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At the angle of the mouth, spoke‐like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near‐term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near‐term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM‐PM, LAOM‐DAOM, zygomaticus major (ZMM)‐orbicularis oris (OOM), buccinator (BM)‐LAOM, and BM‐PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site. [ABSTRACT FROM AUTHOR]

A novel class of potent Na V 1.7 inhibitors has been discovered. The replacement of diaryl ether in compound I was investigated to enhance mouse Na V 1.7 inhibitory activity, which resulted in the discovery of N -aryl indoles. The introduction of the 3-methyl group is crucial for high Na V 1.7 in vitro potency. The adjustment of lipophilicity led to the discovery of 2e . Compound 2e (DS43260857) demonstrated high in vitro potencies against both human and mouse Na V 1.7 with high selectivity over Na V 1.1, Na V 1.5, and hERG. In vivo evaluations revealed 2e demonstrating potent efficacy in PSL mice with excellent pharmacokinetics., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)