The activation of platelets and proliferation of vascular smooth muscle cells (VSMCs) in the vascular intima play an essential role in the pathological mechanism of vascular restenosis (RS). Rosmarinic acid (RA) is a natural phenolic acid compound. However, its mechanism of action on platelets and VSMCs is still unclear. This study investigated the effects of RA on platelet function, VSMCs phenotypic conversion, proliferation, and migration in vascular remodeling with a specific focus on the Keap1-Nrf2-ARE signaling pathway. RA inhibited platelet aggregation and Ca 2+ release and significantly reduced the release of platelet microvesicles. In addition, RA inhibited the phenotypic transition of VSMCs in vitro and in vivo. In vitro experiments showed that RA could effectively inhibit the proliferation and migration of VSMCs induced by the platelet-derived growth factor (PDGF)-BB. PDGF-BB triggered ROS generation and a decrease in mitochondrial membrane potential, which were inhibited by RA. Mechanistically, after artery injury or treatment with PDGF-BB, VSMCs presented with inhibition of the Nrf2/antioxidant response element (ARE) signaling pathway. RA treatment reversed this profile by activating the Nrf2/ARE signaling pathway; stabilizing Keap1 protein; upregulating HO-1, NQO1, GCLM, and GST protein levels; promoting typical Nrf2 nuclear translocation; and preventing VSMCs from oxidative stress damage. On the other hand, RA also inhibited the NF-κB pathway to reduce inflammation. In summary, these results indicate that RA inhibits platelet function and attenuates the proliferation, migration, and phenotypic transition of VSMCs induced by PDGF-BB in vitro and vascular remodeling in vivo. Therefore, RA treatment may be a potential therapy for preventing or treating RS.

In order to meet the cost requirement of lateral and longitudinal velocity measured directly in vehicle active safety control systems, based on 3-DOF vehicle model and the Recursive Least Squares (RLS) which can identify the tire cornering stiffness online, a control algorithm using Extended Kalman Filter(EKF) to estimate lateral and longitudinal velocity is proposed. The estimation values are compared with simulator values from CarSim. The compared results demonstrated that the proposed algorithm could estimate the lateral and longitudinal velocity accurately and robustly.

Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein, we investigated the DLX6-AS1 (Dlx6-os1 in mice) role in DN pathogenesis. We found that DLX6-AS1 expression in DN patients correlated with the extent of albuminuria. Dlx6-os1 overexpression induced cellular damage and inflammatory responses in cultured podocytes through miR-346-mediated regulation of the GSK-3β pathway. In various established diabetic and newly developed knockout mouse models, Dlx6-os1 knockdown/knockout significantly reduced podocyte injury and albuminuria. The Dlx6-os1 effects were remarkably modulated by miR-346 mimics or mutants and significantly diminished in podocyte-specific GSK-3β-knockout mice. Thus, DLX6-AS1 (Dlx6-os1) promotes DN development by accelerating podocyte injury and inflammation through the upregulation of the GSK-3β pathway, providing a novel molecular target for DN therapy.

This article describes how by analyzing historical sales data of supermarkets, once data is cleaned, sampled and put through a series of operations, it can be transformed into a sequence database. Finally, the data is used in the SPM of Map-Reduce algorithm to data mining. This experiment has two stages. In the first stage, the sequences of product categories are mined to place the product categories. In the second stage, the products are mined for each category, add profit targets for calculating sequential pattern values. This is so that it can reorder the results to find the most profit products. Thus, readers can adjust products placement and improve the profits of the supermarket.