Vossdalgaard4236

ntimicrobial activity and mechanism of antimicrobial peptides (AMPs).RNAi therapy has been developed and explored for treating retinal conditions since last decades. The progression of retinal diseases including the age-related macular degeneration and glaucoma is associated with the malfunction of specific retinal cells. Therefore, to deliver therapeutic RNAi to selective retinal tissues with desired gene downregulation is crucial for the treatment of retinal diseases via RNAi therapy. Lipid-based nanoparticles are potent delivery vectors for RNAi therapeutics to achieve high gene silencing efficiency. The surface charge has been demonstrated to affect the intraocular behaviors and retinal distribution of intravitreally administered lipid nanoparticles (LNPs), which could subsequently affect the gene knockdown efficiency in specific retinal layers. Here, we evaluated three charged LNPs for their ability to deliver siRNA and facilitate gene downregulation both in vitro and in vivo. LNPs with different surface charges ranging from neutral to positive (5-34 mV) were successfully formulated. All types of charged LNPs managed gene knockdown in both mammalian cell line and primary neurons. At 48 h post intravitreal injection, neutral LNPs (6.2 mV) and mildly positive LNPs (15.9 mV) mediated limited retinal gene suppression ( less then 10%) and the more positive LNPs (31.2 mV) led to ∼25% gene suppression in the retinal ganglion cell (RGC) layer. No gene silencing in the retinal pigmented epithelium layer was facilitated by any LNPs independent of the charges. In summary, this study has shown that positive LNPs with an optimized charge managed specific gene downregulation in the RGC layer. These RNAi carriers hold potential for the treatment of RGC-associated retinal diseases.A great deal of effort has been focused on developing a metal-free catalytic system for epoxidation of unreactive alkenes. Fluoroketones are thought as remarkably promising catalysts for epoxidation reactions. The combination of fluorinated alcohols and catalytic amounts of hexafluoroacetone (HFA) gives a versatile and effective medium for epoxidation of various olefins with hydrogen peroxide. However, the fundamental physicochemical properties of HFA remained largely unclear, although they were very important to understand the related interactions. Here, we performed a joint study on the electron affinity and electronic structure of HFA employing negative ion photoelectron (NIPE) spectroscopy and quantum chemistry calculations. Two distinct bands with complicated vibrational progressions were observed in the 193 nm NIPE spectrum. The adiabatic/vertical detachment energies (ADE/VDE) were derived to be 1.42/2.06 and 4.43/4.86 eV for the ground singlet state and excited triplet state, respectively. Using the optimized geometries and vibrational frequencies of the anion and the neutral, the Franck-Condon factors were calculated for electron detachments to produce HFA in its lowest singlet and triplet states. Good agreements are obtained hereby for both bands between the experimental and calculated NIPE spectra, when taking into account combination vibrational excitations, unequivocally revealing that HFA possesses a singlet ground state with a giant singlet-triplet energy difference (ΔEST). The electron affinity (EA) and ΔEST of HFA were therefore determined to be EA = 1.42 ± 0.02 eV and ΔEST = -3.01 eV.The search for new environmental-friendly materials for energy storage is ongoing. In the presented paper, we propose polymer microgels as a new class of redox-active colloids (RACs). The microgel stable colloids are perspective low-viscosity fluids for advanced flow batteries with high volumetric energy density. In this research, we describe the procedure for the anchoring of 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO) redox-active sites to the polymeric chains of water-soluble microgels based on poly(N-isopropylacrylamide)-poly(acrylic acid) interpenetrating networks. Using cyclic voltammetry and EPR spectroscopy, we show that ca. 14% of 4-amino-TEMPO groups retain electroactive properties and demonstrate the reversible redox response. It allows achieving a stable capacity of 2.5 mAh/g, enabling the low-viscous catholyte with a capacity of more than 100 mAh/L.While density functional theory (DFT) is perhaps the most used electronic structure theory in chemistry, many of its practical aspects remain poorly understood. For instance, DFT at the generalized gradient approximation (GGA) tends to fail miserably at describing gas-phase reaction barriers, while it performs surprisingly well for many molecule-metal surface reactions. GGA-DFT also fails for many systems in the latter category, and up to now it has not been clear when one may expect it to work. We show that GGA-DFT tends to work if the difference between the work function of the metal and the molecule's electron affinity is greater than ∼7 eV and to fail if this difference is smaller, with sticking of O2 on Al(111) being a spectacular example. Using dynamics calculations we show that, for this system, the DFT problem may be solved as done for gas-phase reactions, i.e., by resorting to hybrid functionals, but using screening at long-range to obtain a correct description of the metal. Our results suggest the GGA error in the O2 + Al(111) barrier height to be functional driven. Our results also suggest the possibility to compute potential energy surfaces for the difficult-to-treat systems with computationally cheap nonself-consistent calculations in which a hybrid functional is applied to a GGA density.Transplacental transfer of environmental chemicals results in direct risks to fetal development. Although numerous studies have investigated transplacental transfer efficiencies (TTEs) of environmental chemicals, the underlying mechanisms and influencing factors remain poorly understood. The present study aims to synthesize a current state of knowledge on the TTEs of major environmental chemicals and explore the roles of chemicals' molecular descriptors and placental transporters in the transplacental transfer. The results indicate great variations in TTEs (median 0.29-2.86) across 51 chemicals. Chemical-dependent TTEs may partially be attributed to the influences of chemicals' molecular descriptors. Predictive models based on experimental TTEs and 1790 computed molecular descriptors indicate that a very limited number of molecular descriptors, such as the topological polar surface area, may substantially influence and efficiently predict chemicals' TTEs. RGD(ArgGlyAsp)Peptides In addition, molecular docking analyses were conducted to determine the binding affinities between 51 chemicals and six selected transporters, including BCRP, MDR1, hENT1, FRα, SERT, and MRP1.