Chronic infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. In our previous studies, we found that HPV16 E6/E7 up-regulated HIF-1α at protein level and further up-regulated GLUT1 at both protein and mRNA levels in well-established lung cancer cell lines. In one of our further mechanism study, the results demonstrated that HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-LKB1-HIF-1α-GLUT1 axis. However, there are multiple pathways involved in HPV16 E6/E7 regulation of HIF-1α expression. In current study, using double directional genetic manipulation in well-established lung cancer cell lines, we showed that both E6 and E7 down-regulated the expression of RRAD at both protein and mRNA levels. Like LKB1, RRAD is one of the cancer suppressor genes. The loss of RRAD further activated NF-κB by promoted cytoplasmic p65 translocated to nucleus, and up-regulated the expression level of the p-p65 in nucleus. Furthermore, p-p65 up regulated HIF-1α and GLUT1 at both protein and mRNA levels. Thus, we proposed HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-RRAD-p65-HIF-1α-GLUT1 axis. In conclusion, we demonstrated for the first time that E6 and E7 promoted the expression of HIF-1α and GLUT1 by relieving the inhibitory effect of RRAD which resulted in the activation of NF-κB by promoting cytoplasmic p65 translocated to nucleus, and up-regulated the expression of the p-p65 in nucleus in lung cancer cells. Our findings provided new evidence to support the critical role of RRAD in the pathogenesis of HPV-related lung cancer, and suggested novel therapeutic targets.
AC heavy-haul trains produce a huge amount of regenerative braking energy when they run on long downhill sections. If this energy can be used by uphill trains in the same power supply section, a reduction in coal transportation cost and an improvement in power quality would result. To accurately predict the energy consumption and regenerative braking energy of heavy-haul trains on large long slopes, a single-particle model of train dynamics was used. According to the theory of railway longitudinal section simplification, the energy consumption and the regenerative braking energy model of a single train based on the train attributes, line conditions, and running speed was established. The model was applied and verified on the Shenshuo Railway. The results indicate that the percentage error of the proposed model is generally less than 10%. The model is a convenient and simple research alternative, with strong engineering feasibility. Based on this foundation, a model of train energy consumption was established under different interval lengths by considering the situation of regenerative braking energy in the multi-train operation mode. The model provides a theoretical foundation for future train diagram layout work with the goal of reducing the total train energy consumption.
Liquid-based cytology and RT-PCR can be performed to detect LUNX mRNA expression in bronchial brushing specimens, and this technique may be a useful adjunct to cytological diagnosis of lung cancer. The sensitivity of the technique was greater than that of cytology but its lower specificity should be taken into account.
Cervical liquid-based cytology plays an important role in the diagnosis of cervical squamous intraepithelial lesion (SIL). However, cytological evaluation alone has a relatively low sensitive. To overcome this problem, HPV DNA testing or HPV DNA combined with cytology has been applied. HPV DNA testing significantly improved the sensitivity, but the specificity is low, especially in cancer and high-grade SIL (HSIL) cases. The aim of this study was to evaluate the diagnostic utility of p16 overexpression in cervical cells of patients with HSIL and cancer. The expression of p16 was detected by immunostaining in liquid-based cells from cervical brushing in 278 patients which including: Cancer (n = 13), HSIL (n = 112), low-grade SIL (LSIL) (n = 45), and Benign (n = 108). The expression levels of p16 were significantly higher in the cancer and HSIL groups when compared with the LSIL and Benign groups (P < 0.01). The accurate diagnostic rates of cancer and HSIL were significantly increased by p16 immunostaining plus cytology than that by cytology alone (P < 0.01). The false negative or false positive of p16 immunostaining occurred with a unicellular pattern. With sensitivity of 96.0% and accuracy of 91.7%, the diagnostic performance of p16 immunostaining was much better than that of cytology alone with sensitivity of 36.0% and accuracy of 70.9% (P < 0.01). p16 immunostaining in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia but also help to distinguish HSIL from LSIL and the triage of transient infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.