Highlights d TMEM63B is a hypo-osmolarity-activated cation channel d Deficiency of TMEM63B causes hearing loss in mice d TMEM63B is localized in hair cells and required for outer hair cell survival d TMEM63B mediates Ca 2+ -dependent regulatory volume decrease in outer hair cells

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MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.

Current as high as 3.7kA has been generated using a single photoconductive semiconductor switch (PCSS) excited by a laser pulse with the energy of ∼8mJ and under a bias of 28kV. The PCSS with electrode gap of 14mm was fabricated from semi-insulating GaAs. Under different bias voltages the “on” resistances of the PCSS were measured. The longevity of the PCSS reached 350 shots at 20kV and 400A. The breakdown mechanism of the PCSS is analyzed based on the breakdown characteristics. It is shown that the breakdown of GaAs PCSS can be described by the electron-trapping breakdown theory.

Hair cell degeneration is a major cause of sensorineural hearing loss. Hair cells in mammalian cochlea do not spontaneously regenerate, posing a great challenge for restoration of hearing. Here, we establish a robust, high-throughput cochlear organoid platform that facilitates 3D expansion of cochlear progenitor cells and differentiation of hair cells in a temporally regulated manner. High-throughput screening of the FDA-approved drug library identified regorafenib, a VEGFR inhibitor, as a potent small molecule for hair cell differentiation. Regorafenib also promotes reprogramming and maturation of hair cells in both normal and neomycin-damaged cochlear explants. Mechanistically, inhibition of VEGFR suppresses TGFB1 expression via the MEK pathway and TGFB1 downregulation directly mediates the effect of regorafenib on hair cell reprogramming. Our study not only demonstrates the power of a cochlear organoid platform in highthroughput analyses of hair cell physiology but also highlights VEGFR-MEK-TGFB1 signaling crosstalk as a potential target for hair cell regeneration and hearing restoration.

Significance The mechanistic target of rapamycin (mTOR) plays a central role in growth, metabolism, and aging. It is assembled into two multiprotein complexes, namely, mTORC1 and mTORC2. We previously demonstrated the efficacy of sirolimus in ARHL in mice by decreasing mTORC1. However, the aspect of mTORC2 regulation in the cochlea is poorly characterized. Herein, based on pharmacological and genetic interventions, we found that a high dose of sirolimus resulted in severe hearing loss by reducing the mTORC2/AKT signaling pathway in the cochlea. Furthermore, selective activation of mTORC2 could protect against hearing loss induced by acoustic trauma and cisplatin-induced ototoxicity. Hence, the therapeutic activation of mTORC2 in conjunction with decreasing mTORC1 might represent a promising and effective strategy in preventing hearing loss.

Aimin (2015) 'Low-frequency noise properties in Pt-indium gallium zinc oxide Schottky diodes.', Applied physics letters., 107 (9). 093505.

Laccase, as a copper-containing polyphenol oxidase, primarily functions in the process of lignin, anthocyanin biosynthesis, and various abiotic/biotic stresses. In this study, forty-eight laccase members were identified in the eggplant genome. Only forty-two laccase genes from eggplant (SmLACs) were anchored unevenly in 12 chromosomes, the other six SmLACs were mapped on unanchored scaffolds. Phylogenetic analysis indicated that only twenty-five SmLACs were divided into six different groups on the basis of groups reported in Arabidopsis. Gene structure analysis revealed that the number of exons ranged from one to 13. Motif analysis revealed that SmLACs included six conserved motifs. In aspects of gene duplication analysis, twenty-one SmLACs were collinear with LAC genes from Arabidopsis, tomato or rice. Cis-regulatory elements analysis indicated many SmLACs may be involved in eggplant morphogenesis, flavonoid biosynthesis, diverse stresses and growth/development processes. Expression analysis further confirmed that a few SmLACs may function in vegetative and reproductive organs at different developmental stages and also in response to one or multiple stresses. This study would help to further understand and enrich the physiological function of the SmLAC gene family in eggplant, and may provide high-quality genetic resources for eggplant genetics and breeding.