Roles of supporting cells in the maintenance and regeneration of the damaged inner ear: A literature review.

The inner ear sensory epithelium consists of two major types of cells: hair cells (HCs) and supporting cells (SCs). Critical functions of HCs in the perception of mechanical stimulation and mechanosensory transduction have long been elucidated. SCs are indispensable components of the sensory epithelia, and they maintain the structural integrity and ionic environment of the inner ear.

Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14.

Co-transduction of dual-adeno-associated virus vectors in the neonatal and adult mouse utricles.

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues.

Epithelial-Mesenchymal Transition Participates in the Formation of Vestibular Flat Epithelium.

The vestibular sensory epithelium of humans and mice may degenerate into a layer of flat cells, known as flat epithelium (FE), after a severe lesion. However, the pathogenesis of vestibular FE remains unclear. To determine whether the epithelial-mesenchymal transition (EMT) participates in the formation of vestibular FE, we used a well-established mouse model in which FE was induced in the utricle by an injection of streptomycin into the inner ear.

Diploic vein as a newly treatable cause of pulsatile tinnitus: A case report.

Background: Pulsatile tinnitus (PT) is an annoying sound that can be eliminated with targeted treatment of the cause. However, the causes of PT have not been fully elucidated.

Case Summary: A 38-year-old woman with right-sided objective PT underwent preoperative computed tomography arteriography and venography (CTA/V).

[Distribution of exogenous nitrogen fractions and their fate in moss-dominated biological soil crusts].

Nitrogen (N) labeled with N was evenly added into plots of moss-dominated biological soil crusts (BSCs) and bare soil on the Chinese Loess Plateau. After that, the surface BSCs and bare soil samples were continuously collected within 1-30 days. The N content of each N fraction in soil, microorganisms, and mosses was measured for each sample.

AAV8-mediated Atoh1 overexpression induces dose-dependent regeneration of vestibular hair cells in adult mice.

Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration.

[Distribution characteristics of exogenous carbon in different carbon fractions in biocrusts-covered soil].

The distribution characteristics of exogenous carbon (C) in the C fractions of biocrusts-covered soil are critical for understanding the geochemical cycling of C with biocrusts in drylands. A C pulse labeling experiment was conducted for moss-dominated biocrusts-covered soil and bare soil on the Loess Plateau of China with semiarid climate, with the content of C in different C fractions being continuously measured to determine the biocrust effects on the distribution of exogenous C in each C fraction. Our results showed that, 1) the C abundance of each C fraction in the biocrusts-covered soil was steadily changed with time, due to the relatively low rate of nutrient cycling in the biocrusts-covered soil and also to the relatively low biomass of moss in the biocrusts-covered soil as compared with vascular plants.

Suggestion of a Modified Classification for Congenital Middle Ear Cholesteatoma: Based on the Clinical Characteristics and Staging of Fifty-Seven Patients.

To explore more refined classification methods of congenital middle ear cholesteatoma (CMEC) based on two existing staging systems. This study involved a retrospective data review of 57 patients (61 ears involved) with CMEC requiring the surgical treatment. Patients were classified into different stages according to Nelson, Potsic, and Modified Nelson staging system.

Cellular origin and response of flat epithelium in the vestibular end organs of mice to Atoh1 overexpression.

A flat epithelium (FE) may be found in the vestibular end organs of humans and mice with vestibular dysfunction. However, the pathogenesis of FE is unclear and inducing hair cell (HC) regeneration is challenging, as both HCs and supporting cells (SCs) in vestibular FE are damaged. To determine the cellular origin of vestibular FE and examine its response to Atoh1 overexpression, we fate-mapped vestibular epithelial cells in three transgenic mouse lines (vGlut3-iCreER:Rosa26, GLAST-CreER:Rosa26, and Plp-CreER:Rosa26) after inducing a lesion by administering a high dose of streptomycin.

Synaptopathy as a Mechanism for Age-Related Vestibular Dysfunction in Mice.

Age-related decline of inner ear function contributes to both hearing loss and balance disorders, which lead to impaired quality of life and falls that can result in injury and even death. The cellular mechanisms responsible for the ear's functional decline have been controversial, but hair cell loss has been considered the key cause for a long time. However, recent studies showed that in the cochlea, loss of inner hair cell (IHC) synapses precedes hair cell or neuronal loss, and this synaptopathy is an early step in the functional decline.

Auditory metabolomics, an approach to identify acute molecular effects of noise trauma.

Animal-based studies have provided important insights into the structural and functional consequences of noise exposure on the cochlea. Yet, less is known about the molecular mechanisms by which noise induces cochlear damage, particularly at relatively low exposure levels. While there is ample evidence that noise exposure leads to changes in inner ear metabolism, the specific effects of noise exposure on the cochlear metabolome are poorly understood.

Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice.

Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) has been shown to be a useful approach to local drug delivery into the inner ear. The goal of this article is to describe, in detail, the surgical techniques involved in canalostomy in both adult and neonatal mice.

Enantioselective Nazarov cyclization of indole enones cooperatively catalyzed by Lewis acids and chiral Brønsted acids.

Enantioselective control of the chirality of a tertiary α-carbon in the products of a Nazarov cyclization of enones is challenging because the reaction involves an enantioselective proton transfer process. We herein report the use of cooperative catalysis using Lewis acids and chiral Brønsted acids to control the stereochemistry of the tertiary α-carbon in the products of this reaction. Specifically, with ZnCl and a chiral spiro phosphoric acid as catalysts, we realized the first enantioselective construction of cyclopenta[]indoles with chiral tertiary α-carbons Nazarov cyclization of indole enone substrates with only one coordinating site.

Severe streptomycin ototoxicity in the mouse utricle leads to a flat epithelium but the peripheral neural degeneration is delayed.

The damaged vestibular sensory epithelium of mammals has a limited capacity for spontaneous hair cell regeneration, which largely depends on the transdifferentiation of surviving supporting cells. Little is known about the response of vestibular supporting cells to a severe insult. In the present study, we evaluated the impact of a severe ototoxic insult on the histology of utricular supporting cells and the changes in innervation that ensued.

The histone deacetylase inhibitor sodium butyrate protects against noise-induced hearing loss in Guinea pigs.

Noise-induced hearing loss (NIHL) severely impacts the quality of life of affected individuals. Oxidative stress resulting from noise exposure is a significant cause of NIHL. Although histone deacetylase (HDAC) inhibitors were shown to protect against NIHL, the underlying mechanism remains unclear, and it is not known how they act on noise-induced oxidative stress.

Cochleovestibular gene transfer in neonatal mice by canalostomy.

Impairments of the inner ear result in sensorineural hearing loss and vestibular dysfunction in humans. A large proportion of these disorders are congenital, and involve both auditory and vestibular systems. Therefore, genetic interventions to correct deficits must be administered during early developmental stages.

Highly Enantioselective Copper- and Iron-Catalyzed Intramolecular Cyclopropanation of Indoles.

We report the first intramolecular enantioselective cyclopropanation of indoles, which was accomplished in good to high yield (up to 94%) with excellent enantioselectivity (up to >99.9% ee) by using copper or iron complexes of chiral spiro bisoxazolines as catalysts. This reaction is a straightforward, efficient method for constructing polycyclic compounds with an all-carbon quaternary stereogenic center at the 3-position of the indole skeleton, a core structure shared by numerous natural products and bioactive compounds.

Sigmoid Sinus Wall Reconstruction for Pulsatile Tinnitus Caused by Sigmoid Sinus Wall Dehiscence: A Single-Center Experience.

Objective: To evaluate clinical characteristics and present surgical outcomes of PT caused by sigmoid sinus wall dehiscence (SSWD).

Methods: This study retrospectively reviewed 34 patients with PT who were diagnosed with SSWD in our institution between December 2008 and July 2013. Among them, 27 patients underwent sigmoid sinus wall reconstruction (surgery group) and 7 patients refused surgery (non-surgery group).

Enantioselective Synthesis of Spirobarbiturate-Cyclohexenes through Phosphine-Catalyzed Asymmetric [4 + 2] Annulation of Barbiturate-Derived Alkenes with Allenoates.

An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated.

E2F1-CDK1 pathway activation in kanamycin-induced spiral ganglion cell apoptosis and the protective effect of CR8.

Cochlear hair cell loss results in the secondary loss of spiral ganglion cells (SGCs). The death of these SGCs is due to apoptosis. The E2F1-cyclin dependent kinase 1 (CDK1) pathway is believed to represent an important mechanism of neuronal cell death.

Chiral phosphine-catalyzed tunable cycloaddition reactions of allenoates with benzofuranone-derived olefins for a highly regio-, diastereo- and enantioselective synthesis of spiro-benzofuranones.

The first regioselective catalytic asymmetric [3 + 2] cycloaddition of benzofuranone-derived olefins with allenoates and substituted allenoates has been developed in the presence of ()-SITCP, affording different functionalized 3-spirocyclopentene benzofuran-2-ones in good yields with high enantioselectivities under mild conditions. The substrate scope has also been examined. The regioselective outcomes for this phosphine-catalyzed [3 + 2] cycloaddition reaction can be rationalized using DFT calculations.

Transmastoid approach for resurfacing the superior semicircular canal dehiscence with a dumpling structure.

Background: Superior semicircular canal dehiscence (SSCD) is gradually recognized by otologists in recent years. The patients with SSCD have a syndrome comprising a series of vestibular symptoms and hearing function disorders which can be cured by the operation. In this study, we evaluated the characteristics of patients with SSCD and determined the effectiveness of treating this syndrome by resurfacing the canal via the transmastoid approach using a dumpling structure.