Background Growing evidence has indicated that tumor-associated macrophages (TAMs) promote tumor angiogenesis. However, the mechanisms underlying the pro-angiogenic switch of TAMs remains unclear. Here, we examined how exosomal miR-301a-3p secreted by esophageal squamous cell carcinoma (ESCC) cells triggers the pro-angiogenic switch of TAMs. Methods We quantified miR-301a-3p levels in ESCC tumors using qRT-PCR. Macrophage phenotypes were identified using flow cytometry and qRT-PCR. The pro-angiogenic ability of TAMs was measured using the CCK-8 assay, scratch assay, Transwell migration and invasion assay, and tube formation assay. The mechanism by which exosomal miR-301a-3p secreted by ESCC cells triggers the pro-angiogenic switch of TAMs was elucidated using western blots, qRT-PCR, and a dual-luciferase reporter assay. Results We observed anomalous miR-301a-3p overexpression in ESCC tumor tissues and cell lines. Then, we verified that ESCC-derived exosomes promoted angiogenesis by inducing macrophage polarization into M2 type, and exosomal miR-301a-3p secreted by ESCC cells was responsible for this effect. Finally, we discovered that exosomal miR-301a-3p promoted M2 macrophage polarization via the inhibition of PTEN and activation of the PI3K/AKT signaling pathway, subsequently promoting angiogenesis via the secretion of VEGFA and MMP9. Conclusion The pro-angiogenic switch of TAMs is triggered by exosomal miR-301a-3p secreted from ESCC cells via the PTEN/PI3K/AKT signaling pathway. Although tumor angiogenesis can be regulated by a wide range of factors, exosomal miR-301a-3p could hold promise as a novel anti-angiogenesis target for ESCC treatment.

No abstract

No abstract

Purpose Most manufacturing plants choose the easy way of completely separating human operators from robots to prevent accidents, but as a result, it dramatically affects the overall quality and speed that is expected from human–robot collaboration. It is not an easy task to ensure human safety when he/she has entered a robot’s workspace, and the unstructured nature of those working environments makes it even harder. The purpose of this paper is to propose a real-time robot collision avoidance method to alleviate this problem. Design/methodology/approach In this paper, a model is trained to learn the direct control commands from the raw depth images through self-supervised reinforcement learning algorithm. To reduce the effect of sample inefficiency and safety during initial training, a virtual reality platform is used to simulate a natural working environment and generate obstacle avoidance data for training. To ensure a smooth transfer to a real robot, the automatic domain randomization technique is used to generate randomly distributed environmental parameters through the obstacle avoidance simulation of virtual robots in the virtual environment, contributing to better performance in the natural environment. Findings The method has been tested in both simulations with a real UR3 robot for several practical applications. The results of this paper indicate that the proposed approach can effectively make the robot safety-aware and learn how to divert its trajectory to avoid accidents with humans within the workspace. Research limitations/implications The method has been tested in both simulations with a real UR3 robot in several practical applications. The results indicate that the proposed approach can effectively make the robot be aware of safety and learn how to change its trajectory to avoid accidents with persons within the workspace. Originality/value This paper provides a novel collision avoidance framework that allows robots to work alongside human operators in unstructured and complex environments. The method uses end-to-end policy training to directly extract the optimal path from the visual inputs for the scene.

Esophageal squamous cell carcinoma (ESCC) has high morbidity and mortality rates owing to its ability to infiltrate and metastasize. Microvessels formed in early-stage ESCC promote metastasis. Phosphatase and tensin homolog (PTEN) mediates macrophage polarization, but its effect and mechanism on early ESCC angiogenesis are unclear. To explore the molecular mechanism underlying early ESCC metastasis through blood vessels, we investigated the relationship between PTEN/phosphoinositide 3-kinase (PI3K)/p-AKT protein levels, number of infiltrated macrophages, and angiogenesis in ESCC and ESCC-adjacent normal esophageal mucosa tissues from 49 patients. Additionally, PTEN was overexpressed or silenced in the esophageal cancer cell line EC9706, and its supernatant served as conditioning medium for M1 tumor-associated macrophages (TAMs). The culture medium of macrophages served as conditioning medium for esophageal tumor-associated vascular endothelial cells (TECs) to study the biological behavior of PTEN-plasmid, PTEN-siRNA, and control TECs. We found that M1 TAM infiltration in ESCC tissues was low, whereas M2 TAM infiltration was high. Microvessel density was large, PTEN was down-regulated, and the PI3K/AKT pathway was activated in ESCC specimens. These parameters significantly related to the depth of tumor invasion, lymph node metastasis, and pathological staging of ESCC. Silencing of PTEN in EC9706 cells significantly activated the PI3K/AKT signaling pathway in macrophages, promoting M1-to-M2 TAM polarization and enhancing TECs’ ability to proliferate, migrate, invade, form tubes, and secrete vascular endothelial growth factor. We believe that PTEN silencing in esophageal cancer cells activates the PI3K/AKT signaling pathway in macrophages via the tumor microenvironment, induces M2 TAM polarization, and enhances the malignant behavior of TECs, thereby promoting ESCC angiogenesis. Our findings lay an empirical foundation for the development of novel diagnostic and therapeutic strategies for ESCC.