An adaptive finite element method based on Superconvergent Cluster Recovery for the Cahn-Hilliard equation

In this study, we construct an error estimate for a fully discrete finite element scheme that satisfies the criteria of unconditional energy stability, as suggested in [1]. Our theoretical findings, in more detail, demonstrate that this system has second-order accuracy in both space and time. Additionally, we offer a powerful space and time adaptable approach for solving the Cahn-Hilliard problem numerically based on the posterior error estimation. The major goal of this technique is to successfully lower the calculated cost by controlling the mesh size using a Superconvergent Cluster Recovery (SCR) approach in accordance with the error estimation. To demonstrate the effectiveness and stability of the suggested SCR-based algorithm, numerical results are provided

An Implantable Peripheral Nerve Recording and Stimulation System for Experiments on Freely Moving Animal Subjects

A new study with rat sciatic nerve model for peripheral nerve interfacing is presented using a fully-implanted inductively-powered recording and stimulation system in a wirelessly-powered standard homecage that allows animal subjects move freely within the homecage. The Wireless Implantable Neural Recording and Stimulation (WINeRS) system offers 32-channel peripheral nerve recording and 4-channel current-controlled stimulation capabilities in a 3 × 1.5 × 0.5 cm3 package. A bi-directional data link is established by on-off keying pulse-position modulation (OOK-PPM) in near field for narrow-band downlink and 433 MHz OOK for wideband uplink. An external wideband receiver is designed by adopting a commercial software defined radio (SDR) for a robust wideband data acquisition on a PC. The WINeRS-8 prototypes in two forms of battery-powered headstage and wirelessly-powered implant are validated in vivo, and compared with a commercial system. In the animal study, evoked compound action potentials were recorded to verify the stimulation and recording capabilities of the WINeRS-8 system with 32-ch penetrating and 4-ch cuff electrodes on the sciatic nerve of awake freely-behaving rats. Compared to the conventional battery-powered system, WINeRS can be used in closed-loop recording and stimulation experiments over extended periods without adding the burden of carrying batteries on the animal subject or interrupting the experiment

In vitro and intracellular inhibitory activities of nosiheptide against Mycobacterium abscessus

The high level of inherent drug resistance of Mycobacterium abscessus makes the infection caused by it very difficult to be treated. The objective of this study was to evaluate the potential of nosiheptide (NOS) as a new drug candidate for treating M. abscessus infections. The microplate AlamarBlue assay was performed to determine the minimum inhibitory concentrations (MICs) of NOS for 28 reference strains of rapidly growing mycobacteria (RGM) and 77 clinical isolates of M. abscessus. Time-kill kinetic and post-antibiotic effect (PAE) of NOS against M. abscessus was evaluated. Its bactericidal activity against M. abscessus in macrophages was determined by an intracellular colony numerating assay. NOS manifested good activity against the reference strains of RGM and M. abscessus clinical isolates in vitro. The MICs of NOS against M. abscessus clinical isolates ranged from 0.0078 to 1 μg/ml, and the MIC50 and MIC90 were 0.125 μg/ml and 0.25 μg/ml, respectively. The pattern of growth and kill by NOS against M. abscessus was moderate with apparent concentration-dependent characteristics, and the PAE value of NOS was found to be ~6 h. Furthermore, NOS had low cell toxicity against the THP-1 cell line after 48 h of exposure (IC50 = 106.9 μM). At 4 μg/ml, NOS exhibited high intracellular bactericidal activity against M. abscessus reference strains with an inhibitory rate of 66.52% ± 1.51%, comparable with that of clarithromycin at 2 μg/ml. NOS showed suitable inhibitory activities against M. abscessus in vitro and in macrophages and could be a potential drug candidate to treat M. abscessus infection

The adenosine A2A receptor antagonist KW6002 distinctly regulates retinal ganglion cell morphology during postnatal development and neonatal inflammation

Adenosine A2A receptors (A2ARs) appear early in the retina during postnatal development, but the roles of the A2ARs in the morphogenesis of distinct types of retinal ganglion cells (RGCs) during postnatal development and neonatal inflammatory response remain undetermined. As the RGCs are rather heterogeneous in morphology and functions in the retina, here we resorted to the Thy1-YFPH transgenic mice and three-dimensional (3D) neuron reconstruction to investigate how A2ARs regulate the morphogenesis of three morphologically distinct types of RGCs (namely Type I, II, III) during postnatal development and neonatal inflammation. We found that the A2AR antagonist KW6002 did not change the proportion of the three RGC types during retinal development, but exerted a bidirectional effect on dendritic complexity of Type I and III RGCs and cell type-specifically altered their morphologies with decreased dendrite density of Type I, decreased the dendritic field area of Type II and III, increased dendrite density of Type III RGCs. Moreover, under neonatal inflammation condition, KW6002 specifically increased the proportion of Type I RGCs with enhanced the dendrite surface area and volume and the proportion of Type II RGCs with enlarged the soma area and perimeter. Thus, A2ARs exert distinct control of RGC morphologies to cell type-specifically fine-tune the RGC dendrites during normal development but to mainly suppress RGC soma and dendrite volume under neonatal inflammation

Hypolipidemic and antiinflammation activities of fermented soybean fibers from meju in C57BL/6 J mice

Meju, a naturally fermented soy block used to produce soy paste and soy sauce in Korea, is suggested to exhibit hypolipidemic and antiinflammatory activities; however, its mechanisms of action are elusive. Here, we report that the water-soluble fibers but not the amino acids and peptides from meju exhibited hypolipidemic activity in vivo. Feeding of fermented soybean fibers (FSF) from meju reduced plasma cholesterol, triglyceride, adipocyte size, and hepatic lipid accumulation in C57BL/6 J mice. FSF treatment reduced HMG-CoA reductase expression, whereas the expression of genes in the fatty acid uptake and subsequent beta-oxidation were significantly induced in the livers. Hepatic lipogenic genes, including Srebp1c and Lxrα, were unaltered. Feeding with the fermented soybean peptides and amino acids (FSPA) induced the expression of lipogenic genes, which may have canceled the induction of low-density lipoprotein receptor and Cyp7a1 gene expressions in FSPA livers. The plasma concentrations of C-reactive protein, TNF-α, and interlukin-6 were significantly reduced in the FSF, FSPA, and meju groups compared with the control groups, suggesting that both of the fibers and peptides/amino acids from meju may be beneficial. These findings suggest that soluble fibers from meju are critical hypolipidemic components that regulate hepatic gene expressions and reduce proinflammatory cytokines in vivo

Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance

Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise. However, the precise mechanisms by which exercise and ROS promote metabolic health remain unclear. Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance. Conversely, reductions in skeletal muscle NOX4 in aging and obesity contribute to the development of insulin resistance. NOX4 deletion in skeletal muscle compromised exercise capacity and antioxidant defense and promoted oxidative stress and insulin resistance in aging and obesity. The abrogated adaptive mechanisms, oxidative stress, and insulin resistance could be corrected by deleting the H2O2-detoxifying enzyme GPX-1 or by treating mice with an agonist of NFE2L2, the master regulator of antioxidant defense. These findings causally link NOX4-derived ROS in skeletal muscle with adaptive responses that promote muscle function and insulin sensitivity

Restoration of autophagy by puerarin in ethanol-treated hepatocytes via the activation of AMP-activated protein kinase

a b s t r a c t We investigated the effects of puerarin, the major isoflavone in Kudzu roots, on the regulation of autophagy in ethanol-treated hepatocytes. Incubation in ethanol (100 mM) for 24 h reduced cell viability by 20% and increased the cellular concentrations of cholesterol and triglycerides by 40% and 20%, respectively. Puerarin stimulation significantly recovered cell viability and reduced cellular lipid accumulation to a level comparable to that in untreated control cells. Ethanol incubation reduced autophagy significantly as assessed by microtubule-associated protein1 light chain 3 (LC3) expression using immunohistochemistry and immunoblot analysis. The reduced expression of LC3 was restored by puerarin in a dose-dependent manner in ethanol-treated cells. The effect of puerarin on mammalian targets of rapamycin (mTOR), a key regulator of autophagy, was examined in ethanol-treated hepatocytes. Immunoblotting revealed that puerarin significantly induced the phosphorylation of 5 0 AMP-activated protein kinase (AMPK), thereby suppressing the mTOR target proteins S6 ribosomal protein and 4E-binding protein 1. These data suggest that puerarin restored the viability of cells and reduced lipid accumulation in ethanol-treated hepatocytes by activating autophagy via AMPK/mTOR-mediated signaling

Cyanidin is an agonistic ligand for peroxisome proliferator-activated receptor-alpha reducing hepatic lipid

a b s t r a c t a r t i c l e i n f o To investigate the underlying mechanism of targets of cyanidin, a flavonoid, which exhibits potent anti-atherogenic activities in vitro and in vivo, a natural chemical library that identified potent agonistic activity between cyanidin and peroxisome proliferator-activated receptors (PPAR) was performed. Cyanidin induced transactivation activity in all three PPAR subtypes in a reporter gene assay and time-resolved fluorescence energy transfer analyses. Cyanidin also bound directly to all three subtypes, as assessed by surface plasmon resonance experiments, and showed the greatest affinity to PPARα. These effects were confirmed by measuring the expression of unique genes of each PPAR subtype. Cyanidin significantly reduced cellular lipid concentrations in lipid-loaded steatotic hepatocytes. In addition, transcriptome profiling in lipid-loaded primary hepatocytes revealed that the net effects of stimulation with cyanidin on lipid metabolic pathways were similar to those elicited by hypolipidemic drugs. Cyanidin likely acts as a physiological PPARα agonist and potentially for PPARβ/δ and γ, and reduces hepatic lipid concentrations by rewiring the expression of genes involved in lipid metabolic pathways