RNA, ribonucleic acid

RNA,核糖核酸
  • 文章类型: Journal Article
    病毒是具有生物活性的寄生虫,仅存在于宿主内部,它们是亚微观水平的。新型冠状病毒病,或COVID-19,通常由SARS-CoV-2病毒引起,与严重急性呼吸道综合症(SARS)相当。由于全球化,随着时间的推移,SARS-CoV-2的自然改变或变化对人类健康产生了重大风险。这些病毒可以在大气中以不同的方式生存和生存,除非它们到达另一个宿主体内。在这个阶段,我们将讨论通过某些环境媒体传播和检测这种致命的SARS-CoV-2病毒的细节,比如大气,水,空气,污水,土壤,温度,相对湿度,和生物气溶胶,为了更好地理解扩散,生存,COVID-19的感染潜力和诊断。
    Viruses are biologically active parasites that only exist inside a host they are submicroscopic level. The novel coronavirus disease, or COVID-19, is generally caused by the SARS-CoV-2 virus and is comparable to severe acute respiratory syndrome (SARS). As a result of globalization, natural alterations or changes in the SARS-CoV-2 have created significant risks to human health over time. These viruses can live and survive in different ways in the atmosphere unless they reach another host body. At this stage, we will discuss the details of the transmission and detection of this deadly SARS-CoV-2 virus via certain environmental media, such as the atmosphere, water, air, sewage water, soil, temperature, relative humidity, and bioaerosol, to better understand the diffusion, survival, infection potential and diagnosis of COVID-19.
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  • 文章类型: Journal Article
    一氧化氮(NO)是一种重要的气体发射器,对许多细菌和病毒感染的先天免疫反应的发展具有重要意义。同时还调节血管生理学。从内源性一氧化氮合酶的上调产生NO是抑制宿主防御中病毒复制的有效方法,并需要对抗病毒疗法的开发进行研究。随着与几种呼吸道病毒感染有关的全球大流行的发病率增加,有必要开发广泛的治疗平台来抑制病毒复制并实现更有效的宿主清除,以及制造新材料来阻止医疗设备中的病毒传播。在产生稳定的NO供体化合物及其掺入大分子支架和聚合物基材中的最新进展为开发基于NO的治疗剂以在杀菌和接触血液的表面的应用中长期释放NO创造了新的范例。尽管有大量的研究,很少考虑释放NO的支架和基质来减少病毒感染的被动传播或治疗几种呼吸道病毒感染。这篇综述的目的是强调开发气态NO的最新进展,没有前药,和NO供体化合物用于抗病毒治疗;讨论NO作为抗病毒剂的局限性;并概述了指导材料设计下一代NO释放抗病毒平台的未来前景。
    Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms.
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  • 文章类型: Journal Article
    短链脂肪酸(SCFA)在结肠癌的细胞和动物模型中表现出抗癌活性。醋酸盐,丙酸盐,和丁酸盐是由膳食纤维通过肠道微生物群发酵产生的三种主要SCFA,对人体健康具有有益作用。以往对SCFA抗肿瘤机制的研究大多集中在参与抗肿瘤通路的特定代谢产物或基因上,如活性氧(ROS)生物合成。在这项研究中,我们对乙酸盐的影响进行了系统和无偏见的分析,丙酸盐,和丁酸盐对人结肠直肠腺癌细胞生理浓度下ROS水平以及代谢和转录组特征的影响。我们观察到在处理的细胞中ROS水平显著升高。此外,显著调节的信号涉及代谢和转录组水平的重叠途径,包括ROS反应和代谢,脂肪酸运输和代谢,葡萄糖反应和代谢,线粒体运输和呼吸链复合物,一碳代谢,氨基酸运输和代谢,和谷氨酰胺分解,它们与ROS的产生直接或间接相关。此外,代谢和转录组调节以SCFAs类型依赖的方式发生,从乙酸到丙酸再到丁酸的程度逐渐增加。本研究全面分析了SCFA如何诱导ROS产生并调节结肠癌细胞的代谢和转录水平。这对于理解SCFA对结肠癌抗肿瘤活性的作用机制至关重要。
    Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    COVID-19大流行强调了公众对室内空气传播疾病的认识,并强调需要可靠的空气消毒技术。这种意识的提高将与不断出现的SARS-CoV变体一起在大流行后时代继续存在,需要有效和明确的协议,方法,和空气消毒装置。基于紫外线(UV)的空气消毒在灭活病毒生物气溶胶方面表现出了有希望的结果。然而,报告的所需UVC剂量的数据多样性阻碍了确定最佳UVC实践,并导致公众和监管机构之间的混淆.本文回顾了有关影响UVC空气消毒系统功效的关键参数的可用信息,因此,所需剂量包括系统的组件以及操作和环境因素。在文献中有一个共识,即湿度和空气温度的相互关系对UVC敏感性有显著影响。这转化为在不同条件下改变室内环境中商业化设备的UVC功效。据报道,采样和雾化技术对结果解释有重大影响,建议同时使用几种采样方法来生成可比和结论性的数据。我们还考虑了UVC的安全问题和潜在的安全替代品,远紫外线。最后,代表了每个关键参数的差距和该领域未来的研究需求。本文是巩固文献的第一步,以开发UVC空气消毒设备的标准验证协议,该协议被确定为研究需求之一。
    The COVID-19 pandemic highlighted public awareness of airborne disease transmission in indoor settings and emphasized the need for reliable air disinfection technologies. This increased awareness will carry in the post-pandemic era along with the ever-emerging SARS-CoV variants, necessitating effective and well-defined protocols, methods, and devices for air disinfection. Ultraviolet (UV)-based air disinfection demonstrated promising results in inactivating viral bioaerosols. However, the reported data diversity on the required UVC doses has hindered determining the best UVC practices and led to confusion among the public and regulators. This article reviews available information on critical parameters influencing the efficacy of a UVC air disinfection system and, consequently, the required dose including the system\'s components as well as operational and environmental factors. There is a consensus in the literature that the interrelation of humidity and air temperature has a significant impact on the UVC susceptibility, which translate to changing the UVC efficacy of commercialized devices in indoor settings under varying conditions. Sampling and aerosolization techniques reported to have major influence on the result interpretation and it is recommended to use several sampling methods simultaneously to generate comparable and conclusive data. We also considered the safety concerns and the potential safe alternative of UVC, far-UVC. Finally, the gaps in each critical parameter and the future research needs of the field are represented. This paper is the first step to consolidating literature towards developing a standard validation protocol for UVC air disinfection devices which is determined as the one of the research needs.
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  • 文章类型: Journal Article
    自2019年12月以来,严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)已成为一种新兴的人类病毒,世界人口易患2019年冠状病毒病(COVID-19)。SARS-CoV-2比以前的冠状病毒具有更高的传播能力,由核糖核酸(RNA)病毒性质相关的高突变率,导致SARS-CoV-2变体在全球传播时出现。中和抗体被鉴定为针对COVID-19的即时和直接作用治疗剂。单结构域抗体(sdAb),作为具有非复杂结构和内在稳定性的小生物分子,可以获得与常规抗体相当的抗原结合能力,作为一种有吸引力的中和溶液。SARS-CoV-2刺突蛋白附着于肺上皮细胞上的人血管紧张素转换酶2(ACE2)受体以引发病毒感染,作为潜在的治疗靶点。sdAb已经显示出广泛的中和对SARS-CoV-2的各种突变,有效阻止和预防感染,同时有效阻止突变逃逸。此外,sdAb可以发展成为针对COVID-19的多价抗体或吸入性生物治疗剂。
    With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.
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  • 文章类型: Journal Article
    内在蛋白质的灵活性对于高度动态的复合物集合的分子间识别和适应性具有压倒性的相关性,这种现象对于理解许多生物过程至关重要。这些构象集合-遇到复合物-缺乏独特的组织,这阻止了明确定义的高分辨率结构的确定。对于涉及癌蛋白SET/模板激活因子Iβ(SET/TAF-Iβ)的复合物,一种组蛋白伴侣,其功能和相互作用受到其固有结构可塑性的显着影响。除了它在染色质重塑中的作用,SET/TAF-Iβ是蛋白磷酸酶2A(PP2A)的抑制剂,这是一个关键的磷酸酶抵消转录和信号事件控制DNA损伤反应(DDR)介质的活性。在DDR期间,在血红素蛋白从线粒体迁移到细胞核时,SET/TAF-Iβ被细胞色素c(Cc)隔离。这里,我们报道了核SET/TAF-Iβ:Cc多构象集合能够激活PP2A。特别是,N端折叠,SET/TAF-Iβ的球状区域(也称SET/TAF-IβΔC)-表现出意想不到的,本质上高度动态的行为-足以被Cc以扩散相遇的方式识别。Cc介导的PP2A抑制阻断是使用整合的结构和计算方法破译的,结合小角度X射线散射,电子顺磁共振,核磁共振,量热法和分子动力学模拟。
    Intrinsic protein flexibility is of overwhelming relevance for intermolecular recognition and adaptability of highly dynamic ensemble of complexes, and the phenomenon is essential for the understanding of numerous biological processes. These conformational ensembles-encounter complexes-lack a unique organization, which prevents the determination of well-defined high resolution structures. This is the case for complexes involving the oncoprotein SET/template-activating factor-Iβ (SET/TAF-Iβ), a histone chaperone whose functions and interactions are significantly affected by its intrinsic structural plasticity. Besides its role in chromatin remodeling, SET/TAF-Iβ is an inhibitor of protein phosphatase 2A (PP2A), which is a key phosphatase counteracting transcription and signaling events controlling the activity of DNA damage response (DDR) mediators. During DDR, SET/TAF-Iβ is sequestered by cytochrome c (Cc) upon migration of the hemeprotein from mitochondria to the cell nucleus. Here, we report that the nuclear SET/TAF-Iβ:Cc polyconformational ensemble is able to activate PP2A. In particular, the N-end folded, globular region of SET/TAF-Iβ (a.k.a. SET/TAF-Iβ ΔC)-which exhibits an unexpected, intrinsically highly dynamic behavior-is sufficient to be recognized by Cc in a diffuse encounter manner. Cc-mediated blocking of PP2A inhibition is deciphered using an integrated structural and computational approach, combining small-angle X-ray scattering, electron paramagnetic resonance, nuclear magnetic resonance, calorimetry and molecular dynamics simulations.
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  • 文章类型: Journal Article
    含银纳米粒子(AgNPs)的产品在我们的日常生活中得到了广泛的应用。在过去的几年中,AgNP在生活的许多方面的广泛引入引起了研究人员对其对生物和环境生活的安全性和毒性的担忧。本研究旨在探讨AgNPs戒断的后续影响,短期口服后。将18只大鼠随机分为三组(对照组“1”和AGNP治疗组“2”和“3”;每组6只动物)。对照组接受正常食物和自来水,而组2和3接受0.5ml含有25ppmAgNP的溶液14天。第2组大鼠在第14天处死,而第3组又放置14天的颗粒停止,然后在第28天安乐死。功能评估是通过肝酶测定完成的,过氧化氢活性,肝Bdnf表达,和P53免疫反应性。通过苏木精和曙红进行肝组织结构评估,高碘酸-希夫以及马森三色污渍。结果显示,与对照组相比,仅第2组的过氧化氢显著升高。肝Bdnf和肝酶均无明显影响。停止纳米颗粒后14天发现肝组织结构异常和凋亡增强。结论:AgNP口服给药后的结构和功能损伤在颗粒戒断后继续,有趣的是,它们不需要对肝酶测定进行明显的反射。
    Products containing Silver nanoparticles (Ag NPs) are becoming vastly used in our daily life. The widespread increased introduction of Ag NPs in many aspects of life has raised researchers\' concerns regarding their safety and toxicity for biological and environmental life in the past few years. The current study aimed to explore the subsequent effects of Ag NPs withdrawal, following short-term oral administration. Eighteen rats were assigned randomly into three groups (control group \"1\" and AG NPs treated groups \"2\" and \"3\"; 6 animals each). The control group received normal food and tap water while groups 2 & 3 received 0.5 ml of a solution containing 25 ppm Ag NPs for 14 days. Group 2 rats were sacrificed on day 14 whereas group 3 was left for another 14 days of particle cessation followed by euthanasia on day 28. Functional assessment was done by liver enzyme assays, hydrogen peroxide activity, hepatic Bdnf expression, and P53 immunoreactivity. Hepatic tissue structural assessment was done via hematoxylin and eosin, periodic acid-Schiff as well as Masson\'s trichrome stains. The results revealed a significant elevation of Hydrogen peroxide in group 2 only compared to the control group. Hepatic Bdnf and liver enzymes were both insignificantly affected. Structural abnormalities and enhanced apoptosis in hepatic tissue were found 14 days after ceasing the nanoparticles. In conclusion: Structural and functional insults following Ag NPs oral administration continues after particle withdrawal, and interestingly they do not necessitate apparent reflection on liver enzyme assays.
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  • 文章类型: Case Reports
    IgG4相关疾病是涉及唾液腺的罕见多系统疾病,腹膜后,胰腺,胆道,还有肝脏.孤立的胆管狭窄和胆囊受累在这类患者中很少见,胆管炎和体重减轻的表现可能会误导诊断为恶性肿瘤。这里,我们报道了一个有趣的IgG4相关胆管狭窄伴胆囊受累的病例,表现为胆管炎和体重减轻。最初的症状和影像学检查被引导到胆管癌和胰腺癌的恶性可能性。然而,超声内镜,血清学,和组织病理学确定了IgG4相关疾病的诊断。患者在没有任何胆道干预和抗生素的情况下接受治疗,类固醇,和类固醇保护剂。类固醇锥度期间疾病复发,在增加剂量后有所改善。该疾病在随访中得到了医学治疗。我们证明了类固醇保护剂治疗IgG4相关疾病的有效性,尤其是避免类固醇相关的不良反应。由于与肝胆恶性肿瘤的共同临床特征和非侵入性管理措施的有效性,该病例突显了对IgG4疾病的诊断和延迟管理的可能误导。
    IgG4-related diseases are rare multisystem disorders involving salivary glands, retroperitoneum, pancreas, biliary tract, and liver. Isolated biliary strictures and gall bladder involvement are rare in such patients, and presentation with cholangitis and weight loss can misguide the diagnosis toward malignancy. Here, we report an interesting case of IgG4-related biliary stricture with gall bladder involvement, presented with cholangitis and weight loss. The initial symptoms and imaging were guided toward the malignant possibilities of cholangiocarcinoma and pancreatic carcinoma. However, endosonography, serology, and histopathology clinched the diagnosis of IgG4-related disease. The patient was managed without any biliary intervention and with antibiotics, steroids, and steroid-sparing agents. There was a relapse of disease during the steroids taper that improved after hiking its doses. The disease responded with medical management on follow-up. We demonstrated the effectiveness of steroid-sparing agents to treat IgG4-related diseases, especially to avert the steroid-related adverse effects. This case highlights the possible mislead for the diagnosis and delayed management of IgG4 disease due to shared clinical features with hepatobiliary malignancies and the effectiveness of noninvasive measures of management.
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  • 文章类型: Journal Article
    机器学习方法在提高DNA(脱氧核糖核酸)和蛋白质序列的预测和分类的准确性方面发挥了重要作用。在真核生物中,由于许多假阳性,剪接位点的识别和预测并不是一项简单的工作。为了解决这个问题,在这里,在本文中,我们代表了双向长短期记忆(LSTM)基于递归神经网络(RNN)的深度学习模型,该模型已被开发用于识别和预测从真核DNA序列预测外显子的剪接位点。在初级mRNA转录物的剪接机制中,内含子,基因的非编码区被剪接出来,外显子,基因的编码区连接。该双向LSTM-RNN模型使用内含子特征,所述内含子特征以剪接位点供体(GT)开始并以剪接位点受体(AG)结束,按照其长度约束的顺序。通过增加训练时的历元数来改进该模型。所设计的模型达到了95.5%的最高精度。该模型与庞大的序列数据(如完整的基因组)兼容。
    Machine learning methods played a major role in improving the accuracy of predictions and classification of DNA (Deoxyribonucleic Acid) and protein sequences. In eukaryotes, Splice-site identification and prediction is though not a straightforward job because of numerous false positives. To solve this problem, here, in this paper, we represent a bidirectional Long Short Term Memory (LSTM) Recurrent Neural Network (RNN) based deep learning model that has been developed to identify and predict the splice-sites for the prediction of exons from eukaryotic DNA sequences. During the splicing mechanism of the primary mRNA transcript, the introns, the non-coding region of the gene are spliced out and the exons, the coding region of the gene are joined. This bidirectional LSTM-RNN model uses the intron features that start with splice site donor (GT) and end with splice site acceptor (AG) in order of its length constraints. The model has been improved by increasing the number of epochs while training. This designed model achieved a maximum accuracy of 95.5%. This model is compatible with huge sequential data such as the complete genome.
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