GPC

GPC
  • 文章类型: Journal Article
    肝癌,主要是肝细胞癌(HCC),是全球癌症相关死亡的第二大原因。它的典型特征是快速进展,预后不良,和高死亡率。鉴于这些挑战,寻找有助于早期诊断和靶向治疗的分子靶标仍然势在必行.Glypican3(GPC3),一种细胞表面糖蛋白,作为解决HCC组织中过表达的HCC的有希望的候选者;GPC3是用于肝癌诊断的可靠的免疫组织化学标记物,并且是通过血清中可溶性GPC3进行液体活检的潜在标记物。已经开发了针对GPC3的各种免疫疗法,包括疫苗,抗GPC3免疫毒素,和嵌合抗原受体修饰的细胞。这次审查全面涵盖了结构,物理化学性质,生物学功能,以及GPC3的临床应用。它探讨了以GPC3为中心的诊断和治疗策略,为在具有挑战性的HCC中改善早期检测和靶向治疗提供了希望。
    Liver cancer, primarily hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths globally. It is typically characterized by rapid progression, poor prognosis, and high mortality rates. Given these challenges, the search for molecular targets aiding early diagnosis and targeted therapy remains imperative. Glypican 3 (GPC3), a cell-surface glycoprotein, emerges as a promising candidate for addressing HCC Overexpressed in HCC tissues; GPC3 is a credible immunohistochemical marker for liver cancer diagnosis and a potential marker for liquid biopsy through soluble GPC3 in serum. Various immunotherapies targeting GPC3 have been developed, including vaccines, anti-GPC3 immunotoxins, and chimeric antigen receptor-modified cells. This review comprehensively covers the structure, physicochemical properties, biological functions, and clinical applications of GPC3. It explores diagnostic and treatment strategies centered around GPC3, offering hope for improved early detection and targeted therapies in the challenging landscape of HCC.
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  • 文章类型: Journal Article
    本教程介绍了SEC-MALS的理论和应用,具有最小方程,并专注于合成聚合物表征,作为聚合物科学家想要了解更多关于SEC-MALS的切入点。我们讨论了静态光散射的原理,概述其产生绝对重均摩尔质量值的能力,并将其应用扩展到SEC-MALS。强调实用元素,使研究人员能够理解Mn的值,Mw,并在SEC-MALS实验中确定实验条件和输入值,例如比折射率增量(dn/dc),影响结果。几个说明性的SEC-MALS实验证明了分离质量对Mn(与Mw相反)的影响,来自样品制备的SEC色谱图中污染物的出现,浓度对数据质量的影响,以及聚合物拓扑结构如何影响SEC中的分子量表征。最后,我们处理实际考虑,常见问题,和持续的误解。
    This tutorial review presents the theory and application of SEC-MALS with minimal equations and a focus on synthetic polymer characterization, serving as an entry point for polymer scientists who want to learn more about SEC-MALS. We discuss the principles of static light scattering, outline its capability to generate absolute weight-average molar mass values, and extend its application to SEC-MALS. Practical elements are emphasized, enabling researchers to appreciate how values for M n , M w , and Đ are determined in an SEC-MALS experiment and how experimental conditions and input values, such as the specific refractive index increment ( d n / d c ), influence the results. Several illustrative SEC-MALS experiments demonstrate the impact of separation quality on M n (as opposed to M w ), the appearance of contaminants in SEC chromatograms from sample preparation, the influence of concentration on data quality, and how polymer topology affects molecular weight characterization in SEC. Finally, we address practical considerations, common issues, and persistent misconceptions.
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  • 文章类型: Journal Article
    拉沙病毒估计每年导致数千人死亡,主要是由于其自然宿主的溢出效应,Mastomys啮齿动物。创建疫苗和抗体疗法的努力必须考虑到拉沙病毒糖蛋白复合物(GPC)的进化变异性,介导病毒进入细胞,是中和抗体的靶标。要绘制GPC可访问的进化空间,我们使用假病毒深度突变扫描来测量几乎所有GPC氨基酸突变如何影响细胞进入和抗体中和.我们的实验在整个GPC中定义了功能约束。我们用一组单克隆抗体定量GPC突变如何影响中和。所有测试的抗体都通过天然拉沙病毒谱系中存在的突变而逃脱。总的来说,我们的工作描述了一种生物安全2级方法来阐明GPC可进入的突变空间,并展示了抗原变异的前瞻性表征如何有助于治疗和疫苗的设计.
    Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus\'s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.
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  • 文章类型: Journal Article
    历史上,对刺激相关时频模式的分析一直是大多数脑电图(EEG)研究的基石.已经多次研究了在感觉和认知任务期间与精神病性障碍相关的高频波的异常振荡。然而,静息状态低频带的任何明显差异尚未确定。对α和δ波段波的频谱分析表明,独立于刺激的EEG在识别病理性大脑的异常活动模式方面的有效性。一个包含多个频带的广义模型应该更有效地将潜在的脑电图生物标志物与首发精神病(FEP)相关联。导致准确的诊断。我们探索了多种机器学习方法,包括随机森林,支持向量机,和高斯过程分类器(GPC),证明静息状态功率谱密度(PSD)区分FEP患者与健康对照的实用性。本文对PSD分析的预处理方法进行了全面的讨论,并对不同模型进行了详细的比较。GPC模型优于其他模型,特异性为95.78%,表明PSD可以作为一种有效的特征提取技术,用于分析和分类精神疾病的静息状态EEG信号。
    Historically, the analysis of stimulus-dependent time-frequency patterns has been the cornerstone of most electroencephalography (EEG) studies. The abnormal oscillations in high-frequency waves associated with psychotic disorders during sensory and cognitive tasks have been studied many times. However, any significant dissimilarity in the resting-state low-frequency bands is yet to be established. Spectral analysis of the alpha and delta band waves shows the effectiveness of stimulus-independent EEG in identifying the abnormal activity patterns of pathological brains. A generalized model incorporating multiple frequency bands should be more efficient in associating potential EEG biomarkers with first-episode psychosis (FEP), leading to an accurate diagnosis. We explore multiple machine-learning methods, including random-forest, support vector machine, and Gaussian process classifier (GPC), to demonstrate the practicality of resting-state power spectral density (PSD) to distinguish patients of FEP from healthy controls. A comprehensive discussion of our preprocessing methods for PSD analysis and a detailed comparison of different models are included in this paper. The GPC model outperforms the other models with a specificity of 95.78% to show that PSD can be used as an effective feature extraction technique for analyzing and classifying resting-state EEG signals of psychiatric disorders.
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  • 文章类型: Journal Article
    最近对在食品生产中使用蜡质淀粉的兴趣是由于用天然淀粉类似物代替化学改性淀粉作为质地形成剂的可能性。然而,缺乏相关研究,比较不同品种的市售蜡质淀粉的分子和功能特性。因此,这项研究的目的是比较马铃薯中的天然蜡质淀粉,玉米,还有米饭,特别注意与分子结构有关的流变特性。被调查的马铃薯,玉米,由于淀粉的植物来源和品种,大米淀粉制剂的分子特性明显不同。蜡质淀粉的分子量明显高于正常淀粉的分子量。这种现象伴随着溶液中蜡质淀粉大分子的更松散的构象。直链淀粉的存在赋予了将淀粉溶胶凝结成凝胶的能力,导致淀粉糊的流变特性发生实质性变化,和蜡质淀粉糊的特点是更粘稠的流动性和更光滑的质地。分层聚类分析表明,功能特性之间的差异对于正常比蜡质制剂更明显。其中马铃薯淀粉,不管它的品种,具有最独特的特点。
    Recent interest in the use of waxy starches in food production is due to the possibility of replacing chemically modified starches as texture-forming agents with native starch analogues. However, there is a lack of a coherent research comparing different varieties of commercially available waxy starches with respect to their molecular and functional properties. Therefore, the objective of this study was to compare native waxy starches from potatoes, corn, and rice, with particular attention to rheological characteristics in relation to molecular structure. The investigated potato, corn, and rice starch preparations were characterized by significantly different molecular properties due to both botanical origin of starch and variety. The molecular weights of waxy starches were significantly higher than those of their normal counterparts. This phenomenon was accompanied by a more loose conformation of the waxy starch macromolecule in solution. The presence of amylose confers the ability to coagulate starch sol into gel, resulting in substantial changes in the rheological properties of starch paste, and waxy starch pastes being characterized by more viscous flow and smoother texture. Hierarchical cluster analysis indicated that differences between functional properties are more notable for normal than for waxy preparations, in which potato starch, regardless of its variety, was characterized by the most unique characteristics.
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  • 文章类型: Journal Article
    通过自由基聚合获得基于藻酸钠(SA)和部分中和的聚(丙烯酸)的水凝胶。水凝胶与N交联,N'-亚甲基双丙烯酰胺(MBA),同时将所得聚合物接枝到SA上。FTIR光谱的结果表明,所有的水凝胶都被有效地合成,海藻酸钠与聚(丙烯酸钠)基质化学键合。熔化热和玻璃化转变参数的DSC分析表明,水凝胶结构由于交联过程而发生了变化。在不同浓度下测试海藻酸钠和MBA以确定它们如何影响水凝胶性质。非常高含量的生物聚合物,即,海藻酸钠,用于我们的研究,高达33重量%。这导致持久和稳定的水凝胶具有非常高的吸水能力,与仅基于合成聚合物的水凝胶相当。膨胀能力与存在的MBA数量成反比。通过增加水凝胶中海藻酸钠的量,水凝胶吸收水的能力降低。然而,即使对于SA含量最高的水凝胶,吸水率仍保持在350g·g-1时相对较高。
    Hydrogels based on sodium alginate (SA) and partially neutralised poly(acrylic acid) were obtained by radical polymerisation. The hydrogels were cross-linked with N,N\'-methylenebisacrylamide (MBA), simultaneously grafting the resulting polymer onto SA. The findings of the FTIR spectroscopy showed that all of the hydrogels were effectively synthesized and sodium alginate was chemically bonded with the poly(sodium acrylate) matrix. DSC analysis of the melting heat and glass transition parameters indicated that the hydrogel structure had changed as a result of the cross-linking process. Sodium alginate and MBA were tested at different concentrations to determine how they affected the hydrogel properties. A very high content of the biopolymer, i.e., sodium alginate, was used in our research, up to 33 wt%. This resulted in durable and stable hydrogels with a very high ability to uptake water, comparable to hydrogels based on synthetic polymers only. The ability to swell is inversely proportional to the quantity of MBA present. By increasing the amount of sodium alginate in the hydrogel, the ability of the hydrogel to absorb water is reduced. However, water uptake remains relatively high at 350 g·g-1, even for the hydrogel with the highest SA content.
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  • 文章类型: Journal Article
    籽粒蛋白质含量(GPC)是面包小麦的重要品质性状,受关键转录因子TaNAM的影响。然而,TaNAM的监管机制在很大程度上仍然难以捉摸。在这项研究中,TaNAM在调节影响GPC的氮再动员方面发挥了新作用。由成簇的规则间隔的短回文重复序列/Cas9产生的TaNAM敲除突变体表现出显著延迟的衰老和较低的GPC,而TaNAM-6A的过表达导致早衰和更高的GPC。进一步分析表明,TaNAM直接激活TaNRT1.1和TaNPF5.5s基因,参与氮的再动员。该活性有助于将氮从叶子转移到谷物以进行蛋白质合成。此外,TaNAM-6A的精英等位基因,与高GPC相关,被确定为优质小麦育种的候选基因。总的来说,我们的工作不仅阐明了TaNAM-6A影响面包小麦GPC的潜在机制,但也强调了从衰老叶片到谷物的氮再动员对蛋白质积累的重要性。此外,本研究为小麦品质性状的改良提供了新的目标和途径,特别是GPC。
    Grain protein content (GPC) is a crucial quality trait in bread wheat, which is influenced by the key transcription factor TaNAM. However, the regulatory mechanisms of TaNAM have remained largely elusive. In this study, a new role of TaNAM was unveiled in regulating nitrogen remobilisation which impacts GPC. The TaNAM knockout mutants generated by clustered regularly interspaced short palindromic repeats/Cas9 exhibited significantly delayed senescence and lower GPC, while overexpression of TaNAM-6A resulted in premature senility and much higher GPC. Further analysis revealed that TaNAM directly activates the genes TaNRT1.1 and TaNPF5.5s, which are involved in nitrogen remobilisation. This activity aids in the transfer of nitrogen from leaves to grains for protein synthesis. In addition, an elite allele of TaNAM-6A, associated with high GPC, was identified as a candidate gene for breeding high-quality wheat. Overall, our work not only elucidates the potential mechanism of TaNAM-6A affecting bread wheat GPC, but also highlights the significance of nitrogen remobilisation from senescent leaves to grains for protein accumulation. Moreover, our research provides a new target and approach for improving the quality traits of wheat, particularly the GPC.
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  • 文章类型: Journal Article
    对由Al(iBu)3/[Ph3C][B(C6F5)4]活化的二胺-双(酚盐)配合物合成的一系列乙烯/1-辛烯共聚物进行制备性升温洗脱分馏(TREF)。所使用的络合物在金属中心(Zr或Ti)或配体侧臂中的胺供体(NMe2或NiPr2)的类型上有所不同。然后通过FTIR表征获得的馏分,DSC和GPC方法。发现所有共聚物都具有非常宽的化学成分分布,最不均匀的是由带有NiPr2供体基团的配体的钛络合物产生的共聚物。共聚单体掺入到馏分的大分子中的差异高达8.3mol%。级分的熔融温度和分子量随着洗脱温度的升高而几乎线性变化。还使用溶剂/非溶剂技术通过分子量对由锆催化剂生产的共聚物进行分馏,随后分析馏分。结果表明,馏分具有相似的组成,低分子量分布和非常宽的共聚单体分布。因此,如对于用齐格勒-纳塔催化剂合成的共聚物所观察到的,级分中的共聚单体含量不是分子量的函数。
    A series of ethylene/1-octene copolymers synthesized with diamine-bis(phenolate) complexes activated with Al(iBu)3/[Ph3C][B(C6F5)4] were subjected to preparative temperature rising elution fractionation (TREF). The complexes used differed in the type of metallic center (Zr or Ti) or the amine donor in the pendant arm of the ligand (NMe2 or NiPr2). The obtained fractions were then characterized via FTIR, DSC and GPC methods. It was found that all the copolymers had very broad chemical composition distributions, and the most heterogeneous was the copolymer produced by the titanium complex bearing a ligand with the NiPr2 donor group. The difference in the comonomer incorporation into the macromolecules of the fractions was as high as 8.3 mol%. The melting temperature and molecular weight of the fractions changed nearly linearly with the increased elution temperature. Copolymers produced by zirconium catalysts were also fractionated by molecular weight using the solvent/non-solvent technique with subsequent analysis of the fractions. It was shown that the fractions have a similar composition, low molecular weight distribution and very broad comonomer distribution. Therefore, the comonomer content in the fractions was not a function of the molecular weight as was observed for the copolymers synthesized with the Ziegler-Natta catalysts.
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  • 文章类型: Journal Article
    超分子聚合物在不同领域发现广泛应用,分子量对其适用性有重要影响。因此,超分子聚合物分子量的测量具有极其重要的意义。需要低浓度条件的凝胶渗透色谱(GPC)是分子量测定的常用表征,这不适用于具有浓度无关性的超分子聚合物。这里,为了打破这个门槛,我们合成了包含二苯并-24-冠-8(DB24C8)部分以及二苄基铵盐(DBA)基团的M1,能够自组装成末端以醛基终止的超分子聚合物。加入(4-(1,2,2-三苯基乙烯基)苯基)甲胺(TPE-NH2)后,超分子聚合物经历了向聚轮烷的过渡,它是由亚胺键的产生引起的。通过GPC,获得聚轮烷的分子量,然后可以借助转化效率获得超分子聚合物的分子量。
    Supramolecular polymers find wide applications across diverse domains, and the molecular weight exerts a critical influence on their applicability. Consequently, the measurement of molecular weight for supramolecular polymers assumes paramount significance. Gel Permeation Chromatography (GPC) requiring low-concentration condition is a common characterization employed for molecular weight determination, which is not suitable for supramolecular polymers possessing concentration-independence property. Here, to break this threshold, we synthesized M1 embodying dibenzo-24-crown-8 (DB24C8) moiety as well as dibenzylammonium salt (DBA) group, which was capable of self-assembling into supramolecular polymers terminated with aldehyde groups at its end. Upon the addition of (4- (1,2,2-Triphenylvinyl) phenyl) methylamine (TPE-NH2), supramolecular polymers underwent a transition into polyrotaxanes, for which it was led by the generation of imine bonds. By virtue of GPC, the molecular weight of polyrotaxanes was obtained, then it was available to gain the molecular weight of supramolecular polymers with the help of transformation efficiency.
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  • 文章类型: Journal Article
    聚烯烃是按体积计商业上最相关的聚合物。容易获得的原料及其定制的微观结构允许聚烯烃适应许多应用领域。烯烃共聚物的重要分子设计特征是具有相应平均值的摩尔质量分布(MMD),共聚单体类型,化学成分分布(CCD)与相应的平均值和立构规整度分布(TD)。先进的分离技术,即高温凝胶渗透色谱(HT-GPC)及其与高温二维液相色谱(HT2D-LC)形式的高温高效液相色谱(HT-HPLC)的联用已成功应用在这项工作中。这可以深入分析由乙烯组成的复杂聚烯烃三元共聚物的分子异质性,乙酸乙烯酯和支链乙烯基酯单体。通过使用基于滤波器的红外检测,进一步扩展了HT-GPC的能力,从而可以沿摩尔质量轴获得甲基-和羰基的分布。使用多孔石墨碳(PGC)作为HT-HPLC分离的固定相,从实验数据中提供了有关这些复杂聚烯烃的CCD的信息,这是HT2D-LC连音方法的一部分。后者揭示了完整的MMDxCCD分布函数,这是全面分析聚烯烃三元共聚物双变量分子结构的关键。
    Polyolefins are the most commercially relevant polymers by volume. A readily available feedstock and their tailor-made microstructure allow to adapt polyolefins to many fields of application. Important molecular design features of olefin copolymers are the molar mass distribution (MMD) with the corresponding average values, comonomer type, chemical composition distribution (CCD) with the corresponding average and the tacticity distribution (TD). Advanced separation techniques i.e., high-temperature gel permeation chromatography (HT-GPC) as well as its hyphenation with high-temperature high performance liquid chromatography (HT-HPLC) in the form of high-temperature two-dimensional liquid chromatography (HT 2D-LC) have been successfully applied in this work. This allowed to deeply analyze the molecular heterogeneities of complex polyolefin terpolymers consisting of ethylene, vinyl acetate and branched vinyl ester monomers. By using filter-based infrared detection, the capabilities of HT-GPC are further extended so that the distribution of methyl- and carbonyl groups could be obtained along the molar mass axis. Using porous graphitic carbon (PGC) as a stationary phase for HT-HPLC separation provided information about the CCD of these complex polyolefins from experimental data as part of the hyphenated approach of HT 2D-LC. The latter revealed the full MMD x CCD distribution function, which is the key for a comprehensive analysis of the bivariate molecular structure of the polyolefin terpolymers.
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