Phosgene

光气
  • 文章类型: Journal Article
    考虑到光气的高毒性和广泛应用,迫切需要开发一种简单而灵敏的检测光气的方法。在这项工作中,我们设计并合成了含有苯并咪唑和苯并噻唑荧光团的新型比率荧光探针1。探针1对光气表现出优异的灵敏度(<30s)和选择性(LOD=3.82nM)以及显著的比率荧光变化。此外,1负载聚苯乙烯膜测试条用于通过肉眼和智能手机的RGBAPP方便,有效地检测光气气体(0.5ppm),这表明该探针在气相光气检测中具有很大的潜力。
    Considering the high toxicity and widespread application of phosgene, there is an urgent need to develop a simple and sensitive method for detecting phosgene. In this work, we designed and synthesized a novel ratiometric fluorescent probe 1 containing fluorophores of benzimidazole and benzothiazole. Probe 1 showed excellent sensitivity (< 30 s) and selectivity (LOD = 3.82 nM) for phosgene and significant ratiometric fluorescence changes. In addition, 1-loaded polystyrene membrane test strips were used to conveniently and efficiently detect phosgene gas (0.5 ppm) via the naked eye and the RGB APP of the smartphone, indicating that this probe has great potential for phosgene detection in the gaseous phase.
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  • 文章类型: Journal Article
    光气是世界范围内广泛使用的化学材料。尚未开发出有效的方法来逆转其病理损伤。一些研究表明,肺组织中的神经元炎症参与其中,但具体机制尚未见报道。
    分析光气吸入性肺损伤(P-ALI)后肺组织全转录组基因测序生物信息学和蛋白表达谱的变化,寻找影响P-ALI预后的主要因素和途径。
    通过光气制备P-ALI的大鼠模型。将大鼠分为P-ALI组和空白组。采用苏木精-伊红(HE)染色和肺干湿比测定评价肺损伤。ELISA法检测炎症因子水平。高通量测序用于测量每个基因的表达谱。通过差异蛋白质组的无标记相对定量来确定蛋白质表达谱。
    肺损伤,如肺泡壁结构紊乱和炎症因子(IL-1β,IL-18和IL-33)在P-ALI组中显著升高(p<0.05)。有225个差异表达的lncRNAs,包括85个上调基因和140个下调基因。它们也是转录组基因表达变化最显著的基因组,主要构成细胞质,突触结构和转运蛋白,参与氨基酸和碳代谢。有42个差异表达的circRNAs,包括25个上调基因和17个下调基因,主要参与细胞组成,增长,分化,和分裂。只有10个差异表达的miRNAs基因,均上调,主要参与炎症反应途径。蛋白质组鉴定显示79种差异表达的蛋白质。KEGG富集分析表明,它主要参与N-聚糖生物合成途径。
    我们发现差异调节基因(lncRNAs,circRNAs,和miRNA)主要与神经元反射和突触信号有关,包括神经递质的传递,离子信号通路传导,神经元投射,和突触小泡循环。它们影响炎症因子和其他代谢途径。这一发现可以在未来的研究中探索。
    UNASSIGNED: Phosgene is a chemical material widely used worldwide. No effective method has been developed to reverse its pathological injuries. Some studies have shown that neuronal inflammation in lung tissue is involved, but the specific mechanism has not been reported.
    UNASSIGNED: To analyze the expression alterations of whole transcriptome gene sequencing bioinformatics and protein expression profile in lung tissue after phosgene aspiration lung injury (P-ALI) and find the main factors and pathways affecting the prognosis of P-ALI.
    UNASSIGNED: Rat models of P-ALI were made by phosgene. Rats were divided into a P-ALI group and a blank group. Hematoxylin-eosin (HE) staining and lung wet/dry ratio measurement were used to evaluate the lung injury. The levels of inflammatory factors were measured by ELISA. High-throughput sequencing was used to measure the expression profile of each gene. Protein expression profiles were determined by label-free relative quantification of the differential proteome.
    UNASSIGNED: Lung injury such as the disordered structure of alveolar wall and inflammatory factors (IL-1β, IL-18, and IL-33) were significantly increased in the P-ALI group (p < 0.05). There were 225 differentially expressed lncRNAs, including 85 upregulated and 140 downregulated genes. They were also the genomes with the most significant changes in transcriptome gene expression, mainly constituting cytoplasmic, synaptic structures and transporters, and involved in amino acid and carbon metabolism. There were 42 differentially expressed circRNAs, including 25 upregulated genes and 17 downregulated genes, mainly involved in cell composition, growth, differentiation, and division. There were only 10 differentially expressed miRNAs genes, all upregulated and mainly involved in the inflammatory response pathway. Proteome identification showed 79 differentially expressed proteins. KEGG enrichment analysis showed that it was mainly involved in the N-glycan biosynthesis pathway.
    UNASSIGNED: We discovered that differentially regulated genes (lncRNAs, circRNAs, and miRNAs) were primarily associated with neuronal reflexes and synaptic signaling, including neurotransmitter transmission, ion signaling pathway conduction, neuronal projection, and synaptic vesicle circulation. They affected inflammatory factors and other metabolic pathways. This finding could be explored in future studies.
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  • 文章类型: Journal Article
    光气是一种有毒气体,在意外暴露时会引起急性肺损伤(ALI)。由于操作不当导致的事故导致光气引起的急性肺损伤(P-ALI),仍然会造成人员伤亡。P-ALI的病理机制仍未得到充分研究。因此,我们对从P-ALI的BALF所有亚群中分离的细胞进行了scRNA-seq,发现Gal3表达在气体组中明显高于对照组。进一步分析揭示了肺泡巨噬细胞(AM)和肺泡上皮细胞(AEC)之间的配体-受体对应关系,Gal3在这种互动中起着关键作用。为了证实和阐述这一发现,我们选择了前一周的四个时间点:假(第0天),在P-ALI小鼠模型的第1天,第3天和第7天,发现Gal3在P-ALI中表达显着升高,在AM细胞中最大量表达。这通过使用Gal3抑制剂进一步证实。Gal3的抑制和AMs的消除都减弱了小鼠上皮细胞的焦亡,正如在体外实验中所证实的那样,并揭示了Gal3/caspase-8/GSDMD信号通路。这些发现表明,抑制Galectin-3可以通过抑制Gal3/caspase-8/GSDMD信号通路来改善AEC的细胞凋亡,从而减少P-ALI小鼠的肺泡损伤。这一发现为改善P-ALI的治疗功效提供了新的见解。
    Phosgene is a type of poisonous gas that can cause acute lung injury (ALI) upon accidental exposure. Casualties still occur due to phosgene-induced acute lung injury (P-ALI) from accidents resulting from improper operations. The pathological mechanisms of P-ALI are still understudied. Thus, we performed scRNA-seq on cells isolated from all subpopulations of the BALF in P-ALI and found that Gal3 expression was significantly higher in the gas group than in the control group. Further analysis revealed a ligand-receptor correspondence between alveolar macrophages (AMs) and alveolar epithelial cells (AEC), with Gal3 playing a key role in this interaction. To confirm and elaborate on this discovery, we selected four time points during the previous week: sham (day 0), day 1, day 3, and day 7 in the P-ALI mouse model and found that Gal3 expression was significantly elevated in P-ALI, most abundantly expressed in AM cells. This was further confirmed with the use of a Gal3 inhibitor. The inhibition of Gal3 and elimination of AMs in mice both attenuated epithelial cell pyroptosis, as confirmed in in vitro experiments, and revealed the Gal3/caspase-8/GSDMD signaling pathway. These findings suggest that Galectin-3 inhibition can ameliorate AEC pyroptosis by inhibiting the Gal3/caspase-8/GSDMD signaling pathway, thus reducing alveolar damage in mice with P-ALI. This finding provides novel insights for improving treatment efficacy for P-ALI.
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  • 文章类型: Journal Article
    在没有确定的碳源的情况下,报道的由漂白粉形成光气的情况受到质疑。除作者调查的干扰和混杂效应外,其他干扰和混杂效应可能导致人为结果。
    In the absence of an identified source of carbon, the reported formation of phosgene from bleach powder is questioned. Interferences and confounding effects other than those investigated by the authors may have led to artifactual results.
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  • 文章类型: Journal Article
    暴露于光气,一种无色的有毒气体,会导致各种健康问题,包括眼睛刺激,干燥灼热的喉咙,呕吐,咳嗽,产生泡沫痰,呼吸困难,和胸痛。本系统综述旨在通过系统分析现有文献,全面概述光气毒性的临床表现和治疗方法。搜索是在各种科学在线数据库上进行的,包括基于PRISMA指南的纳入和排除标准的相关研究。使用混合方法评估工具(MMAT)评估研究的质量。筛选过程后,本研究纳入了13篇文章。发现吸入是光气暴露的主要健康问题,伴有咳嗽和呼吸困难等呼吸道症状。在某些情况下还观察到胸痛和肺水肿。此外,肺裂是最常见的体检报告.除了呼吸道健康问题,其他器官如心脏,皮肤,眼睛,在一些研究中也报道了肾脏和肾脏。症状可在暴露后几分钟到几小时内出现,症状的严重程度取决于吸入的光气量。结果表明,支气管扩张剂可以减轻光气引起的支气管收缩症状。在低氧血症的情况下,氧气治疗对于恢复氧气水平和改善呼吸功能至关重要。在严重的情况下,气管插管和有创机械通气用于人工呼吸,以及通过抽吸去除气管分泌物和肺水肿液作为支持治疗的关键组成部分。
    Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry and burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. This systematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgene toxicity by systematically analyzing available literature. The search was carried out on various scientific online databases to include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in this study after the screening process. Inhalation was found to be the primary health problem of phosgene exposure with respiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in some cases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tract health issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. The symptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount of inhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction caused by phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in cases of hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificial respiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucial components of supportive therapy.
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  • 文章类型: English Abstract
    光气不仅是一种危险的窒息化学战剂,也是重要的化工原料,广泛应用于化工生产中。据统计,中国有1000多家光气生产企业,年生产量超过300万吨,员工数十万。因此,一旦在生产过程中发生泄漏事故,储存和运输,它经常造成大量人员伤亡。在过去的20年里,我国光气中毒事故时有发生,由于微弱的刺激,高密度,事故现场有高浓度的光气,它经常导致暴露者的急性高浓度吸入,触发急性肺损伤(ALI),并且很可能进展为急性呼吸窘迫综合征(ARDS),死亡率高达40%-50%。鉴于突发性的特点,质量,隐藏,快速和高度致命的光气,其毒性和致病机理尚不清楚,对于突发性群体光气中毒尚无有效的治疗方法和规范的指导。为了提高临床治疗的有效率,降低死亡率,本文综述了光气中毒的病理生理机制,临床表现,现场处理,研究进展,结合多年来对光气的广泛基础研究和对突发性团块光气中毒的现场治疗的丰富经验,进行创新的临床治疗。本共识旨在为突发群体性光气中毒患者的临床抢救和治疗提供指导,提高治疗水平。
    Phosgene is not only a dangerous asphyxiating chemical warfare agent, but also an important chemical raw material, which is widely used in chemical production. According to statistics, there are more than 1 000 phosgene production enterprises in China, with an annual production volume of more than 3 million tons and hundreds of thousands of employees. Therefore, once the leakage accident occurs during production, storage and transportation, it often causes a large number of casualties. In the past 20 years, phosgene poisoning accidents in China have occurred from time to time, and due to the weak irritation, high density, and high concentration of phosgene at the scene of the accident, it often results in acute high-concentration inhalation of the exposed, triggering acute lung injury (ALI), and is very likely to progress to acute respiratory distress syndrome (ARDS), with a mortality rate up to 40%-50%. In view of the characteristics of sudden, mass, concealed, rapid and highly fatal phosgene, and the mechanism of its toxicity and pathogenicity is still not clear, there is no effective treatment and standardized guidance for the sudden group phosgene poisoning. In order to improve the efficiency of clinical treatment and reduce the mortality, this paper has summarized the pathophysiological mechanism of phosgene poisoning, clinical manifestations, on-site treatment, research progress, and innovative clinical therapies by combining the extensive basic research on phosgene over the years with the abundant experience in the on-site treatment of sudden mass phosgene poisoning. This consensus aims to provide guidance for the clinical rescue and treatment of patients with sudden mass phosgene poisoning, and to improve the level of treatment.
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  • 文章类型: Journal Article
    我们提出了猪受试者中光气诱导的肺损伤的病理生理后果的第一个计算模型。先前在几个大型健康幼年雌性猪队列中进行的实验数据(来自37名受试者的111个数据点),包括个体动脉血气读数,呼吸率和心率,用于开发计算模型。在模型输出(PaO2和PaCO2)和实验数据之间观察到紧密匹配,对于最终麻醉和有意识的受试者。该模型用于研究在暴露后不同时间点开始治疗时,持续气道正压通气(CPAP)作为院前治疗方法的有效性。该模型预测,当暴露后约8小时内开始10cmH2OCPAP时,可获得临床相关的益处。供应低流量氧气(40%)而不是医用空气比应用更高的CPAP压力水平产生更大的临床益处。这种新模型可以作为一种工具,用于对不同病因的化学肺损伤的通气策略和药物治疗进行研究。以及在未来的实验研究中帮助改进和减少动物的使用。
    We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive airway pressure (CPAP) as a pre-hospital treatment method when treatment is initiated at different time points post exposure. The model predicts that clinically relevant benefits are obtained when 10 cmH2O CPAP is initiated within approximately 8 h after exposure. Supplying low-flow oxygen (40%) rather than medical air produced larger clinical benefits than applying higher CPAP pressure levels. This new model can be used as a tool for conducting investigations into ventilation strategies and pharmaceutical treatments for chemical lung injury of diverse aetiology, and for helping to refine and reduce the use of animals in future experimental studies.
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  • 文章类型: Journal Article
    光气,一种特别危险的气体,对公众的健康和安全构成严重关切。本研究描述了一种用于光气的荧光比率探针,该探针采用以氨基为识别位点的2-(萘-2-基)苯并[d]恶唑-5-胺(NOA)。NOA通过分子内电荷转移机制检测光气。NOA的富电子胺基攻击光气的亲电子羰基,导致在20s内的快速反应。NOA显示60nM的低检测限,同时保持对光气的高选择性和灵敏度。将最终产物分离并通过核磁共振波谱验证。该探针不仅可以在溶液环境中快速检测光气,而且可以在其固态中检测光气。还展示了该探针在指纹成像和生物成像中的应用。
    Phosgene, an exceptionally hazardous gas, poses a grave concern for the health and safety of the general public. The present study describes a fluorescent ratiometric probe for phosgene employing 2-(naphthalen-2-yl) benzo[d]oxazol-5-amine (NOA) with an amino group as the recognition site. NOA detects phosgene through the intramolecular charge transfer mechanism. The electron-rich amine group of NOA attacks the electrophilic carbonyl group of phosgene, resulting in a quick response within 20 s. NOA demonstrates a low detection limit of 60 nM while maintaining high selectivity and sensitivity toward phosgene. The final product was isolated and verified by nuclear magnetic resonance spectroscopy. The probe can detect phosgene not just quickly in a solution environment but also in its solid state. The probe\'s applications in fingerprint imaging and bioimaging are also demonstrated.
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  • 文章类型: Journal Article
    光气是一种高隐蔽性、剧毒的气体,严重威胁人类健康和公共安全。因此,光气的检测对世界安全具有重要意义。在这里,报道了一种基于2-(2-氨基苯基)咪唑并[1,5-a]吡啶的新型荧光探针,用于光气的快速检测。探针本身只发出微弱的绿色荧光,光气使其产生强烈的蓝色荧光。在识别过程中,光气同时与探针分子中的氨基位点和咪唑部分相互作用,导致具有高荧光量子产率的四环融合刚性结构。该探头不仅具有效率高的特点,高灵敏度(检测限2.68nM),和高选择性,但也有显著的光谱变化。最后,便携式测试条用于检测气相中的光气,并且可以容易地观察到测试条的荧光颜色变化。最令人兴奋的是,带有探针PMPY-NH2的便携式测试条可以对1ppm的光气产生强烈的荧光响应,远低于严重威胁人类健康的光气水平。
    Phosgene is a highly concealed and highly toxic gas that seriously threatens human health and public security. Therefore, the detection of phosgene is of great significance to world security. Herein, a new type of fluorescent probe based on 2-(2-aminophenyl) imidazo [1,5-a] pyridine is reported for the rapid detection of phosgene. The probe itself only emits a faint green fluorescence, while phosgene allows it to produce a strong blue fluorescence. During the recognition process, phosgene interacts simultaneously with both amino site and imidazole moiety in the probe molecule, resulting in a four-ring-fused rigid structure with high fluorescence quantum yield. The probe not only has the characteristics of high efficiency, high sensitivity (detection limit 2.68 nM), and high selectivity, but also has remarkable spectral changes. Finally, a portable test strip is used to detect phosgene in the gas phase, and the fluorescent color change of the test strip can be easily observed. The most exciting thing is that the portable test strip with the probe PMPY-NH2 can produce a strong fluorescence response to 1 ppm of phosgene, which is far lower than the level of phosgene that seriously threatens to human health.
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  • 文章类型: Journal Article
    吸入的毒物用于不同的目的,从农业等工业应用,卫生,和熏蒸人群控制和化学战,急性暴露会导致持续的呼吸系统并发症。第一次世界大战期间故意释放化学战剂(CWA)给幸存者造成了终身伤害,国际条约禁止使用CWA。然而,在过去的二十年里,中东和东欧的化学战使用量激增,向肺部有毒物质转移。工业和农业化学品在流氓活动中的潜在用途是一个主要问题,因为它们通常在人口稠密地区附近储存和运输,故意或意外释放可能导致严重伤害和死亡。尽管法律和监管机构规范使用,storage,运输,排放,和处置,吸入性暴露会持续导致肺损伤.工业刺激物(例如,氨)加重上呼吸道,导致肺炎,支气管收缩,和呼吸困难。刺激性气体(例如,丙烯醛,氯化苦)影响上皮屏障的完整性,并通过反应性中间体或通过富含半胱氨酸的蛋白质的直接内收引起组织损伤。CWA的症状(例如,氯气,光气,芥子气)从气道阻塞和肺水肿发展为急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS),几天后导致呼吸抑制。急诊治疗仅限于使用支气管扩张剂控制气道收缩的支持性护理,并通过机械通气进行抢救以改善气体交换。急性暴露引起的并发症可促进阻塞性肺疾病和/或肺纤维化,这需要长期的临床护理。重要声明:在民用和军事环境中,吸入的化学威胁日益受到关注,并且对减少急性肺损伤和因暴露引起的延迟临床并发症的需求增加。这篇简短的评论强调了我们目前对某些关注的化学物质的急性毒性和病理生理学的理解。它讨论了潜在的早期治疗发展以及在制定适用于大规模伤亡情况下的管理对策方面的挑战。
    Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
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