• Childers Carey ha publicado una actualización hace 11 horas, 31 minutos

    09 μM. A thin film of CuG was prepared by casting the gel and used as a test strip for the visual detection of cyanide in water.We have developed a macromolecular prodrug platform based on poly(l-lysine succinylated) (PLS) that targets scavenger receptor A1 (SR-A1), a receptor expressed by myeloid and endothelial cells. We demonstrate the selective uptake of PLS by murine macrophage, RAW 264.7 cells, which was eliminated upon cotreatment with the SR-A inhibitor polyinosinic acid (poly I). Further, we observed no uptake of PLS in an SR-A1-deficient RAW 264.7 cell line, even after 24 h incubation. In mice, PLS distributed to lymphatic organs following i.v. injection, as observed by ex vivo fluorescent imaging, and accumulated in lymph nodes following both i.v. and i.d. administrations, based on immunohistochemical analysis with high-resolution microscopy. As a proof-of-concept, the HIV antiviral emtricitabine (FTC) was conjugated to the polymer’s succinyl groups via ester bonds, with a drug loading of 14.2% (wt/wt). The prodrug (PLS-FTC) demonstrated controlled release properties in vitro with a release half-life of 15 h in human plasma and 29 h in esterase-inhibited plasma, indicating that drug release occurs through both enzymatic and nonenzymatic mechanisms. Upon incubation of PLS-FTC with human peripheral blood mononuclear cells (PBMCs), the released drug was converted to the active metabolite FTC triphosphate. In a pharmacokinetic study in rats, the prodrug achieved ∼7-19-fold higher concentrations in lymphatic tissues compared to those in FTC control, supporting lymphatic-targeted drug delivery. We believe that the SR-A1-targeted macromolecular PLS prodrug platform has extraordinary potential for the treatment of infectious diseases.Excited state vibrations are crucial for determining the photophysical and photochemical properties of molecular compounds. Stimulated Raman scattering can coherently stimulate and probe molecular vibrations with optical pulses, but it is generally restricted to ground state properties. Working under resonance conditions enables cross-section enhancement and selective excitation to a targeted electronic level but is hampered by an increased signal complexity due to the presence of overlapping spectral contributions. Here, we show how detailed information about ground and excited state vibrations can be disentangled by exploiting the relative time delay between Raman and probe pulses to control the excited state population, combined with a diagrammatic formalism to dissect the pathways concurring with the signal generation. The proposed method is then exploited to elucidate the vibrational properties of the ground and excited electronic states in the paradigmatic case of cresyl violet. We anticipate that the presented approach holds the potential for selective mapping of the reaction coordinates pertaining to transient electronic stages implied in photoactive compounds.The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 11, 21, and 41 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5′-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB formeleased from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.We disclose that a predried form of methyliminodiacetic acid (MIDA), MIDA anhydride, acts as both a source of the MIDA ligand and an in situ desiccant to enable a mild and simple MIDA boronate synthesis procedure. This method expands the range of sensitive boronic acids that can be converted into their MIDA boronate counterparts. Further utilizing unique properties of MIDA boronates, we have developed a MIDA Boronate Maker Kit which enables the direct preparation and purification of MIDA boronates from boronic acids using only heating and centrifuge equipment that is widely available in laboratories that do not specialize in organic synthesis.Terreuspyridine (1), the first 3,5-demethylorsellinic acid (DMOA) derived meroterpenoid alkaloid, was isolated from the fungus Aspergillus terreus, which represents a new type of meroterpenoid possessing an unexpected tetracyclic 6/6/6/6 architecture. The structure of 1 with absolute configuration was determined by X-ray diffraction analysis. Biogenetically, it was proposed to be derived from the fusion of a DMOA-meroterpenoid and a glutamate. Terreuspyridine (1) exhibited moderate inhibitory activity against the BChE with an IC50 value of 16.4 μM.Cryopreservation is the only fully established procedure to extend the lifespan of living cells and tissues, a key to activities spanning from fundamental biology to clinical practice. Despite its prevalence and impact, the central aspects of cryopreservation, such as the cell’s physicochemical environment during freezing, remain elusive. Here we address that question by coupling in situ microscopic directional freezing to visualize cells and their surroundings during freezing with the freezing-medium phase diagram. We extract the freezing-medium spatial distribution in cryopreservation, providing a tool to describe the cell vicinity at any point during freezing. read more We show that two major events define the cells’ local environment over time the interaction with the moving ice front and the interaction with the vitreous moving front, a term we introduce here. Our correlative strategy may be applied to cells relevant to clinical research and practice and may help in the design of new cryoprotective media based on local physicochemical cues.