In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Recycling of multilayer packaging using a reversible cross-linking adhesive

Plastic-based multilayer packaging has an important function on the packaging market, but is currently not recyclable as the polymer layers used are usually thermodynamically immiscible. This work therefore follows the approach to prepare separable multilayer packaging using a packaging adhesive modified with thermally unstable adducts, and proposes a corresponding recycling process. For this purpose, typical multilayer structures (polyethylene (PE)// polyethylene terephtalate (PET), PET//aluminum, and PE//aluminum) were prepared by curing furan-/maleimide-functionalized polyurethane (PU)-prepolymers with a three-functional cross-linking agent. Adhesions of up to over 3N per 15 mm test specimen were measured or substrate failures of PET films were observed. However, heating in dimethylsulfoxide, the retro-Diels–Alder reaction takes place and the cross-linked adhesive turns thermoplastic and dissolves in the solvent. Thus, the laminate separates and the pure PE, PET, and aluminum foils can be recovered without any PU residue.     

Lecture capture with real‐time rearrangement of visual elements: impact on student performance

The primary goal of this study is to create and test a lecture‐capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the instructor and students' images, into lecture videos that are embedded in a website for students to review after school. The present study employed a two‐group experimental design, with 153 participants (145 females and 8 males) making up an experimental group in which lecture courses were recorded using the new lecture‐capture system, and 149 participants (140 females and 9 males) forming a control group whose lectures were recorded by traditional means. All participants were in the freshman college and studying Introduction to Computer and Information Science in one of six classes, and were randomly assigned to one of the two groups. The participants' midterm examination and final examination scores were collected as indicators of their academic performance, with their mathematics entrance scores used as a pre‐test. The findings obtained from analysis of covariance (ANCOVA) suggest that appropriate rearrangement of visual elements in lecture videos can significantly impact students' learning performance.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Photovoltaic Power Supply Unit for the Basic Stations of Cellular Companies

The data on the use of solar photovoltaic plants (PVPs) for providing a reliable and guaranteed power supply to telecommunication systems and cellular communication systems in the conditions prevalent in Uzbekistan are given. The research-based structures developed by OOO MIR SOLAR and the selection of PVP elements ensuring their reliable operation are described. The main influencing factors are discussed, and the use of effective combinations of different types of panels (from monocrystalline and polycrystalline silicon) and a specially developed controller are considered.     

Modeling the Motion of a Saw Ginning Machine

The dynamic characteristics of a saw gin as a subsystem with lumped and distributed parameters are considered in the paper. On the basis of investigation of the machine assembly, graphs are drawn that allow establishing the maximum values of the angle of relative rotation and the angle of rotation of the saw cylinder shaft under torsion.     

Carbon supported bimetallic Ru‐Co catalysts for H2 production through NaBH4 and NH3BH3 hydrolysis

This work investigates the effect of the addition of small amounts of Ru (0.5‐1 wt%) to carbon supported Co (10 wt%) catalysts towards both NaBH₄ and NH₃BH₃ hydrolysis for H₂ production. In the sodium borohydride hydrolysis, the activity of Ru‐Co/carbon catalysts was sensibly higher than the sum of the activities of corresponding monometallic samples, whereas for the ammonia borane hydrolysis, the positive effect of Ru‐Co systems with regard to catalytic activity was less evident. The performances of Ru‐Co bimetallic catalysts correlated with the occurrence of an interaction between Ru and Co species resulting in the formation of smaller ruthenium and cobalt oxide particles with a more homogeneous dispersion on the carbon support. It was proposed that Ru^°, formed during the reduction step of the Ru‐Co catalysts, favors the H₂ activation, thus enhancing the reduction degree of the cobalt precursor and the number of Co nucleation centers. A subsequent reduction of cobalt and ruthenium species also occurs in the hydride reaction medium, and therefore the state of the catalyst before the catalytic experiment determines the state of the active phase formed in situ. The different relative reactivity of the Ru and Co active species towards the two investigated reactions accounted for the different behavior towards NaBH₄ and NH₃BH₃ hydrolysis.     

The Role of Excitation Photons Energy in the Photoinduced Carrier Dynamics in InGaAs/InAlAs Superlattice Heterostructures

Technical Physics Letters - The influence of excitation photons energy on the relaxation times of photoexcited carriers is studied. The involved relaxation mechanisms are evaluated and the...     

Influence of the Design of Metal Receivers of Slab Continuous-Casting Machines on the Motion of Flow in the Tundish in the Case of Deviations of the Metal Stream from the Required Position. Part II. Procedure of Simulation1

Refractories and Industrial Ceramics - We study the problem of evaluation of the influence of design of the metal receiver of a large-capacity tundish of slab continuous-casting machine on the...