bacterial infections

细菌感染
  • 文章类型: Journal Article
    宫颈坏死性筋膜炎(CNF)是一种威胁生命的细菌感染,具有诊断挑战。目前,CNF中炎性指标的诊断准确性证据不足.
    本研究旨在确定关键炎症指标并评估其对CNF的诊断准确性。
    于2020年1月至2023年12月在三级医疗机构进行了诊断性病例对照研究。评估入院时CNF和非CNF患者的实验室数据。通过多变量逻辑回归和受试者工作特征曲线分析的一致结果确定关键炎症指标。这些指标的诊断准确性,结合测试的结果,被计算。
    在所调查的67例患者中有21例证实了CNF。C反应蛋白(CRP)和中性粒细胞与淋巴细胞比值(NLR)被确定为关键的炎症指标。灵敏度分别为0.905和0.810,特异性分别为0.870和0.913,CRP阈值为165.0mg/L,NLR为15.8。在并行和串行测试中组合CRP和NLR分别将敏感性提高到0.952和特异性提高到1.0。
    CRP和NLR已被证实为关键炎症指标,对CNF诊断具有令人满意的诊断能力,为未来的研究奠定了坚实的基础。
    UNASSIGNED: Cervical necrotizing fasciitis (CNF) is a life-threatening bacterial infection with a diagnostic challenge. Currently, there is insufficient evidence on the diagnostic accuracy of inflammatory indicators in CNF.
    UNASSIGNED: This study aims to identify key inflammatory indicators and assess their diagnostic accuracy for CNF.
    UNASSIGNED: A diagnostic case-control study was conducted at a tertiary healthcare facility from January 2020 to December 2023. Laboratory data from patients with CNF and non-CNF at admission were evaluated. Key inflammatory indicators were identified through consistent outcomes from multivariable logistic regression and receiver operating characteristic curves analyses. The diagnostic accuracy of these indicators, with the results of combined tests, were calculated.
    UNASSIGNED: CNF was confirmed in 21 of the 67 patients investigated. C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) were identified as key inflammatory indicators, with sensitivities of 0.905 and 0.810, and specificities of 0.870 and 0.913, respectively, at CRP threshold of 165.0 mg/L and NLR of 15.8. Combining CRP and NLR in parallel and serial tests increased sensitivity to 0.952 and specificity to 1.0, respectively.
    UNASSIGNED: CRP and NLR have been verified as key inflammatory indicators with satisfactory diagnostic abilities for CNF diagnosis, providing a strong foundation for future studies.
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  • 文章类型: Journal Article
    细菌抗生素耐药性已被认为是对公共卫生的全球威胁。它挑战了目前在临床实践中使用的抗生素,并导致严重且通常致命的传染病。对抗抗生素抗性细菌(ARB)的斗争变得越来越紧迫。虽然了解抗性的分子机制是先决条件,之前已经提出了几种主要机制,包括细菌外排系统,降低细胞膜通透性,抗生素被酶灭活,目标修改,和目标保护。在这种情况下,这篇综述提出了一组有希望和潜在的策略,以对抗抗生素耐药性/耐药细菌。不同类型的直接作用和间接电阻断路器,如外排泵抑制剂,抗生素佐剂,和氧化处理进行了讨论。此外,重点介绍了用于快速耐药性鉴定的新兴多组学方法和有希望的现有抗生素替代品.总的来说,这篇综述表明,需要继续努力和投资于研究,以开发新的抗生素和现有抗生素的替代品,并将其转化为环境和临床应用。
    Bacterial antibiotic resistance has been recognized as a global threat to public health. It challenges the antibiotics currently used in clinical practice and causes severe and often fatal infectious diseases. Fighting against antibiotic-resistant bacteria (ARB) is growing more urgent. While understanding the molecular mechanisms that underlie resistance is a prerequisite, several major mechanisms have been previously proposed including bacterial efflux systems, reduced cell membrane permeability, antibiotic inactivation by enzymes, target modification, and target protection. In this context, this review presents a panel of promising and potential strategies to combat antibiotic resistance/resistant bacteria. Different types of direct-acting and indirect resistance breakers, such as efflux pump inhibitors, antibiotic adjuvants, and oxidative treatments are discussed. In addition, the emerging multi-omics approaches for rapid resistance identification and promising alternatives to existing antibiotics are highlighted. Overall, this review suggests that continued effort and investment in research are required to develop new antibiotics and alternatives to existing antibiotics and translate them into environmental and clinical applications.
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  • 文章类型: Journal Article
    革兰氏阳性金黄色葡萄球菌是与抗生素耐药性相关的主要死亡病原体之一。耐甲氧西林金黄色葡萄球菌(MRSA)分泌的β-内酰胺酶(Bla)水解几乎所有的β-内酰胺抗生素,只有少数抗生素可用于MRSA感染的临床治疗。因此,此处设计Bla反应肽(BLAP),其具有通过模拟人防御素-6的宿主防御机制来抑制MRSA感染的能力。包含自组装肽序列的BLAP可以特异性地响应分泌的Bla并原位组装周围的MRSA。组装的纳米纤维网络能够捕获MRSA,有效防止其侵入宿主细胞。因此,肌内注射BLAP可显著抑制小鼠细菌感染和脓肿形成。仿生BLAP在有效治疗耐药革兰氏阳性细菌感染方面具有巨大潜力。
    Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The β-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all β-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.
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  • 文章类型: Journal Article
    目的:探讨miR-370-3p对LPS触发的影响,特别是其通过靶向巨噬细胞中的TLR4-NLRP3-caspase-1细胞焦亡途径参与疾病进展。
    方法:人巨噬细胞RAW264.7分为6组:对照组,LPS,LPS+抑制剂-NC,LPS+miR-370-3p抑制剂,LPS+模拟-NC和LPS+miR-370-3p模拟物。采用RT-qPCR检测miR-370-3p的表达水平并进行比较分析。CCK-8和流式细胞术测定用于检测细胞活力和凋亡。ELISA法检测细胞上清液中IL-1β和TNF-α的含量。WB测定用于检测TLR4、NLRP3、Caspase-1和GSDMD水平。
    结果:LPS诱导后,巨噬细胞miR-370-3p水平降低,细胞活力下降,细胞凋亡增加。同时,细胞中TLR4、NLRP3、Caspase-1和GSDMD水平升高,细胞上清液中IL-1β和TNF-α水平升高。与LPS组比拟,miR-370-3p在LPS+miR-370-3p模拟组细胞中显著较高的表达水平伴随着显著较高的细胞活力,显著降低细胞凋亡率,细胞中TLR4,NLRP3,Caspase-1和GSDMD的水平显着降低,并显著降低细胞上清液中IL-1β和TNF-α的水平。
    结论:MiR-370-3p可能通过靶向抑制巨噬细胞TLR4-NLRP3-caspase-1途径参与抗感染免疫反应。
    OBJECTIVE: To explore the effect of miR-370-3p on LPS triggering, in particular its involvement in disease progression by targeting the TLR4-NLRP3-caspase-1 cellular pyroptosis pathway in macrophages.
    METHODS: Human macrophage RAW264.7 was divided into 6 groups: control, LPS, LPS + inhibitor-NC, LPS + miR-370-3p inhibitor, LPS + mimics-NC and LPS + miR-370-3p mimics. RT-qPCR was used to detect the expression level of miR-370-3p and analyzed comparatively. CCK-8 and flow cytometry assays were used to detect cell viability and apoptosis. ELISA assay was used to detect the levels of IL-1β and TNF-α in the supernatant of the cells. The WB assay was used to detect TLR4, NLRP3, Caspase-1 and GSDMD levels.
    RESULTS: After LPS induction, macrophage miR-370-3p levels decreased, cell viability decreased, and apoptosis increased. At the same time, the levels of TLR4, NLRP3, Caspase-1 and GSDMD increased in the cells, and the levels of IL-1β and TNF-α increased in the cell supernatant. Compared with the LPS group, the significantly higher expression level of miR-370-3p in the cells of the LPS + miR-370-3p mimics group was accompanied by significantly higher cell viability, significantly lower apoptosis rate, significantly lower levels of TLR4, NLRP3, Caspase-1, and GSDMD in the cells, and significantly lower levels of IL-1β and TNF-α in the cell supernatant.
    CONCLUSIONS: MiR-370-3p may be involved in anti-infective immune responses by targeting and inhibiting the macrophage TLR4-NLRP3-caspase-1 cellular pyroptosis pathway.
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  • 文章类型: Journal Article
    Type IV interferon (IFN-υ) is a recently discovered cytokine crucial for host defense against viral infections. However, the role and mechanisms of IFN-υ in bacterial infections remain unexplored. This study investigated the antibacterial and antiviral functions and mechanisms of grass carp ( Ctenopharyngodon idella) IFN-υ (CiIFN-υ) both in vivo and in vitro. The CiIFN-υ gene was first identified and characterized in grass carp. Subsequently, the immune expression of CiIFN-υ significantly increased following bacterial challenge, indicating its response to bacterial infections. The eukaryotic recombinant expression plasmid of CiIFN-υ was then constructed and transfected into fathead minnow (FHM) cells. Supernatants were collected and incubated with four bacterial strains, followed by plate spreading and colony counting. Results indicated that CiIFN-υ exhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria. In vivo experiments further confirmed the antibacterial function, showing high survival rates, low tissue edema and damage, reduced tissue bacterial load, and elevated proinflammatory response at the early stages of bacterial infection. In addition, the antiviral function of CiIFN-υ was confirmed through in vitro and in vivo experiments, including crystal violet staining, survival rates, tissue viral burden, and RT-qPCR. This study highlights the antibacterial function and preliminary mechanism of IFN-υ, demonstrating that IFN-υ possesses dual functions against bacterial and viral infections.
    IV型干扰素(IFN-υ)是最近发现的一种在宿主抵御病毒感染中起重要作用的细胞因子。IFN-υ在细菌感染中是否发挥重要作用,以及作用机制如何,目前仍不得而知。该研究探讨了草鱼IFN-υ(CiIFN-υ)在体内和体外的抗菌和抗病毒功能及机制。首先,对草鱼CiIFN-υ基因进行了鉴定和特征描述。CiIFN-υ表达水平在细菌感染后显著增加,表明CiIFN-υ对细菌感染有响应。接着,我们构建了CiIFN-υ的真核重组表达质粒,将其转染到FHM细胞中,收集上清液,将含有CiIFN-υ蛋白的上清液分别与四种菌株共孵育,涂布在LB培养板上并进行菌落计数等。结果表明,CiIFN-υ对革兰氏阴性菌比革兰氏阳性菌具有更强的抗菌活性,且能凝集革兰氏阴性菌,不能凝集革兰氏阳性菌。此外,体内实验也很好的验证了其抗菌功能,在细菌感染的早期阶段,促炎反应增强,随后组织水肿和组织损伤小,组织细菌载量少,存活率高。最后,通过细胞结晶紫染色、统计草鱼存活率、组织病毒载量和RT-qPCR等实验证实了CiIFN-υ的抗病毒功能。该研究强调了IFN-υ的抗菌功能和初步机制,研究结果表明草鱼的IFN-υ具有抗细菌和病毒感染的双重功能。.
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  • 文章类型: Journal Article
    背景:抗生素耐药性是一个严重的全球公共卫生问题。然而,关于中国新生儿抗菌药物敏感性趋势的报道很少,现有的大部分证据都来自成人研究。我们的目的是评估中国患有侵袭性细菌感染(IBIs)的足月新生儿中常见病原体的抗菌药物敏感性趋势。
    方法:这项横断面调查研究分析了来自17家医院的中国IBIs新生儿的抗菌药物敏感性,从2012年1月到2021年12月。应用Joinpoint回归模型来说明趋势并计算年平均百分比变化(AAPC)。使用Mantel-Haenszel线性-线性关联卡方检验,我们进一步比较了2019年至2021年间病原体的抗生素最低抑制浓度(MIC),以提供变化的精确估计.
    结果:具有超广谱β-内酰胺酶阴性菌株的大肠杆菌比例从0.0增加到88.5%(AAPC=62.4%,95%置信区间(CI):44.3%,82.9%),2014年和2018年有两个断点(p趋势<0.001)。B组链球菌对红霉素和克林霉素的敏感性分别增加了66.7%和42.8%,分别(AAPC=55.2%,95%CI:23.2%,95.5%,p趋势=0.002;AAPC=54.8%,95%CI:9.6%,118.6%,p趋势<0.001),金黄色葡萄球菌对青霉素的影响也是如此(AAPC=56.2%;95%CI:34.8%,81.0%,p趋势<0.001)。然而,肠球菌属的敏感性。氨苄青霉素从100.0降至25.0%(AAPC=-11.7%,95%CI:-15.2%,-8.1%,p趋势<0.001),大肠杆菌对氨苄西林的抗生素敏感性没有显著改善,庆大霉素,和头孢菌素.此外,与2019年相比,2021年相关抗生素MIC值相对较低的GBS/金黄色葡萄球菌比例也有所上升。
    结论:在过去十年中,中国足月新生儿中最流行的病原体的抗菌药物敏感性似乎有所改善或保持稳定。暗示抗生素管理政策和实践的有效性已经逐渐出现。
    BACKGROUND: Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China.
    METHODS: This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes.
    RESULTS: The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend < 0.001). The susceptibility of group B Streptococcus (GBS) to erythromycin and clindamycin increased by 66.7% and 42.8%, respectively (AAPC = 55.2%, 95% CI: 23.2%, 95.5%, p-trend = 0.002; AAPC = 54.8%, 95% CI: 9.6%, 118.6%, p-trend < 0.001), as did Staphylococcus aureus to penicillin (AAPC = 56.2%; 95% CI: 34.8%, 81.0%, p-trend < 0.001). However, the susceptibility of Enterococcus spp. to ampicillin declined from 100.0 to 25.0% (AAPC = - 11.7%, 95% CI: - 15.2%, - 8.1%, p-trend < 0.001), and no significant improvement was observed in the antibiotic susceptibility of Escherichia coli to ampicillin, gentamicin, and cephalosporin. Additionally, the proportion of GBS/Staphylococcus aureus with relatively low MIC values for relevant antibiotics also increased in 2021 compared to 2019.
    CONCLUSIONS: Antimicrobial susceptibility of the most prevalent pathogens in full-term neonates seemed to have improved or remained stable over the last decade in China, implying the effectiveness of policies and practice of antibiotic stewardship had gradually emerged.
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  • 文章类型: Journal Article
    在重症监护病房(ICU)保持清洁卫生的环境对于确保患者安全至关重要,预防感染,减少与医疗保健相关的并发症。随着感染的流行以及病毒和细菌对标准抗菌剂的耐药性的出现,迫切需要创新的防腐解决方案。纳米技术越来越多地应用于医学,特别是侧重于减轻各种病原体的活动,包括那些与医院获得性感染有关的。本文探讨了纳米技术的当前影响,特别关注细菌感染和SARS-CoV-2,这对医疗保健系统造成了严重的压力,然后讨论纳米技术如何增强现有的治疗方法。我们强调了基于纳米技术的杀菌剂Bio-Kil在减少ICU细菌计数方面的有效性。目的是教育医疗保健专业人员纳米技术在解决流行传染病方面的现有作用和前景。
    To maintain a clean and hygienic environment in the intensive care unit (ICU) is crucial for ensuring patient safety, preventing infections, and reducing healthcare-associated complications. With the increasing prevalence of infections and the emergence of viral and bacterial resistance to standard antiseptics, there is a pressing need for innovative antiseptic solutions. Nanotechnology is increasingly being employed in medicine, particularly focusing on mitigating the activities of various pathogens, including those associated with hospital-acquired infections. This paper explores the current impact of nanotechnology, with a particular focus on bacterial infections and SARS-CoV-2, which significantly strain healthcare systems, and then discusses how nanotechnology can enhance existing treatment methodologies. We highlight the effectiveness of the nanotechnology-based bactericide Bio-Kil in reducing bacterial counts in an ICU. The aim is to educate healthcare professionals on the existing role and prospects of nanotechnology in addressing prevalent infectious diseases.
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  • 文章类型: Journal Article
    人类和细菌之间的对抗正在进行中,对抗细菌感染的策略不断发展。随着RNA测序技术的进步,与细菌感染相关的非编码RNA(ncRNAs)已经引起了极大的关注。最近,长ncRNAs(lncRNAs)已被鉴定为无菌炎症反应和细胞防御的调节因子。它们参与调节细胞核和细胞质中的宿主抗微生物免疫。越来越多的证据表明,lncRNAs对于细菌感染期间宿主和病原体之间复杂的相互作用至关重要。本文着重阐述了lncRNAs在临床标志中的潜在应用,细胞损伤,豁免权,毒力,以及细菌感染中的耐药性。此外,我们讨论了在细菌感染背景下研究lncRNAs的挑战和局限性,并强调了这个有前途的领域的明确方向。
    The confrontation between humans and bacteria is ongoing, with strategies for combating bacterial infections continually evolving. With the advancement of RNA sequencing technology, non-coding RNAs (ncRNAs) associated with bacterial infections have garnered significant attention. Recently, long ncRNAs (lncRNAs) have been identified as regulators of sterile inflammatory responses and cellular defense against live bacterial pathogens. They are involved in regulating host antimicrobial immunity in both the nucleus and cytoplasm. Increasing evidence indicates that lncRNAs are critical for the intricate interactions between host and pathogen during bacterial infections. This paper emphatically elaborates on the potential applications of lncRNAs in clinical hallmarks, cellular damage, immunity, virulence, and drug resistance in bacterial infections in greater detail. Additionally, we discuss the challenges and limitations of studying lncRNAs in the context of bacterial infections and highlight clear directions for this promising field.
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  • 文章类型: Journal Article
    具有良好生物相容性和有效抗微生物性能的组织粘合剂的开发对于解决急诊和临床环境中手术部位感染的高发生率至关重要。在这里,由壳聚糖双胍(CSG)组成的可注射水凝胶粘合剂,氧化葡聚糖(ODex)和单宁(TA)主要通过席夫碱反应合成,氢键,和静电相互作用。将TA引入CSG/ODex水凝胶中以制备物理化学双交联水凝胶。掺入2重量%TA(CSG/ODex-TA2)的水凝胶制剂表现出快速凝胶化,中等的机械性能,组织粘连良好,和TA的持续释放行为。体外和体内研究均表明,与CSG/ODex水凝胶和市售纤维蛋白胶相比,CSG/ODex-TA2显示出显着增强的粘附和抗菌效果。利用CSG的正电荷,CSG/ODex-TA2水凝胶具有很强的接触抗菌作用,而TA的持续释放提供了扩散抗菌能力。通过将接触和扩散抗菌机制整合到水凝胶中,开发了一种有前景的方法来提高抗菌效率并加速感染耐甲氧西林金黄色葡萄球菌(MRSA)的伤口的愈合.CSG/ODex-TA2水凝胶具有优越的生物相容性,止血特性,和抗菌能力,使其成为改善体内伤口护理和对抗细菌感染的有希望的候选者。
    The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections.
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  • 文章类型: Journal Article
    细菌感染带来的医疗保健负担需要能够在医院和集中实验室之外执行的稳健且可访问的诊断方法。这里,我们报道了比例发光(PEARL)病原体测定,一个灵敏且易于操作的检测致病菌的平台。PEARL利用颜色可变的CRISPR-Cas12a传感器和重组酶聚合酶扩增来引起对目标输入的比率生物发光响应。该平台能够根据反应的颜色变化对Atmoolar细菌基因组脱氧核糖核酸进行稳健且可视化的鉴定。此外,颜色可变的Cas12a传感器的组件可以在环境温度下冻干储存3个月,然后用来自粗细菌裂解物的扩增子完全激活,减少对冷链存储和繁琐的处理步骤的要求。我们证明了PEARL测定法适用于鉴定不同临床标本中铜绿假单胞菌引起的感染。包括人造板,小便,和来自伤口的拭子。这些结果表明,PEARL有可能被未经培训的人员使用,这将促进社区和资源有限地区的分布式病原体诊断。
    The healthcare burden imposed by bacterial infections demands robust and accessible diagnostic methods that can be performed outside hospitals and centralized laboratories. Here, we report Pathogen Assay with Ratiometric Luminescence (PEARL), a sensitive and easy-to-operate platform for detecting pathogenic bacteria. The PEARL leveraged a color-changeable CRISPR-Cas12a sensor and recombinase polymerase amplification to elicit ratiometric bioluminescence responses to target inputs. This platform enabled robust and visualized identification of attomolar bacteria genome deoxyribonucleic acid according to the color changes of the reactions. In addition, the components of the color-changeable Cas12a sensor could be lyophilized for 3 month storage at ambient temperature and then be fully activated with the amplicons derived from crude bacterial lysates, reducing the requirements for cold-chain storage and tedious handling steps. We demonstrated that the PEARL assay is applicable for identifying the infections caused by Pseudomonas aeruginosa in different clinical specimens, including sputa, urines, and swabs derived from wounds. These results revealed the potential of PEARL to be used by untrained personnel, which will facilitate decentralized pathogen diagnosis in community- and resource-limited regions.
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