Angelicin is a member of a well-known class of chemical photosensitizes that have anticancer proper-ties in several cancer cell lines. However, the effects and the potential underlying mechanisms of angelicin action on human lung cancer cells remain unclear. Here, we report that angelicin has an essential role in inhibiting human lung carcinoma growth and metastasis. We found that angelicin markedly induced cell apoptosis and arrested the cell cycle in vitro. Angelicin also inhibited the migration of non-small cell lung cancer (NSCLC) A549 cells in a Transwell assay in a dose-dependent manner. In addition, after angelicin treatment, the expression levels of Bax, cleaved caspase-3 and cleaved caspase-9 were increased, and Bcl-2 expression was decreased. Moreover, our results indicate that angelicin inhibits NSCLC growth not only by downregulating cyclin B1, cyclin E1 and Cdc2, which are related to the cell cycle, but also by reducing MMP2 and MMP9 and increasing E-cadherin expression levels. Furthermore, extracellular signal-regulated kinase (ERK)1/2 and c-Jun NH2-terminal protein kinase (JNK)1/2 phosphorylation increased in parallel with the angelicin treatments. The inhibition of ERK1/2 and JNK1/2 by specific inhibitors significantly abrogated angelicin-induced cell apoptosis, cell cycle arrest and migration inhibition. We established in vivo A549 cell transplant and metastasis models and found that angelicin exerted a significant inhibitory effect on A549 cell growth and lung metastasis. Overall, our results suggested that angelicin is able to inhibit NSCLC A549 cell growth and metastasis by targeting ERK and JNK signaling, which demonstrates potential for NSCLC therapy.
High-precision navigation using low-cost handsets has profound potential for mass-market applications, which has been being boosted by the release of raw GNSS data from Google Android smart devices. However, integer ambiguity fixing for centimeter-level GNSS positioning is prevented by the unaligned chipset initial phase biases (IPBs) found within Android carrier-phase data. In this study, we thus investigate the temporal behaviors of those chipset IPBs using zero baselines where smart devices are linked to external survey-grade antennas, and find that the IPBs are generally stable over time as the mean standard deviation of single-epoch IPB estimates derived from continuous carrier-phase data is as low as 0.04 cycles for all satellites. Unfortunately, these chipset IPBs differ randomly among satellites and change unpredictably if carrier-phase signals are re-tracked, discouragingly suggesting that the chipset IPBs cannot be pre-calibrated or even calibrated on the fly.We therefore have to presumably correct for them in a post-processing manner with the goal of inspecting the potential of Android GNSS ambiguity resolution if hopefully the IPBs can be gone. For a vehicle-borne Nexus 9 tablet with respect to a survey-grade receiver located 100-2000 m away, we achieve the first ambiguity-fixed solution within 321 s and finally 51.6% of all epochs are resolved; the ambiguityfixed epochs can achieve a positioning accuracy of 1.4, 2.2 and 3.6 cm for the east, north and up components, respectively, showing an improvement of 30%-80% compared to the ambiguity-float solutions. While all smart devices above are connected to external survey-grade antennas, we find that a Xiaomi 8 smartphone can be coupled effectively with a miniaturized portable patch antenna, and then achieve commensurate carrier-phase tracking and ambiguity-fixing performance to those of a commercial µ-blox receiver with its dedicated patch antenna. This is encouraging since a compact and inexpensive patch antenna paired with smart devices can promote the democratization of high-precision GNSS.
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