• 【通过使用嵌合噬菌体靶向的金纳米棒对特定细菌物种进行光热消融来控制噬菌体。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1913234117 复制DOI
    作者列表:Peng H,Borg RE,Dow LP,Pruitt BL,Chen IA
    BACKGROUND & AIMS: :The use of bacteriophages (phages) for antibacterial therapy is under increasing consideration to treat antimicrobial-resistant infections. Phages have evolved multiple mechanisms to target their bacterial hosts, such as high-affinity, environmentally hardy receptor-binding proteins. However, traditional phage therapy suffers from multiple challenges stemming from the use of an exponentially replicating, evolving entity whose biology is not fully characterized (e.g., potential gene transduction). To address this problem, we conjugate the phages to gold nanorods, creating a reagent that can be destroyed upon use (termed "phanorods"). Chimeric phages were engineered to attach specifically to several Gram-negative organisms, including the human pathogens Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae, and the plant pathogen Xanthomonas campestris The bioconjugated phanorods could selectively target and kill specific bacterial cells using photothermal ablation. Following excitation by near-infrared light, gold nanorods release energy through nonradiative decay pathways, locally generating heat that efficiently kills targeted bacterial cells. Specificity was highlighted in the context of a P. aeruginosa biofilm, in which phanorod irradiation killed bacterial cells while causing minimal damage to epithelial cells. Local temperature and viscosity measurements revealed highly localized and selective ablation of the bacteria. Irradiation of the phanorods also destroyed the phages, preventing replication and reducing potential risks of traditional phage therapy while enabling control over dosing. The phanorod strategy integrates the highly evolved targeting strategies of phages with the photothermal properties of gold nanorods, creating a well-controlled platform for systematic killing of bacterial cells.
    背景与目标: :越来越多地考虑将噬菌体(噬菌体)用于抗菌治疗,以治疗抗药性感染。噬菌体已经进化出多种针对其细菌宿主的机制,例如高亲和力,对环境无害的受体结合蛋白。然而,传统的噬菌体疗法由于使用生物学无法完全表征(例如,潜在的基因转导)的指数复制,进化的实体而遭受多重挑战。为了解决这个问题,我们将噬菌体与金纳米棒结合,产生一种可以在使用时被破坏的试剂(称为“ phanorods”)。嵌合噬菌体经过工程改造,可以特异性附着于几种革兰氏阴性生物,包括人类病原体大肠杆菌,铜绿假单胞菌和霍乱弧菌,以及植物病原体黄单胞菌。生物共轭的体细胞可以通过光热消融选择性地靶向并杀死特定的细菌细胞。在近红外光激发后,金纳米棒通过非辐射衰变途径释放能量,从而局部产生热量,从而有效杀死目标细菌细胞。在铜绿假单胞菌生物膜的背景下突出了特异性,其中幽门架辐射杀死细菌细胞,同时对上皮细胞的损害最小。局部温度和粘度测量显示细菌高度局部化和选择性消融。辐照体也破坏了噬菌体,防止了复制并降低了传统噬菌体疗法的潜​​在风险,同时能够控制剂量。 phanorod策略将高度进化的噬菌体靶向策略与金纳米棒的光热特性相结合,为系统杀死细菌细胞创造了一个可控平台。
  • 【金纳米粒子的X射线荧光定量成像使用联合L1和总变异正则化重建。】 复制标题 收藏 收藏
    DOI:10.21037/qims.2019.10.15 复制DOI
    作者列表:Shi J,Granger B,Xu K,Yang Y
    BACKGROUND & AIMS: Background:This work proposed a joint L1 and total variation (TV) regularized reconstruction method for X-ray fluorescence tomography (XFT), and investigated the performance of this method in quantitative imaging of gold nanoparticles (GNPs). Methods:We developed a dual-modality XFT/CT imaging system which consisted of a benchtop X-ray source, a translation/rotation stage, a silicon drift detector for X-ray fluorescence (XRF) detection, and a flat panel detector for transmission X-ray detection. A pencil-beam collimator was 3D printed with steel and employed in sample excitation. The sensitivity of the XFT imaging system was determined by imaging water phantoms with multiple inserts containing GNP solutions of various concentrations (0.02-0.16 wt.%). A joint L1 and total variation (TV) regularized algorithm was developed for XFT reconstruction, where the L1 regularization was used to reduce image artifacts and the TV regularization was used to preserve the shape of targets. Nonlinear conjugate gradient (NCG) descent algorithm with backtracking line search was adopted to solve the reconstruction problem. We compared the L1 + TV regularization method with filtered back projection (FBP), maximum likelihood expectation maximization (ML-EM), L1 regularization, and TV regularization methods. Contrast-to-noise ratio (CNR), Dice similarity coefficient (DSC) and localization error (LE) metrics were used to compare the performance of different methods. The CT and XFT imaging doses were also measured using EBT2 radiochromic films. Results:The 3D printed pencil-beam collimator shaped an excitation beam with a 2 mm full width at half maximum at the imaging isocenter. Based on the phantom imaging experiments, the joint L1 and TV regularization method performed better than FBP, ML-EM, L1 regularization and TV regularization methods, with higher localization accuracy (offset <0.6 mm), CNR and DSC values. Compared with CT, XFT with L1 + TV regularized reconstruction demonstrated higher sensitivity in GNP imaging, and could detect GNP at a concentration of 0.02 wt.% or lower. Moreover, there existed a significant linear correlation (R2>0.99) between the reconstructed and true GNP concentration. The estimated XFT imaging dose is about 41.22 cGy under current setting. Conclusions:The joint L1 + TV regularized reconstruction algorithm performed better in noise suppression and shape preservation. Using the L1 + TV regularized reconstruction, the XFT system is able to localize GNP targets with submillimeter accuracy and quantify GNP distribution at a concentration of 0.02 wt.% or lower.
    背景与目标: 背景:这项工作提出了一种用于X射线荧光层析成像(XFT)的联合L1和总变异(TV)正则化重构方法,并研究了该方法在金纳米颗粒(GNP)定量成像中的性能。
    方法:我们开发了一种双模态XFT / CT成像系统,该系统由台式X射线源,平移/旋转台,用于X射线荧光(XRF)检测的硅漂移检测器和用于透射的平板检测器组成X射线检测。笔形光束准直器用钢进行3D打印,并用于样品激发。 XFT成像系统的灵敏度是通过对带有多个插入物的水体模进行成像来确定的,这些插入物包含各种浓度(0.02-0.16 wt。%)的GNP溶液。针对XFT重建,开发了联合的L1和总变异(TV)正则化算法,其中L1正则化用于减少图像伪影,而TV正则化用于保留目标的形状。采用带回溯线搜索的非线性共轭梯度下降算法来解决重构问题。我们将L1 TV正则化方法与滤波后向投影(FBP),最大似然期望最大化(ML-EM),L1正则化和TV正则化方法进行了比较。对比噪声比(CNR),骰子相似系数(DSC)和定位误差(LE)指标用于比较不同方法的性能。还使用EBT2射线变色胶片测量了CT和XFT成像剂量。
    结果:3D打印的笔形光束准直器塑造了一个激发光束,在成像等角点处的半峰全宽为2 mm。基于幻像成像实验,联合L1和TV正则化方法的性能优于FBP,ML-EM,L1正则化和TV正则化方法,具有更高的定位精度(偏移<0.6 mm),CNR和DSC值。与CT相比,采用L1 TV常规重建的XFT在GNP成像中显示出更高的灵敏度,并且可以检测到0.02 wt。%或更低的GNP。此外,重建的和实际的GNP浓度之间存在显着的线性相关性(R2> 0.99)。在当前设置下,估计的XFT成像剂量约为41.22 cGy。
    结论:联合L1 TV正则化重构算法在抑制噪声和保持形状方面表现更好。使用L1 TV正则化重建,XFT系统能够以亚毫米级精度定位GNP目标,并以0.02 wt。%或更低的浓度量化GNP分布。
  • 【在SOS色度测试中,没有金,银,氧化锌和二氧化钛纳米颗粒的潜在遗传毒性证据。】 复制标题 收藏 收藏
    DOI:10.1002/jat.2830 复制DOI
    作者列表:Nam SH,Kim SW,An YJ
    BACKGROUND & AIMS: :Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l(-1) for Au NPs, 32.3 mg l(-1) for Ag NPs and 100 mg l(-1) for ZnO NPs and TiO2 NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO2 NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are classified as non-genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest.
    背景与目标: :金纳米颗粒(Au NPs),银纳米颗粒(Ag NPs),氧化锌纳米颗粒(ZnO NPs)和二氧化钛纳米颗粒(TiO2 NPs)广泛用于化妆品,如防腐剂,着色剂和防晒霜。这项研究使用大肠杆菌PQ37进行了SOS色度测试,研究了金纳米颗粒,银纳米颗粒,氧化锌纳米颗粒和二氧化钛纳米颗粒的遗传毒性。纳米金的最大暴露浓度分别为:金纳米颗粒为3.23μg-1(-1),银纳米颗粒为32.3μg-1(-1),锌纳米颗粒和二氧化钛纳米颗粒的最大暴露浓度为100μg-1(-1)。另外,为了比较纳米粒子和相应溶解离子的遗传毒性,以与纳米粒子相同的方式评估离子。由于TiO2 NPs的溶解度极低,因此未评估钛离子的遗传毒性。在各种测试浓度范围内,Au NPs,Ag NPs,ZnO NPs,TiO2 NPs和Au,Ag和Zn离子对SOS色度测试均无影响,所有化学药品的最大IF(IFmax)值均在1.5以下。由于该结果,根据本研究中使用的SOS色度测试,将纳米级的Au NPs,Ag NPs,ZnO NPs,TiO2 NPs以及Au,Ag和Zn的离子归类为非遗传毒性。据我们所知,这是第一项使用SOS色度分析评估Au NP,Ag NP,ZnO NP和TiO2 NP的遗传毒性的研究。
  • 【温度响应型聚合物-金纳米复合材料作为智能治疗系统。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.31284 复制DOI
    作者列表:Owens DE 3rd,Eby JK,Jian Y,Peppas NA
    BACKGROUND & AIMS: :The objective of this study was to synthesize and characterize a thermally responsive polymer-metal nanocomposite system comprised of a solid gold nanoparticle core and thermally responsive interpenetrating polymer network (IPN) shell, which was surface functionalized or PEGylated with a covalently bound linear poly(ethylene glycol) chain layer. Gold nanoparticles (50 nm diameter) were prepared using standard gold chloride and citrate reduction method. These particles were then encapsulated inside of a polyacrylamide (PAAm)/poly(acrylic acid) (PAA) IPN shell via an in situ inverse emulsion polymerization. The surface of the nanocomposite system was then PEGylated via covalent grafting of a linear methoxy-PEG-N-hydroxysuccinimide (M.W. 3400) to the primary amine groups of the PAAm network. Scanning and transmission electron microscopy were used to confirm the successful synthesis and encapsulation of gold nanoparticles within the IPN shell. Dynamic light scattering was used to examine the temperature swelling response of the IPN particles. Zeta-potential analysis was used to confirm the successful PEGylation of the final nanocomposite system.
    背景与目标: :本研究的目的是合成和表征由固体金纳米颗粒核和热响应互穿聚合物网络(IPN)壳组成的热响应聚合物-金属纳米复合材料系统,该系统表面进行功能化或与共价键合的线性聚PEG聚乙二醇化乙二醇)链层。使用标准氯化金和柠檬酸盐还原法制备金纳米颗粒(直径为50 nm)。然后通过原位逆乳液聚合将这些颗粒封装在聚丙烯酰胺(PAAm)/聚(丙烯酸)(PAA)IPN壳内部。然后通过将线性甲氧基-PEG-N-羟基琥珀酰亚胺(M.W.3400)共价接枝到PAAm网络的伯胺基团上,将纳米复合系统的表面进行PEG化。扫描和透射电子显微镜用于确认IPN壳内金纳米颗粒的成功合成和封装。动态光散射用于检查IPN颗粒的温度溶胀响应。 Zeta电位分析用于确认最终纳米复合系统的成功PEG化。
  • 【利用免疫靶向金纳米粒子的光热成像,实现对肿瘤边缘的实时检测。】 复制标题 收藏 收藏
    DOI:10.2147/IJN.S34157 复制DOI
    作者列表:Jakobsohn K,Motiei M,Sinvani M,Popovtzer R
    BACKGROUND & AIMS: BACKGROUND:One of the critical problems in cancer management is local recurrence of disease. Between 20% and 30% of patients who undergo tumor resection surgery require reoperation due to incomplete excision. Currently, there are no validated methods for intraoperative tumor margin detection. In the present work, we demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast agent for photothermal molecular imaging of cancer. METHODS:Phantoms containing different concentrations of GNPs were irradiated with continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. RESULTS:The results clearly demonstrate the ability to distinguish between cancerous cells specifically targeted with GNPs and normal cells. This technique, which allows highly sensitive discrimination between adjacent low GNP concentrations, will allow tumor margin detection while the temperature increases by only a few degrees Celsius (for GNPs in relevant biological concentrations). CONCLUSION:We expect this real-time intraoperative imaging technique to assist surgeons in determining clear tumor margins and to maximize the extent of tumor resection while sparing normal background tissue.
    背景与目标: 背景:癌症治疗中的关键问题之一是疾病的局部复发。接受肿瘤切除手术的患者中有20%至30%由于切除不完全而需要再次手术。目前,尚无经验证的术中肿瘤边缘检测方法。在本工作中,我们证明了金纳米颗粒(GNP)作为癌症光热分子成像的新型造影剂的潜在用途。
    方法:用连续波激光辐照含有不同浓度GNP的人体模型,并用热像仪测量,以检测所辐照人体模型的温度场。
    结果:这些结果清楚地表明了区分GNPs特异性靶向癌细胞和正常细胞的能力。这项技术可以在相邻的低GNP浓度之间进行高度灵敏的区分,当温度仅升高几摄氏度时(对于相关生物浓度的GNP),就可以检测肿瘤边缘。
    结论:我们希望这种实时术中成像技术能够帮助外科医生确定清楚的肿瘤切缘,并在保留正常背景组织的同时最大程度地扩大肿瘤切除范围。
  • 【锰卟啉MnHex-2-PyP的抗肿瘤和放射增敏作用的机理。】 复制标题 收藏 收藏
    DOI:10.1089/ars.2016.6889 复制DOI
    作者列表:Shin SW,Choi C,Lee GH,Son A,Kim SH,Park HC,Batinic-Haberle I,Park W
    BACKGROUND & AIMS: AIMS:Cationic manganese (Mn)-substituted N-pyridylporphyrin-based potent mimics of the family of superoxide dismutases (SODs) protect normal tissues from injury related to ionizing radiation (IR) by reducing levels of reactive oxygen and nitrogen species (ROS/RNS). Furthermore, Mn-porphyrins have demonstrated antitumor and radiosensitizing effects on cancer cells by promoting IR-induced tumor vasculature damage and apoptotic processes. In this study, we explored the underlying mechanisms of Mn-porphyrin-mediated tumor radiosensitization using murine mammary carcinoma 4T1 and melanoma B16 cells in vitro and in vivo. RESULTS:Combination treatment with MnTnHex-2-PyP and IR substantially reduced cell viability, clonogenic cell survival, and DNA damage repair and synergistically increased IR-induced apoptosis of 4T1 and B16 cells. MnTnHex-2-PyP in combination with IR caused a significant delay in growth of 4T1 and B16 xenograft tumors. MnTnHex-2-PyP dose-dependently enhanced IR-mediated production of H2O2-derived species, but not superoxide. Catalase overexpression reversed MnTnHex-2-PyP-enhanced ROS production and apoptosis. Demonstrated suppression of phosphorylation of several mitogen-activated protein (MAP) kinases and activation of NF-κB by MnTnHex-2-PyP/IR, which presumably inhibited activation of the antiapoptotic pathway, are in agreement with our other data on the apoptosis of cancer cells. Innovation and Conclusions: MnTnHex-2-PyP exerted a radiosensitizing effect on 4T1 and B16 tumor models in vitro and in vivo via pro-oxidative actions and therefore bears a large therapeutic potential. When combined with IR, it attenuated DNA damage repair and triggered a shift from prosurvival pathways to apoptotic cell death, likely due to increased ROS production and disturbed cellular redox balance, acting at the level of nuclear factor κB (NF-κB). Antioxid. Redox Signal. 27, 1067-1082.
    背景与目标: 目的:超氧化物歧化酶(SOD)家族的阳离子锰(Mn)取代的基于N-吡啶基卟啉的强效模拟物可通过降低活性氧和氮的含量(ROS / RNS)保护正常组织免受与电离辐射(IR)相关的伤害)。此外,锰卟啉通过促进IR诱导的肿瘤脉管系统损伤和凋亡过程,已显示出对癌细胞的抗肿瘤和放射增敏作用。在这项研究中,我们探索了在体外和体内使用鼠乳腺癌4T1和黑色素瘤B16细胞进行Mn-卟啉介导的肿瘤放射增敏的潜在机制。
    结果:MnTnHex-2-PyP和IR联合治疗可显着降低细胞活力,克隆细胞存活和DNA损伤修复,并协同增加IR诱导的4T1和B16细胞凋亡。 MnTnHex-2-PyP与IR的结合导致4T1和B16异种移植肿瘤的生长显着延迟。 MnTnHex-2-PyP剂量依赖性地增强了IR介导的H2O2衍生物质的产生,但不增强超氧化物的产生。过氧化氢酶的过表达逆转了MnTnHex-2-PyP增强的ROS的产生和凋亡。 MnTnHex-2-PyP / IR证实抑制了几种促分裂原活化蛋白(MAP)激酶的磷酸化和NF-κB的激活,据推测抑制了抗凋亡途径的激活,这与我们有关癌症细胞凋亡的其他数据一致细胞。创新与结论:MnTnHex-2-PyP通过促氧化作用在体内外对4T1和B16肿瘤模型产生放射增敏作用,因此具有很大的治疗潜力。当与IR结合使用时,它减弱了DNA损伤修复,并触发了从存活途径到凋亡细胞死亡的转变,这可能是由于ROS产生增加和细胞氧化还原平衡受到破坏,作用于核因子κB(NF-κB)。抗氧化。氧化还原信号。 27,1067-1082。
  • 【通过金纳米颗粒靶向恶性外泌体的肿瘤微环境调节:对癌症诊断和治疗的意义。】 复制标题 收藏 收藏
    DOI:10.3390/ijms18010162 复制DOI
    作者列表:Roma-Rodrigues C,Raposo LR,Cabral R,Paradinha F,Baptista PV,Fernandes AR
    BACKGROUND & AIMS: :Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.
    背景与目标: :外泌体是在内体途径中形成的纳米囊泡,在旁分泌和自分泌细胞通讯中起重要作用。癌细胞分泌的外泌体,恶意外泌体在肿瘤微环境成熟和癌症进展中具有重要作用。对外泌体在肿瘤发生中的作用的了解开创了癌症诊断和治疗的新纪元,由于循环外泌体在体液中的稳定性以及利用恶性外泌体的释放和/或摄取来抑制或抑制恶性外泌体的利用,利用循环外泌体作为肿瘤生物标志物。延缓肿瘤的发展。近年来,纳米技术为开发大量新的诊断和治疗平台铺平了道路,从而促进了诊断学的发展。金纳米粒子(AuNPs)独特的物理和化学性质使其成为实现该目标的合适载体。 AuNPs的特性,例如易于合成并具有所需的形状和大小,高的表面体积比以及根据需要对其表面进行修饰的可能性,都增强了AuNPs在纳米热力学中的作用,从而允许使用相同的配方进行外泌体的检测和抑制恶意囊泡对癌症进展的影响。
  • 【二硫键诱导的自组装靶:一种通过未修饰的金纳米颗粒对DNA / RNA进行无标记比色检测的新策略。】 复制标题 收藏 收藏
    DOI:10.1038/srep45837 复制DOI
    作者列表:Shokri E,Hosseini M,Davari MD,Ganjali MR,Peppelenbosch MP,Rezaee F
    BACKGROUND & AIMS: :A modified non-cross-linking gold-nanoparticles (Au-NPs) aggregation strategy has been developed for the label free colorimetric detection of DNAs/RNAs based on self-assembling target species in the presence of thiolated probes. Two complementary thiol- modified probes, each of which specifically binds at one half of the target introduced SH groups at both ends of dsDNA. Continuous disulfide bond formation at 3' and 5' terminals of targets leads to the self-assembly of dsDNAs into the sulfur- rich and flexible products with different lengths. These products have a high affinity for the surface of Au-NPs and efficiently protect the surface from salt induced aggregation. To evaluate the assay efficacy, a small part of the citrus tristeza virus (CTV) genome was targeted, leading to a detection limit of about 5 × 10-9 mol.L-1 over a linear ranged from 20 × 10-9 to 10 × 10-7 mol.L-1. This approach also exhibits good reproducibility and recovery levels in the presence of plant total RNA or human plasma total circulating RNA extracts. Self-assembled targets can be then sensitively distinguished from non-assembled or mismatched targets after gel electrophoresis. The disulfide reaction method and integrating self-assembled DNAs/RNAs targets with bare AuNPs as a sensitive indicator provide us a powerful and simple visual detection tool for a wide range of applications.
    背景与目标: :已开发出一种改进的非交联金纳米粒子(Au-NPs)聚集策略,用于在硫醇化探针存在下基于自组装靶物种的DNA / RNA的无标记比色检测。两个互补的巯基修饰探针,每个探针都与dsDNA两端的目标导入的SH基团的一半特异性结合。在靶标的3'和5'末端连续形成二硫键,导致dsDNA自组装成具有不同长度的富硫和柔性产物。这些产品对Au-NPs的表面具有很高的亲和力,并有效地保护了表面免于盐诱导的聚集。为了评估测定的功效,针对了小部分的柑桔类Tristeza病毒(CTV)基因组,在20 limit×10-9至10的线性范围内导致检出限约为5×10-9 mol.L-1。 ×10-7 mol.L-1。在存在植物总RNA或人血浆总循环RNA提取物的情况下,该方法还具有良好的重现性和回收率。凝胶电泳后,可以将自组装的靶标与未组装或错配的靶标区分开。二硫键反应方法以及将自组装的DNA / RNA靶标与裸金纳米颗粒结合在一起作为敏感指示剂,为我们提供了功能强大且简单的视觉检测工具,可用于广泛的应用。
  • 【LysR型转录因子HbrL是荚膜红细菌中铁稳态和卟啉合成的全局调节剂。】 复制标题 收藏 收藏
    DOI:10.1111/mmi.12431 复制DOI
    作者列表:Zappa S,Bauer CE
    BACKGROUND & AIMS: :The purple bacterium Rhodobacter capsulatus is unique among Rhodobacteriacae as it contains a putative iron response regulator (Irr) but does not possess a copy of the ferric uptake regulator (Fur). Interestingly, an in-frame deletion mutant of Irr shows no major role in iron homeostasis. Instead, we showed that the previously identified activator of haem gene expression HbrL is a crucial regulator of iron homeostasis. We demonstrated that an HbrL deletion strain is unable to grow in iron-limited medium in aerobic, semi-aerobic and photosynthetic conditions and that suppressor strains can be isolated with mutations in iron uptake genes. Gene expression studies revealed that HbrL is a transcriptional activator of multiple ferrous and ferric iron uptake systems in addition to a haem uptake system. Finally, HbrL activates the expression of numerous haem biosynthesis genes. Thus, HbrL has a central role in controlling the amount of iron transport in conjunction with the synthesis of its cognate tetrapyrrole haem.
    背景与目标: :紫色细菌荚膜红细菌在红细菌中是独特的,因为它含有推定的铁反应调节剂(Irr),但不具有铁摄取调节剂(Fur)的副本。有趣的是,Irr的框内缺失突变体在铁稳态中没有主要作用。相反,我们表明先前鉴定的血红素基因表达HbrL激活剂是铁稳态的关键调节剂。我们证明了HbrL缺失菌株不能在有氧,半需氧和光合作用条件下的铁限制培养基中生长,并且可以分离出具有铁摄取基因突变的抑制菌株。基因表达研究表明,除血红素摄取系统外,HbrL还是多种亚铁和三价铁摄取系统的转录激活因子。最后,HbrL激活众多血红素生物合成基因的表达。因此,HbrL及其同源四吡咯血红素的合成在控制铁的运输中起着中心作用。
  • 【一项回顾性研究,对临床实践中对铸造金粘结修复体的性能进行评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.jdent.2006.06.007 复制DOI
    作者列表:Jamous I,Sidhu S,Walls A
    BACKGROUND & AIMS: OBJECTIVES:To evaluate the performance of cast gold bonded restorations in clinical practice. MATERIALS AND METHODS:The records of all patients treated with cast gold bonded restorations between 1997 and 2004 of The Dental Hospital of Newcastle upon Tyne were reviewed. The following data were recorded: sex of patient, location of teeth (anterior or posterior), position of teeth (upper or lower) and type of cement (glass ionomer, zinc phosphate or resin cement). The survival time was calculated for each restoration; and the reason for failure (either debond or change of treatment plan) identified for each case. The restorations were stratified according to the age of the patient into 10-year age bands and survival analysis was used to identify variables associated with increased risk of failure. RESULTS:Restorations luted with resin cement showed the highest rate of survival after 7 years of follow-up. The alternative lutes had significantly worse survival (p<0.05). Restorations on anterior teeth had poorer survival than on posterior teeth but there were no differences between those placed in the mandible and the maxilla. CONCLUSIONS:Within the limitations of this study resin cements are most appropriate for this type of restoration with 80% survival at 7 years. Restorations placed on posterior teeth survived better.
    背景与目标: 目的:评估铸金结合修复体在临床中的性能。
    材料与方法:回顾性分析了泰恩河畔纽卡斯尔牙科医院1997年至2004年之间所有使用铸金结合修复体治疗的患者的记录。记录以下数据:患者性别,牙齿位置(前牙或后牙),牙齿位置(上牙或下牙)和粘固剂的类型(玻璃离聚物,磷酸锌或树脂粘固剂)。计算每个修复体的存活时间;并确定每种情况下的失败原因(脱骨或改变治疗计划)。根据患者的年龄将修复体分为10岁年龄段,并使用生存分析确定与失败风险增加相关的变量。
    结果:经过7年的随访,树脂胶泥恢复的存活率最高。替代的卢特的存活率明显较差(p <0.05)。与前牙相比,前牙的修复生存性较差,但下颌骨和上颌骨的修复之间没有差异。
    结论:在本研究的局限性内,树脂水泥最适合此类修复,其7年生存率达80%。后牙的修复效果更好。
  • 【金纳米粒子的微波辐射对利什曼原虫的前鞭毛和无鞭毛体的抗寄生虫作用。】 复制标题 收藏 收藏
    DOI:10.3109/02656736.2012.758875 复制DOI
    作者列表:Sazgarnia A,Taheri AR,Soudmand S,Parizi AJ,Rajabi O,Darbandi MS
    BACKGROUND & AIMS: PURPOSE:This study aimed to determine the efficacy of thermotherapy in the presence of gold nanoparticles (GNPs) and microwave (MW) radiation at a frequency of 2450 MHz on the survival of Leishmania major promastigotes and amastigotes. MATERIALS AND METHODS:L. major promastigotes (strain MRHO/IR/75/ER) were cultured in RPMI-1640 medium supplemented with foetal bovine serum and antibiotic. The promastigotes were incubated with GNPs for 2 h. After washing, thermotherapy was performed by MW irradiation. After 48 h the promastigote survival rate was assessed using Alamar Blue assay. In the second part of the study, after culture and proliferation of J744 cells, the infected macrophages were incubated with the GNPs and were inserted under MW irradiation. After 24 h, the number of amastigotes in the macrophages was determined after Giemsa staining by a light microscope. RESULT:Increased exposure time of the microwave to the parasites in the presence of GNPs induced a significant decline in promastigotes survival rate in comparison to similar samples without GNPs. The least survival of amastigotes was also recorded in the groups containing GNPs. The presence of GNPs during MW irradiation was more lethal for promastigotes and amastigotes in comparison to MW alone. CONCLUSION:Thermotherapy using MW radiation in the presence of GNPs may be proposed as a new approach to treat leishmaniasis in future studies.
    背景与目标: 目的:本研究旨在确定在2450 MHz频率存在金纳米颗粒(GNP)和微波(MW)辐射的情况下,热疗法对利什曼原虫主要前鞭毛体和拟吻足动物的存活的功效。
    材料与方法:L.在补充胎牛血清和抗生素的RPMI-1640培养基中培养主要的前鞭毛体(菌株MRHO / IR / 75 / ER)。将前鞭毛体与GNP一起温育2小时。洗涤后,通过MW照射进行热疗。 48小时后,使用Alamar Blue分析法评估前鞭毛体的存活率。在研究的第二部分中,在培养和增殖J744细胞后,将感染的巨噬细胞与GNP一起孵育,并在MW辐射下插入。 24小时后,在吉姆萨染色后,用光学显微镜测定巨噬细胞中变形虫的数目。
    结果:与不含GNP的类似样品相比,存在GNP的情况下微波暴露于寄生虫的时间增加,导致前鞭毛体成活率显着下降。在含有GNP的组中,amastigotes的存活率也最低。与单独的MW相比,MW照射期间GNPs的存在对前鞭毛体和扁桃体更具致死性。
    结论:在未来的研究中,在存在GNPs的情况下使用MW辐射进行热疗可能是治疗利什曼病的一种新方法。
  • 【直接证据证明肿瘤坏死因子和新型衍生物胶体金结合的肿瘤坏死因子可以快速,选择性地诱导肿瘤新血管通透性。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22270 复制DOI
    作者列表:Farma JM,Puhlmann M,Soriano PA,Cox D,Paciotti GF,Tamarkin L,Alexander HR
    BACKGROUND & AIMS: :Tumor necrosis factor (TNF) causes regression of advanced cancers when used in isolation perfusion with melphalan; evidence suggests these effects are mediated via selective yet uncharacterized actions on tumor neovasculature. A novel derivative, colloidal gold bound TNF (cAu-TNF) has been shown to have similar antitumor effects as native TNF with less systemic toxicity in mice. These studies were done to determine their effects on tumor neovasculature, using in vivo video microscopy. Female C57BL/6 mice bearing 20 mm(2) MC38 or LLC tumors that are TNF sensitive and resistant tumors, respectively, had dorsal skinfold chambers implanted. The rate of interstitial accumulation of Texas red fluorescently labeled albumin in tumor and normal vasculature was measured after intravenous TNF, cAu-TNF or PBS. Changes in interstitial fluorescent intensity over time were quantified as a reflection of alterations in vascular permeability. MC38 bearing mice treated with TNF or cAu-TNF demonstrated a rapid, selective and significant increase in tracer accumulation in areas of neovasculature compared to those of normal vasculature. Experiments in LLC tumor bearing mice showed similar results. Monoclonal antibody against tissue factor partially abrogated the effects of TNF on MC38 neovasculature. These data provide direct evidence that TNF and cAu-TNF selectively and rapidly alter permeability in tumor neovasculature; a phenomenon that may be exploited to enhance selective delivery of chemotherapeutics to tumor.
    背景与目标: :肿瘤坏死因子(TNF)与美法仑单独灌注使用时可导致晚期癌症消退;证据表明这些作用是通过对肿瘤新脉管系统的选择性但未表征的作用介导的。一种新型衍生物,胶体金结合TNF(cAu-TNF)已显示出与天然TNF相似的抗肿瘤作用,并且对小鼠的全身毒性较小。使用体内视频显微镜,进行了这些研究以确定它们对肿瘤新脉管系统的影响。携带20毫米(2)MC38或LLC肿瘤的雌性C57BL / 6小鼠分别是TNF敏感和耐药性肿瘤,已植入了背部皮褶室。静脉注射TNF,cAu-TNF或PBS后,测量德克萨斯州红色荧光标记白蛋白在肿瘤和正常脉管系统中的间质累积率。间质荧光强度随时间的变化被量化为反映血管通透性变化的反映。与正常脉管系统的小鼠相比,用TNF或cAu-TNF治疗的MC38荷瘤小鼠在示踪剂在新脉管系统区域的蓄积迅速,选择性且显着增加。在LLC荷瘤小鼠中进行的实验显示了相似的结果。针对组织因子的单克隆抗体部分消除了TNF对MC38新脉管系统的影响。这些数据提供了直接的证据,表明TNF和cAu-TNF选择性和迅速地改变了肿瘤新脉管系统的通透性。一种可以用来增强化学疗法向肿瘤的选择性递送的现象。
  • 【金纳米颗粒在水中和反胶束中被磺化咪唑鎓盐稳定。】 复制标题 收藏 收藏
    DOI:10.1098/rsos.170481 复制DOI
    作者列表:Monti GA,Fernández GA,Correa NM,Falcone RD,Moyano F,Silbestri GF
    BACKGROUND & AIMS: :Herein we describe the synthesis of gold nanoparticles (Au-NPs) in presence of sulphonated imidazolium salts [1,3-bis(2,6-diisopropyl-4-sodiumsulfonatophenyl)imidazolium (L1), 1-mesityl-3-(3-sulfonatopropyl)imidazolium (L2) and 1-(3-sulfonatopropyl)imidazolium (L3)] in water and in a confinement environment created by reverse micelles (RMs). The Au-NPs were characterized-with an excellent agreement between different techniques-by UV-vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential. In homogeneous media, the Au-NPs interact with the imidazolium ring and the sulphonate groups were directed away from the NPs' surface. This fact is responsible for the Au-NPs' stability-over three months-in water. Based on the obtained zeta potential values we assume the degree of coverage of the Au-NPs by the imidazolium salts. In n-heptane/sodium 1,4-bis (2-ethylhexyl) sulfosuccinate (AOT)/water RMs, the Au-NPs formed in presence of sulphonated imidazolium salts present different patterns depending on the ligand used as stabilizer. Interestingly, the Au-NPs are more stable in time when the salts are present in AOT RMs (three weeks) in comparison with the same RMs system but in absence of ligands (less than an hour). Clearly, the sulphonated imidazolium salts are very effective Au-NPs stabilizers in a different medium and this generates a plus to be able to use them for multiple purposes.
    背景与目标: :在此,我们描述了在磺化咪唑鎓盐[1,3-双(2,6-二异丙基-4-钠磺酰基苯基)咪唑鎓(L1),1-甲磺酰基-3-(3)的存在下金纳米颗粒(Au-NPs)的合成-磺基丙基)咪唑鎓(L2)和1-(3-磺基丙基丙基)咪唑鎓(L3)]在水中和在由反胶束(RM)形成的封闭环境中。通过紫外可见光谱,透射电子显微镜(TEM),动态光散射(DLS)和Zeta电位,对Au-NP进行了表征-在不同技术之间有着极好的一致性。在均相介质中,Au-NP与咪唑鎓环相互作用,并且磺酸盐基团被引导远离NPs表面。这一事实是金纳米颗粒在水中三个月内稳定的原因。基于获得的ζ电位值,我们假设咪唑鎓盐对Au-NP的覆盖程度。在正庚烷/ 1,4-双(2-乙基己基)磺基琥珀酸钠(AOT)/水RMs中,根据用作稳定剂的配体,在磺化咪唑鎓盐存在下形成的Au-NPs具有不同的模式。有趣的是,与相同的RMs系统但没有配体(少于一个小时)相比,当盐存在于AOT RMs中时(三周),Au-NPs在时间上更稳定。显然,磺化的咪唑鎓盐在不同的介质中是非常有效的Au-NPs稳定剂,这产生了可将其用于多种目的的优势。
  • 【表征,制图和减轻手工采矿金矿中汞蒸气的排放。】 复制标题 收藏 收藏
    DOI:10.1016/j.envres.2012.10.015 复制DOI
    作者列表:Cordy P,Veiga M,Crawford B,Garcia O,Gonzalez V,Moraga D,Roeser M,Wip D
    BACKGROUND & AIMS: :Artisanal miners sell their gold to shops that are usually located in the urban core, where the mercury-gold amalgam is burned to evaporate the mercury that was added during ore processing. People living and working near these gold shops are exposed to intermittent and extreme concentrations of mercury vapour. In the urban centres of Segovia, Colombia, and Andacollo, Chile, the average concentrations measured by mobile mercury vapour analyzer transects taken repeatedly over several weeks were 1.26 and 0.338μgm(-3), respectively. By World Health Organization standards, these towns are exposed to significant health hazard, and globally, the millions of miners, as well as non-miners who live near gold shops, are at serious risk of neurological and renal deficits. Measurements taken in Suriname, Ecuador and Peru reveal this to be a widespread phenomenon with unique regional variations and myriad attempts at remediation. Maps of average mercury concentrations show the spatial distribution of the hazard in relation to residential buildings and schools. Measurements from towers show the temporal variability of mercury concentrations, and suggest that large quantities of mercury are available for long-range atmospheric transport. Mercury mapping in Segovia in 2011 suggest a 10% reduction in airborne mercury concentrations over 2010, despite a 30% increase in gold production. This is attributable to the adoption of retorts by miners and regulations banning new processing centres to the rural periphery. This is the first full description of artisanal mining gold shop practices and of the character, quantity, and remediation of mercury emissions within urban mining centres.
    背景与目标: :手工采矿者将黄金出售给通常位于城市中心的商店,在那里燃烧汞金汞合金,以蒸发矿石加工过程中添加的汞。在这些金店附近生活和工作的人们暴露于间歇性和极高浓度的汞蒸气中。在哥伦比亚的塞哥维亚和智利的安达科洛的城市中心,通过移动水银蒸汽分析仪横断面测量的平均浓度在数周内重复测量,分别为1.26和0.338μgm(-3)。按照世界卫生组织的标准,这些城镇面临严重的健康危害,全球范围内,数百万矿工以及居住在金店附近的非矿工都面临严重的神经系统疾病和肾功能不全的风险。在苏里南,厄瓜多尔和秘鲁进行的测量表明,这是一种普遍现象,具有独特的地区差异和无数次的补救尝试。平均汞浓度图显示了与住宅建筑物和学校有关的危害的空间分布。从塔上进行的测量表明汞浓度随时间变化,并表明大量汞可用于远程大气传输。尽管黄金产量增加了30%,2011年塞哥维亚的汞测绘表明空气中的汞浓度比2010年降低了10%。这是由于矿工采用了反蒸煮法,以及禁止向农村边缘地区建立新加工中心的法规。这是对手工采矿金店做法以及城市采矿中心内汞排放的特征,数量和补救措施的首次完整描述。
  • 【乳胶中基于胶体金的侧向流免疫色谱分析技术对广谱法测定麦角甾醇及其类似物的检测。】 复制标题 收藏 收藏
    DOI:10.1016/j.foodchem.2020.126697 复制DOI
    作者列表:Yin M,Hu X,Sun Y,Xing Y,Xing G,Wang Y,Li Q,Wang Y,Deng R,Zhang G
    BACKGROUND & AIMS: :Based on colloidal gold and broad-spectrum monoclonal antibody that binds to zeranol and its five analogues with high sensitivity, a lateral flow immunochromatographic assay (LFIA) in a competitive format was developed to specifically determine residues of zeranol, an illegal growth promoter in livestock. In this study, the assay had high sensitivity and was broad-spectrum only for zeranol and its five analogues, and the results were obtained within 10 min without needing sophisticated procedures. The cutoff values for zeranol and its five analogues were 10 ng/mL, and the IC50 values for zeranol, β-zearalanol, zearalanone, α-zearalenol, β-zearalenol and zearalenone were 1.250, 1.800, 1.775, 1.225, 1.709 and 1.319 ng/mL, respectively. The recovery rates were ranged from 85.6 to 93.9%, with the coefficient of variations less than 12.4%. The results demonstrated that the LFIA could be used for rapid, simultaneous, semi-quantitative and quantitative detection of residues of zeranol and its five analogous in milk.
    背景与目标: :基于胶体金和广谱单克隆抗体,它们以高灵敏度结合至沙仑醇及其五种类似物,开发了一种竞争性形式的侧流免疫色谱测定法(LFIA),用于特异性测定家畜非法生长促进剂沙仑醇的残留量。在这项研究中,该测定法具有很高的灵敏度,并且仅对麦醇及其五种类似物具有广谱性,并且无需复杂的程序即可在10分钟内获得结果。 zeranol及其5个类似物的截断值为10 ng / mL,zeranol,β-玉米赤霉烯醇,玉米赤霉烯酮,α-玉米赤霉烯醇,β-玉米赤霉烯醇和玉米赤霉烯酮的IC50值为1.250、1.800、1.775、1.225、1.709和1.319 ng / mL。回收率介于85.6%至93.9%之间,变异系数小于12.4%。结果表明,LFIA可用于快速,同时,半定量和定量检测牛奶中的麦角甾醇及其五种类似物的残留。

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