Multiple mechanisms

  • 文章类型: Journal Article
    亚硒酸盐微生物还原成元素硒纳米颗粒(SeNP)被认为是亚硒酸盐对许多细菌的有效解毒过程。在这项研究中,变液杆菌。ES129和海洋芽孢杆菌。选择具有高亚硒酸盐还原效率或耐受性的ES111用于系统和比较研究其在亚硒酸盐去除和有价值的SeNPs回收中的性能。亚硒酸盐还原的动力学监测表明,在ES129的浓度为4.24mM和ES111的浓度为4.88mM时,亚硒酸盐向SNP的转化效率最高。超显微分析表明,ES111和ES129产生的SeNPs已在细胞质中形成,随后通过细胞裂解过程释放到细胞外空间。此外,转录组分析表明,参与杆菌锂醇生物合成的基因的表达,硒化合物代谢和脯氨酸代谢在亚硒酸盐还原过程中显著上调,这表明亚硒酸盐向Se0的转化可能涉及多种途径。此外,与核苷酸切除修复和抗氧化相关酶相关的基因的上调可能增强细菌对亚硒酸盐的耐受性。一般来说,探索高耐亚硒酸盐细菌的亚硒酸盐还原和耐受机制,对于有效利用微生物进行环境修复具有重要意义。
    The microbial reduction of selenite to elemental selenium nanoparticles (SeNPs) is thought to be an effective detoxification process of selenite for many bacteria. In this study, Metasolibacillus sp. ES129 and Oceanobacillus sp. ES111 with high selenite reduction efficiency or tolerance were selected for systematic and comparative studies on their performance in selenite removal and valuable SeNPs recovery. The kinetic monitoring of selenite reduction showed that the highest transformation efficiency of selenite to SeNPs was achieved at a concentration of 4.24 mM for ES129 and 4.88 mM for ES111. Ultramicroscopic analysis suggested that the SeNPs produced by ES111 and ES129 had been formed in cytoplasm and subsequently released to extracellular space through cell lysis process. Furthermore, the transcriptome analysis indicated that the expression of genes involved in bacillithiol biosynthesis, selenocompound metabolism and proline metabolism were significantly up-regulated during selenite reduction, suggesting that the transformation of selenite to Se0 may involve multiple pathways. Besides, the up-regulation of genes associated with nucleotide excision repair and antioxidation-related enzymes may enhance the tolerance of bacteria to selenite. Generally, the exploration of selenite reduction and tolerance mechanisms of the highly selenite-tolerant bacteria is of great significance for the effective utilization of microorganisms for environmental remediation.
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  • 文章类型: Journal Article
    目的:内在皮肤老化是一个不可避免的过程,在真皮-表皮连接(DEJ)中,细胞外基质沉积减少,机械完整性受损。透明质酸是最有前途的天然成分之一。在这项研究中,揭示了新型透明质酸复合物对抗内在皮肤老化的多种机制。
    方法:采用免疫组织化学分析和酶联免疫吸附试验评价低分子量透明质酸钠的效果。其乙酰化衍生物和HA复合物对正常人成纤维细胞中基质金属蛋白酶-1(MMP-1)和I型胶原的表达。然后,进行了免疫组织化学分析和苏木精和伊红染色,以评估HA复合物在重建皮肤等效物中的相同效果,以及它对组织学结构和DEJ的好处。
    结果:在正常人真皮成纤维细胞中,透明质酸复合物,其中含有低分子量透明质酸钠及其乙酰化衍生物,通过增加I型胶原表达具有协同作用。同时,MMP-1的产生受到抑制。这在随后的皮肤等效实验中得到了证实,有趣的是,还发现透明质酸复合物可增加两种DEJ蛋白的表达。
    结论:本概念验证研究中的多机制透明质酸复合物通过抑制MMP-1的表达,增强I型胶原的积累和DEJ蛋白的表达,在体外表现出皮肤抗衰老作用。这揭示了研究各种类型透明质酸更多生物活性的新途径。
    OBJECTIVE: Intrinsic skin aging is an inevitable process with reduced extracellular matrix deposition and impaired mechanical integrity in the dermal-epidermal junction (DEJ). Hyaluronan is one of the most promising natural ingredients. In this research, multiple mechanisms of a novel hyaluronan complex against intrinsic skin aging were revealed.
    METHODS: Immunohistochemical analysis and enzyme-linked immunosorbent assay were employed to evaluate the effect of low-molecular weight sodium hyaluronan, its acetylated derivative and HA complex on expression of matrix metalloproteinase-1 (MMP-1) and type I collagen in normal human fibroblasts. Then, immunohistochemical analysis and hematoxylin and eosin staining was carried out to evaluate identical effects of HA complex in reconstructed skin equivalents, as well as its benefits on histological structure and DEJ.
    RESULTS: In normal human dermal fibroblasts, the hyaluronan complex, which contains low-molecular weight sodium hyaluronate and its acetylated derivative, has synergistic effects by increasing type I collagen expression. At the same time, MMP-1 production was inhibited. This was confirmed in subsequent experiments with skin equivalent, and intriguingly, the hyaluronan complex was also found to increase the expression of two DEJ proteins.
    CONCLUSIONS: The multimechanism hyaluronan complex in this proof-of-concept study exhibited skin antiaging effects in vitro through inhibiting the expression of MMP-1 and enhancing type I collagen accumulation and the expression of DEJ proteins, which reveals new avenues for investigating more biological activities of various types of hyaluronan.
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  • 文章类型: Journal Article
    在这项研究中,通过FeSO4/K2FeO4浸渍和氧化组合两步负载在活性炭上制备了一种新型的原位铁负载活性炭(AFPAC),以增强从水溶液中去除Cr(VI)。AFPAC对Cr(VI)的去除效率比新鲜活性炭(AC)大大提高了70%以上,这是由于原位形成的丰富的铁氧化物以及铁氧化物与活性炭之间的协同作用。研究了不同水质参数下AFPAC对Cr(VI)的吸附行为。AFPAC对Cr(VI)的最大单层吸附能力高达26.24mg/g,28.65mg/g,在25°C时和32.05mg/g,在pH4下分别为35°C和45°C。密度泛函理论(DFT)结果表明,K2Cr2O7在FeOOH表面的吸附能为-2.52eV,大于裸露的AC表面上的值,K2Cr2O7在FeOOH表面的吸附过程中发生了更多的电荷转移,极大地促进了Cr=O-Fe的形成。通过AFPAC去除Cr(VI)包括静电引力,氧化还原反应,配位络合,和共沉淀。Cr(VI)在AFPAC上的吸附过程包括三个反应步骤:(1)AFPAC快速质子化,Cr2O72-会静电吸引到带正电荷的AFPAC表面。(2)通过碳与活性炭上的氧官能团结合以及FeSO4和K2FeO4的氧化还原反应过程,将Cr2O72-还原为Cr2O3。(3)形成内球配合物,并通过氧化铁吸附在AFPAC上,然后共沉淀。
    In this study, a novel in situ iron-loaded activated carbon (AFPAC) was prepared by a FeSO4/K2FeO4 impregnation and oxidation combination two-step supported on activated carbon for enhanced removal of Cr(VI) from aqueous solutions. Cr(VI) removal efficiency greatly increased by AFPAC more than 70% than that of fresh activated carbon (AC), which is due to rich iron oxides formed in situ and the synergistic effect between iron oxides and activated carbon. Cr(VI) adsorption behaviors on AFPAC under different water quality parameters were investigated. The maximum monolayer adsorption capacities for Cr(VI) by AFPAC are as high as 26.24 mg/g, 28.65 mg/g, and 32.05 mg/g at 25 °C, 35 °C and 45 °C at pH 4, respectively. Density functional theory (DFT) results showed that the adsorption energy of K2Cr2O7 on the surface of FeOOH was - 2.52 eV, which was greater than that on the surface of bare AC, and more charge transfer occurred during the adsorption of K2Cr2O7 on the surface of FeOOH, greatly promoting the formation of Cr = O-Fe. Cr(VI) removal by AFPAC included electrostatic attraction, redox reaction, coordinate complexation, and co-precipitation. Cr(VI) adsorption process on AFPAC consisted of the three reaction steps: (1) AFPAC was fast protonation and Cr2O72- would electrostatically attract to the positively charged AFPAC surface. (2) Cr2O72- was reduced into Cr2O3 by the carbons bond to the oxygen functionalities on activated carbon and the redox reaction process of FeSO4 and K2FeO4. (3) The inner-sphere complexes were formed, and adsorbed on AFPAC by iron oxides and then co-precipitation.
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  • 文章类型: Journal Article
    世界范围内日益严重的细菌耐药性促使人们不可避免地发现和设计潜在的抗菌药物。在这项工作中,一系列简短的,设计并成功合成了镜像对称肽,以“RRR”为中心,两端用疏水氨基酸标记。基于结构-活动关系分析,筛选LWWR(LWWRRWWL-NH2)作为理想的镜像对称肽用于进一步研究。不出所料,LWWR对标准细菌和抗生素抗性菌株显示出广谱抗菌活性。毫无疑问,LWWR在复杂的生理环境中的高稳定性是其抗菌活性最大化的重要保证。的确,LWWR还表现出快速的杀菌速度和低的细菌耐药性倾向,基于非受体介导的膜作用和细胞内机制的多重作用。令人惊讶的是,尽管与多粘菌素B和蜂毒素相比,LWWR显示出相似的体内抗菌活性,LWWR的体内安全性远高于它们,所以LWWR有更好的治疗潜力。总之,理想的镜像对称肽LWWR有望作为一种潜在的抗菌药物来应对抗生素耐药危机.重要性声明:见证抗生素耐药性日益严重的问题,一系列简短的,本研究设计并合成了基于对称中心“RRR”和疏水末端的镜像对称肽。其中,LWWR(LWWRRWWL-NH2)由于其多种机制和良好的稳定性,在体外和体内均具有广谱抗菌活性。同时,LWWR的低耐药性和毒性也表明了其临床应用的潜力。这项研究的结果将为潜在的抗菌剂的设计和开发提供一些启示,并有助于在全球范围内尽快消除细菌感染。
    The increasingly severe bacterial resistance worldwide pushes people to discover and design potential antibacterial drugs unavoidably. In this work, a series of short, mirror-symmetric peptides were designed and successfully synthesized, centered on \"RRR\" and labeled with hydrophobic amino acids at both ends. Based on the structure-activity relationship analysis, LWWR (LWWRRRWWL-NH2) was screened as a desirable mirror-symmetric peptide for further study. As expected, LWWR displayed broad-spectrum antibacterial activity against the standard bacteria and antibiotic-resistant strains. Undoubtedly, the high stability of LWWR in a complex physiological environment was an essential guarantee to maximizing its antibacterial activity. Indeed, LWWR also exhibited a rapid bactericidal speed and a low tendency to develop bacterial resistance, based on the multiple actions of non-receptor-mediated membrane actions and intra-cellular mechanisms. Surprisingly, although LWWR showed similar in vivo antibacterial activity compared with Polymyxin B and Melittin, the in vivo safety of LWWR was far higher than that of them, so LWWR had better therapeutic potential. In summary, the desirable mirror-symmetric peptide LWWR was promised as a potential antibacterial agent to confront the antibiotics resistance crisis. STATEMENT OF SIGNIFICANCE: Witnessing the growing problem of antibiotic resistance, a series of short, mirror-symmetric peptides based on the symmetric center \"RRR\" and hydrophobic terminals were designed and synthesized in this study. Among, LWWR (LWWRRRWWL-NH2) presented broad-spectrum antibacterial activity both in vitro and in vivo due to its multiple mechanisms and good stability. Meanwhile, the low drug resistance and toxicity of LWWR also suggested its potential for clinical application. The findings of this study will provide some inspiration for the design and development of potential antibacterial agents, and contribute to the elimination of bacterial infections worldwide as soon as possible.
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  • 文章类型: Journal Article
    这项研究的目的是确定青春期的睡眠质量和数量是否以及如何与成年期的教育程度相关。这项研究还调查了这种关系是否因性别而异。
    使用全国青少年与成人健康纵向研究的数据,本研究采用了兄弟姐妹固定效应方法,该方法考虑了未观察到的家庭背景因素,例如遗传和社会环境。进行了性别分层分析,以考虑青少年睡眠与受教育程度之间的潜在性别关系。
    控制未观察到的家庭水平异质性减弱了青少年睡眠特征和教育程度之间的关联,尽管男孩和女孩的方式不同。性别分层模型表明,对于男孩来说,只有短睡眠时间和受教育程度之间的关联对于调整同胞固定效应是稳健的.相比之下,对于女孩来说,在三项睡眠质量测量中,即使在控制了未观察到的家庭异质性之后,只有入睡或入睡困难仍然与受教育程度显着相关。兄弟姐妹固定效应估计表明,短睡眠时间(每晚6小时或更少)仅与男孩的受教育年限呈负相关(b=-0.443),而入睡或入睡困难仅与女孩的受教育年限减少有关(b=-0.556)。所观察到的关联的潜在机制也因性别而异。对于男孩来说,短睡眠时间和受教育程度之间的关联部分解释为教育的组合,社会,和心理因素。只有中等教育因素解释了女孩入睡或入睡困难与教育依恋之间的部分联系。
    该研究发现,青少年睡眠特征与受教育程度之间的关系以及这种关系的潜在机制因性别而异,这就需要关注针对性别的干预措施。
    The objective of this study is to determine whether and how sleep quality and quantity during adolescence are related to educational attainment in adulthood. This study also investigates whether this relationship varies by gender.
    Using data from the National Longitudinal Study of Adolescent to Adult Health, the present study employed a sibling fixed effect approach that takes into account unobserved family background factors such as genetics and social environments. Gender-stratified analyses were conducted to consider the potential gendered relationship between adolescent sleep and educational attainment.
    Controlling for unobserved family-level heterogeneity attenuated the associations between adolescent sleep characteristics and educational attainment, albeit in different ways for boys and girls. Gender-stratified models suggest that, for boys, only the association between short sleep duration and educational attainment was robust to adjustment for sibling fixed effects. In contrast, for girls, among three sleep quality measures, only trouble falling or staying asleep remained significantly associated with educational attainment even after controlling for unobserved family heterogeneity. Sibling fixed effects estimates suggest that short sleep duration (6 or fewer hours per night) was negatively associated with years of schooling only among boys (b = -0.443), whereas trouble falling or staying asleep was associated with a reduction in years of schooling only among girls (b = -0.556). The mechanisms underlying the observed associations also differed by gender. For boys, the association between short sleep duration and educational attainment was partially explained by a combination of educational, social, and psychological factors. Only intermediate educational factors explained part of the association between trouble falling or staying asleep and educational attachment among girls.
    The study\'s finding that the relationship between adolescent sleep characteristics and educational attainment and the mechanisms underlying this relationship differ by gender calls attention to the need for gender-specific interventions.
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  • 文章类型: Journal Article
    With the aim of tackling the increasingly serious antimicrobial resistance and improving the clinical potential of AMPs, a facile de novo strategy was adopted in this study, and a series of new peptides comprising repeating unit (WRX)n (X represents I, L, F, W, and K; n = 2, 3, 4, or 5) and amidation at C-terminus were designed. Most of the newly designed peptides exhibited a broad range of excellent antimicrobial activities against various bacteria, especially difficult-to-kill multidrug-resistant bacteria clinical isolates. Among (WRK)4 and (WRK)5, with n = 4 and n = 5 of repeating unit WRK, the highest selectivity for anionic bacterial membranes over a zwitterionic mammalian cell membrane is presented with strong antimicrobial potential and low toxicity. Additionally, both (WRK)4 and (WRK)5 emerged with fast killing speed and low tendency of resistance in sharp contrast to the conventional antibiotics ciprofloxacin, gentamicin, and imipenem, as well as having antimicrobial activity through multiple mechanisms including a membrane-disruptive mechanism and an intramolecular mechanism (nucleic acid leakage, DNA binding and ROS generation) characterized by a series of assays. Furthermore, (WRK)4 exerted impressive therapeutic effects in vivo similarly to polymyxin B but displayed much lower toxicity in vivo than polymyxin B. Taken together, the newly designed peptides (WRK)4 and (WRK)5 presented tremendous potential as novel antimicrobial candidates in response to the growing antimicrobial resistance.
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  • 文章类型: Journal Article
    In response to the dramatically increasing antimicrobial resistance, a series of new symmetric peptides were designed and synthesized in this study by a \"WWW\" motif as the symmetric center, arginine as the positive charge amino acid and the terminus symmetrically tagged with hydrophobic amino acids. Amongst the new symmetric peptide FRRW (FRRWWWRRF-NH2) presented the highest cell selectivity for bacteria over mammalian cell and exerted excellent antimicrobial potential against a broad of bacteria, especially difficult-to-kill multidrug-resistant strains clinical isolates. FRRW also displayed perfect stability in physiological salt ions and rapid killing speed as well as acted on multiple mechanisms including non-receptor mediated membrane and intra-molecular mechanisms. Importantly, FRRW emerged a low tendency of resistance in contrast to traditional antibiotics ciprofloxacin and gentamicin. What\'s more, FRRW could resist or alleviate or even reverse the ciprofloxacin- and gentamicin-resistance by changing the permeability of bacterial membrane and inhibiting the efflux pumps of bacteria. Furthermore, FRRW exhibited remarkable effectiveness and higher safety in vivo than polymyxin B. In summary, the new symmetric peptide FRRW was promised to be as a new antimicrobial candidate for overcoming the increasing bacterial resistance.
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  • 文章类型: Journal Article
    In the development of tight gas reservoirs, gas flow through porous media usually takes place deep underground with multiple mechanisms, including gas slippage and stress sensitivity of permeability and porosity. However, little work has been done to simultaneously incorporate these mechanisms in the lattice Boltzmann model for simulating gas flow through porous media. This paper presents a lattice Boltzmann model for gas flow through porous media with a consideration of these effects. The apparent permeability and porosity are calculated based on the intrinsic permeability, intrinsic porosity, permeability modulus, porosity sensitivity exponent, and pressure. Gas flow in a two-dimensional channel filled with a homogeneous porous medium is simulated to validate the present model. Simulation results reveal that gas slippage can enhance the flow rate in tight porous media, while stress sensitivity of permeability and porosity reduces the flow rate. The simulation results of gas flow in a porous medium with different mineral components show that the gas slippage and stress sensitivity of permeability and porosity not only affect the global velocity magnitude, but also have an effect on the flow field. In addition, gas flow in a porous medium with fractures is also investigated. It is found that the fractures along the pressure-gradient direction significantly enhance the total flow rate, while the fractures perpendicular to the pressure-gradient direction have little effect on the global permeability of the porous medium. For the porous medium without fractures, the gas-slippage effect is a major influence factor on the global permeability, especially under low pressure; for the porous medium with fractures, the stress-sensitivity effect plays a more important role in gas flow.
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  • 文章类型: Journal Article
    Nano zero-valent iron (nZVI), as a high-efficiency adsorbent for heavy metals, often suffers being oxidized and assembling together due to small size and super reactivity, further decreasing its adsorption performance and limiting application ranges. Herein, we have designed a novel adsorbent with high-dispersion nZVI stabilized by as-prepared artificial humic acid (AHA-nZVI) derived from hydrothermal humification (HTH) technology. Introduction of artificial humic acid (A-HA) can effectively reduce the oxidation and agglomeration of nZVI, leading to superior kinetic removal efficiency of Pb2+ (> 99.2%) and huge Langmuir removal capacity of 649.0 mg/g. The combination of nZVI and A-HA (contained abundant functional groups, i.e. -OH and -COOH) via C-O-Fe bonding makes nZVI have good dispersion and oxidation resistance. Multiple interaction mechanisms including reduction reaction, complexation and co-precipitation between heavy metals and AHA-nZVI samples are realized. Overall, AHA-nZVI is a promising material for high-performance heavy metal contaminated water treatment.
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  • 文章类型: Journal Article
    Adaptation to changes of the environment is an essential function of the visual system. Recent studies have revealed that prolonged viewing of a point-light display of a human walker can produce the perception of a point-light walker facing in the opposite direction in a subsequent ambiguous test. Similar effects of biological motion adaptation have been documented for various properties of the point-light walkers. However, the time course and controlling mechanisms for biological motion adaptation have not yet been examined. The present study investigated whether a single mechanism or multiple mechanisms controlled biological motion adaptation. In Experiment 1, a relatively long duration of initial adaptation to one facing direction of a point-light walker was followed by a relatively short duration of deadaptation in which the adapter was a point-light walker of the opposite facing direction. Chimeric ambiguous walkers were used to test the aftereffect in a top-up manner. We observed spontaneous recovery of the adaptation effects in the post-test period. The Experiment 2 further delineated the build-up and decay of biological motion adaptation that accorded well with the duration scaling law (i.e., effects of adaptation become stronger and longer-lasting as adaptation duration increases). Further analysis indicated that the slower but not the faster component of the adaptation effects complied with the law. These findings suggest that biological motion adaptation is controlled by the multiple mechanisms tuned to differing timescales.
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