2026-06-09 | Quinazoline alleviates inner ear damage by enhancing the proliferation and differentiation of neural stem cells.

Neural stem cell (NSC) transplantation exerts therapeutic effects on inner ear damage and pretreatment with quinazoline compounds may further enhance this efficacy. This study aimed to investigate whether quinazoline alleviates inner ear damage by enhancing the proliferation and differentiation of NSCs. Forty Hartley guinea pigs were randomly assigned to four groups. Hippocampal NSCs isolated from neonatal guinea pigs were pretreated with quinazoline and transplanted into animals with cisplatin-induced hearing loss. Evaluations included NSC proliferation and differentiation, auditory brainstem response (ABR) thresholds and miR-183 expression in cochlear tissues. Quinazoline pretreatment significantly enhanced NSC proliferation and differentiation (P<0.05). After transplantation, the group receiving quinazoline-pretreated NSCs showed a significantly lower ABR threshold (reflecting an approximately 10 dB improvement in hearing recovery) than the group receiving untreated NSCs (P<0.05). This was accompanied by more pronounced structural repair of the cochlea and a significant upregulation of miR-183 expression (P<0.05). Quinazoline promotes the repair of inner ear injury by enhancing the proliferation and differentiation of NSCs, a mechanism that appears to be associated with the upregulation of miR-183 expression.

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2026-06-04 | Tonotopic specialization of MYO7A isoforms in auditory hair cells.

Mutations in Myo7a cause Usher syndrome type 1B and non-syndromic deafness, but the precise function of MYO7A in sensory hair cells remains unclear. Using long-read sequencing, we identify and characterize a novel isoform, MYO7A-N, expressed in auditory hair cells alongside the canonical MYO7A-C. Isoform-specific knock-in mouse models reveal that inner hair cells primarily express MYO7A-C, while outer hair cells express both isoforms in opposing tonotopic gradients. Both isoforms are localized to the upper tip-link insertion site, consistent with a role in the tip link for mechanotransduction. Loss of MYO7A-N leads to outer hair cell degeneration and progressive hearing loss. Cryo-EM structures reveal isoform-specific differences at actomyosin interfaces, correlating with distinct ATPase activities. These findings reveal an unexpected layer of molecular diversity within the mechanotransduction machinery. We propose that MYO7A isoform specialization enables fine-tuning of tip-link tension, thus hearing sensitivity, and contributes to the frequency-resolving power of the cochlea.

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2026-05-27 | OSBPL2 deficiency impaired autophagy and induced apoptosis in auditory cells via AMPK-TFEB signalling pathway.

OSBPL2 was identified as a causal gene responsible for autosomal dominant non-syndromic hearing loss. Previous study revealed that OSBPL2-mediated AMPK signalling was crucial for cholesterol-homeostasis in inner ear. AMPK is the downstream component of a kinase cascade as the key regulator of autophagy, metabolism, cell growth and apoptosis, etc. In addition, OSBPL2 deficiency could lead to autophagy impairment in auditory cells, indicating the potential role of OSBPL2-mediated AMPK signalling in autophagy. In the present study, autophagy function was characterized in hair cells (HCs) of Osbpl2-knockout mice and in Osbpl2-knockdown HEI-OC1 cells. The results showed that OSBPL2 deficiency impaired autophagy by inhibiting AMPK-TFEB signalling, resulting in aberrant accumulation of lipid droplets and apoptosis in auditory cells, which could be partially reversed by trehalose treatment. This study revealed the implications of OSBPL2 for autophagy in auditory cell and contributed to elucidating the pathogenesis of OSBPL2 mutations in hearing loss.

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