Mcdonaldbjerregaard5484

Therapeutic recombinant proteins have numerous advantages and benefits over chemical drugs, particularly high specificity and good biocompatibility. However, the therapeutic potential and clinical application of current anticancer protein drugs are limited as most biomarkers are located within cells, and multiple physiological barriers exist between the point of administration and the intracellular biomarker. Herein, we report a novel strategy to accurately deliver a cell-permeable dominant-negative TATm-Survivin (TmSm) protein (T34A) to intracellular survivin in cancer cells by overcoming multiple barriers in vivo. A poly(d,l-lactide-co-glycolide) (PLGA) inner core, a polyethylene glycol (PEG) modification, and a TATm peptide were simultaneously introduced to mediate tumor tissue targeting and response to pH-triggered TmSm release. Compared to free TmSm, the PEGylated-PLGA nanoparticle platform achieved a significantly higher cellular uptake efficiency (1.79-fold for A549 and 1.77-fold for Capan-2), effectively decreased IC50 (1.22-fold for A549 and 1.17-fold for Capan-2), and largely elevated apoptosis in different cancer cells (1.17-fold for A549 and 1.15-fold for Capan-2). Besides, this newly developed nanoplatform showed increased protein drug accumulation in the tumor site in A549-bearing nude mice and reached a tumor inhibition rate of 55.81% (1.35-fold versus free TmSm) by reducing the expression of intracellular survivin. All these results confirmed that our newly developed delivery strategy is a very promising tool, which helps protein drugs to cross multiple barriers in vivo and achieves precise targeting to intracellular biomarkers. This strategy could also be applied to other types of protein drugs to further improve their clinical anticancer therapeutic efficacy.Recently, research attention has been directed towards the coordination driven synthesis of gels, including coordination polymer gels (CPGs) and metal-organic cage based gels, which have shown applications in diverse fields, including optoelectronics, catalysis, sensing, gas-storage, and self-healing. A wide variety of CPGs and metal-organic cage based gels have been reported, to date, by choosing the right combination of metal ions and rationally designed organic linkers. In this article, we focused on recent developments in CPGs and metal-organic cage based gels and their applications.Electron-beam lithography is widely applied in nanofabrication due to its high resolution. However, it suffers from low throughput due to its patterning process. All the pixels within a pattern's boundary are needed to be scanned for patterning, which is inefficient for a large area closed polygon structure. Introducing an additional step to perform the polygon-filling function for patterning will significantly improve the fabrication throughput. In this work, we introduce a practical polygon-filling process for electron beam lithography, termed plasma-assisted filling electron beam lithography (PFEBL), that makes use of post-exposure plasma treatment on the resist which only crosslinks the top surface of the resist. Using this technique, we only need to expose the outline of the patterns during the writing process and could still obtain the full structure after post-exposure plasma treatment and development. We show that the lithography patterning efficiency could be enhanced 50 times and above while sub-10 nm resolution patterning with a sharp boundary feature size can still be obtained. The plasma exposure mechanism and development mechanism were discussed for the characteristics of the resist that enables this filling process. Our approach allows large area closed polygon structures to be patterned with high patterning efficiency, which could find uses in various applications in nanophotonic and optoelectronic devices.Creating ultralight monolithic metal foams remains an outstanding challenge despite their important applications, e.g., in electronics, sensors and energy storage. Herein, a facile methodology is developed for one-step fabrication of silver/polyvinylpyrrolidone (PVP) nanowire (AgPNW) hydrogel and high-quality robust ultralight AgPNW aerogel (AgPNWA) on a large scale. The hydrogel is directly formed by in situ assembling hydrothermally-synthesized AgPNWs. The resultant ultralight AgPNWA exhibits very high electrical conductivity. The application of this one-step fabricated AgPNWA to enhance phase change materials (PCMs) for high-efficiency thermal energy storage is investigated. The AgPNWA-paraffin composite (APC) shows ∼350% thermal-efficiency enhancement, ∼463% mechanical hardening, and strong reliability against thermal cycling due to the potentially strong AgPNW-paraffin interfacial interaction. It is also observed that the thickness of the APC shrinks significantly but there is no change in its diameter during thermal cycles. Analytical models of liquid capillary filling of deformable fiber-based 3D networks are derived for the first time and are applied to analyze the thermal-cycling-induced-shape-stabilization behavior of the APC and the vaporization-induced collapse behavior of the AgPNW network. This work provides important insights into designing a facile 3D assembly of nanomaterials, and thermal energy storage materials with high performance and reliability.Although van der Waals heterostructures composed of graphene and hexagonal boron nitride (h-BN) have attracted wide interest, it is still challenging to prepare them with high quality and controllability. Since contamination induced by transfer cannot be avoided in the case of growth on a metal catalyst, the non-catalytic growth of graphene and h-BN is highly desired. However, unlike graphene, few studies have reported the non-catalytic growth of h-BN, and the lack of controllability in terms of crystal orientation and nucleation density, and size of h-BN has hindered the practical applications of the heterostructures. In this work, we demonstrate the heteroepitaxial growth of aligned monolayer h-BN single-crystals on exfoliated graphite by chemical vapour deposition (CVD) without a metal catalyst. Triangular shaped domains were aligned with each other, which suggests the epitaxy between h-BN and the underlying graphite. Characterisation by Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy also confirmed that the h-BN/graphite samples were of high quality. A growth kinetics study over different temperatures indicated an increase in the growth rate at high temperature. Control of nucleation density was realised by changing the hydrogen pressure during CVD or by the heating temperature in air before CVD. Under the optimised growth conditions, the edge length of h-BN single-crystals grew to ∼1 μm, which is the largest size to date for non-catalytic growth. These results will help to obtain structure-controlled, large-area, and impurity-free heterostructures based on h-BN and graphene.Despite extensive studies on the distinctive properties of water confined in a nanospace, the underlying mechanism and significance of the lengthscale involved in the confinement effects are still subjects of controversy. The dielectric constant and the refractive index in particular are key parameters in modeling and understanding nanoconfined water, yet experimental evidence is lacking. We report the measurement of the refractive indices of water in 10-100 nm spaces by exploiting the confinement of water and localized surface plasmons in a physicochemically well-defined nanocavity. The results revealed significantly low values and the scaling behavior of the out-of-plane refractive index n⊥ of confined water. They are attributed to the polarization suppression at the interfaces and the long-range correlation in electronic polarization facilitated by the strengthened H-bonding network. Using the refractive index as a sensing probe, we also observed anomalous stability of water structures over a wide range of temperature. Our measurement results provide essential feedback information for benchmarking water models and molecular interactions under nanoconfinement. This study also opens up a new methodology of using plasmon resonance in characterizing nanoconfined molecules and chemical reactions, and thus gives us fundamental insight into confinement effects.Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46-4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74-1.67, and 1.13, 95% CI 0.79-1.61, respectively). Selleck EMD638683 Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99-1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90-1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.Outfitted with abundant hydrogen bonding and coordination active groups, carboxymethyl chitosan (CMC) possesses a class of naturally occurring ligands for coordination with metal ions, establishing its excellent potential for various fields. Herein, by incorporating the naturally derived CMC into a thermally reconfigurable agarose (Agar) gel medium, a novel type of metal-biopolymer coordinated double network hydrogel (DN gel) was successfully fabricated via the strong coordination interactions. The interpenetrated CMC was confirmed to retain its excellent chelating abilities within the bulk gel matrix, which resulted in a series of metal-coordinated DN gels through spontaneous self-associative complexation with metal ions such as Cu2+, Zn2+, Ni2+, Co2+, Fe3+, and Cr3+. Moreover, these two types of physical cross-links are functionally independent and reversible, which enables the programming of the hydrogel with multi-functionality, including pH-regulated shape memory behavior, multi-staged self-healing properties and durable antibacterial activities. Thus, we believe that the successful preparation of such a coordination-driven DN gel will lead to the development of biopolymer-based multifunctional hydrogels, as well as provide new insight into nanocomponent assembly and soft electronic biosensing systems for biomedical applications.