Weeksdixon7893

In such case, a mutual interdependence should exist between Ps, E(0)c and TC. A model is built up, able to predict coercitivity, however E(0)c and TC yield values several orders of magnitude higher than the experimental ones. Therefore, one has to introduce a background dielectric constant of several hundreds to accommodate the result of the model with the experimental data. The poling history of the film has to be taken into account, together with the presence of a small bias field. The model is able to predict self-consistently the equation of state of a ferroelectric, and in particular the linear decrease of the coercive field with temperature. The microscopic parameters, in particular the background dielectric constant and the density of elemental dipoles may be expressed directly from experimental quantities.Despite electrospinning having multiple advantages over other methods such as creating materials with a superfine fiber diameter, high specific surface area, and good mechanical properties, the pore diameter of scaffolds prepared directly using conventional electrospinning is often smaller than a few tens of microns, which may not be suitable for three-dimensional (3-D) cell culture and tissue growth. In order to achieve satisfactory results for use in tissue engineering, the pore size of the scaffold should be increased to a size dependent on the specific cells being cultured. Many methods for enlarging the pore size of electrospun scaffolds have been described in the literature. In the present review, we have summarized the preparation of macroporous electrospun scaffold techniques for the skin, blood vessels, bone, cartilage and nerve tissue engineering for different applications, and further discuss the influence of changing pore-enlarging process parameters on the properties of the scaffolds, such as mechanical properties, and hydrophilicity and hydrophobicity, etc. We believe that changes in scaffold pore size and related physical properties can have a profound impact on cell behavior, such as adhesion, proliferation and infiltration, and the significance of their influence on applications of electrospun tissue engineering scaffolds is worthy of further investigation in the future.In this work, the liquid-liquid phase equilibria and interfacial properties of methyl ester + water binary mixtures are determined at atmospheric pressure and from 278 to 358 K combining the direct coexistence technique and molecular dynamics simulations. Methyl esters are modelled using new parametrizations based on the united atom TraPPE model force field proposed recently by us [E. Feria, J. Algaba, J. M. Míguez, A. Mejía, P. Gómez-Álvarez and F. J. Blas, Phys. Chem. Chem. Phys., 2019, 22, 4974-4983] that are able to predict the vapour-liquid interfacial properties of pure methyl esters with high accuracy. In the case of water, we consider the well-known TIP4P/2005 model, the most popular rigid and non-polarizable model to describe the interfacial properties of pure water. The simulations are performed using the direct coexistence technique in the isothermal-isobaric or NPzT ensemble in combination with molecular dynamics. We obtain density profiles, temperature-densities and temperature-composition projections of the phase diagrams, and interfacial tensions. The liquid-liquid interfacial tension is calculated from the normal and tangential components of the pressure tensor according to the mechanical virial route. We pay attention particularly to the ability of the molecular models in predicting the experimental behavior of the systems. Simulation results are able to account for the liquid-liquid phase equilibria of these binary mixtures, in good agreement with the experimental data taken from the literature. https://www.selleckchem.com/products/bgj398-nvp-bgj398.html Unfortunately, experimental values for interfacial tensions are substantially overestimated by predictions from computer simulations in all cases. To our knowledge, this is the first time that the liquid-liquid phase equilibrium and interfacial properties of methyl ester + water mixtures have been predicted from computer simulations.Fluorescence resonance energy transfer (FRET) in pairs of chromophores has mostly been achieved using covalently bound chromophores. In this study, we have demonstrated energy transfer in FRET pairs by taking advantage of the self-assembly of the chromophores on metal cholate hydrogel fibers.A new supramolecular approach to broad spectrum antivirals utilizes host guest chemistry between molecular tweezers and lysine/arginine as well as choline. Basic amino acids in amyloid-forming SEVI peptides (semen-derived enhancers of viral infection) are included inside the tweezer cavity leading to disaggregation and neutralization of the fibrils, which lose their ability to enhance HIV-1/HIV-2 infection. Lipid head groups contain the trimethylammonium cation of choline; this is likewise bound by molecular tweezers, which dock onto viral membranes and thus greatly enhance their surface tension. Disruption of the envelope in turn leads to total loss of infectiosity (ZIKA, Ebola, Influenza). This complexation event also seems to be the structural basis for an effective inihibition of cell-to-cell spread in Herpes viruses. The article describes the discovery of novel molecular recognition motifs and the development of powerful antiviral agents based on these host guest systems. It explains the general underlying mechanisms of antiviral action and points to future optimization and application as therapeutic agents.This article reports the synthesis and characterization of a novel self-immolative linker, based on thiocarbonates, which releases a free thiol upon activation via enzymes. We demonstrate that thiocarbonate self-immolative linkers can be used to detect the enzymes penicillin G amidase (PGA) and nitroreductase (NTR) with high sensitivity using absorption spectroscopy. Paired with modern thiol amplification technology, the detection of PGA and NTR were achieved at concentrations of 160 nM and 52 nM respectively. In addition, the PGA probe was shown to be compatible with both biological thiols and enzymes present in cell lysates.G protein-coupled receptors (GPCRs) as the most important class of pharmacological targets regulate G-protein and β-arrestin-mediated signaling through allosteric interplay, which are responsible for different biochemical and physiological actions like therapeutic efficacy and side effects. However, the allosteric mechanism underlying preferentially recruiting one transducer versus the other has been poorly understood, limiting drug design. Motivated by this issue, we utilize accelerated molecular dynamics simulation coupled with potential of mean force (PMF), molecular mechanics Poisson Boltzmann surface area (MM/PBSA) and protein structure network (PSN) to study two ternary complex systems of a representative class A GPCR (μ-opioid receptor (μOR)) bound by an agonist and one specific transducer (G-protein and β-arrestin). The results show that no significant difference exists in the whole structure of μOR between two transducer couplings, but displays transducer-dependent changes in the intracellular binding region of μOR, where the β-arrestin coupling results in a narrower crevice with TM7 inward movement compared with the G-protein. In addition, both the G-protein and β-arrestin coupling can increase the binding affinity of the agonist to the receptor. However, the interactions between the agonist and μOR also exhibit transducer-specific changes, in particular for the interaction with ECL2 that plays an important role in recruiting β-arrestin. The allosteric network analysis further indicates that Y1483.33, F1523.37, F1563.41, N1914.49, T1603.45, Y1062.42, W2936.48, F2896.44, I2485.54 and Y2525.58 play important roles in equally activating G-protein and β-arrestin. In contrast, M1613.46 and R1653.50 devote important contributions to preferentially recruit G-protein while D1643.49 and R179ICL2 are revealed to be important for selectively activating β-arrestin. The observations provide useful information for understanding the biased activation mechanism.Extracellular vesicle (EV) delivery of TNF-related apoptosis-inducing ligand (TRAIL) (EV-T) has been shown to be highly efficient for cancer treatment when combined with the potent cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH727965, Dina). However, only topical administration was previously tested for cancer treatment, leaving unknown the efficacy of systemic therapy by EV-T and Dina. In this study we hypothesize that the systemic application of EV-T and Dina can be performed through EV-mediated co-delivery of TRAIL and Dina. Dina was first post-loaded into EV-Ts by sonication to prepare EV-mediated co-delivery of TRAIL and Dina, designated Dina@EV-T. Then Dina@EV-Ts were shown to be stable, readily endocytosed into cancer cells, and highly effective at inducing intensive apoptosis in resistant cancer lines but not in normal cells. Moreover, systemically infused Dina@EV-Ts showed evident tumor tropism suggesting their good potential for tumour-targeted delivery of therapeutics. Importantly, the systemic therapy with Dina@EV-Ts showed the best efficacy in vivo when compared with other treatments. The augmented therapeutic efficacy appeared to be associated with the concomitant suppression of prosurvival CDK1 and anti-apoptotic proteins including CDK9, cFLIP, MCL-1, BCL-2 and Survivin by Dina@EV-T treatment. Additionally, there were no adverse side effects observed for the systemic Dina@EV-T therapy. In conclusion, our data suggest that the co-delivery of TRAIL and Dina by EVs potentially constitutes a novel tumour-targeted therapy, which is highly effective and safe for the treatment of refractory tumors.Mononuclear high-valent iron(IV)-oxo intermediates are excellent oxidants towards oxygenation reactions by heme and nonheme metalloenzymes and their model systems. One of the most important functions of these intermediates in nature is to detoxify various environmental pollutants. Organic substrates, such as halogenated phenols, are known to be water pollutants which can be degraded to their less hazardous forms through an oxidation reaction by iron(IV)-oxo complexes. Metalloproteins in nature utilize various types of second-coordination sphere interactions to anchor the substrate in the vicinity of the active site. This concept of substrate-binding is well-known for natural enzymes, but is elusive for the relevant biomimetic model systems. Herein, we report the oxidative reactivity patterns of an iron(IV)-oxo intermediate, [FeIV(O)(2PyN2Q)]2+, (2PyN2Q = 1,1-di(pyridin-2yl)-N,N-bis(quinolin-2-ylmethyl)methanamine) with a series of mono-, di- and tri-halophenols. A detailed experimental study shows that the dehalogenation reactions of the halophenols by such iron(IV)-oxo intermediates proceed via an initial hydrogen atom abstraction from the phenolic O-H group. Furthermore, based on the size and nucleophilicity of the halophenol, an intermediate substrate-bound species forms that is a phenolate adduct to the ferric species, which thereafter leads to the formation of the corresponding products.Adoptive immunotherapies based on the transfer of functional immune cells hold great promise in treating a wide range of malignant diseases, especially cancers, autoimmune diseases, and infectious diseases. However, manufacturing issues and biological barriers lead to the insufficient population of target-selective effector cells at diseased sites after adoptive transfer, hindering effective clinical translation. The convergence of immunology, cellular biology, and materials science lays a foundation for developing biomaterial-based engineering platforms to overcome these challenges. Biomaterials can be rationally designed to improve ex vivo immune cell expansion, expedite functional engineering, facilitate protective delivery of immune cells in situ, and navigate the infused cells in vivo. Herein, this review presents a comprehensive summary of the latest progress in biomaterial-based strategies to enhance the efficacy of adoptive cell therapy, focusing on function-specific biomaterial design, and also discusses the challenges and prospects of this field.