The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells (NPCs). Here, we provide evidence that the NF-κB pathway plays also a fundamental role during the differentiation of NPCs into astrocytes. First, we show that the NF-κB pathway is essential to initiate astrocytic differentiation as its early inhibition induces NPC apoptosis and impedes their differentiation. Second, we demonstrate that persistent NF-κB activation affects NPC-derived astrocyte differentiation. Tumor necrosis factor (TNF)-treated NPCs show NF-κB activation, maintain their multipotential and proliferation properties, display persistent expression of immature markers and inhibit astrocyte markers. Third, we analyze the effect of NF-κB activation on the main known astrocytic differentiation pathways, such as NOTCH and JAK-STAT. Our findings suggest that the NF-κB pathway plays a dual fundamental role during NPC differentiation into astrocytes it promotes astrocyte specification, but its persistent activation impedes their differentiation.The objective of the present research was to quantify the association between dental caries self-report and socioeconomic indicators in Mexican children. An ecological study included a self-report of dental caries in schoolchildren enrolled in public elementary and middle schools derived from the National School Health Survey. A total of 73,560 schoolchildren (representing 19,745,366 students) aged 5 to 16 years were included. Socioeconomic variables included were scales depicting physical characteristics of housing, purchasing power, etc. used in national surveys in Mexico to measure deprivation, poverty, and income inequality in official data. Data were analyzed in Stata using Spearman's correlation test. For the most part, no association (p > 0.05) was found between caries self-report, socioeconomic variables, or the Gini index. However, caries self-report in elementary schoolchildren and total (elementary + middle-school) schoolchildren groups was positively correlated (p less then 0.05) with two poverty variables extreme poverty by income (value of personal food purchases per month) and poverty by income (value of personal food and non-food purchases per month). National data for dental caries self-report were associated-at the ecological level-with a few socioeconomic indicators but not with most of the usual and customary indicators used in national surveys in Mexico.Antithrombin (AT) is a serine protease inhibitor, its activity is highly accelerated by heparin. Mutations at the heparin-binding region lead to functional defect, type II heparin-binding site (IIHBS) AT deficiency. The aim of this study was to investigate and compare the molecular background of AT Budapest 3 (p.Leu131Phe, ATBp3), AT Basel (p.Pro73Leu), and AT Padua (p.Arg79His) mutations. Advanced in silico methods and heparin-binding studies of recombinant AT proteins using surface plasmon resonance method were used. Crossed immunoelectrophoresis and Differential Scanning Fluorimetry (NanoDSF) were performed in plasma samples. Heparin affinity of AT Padua was the lowest (KD = 1.08 × 10-6 M) and had the most severe consequences affecting the allosteric pathways of activation, moreover significant destabilizing effects on AT were also observed. KD values for AT Basel, ATBp3 and wild-type AT were 7.64 × 10-7 M, 2.15 × 10-8 M and 6.4 × 10-10 M, respectively. Heparin-binding of AT Basel was slower, however once the complex was formed the mutation had only minor effect on the secondary and tertiary structures. Allosteric activation of ATBp3 was altered, moreover decreased thermostability in ATBp3 homozygous plasma and increased fluctuations in multiple regions of ATBp3 were observed by in silico methods suggesting the presence of a quantitative component in the pathogenicity of this mutation due to molecular instability.In this paper, torsional fatigue failure of 30CrMnSiNi2A steel which exhibited non-Masing behavior was studied under different constant shear strain amplitudes, using thin-walled tubular specimens. The relationship between shear fatigue and the evolution of meso-deformation inhomogeneity and the prediction method of the torsional fatigue life curve were investigated. Shear fatigue of the material under constant amplitude was researched by numerical simulation with reference to tests, by using crystal plasticity of polycrystalline representative volume element (RVE) as the material model. Considering the non-Masing behavior of material, when determining the parameter values of the crystal plasticity model the correlation between these parameters and strain amplitude was taken into account. The meso-deformation inhomogeneity with increments in the number of cycles was characterized by using the statistical shear strain standard deviation of RVE as the basic parameter. Considering the effect of strain amplitude on fatigue damage, ratio cycle peak stress/yield stress was taken as the weight to measure the torsional fatigue damage and an improved fatigue indicator parameter (FIP) to measure the inhomogeneous deformation of the material was proposed. The torsional fatigue life curve of 30CrMnSiNi2A steel was predicted by the critical value of the FIP and then the result was confirmed.Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. Selleckchem BMS-911172 In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy.