Copper

  • 文章类型: Journal Article
    植入物广泛用于骨科和牙科科学领域。钛(TI)及其合金已成为应用最广泛的植入材料,但植入物相关感染仍然是植入物手术后常见且严重的并发症.此外,钛表现出生物惰性,防止植入物和骨组织强烈结合,并可能导致植入物松动和脱落。因此,预防植入物感染和提高其骨诱导能力是重要目标。
    研究纳米银/聚乳酸乙醇酸(NSPTICU)涂层钛铜合金植入物的抗菌活性和骨诱导能力,为抑制植入物相关感染和促进骨整合提供新的途径。
    我们首先通过研究MC3T3-E1细胞的增殖和分化来检查NSPTICU植入物的体外成骨能力。此外,通过显微计算机断层扫描(micro-CT)研究了NSPTICU植入物诱导SD大鼠成骨活性的能力,苏木精-伊红(HE)染色,masson染色,免疫组织化学和范吉森(VG)染色。用革兰氏阳性金黄色葡萄球菌(Sa)和革兰氏阴性大肠杆菌(E。大肠杆菌)细菌。Sa被用作试验细菌,通过粗视标本采集研究了NSPTICU植入大鼠体内的抗菌能力,细菌菌落计数,HE染色和Giemsa染色。
    茜素红染色,碱性磷酸酶(ALP)染色,实时定量聚合酶链反应(qRT-PCR)和蛋白质印迹分析显示,NSPTICU促进MC3T3-E1细胞的成骨分化。体外抗菌结果表明,NSPTICU植入物表现出更好的抗菌性能。动物实验表明,NSPTICU可抑制炎症反应,促进骨缺损的修复。
    NSPTICU具有出色的抗菌和骨诱导能力,骨缺损的治疗具有广阔的应用前景。
    UNASSIGNED: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals.
    UNASSIGNED: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration.
    UNASSIGNED: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining.
    UNASSIGNED: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects.
    UNASSIGNED: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.
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  • 文章类型: Journal Article
    骨质疏松和骨折常发生在精神科病房。尽管最近的研究表明精神病患者的骨矿物质密度(BMD)降低,许多风险因素仍然未知。本研究旨在探讨封闭式病房长期住院精神病患者BMD降低的危险因素。
    对住院超过20周的精神病患者进行了横断面研究。根据BMD将患者分为三组:正常,骨质减少,和骨质疏松症。使用简明精神病评定量表(BPRS)评估精神病症状。收集精神病的相关病史,并测定与骨质疏松相关的生物标志物。进行单变量和多变量有序逻辑回归分析,以确定与BMD类别显着相关的变量。其他分析评估了确定的临床变量与生物标志物和可能与骨质疏松症相关的精神症状之间的关联。
    71名患者(28名正常BMD,17骨量减少,和26名骨质疏松症)参与了这项研究。多变量序数逻辑分析表明,未治疗精神病(DUP)的持续时间是危险因素(比值比=0.77,95%置信区间:0.63-0.91,p=0.006),调整性别和年龄的主要混杂因素。其他分析显示BPRS有显著差异,BPRS阴性症状评分,短DUP组(DUP≤1年)和长DUP组(DUP>1年)之间的Cu/Zn比。
    DUP可能会影响长期精神病患者的BMD,可能部分是由于阴性症状和微量营养素异常的严重程度增加。缩短未治疗期可能会降低骨质疏松症的风险。
    UNASSIGNED: Osteoporosis and bone fractures occur often on psychiatric wards. Although recent studies showed that bone mineral density (BMD) decreases in psychiatric patients, many risk factors remain unknown. This study aimed to explore the risk factors for decreased BMD in long-term psychiatric inpatients in a closed ward.
    UNASSIGNED: A cross-sectional study of psychiatric inpatients hospitalized for over 20 weeks was conducted. Patients were divided into three groups according to BMD: normal, osteopenia, and osteoporosis. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). The relevant history of psychiatric diseases was collected, and biomarkers related to osteoporosis were measured. Univariable and multivariable ordinal logistic regression analyses were performed to identify variables significantly associated with BMD category. Additional analyses evaluated the associations between an identified clinical variable and biomarkers and psychiatric symptoms that may be related to osteoporosis.
    UNASSIGNED: Seventy-one patients (28 normal BMD, 17 osteopenia, and 26 osteoporosis) participated in the study. The multivariable ordinal logistic analysis showed that the duration of untreated psychosis (DUP) was a risk factor (odds ratio = 0.77, 95% confidence interval: 0.63-0.91, p = 0.006), adjusting for the major confounders of sex and age. Additional analysis showed significant differences in BPRS, BPRS Negative Symptom score, and the Cu/Zn ratio between the short-DUP group (DUP ≤ 1 year) and the long-DUP group (DUP > 1 year).
    UNASSIGNED: The DUP may affect BMD in long-term psychiatric inpatients, presumably partly through increased severity of negative symptoms and micronutrient abnormalities. Shortening the untreated period might reduce the risk of osteoporosis.
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  • 文章类型: Journal Article
    氨基酸差向异构化,将L-氨基酸转化为D-氨基酸的过程,会导致蛋白质结构的改变,随后,其生物学功能。这种修饰不会引起蛋白质m/z的变化,并且在蛋白质分析过程中可能会被忽略。天冬氨酸差向异构化(AAE)比其他氨基酸更快,并且可以被自由基和过氧化物加速。在这项工作中,已开发并验证了一种新颖的位点特异性HPLC方法,该方法使用手性固定相确定过氧化物酶2的活性位点模型肽(AP)中的AAE。该方法具有良好的线性(1-200μg/mL)和定量限(LOQ),低,中等,高浓度在85%到115%之间。使用开发的方法研究了AP中AAE的动力学,结果表明,当抗坏血酸和Cu2+共存时,AP的empimerized迅速。AAE程度随时间增加,与过氧化氢的产生呈正相关。
    Amino acid epimerization, a process of converting L-amino acids to D-amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 - 200 μg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation.
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  • 文章类型: Journal Article
    在这里,我们使用N,N,O供体配体(HL),即2-((2-羟丙基)亚氨基)甲基)-6-甲氧基苯酚。对该协调饱和系统的β-内酰胺酶样活性的光谱光度研究表明,其催化效率低下,以硝化氮为模型底物。由于其从DFT计算预测的窄带隙(2.40eV)及其对UV光的较高响应性,该复合物作为有前途的光催化剂引起了极大的兴趣。因此,在长时间的紫外线照射下,在空穴清除剂(H2O-MeOH)的存在下,C1有效地参与了高氯酸盐光催化还原为Cl-的过程,并且其本身被光裂解,产生了新的深棕色的氯还原双核晶体络合物C2{[CuL(H2O)2Cl3]H2O}。此外,C2被用作功能性β-内酰胺酶模型,并被发现在70:30(V/V)MeOH-H2O介质中对硝基青素的水解具有显着的催化能力。已经推测该前催化剂C2产生在水解中起关键因素的水性桥接活性催化剂。这种现象再次通过电位pH滴定实验确定,其中C2在碱性pH范围内仅显示一个pKa值(7.11)。表明桥接水分子的去质子化。根据其他几个动力学研究,可以推测,硝化氮的水解是由桥接氢氧化物的亲核攻击引发的,然后是中间体的非常快速的质子化以提供水解产物。值得注意的是,在存在外部氯化物浓度的情况下,硝化氮的水解速率受到极大抑制。据我们所知,这是有关这种四核铜(II)席夫碱配合物的光化学行为的第一份报告。我们目前的兴趣集中在发明一种有效的β-内酰胺酶抑制治疗剂,并通过全面的化学分析阐明其机制。
    Herein, we present a dark-green crystalline tetranuclear Cu(II) Schiff base complex {C1 = [Cu4L4](ClO4)4(DMF)4(H2O)} using a N,N,O donor ligand (HL), namely 2-(((2-hydroxypropyl)imino)methyl)-6-methoxyphenol. Spectro-photometrical investigation on the β-lactamase-like activity of this coordinately saturated system revealed its catalytic inefficiency towards hydrolysis of nitrocefin as a model substrate. This complex has attracted significant interest as a promising photo-catalyst owing to its narrow band gap (2.40 eV) as predicted from DFT calculations and its higher responsivity towards UV light. Therefore, C1 is effectively involved in the photocatalytic reduction of perchlorate to Cl- in the presence of a hole scavenger (H2O-MeOH) under prolonged UV irradiation and itself becomes photo-cleaved to yield a new dark-brown colored chlorobridged dinuclear crystalline complex C2 {[CuL(H2O)2Cl3]H2O}. Furthermore, C2 was deployed as a functional β-lactamase model and was found to show a remarkable catalytic proficiency towards the hydrolysis of nitrocefin in 70 : 30 (V/V) MeOH-H2O medium. This pro-catalyst C2 has been speculated to generate an aqua bridged active catalyst that plays a crucial factor in hydrolysis. This phenomenon was again experimentally established by potentiometric pH titration where C2 displays only one pKa value (7.11) in the basic pH range, indicating the deprotonation of the bridged water molecule. Based on several other kinetic studies, it may be postulated that the hydrolysis of nitrocefin is initiated by the nucleophilic attack of a bridging hydroxide, followed by very fast protonation of the intermediate to furnish the hydrolyzed product. It is noteworthy that the rate of nitrocefin hydrolysis is greatly inhibited in the presence of external chloride concentration. To the best of our knowledge, this is the first report on the photochemical behavior of such a tetranuclear copper(II) Schiff base complex. Our current interest is focused on inventing a potent β-lactamase inhibitory therapeutic as well as elucidating its mechanism through comprehensive chemical analysis.
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  • 文章类型: Journal Article
    人类阳离子抗微生物蛋白(hCAP)对应于151-162个hCAP的重叠序列,命名为KR-12肽是唯一类型的人类Cathelicidin的最小部分,已被证明可修改为更有效的抗菌剂。在这项研究中,计算机模拟分析,由电位滴定和等温滴定量热技术支持,进行以鉴定KR-12的潜在Cu(II)结合位点。在给定理论水平(GFN2-xTB/ALPB)下对呈现的数据的分析揭示了哪些肽链片段参与最有利的KR-12-Cu(II)结合模式。基于量子化学方法,提出了Cu(II)与肽的最有利的配位模式,并讨论了相互作用的化学性质。结果表明,KR-12主要通过主链的氧原子与金属离子相互作用;然而,预期对Cu(II)的相互作用至关重要的两种类型的氨基酸是D(天冬氨酸)和R29(精氨酸)。已经证明,为了解释肽-金属离子系统中相互作用过程的复杂性,使用理论方法有时有必要解释实验结果的细节,并提供对这些动态系统的深入理解。
    The human cationic antimicrobial protein (hCAP) corresponding to the overlapping sequences of 151-162 of hCAP named KR-12 peptide is the smallest portion of the only type of human Cathelicidin, which has been shown to be modifiable into a more effective antimicrobial. In this study, an in silico analysis, supported by potentiometric titration and isothermal titration calorimetry techniques, was performed to identify potential Cu(II) binding sites of KR-12. The analysis of the presented data at the given theoretical level (GFN2-xTB/ALPB) revealed which peptide chain fragments are involved in the most favourable KR-12-Cu(II) binding mode. Based on a quantum chemical approach, the most favourable coordination modes of Cu(II) to peptides are proposed together with the discussion of the chemical nature of the interactions. The presented results demonstrated that KR-12 interacts with metal ions mostly via the main chain\'s oxygen atoms; however, the two types of amino acids that are expected to be vital for the interaction of Cu(II) are D (aspartic acid) and R29 (arginine). It was demonstrated that in order to explain the complexity of the interaction process in peptide-metal ion systems, the use of theoretical methods is sometimes necessary to explain the details of the experimental results and provide an in-depth understanding of these dynamic systems.
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  • 文章类型: Journal Article
    背景:使用微生物生物合成金属纳米颗粒是一种神话般的新兴的生态友好科学,具有明确的尺寸,形状和受控的单分散性。铜纳米颗粒,在其他金属颗粒中,由于它们在电子产品中的应用,引起了越来越多的关注,光学,催化作用,和抗菌剂。
    结果:这项研究解释了来自土壤菌株的铜纳米颗粒的生物合成和表征,NialliaculansG9和拟杆菌。S4c采用环保方法。这些菌株提供了铜离子的最大还原和最大合成CuNPs。CuNPs的生物形成已经通过紫外-可见吸收光谱进行了表征,X射线衍射,傅里叶变换红外光谱,X射线分析和透射电子显微镜分析。使用紫外可见光谱扫描,合成的CuNPsSPR光谱在λ304和308nm处显示出最大吸收峰。所产生的CuNPs的TEM研究揭示了通过G9菌株的尺寸范围为13-100nm的球形/六方纳米颗粒和通过S4c菌株的尺寸范围为5-40nm的球形纳米颗粒的发展。还证实了CuONPs的官能团和化学组成。研究了生物合成的CuNPs对某些人类病原体的抗微生物活性。从G9菌株产生的CuNPs对白色念珠菌ATCC10,231的活性最高,对铜绿假单胞菌ATCC9027的活性最低。来自S4c菌株的CuNPs对大肠杆菌ATCC10,231的活性最高,对肺炎克雷伯菌ATCC13,883的活性最低。
    结论:目前的工作集中在增加两个分离株的CuNPs产量,NialliaculansG9和拟杆菌。S4c,然后被描述为旁边的。所使用的分析和化学组成技术验证了G9和S4c生物合成的纳米铜中CuONPs的存在。与G9菌株相比,S4c的CuNPs更小,形状更多样,根据TEM图像。在抗菌活性方面,发现来自G9和S4c的生物合成的CuNPs分别对白色念珠菌ATCC10,231和大肠杆菌ATCC10,231更有效。
    BACKGROUND: Biosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents.
    RESULTS: This investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs\' SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13-100 nm by the G9 strain and spherical nanoparticles with a size range of 5-40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883.
    CONCLUSIONS: The present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.
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  • 文章类型: Journal Article
    目的:临床比较更广泛的弓丝与标准弓丝的效果,在这两种情况下都使用常规支架,在调平和对齐过程中上颌和下颌弓的横向和切牙变化。
    方法:将52例出现拥挤的患者分为两组;一组接受宽Damon弓丝,另一组接受标准的3MOrthoFormIII卵形弓丝。所有参与者均使用相似的弓丝序列(0.014、0.018、0.016×0.022/0.016×0.025、0.019×0.025NiTi/CuNiTi弓丝)接受常规托槽治疗。从治疗前(T0)和插入0.019×0.025NiTi弓丝(T1)后六周的藻酸盐印模中获得数字铸模。获得每位患者的治疗前(T0)和对齐后(T1)侧位头颅图。主要结果是横弓尺寸和切牙倾斜度的变化。次要结果是切牙位置的水平和垂直线性变化。
    结果:收集了47例患者的完整数据。各组治疗期间牙弓宽度均有显著增加,3M组上磨间宽度除外(P=0.071)。Damon丝引起上颌第二磨牙间宽度的统计学显着增加(P=0.042),下颌第一前磨牙间(P=0.043),与3M组相比,第二前磨牙间(P=0.008)和磨牙间宽度(P=0.033)。各组内切牙前倾增加和切牙位置线性变化显著,Damon组的下颌切牙前移(P=0.004)和水平前移(P=0.038)较少。
    结论:Damon弓丝使上颌第二磨牙间宽度和下颌第一前磨牙间宽度增加相对较大,第二磨牙间,和摩尔间宽度,下颌切牙的前倾和水平前移较少。该研究提供了宝贵的证据,表明使用带有自锁托槽的宽弓丝是在该系统中观察到的任何更大扩张背后的原因,而不是自锁托槽系统所施加的独特机械和生物学特征。
    结论:我们的结果表明,与通常与常规托槽一起使用的较窄的标准弓丝相比,Damon弓丝可能是更好的选择,尤其是在下颌弓,在计划用非提取方法解决轻度至中度拥挤的情况下。然而,由于在没有后交叉咬合的情况下的足弓扩张提出了长期稳定性的问题,应谨慎解释使用宽导线的报告优势,并应在保留阶段加以考虑,考虑到实现良好的治疗后闭塞对于增强治疗后稳定性是重要的。
    OBJECTIVE: To clinically compare the effects of broader archwires to standard archwires, using conventional brackets in both cases, on the transverse and incisor changes in maxillary and mandibular arches during leveling and alignment.
    METHODS: Fifty-two patients presenting with crowding were allocated into two groups; one group received the broad Damon archwires while the other received standard 3M OrthoForm III Ovoid archwires. All participants were treated with conventional brackets using similar archwire sequences (0.014, 0.018, 0.016 × 0.022/0.016 × 0.025, 0.019 × 0.025 NiTi/CuNiTi archwires). Digital casts were obtained from alginate impressions before treatment (T0) and six weeks after inserting 0.019 × 0.025 NiTi archwires (T1). Pretreatment (T0) and post-alignment (T1) lateral cephalograms were obtained for each patient. The primary outcomes were the changes in the transverse arch dimensions and incisor inclination. The secondary outcomes were the horizontal and vertical linear changes in incisor position.
    RESULTS: Complete data were collected for 47 patients. There was a significant increase in arch width during treatment within each group, except for upper inter-molar width in 3M group (P = 0.071). Damon wire induced a statistically significant increase in maxillary inter-second premolar width (P = 0.042), and mandibular inter-first premolar (P = 0.043), inter-second premolar (P = 0.008) and inter-molar widths (P = 0.033) compared to 3M group. The increase in incisor proclination and the linear change in incisor position were significant within each group, with less mandibular incisor proclination (P = 0.004) and horizontal advancement (P = 0.038) in the Damon group.
    CONCLUSIONS: Damon archwires created a comparatively greater increase in the maxillary inter-second premolar width and the mandibular inter-first premolar, inter-second premolar, and inter-molar widths, and less proclination and horizontal advancement in mandibular incisors. The study provides invaluable evidence that using broad archwires with self-ligating brackets is the reason behind any greater expansion observed in this system rather than the unique mechanical and biological features exerted by the self-ligating system.
    CONCLUSIONS: Our results suggest that Damon archwire might be a better alternative compared to the narrower standard archwires that are usually used with conventional brackets, especially in the mandibular arch, in cases where mild to moderate crowding is planned to be resolved with a non-extraction approach. However, as arch expansion in the absence of posterior crossbites raises the question of long-term stability, the reported advantage of the use of wide wires should be interpreted with caution and should be considered in the retention phase, bearing in mind that achieving a good post-treatment occlusion is important for enhancing post-treatment stability.
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  • 文章类型: Journal Article
    本研究探讨了使用Cu2S-MPA/NGOD复合材料进行共振能量转移和吸附调制的原理。这些复合材料可以有效地控制电化学发光(ECL)的猝灭过程。在合成Cu2S-MPA期间添加巯基丙酸(MPA)以增强其与氮掺杂的石墨烯量子点(NG0D)的附着。NGODs的紫外吸收峰与鲁米诺ECL的发射峰一致,使共振能量转移和增强Cu2S-MPA的猝灭能力。同时,还有另一种淬火策略。当容易还原的Cu离子与NGOD结合时,它们会部分还原为Cu。这削弱了对活性氧(ROS)的电催化作用,并对电子转移产生了不利影响。在最优条件下,免疫传感器ECL强度在0.00001-40ng/mL范围内随癌胚抗原(CEA)浓度的对数线性下降,检测限为0.269fg/mL。该传感器可有效用于实际血清样品中CEA的鉴定。
    This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu2S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu2S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu2S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu+ ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples.
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  • 文章类型: Journal Article
    背景:这项1/2期研究评估了双硫仑和铜(DSF/Cu)联合放射治疗(RT)和替莫唑胺(TMZ)对新诊断的胶质母细胞瘤(GBM)患者的安全性和初步疗效。
    方法:患者接受标准RT和TMZ,DSF(每日250-375mg)和Cu,然后是佐剂TMZ加DSF(500mg/天)和Cu。药代动力学分析使用高效液相色谱-质谱法确定血浆和肿瘤中的药物浓度。
    结果:33名患者,中位随访时间为26.0个月,被治疗,包括12个IDH突变体,9NF1-突变体,3BRAF突变体,和其他9个IDH野生型病例。在阶段1臂中,18名患者接受了治疗;剂量限制性毒性(DLT)概率在250mg/天时为10%(95%CI:3-29%),在375mg/天时为21%(95%CI:7-42%)。2期组以250mg/天治疗另外15名患者。与未使用DSF/Cu治疗的机构对应物相比,IDH突变体和NF1突变体队列之间的总生存期或无进展生存期没有显着差异。然而,3例BRAF突变患者出现延长缓解.二乙基-二硫代氨基甲酸酯-铜,DSF/Cu的拟议活性代谢物,在血浆中检测到,但在肿瘤中未检测到。
    结论:DSF与RT和TMZ的最大耐受剂量为375mg/天。DSF/Cu对大多数患者显示有限的临床疗效。然而,在BRAF突变体GBM中观察到有希望的疗效,保证进一步调查。
    OBJECTIVE: This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM).
    METHODS: Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry.
    RESULTS: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors.
    CONCLUSIONS: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation.
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  • 文章类型: Journal Article
    根据估计,30%到40%,全球的水果被浪费了,导致收获后损失,并在全球范围内造成100至1000亿美元的经济损失。其中,所有水果中被丢弃的橙子的比例约为20%。利用橙皮的一种新颖且增值的方法是纳米科学。在本研究中,进行了一种合成方法来制备金属纳米颗粒(铜和银);通过利用食物废物(柑橘植物皮)作为生物活性还原剂。此外,柑橘提取物对金属盐氯化铜和硝酸银具有还原活性,形成Cu-NP(铜纳米颗粒)和Ag-NP(银纳米颗粒)。研究了两种制备的纳米颗粒的体外潜力,以对抗植物病原菌欧文氏菌(Pectobacteriumcarotovorum)和病原体对人类健康大肠杆菌的影响(E。大肠杆菌)和金黄色葡萄球菌(S.金黄色葡萄球菌)。此外,通过与植物(马铃薯切片)的相互作用来检查两种类型的纳米颗粒的体内拮抗潜力。此外,还检查了其他抗致病性(抗病毒和抗真菌)特性。进行统计分析以解释合成的Ag-NP和Cu-NP之间的显著性水平和抗致病性有效性。表面形貌,通过扫描电子显微镜分析了颗粒的元素描述和尺寸,透射电子显微镜,能量色散光谱和zetasizer(此外,多分散指数和zeta电位)。通过UV-Vis光谱法(铜在339nm处的激发峰和银在415nm处的激发峰)进行颗粒制备的理由,并且通过X射线衍射观察结晶性质。因此,制备的颗粒对植物中的软腐病病原体非常有效,也可以有效地用于一些其他多功能应用,如生物活性运动服,手术礼服,生物活性绷带和手腕或膝盖压缩绷带,等。
    According to an estimate, 30% to 40%, of global fruit are wasted, leading to post harvest losses and contributing to economic losses ranging from $10 to $100 billion worldwide. Among, all fruits the discarded portion of oranges is around 20%. A novel and value addition approach to utilize the orange peels is in nanoscience. In the present study, a synthesis approach was conducted to prepare the metallic nanoparticles (copper and silver); by utilizing food waste (Citrus plant peels) as bioactive reductants. In addition, the Citrus sinensis extracts showed the reducing activity against metallic salts copper chloride and silver nitrate to form Cu-NPs (copper nanoparticles) and Ag-NPs (Silver nanoparticles). The in vitro potential of both types of prepared nanoparticles was examined against plant pathogenic bacteria Erwinia carotovora (Pectobacterium carotovorum) and pathogens effect on human health Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, the in vivo antagonistic potential of both types of prepared nanoparticles was examined by their interaction with against plant (potato slices). Furthermore, additional antipathogenic (antiviral and antifungal) properties were also examined. The statistical analysis was done to explain the level of significance and antipathogenic effectiveness among synthesized Ag-NPs and Cu-NPs. The surface morphology, elemental description and size of particles were analyzed by scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy and zeta sizer (in addition polydispersity index and zeta potential). The justification for the preparation of particles was done by UV-Vis Spectroscopy (excitation peaks at 339 nm for copper and 415 nm for silver) and crystalline nature was observed by X-ray diffraction. Hence, the prepared particles are quite effective against soft rot pathogens in plants and can also be used effectively in some other multifunctional applications such as bioactive sport wear, surgical gowns, bioactive bandages and wrist or knee compression bandages, etc.
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