FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

Dynamic scene stitching driven by visual cognition model.

Dynamic scene stitching still has a great challenge in maintaining the global key information without missing or deforming if multiple motion interferences exist in the image acquisition system. Object clips, motion blurs, or other synthetic defects easily occur in the final stitching image. In our research work, we proceed from human visual cognitive mechanism and construct a hybrid-saliency-based cognitive model to automatically guide the video volume stitching. The model consists of three elements of different visual stimuli, that is, intensity, edge contour, and scene depth saliencies. Combined with the manifold-based mosaicing framework, dynamic scene stitching is formulated as a cut path optimization problem in a constructed space-time graph. The cutting energy function for column width selections is defined according to the proposed visual cognition model. The optimum cut path can minimize the cognitive saliency difference throughout the whole video volume. The experimental results show that it can effectively avoid synthetic defects caused by different motion interferences and summarize the key contents of the scene without loss. The proposed method gives full play to the role of human visual cognitive mechanism for the stitching. It is of high practical value to environmental surveillance and other applications.

Long noncoding RNAs and novel inflammatory genes determined by RNA sequencing in human lymphocytes are up-regulated in permanent atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia in clinical practice. Currently, approximately 33.5 million individuals are affected by AF globally. AF involves multiple complicated mechanisms which have not been fully investigated yet. RNA sequencing (RNAseq) is an outstanding method for investigation of diseases due to its high-throughput information. Here, RNAseq was applied to determine mRNA and long noncoding RNA (lncRNA) expression profiles in human lymphocytes from 6 permanent atrial fibrillation (pmAF) patients and 6 healthy controls. Quantitative real-time PCR (qRT-PCR) was applied to further validate 3 lncRNAs and 4 inflammatory mRNAs. It was discovered that there were numerous differentially-expressed mRNAs and lncRNAs between these two groups. GO analysis indicated that differentially-expressed mRNAs were mainly involved in native immunity, inflammation, signaling transduction and so forth, and they were also enriched in pathways like TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor pathway and NOD-like receptor pathway. Moreover, co-expression network demonstrated that dysregulated mRNAs and lncRNAs in pmAF lymphocytes participated in inflammation, autophagy, mitochondrial functions, oxidative stress, etc. Further validation by qRT-PCR demonstrated mRNAs and lncRNAs were significantly higher in lymphocytes from pmAF patients compared with controls. In conclusion, mRNA and lncRNA expression profiles in lymphocytes are significantly different between pmAF and controls, differentially-expressed mRNAs and lncRNAs are involved in pathways closely associated with inflammation, oxidative stress, autophagy, cell apoptosis and collagen synthesis, suggesting lymphocytes might play indispensable roles in the development of pmAF.