To date, the role of Dickkopf 3 (Dkk3) on the pathogenesis of familial dilated cardiomyopathy (FDCM), and whether and how Dkk3 interferes with Wnt signaling in heart tissues remains unknown. Here, we demonstrate that strong Dkk3 expression was markedly downregulated in adult hearts from WT mice, and Dkk3 expression was upregulated suddenly in hearts from DCM mouse models. Using Dkk3 transgenic and knockout mice, as well as cTnT R141W transgenic mice, which manifests progressive chamber dilation and contractile dysfunction and has pathologic phenotypes similar to human DCM patients, we determined that transgenic expression of Dkk3 increased survival rate, improved cardiac morphology breakage and dysfunction, and ameliorated cardiac pathological changes in the cTnT R141W mice. In contrast, Dkk3 knockout reduced the survival rate and aggravated the pathological phenotypes of the cTnT R141W mice. The protective effects of Dkk3 appeared clearly at 3 months of age, peaked at 6 months of age, and decreased at 10 months of age in the cTnT R141W mice. Furthermore, we determined that Dkk3 upregulated Dvl1 (Dishevelled 1) and key proteins of the canonical Wnt pathway (cytoplasmic and nuclear β-catenin, c-Myc, and Axin2) and downregulated key proteins of the noncanonical Wnt pathway (c-Jun N-terminal kinase (JNK), Ca 2+ /calmodulin-dependent protein kinase II (CAMKII), and histone deacetylase 4 (HDAC4)). In contrast, Dkk3 knockout reversed these changes in the cTnT R141W mice. In summary, Dkk3 could prevent FDCM development in mice, especially in the compensatory stage, and probably through activation of the canonical and inhibition of the noncanonical Wnt pathway, which suggested that Dkk3 could serve as a therapeutic target for the treatment of cardiomyopathy and heart failure.

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Sparse code multiple access (SCMA) is one of the most intensively investigated non-orthogonal multiple access (NOMA) techniques for the fifth generation communication (5G) system. In this paper, a new multi-stage optimization approach for codebook design is proposed for the uplink SCMA system. The proposed schemes includes two parts: i) multi-dimensional mother constellation design ii) mapping matrix design. Firstly, the multi-dimensional complex mother constellation design is implemented by a series of twodimensional real constellations which can be obtained by the lattice theory and the symbol switch algorithm (SSA). The Secondly, we construct user-specific mapping matrix by optimizing the phase rotation of the user constellation to effectively reduce the interference between the multi-user codewords superimposed on every single time-domain resource elements (REs). Finally, the multi-user codebooks are generated by combining the multi-dimensional mother constellation and the user-specific mapping matrix. The simulation results demonstrate that the proposed codebooks can greatly decrease bit error rate (BER) value compared to the existing codebooks under different channels, different codebook sizes and different overloading ratios, and the performance is also improved for the large-scale SCMA codebook. More importantly, in order to verify the proposed codebook applicability, two different message passing algorithm (MPA) are used to simulate the SCMA system with different codebook sizes, both of which obtain faster convergence speed and better BER performance than other existing codebooks.INDEX TERMS SCMA, codebook design, mapping matrix, BER, message passing algorithm.