Coyneditlevsen9605

Expansile nanoparticles (eNPs) are a promising pH-responsive polymeric drug delivery vehicle, as demonstrated in multiple intraperitoneal cancer models. However, previous delivery routes were limited to intraperitoneal injection and to a single agent, paclitaxel. In this study, we preliminarily evaluate the biodistribution and in vivo toxicity of eNPs in mice after intravenous injection. The eNPs localize predominantly to the liver, without detectable acute toxicity in the liver or other key organs. On the basis of these results, we encapsulated FQI1, a promising lead compound for treatment of hepatocellular carcinoma, in eNPs. #link# eNPs are taken up by click here and noncancerous human liver cells in vitro, although at different rates. FQI1-loaded eNPs release FQI1 in a pH-dependent manner and limit proliferation equivalently to unencapsulated FQI1 in immortalized hepatocytes in vitro. eNPs are a versatile platform delivery system for therapeutic compounds and have potential utility in the treatment of liver disease.Highly sensitive and flexible pressure sensors were developed based on dielectric membranes composed of insulating microbeads contained within polyvinylidene fluoride (PVDF) nanofibers. The membrane is fabricated using a simple electrospinning process. The presence of the microbeads enhances porosity, which in turn enhances the sensitivity (1.12 kPa-1 for the range of 0-1 kPa) of the membrane when used as a pressure sensor. The microbeads are fixed in position and uniformly distributed throughout the nanofibers, resulting in a wide dynamic range (up to 40 kPa) without any sensitivity loss. The fluffy and nonsticky PVDF nanofiber features low hysteresis and ultrafast response times (∼10 ms). The sensor has also demonstrated reliable pressure detection over 10 000 loading cycles and 250 bending cycles at a 13 mm bending radius. These pressure sensors were successfully applied to detect heart rate and respiratory signals, and an array of sensors was fabricated and used to recognize spatial pressure distribution. The sensors described herein are ultrathin and ultralight, with a total thickness of less than 100 μm, including the electrodes. All of the materials comprising the sensors are flexible, making them suitable for on-body applications such as tactile sensors, electronic skins, and wearable healthcare devices.Recombinant proteins have increased our knowledge regarding the physiological role of proteins; however, affinity purification tags are often not cleaved prior to analysis, and their effects on protein structure, stability and assembly are often overlooked. In this study, the stabilizing effects of an N-terminus dual-FLAG (FT2) tag fusion to transthyretin (TTR), a construct used in previous studies, are investigated using native ion mobility-mass spectrometry (IM-MS). A combination of collision-induced unfolding and variable-temperature electrospray ionization is used to compare gas- and solution-phase stabilities of FT2-TTR to wild-type and C-terminal tagged TTR. Despite an increased stability of both gas- and solution-phase FT2-TTR, thermal degradation of FT2-TTR was observed at elevated temperatures, viz., backbone cleavage occurring between Lys9 and Cys10. This cleavage reaction is consistent with previously reported metalloprotease activity of TTR [Liz et al. 2009] and is suppressed by either metal chelation or excess zinc. This study brings to the fore the effect of affinity tag stabilization of TTR and emphasizes unprecedented detail afforded by native IM-MS to assess structural discrepancies of recombinant proteins from their wild-type counterparts.Solid state electrolytes (SSEs) offer a great potential to enable high performance and safe lithium (Li) batteries. However, the scale-up synthesis and processing of SSEs is a major challenge. In this work, three-dimensional (3D) networks of lithium lanthanum titanite (LLTO) nanofibers are produced through a scale-up technique based on solution blowing. Compared with the conventional electrospinning method, the solution blowing technique enables high speed fabrication of SSEs (e.g. fifteen times faster) with superior productivity and quality. Additionally, the room temperature ionic conductivity of composite polymer electrolytes (CPEs) formed from solution-blown LLTO fibers is 70% higher than the ones formed from electrospun fibers (1.9×10 -4 S cm-1 vs. 1.1×10-4 S cm-1 for 10 wt.% LLTO fibers). Furthermore, the cyclability of the CPEs made from solution blown fibers in the symmetric Li cell is more than 2.5 times than the CPEs made from electropun fibers. These comparisons show that solution blown ion-conductive fibers hold great promise for applications in Li metal batteries.We have utilized multiparametric surface plasmon resonance and impendance-based quartz crystal microbalance instruments to study the distribution coefficients of catechol derivatives in cell model membranes. Our findings verify that the octanol-water partitioning coefficient is a poor descriptor of the total lipid affinity for small molecules which show limited lipophilicity in the octanol-water system. Notably, 3-methoxytyramine, the methylated derivative of the neurotransmitter dopamine, showed substantial affinity to the lipids despite its nonlipophilic nature predicted by octanol-water partitioning. The average ratio of distribution coefficients between 3-methoxytyramine and dopamine was 8.0. We also found that the interactions between the catechols and the membranes modeling the cell membrane outer leaflet are very weak, suggesting a mechanism other than the membrane-mediated mechanism of action for the neurotransmitters at the postsynaptic site. The average distribution coefficient for these membranes was one-third of the average value for pure phosphatidylcholine membranes, calculated using all compounds. In the context of our previous work, we further theorize that membrane-bound enzymes can utilize membrane headgroup partitioning to find their substrates. This could explain the differences in enzyme affinity between soluble and membrane-bound isoforms of catechol-O-methyltransferase, an essential enzyme in catechol metabolism.