4-Butyrolactone

4 - 丁内酯
  • 文章类型: Journal Article
    青枯雷尔氏菌物种复合体(RSSC)包括具有全球分布和广泛宿主范围的土壤传播细菌植物病原体。毒力因子通过四个分层组织的细胞-细胞接触独立的群体感应(QS)信号系统进行调节:Phc,使用(R)-3-羟基棕榈酸甲酯[(R)-3-OHPAME]或(R)-3-羟基肉豆蔻酸甲酯[(R)-3-OHMAME]作为信号,N-酰基高丝氨酸内酯(AHL)依赖性RasI/R和SolI/R系统,以及最近发现的邻氨基苯甲酸依赖性系统。独特的PhcQS系统已被广泛研究;然而,两个AHLQS系统的作用直到最近才得到解决。在这篇微观评论中,我们介绍并讨论了RSSC中SolI/R和RasI/RQS系统的当前数据。我们还介绍了这些AHLQS系统在RSSC中的分布和频率,讨论可能的生态作用和进化意义。复杂的QS分层网络强调了细胞-细胞信号传导在RSSC毒力中的关键作用。
    Ralstonia solanacearum species complex (RSSC) includes soilborne bacterial plant pathogens with worldwide distribution and wide host ranges. Virulence factors are regulated via four hierarchically organized cell-cell contact independent quorum-sensing (QS) signalling systems: the Phc, which uses as signals (R)-methyl 3-hydroxypalmitate [(R)-3-OH PAME] or (R)-methyl 3-hydroxymyristate [(R)-3-OH MAME], the N-acyl homoserine lactone (AHL)-dependent RasI/R and SolI/R systems, and the recently identified anthranilic acid-dependent system. The unique Phc QS system has been extensively studied; however, the role of the two AHL QS systems has only recently been addressed. In this microreview, we present and discuss current data of the SolI/R and RasI/R QS systems in the RSSC. We also present the distribution and frequency of these AHL QS systems in the RSSC, discuss possible ecological roles and evolutive implications. The complex QS hierarchical networks emphasizes the crucial role of cell-cell signalling in the virulence of the RSSC.
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  • 文章类型: Journal Article
    据报道,羧基/胆碱酯酶(CCE)基因的过表达与节肢动物中许多农药抗性病例有关。然而,很少有文献记载CCE基因参与柑橘全甲的螺氯芬抗性。在以前的研究中,我们发现,氟氯芬抗性与P450和CCE酶活性增加有关。在这项研究中,我们确定了两个CCE基因,PcCCE3和PcCCE5,在抗螺氯芬菌株和暴露于螺氯芬后显著上调。PcCCE3和PcCCE5的RNA干扰增加了螺旋藻的敏感性。体外代谢表明,PcCCE3和PcCCE5可以与螺氯芬相互作用,但代谢物仅在PcCCE3治疗中检测到。我们的结果表明,PcCCE3通过直接代谢参与螺氯芬抗性,PcCCE5可能通过被动结合和隔离参与螺氯芬抗性,这提供了新的见解氟氯芬在香茅中的抗性。
    Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.
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  • 文章类型: English Abstract
    近年来,随着细胞之间通信的范式已经被澄清,细菌响应各种细胞外信号而改变其基因表达模式的能力引起了人们的极大兴趣。特别是,细菌种群之间的细胞内和细胞间通讯,称为群体感应(QS),对于协调生理和遗传活动至关重要。QS研究至关重要,特别是在阐明食源性病原体感染过程的调节机制方面。阐明沙门氏菌中的QS机制可以有效地沉默对抗该细菌的毒力因子。这项研究的目的是;创建在沙门氏菌QS活性中起至关重要作用的luxS基因突变体,并确定该突变对细菌中毒力基因表达的影响,并确定合成的N-己酰-高丝氨酸内酯(C6HSL)对沙门氏菌野生菌株和luxS基因突变体的生物膜形成和AI-2信号通路的影响。通过基于同源区域重组将基因区域与氯霉素基因盒重组来构建luxS基因突变体。在以这种方式获得的luxS突变体中,八个不同毒力基因的表达(hilA,invA,inv,glgC,fimF,flf,lpfA,gyrA),在沙门氏菌致病性中具有重要作用,通过定量实时逆转录酶聚合酶链反应(rRT-qPCR)方法进行测定,并与天然菌株进行比较。作为这些研究的结果,已确定,在luxS突变菌株中,所检查的每个基因的表达均显着降低。根据时间分析沙门氏菌菌株的相对AI-2活性。确定最高活性发生在第四小时,与野生菌株相比,luxS突变体的AI-2活性降低。最后,确定C6HSL增加了鼠伤寒沙门氏菌DMC4,SL1344野生菌株的生物膜活性,和突变体,主要是在72小时。总之,我们的结果证明,C6HSL刺激了所有菌株中的QS通讯,并增加了沙门氏菌生物膜的形成和自动诱导活性。这种情况决定了沙门氏菌通过使用QS系统对外部信号做出反应。此外,这项研究有助于提供有关种间通讯机制的更多信息,以制定预防该病原体生物膜形成的策略。
    In recent years, as the paradigm of communication between cells has been clarified, the ability of bacteria to change their gene expression patterns in response to various extracellular signals has attracted great interest. In particular, intracellular and intercellular communication between bacterial populations, called quorum sensing (QS), is essential for coordinating physiological and genetic activities. QS studies are critical, particularly in elucidating the regulatory mechanisms of infectious processes in food-borne pathogens. Elucidating the QS mechanisms in Salmonella is effective in silencing the virulence factors in the fight against this bacterium. The aims of this study were; to create luxS gene mutants that play a vital role in the QS activity of Salmonella and to determine the effect of this mutation on the expression of virulence genes in the bacteria and to determine the impact of synthetic N-hexanoyl-homoserine lactone (C6HSL) on biofilm formation and AI-2 signaling pathway of Salmonella wild strain and luxS gene mutants. luxS gene mutants were constructed by recombining the gene region with the chloramphenicol gene cassette based on homologous region recombination. In the luxS mutants obtained in this way, the expression of eight different virulence genes (hilA, invA, inv, glgC, fimF, fliF, lpfA, gyrA), which have essential roles in Salmonella pathogenicity, was determined by quantitative real-time reverse transcriptase polymerase chain reaction (rRT-qPCR) method and compared with natural strains. As a result of these studies, it was determined that the expression of each gene examined was significantly reduced in luxS mutant strains. The relative AI-2 activities of Salmonella strains were analyzed depending on time. It was determined that the highest activity occurred at the fourth hour and the AI-2 activities of luxS mutants were reduced compared to the wild strain. Finally, it was determined that C6HSL increased the biofilm activity of Salmonella Typhimurium DMC4, SL1344 wild strains, and mutants, mainly at the 72nd hour. In conclusion, our results proved that C6HSL stimulated QS communication in all strains and increased biofilm of Salmonella formation and autoinducer activity. This situation determines that Salmonella responds to external signals by using QS systems. In addition, this research contributed to provide additional information on interspecies communication mechanisms to develop strategies to prevent biofilm formation of this pathogen.
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  • 文章类型: Journal Article
    在这里,我们提出了一种高效的方法,用于构建复杂的5-5-6稠环系统,通常在多环呋喃丁内酯衍生的类和去甲类天然产物家族中发现,具有显着的非对映选择性,利用分子内Diels-Alder反应作为基石。值得注意的是,与炔丙基酯对应物相比,采用炔丙基醚系链作为亲二烯体在转化过程中产生显着增强,正如我们之前的Havellocate全合成所证明的那样。这一进展对未来的调查具有可喜的意义,提供了一个流线型的途径,用于快速组装这种多样化的天然产物家族的三环核心特征。
    Herein, we present a highly efficient method for constructing the intricate 5-5-6 fused ring system commonly found in the polycyclic furanobutenolide-derived cembranoid and norcembranoid natural product family with remarkable diastereoselectivity, utilizing an intramolecular Diels-Alder reaction as the cornerstone. Notably, employing a propargyl ether tether as the dienophile yields significant enhancements in the transformation process compared to its propargyl ester counterpart, as demonstrated in our previous total synthesis of havellockate. This advancement holds promising implications for future investigations, offering a streamlined pathway for rapidly assembling the tricyclic core characteristic of this diverse family of natural products.
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  • 文章类型: Journal Article
    铜绿假单胞菌(P.铜绿假单胞菌)生物膜的形成是抗生素耐药性增强的关键原因。群体感应(QS)参与调节生物膜的形成;QS抑制剂阻断QS信号通路作为解决细菌耐药性的新策略。本研究探讨了L-HSL(N-(3-环丁内酯)-4-三氟苯基乙酰胺)作为铜绿假单胞菌QS抑制剂的潜力和机理。结果表明,L-HSL能有效抑制铜绿假单胞菌生物膜的形成,分散预先形成的生物膜。L-HSL抑制了细胞外多糖的产生和铜绿假单胞菌的运动能力。秀丽隐杆线虫感染实验表明,L-HSL无毒,可保护秀丽隐杆线虫免受铜绿假单胞菌感染。转录组学分析显示L-HSL下调与QS途径和生物膜形成相关的基因。L-HSL作为铜绿假单胞菌感染的治疗药物显示出有希望的潜力。关键点:•化学合成N-(3-环丁内酯)-4-三氟苯基乙酰胺,命名为L-HSL。•L-HSL对铜绿假单胞菌的生长不产生存活压力,并且可以抑制QS系统。•KEGG富集分析发现,L-HSL处理后,QS相关基因下调。
    Pseudomonas aeruginosa (P. aeruginosa) biofilm formation is a crucial cause of enhanced antibiotic resistance. Quorum sensing (QS) is involved in regulating biofilm formation; QS inhibitors block the QS signaling pathway as a new strategy to address bacterial resistance. This study investigated the potential and mechanism of L-HSL (N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide) as a QS inhibitor for P. aeruginosa. The results showed that L-HSL effectively inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa. The production of extracellular polysaccharides and the motility ability of P. aeruginosa were suppressed by L-HSL. C. elegans infection experiment showed that L-HSL was non-toxic and provided protection to C. elegans against P. aeruginosa infection. Transcriptomic analysis revealed that L-HSL downregulated genes related to QS pathways and biofilm formation. L-HSL exhibits a promising potential as a therapeutic drug for P. aeruginosa infection. KEY POINTS: • Chemical synthesis of N-(3-cyclic butyrolactone)-4-trifluorophenylacetamide, named L-HSL. • L-HSL does not generate survival pressure on the growth of P. aeruginosa and can inhibit the QS system. • KEGG enrichment analysis found that after L-HSL treatment, QS-related genes were downregulated.
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  • 文章类型: Journal Article
    转移性乳腺癌的骨转移通常由于破骨细胞活性而导致溶骨性病变,促进骨破坏和肿瘤进展。生物活性真菌分离株,4-乙酰基-蒽醌醇B(4-AAQB)和赤霉素A,具有多种药理和生物活性。然而,它们对乳腺癌骨转移治疗的影响尚不清楚.我们的研究旨在研究4-AQB或赤霉素A对乳腺癌骨转移的影响。4-AQB和赤霉素A对乳腺癌诱导的破骨细胞生成的影响,乳腺癌迁移,促转移细胞因子(TGF-β)和标志物(MMP-9)的产生,以及潜在的MAPK信号转导进行了评估。结果表明,4-AAQB和赤霉素A可有效抑制乳腺癌诱导的破骨细胞生成和迁移,并通过Erk或JNK信号转导减少TGF-β和MMP-9的产生,特别是在乳腺癌细胞或乳腺癌细胞诱导的破骨细胞中。基于这些发现,4-AQB或赤霉素A在预防乳腺癌骨转移方面显示出希望。
    Bone metastasis in metastatic breast cancer commonly results in osteolytic lesions due to osteoclast activity, promoting bone destruction and tumor progression. The bioactive fungal isolates, 4-acetyl-antroquinonol B (4-AAQB) and erinacine A, have diverse pharmacological and biological activities. However, their effects on breast cancer bone metastasis treatment remain unclear. Our study aimed to examine the impact of 4-AAQB or erinacine A on breast cancer metastases in bone. The effects of 4-AAQB and erinacine A on breast cancer-induced osteoclastogenesis, breast cancer migration, production of prometastatic cytokine (TGF-β) and marker (MMP-9), as well as potential MAPK signaling transductions were assessed. The results revealed that 4-AAQB and erinacine A effectively suppressed breast cancer-induced osteoclastogenesis and migration, and reduced TGF-β and MMP-9 production via Erk or JNK signaling transductions, specifically in breast cancer cells or in breast cancer cells-induced osteoclasts. Based on these findings, either 4-AAQB or erinacine A showed promise in preventing breast cancer metastases in bone.
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  • 文章类型: Journal Article
    四种未描述的聚酮化合物,beshanzoneA(1)和B(2)以及beshanhexanolsA(3)和B(4),从与极度濒危的中国特有针叶树冷杉相关的两种内生真菌的水稻发酵中分离出三种已知的(5-7)。γ-丁内酯衍生物1、2和5分离自Phomopsissp。BSZ-AZ-2,一种有趣的菌株,这次引起了我们的注意。在对青霉菌BSZ-P-4-1的后续研究中获得了环己醇衍生物3、4、6和7。化合物1-4的化学结构包括绝对构型通过光谱法测定,Mo2(OAc)4诱导电子圆二色性(IECD),GIAONMR计算和DP4+概率分析。特别是,化合物2包含一个新的5/5双环系统,其可以通过水解随后进行Aldol反应从已知化合物5生物源衍生。评估所有分离株对一小组细菌和真菌病原体的抗微生物活性。化合物6和7对白色念珠菌表现出中等抑制活性,MIC值为16和32μg/mL,分别。
    Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 μg/mL, respectively.
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  • 文章类型: Journal Article
    玉米穗腐病和轮枝镰刀菌引起的伏马菌素对粮食安全构成严重威胁。为了找到更高活性的杀真菌和抗毒候选物,具有基于天然存在的铅黄素的结构多样性,合理设计合成了一系列新型螺哌啶基-α-亚甲基-γ-丁内酯。体外生物测定结果表明,化合物7c具有广谱的体外活性,其EC50值从3.51降至24.10μg/mL,比阳性对照黄原苷和奥齐哌林更活跃。此外,即使在20μg/mL的浓度下,化合物7c也对伏马菌素具有48%的抑制率。荧光猝灭和分子对接验证了7c和氧硫哌林在FvoshC的靶向性。RNA测序分析发现,内质网中的FUM基因簇和蛋白质加工下调。我们的研究发现螺哌啶基-α-亚甲基-γ-丁内酯是一种新型的基于FvoshC靶标的支架,具有抗毒素活性。
    Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 μg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 μg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
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  • 文章类型: Journal Article
    双目毛虫(鳞翅目:夜蛾科)是大豆种植园中普遍存在的害虫,使用天然和合成化学产品进行管理。然而,某些人群中抗药性的出现强调了探索替代杀虫剂的必要性。Flupyradifrone,一种神经毒性杀虫剂,以前没有用于控制双歧杆菌。这项研究评估了氟吡唑酮在双歧杆菌管理中的潜力。最初,毒性和抗摄食作用,以及组织病理学和细胞毒性影响,对双花双歧杆菌上的氟吡唑酮进行了评估。随后,验证了氟吡唑酮对食肉动物Podisusnigrispinus(半翅目:Pentatomidae)的中肠和脂肪体的间接影响。结果表明毛虫对氟吡唑酮的敏感性,LC50为5.10gL-1。此外,杀虫剂对生存产生不利影响,诱导抗进食反应,并对毛虫的中肠造成伤害。然而,flupyradifurone还通过毛虫的间接中毒导致捕食者P.nigrispinus的副作用,包括中肠和脂肪的身体损伤。虽然氟吡唑酮对双歧杆菌有毒性,暗示了它对这种害虫的化学控制的潜力,对捕食者的间接负面影响表明,需要将其与杀虫剂和捕食者一起控制在害虫综合管理计划中。
    The caterpillar Anticarsia gemmatalis (Lepidoptera: Noctuidae) is a prevalent pest in soybean plantations, managed using both natural and synthetic chemical products. However, the emergence of resistance in some populations emphasizes the need to explore alternative insecticides. Flupyradifurone, a neurotoxic insecticide, has not been previously used for controlling A. gemmatalis. This study evaluated the potential of flupyradifurone in the management of A. gemmatalis. Initially, the toxicity and anti-feeding effects, as well as histopathological and cytotoxic impacts, of flupyradifurone on A. gemmatalis were evaluated. Subsequently, the indirect effects of flupyradifurone on the midgut and fat body of the predator Podisus nigrispinus (Hemiptera: Pentatomidae) were verified. The results indicate the susceptibility of caterpillars to flupyradifurone, with an LC50 of 5.10 g L-1. Furthermore, the insecticide adversely affects survival, induces an anti-feeding response, and inflicts damage on the midgut of the caterpillars. However, flupyradifurone also leads to side effects in the predator P. nigrispinus through indirect intoxication of the caterpillars, including midgut and fat body damage. While flupyradifurone demonstrates toxicity to A. gemmatalis, suggesting its potential for the chemical control of this pest, the indirect negative effects on the predator indicate the need for its controlled use in integrated pest management programs with the insecticide and the predator.
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  • 文章类型: Journal Article
    人类肠道微生物群在转化secoisolariciresinol二葡萄糖苷中起着至关重要的作用,在亚麻籽中发现的木酚素,对于肠二醇,具有一系列健康益处:抗氧化,抗肿瘤,和雌激素/抗雌激素作用。考虑到亚麻籽饼中的高含量,这项研究调查了将亚麻籽饼与发酵大豆产品共发酵的潜力,以分离出在受控环境(体外)中有效地将secoisolariciresinol二葡萄糖苷转化为肠二醇的细菌菌株。与臭豆腐微生物群的共发酵过程显着改变了木酚素,产生12个通过靶向代谢组学鉴定的中间木酚素代谢物。一种特别有前途的菌株,ZB26表现出令人印象深刻的转化secoisolariciresinol二葡萄糖苷的能力。实现了87.42±0.33%的转化率,与己基异瑞林和肠二醇的产生率为94.22±0.51%和2.91±0.03%,分别。进一步优化显示,在特定条件下(0.5mM谢奥异赖辛醇二葡糖苷,pH8,30°C3天),ZB26可以转化甚至更高百分比(97.75±0.05%)的塞科isolaricisuresinol二葡糖苷以产生塞科isolaricisenesinol(103.02±0.16%)和肠二醇(3.18±0.31%)。这些发现表明,已鉴定的菌株ZB26具有开发富含木脂素的功能性食品和成分的潜力。
    Human intestinal microbiota plays a crucial role in converting secoisolariciresinol diglucoside, a lignan found in flaxseed, to enterodiol, which has a range of health benefits: antioxidative, antitumor, and estrogenic/anti-estrogenic effects. Given the high secoisolariciresinol diglucoside content in flaxseed cake, this study investigated the potential of co-fermenting flaxseed cake with fermented soybean product to isolate bacterial strains that effectively convert secoisolariciresinol diglucoside to enterodiol in a controlled environment (in vitro). The co-fermentation process with stinky tofu microbiota significantly altered the lignan, generating 12 intermediate lignan metabolites as identified by targeted metabolomics. One particular promising strain, ZB26, demonstrated an impressive ability to convert secoisolariciresinol diglucoside. It achieved a conversion rate of 87.42 ± 0.33%, with secoisolariciresinol and enterodiol generation rates of 94.22 ± 0.51% and 2.91 ± 0.03%, respectively. Further optimization revealed, under specific conditions (0.5 mM secoisolariciresinol diglucoside, pH 8, 30 °C for 3 days), ZB26 could convert an even higher percentage (97.75 ± 0.05%) of the secoisolariciresinol diglucoside to generate secoisolariciresinol (103.02 ± 0.16%) and enterodiol (3.18 ± 0.31%). These findings suggest that the identified strains ZB26 have promising potential for developing functional foods and ingredients enriched with lignans.
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