Stougaardsalas1562

A novel "non-aromatic pool" synthetic strategy for the synthesis of benzofuran-based natural products via oxidative haloaromatization of enones is reported. This approach is successfully applied in the first total synthesis of the natural product aspergillusene B. In comparison with a separately executed "aromatic pool" synthesis, the "non-aromatic pool" protocol demonstrates equivalent efficiency but offers a much higher degree of modularity.Reversible and switchable wrinkling surfaces in response to various external stimuli have extensive potential applications. In this Letter, we prepared the reversible wrinkling on poly(dimethylsiloxane) (PDMS) surfaces, responsive to the solvents, by ultraviolet-ozone (UVO) treatment with/without mechanical prestrain. Based on the solvent-responsive wrinkling, three types of optical transparency dynamics were achieved easily in a single and simple film-substrate system, including (I) completely reversible transparency with controlled relaxation time and isotropic light scattering; (II) completely reversible transparency with anisotropic light scattering and tunable diffusion degree; and (III) incompletely reversible transparency. The reversibility and stability of wrinkles can be controlled by tailoring the solvent type, UVO exposure time, and mechanical prestrain. The underlying mechanisms for the three wrinkling dynamics have been clearly elucidated. The extremely simple material system and the facile but efficient technique pave a novel way for realizing versatile optical dynamics for smart displays.A transition-metal-free indole synthesis using radical coupling of 2-halotoluenes and imines via the later-stage C-N bond construction was reported for the first time. It includes an aminyl radical generation by C-H cleaving addition of 2-halotoluenes to imines via the carbanion radical relay and an intramolecular coupling of aryl halides with aminyl radicals. One standard condition can be used for all halides including F, Cl, Br, and I. No extra oxidant or transition metal is required.Lipases are important hydrolytic enzymes used in a spectrum of technological applications, such as the pharmaceutical and detergent industries. Because of their versatile nature and ability to accept a broad range of substrates, they have been extensively used for biotechnological and industrial applications. Current assays to measure lipase activity primarily rely on low-sensitivity measurements of pH variations or visible changes of material properties, like hydration, and often require high amounts of proteins. Fluorescent readouts, on the other hand, offer high contrast and even single-molecule sensitivity, albeit they are reliant on fluorogenic substrates that structurally resemble the native ones. Here we present a method that combines the highly sensitive readout of fluorescent techniques while reporting enzymatic lipase function on native substrates. The method relies on embedding the environmentally sensitive fluorescent dye pHrodo and native substrates into the bilayer of liposomes. The charged products of the enzymatic hydrolysis alter the local membrane environment and thus the fluorescence intensity of pHrodo. The fluorescence can be accurately quantified and directly assigned to product formation and thus enzymatic activity. We illustrated the capacity of the assay to report the function of diverse lipases and phospholipases both in a microplate setup and at the single-particle level on individual nanoscale liposomes using total internal reflection fluorescence (TIRF). The parallelized sensitive readout of microscopy combined with the inherent polydispersity in sizes of liposomes allowed us to screen the effect of membrane curvature on lipase function and identify how mutations in the lid region control the membrane curvature-dependent activity. We anticipate this methodology to be applicable for sensitive activity readouts for a spectrum of enzymes where the product of the enzymatic reaction is charged.Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supranormal concentrations suppress preretinal neovascularization. Herein we investigated the pharmacokinetics of opticin following intravitreal injection in rabbits. SAR405 To measure simultaneously concentrations of human and rabbit opticin, a selected reaction monitoring mass spectrometry assay was developed. The mean concentration of endogenous rabbit opticin in 7 uninjected eyes was measured and found to be 19.2 nM or 0.62 μg/mL. When the vitreous was separated by centrifugation into a supernatant and collagen-containing pellet, 94% of the rabbit opticin was in the supernatant. Intravitreal injection of human opticin (40 μg) into both eyes of rabbits was followed by enucleation at 5, 24, and 72 h and 7, 14, and 28 days postinjection (n = 6 at each time point) and measurement of vitreous human and rabbit opticin concentrations in the supernatant and collagen-containing pellet following centrifugation. The volume of distribution of human opticin was calculated to be 3.31 mL, and the vitreous half-life was 4.2 days. Assuming that rabbit and human opticin are cleared from rabbit vitreous at the same rate, opticin is secreted into the vitreous at a rate of 0.14 μg/day. We conclude that intravitreally injected opticin has a vitreous half-life that is similar to currently available antiangiogenic therapeutics. While opticin was first identified bound to vitreous collagen fibrils, here we demonstrate that >90% of endogenous opticin is not bound to collagen. Endogenous opticin is secreted by the nonpigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate, and the turnover in vitreous is approximately 15% per day.Tumor-targeted drug delivery via chemotherapy is very effective on cancer treatment. For potential anticancer agent such as Camptothecin (CPT), high chemotherapeutic efficacy and accurate tumor targeting are equally crucial. Inspired by special CD44 binding capability from hyaluronic acid (HA), in this study, novel HA-coated CPT nanocrystals were successfully prepared by an antisolvent precipitation method for tumor-targeted delivery of hydrophobic drug CPT. These HA-coated CPT nanocrystals demonstrated high drug loading efficiency, improved aqueous dispersion, prolonged circulation, and enhanced stability resulting from their nanoscaled sizes and hydrophilic HA layer. Moreover, as compared to crude CPT and naked CPT nanocrystals, HA-coated CPT nanocrystals displayed dramatically enhanced in vitro anticancer activity, apoptosis-inducing potency against CD44 overexpressed cancer cells, and lower toxic effect toward normal cells due to pH-responsive drug release behavior and specific HA-CD44 mediated endocytosis. Additionally, HA-coated CPT nanocrystals performed fairly better antimigration activity and biocompatibility. The possible molecular mechanism regarding this novel drug formulation might be linked to intrinsic mitochondria-mediated apoptosis by an increase of Bax to Bcl-2 ratio and upregulation of P53. Consequently, HA-coated CPT nanocrystals are expected to be an effective nanoplatform in drug delivery for cancer therapy.The present study systematically investigates the morphology and crystallization process of inorganic CsPbBr3 perovskite layer films fabricated by thermal coevaporation in conjunction with continuous low-temperature thermal annealing to promote in situ dynamic thermal crystallization. The results confirm for the first time that both the crystal grain size and the compactness of the CsPbBr3 films can be tuned during the thermal coevaporation fabrication process via in situ dynamic thermal crystallization. The performance of the PeLEDs employing the CsPbBr3 films as the emitter layer is investigated in detail with respect to the substrate temperature and deposition rate employed during deposition of the CsPbBr3 film. This study provides guidelines for developing suitable film production processes and highlights future challenges that must be addressed to facilitate the commercial development of large-area, uniform, and flexible perovskite-based optoelectronic devices.Resveratrol (RES) is a nutraceutical with promising anti-inflammatory properties for the treatment of inflammatory bowel diseases (IBD). However, the clinical effectiveness of resveratrol as an oral anti-inflammatory agent is hindered by its extremely poor solubility and poor stability. In this study, we encapsulated resveratrol in β-lactoglobulin (BLG) nanospheres and systematically analyzed their formulation parameters in vitro followed by a thorough in vivo anti-inflammatory testing in a highly specialized spontaneous murine UC model (Winnie mice model). Complexation of resveratrol with BLG increased the aqueous solubility of resveratrol by ≈1.7 times with 10% w/w loading. Additionally, the in vitro dissolution of resveratrol from the particles was found to be higher compared to resveratrol alone, resulting in >90% resveratrol dissolution in ∼8 h. The anti-inflammatory activity of resveratrol was examined for the first time in Winnie mice, a mouse model that closely represents the clinical signs of IBD. At a 50 mg/kg oral dose for 2 weeks, BLG-RES significantly improved both % body weight and disease activity index (DAI), compared to free resveratrol in Winnie mice. Importantly, histological evaluations revealed a similar trend with striking improvement in the pathology of the colon via an increase in goblet cell numbers and recovery of colonic epithelium. BLG-RES significantly increased the expression level of cytokine interleukin-10 (Il10), which confirms the reduction in inflammation potentially because of the increased dissolution and stability of resveratrol by complexation with BLG. This comprehensive study demonstrates the effectiveness of biocompatible nanomaterials such as BLG in oral delivery of poorly soluble anti-inflammatory molecules such as resveratrol in the treatment of IBD.Inverted/reverse hexagonal (HII) phases are of special interest in several fields of research, including nanomedicine. We used molecular dynamics (MD) simulation to study HII systems composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoyloleoylphosphatidylethanolamine (POPE) at several hydration levels and temperatures. The effect of the hydration level on several HII structural parameters, including deuterium order parameters, was investigated. We further used MD simulations to estimate the maximum hydrations of DOPE and POPE HII lattices at several given temperatures. Finally, the effect of acyl chain unsaturation degree on the HII structure was studied via comparing the DOPE with POPE HII systems. In addition to MD simulations, we used deuterium nuclear magnetic resonance (2H NMR) and small-angle X-ray scattering (SAXS) experiments to measure the DOPE acyl chain order parameters, lattice plane distances, and the water core radius in HII phase DOPE samples at several temperatures in the presence otems composed of molecules other than the PE systems used here and to improve and validate force field parameters by using the target data in the HII phase.Transient strained cyclic intermediates have become valuable intermediates in modern synthetic chemistry. Although silyl triflate precursors to strained intermediates are most often employed, the instability of some silyl triflates warrants the development of alternative precursors. We report the syntheses of silyl tosylate precursors to cyclohexyne, 1,2-cyclohexadiene, and 1,2-cycloheptadiene. The resultant strained intermediates undergo trapping in situ to give cycloaddition products. Additionally, the results of competition experiments between silyl triflates and silyl tosylates are reported.