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.     

Antioxidant and antimicrobial activities of fresh garlic and aged garlic by-products extracted with different solvents

Food Science and Biotechnology - This study aims to investigate antioxidative and antibacterial properties of fresh garlic (non-aged, NG) and aged garlic (AG) by-products extracted with distilled...     

Virtual CNC system. Part II. High speed contouring application

This paper presents a trajectory planning strategy for maintaining the tool positioning accuracy in high speed cornering applications. A 3D contour error estimation algorithm is presented for determining the geometric deviation from arbitrarily shaped toolpaths. Two spline fitting strategies are developed for smoothening sharp corners. The under-corner approach reduces the toolpath length, and therefore the cornering time. This technique yields successful results when used with a high bandwidth servo controller (such as sliding mode control), capable of accurately tracking the commanded toolpath. The over-corner approach is based on stretching out the sharp corner with a smooth curve, which counteracts the ‘undercut’ caused by the large phase lag in low bandwidth servo controllers (such as P–PI control). The cornering feedrate is adjusted in the Virtual CNC platform, developed in the first part of this article, to ensure that contour error violation does not occur. The achieved cornering accuracy is verified in experiments, which are in close agreement with predictions obtained with the Virtual CNC.     

Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative

The compound CWJ-a-5 [1-(4-methylpiperazinyl)-3-phenylisoquinoline hydrochloride] is a novel 3-arylisoquinoline derivative which has exhibited potent antitumor activity. As part of an effort to develop a useful formulation for clinical evaluation of this compound, the aqueous stability of CWJ-a-5 as a function of pH, ionic strength, and temperature, as well as its various physicochemical properties, have been examined. The pKa value obtained by potentiometric titration in methanol-water mixtures was 3.61, at 25 degrees C. The aqueous solubility and the apparent partition coefficient of CWJ-a-5 over the pH range 2.08-9.88 were consistent with those expected of a weak acid of similar pKa value. The degradation of CWJ-a-5 was found to follow apparent first-order kinetics. The pH-rate profiles generated at 80 degrees C were accounted for by acid-catalyzed degradation at low pH and base-catalyzed degradation at high pH. The activation energy was determined as 22.12 kcal/mol for the degradation of CWJ-a-5 in a pH 2.92 solution with a constant ionic strength of 0.2. Increasing the ionic strength up to 0.9 led to a higher degradation rate constant at pH 2.92. However, CWJ-a-5 was very stable even in a pH 2.92 solution, and its shelf-life was calculated to be 2.03 years at 25 degrees C from the Arrhenius plot.     

Flow visualizations and hot-wire measurements on air flow in two different neonate incubators

Flow visualizations and hot-wire measurements on the inside flows of two different incubators are presented in this paper. An anatomically-correct neonate model was fabricated using the rapid prototyping machine, based on the 3-D scanned data. The result showed that air flow in the incubator was affected not only by the air circulation system but also by the design of incubator chamber. Large rotating motions were located around the corners of free space. A number of small eddies were found in regions of high shear flow, in areas such as that between the air inlet and the neonate. But, these small eddies were found to be stationary at that locations. Those small eddies might interfere with convective and evaporative heat transfers from the neonate. This study has led to a better understanding of flow mechanism in an incubator chamber and provided the guidance needed for the advancement of improved computational fluid dynamic models.     

中国、韩国、日本饮食文化及酱牛肉风味的比较分析

主要阐述酱牛肉风味的形成并分析中国、韩国、日本饮食文化及其酱牛肉风味的特点,为今后研究符合不同地区风味特点的酱牛肉提供基础材料.比较与分析结果表明:在中国北方人比较适合不带酱汁而酱香浓郁的酱牛肉,南方人比较适合酱汁较稀并多加糖的酱牛肉;韩国人比较适合酱香浓郁而带些辣味的酱牛肉;日本人比较适合口味清淡、圆润感较强而带有清香的酱牛肉.     

Protein Binding Characteristics of 2′-Benzoyloxycinnamaldehyde

The protein binding characteristic of 2′-Benzoyloxycinnamaldehyde (BCA) was investigated, which has demonstrated a potent antitumor effect against several human solid tumor cell lines and in human tumor xenograft nude mice. Protein binding of BCA in human serum was 86 ± 0.91% and the predominant binding protein of BCA was fatty-acid-free human serum albumin (HSA) (81 ± 0.91%). The binding of BCA to HSA was outlined by one class, and Ka and n of BCA were 1.65 × 10⁵ M^{? 1} and 0.374, respectively. Displacement studies with fluorescence probes suggested that BCA mainly binds to site I on HSA, and BCA-induced enhancement in site II binding. The limited drug–drug interaction experiments suggested that BCA influences both site I and site II drug–HSA bindings via different mechanisms; a competitive displacement and a probable allosteric conformational change in HSA, respectively.     

Virtual CNC system. Part I. System architecture

The paper presents a comprehensive virtual simulation model of a realistic and modular CNC system. The Virtual CNC architecture represents an actual CNC, but with modular feed drives, sensors, motors, and amplifiers. The CNC software library includes a variety of trajectory interpolation and axis control laws. Constant, trapezoidal and cubic acceleration profiles can be selected as a trajectory generation module. The control laws can be selected ranging from a simple PID to complex Pole Placement, Generalized Predictive Control or Sliding Mode Controller with friction compensation. When the Virtual CNC is assembled, its performance can be tested using frequency and time domain response analyses, which are automated. The Virtual CNC includes both analytical tuning methods for linear controllers, as well as Fuzzy Logic based expert auto-tuning system for Adaptive Sliding Mode Control. The paper includes detailed experimental verification of the Virtual CNC.     

Multi-objective evolutionary generation process for specific personalities of artificial creature

An artificial creature has its own genome in which each chromosome consists of many genes that contribute to defining its personality. The large number of genes allows a highly complex system. It becomes increasingly difficult and time-consuming to ensure reliability, variability and consistency for the artificial creature's personality, if gene values are manually assigned for the individual genome. To solve this problem, this paper proposes a multi-objective evolutionary generation process for artificial creatures' specific personalities (MOEGPP), where the dimension of the personality model is defined as that of optimization objectives. Key components of MOEGPP are as follows: i) the complement of (1 - k) dominance; ii) the pruning method considering objective deviation for all genomes;and iii) the inutation using biased normal distribution, to get a set of nondominated genomes with specific personalities according to the defined personality dimension. By proposed MOEGPP, nondominated genomes having specific personalities can be obtained and they are successfully tested by using an artificial creature, Rity, in the virtual 3D world created in a PC.     

The effects of pressure-sensitive adhesives and solubilizers on the skin permeation of testosterone from a matrix-type transdermal delivery system

Matrix-type transdermal delivery systems of testosterone (TS) were formulated with three different pressure-sensitive adhesives (PSA). The effects of PSA, skin permeation enhancers, and solubilizers on the rat skin permeation rate of TS were systematically investigated. Without a solubilizer, the skin permeation rate of TS reached its maximum value when only 2% of TS was loaded in the matrix and the crystal formation in the matrix was very rapid and severe. Two surfactants differing in their hydrophile-lipophile balance (HLB) number were, therefore, considered. Span 80, which was of the lower HLB number, was more effective than Tween 80 in increasing the solubility, and thereby increasing the permeation rate of TS. Moreover, the concentrations of both the solubilizer and the skin permeation enhancer affected the skin permeation rate. Thus, the highest skin permeation rate (4.14 µg/cm²/hr) was achieved when 2% TS was loaded in DuroTak® 87-2516 together with 10% Span 80 and 3% dodecylamine, the permeation enhancer. In vivo study showed that the application of an experimental patch on rat abdominal skin resulted in a prompt and significantly higher plasma concentration of TS than that of a commercial product (Testoderm®) designed to apply on the scrotal skin. The area under the curve (AUC) increased linearly as the loading dose of TS increased up to 6%. Thus, based on these results, a non-scrotal matrix-type transdermal delivery system of TS could be developed.