Evaluation of Electrospun PCL-PLGA for Sustained Delivery of Kartogenin

In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle.     

Correction: Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery

Correction for ‘Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery’ by Christine N. Morrison et al., Chem. Sci., 2020, 11, 1216–1225, https://doi.org/10.1039/C9SC05586J.

The authors regret that in the original article, inhibitory values reported for some metallofragments were incorrect. Unfortunately, DMSO stock solutions of reportedly active ferrocene-based metallofragments were found to decompose in the presence of light, which resulted in inaccurate inhibition values. The authors maintain that the core conclusions of the paper are accurate and the utility of three-dimensional metal complexes for fragment-based drug discovery has merit.In the original article, ‘class A’ metallofragments are comprised of ferrocene derivatives (Fig. 1). Some of these ferrocene fragments (specifically those containing carbonyl groups) are reported as broadly inhibiting several protein targets. It was noted in our original report that the ferrocene scaffold was likely promiscuous due to its lipophilicity and potential redox activity, but that it might still serve as a useful metallofragment for fragment-based drug discovery (FBDD) campaigns. However, re-evaluation of these compounds against the influenza endonuclease (PA_N) failed to reproduce our original inhibition results for the class A metallofragments using freshly prepared stocks, indicating a problem with the materials used in the original study.Open in a separate windowFig. 1Chemical structures of class A metallofragments.Several compounds from class A were originally reported as having near complete (100%) inhibition against PA_N endonuclease at an inhibitor concentration of 200 μM (​and2).2). However, when re-evaluated under identical conditions, using freshly prepared DMSO stock solutions, inhibition was only observed with one fragment of this class (A22, Fig. 1), with the previously reported highly active fragments (A4, A7–A21,

Sets with B-action and linear algebra

Let B be a Boolean ring. Any unital B-module M has a B-action given by for all . We show that any set with B-action may be represented as a subset with B-action of a unital B-module. We extend this to algebras with B-action and apply it to if-then-else algebras over Boolean algebras by viewing them as semilattices with B-action. Received May 23, 1996; accepted in final form February 4, 1998.     

Rapid Quantification of 25-Hydroxyvitamin D<Subscript>3</Subscript> in Human Serum by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

LC-MS/MS is widely utilized today for quantification of vitamin D in biological fluids. Mass spectrometric assays for vitamin D require very careful method optimization for precise and interference-free, accurate analyses however. Here, we explore chemical derivatization and matrix-assisted laser desorption/ionization (MALDI) as a rapid alternative for quantitative measurement of 25-hydroxyvitamin D₃ in human serum, and compare it to results from LC-MS/MS. The method implemented an automated imaging step of each MALDI spot, to locate areas of high intensity, avoid sweet spot phenomena, and thus improve precision. There was no statistically significant difference in vitamin D quantification between the MALDI-MS/MS and LC-MS/MS: mean ± standard deviation for MALDI-MS—29.4?±?10.3 ng/mL—versus LC-MS/MS—30.3?±?11.2 ng/mL (P?=?0.128)—for the sum of the 25-hydroxyvitamin D epimers. The MALDI-based assay avoided time-consuming chromatographic separation steps and was thus much faster than the LC-MS/MS assay. It also consumed less sample, required no organic solvents, and was readily automated. In this proof-of-concept study, MALDI-MS readily demonstrated its potential for mass spectrometric quantification of vitamin D compounds in biological fluids.

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Graphical Abstract ?

     

Demonstration of an integrated capillary electrophoresis-laser-induced fluorescence fiber-optic sensor

A unique integrated separation-based fiber-optic sensor for remote analysis, that incorporates capillary electrophoresis (CE) directly at the fiber sensing terminus is described for the first time. Based on laser-induced fluorescence detection, the sensor offers the potential for high sensitivity. Although the broad-band nature of fluorescence spectra limits selectivity, the high separation power of CE provides a unique dimension of selectivity, while permitting a design of diminutive size. Previously reported fluorescence-based sensors that utilize a chemical reagent phase to impart selectivity tend to be inflexible (not readily adaptable to the detection of different species) and "one-measurement-only" sensors. Conversely, the CE-based fiber-optic sensor described here is both versatile and reusable. The analysis speed and the potential for remote control are further attributes which make the system amenable to remote sensing. A "single-fiber" optical detection arrangement and a "single-reservoir" CE system with the fiber-optic probing the outlet of the separation capillary are employed. A preliminary evaluation of the separation characteristics of this CE-based sensor is presented. Highlights include an observed separation efficiency of up to 3000 theoretical plates (8 cm separation capillary) and migration time reproducibility of less than 10% for frontal mode CE separations. The potential utility of the sensor for remote analysis is demonstrated with separations involving the CE analysis of charged fluorescent dyes, CE analysis of metal complexes based on in situ complexation and micellar electrokinetic capillary chromatographic analysis of neutral fluorescent compounds.     

Broadband Noise in Orthorhombic TaS3

We report experimental results on the broadband noise in sliding charge density wave conductor orthorhombic TaSn. The experimental results are in excellent agreement with a phenomenological model based on fluctuations in threshold field due to deformations of the sliding condensate.     

How to generalise demonic composition

Semigroup Forum - Demonic composition is defined on the set of binary relations over the non-empty set X, $$Rel_X$$ , and is a variant of standard or “angelic” composition. It arises...     

The Casimir effect for fields with arbitrary spin

The Casimir force arises when a quantum field is confined between objects that apply boundary conditions to it. In a recent paper we used the two-spinor calculus to derive boundary conditions applicable to fields with arbitrary spin in the presence of perfectly reflecting surfaces. Here we use these general boundary conditions to investigate the Casimir force between two parallel perfectly reflecting plates for fields up to spin-2. We use the two-spinor calculus formalism to present a unified calculation of well-known results for spin-1/2 (Dirac) and spin-1 (Maxwell) fields. We then use our unified framework to derive new results for the spin-3/2 and spin-2 fields, which turn out to be the same as those for spin-1/2 and spin-1. This is part of a broader conclusion that there are only two different Casimir forces for perfectly reflecting plates—one associated with fermions and the other with bosons.