The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3β/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.
Neutron radiography has been used for in-situ and non-destructive visualization and measurement technique for liquid water in a working proton exchange membrane fuel cell (PEMFC). In an attempt to differentiate water distribution in the anode side from that in the cathode side, a specially designed cell was machined and used for the experiment.The major difference between our design and traditional flow field design is the fact the anode channels and cathode channels were shifted by a channel width, so that the anode and cathode channels do not overlap in the majority of the active areas.The neutron radiography experiments were performed at selected relative humidities, and stoichiometry values of cathode inlet. At each operating condition, the water distribution in anode/cathode gas diffusion layers (GDLs) was obtained. Image processing with four different spatial masks were applied to those images to differentiate liquid water in four different types of areas. Results indicate that the reactant gas relative humidity and stoichiometry significantly influence current density distribution and water distribution.
All-vanadium redox flow batteries (VRFBs) are used as energy storage systems for intermittent renewable power sources. The performance of VRFBs depends on materials of key components and operating conditions, such as current density, electrolyte flow rate and electrolyte composition. Mass transfer overpotential is affected by the electrolyte flow rate and electrolyte composition, which is related to the limiting current density. In order to investigate the effect of operating conditions on mass transport overpotential, this study established a relationship between the limiting current density and operating conditions. First, electrolyte solutions with different states of charge were prepared and used for a single cell to obtain discharging polarization curves under various operating conditions. The experimental results were then analyzed and are discussed in this paper. Finally, this paper proposes a limiting current density as a function of operating conditions. The result helps predict the effect of operating condition on the cell performance in a mathematical model.
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