Kinetics

动力学
  • 文章类型: Journal Article
    正在研究通过使用浮力水生植物(Dal杂草)从水中消除氟化物的有效且经济的方法。实施了两种热解后化学活化改变技术:使用硫酸进行酸性活化(H活化)和使用氢氧化钠进行碱性活化(OH活化)。考虑到不同的起始氟化物水平,例如2-10mg/L,已经进行了分批动力学研究。不同程序因素的影响,包括Dal杂草的剂量,起始氟化物水平,观察pH和接触持续时间以确定它们对氟化物吸附动力学的影响。根据分析的探索性结果,在开始氟含量为10mg/L时,OH-活性炭的去除率为63%,H-活性炭的去除率为83%,吸附剂用量0.8g,在25°C下120分钟后。观察到H-活性炭的最大氟化物吸收能力为78.158mg/g。动力学研究表明,Freundlich等温线模型提供了令人满意的匹配,R2值为0.99。反应顺序性质与动力学类似,类似于伪二阶。热力学研究显示吸热吸附,负ΔG表示自发的氟化物吸收。相比之下,ΔS的正数表明在涉及吸附剂和被吸附物的接触处具有随机行为。对吸附材料的再生能力的研究表明,即使在经历了五个连续的吸附和再生循环之后,吸附剂表现出45%的吸收潜力。溶液中竞争离子的存在对除氟效率产生负面影响,其影响遵循HCO3- An efficient and economical way of eliminating fluoride from water is being investigated by employing the buoyant aquatic plant (Dal weed). Two post-pyrolysis chemical activation alteration techniques were implemented: acidic activation by employing sulfuric acid (H-activation) and alkaline activation using sodium hydroxide (OH-activation). The batch kinetic studies have been carried out considering varying starting fluoride levels such as 2 - 10 mg/L. The impact of diverse procedural factors, including dosage of Dal weed, starting fluoride level, pH and contact duration was observed to determine their influence on fluoride adsorption kinetics. Based on analyzed exploratory results, removal efficacy of 63% for the OH-activated carbon and 83% for H-activated carbon was achieved at commencing fluoride level of 10 mg/L, adsorbent dosage of 0.8 g, at 25 °C after 120 minutes. The maximal fluoride uptake capacity for H-activated carbon was observed to be 78.158 mg/g. Kinetic investigations showed that the Freundlich isotherm model provided a satisfactory match with an R2 value of 0.99. The reaction order nature adhered to kinetics resembling pseudo second order. Thermodynamic investigation revealed endothermic sorption, with negative ΔG indicating spontaneous fluoride uptake. In comparison, the positive number for ΔS suggested random behavior at the contact involving the adsorbent and adsorbate. The investigations into the regeneration capabilities of the adsorbent material revealed that even after undergoing for five consecutive cycles of adsorption and regeneration, the adsorbent exhibited an uptake potential of 45%. The presence of competing ions in the solution negatively impacted defluoridation efficacy, with the influence following the order of HCO3-< NO3-< Cl-< SO42-< PO43-.
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  • 文章类型: Journal Article
    SolarFenton是一种重要且广泛使用的高级氧化工艺(AOP),用于降解药物污染物。本研究的目的是评估混合污染物(阿莫西林,对乙酰氨基酚,和环丙沙星)用于使用太阳能Fenton工艺的水溶液。操作参数,如pH,铁剂量,H2O2剂量,污染物浓度,研究了时间。从实验结果来看,获得了去除混合污染物的理想条件,如pH3,Fe2+0.04mM,H2O24mM,混合污染物的浓度为5mg/L,太阳辐射400W/m2,时间10分钟,分别。利用伪一级动力学研究了混合污染物的降解效率。研究结果表明,混合污染物的降解效率>99%。观察到最大63%的矿化,和羟基自由基清除剂的效果进行了研究。最佳条件用于评估加标废水(市政废水(MWW)和医院废水(HWW))。AMX的最高消除率,ACET,和CIP为65%,89%,MWW占85%,76%,92%,HWW占80%,分别。通过LC-ESI-MS在水基质(水溶液和加标废水)中检测降解的副产物,并对转化产物进行了ECOSAR分析。研究得出的结论是,太阳能Fenton技术对于去除水基质中的混合污染物是有前途且有效的。
    Solar Fenton is an important and extensively used advanced oxidation process (AOP) to degrade pharmaceutical pollutants. The objective of this study was to evaluate the performance of simultaneous degradation of the mixed pollutants (amoxicillin, acetaminophen, and ciprofloxacin) for an aqueous solution using the solar Fenton process. Operating parameters such as pH, iron doses, H2O2 doses, pollutant concentrations, and time were studied. From the experimental results, the ideal conditions were obtained for the removal of mixed pollutants such as pH 3, Fe2+ 0.04 mM, H2O2 4 mM, the concentration of the mixed pollutants 5 mg/L, solar radiation 400 W/m2, and time 10 min, respectively. The pseudo-first-order kinetics were utilized to investigate the degradation efficacy of the mixed pollutants. The result of the study indicates that the degradation efficiency was > 99% for the mixed pollutants. A maximum of 63% mineralization was observed, and hydroxyl radical scavenger effects were studied. The best optimal conditions were applied to assess the spiked wastewater (municipal wastewater (MWW) and hospital wastewater (HWW)). The highest elimination rates for AMX, ACET, and CIP were observed as 65%, 89%, and 85% for MWW and 76%, 92%, and 80% for HWW, respectively. The degraded by-products were detected by LC-ESI-MS in the water matrix (aqueous solution and spiked wastewater), and ECOSAR analysis was performed for the transformed products. The study concluded that the solar Fenton technique is promising and effective for the removal of mixed pollutants from the water matrix.
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  • 文章类型: Journal Article
    镁离子(Mg2+)在利用具有二磷酸基团的底物的II类萜烯环化酶中是至关重要的。有趣的是,这些酶催化不裂解二磷酸基团的反应,而是通过质子化引发反应。在我们最近的研究中,我们在showdoensis链霉菌中发现了一种新型的II类倍半萜环化酶。值得注意的是,我们确定了其晶体结构,并在其活性位点内鉴定了Mg2。这一发现揭示了先前难以捉摸的II类萜烯环化酶中Mg2结合的问题。在这一章中,我们概述了我们发现这种新型酶的方法,包括其纯化步骤,结晶,和动力学分析。
    Magnesium ions (Mg2+) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without cleaving the diphosphate group, instead initiating the reaction through protonation. In our recent research, we discovered a novel class II sesquiterpene cyclase in Streptomyces showdoensis. Notably, we determined its crystal structure and identified Mg2+ within its active site. This finding has shed light on the previously elusive question of Mg2+ binding in class II terpene cyclases. In this chapter, we outline our methods for discovering this novel enzyme, including steps for its purification, crystallization, and kinetic analysis.
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  • 文章类型: Journal Article
    超分辨率成像,尤其是单分子定位方法,引发了一场荧光团工程革命,追逐稀疏的单分子暗亮闪烁变换。然而,从结构上设计荧光团操纵单分子闪烁动力学是一个挑战。在这种追求中,我们通过将可光活化的亚硝基笼式策略创新地整合到自闪烁的磺酰胺中以形成亚硝基笼式磺酰胺罗丹明(NOSR)来开发触发策略。我们的荧光团在光触发的笼式单元释放后表现出可控的自闪烁事件。与自闪烁类似物相比,这种出色的闪烁动力学改善了微管的超分辨率成像完整性。借助最重要的单分子荧光动力学,我们成功地重建了核孔的环状结构和线粒体外膜的轴向形态。我们预见,我们的光活化和自闪烁的合成方法将有助于罗丹明设计超分辨率成像。
    Super-resolution imaging, especially a single-molecule localization approach, has raised a fluorophore engineering revolution chasing sparse single-molecule dark-bright blinking transforms. Yet, it is a challenge to structurally devise fluorophores manipulating the single-molecule blinking kinetics. In this pursuit, we have developed a triggering strategy by innovatively integrating the photoactivatable nitroso-caging strategy into self-blinking sulfonamide to form a nitroso-caged sulfonamide rhodamine (NOSR). Our fluorophore demonstrated controllable self-blinking events upon phototriggered caging unit release. This exceptional blink kinetics improved the super-resolution imaging integrity on microtubules compared to self-blinking analogues. With the aid of paramount single-molecule fluorescence kinetics, we successfully reconstructed the ring structure of nuclear pores and the axial morphology of mitochondrial outer membranes. We foresee that our synthetic approach of photoactivation and self-blinking would facilitate rhodamine devising for super-resolution imaging.
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  • 文章类型: Journal Article
    应变碳环结构单元的合成与药物化学有关,和亚甲基环丁烷在当前的合成技术中尤其具有挑战性。仔细检查[1.1.1]推进剂和二硼试剂的反应性,发现双(儿茶酚)二硼(B2cat2)可以在室温下在几分钟内产生双(硼化)亚甲基环丁烷。该反应构成了通过特殊的非极性烃活化B-B键的第一个例子,也是第一次用硼亲电活化推进剂。包括原位NMR动力学和DFT计算在内的机理研究表明,二硼部分可以通过与推进剂的倒σ键配位而直接活化。并揭示DMF参与二硼酸酯中间体的稳定而不是B-B键的活化。这些结果为二硼和推进剂化学提供了新的可能性,并进一步发展了基于推进剂菌株释放的亚甲基环丁烷的合成。
    The synthesis of strained carbocyclic building blocks is relevant for Medicinal Chemistry, and methylenecyclobutanes are particularly challenging with current synthetic technology. Careful inspection of the reactivity of [1.1.1]propellane and diboron reagents has revealed that bis(catecholato)diboron (B2cat2) can produce a bis(borylated) methylenecyclobutane in a few minutes at room temperature. This reaction constitutes the first example of B-B bond activation by a special apolar hydrocarbon and also the first time that propellane is electrophilically activated by boron. Mechanistic studies including in situ NMR kinetics and DFT calculations demonstrate that the diboron moiety can be directly activated through coordination with the inverted sigma bond of propellane, and reveal that DMF is involved in the stabilization of diboronate ylide intermediates rather than the activation of the B-B bond. These results enable new possibilities for both diboron and propellane chemistry, and for further developments in the synthesis of methylenecyclobutanes based on propellane strain release.
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  • 文章类型: Journal Article
    众所周知,呼吸道含有包括细菌在内的微生物群落,病毒,和真菌。新技术对鉴定未知或与培养无关的物种做出了巨大贡献,并揭示了群落与宿主免疫系统的相互作用。现有的呼吸道微生物组和来自供体肺移植物的移植微生物组的基本平衡提供了肺移植(LT)受体中微环境动态变化的极端爆发。移植物中的菌群失调不仅与修饰的微生物成分有关,而且还涉及宿主移植物的动力学。“这标志着移植物移植损伤的目的地,急性排斥反应,感染,和长期生存的慢性同种异体移植功能障碍发展。当使用基因修饰的猪来源的器官时,微生物组来源的因子可能有助于肺异种移植物的存活。这里,我们回顾了各种移植前适应症的移植肺中微生物群落的动力学和弹性的最先进的知识。概念和分析观点已经沿着时间序列进行了说明,深入了解微生物组和肺移植物。未来在精密工具上的努力,复杂的模型,需要新的靶向治疗方案来改善这些患者的长期生存率.
    The respiratory tract is known to harbor a microbial community including bacteria, viruses, and fungi. New techniques contribute enormously to the identification of unknown or culture-independent species and reveal the interaction of the community with the host immune system. The existing respiratory microbiome and substantial equilibrium of the transplanted microbiome from donor lung grafts provide an extreme bloom of dynamic changes in the microenvironment in lung transplantation (LT) recipients. Dysbiosis in grafts are not only related to the modified microbial components but also involve the kinetics of the host-graft \"talk,\" which signifies the destination of graft allograft injury, acute rejection, infection, and chronic allograft dysfunction development in short- and long-term survival. Microbiome-derived factors may contribute to lung xenograft survival when using genetically multimodified pig-derived organs. Here, we review the most advanced knowledge of the dynamics and resilience of microbial communities in transplanted lungs with various pretransplant indications. Conceptual and analytical points of view have been illustrated along the time series, gaining insight into the microbiome and lung grafts. Future endeavors on precise tools, sophisticated models, and novel targeted regimens are needed to improve the long-term survival in these patients.
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  • 文章类型: Journal Article
    股骨髋臼撞击综合征(FAIS)可引起髋关节疼痛和软骨唇损伤,可通过非手术或手术治疗。蹲下运动需要较大的髋关节屈曲度,并支持许多日常和运动任务,但可能会导致髋关节撞击并引起疼痛。以前尚未研究过物理治疗师主导的护理和关节镜对下蹲过程中生物力学的差异影响。这项研究探讨了在物理治疗师主导的干预下治疗的FAIS患者在下蹲时运动学和时间12个月变化的差异(个性化髋关节治疗,PHT)和关节镜检查。
    在多中心注册的FAIS参与者的子样本(n=36),务实,双臂优势随机对照试验在基线下蹲期间和随机分配至PHT(n=17)或关节镜(n=19)后12个月进行了三维运动分析.时间序列和峰值树干的变化,骨盆,和髋关节生物力学,研究了治疗组之间的下蹲速度和最大深度。
    在PHT组和关节镜组之间没有检测到12个月变化的显着差异。与基线相比,关节镜组随访时蹲下较慢(下降:平均差-0.04m·s-1(95CI[-0.09~0.01]);上升:-0.05m·s-1[-0.11~0.01]%)。在组间或组内未检测到深蹲深度的差异。调整速度后,与基线相比,随访时两个治疗组的躯干屈曲均更大(下降:PHT7.50°[-14.02至-0.98]%;上升:PHT7.29°[-14.69至0.12]%,关节镜16.32°[-32.95至0.30]%)。与基线相比,两个治疗组均显示前骨盆倾斜减少(下降:PHT8.30°[0.21-16.39]%,关节镜-10.95°[-5.54至16.34]%;上升:PHT-7.98°[-0.38至16.35]%,关节镜-10.82°[3.82-17.81]%),髋关节屈曲(下降:PHT-11.86°[1.67-22.05]%,关节镜-16.78°[8.55-22.01]%;上升:PHT-12.86°[1.30-24.42]%,关节镜-16.53°[6.72-26.35]%),和膝关节屈曲(下降:PHT-6.62°[0.56-12.67]%;上升:PHT-8.24°[2.38-14.10]%,关节镜-8.00°[-0.02至16.03]%)。与基线相比,PHT组在随访时在深蹲过程中表现出更多的pi屈(-3.58°[-0.12至7.29]%)。与基线相比,两组在随访时都表现出较低的外髋屈曲力矩(下降:PHT-0.55N·m/BW·HT[%][0.05-1.05]%,关节镜-0.84N·m/BW·HT[%][0.06-1.61]%;上升:PHT-0.464N·m/BW·HT[%][-0.002至0.93]%,关节镜-0.90N·m/BW·HT[%][0.13-1.67]%)。
    探索性数据表明,在12个月的随访中,PHT或髋关节镜检查在引起躯干变化方面均不优越,骨盆,或下肢生物力学。两种治疗方法都可能引起运动学和力矩的变化,然而,这些变化的影响是未知的。
    澳大利亚新西兰临床试验注册中心参考:ACTRN12615001177549。审判登记2015年2月11日。
    UNASSIGNED: Femoroacetabular impingement syndrome (FAIS) can cause hip pain and chondrolabral damage that may be managed non-operatively or surgically. Squatting motions require large degrees of hip flexion and underpin many daily and sporting tasks but may cause hip impingement and provoke pain. Differential effects of physiotherapist-led care and arthroscopy on biomechanics during squatting have not been examined previously. This study explored differences in 12-month changes in kinematics and moments during squatting between patients with FAIS treated with a physiotherapist-led intervention (Personalised Hip Therapy, PHT) and arthroscopy.
    UNASSIGNED: A subsample (n = 36) of participants with FAIS enrolled in a multi-centre, pragmatic, two-arm superiority randomised controlled trial underwent three-dimensional motion analysis during squatting at baseline and 12-months following random allocation to PHT (n = 17) or arthroscopy (n = 19). Changes in time-series and peak trunk, pelvis, and hip biomechanics, and squat velocity and maximum depth were explored between treatment groups.
    UNASSIGNED: No significant differences in 12-month changes were detected between PHT and arthroscopy groups. Compared to baseline, the arthroscopy group squatted slower at follow-up (descent: mean difference -0.04 m∙s-1 (95%CI [-0.09 to 0.01]); ascent: -0.05 m∙s-1 [-0.11 to 0.01]%). No differences in squat depth were detected between or within groups. After adjusting for speed, trunk flexion was greater in both treatment groups at follow-up compared to baseline (descent: PHT 7.50° [-14.02 to -0.98]%; ascent: PHT 7.29° [-14.69 to 0.12]%, arthroscopy 16.32° [-32.95 to 0.30]%). Compared to baseline, both treatment groups exhibited reduced anterior pelvic tilt (descent: PHT 8.30° [0.21-16.39]%, arthroscopy -10.95° [-5.54 to 16.34]%; ascent: PHT -7.98° [-0.38 to 16.35]%, arthroscopy -10.82° [3.82-17.81]%), hip flexion (descent: PHT -11.86° [1.67-22.05]%, arthroscopy -16.78° [8.55-22.01]%; ascent: PHT -12.86° [1.30-24.42]%, arthroscopy -16.53° [6.72-26.35]%), and knee flexion (descent: PHT -6.62° [0.56- 12.67]%; ascent: PHT -8.24° [2.38-14.10]%, arthroscopy -8.00° [-0.02 to 16.03]%). Compared to baseline, the PHT group exhibited more plantarflexion during squat ascent at follow-up (-3.58° [-0.12 to 7.29]%). Compared to baseline, both groups exhibited lower external hip flexion moments at follow-up (descent: PHT -0.55 N∙m/BW∙HT[%] [0.05-1.05]%, arthroscopy -0.84 N∙m/BW∙HT[%] [0.06-1.61]%; ascent: PHT -0.464 N∙m/BW∙HT[%] [-0.002 to 0.93]%, arthroscopy -0.90 N∙m/BW∙HT[%] [0.13-1.67]%).
    UNASSIGNED: Exploratory data suggest at 12-months follow-up, neither PHT or hip arthroscopy are superior at eliciting changes in trunk, pelvis, or lower-limb biomechanics. Both treatments may induce changes in kinematics and moments, however the implications of these changes are unknown.
    UNASSIGNED: Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549. Trial registered 2/11/2015.
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  • 文章类型: Journal Article
    细胞色素c'-α是来自细菌的一氧化氮(NO)结合血红素蛋白,可以在广泛的温度环境中茁壮成长。嗜温的产碱菌木氧化素细胞色素c'-α(AxCP-α)的研究揭示了涉及两个血红素面的不寻常的NO结合机制,其中NO首先结合以形成远端六坐标Fe(II)-NO(6cNO)中间体,然后置换近端His以形成近端五坐标Fe(II)-NO(5cNO)最终产物。在这里,我们表征了来自嗜热嗜氢性嗜热嗜氢细胞色素c'-α(PhCP-α)的热稳定细胞色素c'-α,以了解蛋白质热稳定性如何影响NO结合。电子顺磁性和共振拉曼光谱揭示了PhCP-α5cNO产物的形成,具有时间分辨(停流)UV-可见光吸收,表明涉及6cNO中间体。相对于AxCP-α,PhCP-α中6cNO和5cNO形成的速率分别低11倍和13倍,分别。值得注意的是,在存在和不存在NO的情况下,PhCP-α的X射线晶体结构表明,近端5cNO产物的缓慢形成是由构象刚性引起的:Arg-132残基(与近端His配体相邻)通过Arg-75和Glu-135之间的盐桥(AxCP-α或嗜冷对应物中不存在的相互作用)。总的来说,我们的数据为控制血红素蛋白中NO结合的结构因素提供了新的见解,包括与真核NO传感器相关的5cNO复合物。
    Cytochromes c\'-α are nitric oxide (NO)-binding heme proteins derived from bacteria that can thrive in a wide range of temperature environments. Studies of mesophilic Alcaligenes xylosoxidans cytochrome c\'-α (AxCP-α) have revealed an unusual NO-binding mechanism involving both heme faces, in which NO first binds to form a distal hexa-coordinate Fe(II)-NO (6cNO) intermediate and then displaces the proximal His to form a proximal penta-coordinate Fe(II)-NO (5cNO) final product. Here we characterize a thermally stable cytochrome c\'-α from thermophilic Hydrogenophilus thermoluteolus (PhCP-α) to understand how protein thermal stability affects NO binding. Electron paramagnetic and resonance Raman spectroscopies reveal the formation of a PhCP-α 5cNO product, with time-resolved (stopped-flow) UV-visible absorbance indicating the involvement of a 6cNO intermediate. Relative to AxCP-α, the rates of 6cNO and 5cNO formation in PhCP-α are ∼11-fold and ∼13-fold lower, respectively. Notably, X-ray crystal structures of PhCP-α in the presence and absence of NO suggest that the sluggish formation of the proximal 5cNO product results from conformational rigidity: the Arg-132 residue (adjacent to the proximal His ligand) is held in place by a salt bridge between Arg-75 and Glu-135 (an interaction not present in AxCP-α or a psychrophilic counterpart). Overall, our data provide fresh insights into structural factors controlling NO binding in heme proteins, including 5cNO complexes relevant to eukaryotic NO sensors.
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  • 文章类型: Journal Article
    本文研究了以氨甲基膦酸(AMPA)为吸附剂的氧化石墨烯从水溶液中吸附钍的动力学研究。首先,使用TEM对AMPA-GO吸附剂进行了表征,XRD,和FTIR方法。实验以两种间歇和连续模式进行。在批处理模式下,研究了在不同pH(1-4)下的吸附动力学,温度(298-328K),初始浓度(50-500mgL-1),和剂量(0.1-2gL-1)。结果表明,钍吸附动力学符合拟一级动力学模型,吸附反应是吸热的。在pH为3,吸附剂用量为0.5gL-1,温度为328K时,观察到对钍离子的最大实验吸附容量为138.84mgg-1。结果表明,AMPA-GO吸附剂可以使用7次,吸附容量变化可接受。在连续条件下,进料流量的影响(2-8mLmin-1),初始浓度(50-500mgL-1),和柱床高度(2-8厘米)进行了调查。使用Thomas分析了连续数据,Yoon-Nelson,和Bohart-Adams模特.色谱柱的实验数据与Thomas,和Yoon-Nelson模型.研究结果表明,使用功能化的氧化石墨烯吸附剂具有很大的去除水溶液中钍的能力。
    This article investigated the kinetic studies of thorium adsorption from an aqueous solution with graphene oxide functionalized with aminomethyl phosphonic acid (AMPA) as an adsorbent. First, the AMPA-GO adsorbent was characterized using TEM, XRD, and FTIR methods. Experiments were performed in two batch and continuous modes. In batch mode, adsorption kinetics were studied in different pH (1-4), temperature (298-328 K), initial concentration (50-500 mg L-1), and dosages (0.1-2 g L-1). The results showed that thorium adsorption kinetic follows pseudo-first-order kinetic model and that the adsorption reaction is endothermic. The maximum experimental adsorption capacity of thorium ions was observed 138.84 mg g-1 at a pH of 3, adsorbent dosage of 0.5 g L-1, and a temperature of 328 K. The results showed that AMPA-GO adsorbent can be used seven times with an acceptable change in adsorption capacity. In continuous conditions, the effect of feed flow rate (2-8 mL min-1), initial concentration (50-500 mg L-1), and column bed height (2-8 cm) was investigated. The continuous data was analyzed using the Thomas, Yoon-Nelson, and Bohart-Adams models. The experimental data of the column were well matched with the Thomas, and Yoon-Nelson models. The research results showed that the use of functionalized graphene oxide adsorbents has a great ability to remove thorium from aqueous solutions.
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  • 文章类型: Journal Article
    人胰岛淀粉样多肽(hIAPP)的聚集有助于2型糖尿病(T2D)的发展和进展。hIAPP在体外以数微摩尔浓度在数小时内聚集,但在体内以毫摩尔浓度存在。因此,天然存在的hIAPP聚集抑制剂可提供针对与T2D相关的淀粉样蛋白形成的药物设计模型。这里,我们描述了低pH的综合能力,锌,和胰岛素抑制hIAPP纤颤。胰岛素剂量依赖性地减缓在中性pH附近的hIAPP聚集,但在酸性pH下对聚集动力学的影响较小。我们确定胰岛素以两种方式改变hIAPP聚集。首先,胰岛素将聚集途径转向具有ThT阳性分子结构的大型非纤维状聚集体,而不是淀粉样纤维。第二,可溶性胰岛素抑制hIAPP二聚体形成,这是一个重要的早期聚集事件。Further,我们观察到锌显著调节胰岛素对hIAPP聚集的抑制作用。我们假设这种作用是由控制胰岛素的寡聚状态引起的,并且表明hIAPP与单体胰岛素的相互作用比寡聚胰岛素更强。
    Aggregation of the human islet amyloid polypeptide (hIAPP) contributes to the development and progression of Type 2 Diabetes (T2D). hIAPP aggregates within a few hours at few micromolar concentration in vitro but exists at millimolar concentrations in vivo. Natively occurring inhibitors of hIAPP aggregation might therefore provide a model for drug design against amyloid formation associated with T2D. Here, we describe the combined ability of low pH, zinc, and insulin to inhibit hIAPP fibrillation. Insulin dose-dependently slows hIAPP aggregation near neutral pH but had less effect on the aggregation kinetics at acidic pH. We determine that insulin alters hIAPP aggregation in two manners. First, insulin diverts the aggregation pathway to large nonfibrillar aggregates with ThT-positive molecular structure, rather than to amyloid fibrils. Second, soluble insulin suppresses hIAPP dimer formation, which is an important early aggregation event. Further, we observe that zinc significantly modulates the inhibition of hIAPP aggregation by insulin. We hypothesize that this effect arose from controlling the oligomeric state of insulin and show that hIAPP interacts more strongly with monomeric than oligomeric insulin.
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