PEI

PEI
  • 文章类型: Journal Article
    后COVID-19大流行时代已经出现了更有效的疫苗,都是基于遗传物质。然而,扩大核酸成分作为疫苗的用途,新一代的纳米系统,特别是构建增加RNA/DNA的稳定性,仍然需要半衰期和方便管理。这篇综述强调了mRNA和pDNA疫苗的新发展,这些疫苗被配制成完全由生物聚合材料组成的纳米结构。最近的进展表明,新一代的疫苗可以通过使生物聚合物的结构特征适应核酸的有效性而产生。生物聚合物提供的优势,例如增加的稳定性和靶向能力可能引起免疫领域的革命,以提供迅速适应和有效的制剂,以全球分布。
    [方框:见正文]。
    The post COVID-19 pandemic era has emerged with more efficient vaccines, all based on genetic materials. However, to expand the use of nucleic components as vaccines, a new generation of nanosystems particularly constructed to increase RNA/DNA stability, half-life and facilitate administration are still required. This review highlights novel developments in mRNA and pDNA vaccines formulated into nanostructures exclusively composed by biopolymeric materials. Recent advances suggest that a new generation of vaccines may arise by adapting the structural features of biopolymers with the effectiveness of nucleic acids. The advantages offered by biopolymers, such as increased stability and targeting ability may cause a revolution in the immunization field for offering promptly adaptable and effective formulations for worldwide distribution.
    [Box: see text].
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  • 文章类型: Journal Article
    用于印刷电路板的基板材料必须满足不断增加的要求以跟上电子技术的发展。特别是在雷达和蜂窝广播等高频应用领域,低介电常数和介电损耗因子是关键材料参数。在这项工作中,高温的介电特性,在干燥和环境条件下,在5和10GHz的频率下研究了热塑性PEEK/PEI共混体系。这种材料混合,用合适的填料体系改性,能够用于激光直接成型(LDS)工艺。结果表明,纯PEEK的结晶度对介电性能有显著影响,以及通过退火形成的共混体系中的PEEK相结构。这种现象又可以被利用来最小化30至40重量%的介电常数值。-混合物中的PEI%,甚至考虑到热塑性塑料中存在的水吸收。介电损耗在混合范围内遵循线性混合规则,这对于PEEK/PEILDS化合物也被证明是正确的。
    Substrate materials for printed circuit boards must meet ever-increasing requirements to keep up with electronics technology development. Especially in the field of high-frequency applications such as radar and cellular broadcasting, low permittivity and the dielectric loss factor are key material parameters. In this work, the dielectric properties of a high-temperature, thermoplastic PEEK/PEI blend system are investigated at frequencies of 5 and 10 GHz under dried and ambient conditions. This material blend, modified with a suitable filler system, is capable of being used in the laser direct structuring (LDS) process. It is revealed that the degree of crystallinity of neat PEEK has a notable influence on the dielectric properties, as well as the PEEK phase structure in the blend system developed through annealing. This phenomenon can in turn be exploited to minimize permittivity values at 30 to 40 wt.-% PEI in the blend, even taking into account the water uptake present in thermoplastics. The dielectric loss follows a linear mixing rule over the blend range, which proved to be true also for PEEK/PEI LDS compounds.
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  • 文章类型: Journal Article
    表达平台的持续改进对于响应对进行结构或功能研究所需的重组蛋白的不断增长的需求以及对其作为生物治疗剂的表征是必要的。虽然哺乳动物细胞中的瞬时基因表达(TGE)构成了一种快速且完善的方法,非克隆稳定转染的细胞,或\"池,\"代表另一种选择,当需要重复生产相同的蛋白质时,这是特别有吸引力的。培养量只有几升,稳定的库可以提供数百毫克到克的高质量分泌重组蛋白。在这一章中,我们描述了一种使用市售无血清培养基和聚乙烯亚胺(PEI)作为转染试剂产生表达分泌重组蛋白的中国仓鼠卵巢细胞稳定池的高效和经济的方法。作为如何应用此协议的具体示例,描述了重组His标记的三聚体SARS-CoV-2刺突蛋白胞外域(SmT1)的生产和下游纯化。
    The continuous improvement of expression platforms is necessary to respond to the increasing demand for recombinant proteins that are required to carry out structural or functional studies as well as for their characterization as biotherapeutics. While transient gene expression (TGE) in mammalian cells constitutes a rapid and well-established approach, non-clonal stably transfected cells, or \"pools,\" represent another option, which is especially attractive when recurring productions of the same protein are required. From a culture volume of just a few liters, stable pools can provide hundreds of milligrams to gram quantities of high-quality secreted recombinant proteins.In this chapter, we describe a highly efficient and cost-effective procedure for the generation of Chinese Hamster Ovary cell stable pools expressing secreted recombinant proteins using commercially available serum-free media and polyethylenimine (PEI) as the transfection reagent. As a specific example of how this protocol can be applied, the production and downstream purification of recombinant His-tagged trimeric SARS-CoV-2 spike protein ectodomain (SmT1) are described.
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  • 文章类型: Journal Article
    镁合金,特别是AZ91D,表现出有希望的机械性能,但容易腐蚀,限制了其广泛的工业应用。本手稿研究了电压和聚醚酰亚胺(PEI)的浓度对表面形貌和腐蚀特性的影响AZ91D通过电旋涂。PEI,以其高强度和耐腐蚀性而闻名,使用环保的电旋涂方法应用。该研究优化了聚合物浓度和施加电压以增强AZ91D的防腐性能。原子力显微镜(AFM)和扫描电子显微镜(SEM)揭示了形态变化,而电化学腐蚀测试提供了对耐腐蚀性的见解。结果表明,在14kV电压下,中等浓度的PEI(15%)表现出最有利的耐腐蚀性,强调需要优化这两个参数,以增强AZ91D的防腐蚀保护。结果有助于开发经济有效的镁合金腐蚀防护技术,主要用于汽车应用。
    Magnesium alloys, particularly AZ91D, exhibit promising mechanical properties but are susceptible to corrosion, limiting their widespread industrial applications. This manuscript investigates the impact of voltage and concentration of Polyetherimide (PEI) on surface morphology and corrosion characteristics of AZ91D through electro-spin coating. PEI, known for its high strength and corrosion resistance, is applied using an eco-friendly electro-spin coating method. The study optimizes polymer concentration and applied voltage to enhance the anticorrosive properties of AZ91D. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) reveal the morphological alterations, while electrochemical corrosion tests provide insights into the corrosion resistance. The results show that a moderate PEI concentration (15 %) at 14 kV voltage exhibits the most favorable corrosion resistance, emphasizing the need to optimize both parameters for enhanced protection of AZ91D against corrosion. The results contribute to developing economical and effective corrosion protection techniques for magnesium alloys, mainly for automotive applications.
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  • 文章类型: Journal Article
    如今,废水处理是一个严峻的挑战,主要是因为其复杂的成分,其中包括石油,重金属离子,和染料。开发新的智能膜是解决废水处理中这些重大挑战的策略之一。在这项研究中,我们通过将交联的聚(衣康酸酐)(CL-PITA)纳米颗粒接枝到辐照面上,制备了不对称的聚对苯二甲酸乙二醇酯(PET)膜。然后将这些纳米颗粒用聚乙烯亚胺(PEI)官能化并用HCl质子化以引入许多活性正电性胺基。基本目的是增加表面粗糙度,引入许多亲水基团,并对其进行修改以创建多功能PET膜以分离复杂的环境。结果表明,质子化的PET-g-ITA/DVB(10)-cat膜对水/轻油具有优异的分离效率(SE),水/重油和水包油(O/W)乳液。与PET-g-ITA/DVB(0)-cat相比,经过10次循环后,它在O/W乳液的SE和水/轻油的通量衰减方面表现出优异的性能。更有趣的是,由于许多带正电荷的活性氨基和带负电荷的羧酸酯基团,智能膜表现出较高的去除率。90%为阴离子染料(刚果红)和重金属(Cu2+和Co2+),在复杂的水处理环境中显示出巨大的潜力。
    Nowadays, effluent treatment is a severe challenge mainly because of its complex composition, which includes oil, heavy metal ions, and dyes. Developing new intelligent membranes is one of the strategies to tackle these significant challenges in wastewater treatment. In this study, we fabricated asymmetric polyethylene glycol terephthalate (PET) membranes by grafting cross-linked poly (itaconic anhydride) (CL-PITA) nanoparticles onto the irradiated face. These nanoparticles were then functionalized with polyethyleneimine (PEI) and protonated with HCl to introduce numerous active electropositive amine groups. The fundamental purpose was to increase surface roughness, introduce numerous hydrophilic groups, and modify it to create a multi-functional PET membrane to separate complex environments. The promising results demonstrated that the protonated PET-g-ITA/DVB(10)-cat membrane exhibited excellent separation efficiencies (SE) for water/light oil, water/heavy oil and oil-in-water (O/W) emulsion. Compared to PET-g-ITA/DVB(0)-cat, it showed superior performance in SE for O/W emulsion and flux decay for water/light oil after 10 cycles. More interestingly, owing to numerous positively charged active amino groups and negativley charged carboxylate groups, the intelligent membrane exhibited a high removal rate of ca. 90 % for anionic dye (congo red) and heavy metals (Cu2+ and Co2+), showing great potential in complex water treatment environments.
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  • 文章类型: Journal Article
    设计用于基因治疗或基因敲低的基于核酸的药物的喷雾干燥与许多优点相关,包括储存稳定性和处理以及肺部应用的可能性。在喷雾干燥之前将核酸封装在纳米颗粒中是获得有效制剂的一种策略。这个,然而,强烈依赖于最佳纳米粒子的定义,赋形剂和喷雾干燥条件。在聚合物纳米粒子中,先前已经描述了具有或不具有化学修饰的基于聚乙烯亚胺(PEI)的复合物对于基因或寡核苷酸递送非常有效。线性或支化低分子量PEIs的酪氨酸修饰,或聚丙烯亚胺(PPI)树枝状聚合物,导致了高度复杂的稳定性,改善细胞摄取和转染效率以及高生物相容性。在这项研究中,我们确定了含有大质粒DNA或小siRNA的基于PEI的纳米颗粒的最佳喷雾干燥条件,并进一步探索含有化学修饰聚合物的纳米颗粒的喷雾干燥。聚乙烯醇(PVA),但不是海藻糖或乳糖,特别适合作为赋形剂,与新鲜复合物相比,保留或甚至增强转染效力。大的网眼尺寸也至关重要,而喷雾干燥温度的变化起着次要的作用。喷雾干燥后,获得了约3.3-8.5微米尺寸范围(激光粒度)的微粒,取决于聚合物。一旦它们从喷雾干燥的材料中释放出来,与新鲜的纳米粒子相比,纳米粒子显示出增加的尺寸和显著改变的zeta电位。这可能有助于它们的高功效,这在延长喷雾干燥的材料的储存之后也可以看到。我们得出的结论是,这些喷雾干燥系统为制备易于重建的核酸药物储存形式提供了巨大的潜力,以及作为干粉直接肺部应用。
    Spray-drying of nucleic acid-based drugs designed for gene therapy or gene knockdown is associated with many advantages including storage stability and handling as well as the possibility of pulmonary application. The encapsulation of nucleic acids in nanoparticles prior to spray-drying is one strategy for obtaining efficient formulations. This, however, strongly relies on the definition of optimal nanoparticles, excipients and spray-drying conditions. Among polymeric nanoparticles, polyethylenimine (PEI)-based complexes with or without chemical modifications have been described previously as very efficient for gene or oligonucleotide delivery. The tyrosine-modification of linear or branched low molecular weight PEIs, or of polypropylenimine (PPI) dendrimers, has led to high complex stability, improved cell uptake and transfection efficacy as well as high biocompatibility. In this study, we identify optimal spray-drying conditions for PEI-based nanoparticles containing large plasmid DNA or small siRNAs, and further explore the spray-drying of nanoparticles containing chemically modified polymers. Poly(vinyl alcohol) (PVA), but not trehalose or lactose, is particularly well-suited as excipient, retaining or even enhancing transfection efficacies compared to fresh complexes. A big mesh size is critically important as well, while the variation of the spray-drying temperature plays a minor role. Upon spray-drying, microparticles in a ∼ 3.3 - 8.5 µm size range (laser granulometry) are obtained, dependent on the polymers. Upon their release from the spray-dried material, the nanoparticles show increased sizes and markedly altered zeta potentials as compared to their fresh counterparts. This may contribute to their high efficacy that is seen also after prolonged storage of the spray-dried material. We conclude that these spray-dried systems offer a great potential for the preparation of nucleic acid drug storage forms with facile reconstitution, as well as for their direct pulmonary application as dry powder.
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  • 文章类型: Journal Article
    溅射氧化铟锡(ITO)满足半透明钙钛矿太阳能电池(PSC)和堆叠串联太阳能电池(TSC)中的顶部透明电极(TTE)以及单片TSC中的复合层的要求。然而,高能ITO颗粒会对器件造成损害,降低光伏性能。在这里,已经提出并实施了界面反应溅射策略,以构造具有高透射率和出色载流子传输能力的成本效益高的TTE,旨在实现高性能的半透明串联PSC。选择聚乙烯亚胺(PEI)作为界面反应物,其中PEI上丰富的氨基可以与溅射的ITO纳米颗粒反应,从而在ITO沉积过程中可以形成配位化合物,促进C60/PEI/ITO界面处的载流子传输。此外,高能ITO颗粒的冲击力大大减轻,和下面的C60层和钙钛矿层的完整性得到保证。因此,制备的半透明子电池实现了19.17%的显着增强的功率转换效率(PCE),超过基于C60/ITO的那些(11.64%)。此外,基于PEI的装置表现出优异的储存稳定性,它在2000小时后保留了98%的原始PCE。关于界面反应溅射ITO电极的强度,我们成功地制造了PCE为26.89%的堆叠全钙钛矿TSC和PCE为24.33%的整体式钙钛矿有机TSC。这项工作为使TTE在半透明和串联PSC中功能良好提供了一种简便且仪器化的解决方案。本文受版权保护。保留所有权利。
    Sputtered indium tin oxide (ITO) fulfills the requirements of top transparent electrodes (TTEs) in semitransparent perovskite solar cells (PSCs) and stacked tandem solar cells (TSCs), as well as of the recombination layers in monolithic TSCs. However, the high-energy ITO particles will cause damage to the devices. Herein, the interface reactive sputtering strategy is proposed to construct cost-effective TTEs with high transmittance and excellent carrier transporting ability. Polyethylenimine (PEI) is chosen as the interface reactant that can react with sputtered ITO nanoparticles, so that, coordination compounds can be formed during the deposition process, facilitating the carrier transport at the interface of C60/PEI/ITO. Besides, the impact force of energetic ITO particles is greatly alleviated, and the intactness of the underlying C60 layer and perovskite layer is guaranteed. Thus, the prepared semitransparent subcells achieve a significantly enhanced power conversion efficiency (PCE) of 19.17%, surpassing those based on C60/ITO (11.64%). Moreover, the PEI-based devices demonstrate excellent storage stability, which maintains 98% of their original PCEs after 2000 h. On the strength of the interface reactive sputtering ITO electrode, a stacked all-perovskite TSC with a PCE of 26.89% and a monolithic perovskite-organic TSC with a PCE of 24.33% are successfully fabricated.
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  • 文章类型: Journal Article
    2023年病毒清除研讨会(VCS)由武田于2023年5月24日至25日在维也纳主办,奥地利。本次会议扩大了2009年至2019年举行的前两年一次专题讨论会的结构。如介绍性会议所述,VCS的起源,如2009年VCS会议录中所述,“全球监管和行业认识到挑战,间隙,机会存在,它的正式解决可能有利于整个领域。“本报告概述了会议通过详细的技术讨论取得的进展以及仍需关注的未决问题。2023年VCS由九个单独的简短演讲组成,随后由演讲者进行深入的小组讨论。会议包括监管更新(重点是ICHQ5A(R2)工作),包括从2019年VCS中吸取的经验教训的总结,和这些关键领域的进展映射到2023年VCS主题:病毒清除战略和案例研究,色谱和吸附过滤器的新模式,连续处理,病毒清除策略和过程理解,病毒灭活,上游和下游病毒保留过滤和细胞库,和先进技术(先进的治疗药物产品,下一代测序)。
    The 2023 Viral Clearance Symposium (VCS) was hosted by Takeda on 24 and 25 May 2023 in Vienna, Austria. The present conference extended the structure of the previous biennial symposia held between 2009 and 2019. As recapitulated in the introductory session, the genesis of the VCS, as described in the Proceedings of the 2009 VCS was \"the worldwide regulatory and industry recognition that challenges, gaps, and opportunities exist, that it formally addressed could benefit the field as whole.\" This report provides a synopsis of the progress achieved at the conference resulting from detailed technical discussions and the pending questions that still require attention to address. The 2023 VCS was composed of nine individual sessions of short presentations followed by in-depth panel discussions from the presenters. Sessions included Regulatory Updates (with a focus on ICH Q5A(R2) efforts), including a summary of lessons learned from the 2019 VCS, and progress on these key areas mapped into 2023 VCS topics: Viral Clearance Strategy and Case Studies, New Modalities in Chromatography and Adsorptive Filters, Continuous Processing, Viral Clearance Strategy and Process Understanding, Virus Inactivation, Upstream and Downstream Virus Retentive Filtration and Cell Banks, and Advanced Technologies (advanced therapy medicinal products, next-generation sequencing).
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  • 文章类型: Journal Article
    癌基因RAS家族中的错义突变(HRAS,KRAS,和NRAS)存在于大约20%的人类癌症中,使RAS成为有价值的治疗靶标(Prior等人。,癌症报告80:2969-2974,2020)。尽管数十年来开发RAS治疗性抑制剂的研究努力并不成功,近年来,随着FDA批准的KRASG12C特异性抑制剂进入临床,取得了成功(Skoulidisetal.,NEnglJMed384:2371-2381,2021;Jänne等人。,NEnglJMed387:120-131,2022)。此外,KRASG12D特异性抑制剂目前正在进行临床试验(Wang等人。,JMedChem65:3123-3133,2022)。这些等位基因特异性抑制剂的出现已经推翻了以前的观点,即RAS是不可用的。尽管RAS靶向疗法取得了这些进展,一些经常在癌症中出现的RAS突变体仍然没有易于处理的药物。因此,进一步了解RAS在细胞中的功能和生物学特性,以及开发识别新的治疗漏洞的工具,对于开发抗RAS疗法至关重要.要做到这一点,我们已经利用单体(Mb)技术来开发特定的RAS同工型和突变体的基于蛋白质的特异性抑制剂(Spencer-Smith等人。,NatChemBiol13:62-68,2017;Khan等人。,细胞代表38:110322,2022;Wallon等人。,ProcNatlAcadSci美国119:e2204481119,2022;Khan等人。,小GTPases13:114-127,2021;Khan等人。,癌基因38:2984-2993,2019年)。在这里,我们描述了我们结合使用Mbs和NanoLuc二进制技术(NanoBiT)来分析RAS蛋白质-蛋白质相互作用,并在活细胞中筛选RAS结合小分子,高通量测定。
    Missense mutations in the RAS family of oncogenes (HRAS, KRAS, and NRAS) are present in approximately 20% of human cancers, making RAS a valuable therapeutic target (Prior et al., Cancer Res 80:2969-2974, 2020). Although decades of research efforts to develop therapeutic inhibitors of RAS were unsuccessful, there has been success in recent years with the entrance of FDA-approved KRASG12C-specific inhibitors to the clinic (Skoulidis et al., N Engl J Med 384:2371-2381, 2021; Jänne et al., N Engl J Med 387:120-131, 2022). Additionally, KRASG12D-specific inhibitors are presently undergoing clinical trials (Wang et al., J Med Chem 65:3123-3133, 2022). The advent of these allele specific inhibitors has disproved the previous notion that RAS is undruggable. Despite these advancements in RAS-targeted therapeutics, several RAS mutants that frequently arise in cancers remain without tractable drugs. Thus, it is critical to further understand the function and biology of RAS in cells and to develop tools to identify novel therapeutic vulnerabilities for development of anti-RAS therapeutics. To do this, we have exploited the use of monobody (Mb) technology to develop specific protein-based inhibitors of selected RAS isoforms and mutants (Spencer-Smith et al., Nat Chem Biol 13:62-68, 2017; Khan et al., Cell Rep 38:110322, 2022; Wallon et al., Proc Natl Acad Sci USA 119:e2204481119, 2022; Khan et al., Small GTPases 13:114-127, 2021; Khan et al., Oncogene 38:2984-2993, 2019). Herein, we describe our combined use of Mbs and NanoLuc Binary Technology (NanoBiT) to analyze RAS protein-protein interactions and to screen for RAS-binding small molecules in live-cell, high-throughput assays.
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  • 文章类型: Journal Article
    金核介孔二氧化硅壳(AuMSS)纳米棒是多功能纳米药物,可以同时作为光热,药物输送,和生物成像剂。然而,据报道,一旦被管理,纳米粒子可以用血液蛋白包被,形成蛋白质日冕,直接影响纳米药物的循环时间,生物分布,和治疗性能。因此,开发新的替代品以改善纳米粒子在血液中的半衰期变得至关重要。在这项工作中,首次将聚乙烯亚胺(PEI)和红细胞(RBC)衍生的膜结合起来,以功能化AuMSS纳米棒并同时负载吖啶橙(AO)。获得的结果表明,RBC衍生的膜促进了AuMSS表面电荷的中和,从而改善了纳米载体的胶体稳定性和生物相容性。的确,体外数据显示,PEI/RBC衍生的膜功能化也改善了纳米颗粒的细胞内化,并能够减轻AuMSS和AuMSS/PEI纳米棒的溶血作用。反过来,AuMSS/PEI/RBC_AO纳米棒介导的联合化学-光热疗法能够完全消除HeLa细胞,与效率较低的独立疗法形成对比。这些数据增强了AuMSS纳米材料同时充当光热和化学治疗剂的潜力。
    Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines\' circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles\' half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC-derived membranes promoted the neutralization of the AuMSS\' surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes\' functionalization also improved the nanoparticles\' cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.
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