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Naringenin can Inhibit the Pyroptosis of Osteoblasts by Activating the Nrf2/HO-1 Signaling Pathway and Alleviate the Differentiation Disorder of Osteoblasts Caused by Microgravity. 柚皮苷可通过激活 Nrf2/HO-1 信号通路抑制成骨细胞的炭疽,缓解微重力导致的成骨细胞分化障碍
IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-20 Epub Date: 2024-11-06 DOI: 10.1021/acs.jafc.4c05370
Shuyan Cao, Yi Wang, Yalong Zhang, Jingyi Ren, Bingjie Fan, Ying Deng, Wenzhe Yin

Naringenin (4,5,7-trihydroxyflavone, NAR) is an effective active ingredient in Rhizoma Drynariae, which has many biological functions, encompassing anti-inflammatory and -oxidant functions. Prior research has shown that NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes possessed a significant contribution to osteoporosis. However, the NAR impact on bone loss caused by microgravity remains unclear. Classical microgravity simulation methods were used to induce simulated microgravity (SMG) in mice and cells. Microcomputed tomography, immunohistochemical examination, and hematoxylin and eosin staining were implemented to ascertain alterations in bone microstructure and morphology in mice subsequent to NAR gavage. Cellular investigations were implemented encompassing quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence labeling to investigate the molecular mechanism behind NAR resistance to microgravity-induced bone loss. Our research has shown that NAR can significantly enhance the SMG-stimulated alterations in bone microstructure and morphology in mice, mainly by increasing the trabecular thickness, bone volume fraction, and trabecular number while increasing the bone trabecula number. Cell experiments also showed that SMG caused the activation of inflammatory corpuscles of NLRP3 and induced pyroptosis simultaneously, which can be confirmed by the upregulation of protein and mRNA expression levels such as those of NLRP3, cleaved caspase-1, gasdermin D, and apoptosis-associated speck-like protein. The occurrence of pyroptosis further led to the disorder of osteogenic differentiation, which showed that the osteopontin, Runt-related transcription factor 2, bone morphogenetic protein 2, and alkaline phosphatase expression levels were decreased. The intervention of NAR can activate the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway, reverse this phenomenon via controlling the reactive oxygen species generation in cells and correcting mitochondrial malfunction, weaken the pyroptosis of osteoblasts (OBs), and promote osteogenic differentiation. In summary, NAR could hinder the pyroptosis of OBs caused by SMG and promote osteogenic differentiation via activating the Nrf2/HO-1 pathway. This provides a unique view for inhibiting bone loss under weightlessness and confirms the NAR capacity in treating microgravity-stimulated bone loss, giving new ideas and methods for future space medicine development.

柚皮苷(4,5,7-三羟基黄酮,NAR)是黄连中的一种有效活性成分,具有多种生物功能,包括抗炎和抗氧化功能。先前的研究表明,NOD 样受体含 pyrin 域蛋白 3(NLRP3)炎性体对骨质疏松症有重要作用。然而,NAR对微重力造成的骨质流失的影响仍不清楚。研究人员使用经典的微重力模拟方法在小鼠和细胞中诱导模拟微重力(SMG)。通过微计算机断层扫描、免疫组化检查以及苏木精和伊红染色,确定小鼠在灌胃 NAR 后骨骼微观结构和形态的变化。细胞研究包括实时定量聚合酶链反应、Western 印迹和免疫荧光标记,以研究 NAR 抵抗微重力诱导骨质流失的分子机制。我们的研究表明,NAR能显著增强SMG刺激的小鼠骨微观结构和形态的改变,主要是通过增加骨小梁厚度、骨体积分数和骨小梁数量,同时增加骨小梁数量。细胞实验还表明,SMG 能同时激活 NLRP3 的炎性细胞团和诱导脓毒症,这可以通过 NLRP3、裂解的 caspase-1、gasdermin D 和细胞凋亡相关斑点样蛋白等蛋白和 mRNA 表达水平的上调得到证实。脓毒症的发生进一步导致成骨分化障碍,表现为骨素、Runt 相关转录因子 2、骨形态发生蛋白 2 和碱性磷酸酶表达水平下降。NAR的干预可以激活核因子红细胞2相关因子2/血红素氧合酶-1(Nrf2/HO-1)通路,通过控制细胞内活性氧的生成和纠正线粒体功能失调来逆转这一现象,削弱成骨细胞(OBs)的热休克,促进成骨分化。综上所述,NAR可通过激活Nrf2/HO-1通路阻碍SMG引起的成骨细胞热解,促进成骨分化。这为抑制失重状态下的骨质流失提供了一个独特的视角,证实了NAR在治疗微重力刺激的骨质流失方面的能力,为未来空间医学的发展提供了新的思路和方法。
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引用次数: 0
Efficient Production of the Colorless Carotenoid Phytoene in Yarrowia lipolytica through Metabolic Engineering. 通过代谢工程在脂溶性亚罗酵母中高效生产无色类胡萝卜素。
IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c07735
Kwanghyun Park, Gyeongmin Kim, Seungwoo Cha, Yangsub Ham, Ji-Sook Hahn

Phytoene, a colorless carotenoid with unique ultraviolet (UV)-B absorption properties, offers potential for applications in functional food, cosmetics, and therapeutics. However, their low natural yield poses a challenge for large-scale production. This study aims to enhance phytoene production in the oleaginous yeast Yarrowia lipolytica by introducing a heterologous phytoene synthase gene combined with metabolic engineering approaches. We enhanced phytoene synthesis by overexpressing key genes in the mevalonate pathway and compartmentalizing the biosynthetic pathway within peroxisomes. Moreover, we inhibited the glyoxylate cycle to increase the accumulation of peroxisomal acetyl-CoA available for phytoene production. Our engineered strains demonstrated a significant increase in phytoene production, reaching up to 1.34 g/L titer and 58.74 mg/gDCW yield in the flask-scale fed-batch culture, which are the highest levels reported to date. These results underscore the potential of Y. lipolytica as a robust platform for producing phytoenes and other terpenoids on an industrial scale, offering valuable insights for future efforts in metabolic engineering.

植物烯是一种无色类胡萝卜素,具有独特的紫外线(UV)-B 吸收特性,在功能性食品、化妆品和治疗领域具有潜在的应用前景。然而,它们的天然产量较低,给大规模生产带来了挑战。本研究旨在通过引入异源植物烯合成酶基因并结合代谢工程方法,提高含油酵母 Yarrowia lipolytica 的植物烯产量。我们通过过量表达甲羟戊酸途径中的关键基因,并在过氧物酶体内对生物合成途径进行分区,从而提高了植物烯的合成。此外,我们还抑制了乙醛酸循环,以增加可用于生产植物烯的过氧物酶体乙酰-CoA的积累。我们的工程菌株显著提高了植物烯的产量,在烧瓶饲养批次培养中,植物烯的滴度高达 1.34 克/升,产量为 58.74 毫克/克 DCW,这是迄今为止报道的最高水平。这些结果凸显了脂溶性酵母作为工业规模生产植物烯和其他萜类化合物的强大平台的潜力,为今后的代谢工程工作提供了宝贵的启示。
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引用次数: 0
Flavin-Dependent Monooxgenase Confers Resistance to Chlorantraniliprole and Spinetoram in the Rice Stem Borer Chilo suppressalis Walker (Lepidoptera: Crambidae) 依赖黄素的单氧化酶使水稻蛀螟 Chilo suppressalis Walker(鳞翅目:禾本科)对氯虫苯甲酰胺和辛硫磷产生抗性
IF 6.1 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c09254
Shuai Wang, Jing-Mei Huang, Fang-Rui Guo, Chong Liu, Yuan Xie, Song-Tao Qiao, Yun-Xiao Chen, Shun-Fan Wu, Chris Bass, Cong-Fen Gao
Understanding the role of flavin-containing monooxygenases (FMOs) in the genetic mechanisms of insecticide resistance is essential for developing effective management strategies against the rice stem borer, Chilo suppressalis. In this study, we identified five FMO genes in C. suppressalis, examined their expression patterns, and revealed overexpression of FMO3B and FMO3C in field populations resistant to multiple insecticides, including chlorantraniliprole and spinetoram. Functional characterization using transgenic Drosophila indicated that FMO3B and FMO3C do not confer resistance to abamectin or methoxyfenozide but do mediate resistance to chlorantraniliprole and spinetoram. Knockdown of FMO3B and FMO3C increased sensitivity to these insecticides in C. suppressalis. Molecular docking studies indicated direct binding of chlorantraniliprole and spinetoram to these FMOs, underscoring their role in metabolic resistance. These findings indicate that FMOs are key enzymes in the metabolic resistance of C. suppressalis to chlorantraniliprole and spinetoram, enhancing our understanding of insecticide resistance and aiding the development of management strategies.
了解含黄素单氧化酶(FMOs)在杀虫剂抗性遗传机制中的作用对于制定有效的水稻二化螟防治策略至关重要。在这项研究中,我们确定了抑螟中的五个 FMO 基因,研究了它们的表达模式,并发现在对多种杀虫剂(包括氯虫苯甲酰胺和辛硫磷)具有抗性的田间种群中,FMO3B 和 FMO3C 过表达。利用转基因果蝇进行的功能特性分析表明,FMO3B 和 FMO3C 不会产生对阿维菌素或甲氧喹诺酮的抗性,但会介导对氯虫苯甲酰胺和斯冰特罗姆的抗性。敲除 FMO3B 和 FMO3C 会增加抑尾蛛对这些杀虫剂的敏感性。分子对接研究表明,氯虫苯甲酰胺和辛硫磷与这些 FMOs 直接结合,突出了它们在新陈代谢抗性中的作用。这些研究结果表明,FMOs 是抑制蓟马对氯虫苯甲酰胺和辛硫磷产生代谢抗性的关键酶,从而加深了我们对杀虫剂抗性的了解,并有助于制定管理策略。
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引用次数: 0
Development and Application of a New QuEChERS Method Coupled with UPLC-QTOF-MS/MS for Analysis of Tiafenacil and Its Photolysis Products in Water 开发和应用新型 QuEChERS 方法与 UPLC-QTOF-MS/MS 联用分析水中的噻芬那嘧啶及其光解产物
IF 6.1 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c04618
Zhie Zhou, Shujie Zhang, Jian Chen, Wenjing Luo, Fenfen Kang, Yonglin Ren, Wenwen Zhou
This research centered on the novel pyrimidinedione herbicide, tiafenacil. Residues of tiafenacil and its three photolysis products (PP1 to PP3) in water were analyzed using advanced QuEChERS and UPLC-QTOF-MS/MS techniques, reaching a low limit of quantitation (LOQ) of 10 μg/L. Calibration curves exhibited a high degree of linearity (R2 ≥ 0.993) over a concentration range of 0.01 to 1.00 mg/L. Method validation demonstrated high precision, with intraday relative standard deviation RSDr ≤7.9% and interday RSDR ≤ 6.1%, along with high accuracy (recoveries from 94.4% to 105.0%). Using density functional theory (DFT) at the B3LYP/6-311g (d) level, we calculated the electronic properties of tiafenacil and its PPs (PP1 to PP3). Additionally, frontier molecular orbital (FMO) and fukui function analyses were conducted to explore HOMO–LUMO energies, determine energy band gaps for these substances, and predict reactive sites for their electrophilic, nucleophilic, and radical reactions. Significantly, ecotoxicity assessment, including ECOSAR predictions and acute toxicity tests, revealed that the PPs exhibited higher ecotoxicity to aquatic organisms than tiafenacil. Field experiments showed a half-life of 18.9 days for tiafenacil in water, fitting a first-order kinetic model (R2 = 0.999), with a degradation of 41.5% after 14 days and approximately 89.2% after 60 days. This study significantly advances our understanding of tiafenacil’s environmental fate, evaluates its associated risks, and offers valuable insights for its responsible application.
这项研究以新型嘧啶二酮除草剂噻虫嗪为中心。采用先进的 QuEChERS 和 UPLC-QTOF-MS/MS 技术分析了水中噻虫嗪及其三种光解产物(PP1 至 PP3)的残留量,定量限(LOQ)低至 10 μg/L。在 0.01 至 1.00 mg/L 的浓度范围内,校准曲线呈现高度线性(R2 ≥ 0.993)。方法验证结果表明,该方法具有很高的精密度,日内相对标准偏差 RSDr ≤ 7.9%,日间 RSDR ≤ 6.1%,同时还具有很高的准确度(回收率为 94.4% 至 105.0%)。利用 B3LYP/6-311g (d) 水平的密度泛函理论(DFT),我们计算了噻非那嘧啶及其 PPs(PP1 至 PP3)的电子特性。此外,我们还进行了前沿分子轨道(FMO)和傅魁函数分析,以探索 HOMO-LUMO 能量,确定这些物质的能带隙,并预测其亲电、亲核和自由基反应的反应位点。重要的是,生态毒性评估(包括 ECOSAR 预测和急性毒性测试)显示,与噻虫嗪相比,聚丙烯对水生生物的生态毒性更高。现场实验表明,噻虫嗪在水中的半衰期为 18.9 天,符合一阶动力学模型(R2 = 0.999),14 天后降解率为 41.5%,60 天后降解率约为 89.2%。这项研究极大地推动了我们对噻虫嗪环境归宿的了解,评估了其相关风险,并为其负责任的应用提供了宝贵的见解。
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引用次数: 0
1,3-Dichloro-2-propanol Induced Renal Cell Ferroptosis via the Circadian Clock Protein BMAL1 Targeting GPX4 1,3-二氯-2-丙醇通过靶向 GPX4 的昼夜节律时钟蛋白 BMAL1 诱导肾细胞铁蜕变
IF 6.1 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c05676
Yuelin Chen, Shuang Guan, Meitong Liu, Lingxi Lang, Huanhuan Peng, Jing Lu
1,3-Dichloro-2-propanol (1,3-DCP), a representative chloropropyl alcohol contaminant in food, has shown toxic effects on the kidney. Ferroptosis is a newly identified cell death driven by iron-dependent lipid peroxidation that is associated with renal injury. However, the role of 1,3-DCP in ferroptosis in renal cells remains unclear. In this study, we found that ferroptosis was involved in a 1,3-DCP-induced renal injury. Mechanistically, we revealed that 1,3-DCP triggered ferroptosis by inhibiting GPX4 activity and disturbing iron homeostasis in NRK-52E cells. The circadian clock is crucial in modulating physiological cellular functions through the regulation of various downstream proteins. Furthermore, our findings also showed that 1,3-DCP triggered ferroptosis through interference with the circadian clock. The data showed that the expression of GPX4 was regulated by clock core protein BMAL1. 1,3-DCP interfered with GPX4 rhythmic expression through disordering BMAL1 and led to lipid peroxidation, ultimately inducing ferroptosis. In conclusion, our study uncovered that BMAL1 was responsible for controlling GPX4 to mediate 1,3-DCP-induced ferroptosis. The BMAL1/GPX4 axis may be a potentially novel pathway for ferroptosis. Our work may offer a fresh perspective for toxicological research examining the interactions between food pollutants, circadian clock, and ferroptosis.
1,3-二氯-2-丙醇(1,3-DCP)是食品中具有代表性的氯丙醇污染物,对肾脏有毒性作用。铁中毒是一种新发现的由铁依赖性脂质过氧化驱动的细胞死亡,与肾损伤有关。然而,1,3-二氯丙醇在肾细胞铁氧化过程中的作用仍不清楚。在这项研究中,我们发现铁跃迁参与了二氯丙醇诱导的肾损伤。从机理上讲,我们发现二氯丙醇通过抑制 GPX4 的活性和扰乱 NRK-52E 细胞中铁的稳态来触发铁变态反应。昼夜节律在通过调控各种下游蛋白调节细胞生理功能方面至关重要。此外,我们的研究结果还表明,二氯丙醇通过干扰昼夜节律钟引发铁变态反应。数据显示,GPX4 的表达受时钟核心蛋白 BMAL1 的调控。二氯丙醇通过扰乱 BMAL1 干扰了 GPX4 的节律表达,并导致脂质过氧化,最终诱发铁变态反应。总之,我们的研究发现 BMAL1 负责控制 GPX4 以介导 1,3-DCP 诱导的铁变态反应。BMAL1/GPX4 轴可能是一种潜在的新型铁变态反应途径。我们的工作可能会为研究食物污染物、昼夜节律和铁变态反应之间相互作用的毒理学研究提供一个全新的视角。
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引用次数: 0
Exploring the Biological Potential of Hydroxytyrosol and Derivatives: Synthetic Strategies and Evaluation of Antiproliferative, Antioxidant, and Antimicrobial Activities 探索羟基酪醇及其衍生物的生物潜力:合成策略与抗增殖、抗氧化和抗菌活性评估
IF 6.1 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c06179
Beatriz T. Martins, Nuno Alexandre Faria, Ana Catarina Macedo, Maria Miragaia, Ana Teresa Serra, M. Rosário Bronze, M. Rita Ventura
Phenolic compounds found in Extra Virgin Olive Oil (EVOO) have been associated with various health benefits. Bioavailability studies indicate that the phase I and II metabolites of these phenolic compounds can be detected in human urine and plasma following EVOO consumption. To contribute to the understanding of the biological potential of these phenolic compounds and their metabolites, this study delves into the synthesis, stability, and biological activities of hydroxytyrosol (HT), tyrosol (Tyr), and homovanillic alcohol (HVA), as well as their glucuronide, sulfate, and acetylated metabolites. For the first time, an effective synthesis was developed to allow the selective obtention of 3′- and 4′-glucuronides, as well as sulfates of HT. HT and its acetylated derivative emerged as the most potent compounds across antioxidant assessments, antiproliferative studies against human colorectal adenocarcinoma cell lines, and antimicrobial assays.
特级初榨橄榄油(EVOO)中的酚类化合物具有多种健康益处。生物利用率研究表明,食用特级初榨橄榄油后,可在人体尿液和血浆中检测到这些酚类化合物的 I 期和 II 期代谢物。为了帮助人们了解这些酚类化合物及其代谢物的生物潜力,本研究深入探讨了羟基酪醇(HT)、酪醇(Tyr)和高香草醇(HVA)及其葡萄糖醛酸、硫酸盐和乙酰化代谢物的合成、稳定性和生物活性。首次开发出一种有效的合成方法,可以选择性地获得 HT 的 3′-和 4′-葡萄糖醛酸苷以及硫酸盐。HT 及其乙酰化衍生物在抗氧化评估、针对人类结直肠腺癌细胞系的抗增殖研究以及抗菌试验中都是最有效的化合物。
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引用次数: 0
A Mechanistic Approach on Perception Mode of ABA Receptors (PYLs) to Novel Opabactin Analogues ABA 受体(PYLs)对新型 Opabactin 类似物的感知模式的机理研究
IF 6.1 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-19 DOI: 10.1021/acs.jafc.4c07265
Xianjun Tang, Minghui Chen, Xiaobin Li, Huizhe Lu, Xueqin Zhang, Yiyi Li, Jiaqi Li, Yumei Xiao, Zhaohai Qin
This study explored the structural mechanisms governing the binding of opabactin (OP) analogues 26 to abscisic acid (ABA) receptors by employing a combination of micro-scale thermophoresis (MST), phosphatase activity inhibition assays, and molecular dynamics simulations. The compounds 36 selectively activated PYR1, PYL2, and PYL6, while exhibiting minimal activity against PYL10, thus identifying them as selective ABA receptor agonists. Additionally, these analogues exerted a significant inhibitory effect on the phosphatase HAB1 upon binding to the receptors. The molecular dynamics simulations further elucidated the detailed binding interactions between various OP analogues and the ABA receptor PYR1, highlighting their role in inducing conformational changes within the receptor. Specifically, the study focused on the facilitation of the closure of the Gate and CL1 loops and the fine-tuning of the Latch loop to enhance the plasticity of the binding pocket, thereby influencing receptor–ligand interactions. The investigation emphasized the critical role of conserved water molecules in stabilizing the ligand-PYLs-PP2Cs complexes. Furthermore, free energy decomposition calculations demonstrated that the ligand’s affinity was significantly affected by its ability to establish polar contacts between the polar groups within the ligand tail and the residues at the base of the binding pocket. This research lays a robust foundation for the development of novel ABA functional analogues with improved activity.
本研究采用微尺度热泳(MST)、磷酸酶活性抑制试验和分子动力学模拟相结合的方法,探索了欧巴马汀(OP)类似物 2-6 与脱落酸(ABA)受体结合的结构机制。化合物 3-6 选择性地激活了PYR1、PYL2 和PYL6,同时对PYL10 的活性极低,因此被确定为选择性 ABA 受体激动剂。此外,这些类似物与受体结合后对磷酸酶 HAB1 有明显的抑制作用。分子动力学模拟进一步阐明了各种 OP 类似物与 ABA 受体PYR1 之间的详细结合相互作用,突出了它们在诱导受体构象变化中的作用。具体来说,研究重点是促进门环(Gate)和CL1环(CL1 loop)的闭合以及微调闩锁环(Latch loop),以增强结合口袋的可塑性,从而影响受体与配体之间的相互作用。研究强调了保守水分子在稳定配体-PYLs-PP2Cs复合物中的关键作用。此外,自由能分解计算表明,配体尾部的极性基团与结合口袋底部残基之间建立极性接触的能力对配体的亲和力有显著影响。这项研究为开发具有更高活性的新型 ABA 功能类似物奠定了坚实的基础。
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引用次数: 0
Enantioseparation, Absolute Configuration, and Enantioselective Bioactivity Mechanism of the Chiral Fungicide Nuarimol. 手性杀真菌剂 Nuarimol 的对映体分离、绝对构型和对映体选择性生物活性机制
IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-18 DOI: 10.1021/acs.jafc.4c06972
Yanhong Li, Liangliang Zhou, Wenjie Wei, Hagar M S Salman, Yingying Wu, Minghua Wang

In this study, the nuarimol enantiomers were successfully baseline separated with Rs 1.70 by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The absolute configurations of the nuarimol enantiomers were confirmed as R-(+)-nuarimol and S-(-)-nuarimol. The enantioselective bioactivity assay indicated that R-(+)-nuarimol exhibited greater potency against seven phytopathogenic fungi, with values approximately 1.4-3.5 and 4.5-51.4 times higher than those of rac-nuarimol and S-(-)-nuarimol. The active contribution value of R-enantiomer was 82-98%, showing that R-(+)-nuarimol played a crucial role in bioactivity. Meanwhile, R-(+)-nuarimol exhibited stronger effects in increasing the cell membrane permeability, compromising the cell membrane integrity, and inhibiting ergosterol biosynthesis. Molecular docking analysis showed that R-(+)-nuarimol possessed a stronger binding affinity to sterol 14-α demethylase (CYP51) than S-(-)-nuarimol, with docking energies of -7.42 and -7.36 kcal/mol. This study contributes essential data for screening a high-activity enantiomer of nuarimol and provide guidance for reducing used dosage and increasing the efficiency of nuarimolAQ.

本研究采用超高效液相色谱-串联质谱法(UPLC-MS/MS)成功地对萘利莫尔对映体进行了基线分离,分离比为1.70。萘利莫对映体的绝对构型被确认为 R-(+)-nuarimol 和 S-(-)-nuarimol。对映体选择性生物活性测定结果表明,R-(+)-萘啶醇对七种植物病原真菌具有更强的药效,其药效值约为 rac-nuarimol 和 S-(-)-nuarimol 的 1.4-3.5 倍和 4.5-51.4 倍。R 对映异构体的活性贡献值为 82-98%,表明 R-(+)-萘利莫尔在生物活性中起着关键作用。同时,R-(+)-萘啶醇在增加细胞膜通透性、破坏细胞膜完整性和抑制麦角甾醇生物合成方面表现出更强的作用。分子对接分析表明,与 S-(-)-nuarimol 相比,R-(+)-nuarimol 与甾醇 14-α 去甲基化酶(CYP51)的结合亲和力更强,对接能分别为 -7.42 和 -7.36 kcal/mol。这项研究为筛选萘利莫尔的高活性对映体提供了重要数据,并为减少萘利莫尔AQ的用量和提高其效率提供了指导。
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引用次数: 0
Mitigating the Effects of Starch Derivatives on Cold Denaturation of Gluten Protein: Insights from Hydration Capacity and Conformation Behavior. 减轻淀粉衍生物对谷蛋白冷变性的影响:水合能力和构象行为的启示。
IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-18 DOI: 10.1021/acs.jafc.4c08121
Yang Li, Haocun Kong, Caiming Li, Xiaofeng Ban, Zhengbiao Gu, Yujie Lu, Zhaofeng Li

Mitigating the cold denaturation of gluten protein during frozen storage is crucial for the quality improvement of frozen cereal products. Our previous study observed that starch derivatives, especially short-clustered maltodextrin (SCMD), could significantly improve frozen dough quality, alleviating the deterioration of gluten-network structure. To further reveal the cryoprotection mechanism of SCMD on gluten protein during frozen storage, the modulatory roles of SCMD in the hydration capacity and conformation behavior of gluten protein were explored, in comparison with DE2 maltodextrin (MD) and pregelatinized starch (PGS). Results demonstrated that SCMD significantly facilitated the reservation of bound water and decreased the surface hydrophobicity of gluten protein after 8 weeks of frozen storage. Remarkable effects of SCMD on stabilizing the secondary structure and microenvironment of aromatic amino acids of gluten protein were observed. Further mechanistic investigation showed that when the temperature dropped from 300 to 250 K, the short-clustered structure could stabilize the α-helixes more evidently than linear structures through hydrogen bonds with water and steric hindrance effect, rather than directly with protein. Our findings will provide novel insights into the cold denaturation of gluten protein and useful guidance in selecting the optimum structure to suppress this denaturation, improving the quality of frozen cereal products.

减轻面筋蛋白在冷冻储存过程中的冷变性对提高冷冻谷物产品的质量至关重要。我们之前的研究发现,淀粉衍生物,尤其是短簇麦芽糊精(SCMD),可以显著改善冷冻面团的质量,缓解面筋网络结构的恶化。为了进一步揭示短簇麦芽糊精在冷冻贮藏期间对面筋蛋白的低温保护机制,研究人员将短簇麦芽糊精与 DE2 麦芽糊精(MD)和预糊化淀粉(PGS)进行了比较,探讨了短簇麦芽糊精对面筋蛋白水合能力和构象行为的调节作用。结果表明,经过 8 周的冷冻储存后,SCMD 显著促进了结合水的保留,并降低了面筋蛋白的表面疏水性。观察发现,SCMD 对稳定面筋蛋白的二级结构和芳香族氨基酸的微环境有明显作用。进一步的机理研究表明,当温度从 300 K 降到 250 K 时,短簇结构通过与水的氢键和立体阻碍效应,而不是直接与蛋白质结合,比线性结构更明显地稳定了 α-螺旋。我们的发现将为谷蛋白的低温变性提供新的见解,并为选择最佳结构来抑制这种变性提供有用的指导,从而提高冷冻谷物产品的质量。
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引用次数: 0
l-Isoleucine-Derived Amide-hydrazide Compounds Evaluated as a Novel Potential Agricultural Fungicide. l 异亮氨酸衍生酰胺酰肼化合物作为一种新型潜在农用杀菌剂的评估。
IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Pub Date : 2024-11-18 DOI: 10.1021/acs.jafc.4c06630
Jing Chang, Yufei Gong, Wenfei Zhang, Tiancheng Zhang, Jiacheng Liu, Lingzhi Meng, Qingping Ma, Yu-Cheng Gu, Xue-Wen Hua

Building upon previous structure-activity relationships about the fungicidal amide and hydrazide lead structures, 24 novel amide-hydrazide compounds were designed and synthesized with L-isoleucine as the initial skeleton to explore the impact of substituents in the hydrazide bridge on the fungicidal activity. Among these compounds, A5 exhibited excellent and broad spectrum inhibitory activity, along with satisfactory in vivo protective efficiency against R. solani at concentrations of 200 and 50 μg·mL-1. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations revealed that compound A5 induced significant morphological changes in the R. solani mycelium coupled with vacuole rupture and cytoplasmic inhomogeneity in cellular structures. Transcriptomic and metabolomic analyses indicated that, following A5 treatment, the differentially expressed genes and metabolites were significantly enriched in carbohydrate metabolism-related pathways as well as in lipid metabolism-associated pathways, including glycerophospholipid metabolism, steroid biosynthesis, arachidonic acid metabolism, and sphingolipid metabolism. Additionally, compound A5 demonstrated low toxicity to zebrafish, with survival rates of 100% and 60% at concentrations of 1 and 10 μg·mL-1, respectively, over a period of 7 days. The above results provide theoretical guidance for the development of novel green hydrazide fungicidal candidates.

在以往有关杀菌酰胺和酰肼先导结构的结构-活性关系的基础上,以 L-异亮氨酸为初始骨架,设计并合成了 24 种新型酰胺酰肼化合物,以探索酰肼桥中取代基对杀菌活性的影响。在这些化合物中,A5 表现出优异的广谱抑菌活性,在浓度为 200 和 50 μg-mL-1 时对 R. solani 具有令人满意的体内保护效率。扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察结果表明,化合物 A5 能诱导 R. solani 菌丝发生显著的形态变化,并导致液泡破裂和细胞结构中的细胞质不均匀。转录组和代谢组分析表明,A5 处理后,差异表达的基因和代谢物明显富集于碳水化合物代谢相关途径以及脂质代谢相关途径,包括甘油磷脂代谢、类固醇生物合成、花生四烯酸代谢和鞘脂代谢。此外,化合物 A5 对斑马鱼的毒性很低,浓度分别为 1 μg-mL-1 和 10 μg-mL-1 时,斑马鱼在 7 天内的存活率分别为 100%和 60%。上述结果为开发新型绿色酰肼杀菌候选化合物提供了理论指导。
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Journal of Agricultural and Food Chemistry
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