In this paper, we propose an accurate edge detector using richer convolutional features (RCF). Since objects in natural images possess various scales and aspect ratios, learning the rich hierarchical representations is very critical for edge detection. CNNs have been proved to be effective for this task. In addition, the convolutional features in CNNs gradually become coarser with the increase of the receptive fields. According to these observations, we attempt to adopt richer convolutional features in such a challenging vision task. The proposed network fully exploits multiscale and multilevel information of objects to perform the image-to-image prediction by combining all the meaningful convolutional features in a holistic manner. Using VGG16 network, we achieve state-of-the-art performance on several available datasets. When evaluating on the well-known BSDS500 benchmark, we achieve ODS F-measure of 0.811 while retaining a fast speed (8 FPS). Besides, our fast version of RCF achieves ODS F-measure of 0.806 with 30 FPS.

Background Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic. Methods Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential. Results Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. Conclusions The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC. Graphical abstract

The metastatic organotropism has been one of the cancer's greatest mysteries since the ‘seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression. Moreover, the upregulated paracrine HGF, which binds the c-MET receptor on the migrated cancer cells, provides fertile ‘soil' for the ‘seed', facilitating the landing and proliferation of metastatic cancer cells. Thus, we propose that EGFR-containing exosomes derived from cancer cells could favour the development of a liver-like microenvironment promoting liver-specific metastasis.

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