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.     

Theranostic Interpolation of Genomic Instability in Breast Cancer

Breast cancer is a diverse disease caused by mutations in multiple genes accompanying epigenetic aberrations of hazardous genes and protein pathways, which distress tumor-suppressor genes and the expression of oncogenes. Alteration in any of the several physiological mechanisms such as cell cycle checkpoints, DNA repair machinery, mitotic checkpoints, and telomere maintenance results in genomic instability. Theranostic has the potential to foretell and estimate therapy response, contributing a valuable opportunity to modify the ongoing treatments and has developed new treatment strategies in a personalized manner. “Omics” technologies play a key role while studying genomic instability in breast cancer, and broadly include various aspects of proteomics, genomics, metabolomics, and tumor grading. Certain computational techniques have been designed to facilitate the early diagnosis of cancer and predict disease-specific therapies, which can produce many effective results. Several diverse tools are used to investigate genomic instability and underlying mechanisms. The current review aimed to explore the genomic landscape, tumor heterogeneity, and possible mechanisms of genomic instability involved in initiating breast cancer. We also discuss the implications of computational biology regarding mutational and pathway analyses, identification of prognostic markers, and the development of strategies for precision medicine. We also review different technologies required for the investigation of genomic instability in breast cancer cells, including recent therapeutic and preventive advances in breast cancer.     

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.     

Investigation of structural,optical, electrical,and magnetic properties of Fe-doped La0.7Sr0.3MnO3 manganites

In this work, the physical properties of nanocrystalline samples of La_0.7Sr_0.3Mn_1−xFe_xO₃ (0.0 ≤ x ≤ 0.20) perovskite manganites synthesized by the reverse micelle (RM) technique were explored in detail. The phase purity, crystal structure, and crystallite size of the samples were determined using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. All the samples had rhombohedral crystal structure and crystallite size increased with increase in Fe content in La_0.7Sr_0.3MnO₃. The scanning electron micrographs (SEMs) exhibited smooth surface morphology and nonuniform shape of the particles. The optical properties studied using UV-visible absorption spectroscopy revealed a decrease in the absorbance and optical band gap with an increase in Fe content in La_0.7Sr_0.3MnO₃ compound. The temperature-dependent resistivity measurements revealed semiconducting nature of x = 0 and 0.1 samples up to the studied temperature range, while a metal-to-insulator transition was observed at higher Fe doping. Magnetic studies revealed weak ferromagnetism in all the samples and a reduction in the maximum magnetization with an increase in Fe content. A close correlation between electrical transport and magnetic properties was observed with the doping of Fe ion in La_0.7Sr_0.3MnO₃ at Mn site. These results advocate strong interactions associated with the double exchange mechanism among Fe³⁺ and Mn³⁺ ions.     

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%.     

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.     

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.     

Ag/BiVO4复合纳米纤维光催化性能的研究

本文采用静电纺丝法制备了不同Ag负载含量的Ag/BiVO₄纳米纤维复合材料,并对其相结构,形貌,可见光催化性能进行了表征。结果表明,Ag的引入能够很大程度的提高复合材料的光催化效率,10%Ag负载的Ag/BiVO₄复合纳米纤维能够在可见光辐照20min内将罗丹明B完全降解。这种异质结够有利于光生电子对的分离,提高光生载流子寿命,是Ag/BiVO₄复合纳米纤维光催化性能显著提高的原因。