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We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts. ADP stimulated the growth of bovine choroidal EC (BCEC) and other bovine or human eye-derived EC. ADP induced rapid phosphorylation of extracellular signal-regulated kinase in a dose- and time-dependent manner. ADP-induced BCEC proliferation could be blocked by pretreatment with specific antagonists of the purinergic receptor P2Y1 but not with a vascular endothelial growth factor (VEGF) inhibitor, indicating that the EC mitogenic effects of ADP are not mediated by stimulation of the VEGF pathway. Intravitreal administration of ADP expanded the neovascular area in a mouse model of choroidal neovascularization. Single-cell transcriptomics from human choroidal datasets show the expression of P2RY1, but not other ADP receptors, in EC with a pattern similar to VEGFR2. Although ADP has been reported to be a growth inhibitor for vascular EC, here we describe its growth-stimulating effects for BCEC and other eye-derived EC., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10 B(n,α) 7 Li, consisting in the exposition of patients to neutron beams after administration of a boron compound with preferential accumulation in cancer cells. The high linear energy transfer products of the ensuing reaction deposit their energy at the cell level, sparing normal tissue. Although progress in accelerator-based BNCT has led to renewed interest in this cancer treatment modality, in vivo dose monitoring during treatment still remains not feasible and several approaches are under investigation. While Compton imaging presents various advantages over other imaging methods, it typically requires long reconstruction times, comparable with BNCT treatment duration., Methods: This study aims to develop deep neural network models to estimate the dose distribution by using a simulated dataset of BNCT Compton camera images. The models pursue the avoidance of the iteration time associated with the maximum-likelihood expectation-maximization algorithm (MLEM), enabling a prompt dose reconstruction during the treatment. The U-Net architecture and two variants based on the deep convolutional framelets framework have been used for noise and artifact reduction in few-iteration reconstructed images., Results: This approach has led to promising results in terms of reconstruction accuracy and processing time, with a reduction by a factor of about 6 with respect to classical iterative algorithms., Conclusions: This can be considered a good reconstruction time performance, considering typical BNCT treatment times. Further enhancements may be achieved by optimizing the reconstruction of input images with different deep learning techniques.