Inhibition of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade and Promotes Recovery after Spinal Cord Injury

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib treatment (6 mg/kg/day, IP, starting 3 h post-injury for 7 or 14 days) reduced BTK activation and total BTK levels, attenuated the injury-induced elevations in Iba1, GFAP, CD138, and IgG at 7 or 14 days post-injury without reduction in CD45RA B cells, improved locomotor function (BBB scores), and resulted in a significant reduction in lesion volume and significant improvement in tissue-sparing 11 weeks post-injury. These results indicate that Ibrutinib exhibits neuroprotective effects by blocking excessive neuroimmune responses through BTK-mediated microglia/astroglial activation and B cell/antibody response in rat models of SCI. These data identify BTK as a potential therapeutic target for SCI.     

Investigation of improved dielectric and thermal properties of ternary nanocomposite PMMA/MXene/ZnO fabricated by in-situ bulk polymerization

Electric power system applications demand for high-temperature dielectric materials. The improved performance of polymer nanocomposites requires improvement in their thermal conductivity & stability, dielectric stability and processing technique. However, they often lose their dielectric properties with a rise in temperature. Here, we offer a solution by incorporating electrically conducting material (MXene) and semiconducting inorganic nanoparticles (ZnO NPs) into an insulating PMMA polymer matrix to maintain high dielectric constant, both at the room and high temperature. Therefore, to achieve desirable thermal and dielectric properties is the main objective of the present study based on the homogeneous distribution of the nanofillers by in-situ bulk polymerization assisted by strong sonication in the corresponding polymer. The introduction of MXene and ZnO NPs into the PMMA not only acquires a substantial increment in the dielectric constant, to attain a value 437, with minimum energy loss of 0.36 at 25 Hz, but also improves the thermal conductivity of PMMA up to 14 times by causing the reduction of thermal resistance, which is actually responsible for the poor thermal conductivity of amorphous pure PMMA polymer. More importantly, hybrid PMMA/4:2 wt% MXene:ZnO nanocomposite leads to an excellent thermal stability. Moreover, further characterization of the synthesized nanocomposites by FTIR, SEM and XRD leads to the evaluation of strong interaction of ternary components with PMMA matrix.     

Micromechanical Investigation of the Fatigue Crack Propagation and Damage Development in Al/Al2O3/SiC Hybrid Metal Matrix Composite

Russian Journal of Non-Ferrous Metals - In this study, the micro-mechanisms involved in fatigue crack propagation are investigated qualitatively in a Al/Al2O3/SiC hybrid metal matrix composite...     

Chemo-enzymatic synthesis of amino acid-based surfactants

The application of lipases to the synthesis of amino acid-based surfactants was investigated. Low yields (2–9%) were obtained in the acylation of free amino acids, such as l-serine and l-lysine, as well as their ethyl esters and amides with fatty acids, owing in part to low miscibility of the reactants. When the N-carbobenzyloxy (Cbz)-l-amino acids were used in an effort to improve miscibility of the amino acid derivatives with the acyl donor, a dramatic improvement was observed for N-Cbz-l-serine (92% yield) but not for N _α-Cbz- or N _ζ-Cbz-l-lysine (7 and 2% yield, respectively). As an alternative, and efficient synthesis of N _ζ-acyl-l-lysines was developed, based on the regiospecific chemical acylation of copper(II) lysinate. In pursuit of a general route to amino acid-fatty acid surfactants, the utility of a polyol linker was investigated. Thus, the glycerol ester of N _α′ N _ζ-di-Cbz-l-lysine was prepared and evaluated as a substrate for acylation. As expected, this and other glycer-1-yl esters of N-protected amino acids were excellent substrates for lipase-catalyzed acylation. Their reaction with myristic acid in the presence of Novozyme resulted in the regioselective acylation of the primary hydroxyl group of the glycerol moiety to afford the corresponding 1-O-(N-Cbz-l-aminoacyl)-3-O-myris-toylglycerols with conversions of 50–90%. These were readily deprotected to give a range of 1-O-(aminoacyl)-3-O-myristoyl-glycerols with overall yields of 27–71%.     

Mechanical,Thermal and Electrical Resisitivity Properties of Thermoplastic Composites Filled with Carbon Fibers and Carbon Particles

Composites consisting of carbon fibers (CF) and carbon particles (CP) in polypropylene (PP) matrix were melt-compounded. Composites were analyzed for their mechanical, electrical and thermal properties. Results indicate that the addition of these fillers improved the mechanical properties of the composites. Thermal conductivity was enhanced as the concentration of fillers was increased. Carbon fibers render the composites electrically conductive so we observed a percolation threshold near 10 wt.% of CF for PP/CF (PP and CF composite) and near 25 wt.% of CP for PP/CP (PP and carbon particle composite). All the results indicated that carbon fibers are more effective in improving the properties as compare to the carbon particles.     

Wear behavior of natural diamond tool in cutting tungsten-based alloy

Natural diamond tool is quickly worn out while cutting a workpiece made of a tungsten-based alloy. This paper presents a new approach to reduce tool wear: ultrasonic vibration cutting of a workpiece made of a tungsten-based alloy based on gas–liquid atomization cooling. An atomizer is a device which mixes carbon dioxide gas with vegetable oil and changes the liquid into minute droplets, which are carried by a stream of gas. Atomizer is also a device that incorporates a venture device to translate liquid into a gas stream. The atomized minute droplets act as the cooling and lubricating medium to protect the tools. The system is designed to ensure that droplets can spread all over the surface of a work piece. At a constant spindle speed, feed rate, and cutting depth, the experiments were carried out for investigating the effects of the tool vibration parameters, carbon tetrachloride liquid flow rate, carbon dioxide gas flow, and gas–liquid mass ratio on the tool wear. The experiments showed that the technology of ultrasonic vibration with gas–liquid atomization cooling effectively prolongs the tool life in cutting tungsten-based alloy.     

Evaluation of machinability and economic performance in cryogenic-assisted hard turning of α-β titanium: a step towards sustainable manufacturing

Abstract

Titanium, a difficult-to-cut material, consumes higher time and cost in removing material by machining to produce parts. Machining of Ti alloys has got serious attention owing to its reactive nature with tool materials at elevated temperature that aggravates tool wear. Reportedly, effective and efficient cooling and lubrication at the tool–work interface can ameliorate the machinability of Ti-alloys. In this perspective, this article interrogates the underlying mechanism of critical responses such as surface roughness, temperature, tool life and machining cost under dry, minimum quantity lubrication (MQL) and cryogenic liquid nitrogen (LN2) modes. The effect of cutting speeds and feed rates on such responses have been considered as a function of cooling strategy to standardize the cooling technique as the best alternative for machining. Cryogenic cooling seems to be preponderant regarding machining cost, temperature, surface roughness and tool life in hard turning of a–b titanium alloy. The feasibility of cryogenic cooling was investigated using the iso-response technique in comparison with dry and MQL-assisted hard turning. Experimental results revealed longer tool life and lower machining cost under cryogenic condition followed by MQL and dry machining. Moreover, cryogenic LN2 has been identified as an appropriate alternative to reduce the temperature and surface roughness. On contrary, dry turning evoked a high-temperature and rapid tool wear. In a nutshell, cryogenic assisted hard turning has acceded as a sustainable strategy from an environmental and economic perspective.     

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4–254.2 nm with PDI ranging between 0.279–0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.     

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the ‘thin-film hydration’ method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.