+</sup> and ROS). The expression of NOX5 in the adult human body under unchallenged conditions is restricted to very few sites, among which the two major tissue groups are genital organs (mainly testis) and immune tissues (mainly spleen). In cases of increased cellular proliferation and protein synthesis (e.g., diverse tumors, cultured primary cells, or sites of tissue damage) the expression and activity of NOX5 is often upregulated in various tissues. This and the evolutionary conserved nature of NOX5 would imply a very fundamental role for this enzyme, but intriguingly the genomes of rodents essentially lack the NOX5 gene. The latter fact had been a major obstacle in determining the physiological roles of NOX5 in normal tissues until the very recent generation of a NOX5-deficient rabbit model.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"9 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000178/pdfft?md5=2687164805394d26bf3476b55ab647bc&pid=1-s2.0-S2773176624000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation 通过计算机模拟比较硫醇和硒醇对过硫酸盐的反应性
Pub Date : 2024-08-01 DOI: 10.1016/j.rbc.2024.100035
Andresa Messias , Aníbal Rauber , Sofía Vuletich , Ari Zeida , Jonathan A. Semelak , Darío A. Estrin

Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Particularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a key process which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. In contrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecular basis of selenocysteine's reactivity may provide insights into its unique role in these selenocysteine-containing proteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out by the thiolate/selenate forms and peroxynitrous acid.

In this work, we shed light on the molecular basis of the differential reactivity of both species towards peroxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations of the reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at different levels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution, which enabled the comparison between the simulations and the available experimental data. Our results suggest that the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa, which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to a slightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.

过亚硝酸盐是一种非常活跃的物质,与多种细胞病理生理过程有关。特别是,过亚硝酸盐介导的细胞含硫醇化合物(如半胱氨酸残基)的氧化是一个关键过程,已被广泛研究。半胱氨酸在许多氧化还原生物化学途径中发挥作用。相比之下,硒半胱氨酸是第 21 种氨基酸,只存在于 25 种人类蛋白质中。对硒代半胱氨酸反应性的分子基础进行研究,可能有助于深入了解它在这些含硒代半胱氨酸蛋白质中的独特作用。在这项工作中,我们通过最先进的计算机模拟,揭示了硫醇或硒醇对过亚硝酸盐的不同反应性的分子基础。我们采用隐式溶剂方案,在不同理论水平上对甲硫醇酯和甲硒酸模型体系与过硫酸的反应进行了电子结构计算。此外,我们还采用了多尺度量子力学/分子力学方法,以获得这些化学反应在水溶液中的自由能曲线,从而将模拟结果与现有的实验数据进行比较。我们的研究结果表明,硒半胱氨酸在生理 pH 值下的反应性更大,这主要是由于其 pKa 值更低,在这种条件下反应性阴离子物种的比例更大;其次是由于硒酸盐形式的亲核性更大,其内在反应性略有增强。
{"title":"Comparing thiol and selenol reactivity towards peroxynitrite by computer simulation","authors":"Andresa Messias ,&nbsp;Aníbal Rauber ,&nbsp;Sofía Vuletich ,&nbsp;Ari Zeida ,&nbsp;Jonathan A. Semelak ,&nbsp;Darío A. Estrin","doi":"10.1016/j.rbc.2024.100035","DOIUrl":"10.1016/j.rbc.2024.100035","url":null,"abstract":"<div><p>Peroxynitrite is a very reactive species implicated in a variety of pathophysiological cellular processes. Particularly, peroxynitrite-mediated oxidation of cellular thiol-containing compounds such as cysteine residues is a key process which has been extensively studied. Cysteine plays roles in many redox biochemistry pathways. In contrast, selenocysteine, the 21st amino acid, is only present in 25 human proteins. Investigating the molecular basis of selenocysteine's reactivity may provide insights into its unique role in these selenocysteine-containing proteins. The two-electron oxidation of thiols or selenols by peroxynitrite is a process that is carried out by the thiolate/selenate forms and peroxynitrous acid.</p><p>In this work, we shed light on the molecular basis of the differential reactivity of both species towards peroxynitrite by means of state-of-the-art computer simulations. We performed electronic structure calculations of the reaction in the methanethiolate and methaneselenolate model systems with peroxynitrous acid at different levels of theory using an implicit solvent scheme. In addition, we employed a multi-scale quantum mechanics/molecular mechanics approach for obtaining free energy profiles of these chemical reactions in aqueous solution, which enabled the comparison between the simulations and the available experimental data. Our results suggest that the larger reactivity observed in the selenocysteine case at physiological pH is mainly due to the lower pKa, which affords a larger fraction of the reactive anionic species in these conditions, and in a second place to a slightly enhanced intrinsic reactivity of the selenate form due to its larger nucleophilicity.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"9 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000166/pdfft?md5=b9af632f0685ee493c0ed788423b63f7&pid=1-s2.0-S2773176624000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141850730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The specificity of endogenous fatty acid nitration: only conjugated substrates support the in vivo formation of nitro-fatty acids 内源性脂肪酸硝化的特异性:只有共轭底物才支持体内硝基脂肪酸的形成
Pub Date : 2024-08-01 DOI: 10.1016/j.rbc.2024.100037
Nicole Colussi , Fei Chang , Francisco J. Schopfer

Through multiple pathways, nitrogen dioxide (•NO2) is the main species involved in endogenous nitration reactions. Early studies in the field primarily explored tyrosine nitration, a dominant reaction in the field. It was later shown that lipids are also nitration targets and generate an array of reaction products. Conjugated fatty acids are the preferential substrates of lipid nitration in vivo, generating electrophilic nitro-fatty acids (NO2–FAs), which serve as pleiotropic signaling modulators. In contrast, exposure of bisallylic fatty acids, including linoleic, linolenic and arachidonic acid, to •NO2 does not lead, under biological conditions, to the formation of nitrated species. This review focuses on the reaction mechanisms and products of lipid nitration and substrate specificity, focusing on the differential reactivity of conjugated dienes and bisallylic alkenes.

通过多种途径,二氧化氮(-NO2)是参与内源性硝化反应的主要物质。该领域的早期研究主要探讨酪氨酸硝化,这是该领域的主要反应。后来的研究表明,脂质也是硝化目标,并产生一系列反应产物。共轭脂肪酸是体内脂质硝化的首选底物,可生成亲电的硝基脂肪酸(NO2-FAs),作为多效应信号调节剂。相比之下,在生物条件下,亚油酸、亚麻酸和花生四烯酸等双烯丙基脂肪酸与-NO2接触不会形成硝化物种。本综述侧重于脂质硝化的反应机制和产物以及底物的特异性,重点是共轭二烯和双烯丙基烯的不同反应性。
{"title":"The specificity of endogenous fatty acid nitration: only conjugated substrates support the in vivo formation of nitro-fatty acids","authors":"Nicole Colussi ,&nbsp;Fei Chang ,&nbsp;Francisco J. Schopfer","doi":"10.1016/j.rbc.2024.100037","DOIUrl":"10.1016/j.rbc.2024.100037","url":null,"abstract":"<div><p>Through multiple pathways, nitrogen dioxide (•NO<sub>2</sub>) is the main species involved in endogenous nitration reactions. Early studies in the field primarily explored tyrosine nitration, a dominant reaction in the field. It was later shown that lipids are also nitration targets and generate an array of reaction products. Conjugated fatty acids are the preferential substrates of lipid nitration in vivo, generating electrophilic nitro-fatty acids (NO<sub>2</sub>–FAs), which serve as pleiotropic signaling modulators. In contrast, exposure of bisallylic fatty acids, including linoleic, linolenic and arachidonic acid, to •NO<sub>2</sub> does not lead, under biological conditions, to the formation of nitrated species. This review focuses on the reaction mechanisms and products of lipid nitration and substrate specificity, focusing on the differential reactivity of conjugated dienes and bisallylic alkenes.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"9 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277317662400018X/pdfft?md5=96e201513036acdcd04293b5d3e95639&pid=1-s2.0-S277317662400018X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141853118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Small molecule probes for peroxynitrite detection 用于检测过亚硝酸盐的小分子探针
Pub Date : 2024-07-26 DOI: 10.1016/j.rbc.2024.100034
Aleksandra Grzelakowska , Balaraman Kalyanaraman , Jacek Zielonka

Peroxynitrite (ONOO/ONOOH) is a short-lived but highly reactive species that is formed in the diffusion-controlled reaction between nitric oxide and the superoxide radical anion. It can oxidize certain biomolecules and has been considered as a key cellular oxidant formed under various pathophysiological conditions. It is crucial to selectively detect and quantify ONOO to determine its role in biological processes. In this review, we discuss various approaches used to detect ONOO in cell-free and cellular systems with the major emphasis on small-molecule chemical probes. We review the chemical principles and mechanisms responsible for the formation of the detectable products, and plausible limitations of the probes. We recommend the use of boronate-based chemical probes for ONOO, as they react directly and rapidly with ONOO, they produce minor but ONOO‒specific products, and the reaction kinetics and mechanism have been rigorously characterized. Specific experimental approaches and protocols for the detection of ONOO in cell-free, cellular, and in vivo systems using boronate-based molecular probes are provided (as shown in Boxes 1-6).

亚硝酸过氧化物(ONOO-/ONOOH)是一氧化氮与超氧自由基阴离子在扩散控制反应中形成的一种寿命短但活性高的物质。它能氧化某些生物大分子,被认为是在各种病理生理条件下形成的一种关键细胞氧化剂。选择性地检测和量化 ONOO-,对确定其在生物过程中的作用至关重要。在这篇综述中,我们将讨论用于检测无细胞和细胞系统中 ONOO- 的各种方法,重点是小分子化学探针。我们回顾了形成可检测产物的化学原理和机制,以及探针可能存在的局限性。我们建议使用基于硼酸盐的化学探针来检测 ONOO-,因为它们能直接、快速地与 ONOO-发生反应,产生少量但具有 ONOO-特异性的产物,而且反应动力学和机理已得到严格表征。本文提供了使用硼酸盐分子探针在无细胞、细胞和体内系统中检测 ONOO- 的具体实验方法和方案(如方框 1-6 所示)。
{"title":"Small molecule probes for peroxynitrite detection","authors":"Aleksandra Grzelakowska ,&nbsp;Balaraman Kalyanaraman ,&nbsp;Jacek Zielonka","doi":"10.1016/j.rbc.2024.100034","DOIUrl":"10.1016/j.rbc.2024.100034","url":null,"abstract":"<div><p>Peroxynitrite (ONOO<sup>−</sup>/ONOOH) is a short-lived but highly reactive species that is formed in the diffusion-controlled reaction between nitric oxide and the superoxide radical anion. It can oxidize certain biomolecules and has been considered as a key cellular oxidant formed under various pathophysiological conditions. It is crucial to selectively detect and quantify ONOO<sup>−</sup> to determine its role in biological processes. In this review, we discuss various approaches used to detect ONOO<sup>−</sup> in cell-free and cellular systems with the major emphasis on small-molecule chemical probes. We review the chemical principles and mechanisms responsible for the formation of the detectable products, and plausible limitations of the probes. We recommend the use of boronate-based chemical probes for ONOO<sup>−</sup>, as they react directly and rapidly with ONOO<sup>−</sup>, they produce minor but ONOO<sup>−</sup>‒specific products, and the reaction kinetics and mechanism have been rigorously characterized. Specific experimental approaches and protocols for the detection of ONOO<sup>−</sup> in cell-free, cellular, and <em>in vivo</em> systems using boronate-based molecular probes are provided (as shown in Boxes 1-6).</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000154/pdfft?md5=a4723535d75e5476ac6136a1e8cdeac7&pid=1-s2.0-S2773176624000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diffusion of peroxynitrite, its precursors, and derived reactive species, and the effect of cell membranes 过亚硝酸盐、其前体和衍生活性物种的扩散以及细胞膜的影响
Pub Date : 2024-07-05 DOI: 10.1016/j.rbc.2024.100033
Matías N. Möller, Ana Denicola

Peroxynitrite is a powerful oxidant formed in vivo in sites where superoxide and nitric oxide coincide. Peroxynitrite is cytotoxic through oxidative modification of target biomolecules that can occur by direct or indirect reactions. Indirect reactions usually involve the generation of peroxynitrite-derived radicals that include nitrogen dioxide, hydroxyl radical, and carbonate radical. All these species have different behaviors in vivo, because of their intrinsic reactivity and how effectively they can be compartmentalized by cellular membranes. In this review, we analyze quantitative information on the estimated half-lives and the corresponding estimated diffusion distances of peroxynitrite, its precursors, and its derived reactive species in vivo. Furthermore, we discuss the permeability of cellular and synthetic lipid membranes to the different species and how effective compartmentalization is achieved for some of them, limiting the biological site of reactions.

亚硝酸过氧化物是一种强氧化剂,在超氧化物和一氧化氮同时存在的部位形成。过亚硝酸盐通过直接或间接反应对目标生物大分子进行氧化修饰,从而产生细胞毒性。间接反应通常涉及生成过亚硝酸盐衍生自由基,包括二氧化氮、羟自由基和碳酸自由基。所有这些物种在体内都有不同的表现,这是因为它们的内在反应性以及细胞膜对它们的有效分隔。在这篇综述中,我们分析了有关过氧化亚硝酸盐、其前体及其衍生反应物在体内的估计半衰期和相应的估计扩散距离的定量信息。此外,我们还讨论了细胞膜和合成脂膜对不同物种的渗透性,以及如何对其中一些物种实现有效的分隔,从而限制反应的生物部位。
{"title":"Diffusion of peroxynitrite, its precursors, and derived reactive species, and the effect of cell membranes","authors":"Matías N. Möller,&nbsp;Ana Denicola","doi":"10.1016/j.rbc.2024.100033","DOIUrl":"10.1016/j.rbc.2024.100033","url":null,"abstract":"<div><p>Peroxynitrite is a powerful oxidant formed in vivo in sites where superoxide and nitric oxide coincide. Peroxynitrite is cytotoxic through oxidative modification of target biomolecules that can occur by direct or indirect reactions. Indirect reactions usually involve the generation of peroxynitrite-derived radicals that include nitrogen dioxide, hydroxyl radical, and carbonate radical. All these species have different behaviors in vivo, because of their intrinsic reactivity and how effectively they can be compartmentalized by cellular membranes. In this review, we analyze quantitative information on the estimated half-lives and the corresponding estimated diffusion distances of peroxynitrite, its precursors, and its derived reactive species in vivo. Furthermore, we discuss the permeability of cellular and synthetic lipid membranes to the different species and how effective compartmentalization is achieved for some of them, limiting the biological site of reactions.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"9 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000142/pdfft?md5=330518d6b68fea24fff7146d2022ce23&pid=1-s2.0-S2773176624000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The chemistry of HNO-releasing compounds 释放 HNO 的化合物的化学性质
Pub Date : 2024-06-01 DOI: 10.1016/j.rbc.2024.100031
Renata Smulik-Izydorczyk , Jakub Pięta , Radosław Michalski , Monika Rola , Karol Kramkowski , Angelika Artelska , Jacek Zielonka , Adam Bartłomiej Sikora

HNO (azanone or nitroxyl), formally a product of the one-electron reduction of a nitric oxide, exhibits diverse and unique biological activity. The chemistry, biochemistry, and biological/pharmacological effects of HNO have been studied extensively. Due to rapid dimerization and hence short lifetime in solutions, in chemical and biological studies HNO is typically produced in situ from its thermal donors. To date, a great variety of chemical HNO donors have been synthesized, characterized, and utilized in biological studies. Here, we discuss the chemistry of HNO-releasing compounds, with the emphasis on the complexity of the proposed reaction mechanisms.

HNO(氮酮或硝基)是一氧化氮的单电子还原产物,具有多种独特的生物活性。人们对 HNO 的化学、生物化学和生物/药理作用进行了广泛的研究。由于二聚化速度快,因此在溶液中的寿命短,在化学和生物研究中,通常是在原位从热供体中生成 HNO。迄今为止,已经合成了多种化学 HNO 给体,对其进行了表征,并将其用于生物研究。在此,我们将讨论释放 HNO 的化合物的化学性质,重点是所提出的反应机制的复杂性。
{"title":"The chemistry of HNO-releasing compounds","authors":"Renata Smulik-Izydorczyk ,&nbsp;Jakub Pięta ,&nbsp;Radosław Michalski ,&nbsp;Monika Rola ,&nbsp;Karol Kramkowski ,&nbsp;Angelika Artelska ,&nbsp;Jacek Zielonka ,&nbsp;Adam Bartłomiej Sikora","doi":"10.1016/j.rbc.2024.100031","DOIUrl":"10.1016/j.rbc.2024.100031","url":null,"abstract":"<div><p><strong>HNO</strong> (azanone or nitroxyl), formally a product of the one-electron reduction of a nitric oxide, exhibits diverse and unique biological activity. The chemistry, biochemistry, and biological/pharmacological effects of <strong>H</strong><strong>N</strong><strong>O</strong> have been studied extensively. Due to rapid dimerization and hence short lifetime in solutions, in chemical and biological studies <strong>HNO</strong> is typically produced <em>in situ</em> from its thermal donors. To date, a great variety of chemical <strong>HNO</strong> donors have been synthesized, characterized, and utilized in biological studies. Here, we discuss the chemistry of <strong>HNO</strong>-releasing compounds, with the emphasis on the complexity of the proposed reaction mechanisms.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000129/pdfft?md5=d41d616194237ca22b5077ab1b087f18&pid=1-s2.0-S2773176624000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141281040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protein tyrosine nitration 蛋白质酪氨酸硝化
Pub Date : 2024-06-01 DOI: 10.1016/j.rbc.2024.100030
Harry Ischiropoulos

Protein tyrosine nitration is a post-translational modification originating from the biological chemistry of nitric oxide. This article highlights key milestones, discusses apparent controversies and perspectives that have emerged in the last 35 years of research on protein tyrosine nitration. Since the execution of nitric oxide signaling is accomplished entirely by protein post translational modifications (PTMs), the prospect that protein tyrosine nitration augments nitric oxide signaling remains an intriguing but incomplete concept deserving further consideration.

蛋白质酪氨酸硝化是一种源于一氧化氮生物化学的翻译后修饰。本文重点介绍了过去 35 年中蛋白质酪氨酸硝化研究的重要里程碑,讨论了明显的争议和出现的观点。由于一氧化氮信号转导的执行完全由蛋白质翻译后修饰(PTMs)完成,因此蛋白质酪氨酸硝化可增强一氧化氮信号转导的前景仍然是一个有趣但不完整的概念,值得进一步研究。
{"title":"Protein tyrosine nitration","authors":"Harry Ischiropoulos","doi":"10.1016/j.rbc.2024.100030","DOIUrl":"10.1016/j.rbc.2024.100030","url":null,"abstract":"<div><p>Protein tyrosine nitration is a post-translational modification originating from the biological chemistry of nitric oxide. This article highlights key milestones, discusses apparent controversies and perspectives that have emerged in the last 35 years of research on protein tyrosine nitration. Since the execution of nitric oxide signaling is accomplished entirely by protein post translational modifications (PTMs), the prospect that protein tyrosine nitration augments nitric oxide signaling remains an intriguing but incomplete concept deserving further consideration.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000117/pdfft?md5=9354ac441d5bfc4d3d9c04f3f6b7c502&pid=1-s2.0-S2773176624000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141232253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of sulfane sulfur species in elemental tellurium nanorod formation in mammalian cells 哺乳动物细胞中碲元素纳米棒形成过程中的硫磺物种作用
Pub Date : 2024-06-01 DOI: 10.1016/j.rbc.2024.100029
Yu-ki Tanaka , Hiroki Yanagi , Ayako Shiokawa , Akihiro Matsunaga , Mari Shimura , Satoshi Matsuyama , Yasunori Fukumoto , Noriyuki Suzuki , Yasumitsu Ogra

Tellurium (Te) is an industrially useful element but its oxyanions, such as tellurite and tellurate, are naturally occurring chemical forms that can become a potential source of toxicity to humans and animals. As a means of mitigating the toxicity of Te oxyanions, the formation of less toxic zero-valent elemental Te (Te0) nanostructures has been observed in various species including bacteria, fungi, green algae, and higher plants. In this study, we investigated the formation of Te0 nanorods in human hepatoma HepG2 cells. We detected electron-dense Te nanorods in lysosomes after exposure to potassium tellurite. The amount of Te nanorods in the cells gradually increased with the exposure period. Interestingly, the amount of Te in the insoluble fraction of the culture supernatant was approximately 10 times higher than that in HepG2 cells, suggesting that extracellular reducing agents originating from HepG2 cells transformed tetravalent Te (TeO32−) into Te0 in the culture medium. As an extracellular reducing agent, sulfane sulfur species were considered responsible for the reduction of Te(IV). Then, by inhibiting cystathionine γ-lyase with propargylglycine (PPG), we were able to reduce the amount of sulfane sulfur species generated in the cells. In the presence of PPG, the amount of insoluble Te in the culture supernatant, which was possibly composed of Te0 nanorods, was significantly decreased. The results suggest that sulfane sulfur species are involved in the formation of Te0 nanorods from tellurite in mammalian cells and play a critical role in the amelioration of Te oxyanion toxicity.

碲(Te)是一种工业上有用的元素,但它的氧阴离子(如碲化物和碲酸盐)是天然存在的化学形式,可能对人类和动物产生潜在的毒性。为了减轻碲氧阴离子的毒性,在细菌、真菌、绿藻和高等植物等不同物种中观察到了毒性较低的零价元素碲(Te0)纳米结构的形成。在本研究中,我们研究了 Te0 纳米棒在人类肝癌 HepG2 细胞中的形成。暴露于碲化钾后,我们在溶酶体中检测到了电子致密的 Te 纳米棒。细胞中 Te 纳米棒的数量随着暴露时间的延长而逐渐增加。有趣的是,培养上清中不溶部分的 Te 量比 HepG2 细胞中的高出约 10 倍,这表明来自 HepG2 细胞的细胞外还原剂将培养基中的四价 Te(TeO32-)转化成了 Te0。作为一种细胞外还原剂,硫烷硫种被认为是还原 Te(IV)的罪魁祸首。然后,通过使用丙炔甘氨酸(PPG)抑制胱硫醚γ-裂解酶,我们能够减少细胞中产生的烷硫物种的数量。在 PPG 的存在下,培养上清液中的不溶性 Te(可能由 Te0 纳米棒组成)数量显著减少。这些结果表明,烷硫物种参与了哺乳动物细胞中碲形成 Te0 纳米棒的过程,并在改善碲氧阴离子毒性方面发挥了关键作用。
{"title":"Role of sulfane sulfur species in elemental tellurium nanorod formation in mammalian cells","authors":"Yu-ki Tanaka ,&nbsp;Hiroki Yanagi ,&nbsp;Ayako Shiokawa ,&nbsp;Akihiro Matsunaga ,&nbsp;Mari Shimura ,&nbsp;Satoshi Matsuyama ,&nbsp;Yasunori Fukumoto ,&nbsp;Noriyuki Suzuki ,&nbsp;Yasumitsu Ogra","doi":"10.1016/j.rbc.2024.100029","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100029","url":null,"abstract":"<div><p>Tellurium (Te) is an industrially useful element but its oxyanions, such as tellurite and tellurate, are naturally occurring chemical forms that can become a potential source of toxicity to humans and animals. As a means of mitigating the toxicity of Te oxyanions, the formation of less toxic zero-valent elemental Te (Te<sup>0</sup>) nanostructures has been observed in various species including bacteria, fungi, green algae, and higher plants. In this study, we investigated the formation of Te<sup>0</sup> nanorods in human hepatoma HepG2 cells. We detected electron-dense Te nanorods in lysosomes after exposure to potassium tellurite. The amount of Te nanorods in the cells gradually increased with the exposure period. Interestingly, the amount of Te in the insoluble fraction of the culture supernatant was approximately 10 times higher than that in HepG2 cells, suggesting that extracellular reducing agents originating from HepG2 cells transformed tetravalent Te (TeO<sub>3</sub><sup>2−</sup>) into Te<sup>0</sup> in the culture medium. As an extracellular reducing agent, sulfane sulfur species were considered responsible for the reduction of Te(IV). Then, by inhibiting cystathionine <em>γ</em>-lyase with propargylglycine (PPG), we were able to reduce the amount of sulfane sulfur species generated in the cells. In the presence of PPG, the amount of insoluble Te in the culture supernatant, which was possibly composed of Te<sup>0</sup> nanorods, was significantly decreased. The results suggest that sulfane sulfur species are involved in the formation of Te<sup>0</sup> nanorods from tellurite in mammalian cells and play a critical role in the amelioration of Te oxyanion toxicity.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000105/pdfft?md5=361e503f29b34dd81191f837af98e0d8&pid=1-s2.0-S2773176624000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141244416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protein nitration in the artery wall: A contributor to cardiovascular disease? 动脉壁中的蛋白质硝化:心血管疾病的诱因?
Pub Date : 2024-06-01 DOI: 10.1016/j.rbc.2024.100032
Michael J. Davies

Nitration is a well-established post-translational modification of selected free amino acids, as well as proteins, lipids and nucleic acids. Considerable evidence is now available for the formation of long-lived species containing an added –NO2 function on the aromatic rings of tyrosine (Tyr) and tryptophan (Trp) residues (both free and on proteins), to purine nucleobases (and particularly guanine), and to unsaturated lipids within biological systems. Multiple potential mechanisms that give rise to these nitrated species have been identified including reactions of the potent oxidant and nitrating species peroxynitrous acid/peroxynitrite (ONOOH/ONOO) and via oxidative reactions of heme proteins/enzymes (e.g. peroxidases) with the biologically-relevant anion nitrite (NO2). NO2 is likely to be a key intermediate, though involvement of HNO2, NO2+ and NO2Cl has also been proposed. The resulting nitrated products have been widely employed as qualitative or quantitative biomarkers of nitration events in vitro and in vivo. Increasing evidence suggests that at least some of these products are not benign species, with evidence for pro-inflammatory actions. In this article the mechanisms and role of nitration, and particularly that on proteins within the artery wall, in cardiovascular disease is discussed, together with emerging data suggesting that low levels of nitration occur within biological systems in the absence of added oxidants. Both stimulated and endogenous nitration may play a role in modulating cell signaling, alter the structure and function of both cellular- and extracellular proteins, and contribute to various inflammatory pathologies, including atherosclerosis.

硝化作用是对某些游离氨基酸以及蛋白质、脂类和核酸进行的一种行之有效的翻译后修饰。目前已有大量证据表明,在生物系统中,酪氨酸(Tyr)和色氨酸(Trp)残基(游离的和蛋白质上的)、嘌呤核碱基(尤其是鸟嘌呤)和不饱和脂质的芳香环上会形成含有附加 -NO2 功能的长效物质。已确定了产生这些硝化物种的多种潜在机制,包括强氧化剂和硝化物种过氧化亚氮酸/过氧化亚氮酸(ONOOH/ONOO-)的反应,以及血红素蛋白/酶(如过氧化物酶)与生物相关阴离子亚硝酸盐(NO2-)的氧化反应。-NO2 很可能是一个关键的中间产物,但也有人认为 HNO2、NO2+ 和 NO2Cl 也参与了反应。由此产生的硝化产物已被广泛用作体外和体内硝化事件的定性或定量生物标记。越来越多的证据表明,这些产物中至少有一些不是良性的,有证据表明它们具有促炎作用。本文讨论了硝化在心血管疾病中的机制和作用,特别是动脉壁蛋白质上的硝化,以及新出现的数据表明,在没有添加氧化剂的情况下,生物系统中也会发生低水平的硝化。受刺激的硝化和内源性硝化都可能在调节细胞信号、改变细胞内外蛋白质的结构和功能方面发挥作用,并导致各种炎症性病变,包括动脉粥样硬化。
{"title":"Protein nitration in the artery wall: A contributor to cardiovascular disease?","authors":"Michael J. Davies","doi":"10.1016/j.rbc.2024.100032","DOIUrl":"10.1016/j.rbc.2024.100032","url":null,"abstract":"<div><p>Nitration is a well-established post-translational modification of selected free amino acids, as well as proteins, lipids and nucleic acids. Considerable evidence is now available for the formation of long-lived species containing an added –NO<sub>2</sub> function on the aromatic rings of tyrosine (Tyr) and tryptophan (Trp) residues (both free and on proteins), to purine nucleobases (and particularly guanine), and to unsaturated lipids within biological systems. Multiple potential mechanisms that give rise to these nitrated species have been identified including reactions of the potent oxidant and nitrating species peroxynitrous acid/peroxynitrite (ONOOH/ONOO<sup>−</sup>) and via oxidative reactions of heme proteins/enzymes (e.g. peroxidases) with the biologically-relevant anion nitrite (NO<sub>2</sub><sup>−</sup>). <sup>•</sup>NO<sub>2</sub> is likely to be a key intermediate, though involvement of HNO<sub>2</sub>, NO<sub>2</sub><sup>+</sup> and NO<sub>2</sub>Cl has also been proposed. The resulting nitrated products have been widely employed as qualitative or quantitative biomarkers of nitration events <em>in vitro</em> and <em>in vivo</em>. Increasing evidence suggests that at least some of these products are not benign species, with evidence for pro-inflammatory actions. In this article the mechanisms and role of nitration, and particularly that on proteins within the artery wall, in cardiovascular disease is discussed, together with emerging data suggesting that low levels of nitration occur within biological systems in the absence of added oxidants. Both stimulated and endogenous nitration may play a role in modulating cell signaling, alter the structure and function of both cellular- and extracellular proteins, and contribute to various inflammatory pathologies, including atherosclerosis.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000130/pdfft?md5=145e5634e1cd27124e29854f3c750e6b&pid=1-s2.0-S2773176624000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Purine, nucleoside, and DNA nitration by peroxynitrite: Mechanistic considerations 过氧化亚硝酸对嘌呤、核苷和 DNA 的硝化作用:机理研究
Pub Date : 2024-05-15 DOI: 10.1016/j.rbc.2024.100028
Ana G. Sánchez, Deborah J. Keszenman, R. Daniel Peluffo

Nitro-oxidative stress affects DNA, leading to special chemical modifications of nucleobases and deoxyribose, impacting DNA integrity and stability. Because of the importance of the topic, the state of the knowledge on purine, nucleoside, and DNA nitration by the reactive nitrogen species peroxynitrite was reviewed. Following a description of the chemical and physicochemical characteristics of purines and peroxynitrite, purine nitro-oxidation and its products, the reaction mechanisms, and the recently reported kinetic behavior of 8-NitroGua formation are discussed. Moreover, novel computational studies report structural and conformational DNA changes resulting from the formation of guanine nitration products. Given the relevance of the subject, surprisingly few publications deal with this topic, even considering the past five years.

硝基氧化应激会影响 DNA,导致核碱基和脱氧核糖发生特殊的化学修饰,从而影响 DNA 的完整性和稳定性。鉴于该主题的重要性,我们回顾了活性氮物种过氧化亚硝酸盐对嘌呤、核苷和 DNA 硝化作用的认识现状。在描述了嘌呤和过亚硝酸的化学和物理化学特征之后,讨论了嘌呤硝基氧化及其产物、反应机制以及最近报道的 8-NitroGua 形成的动力学行为。此外,新的计算研究报告了鸟嘌呤硝化产物的形成所导致的 DNA 结构和构象变化。鉴于该主题的相关性,即使考虑到过去五年的情况,涉及该主题的出版物也少得令人吃惊。
{"title":"Purine, nucleoside, and DNA nitration by peroxynitrite: Mechanistic considerations","authors":"Ana G. Sánchez,&nbsp;Deborah J. Keszenman,&nbsp;R. Daniel Peluffo","doi":"10.1016/j.rbc.2024.100028","DOIUrl":"10.1016/j.rbc.2024.100028","url":null,"abstract":"<div><p>Nitro-oxidative stress affects DNA, leading to special chemical modifications of nucleobases and deoxyribose, impacting DNA integrity and stability. Because of the importance of the topic, the state of the knowledge on purine, nucleoside, and DNA nitration by the reactive nitrogen species peroxynitrite was reviewed. Following a description of the chemical and physicochemical characteristics of purines and peroxynitrite, purine nitro-oxidation and its products, the reaction mechanisms, and the recently reported kinetic behavior of 8-NitroGua formation are discussed. Moreover, novel computational studies report structural and conformational DNA changes resulting from the formation of guanine nitration products. Given the relevance of the subject, surprisingly few publications deal with this topic, even considering the past five years.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000099/pdfft?md5=f15d74688ad9863cfd9c5bb5da57af3b&pid=1-s2.0-S2773176624000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Redox Biochemistry and Chemistry
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1