Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte–specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-throughput screen identified SB216763 as a suppressor of the disease phenotype. Early SB216763 therapy prevented heart failure and reduced mortality in the fish model. Zebrafish ventricular myocytes that expressed 2057del2 plakoglobin exhibited 70 to 80% reductions in INa and IK1 current densities, which were normalized by SB216763. Neonatal rat ventricular myocytes that expressed 2057del2 plakoglobin recapitulated pathobiological features seen in patients with ACM, all of which were reversed or prevented by SB216763. The reverse remodeling observed with SB216763 involved marked subcellular redistribution of plakoglobin, connexin 43, and Nav1.5, but without changes in their total cellular content, implicating a defect in protein trafficking to intercalated discs. In further support of this mechanism, we observed SB216763-reversible, abnormal subcellular distribution of SAP97 (a protein known to mediate forward trafficking of Nav1.5 and Kir2.1) in rat cardiac myocytes expressing 2057del2 plakoglobin and in cardiac myocytes derived from induced pluripotent stem cells from two ACM probands with plakophilin-2 mutations. These observations pinpoint aberrant trafficking of intercalated disc proteins as a central mechanism in ACM myocyte injury and electrical abnormalities.

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Suicidal behaviour in Chinese adolescents is prevalent but less than that previously reported in Western peers. While females are more likely to attempt suicide, males are more likely to use lethal methods. Multiple child and family factors are associated with suicidal behaviour. These findings highlight the importance of early screening and intervention of suicidal behaviour in Chinese adolescents.

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High-index dielectric nanoantennas have become an emerging branch of optical nanoantennas, essentially due to their low loss. These types of nanoantennas can achieve both forward and backward unidirectional scattering, enabled by electric dipole and magnetic dipole interaction. Here, we show that the scattering directionality can be further enhanced if higher-order moments are properly balanced and reach the generalized Kerker condition at two different wavelengths in an all-dielectric hollow nanodisk. Moreover, putting the nanodisks in an array of transverse configuration can enhance the unidirectionality to be needle-like, with the main lobe angular beam width α<15°. Finally, we show that such unidirectional radiation properties can be maintained for a local electric dipole source.

Due to the abilities of manipulating the wavefront of light with well-controlled amplitude, and phase and polarization, optical metasurfaces are very suitable for optical holography, enabling applications with multiple functionalities and high data capacity. Here, we demonstrate encoding two- and three-dimensional full-color holographic images by an ultrathin metasurface hologram whose unit cells are subwavelength nanoslits with spatially varying orientations. We further show that it is possible to achieve full-color holographic multiplexing with such kind of geometric metasurfaces, realized by a synthetic spectrum holographic algorithm. Our results provide an efficient way to design multi-color optical display elements that are ready for fabrication.

Previous studies on the propagation direction of valley topological edge states mainly focus on the matching between orbital angular momentum of the excitation source and specific pseudo-spin state of valley edge mode at certain frequency that falls in the bandgap of the topologically distinct bulk components. In this work, we propose topological photonic crystals (PCs) hosting two topological protected bandgaps. It is shown that by constructing the interface between different PC structures with distinct topological phase, edge states can be engineered inside these two bandgaps, which provides a convenient way to achieve flexible wave routing. Particularly, we study three types of meta-structures consisting of these PCs in which the valley edge states routing path highly depends on the operating frequency and inputting port of the excitation source. Our study provides an alternative way in designing topological devices such as wave splitters and frequency division devices.