Evaluating the effects of the route guidance variable message signs on driving behaviors-a driving simulation study.

OBJECTIVE: Route guidance variable message signs (VMS) are widely applied in traffic incident management on highways by providing real-time spatiotemporal guidance information. The improper panel of route guidance VMS is likely to diminish the compliance with guidance and induce risky driving behaviors, disrupting the traffic flow or even causing crashes. This article aims to investigate the effects of route guidance VMS on driving behaviors in three aspects, vehicle operation, visual perception, and route choice. METHODS: A driving simulation study with 32 participants was carried out to investigate the driving performance under four different VMS recognizing conditions: baseline (a typical guide sign) and three route guidance VMS panel schemes. RESULTS: Significant differences in average speed, speed fluctuation, average acceleration, and fixation proportion were found under various VMS recognition conditions. VMS3 had the least negative effects on vehicle operation and visual perception, and the compliance rate under VMS3 was the highest. The possible reasons are as follows: VMS3 has the simplified highway network structure and highlights the road directions with an eye-catching symbol, which can increase the comprehensibility of the guidance information while driving. CONCLUSIONS: Drivers need to take multiple actions under high-speed driving conditions while recognizing VMS, including reading the route guidance VMS, remaking route decisions, and operating the vehicle concurrently. Under such circumstances, the improper VMS panel would attract more drivers' attention and induce excessive risk compensatory behaviors, reducing drivers' compliance with guidance and situation awareness, and increasing crash risks. In addition, some VMS related traffic management strategies were proposed to improve safety and mobility of highways and further provide a basis for the formulation of related standards.

RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis in chronic pancreatitis.

Chronic pancreatitis (CP) is described as a progressive fibro-inflammatory disorder of the exocrine disease, which eventually leads to damage of the gland. Excessive activation of pancreatic stellate cells (PSCs) is a critical participant in the initiation of CP. Autophagy is involved in multiple degeneration and inflammation in acute pancreatitis and CP. In our study, we report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated with pancreatic fibrogenesis in tissues and plasma of CP patients. Knockdown of RB1CC1 restrains alpha smooth muscle actin (α-SMA) and collagen expressions, and autophagy in activated PSCs in vitro. Furthermore, we show that RB1CC1 induces PSC activation via binding to ULK1 promoter and the direct interaction with ULK1 protein. These suppress ULK1 expression and its kinase activity. In mice, knockdown of RB1CC1 blocks autophagy and then inhibits the pancreatic duct ligation-induced pancreatic fibrosis. Consequently, our study highlights that RB1CC1-mediated autophagy is a key event for the activation of PSCs. Inhibition of RB1CC1 alleviates autophagy, which plays a critical role in anti-fibrotic activation in PSCs and CP progression. RB1CC1 could be a novel strategy for the treatment of pancreatic fibrosis.

MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma.

Metastasis remains one of the most intractable challenges in pancreatic ductal adenocarcinoma (PDAC) biology, and epithelial-to-mesenchymal transition (EMT) is essential to the epithelium-originated solid tumor metastasis cascade. Emerging evidence demonstrates that aberrant miRNA expression is involved in pancreatic cancer progression. We found that miR-361-3p was associated with an advanced stage of PDAC and poor prognosis. Hence, the effect of miR-361-3p on metastasis of PDAC cells was evaluated using Transwell assay and wound healing assay in vitro as well as orthotopic and liver metastasis pancreatic cancer models in vivo. Overexpression of miR-361-3p promoted pancreatic cancer cell migration and invasion in vitro, and miR-361-3p-elevated PDAC cells were prone to generating metastatic nodules in vivo. However, miR-361-3p showed no significant effect on the proliferation of PDAC cells in vivo or in vitro. Further study demonstrated that miR-361-3p could enhance EMT and ERK pathway activation, and ERK inhibitor could attenuate miR-361-3p-induced EMT. Luciferase assays, qPCR, and western blot and Ago2 co-immunoprecipitation were performed to identify the direct target of miR-361-3p. Mechanistic investigations identified DUSP2 as a direct target of miR-361-3p, and DUSP2 was revealed to be involved in miR-361-3p-induced EMT by directly leading to the inactivation of the ERK pathway. Moreover, we found that miR-361-3p-induced EMT was dependent on Ago2, the core component of RNA-induced silencing complex, while enforced expression of Ago2 enhanced the miR-361-3p-induced effect by promoting interference efficacy and specificity rather than regulating miR-361-3p stability and biogenesis. Thus, this study revealed that miR-361-3p functions as an oncomiR for promoting metastasis and identified the miR-361-3p/DUSP2/ERK axis as a novel EMT axis dependent on Ago2 in PDAC.