NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

Lysophosphatidic acid receptor 1 (LPA₁) contributes to brain injury following transient focal cerebral ischemia. However, the mechanism remains unclear. Here, we investigated whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation might be an underlying mechanism involved in the pathogenesis of brain injury associated with LPA₁ following ischemic challenge with transient middle cerebral artery occlusion (tMCAO). Suppressing LPA₁ activity by its antagonist attenuated NLRP3 upregulation in the penumbra and ischemic core regions, particularly in ionized calcium-binding adapter molecule 1 (Iba1)-expressing cells like macrophages of mouse after tMCAO challenge. It also suppressed NLRP3 inflammasome activation, such as caspase-1 activation, interleukin 1β (IL-1β) maturation, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, in a post-ischemic brain. The role of LPA₁ in NLRP3 inflammasome activation was confirmed in vitro using lipopolysaccharide-primed bone marrow-derived macrophages, followed by LPA exposure. Suppressing LPA₁ activity by either pharmacological antagonism or genetic knockdown attenuated NLRP3 upregulation, caspase-1 activation, IL-1β maturation, and IL-1β secretion in these cells. Furthermore, nuclear factor-κB (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 were found to be LPA₁-dependent effector pathways in these cells. Collectively, results of the current study first demonstrate that LPA₁ could contribute to ischemic brain injury by activating NLRP3 inflammasome with underlying effector mechanisms.     

Reversible,repeatable and low phase transition behaviour of spin coated nanostructured vanadium oxide thin films with superior mechanical properties

Smooth, uniform and crystalline vanadium oxide thin films were deposited on quartz by spin coating technique with four different rpm i.e., 1000, 2000, 3000 and 4000 and subsequently post annealed at 350, 450 and 550?°C in vacuum. Transmission electron microscopy (TEM), Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) techniques were utilized for microstructural characterizations and phase analysis, respectively, for vanadium oxide powder and deposited film. Nanorods were observed to be grown after vacuum annealing. X-ray photoelectron spectroscopy (XPS) technique was utilized to study the elemental oxidation state of deposited vanadium oxide films. Thermo-optical and electrical properties such as solar transmittance (τ_s), reflectance (ρ_s), absorptance (α_s), infrared (IR) emittance (ε_ir) and sheet resistance (R_s) of different thin films were evaluated. Based on the optical characteristics the optimized condition of the film processing was identified to be spin coated at 3000?rpm. Subsequently, the nanoindentation technique was utilized to measure hardness and Young's modulus of the optimized film. The measured nanomechanical properties were found to be superior to those reported for sputtered vanadium oxide films. Finally, temperature dependent phase transition characteristics of optimized vanadium oxide films were studied by differential scanning calorimetry (DSC) technique. Reversible and repeatable phase transition was found to occur in the range of 44–48?°C which was significantly lower than the phase transition temperature (i.e., 68?°C) of bulk VO₂.     

Enhanced α-Mn2O3 nanorods synthesized by one-pot hydrothermal route for supercapacitors

Journal of Materials Science: Materials in Electronics - Pseudo-capacitors are the emerging energy storage devices which forms a bridge between batteries and conventional capacitors. In the present...     

Fluorine in Drug Design: A Case Study with Fluoroanisoles

Anisole and fluoroanisoles display distinct conformational preferences, as evident from a survey of their crystal structures. In addition to altering the free ligand conformation, various degrees of fluorination have a strong impact on physicochemical and pharmacokinetic properties. Analysis of anisole and fluoroanisole matched molecular pairs in the Pfizer corporate database reveals interesting trends: 1) PhOCF₃ increases log D by ～1 log unit over PhOCH₃ compounds; 2) PhOCF₃ shows lower passive permeability despite its higher lipophilicity; and 3) PhOCF₃ does not appreciably improve metabolic stability over PhOCH₃. Emerging from the investigation, difluoroanisole (PhOCF₂H) strikes a better balance of properties with noticeable advantages of log D and transcellular permeability over PhOCF₃. Synthetic assessment illustrates that the routes to access difluoroanisoles are often more straightforward than those for trifluoroanisoles. Whereas replacing PhOCH₃ with PhOCF₃ is a common tactic to optimize ADME properties, our analysis suggests PhOCF₂H may be a more attractive alternative, and greater exploitation of this motif is recommended.     

Electron microscopy of shock deformation in alumina

Shock recovered samples of a coarse grain (10 μm), high density (>99.9% theoretical) alumina from asymmetric impact tests conducted at 6.5 GPa (e.g. 3.2 times its Hugoniot Elastic Limit) in a single stage gas gun and characterized by X-ray diffractometry, scanning and field emission scanning electron microscopy, and transmission electron microscopy showed prolific presence of reduced crystallite size, higher average microstrain, grain localized micro/nano-scale deformations, micro-cleavages, grain-boundary microcracks, micro-wing crack formation, extensive shear induced deformations and fractures localized at grains, grain boundaries and triple grain junctions, grain localized entanglement of dislocations and their pile up impeded at grain boundaries. A new qualitative model based on micro-shear and micro-twist induced deformation and fracture in single and/or multiple planes in suitably oriented grain and/or grain assembly was developed to explain the experimentally observed damage evolution process.     

Evaluation of hydroxyapatite and β-tri calcium phosphate microplasma spray coated pin intra-medullary for bone repair in a rabbit model

Here we report a comparative study of the healing kinetics of surgically created artificial defects in the tibia of New Zealand white rabbits. Comparison of the healing kinetics was made for uncoated conventional SS316L intramedullary pins, and the same pins with microplasma sprayed (MIPS) pure hydroxyapatite (HAp) and beta-tri calcium phosphate (β-TCP) coatings. After thorough material characterizations including XRD, FTIR, SEM, etc., MIPS coated pins were implanted to such animals. Serum biochemistry, radiology and fluorochrome labelling were used to evaluate the comparative healing kinetics of these implants in vivo. In comparison to those of the uncoated pins, the pins coated with both MIPS HAp and β-TCP showed significant increment of alkaline phosphatase up to 15th postoperative day, insignificant changes in serum phosphorus and calcium with uneventful healing of bone defect. There was development of Havarsian canals and well-defined peripherally placed osteoblasts along with evidence of angiogenesis and comparatively more new bone formation in the defect site. On a comparative scale, the performance of the β-TCP coated intramedullary pins was much better than that of the pure HAp coated pins than the uncoated intramedullary pins.     

Mechanical characterization of a bituminous mix under quasi-static and high-strain rate loading

There are various methods to determine the compressive and tensile strength of asphalt concrete under static loading conditions and most studies on asphalt strength and fracture have been conducted under such loading conditions. However, pavement materials also have to withstand a wide variety of loading and temperature conditions which may vary from quasi-static to high-strain rate impact, and pavement breakdown may occur due to fracture and/or fatigue failure. In the present study, a bituminous mix with 30% RAP has been characterized under quasi-static (10^?3–10^?4 strain/s) and high-strain rate (200–700 strain/s) regimes. The experimental studies have been performed to better understand the compressive, tensile and fracture response of bituminous mixes. Split Hopkinson pressure bar (SHPB) and its modifications were used for high-strain rate characterization of this bituminous mixture. It was observed that the mechanical properties of the hot mix asphalt (HMA) changed significantly under high-strain rate testing. Also, the failure mechanisms observed under the high-strain rate loading were found to be considerably different from those obtained in static testing, where failure of binder was a predominant mechanism. It was observed that high-strain rate loading caused trans-aggregate failures in the specimens; in addition to failure of the binder.     

New observations in micro-pop-in issues in nanoindentation of coarse grain alumina

The present experiments were focused on nanoindentation behaviour and the attendant “micro-pop-in” in a dense (～95% of theoretical) coarse-grain (～20 μm) alumina ceramic as a function of loading rate variations at three constant peak loads in the range of 10⁵–10⁶ μN. Based on the experimental results here we report for the first time, to the best of our knowledge, an increase in intrinsic nano scale contact resistance as well as the nanohardness with the loading rate. These observations were explained in terms of the correlation between the nanoscale plasticity and shear stress active just underneath the nanoindenter.     

Loading Rate Effect on Nanohardness of Soda-Lime-Silica Glass

To understand how hardness, the key design parameter for applications of brittle solids such as glass concerning contact deformation, is affected by loading rate variation, nanoindentation with a Berkovich tip was used to measure the nanohardness of a 330-μm-thick soda-lime-silica glass as a function of loading rate (1 to 1000 mN·s⁻¹). The results showed for the very first time that, with variations in the loading rate, there was a 6 to 9 pct increase in the nanohardness of glass up to a threshold loading rate (TLR), whereafter it did not appreciably increase with further increase in loading rate. Further, the nanohardness data showed an indentation size effect (ISE) that obeyed the Meyer’s law. These observations were explained in terms of a strong shear stress component developed just beneath the nanoindenter and the related shear-induced deformation processes at local microstructural scale weak links. The significant or insignificant presence of shear-induced serrations in load depth plots and corresponding scanning electron microscopic evidence of a strong or mild presence of shear deformation bands in and around the nanoindentation cavity supported such a rationalization. Finally, a qualitative picture was developed for different deformation processes induced at various loading rates in glass.