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The endothelial-mesenchymal transition (EndMT) participates in the progression of diabetic retinopathy (DR), but cell-intrinsic factors modulating this process remain elusive. In this study, we explored the role of lysophosphatidic acid (LPA)--producing enzyme, acylglycerol kinase (AGK), in the EndMT of human retinal microvascular endothelial cells (HRECs) under high-glucose (HG) conditions. We found that AGK was significantly elevated in HG-treated cells. In addition, AGK knockdown reversed the HG-induced EndMT in HRECs, which was evidenced by the increased endothelial markers (CD31 and VE-cadherin) and decreased mesenchymal markers (FSP1 and [alpha]-SMA). Furthermore, downregulation of AGK inhibited the HG-induced activation of transforming growth factor [beta] (TGF- [beta])/Notch pathways, whereas exogenous TGF-[beta]1 (10 ng/mL) impeded the inhibitory effects of AGK knockdown on HG-induced EndMT in HRECs. Additionally, the silencing of AGK abolished the HG-induced upregulation of LPA and its receptor, LPA receptor 1 (LPAR1), and overexpression of LPAR1 further rescued the AGK knockdown-mediated inhibition of the EndMT process. In conclusion, we demonstrate that down-regulation of AGK suppresses HG-induced EndMT in HRECs through regulating the LPAR1/TGF- [beta]/Notch signaling pathway, indicating that AGK might be a potential therapeutic target for the treatment of DR. Key words: high glucose, endothelial-mesenchymal transition, acylglycerol kinase, lysophosphatidic acid, retinal microvascular endothelial cell. La transition de l'endothelium au mesenchyme (TEndM) participe a l'evolution de la retinopathie diabetique (RD), mais les facteurs cellulaires intrins eques de ce processus demeurent hors de portee. Dans cette etude, nous avons explore le role de l'enzyme produisant de l'acide lysophosphatidique (LPA), l'acylglycerol kinase (AGK), dans la TEndM de cellules endotheliales des microvaisseaux retiniens humains (HREC) en situation de taux de glucose eleves (HG). Nous avons observe que l'AGK augmentait de facon marquee dans les cellules exposees a l'HG. De plus, la repression (<< knockdown >>) de l'AGK entrainait une inversion de la TEndM engendree par l'HG dans les cellules HREC, ce dont temoignaient un accroissement des marqueurs epitheliaux (CD31 et cadherine VE) de meme qu'un abaissement des marqueurs mesenchymateux (FSP1 et [alpha]-SMA). En outre, la regulation a la baisse de l'AGK entrainait une inhibition de l'activation des voies de signalisation TGF-p/Notch engendree par l'HG, tandis que le TGF-[beta]1 exogene (10 ng/ml) entrainait une attenuation des effets inhibiteurs de la repression de l'AGK sur la TEndM engendree par l'HG dans les cellules HREC. De plus, l'extinction (<< silencing >>) de l'AGK entrainait une inhibition complete de la regulation a la hausse de la LPA engendree par l'HG et de ses recepteurs LPAR1, et la surexpression de ceux-ci permettait de retablir l'inhibition du processus de TEndM mediee par la repression de l'AGK. En conclusion, nous montrons que la regulation a la baisse de l'acylglycerol kinase inhibe completement la transition de l'endothelium au mesenchyme engendree par l'HG dans les cellules HRECs par l'intermediaire de la regulation de la voie de signalisation LPAR1/TGF-[beta]/Notch, ce qui indique que l'AGK pourrait constituer une cible therapeutique dans le traitement de la RD. [Traduit par la Redaction] Mots-cles : hyperglycemie, transition de l'endothelium au mesenchyme, acylglycerol kinase, acide lysophosphatidique, cellule endotheliale des microvaisseaux retiniens., Introduction Diabetes is a lifelong, metabolic disease characterized by the inability to maintain normal glucose homeostasis, due to insulin resistance or insufficient insulin secretion (King and Bowe 2016; Thomas and [...]

The fractional-order Benjamin-Bona-Mahony-Burgers (BBMB) equation is a generalization of the classical BBMB equation. It's dynamic behaviors is much more complex than that of the corresponding integer-order BBMB equation. The main purpose of this paper is to explore the dynamic behaviors of the fractional-order BBMB equations by using the Fourier spectral method. Firstly, the numerical solution is compared with the exact solution. It is proved that the proposed method is effective and high precision for solving the spatial fractional order BBMB equation. Then, some dynamical behaviors of fractional order BBMB equations are obtained by using the present method, and some novel fractal waves of the the fractional-order BBMB equation on unbounded domain are shown. [ABSTRACT FROM AUTHOR]

Our proclivity toward high-fidelity transmission of knowledge is one of the key mechanisms that underpins our success as a species. This study evaluated overimitation within children with hearing impairments (who had either a cochlear implant or a hearing aid) in relation to those with normal hearing. A total of seventy-two 4-year-old children were shown how to operate novel objects using a series of causally irrelevant actions, followed by causally relevant action. We measured the degree to which children reproduced the irrelevant actions as an indicator of imitative fidelity. Children with either hearing impairments or normal hearing replicated the irrelevant actions at rates above the baseline. However, imitative fidelity of the former group was significantly lower. In addition, children with hearing impairments were also less likely to identify and achieve the outcome by performing the relevant act. This study advances our understanding of social learning in children with hearing impairments and proposes potential weakness of social-cognitive skills within this population.

In this paper, a novel viscoelastic constitutive model which can reflect the phase transformation mechanism of multi-shape memory polymer (M-SMP) is established. In this model, M-SMP is regarded as an inhomogeneous body composed of different phases, and the rheological representations of each phase are established based on the viscoelastic mechanics theory. Combined with the level set method, the conversion relationships of each adjacent two phases of M-SMP are established, and then the relationships between each phase are obtained. The constitutive model is used to simulate the thermodynamic behavior of dual-shape memory polymer (D-SMP) and triple-shape memory polymer (T-SMP), and the simulation results are compared with the experimental results and models of relevant literature. Meanwhile, the shape memory behaviors under different correlation rates are studied and analyzed considering the influence of rate correlation. The results show that the model can describe the thermodynamic behavior of M-SMP more accurately and effectively, and in shape memory process of M-SMP, there is a strong rate correlation here. The model can provide a theoretical basis for the engineering application of M-SMP. [ABSTRACT FROM AUTHOR]