NAR

nar
  • 文章类型: Journal Article
    背景:相对生长速率(RGR)在生物学中的使用历史悠久。在其记录的形式中,RGR=ln[(M+ΔM)/M],其中M是研究开始时生物体的大小,ΔM是时间间隔Δt上的新增长。它说明了比较非独立(混淆)变量的一般问题,例如(X+Y)与X.因此,RGR取决于甚至在相同生长阶段内使用的起始M(X)。同样,RGR缺乏与其派生组件的独立性,净同化率(NAR)和叶片质量比(LMR),作为RGR=NAR×LMR,因此,它们不能通过标准回归或相关分析进行合法比较。
    结果:X或Y的方差很大,或者正在比较的数据集之间的X和Y值几乎没有范围重叠。关系(方向,此类混淆变量之间的曲线性)基本上是预先确定的,因此不应将其报告为研究发现。用M而不是时间来标准化并不能解决问题。我们提出了固有增长率(IGR),lnΔM/lnM,作为一个简单的,在同一生长阶段独立于M的RGR的稳健替代方案。
    结论:尽管首选的选择是完全避免这种做法,我们讨论了将表达式与通用组件进行比较可能仍然有用的情况。如果(1)配对之间的回归斜率产生新的生物学兴趣变量,这些可以提供见解,(2)使用合适的方法支持该关系的统计显著性,比如我们专门设计的随机化测试,或(3)多个数据集进行比较,发现有统计学差异。区分真实的生物关系和虚假的关系,它们来自比较非独立表达式,在处理与植物生长分析相关的派生变量时是必不可少的。
    Relative growth rate (RGR) has a long history of use in biology. In its logged form, RGR = ln[(M + ΔM)/M], where M is size of the organism at the commencement of the study, and ΔM is new growth over time interval Δt. It illustrates the general problem of comparing non-independent (confounded) variables, e.g. (X + Y) vs. X. Thus, RGR depends on what starting M(X) is used even within the same growth phase. Equally, RGR lacks independence from its derived components, net assimilation rate (NAR) and leaf mass ratio (LMR), as RGR = NAR × LMR, so that they cannot legitimately be compared by standard regression or correlation analysis.
    The mathematical properties of RGR exemplify the general problem of \'spurious\' correlations that compare expressions derived from various combinations of the same component terms X and Y. This is particularly acute when X >> Y, the variance of X or Y is large, or there is little range overlap of X and Y values among datasets being compared. Relationships (direction, curvilinearity) between such confounded variables are essentially predetermined and so should not be reported as if they are a finding of the study. Standardizing by M rather than time does not solve the problem. We propose the inherent growth rate (IGR), lnΔM/lnM, as a simple, robust alternative to RGR that is independent of M within the same growth phase.
    Although the preferred alternative is to avoid the practice altogether, we discuss cases where comparing expressions with components in common may still have utility. These may provide insights if (1) the regression slope between pairs yields a new variable of biological interest, (2) the statistical significance of the relationship remains supported using suitable methods, such as our specially devised randomization test, or (3) multiple datasets are compared and found to be statistically different. Distinguishing true biological relationships from spurious ones, which arise from comparing non-independent expressions, is essential when dealing with derived variables associated with plant growth analyses.
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  • 文章类型: Journal Article
    二氧化氮(NO2)是工业时代排放最活跃的污染气体,与人类活动高度相关。跟踪NO2排放并预测其浓度是控制污染和制定规则以保护人们在室内健康的重要步骤,比如在工厂里,在户外环境中。NO2的浓度受到COVID-19封锁期的影响,并由于户外活动的限制而下降。在这项研究中,根据为期两年(2019-2020年)的全时训练,预测了2020年12月阿拉伯联合酋长国(UAE)14个地面站的NO2浓度.统计和机器学习模型,如自回归积分移动平均(ARIMA),季节性自回归综合移动平均线(SARIMA),长短期记忆(LSTM),和非线性自回归神经网络(NAR-NN),与开环和闭环架构一起使用。平均绝对百分比误差(MAPE)用于评估模型的性能,结果范围从“非常好”(具有闭环的Liwa站的MAPE为8.64%)到“可接受”(具有开环的KhadejahSchool站的MAPE为42.45%)。结果表明,基于开环的预测通常比基于闭环的预测更好,因为它们产生了统计学上显着较低的MAPE值。对于这两种循环类型,我们选择了表现最低的车站,中等,和最高MAPE值作为代表性案例。此外,我们证明了MAPE值与NO2浓度值的相对标准偏差高度相关。
    Nitrogen dioxide (NO2) is the most active pollutant gas emitted in the industrial era and is highly correlated with human activities. Tracking NO2 emissions and predicting their concentrations represent important steps toward controlling pollution and setting rules to protect people\'s health indoors, such as in factories, and in outdoor environments. The concentration of NO2 was affected by the COVID-19 lockdown period and decreased because of restrictions on outdoor activities. In this study, the concentration of NO2 was predicted at 14 ground stations in the United Arab Emirates (UAE) during December 2020 based on training over a full time period of two years (2019-2020). Statistical and machine learning models, such as autoregressive integrated moving average (ARIMA), seasonal autoregressive integrated moving average (SARIMA), long short-term memory (LSTM), and nonlinear autoregressive neural network (NAR-NN), are used with both open- and closed-loop architectures. The mean absolute percentage error (MAPE) was used to evaluate the performance of the models, and the results ranged from \"very good\" (MAPE of 8.64% at the Liwa station with the closed loop) to \"acceptable\" (MAPE of 42.45% at the Khadejah School station with the open loop). The results show that the predictions based on the open loop are generally better than those based on the closed loop because they yield statistically significantly lower MAPE values. For both loop types, we selected stations exhibiting the lowest, medium, and highest MAPE values as representative cases. In addition, we demonstrated that the MAPE value is highly correlated with the relative standard deviation of NO2 concentration values.
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  • 文章类型: Journal Article
    环境微气候特征经常受到相当重要的波动,这会对艺术品造成不可挽回的损害。我们探索了人工智能(AI)技术在文化遗产领域的适用性,目的是根据在罗森堡城堡(哥本哈根)收集的数据预测短期微气候值,丹麦皇家收藏。具体来说,这项研究将NAR(非线性自回归)和NARX(非线性外生自回归)模型应用于Rosenborg小气候时间序列。即使这两个模型应用于小数据集,它们显示出预测短期未来值的良好适应能力。这项工作探索了人工智能在博物馆中非常短的微气候变量预测中的应用,作为决策支持系统的潜在工具,将气候引起的艺术品损害限制在其预防性保护范围内。所提出的模型可能是博物馆管理的有用支持工具。
    The environmental microclimatic characteristics are often subject to fluctuations of considerable importance, which can cause irreparable damage to art works. We explored the applicability of Artificial Intelligence (AI) techniques to the Cultural Heritage area, with the aim of predicting short-term microclimatic values based on data collected at Rosenborg Castle (Copenhagen), housing the Royal Danish Collection. Specifically, this study applied the NAR (Nonlinear Autoregressive) and NARX (Nonlinear Autoregressive with Exogenous) models to the Rosenborg microclimate time series. Even if the two models were applied to small datasets, they have shown a good adaptive capacity predicting short-time future values. This work explores the use of AI in very short forecasting of microclimate variables in museums as a potential tool for decision-support systems to limit the climate-induced damages of artworks within the scope of their preventive conservation. The proposed model could be a useful support tool for the management of the museums.
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  • 文章类型: Journal Article
    介绍糖尿病足感染是一种影响患者生命的疾病,可能会导致肢体丧失,而且死亡率很高.使用了太多参数来预测早期死亡率,但没有描述黄金标准方法。中性粒细胞淋巴细胞比率(NLR)被公认为无截肢生存率和死亡率的预测价值。NLR由于炎症诱导的嗜中性粒细胞增多和与皮质醇诱导的应激相关的淋巴细胞减少而增加。由于白蛋白是负急性期反应物,因此预期中性粒细胞白蛋白比率会增加,因为白蛋白水平会降低。这项研究的目的是探讨中性粒细胞白蛋白比率(NAR)对下肢严重截肢(LEA)后早期死亡率的敏感性和价值。方法伦理委员会批准后,对2018年5月至2020年5月期间接受主要LEA的87例患者进行了分析。白细胞(WBC),中性粒细胞,淋巴细胞,C反应蛋白(CRP),肌酐,白蛋白,血小板,记录手术前一天的血红蛋白值.NLR计算为中性粒细胞计数与淋巴细胞计数之比,NAR为中性粒细胞计数与白蛋白值之比,CRP/白蛋白比值(CAR)为CRP值与白蛋白值之比,血小板淋巴细胞比值(PLR)为血小板计数与淋巴细胞计数的比值。在术后第二周也记录每个参数。结果纳入研究的患者中,男性52人(59.8%),女性35人(40.2%)。确定87名患者中有29名(33.3%)在第一年内死亡。检查了术后NAR值与早期死亡率之间的关系。曲线下面积计算为0.873。当截止值应用为0.265时,发现灵敏度为88%,特异性为76%。结论下肢截肢术后中性粒细胞/白蛋白比值升高与截肢术后早期死亡率相关。这个参数可以帮助预测死亡率。截止值被确定为0.265,灵敏度被发现为88%,特异性为76%。
    Introduction Diabetic foot infection is a condition that affects the patient\'s life, may cause limb loss, and has a high mortality. Too many parameters were used for predicting early mortality but the gold standard method wasn\'t described. Neutrophil lymphocyte ratio (NLR) is universally accepted as a predictive value for amputation-free survival and mortality. NLR increases due to inflammation-induced neutrophilia and lymphopenia related to cortisol-induced stress. Increasing in the neutrophil albumin ratio is expected due to decreasing albumin levels because albumin is a negative acute-phase reactant. The aim of this study is to investigate the sensitivity and value of the neutrophil albumin ratio (NAR) for early mortality after major lower extremity amputation (LEA). Methods  Following the approval of the ethics committee, 87 patients who underwent major LEA between May 2018 and May 2020 were analyzed for the study. White blood cell (WBC), neutrophil, lymphocyte, C-reactive protein (CRP), creatinine, albumin, platelet, and hemoglobin values on the day prior to surgery were recorded. NLR was calculated as the ratio of neutrophil count to lymphocyte count, NAR as the ratio of neutrophil count to albumin value, CRP/albumin ratio (CAR) as the ratio of CRP value to albumin value, and platelet lymphocyte ratio (PLR) as the ratio of platelet count to lymphocyte count. Each parameter was also recorded in the postoperative second week. Results Of the patients included in the study, 52 were men (59.8%) and 35 were women (40.2%). It was determined that 29 of 87 patients (33.3%) died within the first year. The relationship between post-operative NAR value and early mortality is examined. The area under the curve was calculated as 0.873. When the cut-off value was applied as 0.265, the sensitivity was found as 88% and specificity as 76%. Conclusions Higher neutrophil/albumin ratio after lower extremity amputation was associated with early mortality after extremity amputation. This parameter can help predict mortality. The cut-off value was determined as 0.265, the sensitivity was found as 88%, and specificity as 76%.
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  • 文章类型: Journal Article
    时间序列预测在大流行期间起着至关重要的作用,因为它提供了可能导致避免疾病传播的重要信息。新型冠状病毒病,COVID-19正在世界各地迅速传播。人口稠密的国家,特别是,比如印度,等待应对这一流行病的迫在眉睫的风险。正在使用不同的预测模型来预测COVID-19的未来病例。他们中的大多数人的困境是他们无法单独捕获数据的线性和非线性特征。
    我们提出了一种集成自回归积分移动平均模型(ARIMA)和非线性自回归神经网络(NAR)的集成模型。ARIMA模型用于提取线性相关关系,NAR神经网络用于对包含数据非线性分量的ARIMA残差进行建模。比较:单一ARIMA模型,根据性能评估参数,比较了ARIMA-NAR模型和其他一些在不同国家的COVID-19数据上应用的现有模型。
    混合组合显示RMSE显着降低(16.23%),与每日观察病例的单一ARIMA模型相比,MAE(37.89%)和MAPE(39.53%)值。对于每日报告的死亡和康复病例,也发现了类似的结果,误差百分比降低。与不同国家用于预测COVID-19的其他模型相比,我们的混合模型的RMSE值较小。
    结果表明,新的混合模型在捕获COVID-19数据的线性和非线性模式方面优于单个ARIMA模型。
    Time-series forecasting has a critical role during pandemics as it provides essential information that can lead to abstaining from the spread of the disease. The novel coronavirus disease, COVID-19, is spreading rapidly all over the world. The countries with dense populations, in particular, such as India, await imminent risk in tackling the epidemic. Different forecasting models are being used to predict future cases of COVID-19. The predicament for most of them is that they are not able to capture both the linear and nonlinear features of the data solely.
    We propose an ensemble model integrating an autoregressive integrated moving average model (ARIMA) and a nonlinear autoregressive neural network (NAR). ARIMA models are used to extract the linear correlations and the NAR neural network for modeling the residuals of ARIMA containing nonlinear components of the data. Comparison: Single ARIMA model, ARIMA-NAR model and few other existing models which have been applied on the COVID-19 data in different countries are compared based on performance evaluation parameters.
    The hybrid combination displayed significant reduction in RMSE (16.23%), MAE (37.89%) and MAPE (39.53%) values when compared with single ARIMA model for daily observed cases. Similar results with reduced error percentages were found for daily reported deaths and cases of recovery as well. RMSE value of our hybrid model was lesser in comparison to other models used for forecasting COVID-19 in different countries.
    Results suggested the effectiveness of the new hybrid model over a single ARIMA model in capturing the linear as well as nonlinear patterns of the COVID-19 data.
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  • 文章类型: Journal Article
    Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. Consecutively, 26 pulmonary tuberculosis patients were enrolled in our study based on the exclusion criteria. We have used Spearman\'s correlation analysis, hierarchical clustering and regression modelling to evaluate the association of 11 biomarkers with culture status after antituberculosis treatment. The results of our study demonstrated that six inflammatory biomarkers of 11, C-reactive protein (CRP), white blood cells (WBC), neutrophils, interferon gamma inducible protein 10, C-reactive protein (CRP) to albumin ratio (CAR) and neutrophil to albumin ratio (NAR), were significantly associated with culture negativity. The predictive ability of a composite model of seven biomarkers was superior to that of any single biomarker based on area under the receiver operating characteristic curve (AUC) analysis, indicating an excellent prediction efficacy (AUC:0.892; 95% CI:0.732-1.0). We also found that the highest significant trends and lower levels of CRP and IP-10 were observed in the two-month treated tuberculosis (TB) patients. We believe that our study may be valuable in providing preliminary results for an additional strategy in monitoring and management of the clinical outcome of pulmonary tuberculosis. Using a panel of predictors added a superior value in predicting culture status after anti-TB therapy.
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  • 文章类型: Journal Article
    像Twitter这样的社交媒体平台是在灾难等事件发生时分享实时信息的主要来源之一。政治事件,等。在灾难期间检测资源推文是一项基本任务,因为推文包含不同类型的信息,例如基础设施损坏,资源,对灾难事件的看法和同情,等。人道主义组织和受害者发布了与资源需求和可用性(NAR)有关的推文。因此,在灾难期间检测NAR鸣叫需要可靠的方法。现有的作品没有很好地关注NAR推文检测,并且性能也很差。因此,本文主要研究灾难期间NAR推文的检测。现有工作通常在多个自然语言处理(NLP)任务上使用功能和适当的机器学习算法。最近,卷积神经网络(CNN)在文本分类问题中得到了广泛的应用。然而,它需要大量的手动标记数据。在灾难期间,没有如此大的标记数据可用于NAR推文。为了克服这个问题,提出了将卷积神经网络与传统的基于特征的分类器进行叠加来检测NAR鸣叫。在我们的方法中,我们提出了几个信息功能,如援助,需要,食物,数据包,地震,等。在分类器和CNN中使用。在另一个分类器(元分类器)中利用所学习的特征(具有信息特征的CNN和分类器的输出)来检测NAR鸣叫。分类器如SVM,KNN,决策树,在提出的模型中使用了朴素贝叶斯。从实验中,我们发现KNN(基分类器)和SVM(元分类器)结合CNN在所提出的模型中的使用优于其他算法。本文使用2015年和2016年尼泊尔和意大利地震数据集进行实验。实验结果证明,与基线方法相比,该模型取得了最好的精度。
    Social media platform like Twitter is one of the primary sources for sharing real-time information at the time of events such as disasters, political events, etc. Detecting the resource tweets during a disaster is an essential task because tweets contain different types of information such as infrastructure damage, resources, opinions and sympathies of disaster events, etc. Tweets are posted related to Need and Availability of Resources (NAR) by humanitarian organizations and victims. Hence, reliable methodologies are required for detecting the NAR tweets during a disaster. The existing works don\'t focus well on NAR tweets detection and also had poor performance. Hence, this paper focus on detection of NAR tweets during a disaster. Existing works often use features and appropriate machine learning algorithms on several Natural Language Processing (NLP) tasks. Recently, there is a wide use of Convolutional Neural Networks (CNN) in text classification problems. However, it requires a large amount of manual labeled data. There is no such large labeled data is available for NAR tweets during a disaster. To overcome this problem, stacking of Convolutional Neural Networks with traditional feature based classifiers is proposed for detecting the NAR tweets. In our approach, we propose several informative features such as aid, need, food, packets, earthquake, etc. are used in the classifier and CNN. The learned features (output of CNN and classifier with informative features) are utilized in another classifier (meta-classifier) for detection of NAR tweets. The classifiers such as SVM, KNN, Decision tree, and Naive Bayes are used in the proposed model. From the experiments, we found that the usage of KNN (base classifier) and SVM (meta classifier) with the combination of CNN in the proposed model outperform the other algorithms. This paper uses 2015 and 2016 Nepal and Italy earthquake datasets for experimentation. The experimental results proved that the proposed model achieves the best accuracy compared to baseline methods.
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  • 文章类型: Journal Article
    在局部晚期直肠癌患者中,尽管在预测病理T(ypT)和N(ypN)分期方面的准确性有限,但仍建议在新辅助同步放化疗后重建骨盆磁共振成像(MRI).新辅助直肠(NAR)评分是无病生存期(DFS)和总生存期(OS)的一种新的短期替代终点。我们测试了重新老化MRIT(yT)和N(yN)与ypT和ypN阶段之间的一致性,分别,并探讨MRINAR(mNAR)评分的预后意义。
    2014年至2018年,43例局部晚期直肠癌患者完成了新辅助同步放化疗,重新做了核磁共振,接受了手术.用加权κ检验yT和yN与ypT和ypN的一致性,分别。小于0.5的kappa值被认为是不可接受的。采用配对t检验比较NAR和mNAR均分。通过Kaplan-Meier曲线估计存活率。
    重新MRI无法预测ypT分期(轻微一致,κ=0.111)或ypN阶段(公平协议,κ=0.278)。平均mNAR评分高于平均NAR评分(20vs.16,P=.0079)。低-中NAR和高NAR患者的中位DFS未达到。30个月(P=0.0063)。低-中NAR和高NAR的患者的中位OS未达到与40个月(P=0.0056)。在mNAR评分较低至中等的患者中,有DFS和OS较长的趋势(两组均未达到,P=0.058)与高mNAR评分的患者相比(两组均未达到,P=.15)。
    重新进行MRI无法预测ypT和ypN分期。平均mNAR评分高于平均NAR评分。与具有高mNAR评分的患者相比,具有低-中等mNAR评分的患者存在较长DFS和OS的趋势。
    In patients with locally advanced rectal cancer, restaging pelvis magnetic resonance imaging (MRI) after neoadjuvant concurrent chemoradiotherapy is recommended despite its limited accuracy in predicting pathologic T (ypT) and N (ypN) stage. Neoadjuvant rectal (NAR) score is a novel short-term surrogate endpoint for disease-free survival (DFS) and overall survival (OS). We tested the agreement between restaging MRI T (yT) and N (yN) with ypT and ypN stages, respectively, and explored the prognostic significance of restaging MRI NAR (mNAR) score.
    Between 2014 and 2018, 43 patients with locally advanced rectal cancer completed neoadjuvant concurrent chemoradiotherapy, had a restaging MRI, and underwent surgery. Weighted kappa was used to test the agreement between yT and yN with ypT and ypN, respectively. A kappa value of less than 0.5 was deemed unacceptable. Paired t test was used to compare NAR and mNAR mean scores. Survival was estimated by Kaplan-Meier curves.
    Restaging MRI could not predict ypT stage (slight agreement, κ = 0.111) or ypN stage (fair agreement, κ = 0.278). The mean mNAR score was higher than the mean NAR score (20 vs. 16, P = .0079). The median DFS for patients with low-intermediate NAR and high NAR was not reached vs. 30 months (P = .0063). The median OS for patients with low-intermediate NAR and high NAR was not reached vs. 40 months (P = .0056). There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores (not reached in both groups, P = .058) compared to patients with high mNAR scores (not reached in both groups, P = .15).
    Restaging MRI could not predict ypT and ypN stage. The mean mNAR score was higher than the mean NAR score. There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores compared to patients with high mNAR scores.
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  • 文章类型: Comparative Study
    To discover the association between eating alone and diet quality among Korean adults who eat alone measured by the mean adequacy ratio (MAR), METHODS: The cross-sectional study in diet quality which was measured by nutrient intakes, indicated as MAR and nutrient adequacy ratio (NAR) with the Korean National Health and Nutrition Examination Survey (KNHANES) VI 2013-2015 data. Study population was 8523 Korean adults. Multiple linear regression was performed to identify the association between eating behaviour and MAR and further study analysed how socioeconomic factors influence the diet quality of those who eat alone.
    We found that the diet quality of people who eat alone was lower than that of people who eat together in both male (β: - 0.110, p = 0.002) and female participants (β: - 0.069, p = 0.005). Among who eats alone, the socioeconomic factors that negatively influenced MAR with the living arrangement, education level, income levels, and various occupation classifications.
    People who eat alone have nutrition intake below the recommended amount. This could lead to serious health problems not only to those who are socially disadvantaged but also those who are in a higher social stratum. Policy-makers should develop strategies to enhance diet quality to prevent potential risk factors.
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  • 文章类型: Journal Article
    硝酸盐呼吸是许多细菌病原体使用的厌氧能量产生的广泛模式,和呼吸硝酸还原酶,不,长期以来已知将氯酸盐还原为有毒氧化剂亚氯酸盐。这里,我们证明了氯酸盐对铜绿假单胞菌的抗菌活性,一种代表性的病原体,可以在感染期间生活在缺氧或缺氧的宿主微环境中。需氧生长的铜绿假单胞菌细胞对妥布霉素敏感但对氯酸盐耐受。在没有氧气或替代电子受体的情况下,细胞耐受妥布霉素,但通过Nar依赖性还原对氯酸盐敏感。绿泥石的事实,氯酸盐还原的产物,在培养上清液中未检测到,表明它可能会快速反应并保留在细胞内。妥布霉素和氯酸盐靶向代谢分层聚集生物膜内的不同群体;妥布霉素杀死有氧外周细胞,而氯酸盐杀死内部的缺氧和缺氧细胞。在由多个聚合填充的矩阵中,妥布霉素介导的表面聚集体死亡能够使氧气更深地渗透到基质中,通过增加存活率和消除氯酸盐敏感性,使选定的聚集种群受益。最后,lasR突变体,通常出现在铜绿假单胞菌感染中,已知可以承受常规抗生素治疗,对氯酸盐过敏。lasR突变体显示出比野生型更快地呼吸硝酸盐和减少氯酸盐的倾向,与提高的氯酸盐敏感性一致。这些发现说明了氯酸盐选择性靶向氧化剂饥饿的病原体的潜力,包括代表感染期间抗生素耐受人群的铜绿假单胞菌的生理状态和基因型。细菌的厌氧生长和存活通常与对常规抗生素的生理耐受性相关。激发在缺氧环境中针对病原体的新策略的开发。一个关键的挑战是确定特定于这种代谢状态的药物靶标。氯酸盐是一种无毒化合物,可以通过广泛的厌氧代谢酶还原为有毒的亚氯酸盐。我们测试了氯酸盐对铜绿假单胞菌的抗菌性能,一种可以生活在缺氧或缺氧微环境中的病原体,包括那些在人类感染中出现的。氯酸盐和抗生素妥布霉素杀死铜绿假单胞菌生物膜中不同的代谢群体,氯酸盐靶向耐受妥布霉素的厌氧细胞。氯酸盐对铜绿假单胞菌突变体特别有效,它们经常从人类感染中分离出来,对某些抗生素更具耐药性。这项工作表明,氯酸盐可能具有作为厌氧前药的潜力。
    Nitrate respiration is a widespread mode of anaerobic energy generation used by many bacterial pathogens, and the respiratory nitrate reductase, Nar, has long been known to reduce chlorate to the toxic oxidizing agent chlorite. Here, we demonstrate the antibacterial activity of chlorate against Pseudomonas aeruginosa, a representative pathogen that can inhabit hypoxic or anoxic host microenvironments during infection. Aerobically grown P. aeruginosa cells are tobramycin sensitive but chlorate tolerant. In the absence of oxygen or an alternative electron acceptor, cells are tobramycin tolerant but chlorate sensitive via Nar-dependent reduction. The fact that chlorite, the product of chlorate reduction, is not detected in culture supernatants suggests that it may react rapidly and be retained intracellularly. Tobramycin and chlorate target distinct populations within metabolically stratified aggregate biofilms; tobramycin kills cells on the oxic periphery, whereas chlorate kills hypoxic and anoxic cells in the interior. In a matrix populated by multiple aggregates, tobramycin-mediated death of surface aggregates enables deeper oxygen penetration into the matrix, benefiting select aggregate populations by increasing survival and removing chlorate sensitivity. Finally, lasR mutants, which commonly arise in P. aeruginosa infections and are known to withstand conventional antibiotic treatment, are hypersensitive to chlorate. A lasR mutant shows a propensity to respire nitrate and reduce chlorate more rapidly than the wild type does, consistent with its heightened chlorate sensitivity. These findings illustrate chlorate\'s potential to selectively target oxidant-starved pathogens, including physiological states and genotypes of P. aeruginosa that represent antibiotic-tolerant populations during infections.IMPORTANCE The anaerobic growth and survival of bacteria are often correlated with physiological tolerance to conventional antibiotics, motivating the development of novel strategies targeting pathogens in anoxic environments. A key challenge is to identify drug targets that are specific to this metabolic state. Chlorate is a nontoxic compound that can be reduced to toxic chlorite by a widespread enzyme of anaerobic metabolism. We tested the antibacterial properties of chlorate against Pseudomonas aeruginosa, a pathogen that can inhabit hypoxic or anoxic microenvironments, including those that arise in human infection. Chlorate and the antibiotic tobramycin kill distinct metabolic populations in P. aeruginosa biofilms, where chlorate targets anaerobic cells that tolerate tobramycin. Chlorate is particularly effective against P. aeruginosalasR mutants, which are frequently isolated from human infections and more resistant to some antibiotics. This work suggests that chlorate may hold potential as an anaerobic prodrug.
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