首页 > 最新文献

Tuberculosis最新文献

英文 中文
Quinoline hybrid derivatives as effective structural motifs in the treatment of tuberculosis: Emphasis on structure-activity relationships 喹啉杂化衍生物作为治疗结核病的有效结构基团:强调结构-活性关系。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-03 DOI: 10.1016/j.tube.2024.102573
Mycobacterium tuberculosis (MTB/Mtb) is the causative agent of tuberculosis (TB), a highly infectious serious airborne illness. TB usually affects the lungs, in 25 % of patients (children or immune impaired adults), mycobacteria can enter the blood stream and infect other bodily areas such the meninges, pleura, lymphatic system, genitourinary system, bones, and joints. Currently, the most challenging aspect of treating this illness is the ineffectiveness of the most potent first-line anti-TB medications, isoniazid, rifampin, pyrazinamide, and ethambutol, which can result in multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB), and in rare instances, completely drug-resistant TB (TDR-TB). As a result, finding new pharmaceutical compounds to treat these diseases is a significant challenge for the scientific community. A number of bio-active molecules have been investigated in this quest, including quinoline, which is considered a promising candidate for the development of TB drugs. It is known that quinoline are low in toxicity and have a wide range of pharmacological properties. Researchers have investigated quinoline scaffolds as anti-TB drugs based on their biological spectrum. The objective of this review is to examine the recent development of quinoline and its structural characteristics crucial to its antitubercular (anti-TB) activity. A molecular analog of the TB treatment can be designed and identified with this information. As a result, future generation quinoline-based anti-TB agents with greater potency and safety can also be explored.
结核分枝杆菌(MTB/Mtb)是肺结核(TB)的病原体,这是一种通过空气传播的高度传染性严重疾病。肺结核通常影响肺部,但 25% 的患者(儿童或免疫力低下的成年人)的分枝杆菌可进入血流并感染其他身体部位,如脑膜、胸膜、淋巴系统、泌尿生殖系统、骨骼和关节。目前,治疗这种疾病的最大挑战在于最有效的一线抗结核药物(异烟肼、利福平、吡嗪酰胺和乙胺丁醇)效果不佳,可能导致耐多药结核病(MDR-TB)、广泛耐药结核病(XDR-TB),在极少数情况下还会出现完全耐药结核病(TDR-TB)。因此,寻找治疗这些疾病的新药物化合物是科学界面临的一项重大挑战。在这一过程中,人们研究了许多生物活性分子,其中包括被认为有望开发出结核病药物的喹啉。众所周知,喹啉毒性低,具有广泛的药理特性。研究人员根据喹啉的生物谱研究了作为抗结核药物的喹啉支架。本综述旨在研究喹啉的最新发展及其对抗结核活性至关重要的结构特征。有了这些信息,就可以设计和确定治疗结核病的分子类似物。因此,还可以探索效力更强、更安全的新一代喹啉类抗结核药物。
{"title":"Quinoline hybrid derivatives as effective structural motifs in the treatment of tuberculosis: Emphasis on structure-activity relationships","authors":"","doi":"10.1016/j.tube.2024.102573","DOIUrl":"10.1016/j.tube.2024.102573","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis (MTB/Mtb)</em> is the causative agent of tuberculosis (TB), a highly infectious serious airborne illness. TB usually affects the lungs, in 25 % of patients (children or immune impaired adults), mycobacteria can enter the blood stream and infect other bodily areas such the meninges, pleura, lymphatic system, genitourinary system, bones, and joints. Currently, the most challenging aspect of treating this illness is the ineffectiveness of the most potent first-line anti-TB medications, isoniazid, rifampin, pyrazinamide, and ethambutol, which can result in multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB), and in rare instances, completely drug-resistant TB (TDR-TB). As a result, finding new pharmaceutical compounds to treat these diseases is a significant challenge for the scientific community. A number of bio-active molecules have been investigated in this quest, including quinoline, which is considered a promising candidate for the development of TB drugs. It is known that quinoline are low in toxicity and have a wide range of pharmacological properties. Researchers have investigated quinoline scaffolds as anti-TB drugs based on their biological spectrum. The objective of this review is to examine the recent development of quinoline and its structural characteristics crucial to its antitubercular (anti-TB) activity. A molecular analog of the TB treatment can be designed and identified with this information. As a result, future generation quinoline-based anti-TB agents with greater potency and safety can also be explored.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination 接种疫苗一年后,牛分枝杆菌致病因子 PhoP、ESAT-6 和 CFP-10 突变体在小鼠器官中持续存在
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.tube.2024.102574
A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile. Mice are the most widely used animal models in tuberculosis research, particularly for pre-clinical vaccine evaluation. In these animal models, the key indicator of infection or vaccine efficacy is the mycobacteria load in the lungs. In this study, we evaluated the long-term protection conferred by vaccinating BALB/c mice with a Mycobacterium bovis triple mutant lacking the virulence genes phoP, esxA, and esxB. Our findings showed that the triple mutant protected the lungs of mice against M. bovis challenge for up to one-year post-vaccination. However, the bacterial load in the spleens predominantly comprised the vaccine strain, and the lungs also contained some of these bacteria. These results suggest that the vaccine strain persisted in the mouse organs for at least one year, which raised concerns about its potential safety for animal vaccination.
我们迫切需要一种牛结核病疫苗。卡介苗(Bacille Calmette-Guérin)是目前唯一获准用于人类的结核病疫苗,但对牛的保护作用却不尽相同。然而,卡介苗是一种高度安全的疫苗,任何替代疫苗不仅要提供比卡介苗更强的保护力,还必须符合并提高其安全性。小鼠是结核病研究中使用最广泛的动物模型,尤其是用于临床前疫苗评估。在这些动物模型中,感染或疫苗疗效的关键指标是肺部的分枝杆菌负荷。在本研究中,我们评估了用缺乏毒力基因 phoP、esxA 和 esxB 的牛分枝杆菌三重突变体为 BALB/c 小鼠接种疫苗所产生的长期保护作用。我们的研究结果表明,三重突变体能在接种后一年内保护小鼠肺部免受牛分枝杆菌的侵袭。然而,脾脏中的细菌负荷主要由疫苗菌株构成,肺部也含有其中一些细菌。这些结果表明,疫苗菌株在小鼠器官中至少存在一年,这引起了人们对其在动物疫苗接种中潜在安全性的担忧。
{"title":"Mycobacterium bovis mutant in the virulence factors PhoP, ESAT-6 and CFP-10 persisted in mouse organs after a year post-vaccination","authors":"","doi":"10.1016/j.tube.2024.102574","DOIUrl":"10.1016/j.tube.2024.102574","url":null,"abstract":"<div><div>A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile. Mice are the most widely used animal models in tuberculosis research, particularly for pre-clinical vaccine evaluation. In these animal models, the key indicator of infection or vaccine efficacy is the mycobacteria load in the lungs. In this study, we evaluated the long-term protection conferred by vaccinating BALB/c mice with a <em>Mycobacterium bovis</em> triple mutant lacking the virulence genes <em>phoP</em>, <em>esxA</em>, and <em>esxB</em>. Our findings showed that the triple mutant protected the lungs of mice against <em>M. bovis</em> challenge for up to one-year post-vaccination. However, the bacterial load in the spleens predominantly comprised the vaccine strain, and the lungs also contained some of these bacteria. These results suggest that the vaccine strain persisted in the mouse organs for at least one year, which raised concerns about its potential safety for animal vaccination.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis 耐多药结核分枝杆菌对贝达喹啉敏感性降低的相关基因特征分析
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-23 DOI: 10.1016/j.tube.2024.102572
Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log2-transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: Rv0678_141_ins_1 and Rv1979c_D249E, with effect estimates of 1.76 (95 % CI: 0.67–2.84) and 1.69 (95 % CI: 0.22–3.17), respectively. Other implicated genes included Rv2699c_-84_del_1, hsaB_I179T, mmpL9_T241A, pncA_C14R, Rv0373c_G621S, Rv0893c_L27F, Rv1770_A4D, and Rv3428c_S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes.
贝达喹啉(BDQ)在缩短耐多药结核病(MDR-TB)的治疗时间和提高治疗成功率方面显示出疗效,因而得到广泛采用。然而,BDQ 的耐药性已经出现。本研究旨在利用公共数据库来帮助检测耐药菌株,从而确定与 BDQ 易感性下降相关的基因特征。研究人员从开源的 CRyPTIC 数据库中选取了 71 个对 BDQ 产生抗药性的分离株和 929 个对 BDQ 易感的分离株进行分析。变异调用是通过 clockwork 管道进行的。对每个基因突变进行单变量逻辑回归,然后进行 LASSO 回归以进一步选择变异。最终,使用对数2转换的最小抑制浓度值作为因变量,建立了多元线性回归模型,并根据 Akaike 信息标准通过逐步回归对变异选择进行了改进。有 10 个基因突变与 BDQ 易感性降低明显相关,其中包括两个关键基因突变:Rv0678_141_ins_1和Rv1979c_D249E的效应估计值分别为1.76(95 % CI:0.67-2.84)和1.69(95 % CI:0.22-3.17)。其他相关基因包括 Rv2699c_-84_del_1、hsaB_I179T、mmpL9_T241A、pncA_C14R、Rv0373c_G621S、Rv0893c_L27F、Rv1770_A4D 和 Rv3428c_S327C。这项研究发现了十个与对 BDQ 易感性降低有关的基因突变,为制定全面的 BDQ 抗性基因目录提供了参考。
{"title":"Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102572","DOIUrl":"10.1016/j.tube.2024.102572","url":null,"abstract":"<div><div>Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log<sub>2</sub>-transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: <em>Rv0678</em>_141_ins_1 and <em>Rv1979c</em>_D249E, with effect estimates of 1.76 (95 % CI: 0.67–2.84) and 1.69 (95 % CI: 0.22–3.17), respectively. Other implicated genes included <em>Rv2699c</em>_-84_del_1, <em>hsaB</em>_I179T, <em>mmpL9</em>_T241A, <em>pncA</em>_C14R, <em>Rv0373c</em>_G621S, <em>Rv0893c</em>_L27F, <em>Rv1770</em>_A4D, and <em>Rv3428c</em>_S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis 吲哚分枝杆菌和人类 beta Defensin-2 作为结核分枝杆菌辅助疗法的协同作用。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-15 DOI: 10.1016/j.tube.2024.102571
Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, Mycobacterium indicus pranii (MIP) and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by Mycobacterium smegmatis (M.smeg) and Mycobacterium tuberculosis (M.tb) (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against M.tb by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.
宿主导向疗法(HDT)通过调节特定的宿主反应(如炎症)可以限制霉菌感染。HDT可作为一种辅助疗法纳入当前的结核病治疗中,以增加细菌清除率并限制组织损伤,从而控制传播。吲哚分枝杆菌(MIP)和人β防御素-2(hBD-2)是治疗结核病(TB)的有前途的单个药物。它们可以直接靶向结核杆菌,增强细胞介导的免疫反应,而这正是传统药物的局限性所在。因此,我们的研究对 MIP 和 hBD-2 的联合应用进行了调查,以评估它们在清除 THP-1 细胞和人类单核巨噬细胞(MDMs)中由烟曲霉分枝杆菌(M.smeg)和结核分枝杆菌(M.tb)(均为无毒株;H37Ra 和毒株;H37Rv)引起的感染方面的功效。针对 MIP 和 hBD-2 的组合观察到了强烈的促炎反应,这也与细菌负荷的显著减少有关。这种组合通过增强受感染细胞的脓毒症,进一步显示出对 M.tb 的保护作用。这项研究表明,在合适的动物模型中进行验证后,这些强效免疫调节剂的联合使用可作为一种有效的治疗模式,作为抗分枝杆菌感染的佐剂。
{"title":"Synergistic role of Mycobacterium indicus pranii and human beta Defensin-2 as adjunctive therapy against Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102571","DOIUrl":"10.1016/j.tube.2024.102571","url":null,"abstract":"<div><div>Host-directed therapies (HDT) via modulation of specific host responses like inflammation can limit mycobacterial infection. HDTs could be included in current TB therapy as an adjunct to increase bacterial clearance and limit tissue damage to control spread. Individually, <em>Mycobacterium indicus pranii (MIP)</em> and human beta defensin-2 (hBD-2) are promising therapies for tuberculosis (TB). They can directly target the TB bacilli and enhance cell-mediated immune responses, which is limiting with conventional drugs. Therefore, our study investigated the combined application of MIP and hBD-2 to evaluate their efficacy in clearing infections caused by <em>Mycobacterium smegmatis</em> (<em>M.</em><em>smeg</em>) and <em>Mycobacterium tuberculosis (M</em>.<em>tb)</em> (both avirulent; H37Ra and virulent strain; H37Rv) in THP-1 cells and human monocyte-derived macrophages (MDMs). A strong pro-inflammatory response was observed against the combination of MIP and hBD-2 which also correlated with a significant reduction in the bacterial load. This combination further showed protection against <em>M.tb</em> by enhancing pyroptosis in the infected cells. The study suggests the combined use of these potent immunomodulators, which could be employed as an effective mode of therapy as adjuvants against mycobacterial infections after validation in a suitable animal model.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combining bioinformatics and machine learning to identify diagnostic biomarkers of TB associated with immune cell infiltration 结合生物信息学和机器学习,确定与免疫细胞浸润相关的结核病诊断生物标志物
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.tube.2024.102570

Objective

The asymptomatic nature of tuberculosis (TB) during its latent phase, combined with limitations in current diagnostic methods, makes accurate diagnosis challenging. This study aims to identify TB diagnostic biomarkers by integrating gene expression screening with machine learning, evaluating their diagnostic potential and correlation with immune cell infiltration.

Methods

We analyzed GSE19435, GSE19444, and GSE54992 datasets to identify differentially expressed genes (DEGs). GO and KEGG enrichment characterized gene functions. Three machine learning algorithms identified potential biomarkers, validated with GSE83456, GSE62525, and RT-qPCR on clinical samples. Immune cell infiltration was analyzed and verified with blood data.

Results

249 DEGs were identified, with PDE7A and DOK3 emerging as potential biomarkers. RT-qPCR confirmed their expression, showing AUCs above 0.75 and a combined AUC of 0.926 for TB diagnosis. Immune infiltration analysis revealed strong correlations between PDE7A, DOK3, and immune cells.

Conclusion

PDE7A and DOK3 show strong diagnostic potential for TB, closely linked to immune cell infiltration, and may serve as promising biomarkers and therapeutic targets.
目的结核病(TB)潜伏期无症状,再加上目前诊断方法的局限性,使得准确诊断具有挑战性。本研究旨在通过将基因表达筛选与机器学习相结合来确定结核病诊断生物标志物,评估其诊断潜力以及与免疫细胞浸润的相关性。方法我们分析了 GSE19435、GSE19444 和 GSE54992 数据集,以确定差异表达基因(DEGs)。GO和KEGG富集描述了基因功能。三种机器学习算法确定了潜在的生物标记物,并通过 GSE83456、GSE62525 和临床样本的 RT-qPCR 进行了验证。结果 发现了 249 个 DEGs,其中 PDE7A 和 DOK3 成为潜在的生物标记物。RT-qPCR 证实了这两种基因的表达,其 AUC 值高于 0.75,对结核病诊断的综合 AUC 值为 0.926。免疫浸润分析显示 PDE7A、DOK3 和免疫细胞之间存在很强的相关性。
{"title":"Combining bioinformatics and machine learning to identify diagnostic biomarkers of TB associated with immune cell infiltration","authors":"","doi":"10.1016/j.tube.2024.102570","DOIUrl":"10.1016/j.tube.2024.102570","url":null,"abstract":"<div><h3>Objective</h3><div>The asymptomatic nature of tuberculosis (TB) during its latent phase, combined with limitations in current diagnostic methods, makes accurate diagnosis challenging. This study aims to identify TB diagnostic biomarkers by integrating gene expression screening with machine learning, evaluating their diagnostic potential and correlation with immune cell infiltration.</div></div><div><h3>Methods</h3><div>We analyzed GSE19435, GSE19444, and GSE54992 datasets to identify differentially expressed genes (DEGs). GO and KEGG enrichment characterized gene functions. Three machine learning algorithms identified potential biomarkers, validated with GSE83456, GSE62525, and RT-qPCR on clinical samples. Immune cell infiltration was analyzed and verified with blood data.</div></div><div><h3>Results</h3><div>249 DEGs were identified, with PDE7A and DOK3 emerging as potential biomarkers. RT-qPCR confirmed their expression, showing AUCs above 0.75 and a combined AUC of 0.926 for TB diagnosis. Immune infiltration analysis revealed strong correlations between PDE7A, DOK3, and immune cells.</div></div><div><h3>Conclusion</h3><div>PDE7A and DOK3 show strong diagnostic potential for TB, closely linked to immune cell infiltration, and may serve as promising biomarkers and therapeutic targets.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis 一种新型 C-4 改性异四氢呋喃可作为一种有效的生物增强剂,增强抗结核药物对结核分枝杆菌的活性。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-27 DOI: 10.1016/j.tube.2024.102569
Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of C-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of M. tuberculosis H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.
结核分枝杆菌是一种致命的病原体,每年夺走数百万人的生命。目前的研究重点是寻找安全有效、副作用和毒性较小的新型抗结核药物。一个重要的方法是找出生物增强剂,提高抗结核药物的疗效,从而减少剂量和缩短治疗时间。本研究调查了 C-4 修饰异四酮作为生物增强剂的使用情况。一系列研究表明,一种名为 C11 的异四酮与一线抗结核药物和注射用抗结核药物联合使用时,能以剂量依赖的方式抑制 H37Rv 株结核杆菌的生长,提高 MIC 和 MBC,并增强对其的杀灭作用。C11 与利福平联用还能减少利福平自发突变体的产生,并在利福平浓度适中时达到突变预防浓度(MPC)。所发现的化合物对 MDR 结核杆菌株有效,对 HepG2 细胞无毒性。我们发现 C11 能诱导巨噬细胞内和细菌内活性氧(ROS)的生成,从而提高药效。
{"title":"A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.tube.2024.102569","DOIUrl":"10.1016/j.tube.2024.102569","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of <em>C</em>-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of <em>M. tuberculosis</em> H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of <em>M. tuberculosis</em> and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection 结核病与 T 细胞结核感染中 T 细胞多样性的影响
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.tube.2024.102567

Tuberculosis is a global threat and is still a leading cause of death due to an infectious agent. The infection is spread through inhalation of M. tb containing aerosol droplets. Bacteria after reaching the lung alveoli are engulfed by alveolar macrophages, leading to an immune response. Then, pro-inflammatory cytokines are released by these macrophages, recruiting other antigen-presenting cells like dendritic cells. These cells phagocytose the bacteria and present mycobacterial antigens to naïve T cells. After activation by DCs, T cells differentiate into various T cells subsets, viz. CD4+, CD8+, Th17, Treg, Tfh cells and others display enormous diversification in their characteristics and functions. This review comprises a comprehensive literature on conventional and unconventional T cells, highlighting the polyfunctional T cells as well, their role in controlling TB infection, and their implications in the spectrum of TB infection. While some subsets such as CD4+ T cells are extensively studied, some T cell subsets such as gamma delta T cells and Tfh cells remain poorly understood in the pathophysiology of tuberculosis, despite having significant potential implications. The goal of TB eradication can be assisted by development of better vaccines against TB, which can effectively induce a robust and long-term T cells memory. The same has been discussed in the latter part of this review. BCG being the standalone commercialised TB vaccine so far has its limitations. Strategies for the enhancement of BCG along with novel studies in vaccine development, has also been discussed in great detail. Lastly, T cells display a complex interplay of an adaptive immune response against TB, with activation and enhancement of the innate immune responses. Therefore, it is critical to fully understand the role of various T cells subsets in pathophysiology of tuberculosis to provide better therapeutic inventions and improve patient care.

结核病是一种全球性威胁,仍然是传染性病原体导致死亡的主要原因。感染是通过吸入含有结核杆菌的气溶胶飞沫传播的。细菌到达肺泡后被肺泡巨噬细胞吞噬,导致免疫反应。然后,这些巨噬细胞会释放促炎细胞因子,招募树突状细胞等其他抗原递呈细胞。这些细胞吞噬细菌,并将分枝杆菌抗原呈现给幼稚的 T 细胞。经 DC 激活后,T 细胞会分化成各种 T 细胞亚群,即 CD4+、CD8+、Th17、Treg、Tfh 细胞等,它们的特征和功能呈现出巨大的多样性。本综述包括有关常规和非常规 T 细胞的全面文献,重点介绍多功能 T 细胞、它们在控制结核感染中的作用及其在结核感染谱中的意义。尽管对 CD4+ T 细胞等一些亚群进行了广泛的研究,但对γ-δ T 细胞和 Tfh 细胞等一些 T 细胞亚群在结核病病理生理学中的作用仍然知之甚少,尽管它们具有重大的潜在影响。开发更好的结核病疫苗可以帮助实现根除结核病的目标,这种疫苗可以有效诱导强大而长期的 T 细胞记忆。本综述的后半部分对此进行了讨论。卡介苗作为迄今为止独立的商业化结核病疫苗有其局限性。本文还详细讨论了卡介苗的强化策略以及疫苗开发方面的新研究。最后,T 细胞显示了针对结核病的适应性免疫反应与先天性免疫反应的激活和增强之间复杂的相互作用。因此,充分了解各种 T 细胞亚群在结核病病理生理学中的作用对于提供更好的治疗发明和改善患者护理至关重要。
{"title":"Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection","authors":"","doi":"10.1016/j.tube.2024.102567","DOIUrl":"10.1016/j.tube.2024.102567","url":null,"abstract":"<div><p>Tuberculosis is a global threat and is still a leading cause of death due to an infectious agent. The infection is spread through inhalation of <em>M. tb</em> containing aerosol droplets. Bacteria after reaching the lung alveoli are engulfed by alveolar macrophages, leading to an immune response. Then, pro-inflammatory cytokines are released by these macrophages, recruiting other antigen-presenting cells like dendritic cells. These cells phagocytose the bacteria and present mycobacterial antigens to naïve T cells. After activation by DCs, T cells differentiate into various T cells subsets, viz. CD4<sup>+</sup>, CD8<sup>+</sup>, Th17, Treg, Tfh cells and others display enormous diversification in their characteristics and functions. This review comprises a comprehensive literature on conventional and unconventional T cells, highlighting the polyfunctional T cells as well, their role in controlling TB infection, and their implications in the spectrum of TB infection. While some subsets such as CD4<sup>+</sup> T cells are extensively studied, some T cell subsets such as gamma delta T cells and Tfh cells remain poorly understood in the pathophysiology of tuberculosis, despite having significant potential implications. The goal of TB eradication can be assisted by development of better vaccines against TB, which can effectively induce a robust and long-term T cells memory. The same has been discussed in the latter part of this review. BCG being the standalone commercialised TB vaccine so far has its limitations. Strategies for the enhancement of BCG along with novel studies in vaccine development, has also been discussed in great detail. Lastly, T cells display a complex interplay of an adaptive immune response against TB, with activation and enhancement of the innate immune responses. Therefore, it is critical to fully understand the role of various T cells subsets in pathophysiology of tuberculosis to provide better therapeutic inventions and improve patient care.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia 印度尼西亚巴布亚地区结核分枝杆菌 1 系的描述
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-14 DOI: 10.1016/j.tube.2024.102568
Indonesia has the third highest number of tuberculosis (TB) patients infected with Mycobacterium tuberculosis (MTB) Lineage 1 (L1). Most of these MTB L1 cases can be found in Indonesia's remote easternmost province of Papua, one of Indonesia's most underdeveloped provinces with a particularly high burden for TB. In this study, we sequenced and described 42 MTB L1 isolates from a well-characterized cohort of patients. We found a genetically diverse MTB L1 population with no association between pathogen genetic relatedness and place of residence or pathogen genetic relatedness and patient ethnicity, which could reflect mixing between different locales and ethnicities or our low sampling fraction. Only a small number showed genetic variants associated with drug resistance (5/42, 11.9 %), probably due to a lack of effective treatment programs. The Papuan isolates showed similarities to other Island Southeast Asian Countries due to the high proportion of L1.2.1.2.1 (30/42, 71.4 %), especially East Timor and the Philippines. This study fills a research gap of MTB L1 in Indonesian Papua and should serve as a stepping stone for further research in the region.
印度尼西亚的结核病(TB)患者中,感染结核分枝杆菌(MTB)1系(L1)的人数位居第三。这些 MTB L1 病例大多出现在印尼最东部偏远的巴布亚省,该省是印尼最不发达的省份之一,结核病发病率特别高。在这项研究中,我们对 42 个 MTB L1 分离物进行了测序和描述,这些分离物来自一个特征明确的患者群体。我们发现 MTB L1 群体的基因具有多样性,病原体基因相关性与居住地或病原体基因相关性与患者种族之间没有关联,这可能反映了不同地区和种族之间的混合或我们的取样比例较低。只有一小部分出现了与耐药性相关的基因变异(5/42,11.9%),这可能是由于缺乏有效的治疗方案。由于 L1.2.1.2.1 的比例较高(30/42,71.4%),巴布亚分离株与其他东南亚岛国(尤其是东帝汶和菲律宾)有相似之处。这项研究填补了印尼巴布亚地区 MTB L1 研究的空白,应成为该地区进一步研究的基石。
{"title":"A description of lineage 1 Mycobacterium tuberculosis from papua, Indonesia","authors":"","doi":"10.1016/j.tube.2024.102568","DOIUrl":"10.1016/j.tube.2024.102568","url":null,"abstract":"<div><div>Indonesia has the third highest number of tuberculosis (TB) patients infected with Mycobacterium tuberculosis (<em>MTB</em>) Lineage 1 (L1). Most of these MTB L1 cases can be found in Indonesia's remote easternmost province of Papua, one of Indonesia's most underdeveloped provinces with a particularly high burden for TB. In this study, we sequenced and described 42 <em>MTB</em> L1 isolates from a well-characterized cohort of patients. We found a genetically diverse <em>MTB</em> L1 population with no association between pathogen genetic relatedness and place of residence or pathogen genetic relatedness and patient ethnicity, which could reflect mixing between different locales and ethnicities or our low sampling fraction. Only a small number showed genetic variants associated with drug resistance (5/42, 11.9 %), probably due to a lack of effective treatment programs. The Papuan isolates showed similarities to other Island Southeast Asian Countries due to the high proportion of L1.2.1.2.1 (30/42, 71.4 %), especially East Timor and the Philippines. This study fills a research gap of MTB L1 in Indonesian Papua and should serve as a stepping stone for further research in the region.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472979224000945/pdfft?md5=a6f4d495c84889622c44816e926c96f8&pid=1-s2.0-S1472979224000945-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exhaled breath analysis: A promising triage test for tuberculosis in young children 呼气分析:有望成为幼儿结核病分诊测试的方法
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-10 DOI: 10.1016/j.tube.2024.102566
The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.
We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.
Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62–96 %), this resulted in a specificity of 42 % (95 % CI 30–55 %).
Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.
小儿肺结核的诊断十分困难,尤其是对于无法自主排痰的幼儿。呼吸测试在诊断呼吸道感染方面已显示出良好的前景,但有关小儿肺结核的数据却十分有限。我们使用手持电池供电的鼻装置分析呼出的气体。在进行数据分析时,我们采用了机器学习方法,将样本分为阳性(微生物确诊)和阴性(不可能是肺结核)两类,以评估诊断的准确性。最佳模型的曲线下面积为 0.73。在灵敏度为 86 %(CI 62-96%)的情况下,特异性为 42 %(95 % CI 30-55%)。
{"title":"Exhaled breath analysis: A promising triage test for tuberculosis in young children","authors":"","doi":"10.1016/j.tube.2024.102566","DOIUrl":"10.1016/j.tube.2024.102566","url":null,"abstract":"<div><div>The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.</div><div>We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.</div><div>Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62–96 %), this resulted in a specificity of 42 % (95 % CI 30–55 %).</div><div>Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo) 评估转录标记以区分自由活动的带状金钱豹(Mungos mungo)的孟氏分枝杆菌感染状况
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1016/j.tube.2024.102565

There is an increasingly urgent need to improve our ability to accurately forecast and control zoonotic diseases in wildlife reservoirs. We are confronted, however, with the continued challenge of accurately determining host infection status across space and time. This dilemma is epitomized with the Mycobacterium tuberculosis Complex (MTBC) pathogens and particularly in free-ranging wildlife, a critical global challenge for both human and animal health. In humans, transcriptional markers have been increasingly identified as a robust tool for diagnosing Mycobacterium tuberculosis (MTB) infection status but have rarely been utilized for diagnosing TB in free-ranging wildlife populations. Here, we report the first use of transcriptional markers to evaluate TB infection status in a free-ranging wildlife species, banded mongoose (Mungos mungo), infected with the MTBC pathogen, Mycobacterium mungi. In this study, we found that GBP5 and DUSP3 were significantly upregulated in free-ranging banded mongoose infected with M. mungi. These results provide the first step in developing an antemortem diagnostic tool for use in free-ranging wildlife species. Our results highlight the potential of transcriptional marker-based assays to advance our ability to detect and manage TB in free-ranging wildlife, especially in field studies and other scenarios when conventional diagnostics are not feasible.

我们越来越迫切需要提高准确预测和控制野生动物贮藏地人畜共患病的能力。然而,我们仍然面临着跨时空准确确定宿主感染状况的挑战。结核分枝杆菌复合体(MTBC)病原体是这一难题的缩影,尤其是在自由活动的野生动物中,这对人类和动物健康都是一个严峻的全球性挑战。在人类中,转录标记已被越来越多地确定为诊断结核分枝杆菌(MTB)感染状况的有力工具,但却很少被用于诊断散养野生动物群体中的结核病。在此,我们报告了首次使用转录标记评估自由活动的野生动物物种--带状金钱豹(Mungos mungo)--感染 MTBC 病原体 Mungi 分枝杆菌后的结核病感染状况。在这项研究中,我们发现 GBP5 和 DUSP3 在自由活动的带状金钱豹感染 M. mungi 后显著上调。这些结果为开发用于散养野生动物的死前诊断工具迈出了第一步。我们的研究结果凸显了基于转录标记的检测方法在提高我们检测和管理散养野生动物结核病的能力方面所具有的潜力,尤其是在野外研究和其他常规诊断方法不可行的情况下。
{"title":"Assessment of transcriptional markers for the differentiation of Mycobacterium mungi infection status in free-ranging banded mongoose (Mungos mungo)","authors":"","doi":"10.1016/j.tube.2024.102565","DOIUrl":"10.1016/j.tube.2024.102565","url":null,"abstract":"<div><p>There is an increasingly urgent need to improve our ability to accurately forecast and control zoonotic diseases in wildlife reservoirs. We are confronted, however, with the continued challenge of accurately determining host infection status across space and time. This dilemma is epitomized with the <em>Mycobacterium tuberculosis</em> Complex (MTBC) pathogens and particularly in free-ranging wildlife, a critical global challenge for both human and animal health. In humans, transcriptional markers have been increasingly identified as a robust tool for diagnosing <em>Mycobacterium tuberculosis</em> (<em>MTB</em>) infection status but have rarely been utilized for diagnosing TB in free-ranging wildlife populations. Here, we report the first use of transcriptional markers to evaluate TB infection status in a free-ranging wildlife species, banded mongoose (<em>Mungos mungo</em>), infected with the MTBC pathogen, <em>Mycobacterium mungi</em>. In this study, we found that <em>GBP5</em> and <em>DUSP3</em> were significantly upregulated in free-ranging banded mongoose infected with <em>M. mungi</em>. These results provide the first step in developing an antemortem diagnostic tool for use in free-ranging wildlife species. Our results highlight the potential of transcriptional marker-based assays to advance our ability to detect and manage TB in free-ranging wildlife, especially in field studies and other scenarios when conventional diagnostics are not feasible.</p></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Tuberculosis
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