Mesoporous electroactive silver doped calcium borosilicates: Structural,antibacterial and myogenic potential relationship of improved bio-ceramics

In this work improved electroactive mesoporous Ag-doped bio-ceramics for medical usages are developed, examining their structural, electrical, in-vitro bioactivity, cell cultures and antibacterial properties against various classical pathogenic bacteria. Ag-containing mesoporous bio-ceramics (MBCs): xmol%Ag₂O - (100-x)[45.8CaO-8.4B₂O₃-45.8SiO₂] where x = 2, 5, 7.5 and 10 were synthesized through a sol-gel method. The small angle X-ray scattering and electron microscopy studies reveal the embedment of silver nanoparticles in the samples. Existence of silver as Ag⁺/Ag⁰ forms in the samples is confirmed by X-ray photoelectron spectroscopy. The N₂ adsorption-desorption analysis evidence the mesoporous structure of the samples. The electrical conductivity of samples increases from 5.4 x 10^?8 S cm^?1 for x = 2 to 1.9 x 10^?6 S cm^?1 for x = 7.5 and then decreases to 0.9 x 10^?6 S cm^?1 for x = 10 at 110 °C. In vitro bioactivity studies revealed that Ag-containing MBCs hold the bone-like hydroxyapatite formation after immersion in human blood plasma like-solution such as Dulbecco's Modi?ed Eagle's Medium. The antibacterial effect of samples against pathogenic bacteria (S. aureus, E. coli, P. monas aeruginosa, and B. cereus) increases with Ag concentration (x = 7.5) and then decreases with Ag content (x = 10). Antibacterial effect is greater for the sample with high electrical conductivity. The cell culture studies evidence not considerable cytotoxic effects for Ag-containing MBCs. Finally, the C2C12 myoblast cell culture studies reveal the significant cell growths and differentiation (myogenesis) for high electrical conducting Ag-containing MBCs.     

Effect of heat treatment and zircon addition on the properties of low-cement castables based on recycled alumina grog

In this investigation, low-cement castables were prepared using 70% alumina grog aggregates obtained from crushed alumina brick waste. The aggregates were thermally treated at 1550 °C for 3 h. Four types of low-cement castables were prepared with various types of aggregates (alumina grog with or without thermal treatment) and fillers (with or without zircon addition), and they were evaluated in terms of their physical, thermal, and chemical properties. Microstructural analysis via scanning electron microscopy (SEM) was performed on the castables before and after slag attack. Compared to the other fabricated castables, the thermally treated alumina grog castables with zircon showed better physical properties, such as a higher bulk density, cold crushing strength, and modulus of rupture and a lower apparent porosity and water absorption. In addition, they had a higher positive linear thermal expansion, refractoriness under load, permanent linear change, and hot modulus of rupture. The results of the SEM with energy dispersive X-ray analysis of the prepared castables confirmed that the mullite and anorthite phases were predominant when zircon was not added and the zircon–mullite phase additionally appeared upon the incorporation of zircon. A quantitative elemental analysis via X-ray fluorescence spectroscopy was employed to determine the composition of the castables. X-ray diffraction analysis showed that the alumina grog castables had a high mullite and low anorthite content, and the thermally treated alumina grog had a high anorthite, low mullite, and high zircon content. The improvement in the mechanical and thermo-mechanical properties of the castables with thermally treated alumina grog and added zircon can be attributed to the formation of the zircon–mullite phase with a low mullite phase content.     

Diluted chemical bath deposition of CdZnS as prospective buffer layer in CIGS solar cell

In this study, dilute chemical bath deposition technique has been used to deposit CdZnS thin films on soda-lime glass substrates. The structural, morphological, optoelectronic properties of as-grown films have been investigated as a function of different Zn²⁺ precursor concentrations. The X-ray diffractogram of CdS thin-film reveals a peak corresponding to (002) plane with wurtzite structure, and the peak shift has been observed with the increase of the Zn²⁺ concentration upon formation of CdZnS thin film. From morphological studies, it has been revealed that the diluted chemical bath deposition technique provides homogeneous distribution of film on the substrate even at a lower concentration of Zn²⁺. Optical characterization has shown that the transparency of the film is influenced by Zn²⁺ concentration and when the Zn²⁺ concentration is varied from 0 M to 0.0256 M, bandgap values of resulting films range from 2.42 eV to 3.90 eV while. Furthermore, electrical properties have shown that with increasing zinc concentration the resistivity of the film increases. Finally, numerical simulation validates and suggests that CdZnS buffer layer with composition of 0.0032 M Zn²⁺ concentration would be a promising candidate in CIGS solar cell.     

Dissolution of Metal Oxides in a Choline Chloride–Sulphosalicylic Acid Deep Eutectic Solvent

Theoretical Foundations of Chemical Engineering - A choline chloride–sulfosalicylic acid deep eutectic solvent (DES) is proposed for dissolving the oxides Co(II), Cu(II), Zn(II), Fe(III),...     

BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

Native Mass Spectrometry for the Study of PROTAC GNE-987-Containing Ternary Complexes

PRO teolysis TA rgeting C himeras (PROTACs) promote the degradation, rather than inhibition, of a drug target as a mechanism for therapeutic treatment. Bifunctional PROTAC molecules allow simultaneous binding of both the target protein and an E3-Ubiquitin ligase, bringing the two proteins into close spatial proximity to allow ubiquitinylation and degradation of the target protein via the cell's endogenous protein degradation pathway. We utilized native mass spectrometry (MS) to study the ternary complexes promoted by the previously reported PROTAC GNE-987 between Brd4 bromodomains 1 and 2, and Von Hippel Lindeau E3-Ubiquitin Ligase. Native MS at high resolution allowed us to measure ternary complex formation as a function of PROTAC concentration to provide a measure of complex affinity and stability, whilst simultaneously measuring other intermediate protein species. Native MS provides a high-throughput, low sample consumption, direct screening method to measure ternary complexes for PROTAC development.     

Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside ( C-10 , chrysoeriol-7-O-β-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into β-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.     

Fluorescent Amino Acid Initiated de novo Cyclic Peptides for the Label-Free Assessment of Cell Permeability**

The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e. g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the cell permeability of cyclic peptide leads. Fluorescent tryptophan analogues 4-cyanotryptophan (4CNW) and β-(1-azulenyl)-L-alanine (AzAla) were incorporated into in vitro translated macrocyclic peptides by initiator reprogramming. We then demonstrate these efficient blue fluorescent emitters are good tools for monitoring peptide penetration into cells.     

Fabrication of ceramic particles from preceramic polymers using stop flow lithography

Stop flow lithography (SFL) combines aspects of microfluidic and photolithography to continuously fabricate particles with uniform planar shapes as dictated by a mask. In this work we aim to expand the palette of materials suitable for SFL processing by investigating the use of UV-crosslinkable preceramic polymers to make ceramic particles. A commercially available methacrylated-polysiloxane was used as the preceramic polymer and was mixed with 2.5 wt% Irgacure 651 photoinitiator. A simple SFL system was assembled to continuously fabricate UV-crosslinked preceramic polymer particles in the shape of hexagons, triangles, and gears with diameters ranging from 100 to 200 μm and thicknesses of 74 μm +/- 4 μm. Particles were harvested from the excess preceramic solution, cleaned and then pyrolyzed at 1000 °C to transform them into silicon oxycarbide ceramic particles. Particle shape was maintained during pyrolysis despite a ～80 % linear shrinkage due to the removal of acryl and methyl side groups, as confirmed via FTIR. After pyrolysis the outer diameters of the SiOC particles ranged from 20 to 40 μm with thicknesses of 10 μm–12 μm. Pyrolyzed particles were successfully recovered and dispersed in water. This work demonstrates a robust path for the fabrication of ceramic particles with specific shapes from preceramic polymers via SFL.