ionophore

离子载体
  • 文章类型: Journal Article
    生物标志物的连续传感,如钾离子或pH值,在可穿戴贴片中需要离子选择性传感器电极的小型化。这种小型化可以通过使用纳米结构碳材料作为基于微针的离子选择性电极和参比电极中的固体接触来实现。在这里,我们比较了三种碳材料作为固体接触:胶体印迹介孔(CIM)碳微粒与~24-28nm介孔,具有3-9nm介孔的介孔碳纳米球,和SuperP炭黑纳米颗粒没有内部孔隙率,但在颗粒聚集体中具有纹理中孔。我们比较了碳结构和成分对材料比电容的影响,关于在孔中掺入离子选择性膜成分的能力,和传感器性能。使用所有三种类型的碳,用涂有金的不锈钢微针获得了功能的K和H离子选择性电极和参考电极。这些传感器在临床相关的浓度范围内给出了近能斯蒂安反应,没有潜在有害的水层,对O2没有反应.它们都表现出足够低的长期潜在漂移值,以允许无需校准,连续运行近1天。尽管三种碳的比容量和孔隙结构不同,在使用每种材料的电极之间没有观察到K+离子感测的电位稳定性的显著差异。在观察到的漂移值中,碳固接触以外的因素可能会发挥作用,也是。然而,用于pH传感,与CIM作为碳固体接触的电极,具有最高的比电容和最好的孔通道,与其他碳材料的电极相比,表现出更好的长期稳定性。
    Continuous sensing of biomarkers, such as potassium ions or pH, in wearable patches requires miniaturization of ion-selective sensor electrodes. Such miniaturization can be achieved by using nanostructured carbon materials as solid contacts in microneedle-based ion-selective and reference electrodes. Here we compare three carbon materials as solid contacts: colloid-imprinted mesoporous (CIM) carbon microparticles with ∼24-28 nm mesopores, mesoporous carbon nanospheres with 3-9 nm mesopores, and Super P carbon black nanoparticles without internal porosity but with textural mesoporosity in particle aggregates. We compare the effects of carbon architecture and composition on specific capacitance of the material, on the ability to incorporate ion-selective membrane components in the pores, and on sensor performance. Functioning K+ and H+ ion-selective electrodes and reference electrodes were obtained with gold-coated stainless-steel microneedles using all three types of carbon. The sensors gave near-Nernstian responses in clinically relevant concentration ranges, were free of potentially detrimental water layers, and showed no response to O2. They all exhibited sufficiently low long-term potential drift values to permit calibration-free, continuous operation for close to 1 day. In spite of the different specific capacitances and pore architecture of the three types of carbon, no significant difference in potential stability for K+ ion sensing was observed between electrodes that used each material. In the observed drift values, factors other than the carbon solid contact are likely to play a role, too. However, for pH sensing, electrodes with CIM as a carbon solid contact, which had the highest specific capacitance and best access to the pores, exhibited better long-term stability than electrodes with the other carbon materials.
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  • 文章类型: Journal Article
    该研究旨在评估饲草质量和narasin掺入对摄入量的影响,消化率,Nellore牛的瘤胃发酵。在随机完整的区组设计中,将28只瘤胃插管的Nellore牛(初始体重[BW]=350±32.4kg)分配给各个围栏,7个街区,根据实验开始时的空腹BW定义。以2×2阶乘排列,在4个实验饮食中的1个中随机分配。作为第一因素饲料质量(中=81克CP/千克干物质[DM],和高=153克CP/千克DM),第二个因素是纳入(N13=饮食加上13mg/kg的narasinDM)或不纳入(N0)narasin(Zimprova;Elanco动物健康,圣保罗,巴西)。实验包括一个28天的时间,其中22天用于适应,最后6天用于数据收集。在DM和营养素摄入量上未观察到haylage质量×narasin相互作用(P≥0.68)。干草质量受影响(P≤0.01)DM摄入量,与中干草相比,饲喂高的牛的值更高。OM增加(P<0.001),NDF,半纤维素,和CP摄入量为摄入HIGH与中间的海拉格。包括N13不影响(P>0.39)DM和牛的营养摄入量。未检测到全道养分消化率的干草质量×narasin相互作用(P≥0.60)。然而,饲喂HIGH草的牛与中相比,DM和所有营养素的消化率均增加(P>0.001)。在所有评估的小时期间,与饲喂HIGH的牛相比,饲喂中糖脂的牛具有更大(P<0.01)比例的乙酸盐。与食用培养基的牛相比,饲喂高糖脂的牛在0h时的丙酸比例更高(P<0.01),而在12小时时,食用中等干草的牛的丙酸比例较高(P<0.01)。HIGHHaylage.检测到瘤胃氨浓度的黑草质量×narasin和黑草质量×收集相互作用时间(P≤0.03),在N13与N13中降低(P<0.03)N0转向消耗高干草。总的来说,高品质的干草可以增加消耗和消化率,更节能的瘤胃发酵。此外,narasin可能是饲用日粮中重要的营养工具,可提高BosindicusNellore牛的瘤胃发酵参数。
    The study aimed to evaluate the effects of forage quality and narasin inclusion on intake, digestibility, and ruminal fermentation of Nellore steers. Twenty-eight rumen-cannulated Nellore steers (initial body weight [BW] = 350 ± 32.4 kg) were allocated to individual pens in a randomized complete block design, with 7 blocks, defined according to the fasting BW at the beginning of the experiment. The steers were randomly assigned within blocks to 1 of 4 experimental diets in 2 × 2 factorial arrangements, being the first-factor forage quality (MEDIUM = 81 g of CP/kg of dry matter [DM], and HIGH = 153 g of CP/kg of DM), and the second factor was the inclusion (N13 = diet plus 13 mg/kg of DM of narasin) or not (N0) of narasin (Zimprova; Elanco Animal Health, São Paulo, Brazil). The experiment consisted of a 28-d period with 22 d for adaptation and the last 6 d for data collection. No haylage quality × narasin interaction (P ≥ 0.68) was observed on DM and nutrient intake. Haylage quality affected (P ≤ 0.01) DM intake, with greater values observed for steers fed HIGH compared with MEDIUM haylage. There was an increase (P < 0.001) in OM, NDF, hemicellulose, and CP intake for steers consuming HIGH vs. MEDIUM haylage. Including N13 did not affect (P > 0.39) DM and nutrient intake of steers. No haylage quality × narasin interactions were detected (P ≥ 0.60) for total tract nutrient digestibility. However, steers fed with HIGH haylage showed an increase (P > 0.001) in DM and digestibility of all nutrients compared with MEDIUM. Steers fed a MEDIUM haylage had a greater (P < 0.01) proportion of acetate compared with steers fed HIGH during all evaluated hours. Steers fed HIGH haylage had a greater (P < 0.01) proportion of propionate at 0 h compared with steers consuming MEDIUM, whereas at 12 h, steers consuming MEDIUM hay had a greater (P < 0.01) proportion of propionate vs. HIGH haylage. A haylage quality × narasin and haylage quality × time of collection interactions were detected (P ≤ 0.03) for rumen ammonia concentration, which was reduced (P < 0.03) in N13 vs. N0 steers consuming HIGH haylage. Collectively, high-quality haylage allows increased consumption and digestibility, with more energy-efficient ruminal fermentation. In addition, narasin might be an important nutritional tool in forage-based diets to enhance the ruminal fermentation parameters of Bos indicus Nellore steers.
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  • 文章类型: Journal Article
    PdRuO2/PVP纳米材料使用简单的方法合成,并使用先进的分析方法如TEM,XRD,XPS,元素测绘和扫描电镜。合成的PdRuO2/PVP纳米材料被用作电位传感器电极中的离子载体,并成功地适应了大量含水样品中的Cr3离子检测。PdRuO2/PVP传感器的几个实验参数,如电位行为,选择性,重复性,响应时间,pH值,滴定,并对实际样品中的回收率进行了调查。在1×10-6-1.0×10-1M的浓度范围内进行电位测定行为特征。进行了六次重复实验表明,测量结果没有偏差。PdRuO2/PVP电位传感器的检测限非常低,值为8.6×10-8M。电位测量表明,合成的PdRuO2/PVP离子载体在宽pH范围内检测Cr3非常有效。2.0-8.0,发现保质期超过1年。因此,发现合成的PdRuO2/PVP电极材料具有高选择性,稳定,适用于Cr3+检测。
    PdRuO2/PVP nanomaterial was synthesized using a straightforward method and characterized using advanced analytical methods such as TEM, XRD, XPS, elemental mapping and SEM. The synthesized PdRuO2/PVP nanomaterial was used as an ionophore in potentiometric sensor electrodes and successfully adapted to Cr3+ ion detection in a large number of aqueous samples. Several experimental parameters of the PdRuO2/PVP sensor such as potentiometric behavior, selectivity, repeatability, response time, pH, titration, and recovery in real samples were investigated. Potentiometric behavioral characteristics were performed in the concentration range 1 × 10-6-1.0 × 10-1 M. The repeated experiments performed six times showed that there was no deviation in the measurements. The limit of detection of the PdRuO2/PVP potentiometric sensor was very low with a value of 8.6 × 10-8 M. The potentiometric measurements showed that the synthesized PdRuO2/PVP ionophore was highly effective in detecting Cr3+ in a wide pH range of 2.0-8.0 and was found to have a shelf life of over 1 year. As a result, the synthesized PdRuO2/PVP electrode material was found to be highly selective, stable, and applicable for Cr3+ detection.
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  • 文章类型: Journal Article
    离子载体是饲料添加剂,其通过破坏跨细胞膜的离子转移来减少革兰氏阳性微生物群体,从而导致改善的生长性能。Narasin(Skycis;Elanco动物保健,格林菲尔德,IN)是FDA批准的离子载体,用于增加生长肥育猪的增重率和改善饲料效率。进行了荟萃回归分析,以评估在生长育肥猪日粮中添加narasin的影响,以预测其对平均日增重(ADG)的影响。饲料效率(G:F),和car体产量。建立了一个包含21份技术报告的数据库,摘要,以及2012年至2021年的参考文献,代表了35项研究中对增长绩效数据的观察,研究长度为35至116d(总体数据)。此外,在这35个观察中,使用每周评估个体周期数据(143个观察值),每两周一次,或每月性能间隔(周期数据)。建立了回归模型方程,和预测变量通过逐步手动前向选择程序进行评估。使用总体数据的ADG模型包括ADG,ADFI,对照组的G:F,添加Narasin剂量,和narasin喂养持续时间分类为长于或短于65d。使用总体数据的G:F模型中包含的预测变量为ADG,ADFI,和G:对照组的F和添加的narasin剂量。对于car体产量,最终模型包括对照组的ADFI和G:F,添加Narasin剂量,和Narasin喂养持续时间超过65d。在ADG的周期模型中,预测因子包括ADG,ADFI,对照组的G:F,添加Narasin剂量,和对照组的平均BW分为大于或小于105kg。对于G:F的周期数据,选择ADG的模型,ADFI,和G:对照组的F和添加的narasin剂量。根据结果,ADG和G:F对添加narasin的总体反应是二次的,并且随着ADG和G:F的增加而趋于降低。对于各个周期数据观察到类似的二次响应。总之,使用数据库中的中值作为预测变量,这项荟萃分析表明,narasin有望将ADG提高1.06%至1.65%,G:F在0.71%和1.71%之间,连续饲喂超过65d时,car体产量降低0.31%。
    Ionophores are feed additives that decrease gram-positive microbial populations by disrupting the ion transfer across cell membranes resulting in improved growth performance. Narasin (Skycis; Elanco Animal Health, Greenfield, IN) is an FDA-approved ionophore utilized for increased rate of weight gain and improved feed efficiency in growing-finishing pigs. A meta-regression analysis was conducted to evaluate the effects of added narasin in growing-finishing pig diets to predict its influence on average daily gain (ADG), feed efficiency (G:F), and carcass yield. A database was developed containing 21 technical reports, abstracts, and refereed papers from 2012 to 2021 representing 35 observations for growth performance data in studies ranging from 35 to 116 d in length (overall data). In addition, within these 35 observations, individual period data were evaluated (143 observations) using weekly, bi-weekly, or monthly performance intervals (period data). Regression model equations were developed, and predictor variables were assessed with a stepwise manual forward selection procedure. The ADG model using the overall data included ADG, ADFI, and G:F of the control group, added narasin dose, and narasin feeding duration categorized as longer or shorter than 65 d. Predictor variables included in the G:F model using overall data were ADG, ADFI, and G:F of the control group and added narasin dose. For carcass yield, the final model included ADFI and G:F of the control group, added narasin dose, and narasin feeding duration of longer than 65 d. In the period model for ADG, the predictors included ADG, ADFI, and G:F of the control group, added narasin dose, and average BW of the control group categorized into greater than or less than 105 kg. For period data for G:F, the model selected ADG, ADFI, and G:F of the control group and added narasin dose. Based on the results, the overall response to added narasin for ADG and G:F was quadratic and tended to decrease as ADG and G:F increased. A similar quadratic response was observed for the individual period data. In summary, using median values from the database for predictor variables, this meta-analysis demonstrated narasin would be expected to improve ADG between 1.06% and 1.65%, G:F between 0.71% and 1.71%, and carcass yield by 0.31% when fed continuously for longer than 65 d.
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  • 文章类型: Journal Article
    微生物植物病原体部署两亲性环状脂肽以降低其环境中的表面张力。虽然植物可以检测到这些分子来激活细胞应激反应,这些脂肽或相关宿主反应在发病机制中的作用尚不完全清楚。禾本科青霉素环脂肽由禾本科镰刀菌真菌产生,是玉米中的毒力因子和毒素。这里,我们表明,gramillin通过破坏膜间的离子平衡来促进单子叶植物和双子叶植物的毒力和坏死。格拉姆林是阳离子传导离子载体,可引起质膜去极化。这种中断触发了蜂窝信号,包括活性氧(ROS)的爆发,转录重编程,和callose生产。格拉姆林诱导的ROS依赖于宿主ILK1和RBOHD基因的表达,在感染和宿主易感性过程中促进真菌对毒力基因的诱导。我们得出的结论是,gramillin的离子载体活性靶向植物膜,以协调F.graminearum真菌的攻击。
    Microbial plant pathogens deploy amphipathic cyclic lipopeptides to reduce surface tension in their environment. While plants can detect these molecules to activate cellular stress responses, the role of these lipopeptides or associated host responses in pathogenesis are not fully clear. The gramillin cyclic lipopeptide is produced by the Fusarium graminearum fungus and is a virulence factor and toxin in maize. Here, we show that gramillin promotes virulence and necrosis in both monocots and dicots by disrupting ion balance across membranes. Gramillin is a cation-conducting ionophore and causes plasma membrane depolarization. This disruption triggers cellular signaling, including a burst of reactive oxygen species (ROS), transcriptional reprogramming, and callose production. Gramillin-induced ROS depends on expression of host ILK1 and RBOHD genes, which promote fungal induction of virulence genes during infection and host susceptibility. We conclude that gramillin\'s ionophore activity targets plant membranes to coordinate attack by the F. graminearum fungus.
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  • 文章类型: Journal Article
    荧光纳米传感器彻底改变了诊断和我们监测细胞动力学的能力。然而,区分传感器信号从自发荧光仍然是一个挑战。这里,我们将基于光电探测器的传感与近红外发射的ZnGa2O4:Cr3+持久发光纳米粒子(PLNPs)结合起来,形成了用于无自发荧光“暗光发光”传感的纳米复合材料。疏水修饰并将持久性发光纳米颗粒掺入基于光电极的纳米颗粒核心中,产生了用于五种分析物(K,Na+,Ca2+,pH值,和O2)通过两种不同的机制。我们通过定量胎牛血清中的K来证明PLN的生存能力,校准相同的pH值PLN,并按比例监测酿酒酵母培养物中的O2代谢,同时克服他们各自的自发荧光特征。这个高度模块化的平台允许轻松调整传感功能,光学性质,和表面化学和承诺在复杂的光学环境高信噪比。
    Fluorescent nanosensors have revolutionized diagnostics and our ability to monitor cellular dynamics. Yet, distinguishing sensor signals from autofluorescence remains a challenge. Here, we merged optode-based sensing with near-infrared-emitting ZnGa2O4:Cr3+ persistent luminescence nanoparticles (PLNPs) to create nanocomposites for autofluorescence-free \"glow-in-the-dark\" sensing. Hydrophobic modification and incorporation of the persistent luminescence nanoparticles into an optode-based nanoparticle core yielded persistent luminescence nanosensors (PLNs) for five analytes (K+, Na+, Ca2+, pH, and O2) via two distinct mechanisms. We demonstrated the viability of the PLNs by quantifying K+ in fetal bovine serum, calibrating the pH PLNs in the same, and ratiometrically monitoring O2 metabolism in cultures of Saccharomyces cerevisiae, all the while overcoming their respective autofluorescence signatures. This highly modular platform allows for facile tuning of the sensing functionality, optical properties, and surface chemistry and promises high signal-to-noise ratios in complex optical environments.
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  • 文章类型: Journal Article
    Enniatins是真菌毒素,具有众所周知的抗菌作用,抗真菌药,抗蠕虫和抗病毒活性,最近作为潜在的线粒体毒性抗癌剂引起了人们的注意。Enniatins的细胞毒性可以追溯到离子通道性质,其中环缩肽结构产生了各种化学计量的nanniatin:阳离子复合物被提议作为膜活性物质。在这项工作中,我们采用了表面增强红外吸收(SEIRA)光谱的组合,系留双层脂质膜(tBLMs)和基于密度泛函理论(DFT)的计算光谱法监测阳离子依赖性(Mz=Na,K+,Cs+,Li+,Mg2+,Ca2)对EnniatinB(EB)掺入膜中的机制,并鉴定形成的功能相关的EBn:Mz复合物。我们发现Na+促进了合作合并,通过自催化机理建模,并由扭曲的2:1-EB2:Na复合物介导。由于采用了“理想的”EB2:K三明治复合物,K(和Cs)导致直接但效率较低的插入膜。相比之下,Li+的存在,Mg2+,和Ca2+通过形成“束带”1:1-EB:Mz+复合物,从膜中(部分)提取EB,从而较不有效地筛选阳离子电荷。我们的结果表明,阳离子依赖性与转运到发挥线粒体毒性抗癌活性的恶性细胞有关。
    Enniatins are mycotoxins with well-known antibacterial, antifungal, antihelmintic and antiviral activity, which have recently come to attention as potential mitochondriotoxic anticancer agents. The cytotoxicity of enniatins is traced back to ionophoric properties, in which the cyclodepsipeptidic structure results in enniatin:cation-complexes of various stoichiometries proposed as membrane-active species. In this work, we employed a combination of surface-enhanced infrared absorption (SEIRA) spectroscopy, tethered bilayer lipid membranes (tBLMs) and density functional theory (DFT)-based computational spectroscopy to monitor the cation-dependence (Mz+=Na+, K+, Cs+, Li+, Mg2+, Ca2+) on the mechanism of enniatin B (EB) incorporation into membranes and identify the functionally relevant EBn : Mz+ complexes formed. We find that Na+ promotes a cooperative incorporation, modelled via an autocatalytic mechanism and mediated by a distorted 2 : 1-EB2 : Na+ complex. K+ (and Cs+) leads to a direct but less efficient insertion into membranes due to the adoption of \"ideal\" EB2 : K+ sandwich complexes. In contrast, the presence of Li+, Mg2+, and Ca2+ causes a (partial) extraction of EB from the membrane via the formation of \"belted\" 1 : 1-EB : Mz+ complexes, which screen the cationic charge less efficiently. Our results point to a relevance of the cation dependence for the transport into the malignant cells where the mitochondriotoxic anticancer activity is exerted.
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  • 文章类型: Journal Article
    使用含有中性离子载体和阳离子交换剂的Na选择性溶剂聚合物(PVC)膜进行的电化学阻抗和计时电位测量显示出低频电阻,这归因于Na+离子跨膜和水溶液之间的界面转移。归属基于观察到的该电阻对溶液中Na浓度的规律依赖性。在非零电流模式的分析过程中,发现交换电流密度的相应值明显大于流过离子选择电极(ISE)的电流。这一事实表明,界面电化学平衡不会被电流破坏,并且意味着可以应用能斯特方程来解释在非零电流模式下获得的数据。例如,恒电位库仑法.
    Electrochemical impedance and chronopotentiometric measurements with Na+-selective solvent polymeric (PVC) membranes containing a neutral ionophore and a cation exchanger revealed low-frequency resistance, which is ascribed to Na+ ion transfer across the interface between the membrane and aqueous solution. The attribution is based on the observed regular dependence of this resistance on the concentration of Na+ in solutions. The respective values of the exchange current densities were found to be significantly larger than the currents flowing through ion-selective electrodes (ISEs) during an analysis in non-zero-current mode. This fact suggests that the interfacial electrochemical equilibrium is not violated by the current flow and implies that the Nernst equation can be applied to interpret the data obtained in non-zero-current mode, e.g., constant potential coulometry.
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  • 文章类型: Journal Article
    饲料添加剂如莫能菌素(MON)和维吉尼亚霉素(VM)通常用于饲粮中以增强瘤胃发酵。然而,MON和VM在特定饲养期的确切效果以及这种组合的优势尚不清楚.本研究旨在研究MON在适应期和精加工期与VM相关的戒断对瘤胃代谢的影响。喂养行为,和内洛尔牛的养分消化率。实验设计为5×5拉丁方,每个时期持续28天。使用了五只瘤胃插管的Nellore一岁公牛(体重414,86±21,71千克),将其分配给五种处理:(1)整个喂养期间的MON;(2)整个喂养期间的VM;(3)适应期的MONVM,在整理期1和2期间仅VM;(4)整个喂养期的MONVM;(5)适应和整理期1期间的MONVM,在整理期2期间仅VM。对于结束期1,饲喂T3的动物具有改善的干物质的潜在降解性(p=0.02)。与接受T2的动物相比,饲喂T3和T5的牛具有最高的粗蛋白降解能力(p=0.01)。饲喂T2和T3的动物在pH6.2(p=0.02)下减少了时间(p<0.01)和面积。此外,与以T2,T3和T5为食的动物相比,以T4为食的动物具有更大的Diplodinium属原生动物种群(p=0.04)。对于整理期2,当与接受T4和T5的动物相比时,饲喂T3的动物具有更大的淀粉降解性(p=0.04)。饲喂T3、T4和T5的动物增加了pH低于5.6的持续时间(p=0.03)。饲喂T3的动物的瘤胃pH5.2和pH5.6的曲线下面积较高(p=0.01),与接受T2的动物相比,饲喂T3和T5的动物在pH6.2下的面积更高(p<0.01)。通过同时利用MON和VM分子对瘤胃发酵参数没有实质性改善,其中较高的淀粉和蛋白质降解性并没有改善瘤胃发酵。
    Feed additives such as monensin (MON) and virginiamycin (VM) are commonly utilized in feedlot diets to enhance rumen fermentation. Nevertheless, the precise effects of combining MON and VM during specific feedlot periods and the advantages of this combination remain unclear. This study was designed to investigate the effects of withdrawal of MON when associated with VM during the adaptation and finishing periods on ruminal metabolism, feeding behavior, and nutrient digestibility in Nellore cattle. The experimental design was a 5 × 5 Latin square, where each period lasted 28 days. Five rumen-cannulated Nellore yearling bulls were used (414,86 ± 21,71 kg of body weight), which were assigned to five treatments: (1) MON during the entire feeding period; (2) VM during the entire feeding period; (3) MON + VM during the adaptation period and only VM during the finishing period 1 and 2; (4) MON + VM during the entire feeding period; (5) MON + VM during the adaptation and finishing period 1 and only VM during the finishing period 2. For the finishing period 1, animals fed T3 had improved potential degradability of dry matter (p = 0.02). Cattle fed T3 and T5 had the highest crude protein degradability when compared to animals receiving T2 (p = 0.01). Animals fed T2 and T3 had reduced the time (p < 0.01) and area under pH 6.2 (p = 0.02). Moreover, animals fed T4 had greater population of protozoa from the genus Diplodinium (p = 0.04) when compared to those from animals fed T2, T3 and T5. For the finishing period 2, animals fed T3 had greater starch degradability when compared to animals receiving T4 and T5 (p = 0.04). Animals fed T3, T4 and T5 had increased the duration of time in which pH was below 5.6 (p = 0.03). The area under the curve for ruminal pH 5.2 and pH 5.6 was higher for the animals fed T3 (p = 0.01), and the area under pH 6.2 was higher for the animals fed T3 and T5 (p < 0.01) when compared to animals receiving T2. There is no substantial improvement on the rumen fermentation parameters by the concurrent utilization of MON and VM molecules, where the higher starch and protein degradability did not improve the rumen fermentation.
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  • 文章类型: Journal Article
    羧酸聚醚离子载体(CPIs)是最普遍的农业抗生素(特别是在美国),并且这些化合物已经使用了几十年。重新定位超出兽医用途的CPI的潜力,例如,通过化学修饰来增强其选择性窗口,是一个令人兴奋的挑战和机遇,考虑到他们对阻力发展的总体韧性。考虑到这些有点争议的化合物的巨大社会影响,令人惊讶的是,它们在细胞中的机制和活性的许多方面仍不清楚。这里,我们报告了CPIroutiennocin和两种立体异构体的比较生物活性,包括其对映异构体。我们使用了一种有效的聚合合成策略来获得这些化合物,并对针对浮游细胞和生物膜的抗菌活性以及化合物对哺乳动物细胞的影响进行了广泛的调查。后者通过标准细胞活力测定和广泛的形态学分析进行评估。有趣的是,在所有测定中观察到对映体对的相似生物活性,强烈表明手性相互作用在作用方式中不起决定性作用。总的来说,我们的发现与涉及细胞膜中CPIs高度动态行为的机械模型一致。
    Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in the US) and these compounds have been in use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications to enhance their selectivity window, is an exciting challenge and opportunity, considering their general resilience towards resistance development. Given the very large societal impact of these somewhat controversial compounds, it is surprising that many aspects of their mechanisms and activities in cells remain unclear. Here, we report comparative biological activities of the CPI routiennocin and two stereoisomers, including its enantiomer. We used an efficient convergent synthesis strategy to access the compounds and conducted a broad survey of antibacterial activities against planktonic cells and biofilms as well as the compounds\' effects on mammalian cells, the latter assessed both via standard cell viability assays and broad morphological profiling. Interestingly, similar bioactivity of the enantiomeric pair was observed across all assays, strongly suggesting that chiral interactions do not play a decisive role in the mode of action. Overall, our findings are consistent with a mechanistic model involving highly dynamic behaviour of CPIs in biological membranes.
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