Inner ear hair cells as mechanoreceptors are extremely important for hearing. Defects in hair cells are a major cause of deafness. Induced pluripotent stem cells (iPSCs) are promising for regenerating inner ear hair cells and treating hearing loss. Here, we investigated migration, differentiation, and synaptic connections of transplanted otic epithelial progenitors (OEPs) derived from human iPSCs in mouse cochlea. Human urinary cells isolated from a healthy donor were reprogramed to form iPSCs that were induced to differentiate into OEPs and hair cell-like cells. Immunocytochemistry, electrophysiological examination, and scanning electron microscopy were used to examine characteristics of induced hair cell-like cells. OEP-derived hair cell-like cells were cocultured with spiral ganglion neurons (SGNs), and the markers of synaptic connections were detected using immunocytochemistry and transmission electron microscope. In vivo, OEPs derived from iPSCs were transplanted into the cochlea of mice by injection through the round window. Migration, differentiation, and synaptic connections of transplanted cells were also examined by thin cochlear sectioning and immunohistochemistry. The induced hair cell-like cells displayed typical morphological characteristics and electrophysiological properties specific to inner hair cells. In vitro, OEP-derived hair cell-like cells formed synaptic connections with SGNs in coculture. In vivo, some of the transplanted cells migrated to the site of the resident hair cells in the organ of Corti, differentiated into hair cell-like cells, and formed synaptic connections with native SGNs. We conclude that the transplantation of OEPs is feasible for the regeneration of hair cells. These results present a substantial reference for a cell-based therapy for the loss of hair cells.

The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity (P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group (P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides (P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.

Optimization of nanofiber surface properties can lead to enhanced tissue regeneration outcomes in the context of bone tissue engineering. Herein, we developed a facile strategy to decorate elctrospun nanofibers using extracellular matrix (ECM) in order to improve their performance for bone tissue engineering. Electrospun PLLA nanofibers (PLLA NF) were seeded with MC3T3-E1 cells and allowed to grow for two weeks in order to harvest a layer of ECM on nanofiber surface. After decellularization, we found that ECM was successfully preserved on nanofiber surface while maintaining the nanostructure of electrospun fibers. ECM decorated on PLLA NF is biologically active, as evidenced by its ability to enhance mouse bone marrow stromal cells (mBMSCs) adhesion, support cell proliferation and promote early stage osteogenic differentiation of mBMSCs. Compared to PLLA NF without ECM, mBMSCs grown on ECM/PLLA NF exhibited a healthier morphology, faster proliferation profile, and more robust osteogenic differentiation. Therefore, our study suggests that ECM decoration on electrospun nanofibers could serve as an efficient approach to improving their performance for bone tissue engineering.

Hypertrophic cardiomyopathy (HCM) is the most prominent cause of sudden cardiac death in young people. Due to heterogeneity in clinical manifestations, conventional HCM drugs have limitations for mitochondrial hypertrophic cardiomyopathy. Discovering more effective compounds would be of substantial benefit for further elucidating the pathogenic mechanisms of HCM and treating patients with this condition. We previously reported the MT-RNR2 variant associated with HCM that results in mitochondrial dysfunction. Here, we screened a mitochondria-associated compound library by quantifying the mitochondrial membrane potential of HCM cybrids and the survival rate of HCM-induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) in galactose media. 1-Deoxynojirimycin (DNJ) was identified to rescue mitochondrial function by targeting optic atrophy protein 1 (OPA1) to promote its oligomerization, leading to reconstruction of the mitochondrial cristae. DNJ treatment further recovered the physiological properties of HCM iPSC-CMs by improving Ca²⁺ homeostasis and electrophysiological properties. An angiotensin II-induced cardiac hypertrophy mouse model further verified the efficacy of DNJ in promoting cardiac mitochondrial function and alleviating cardiac hypertrophy in vivo. These results demonstrated that DNJ could be a potential mitochondrial rescue agent for mitochondrial hypertrophic cardiomyopathy. Our findings will help elucidate the mechanism of HCM and provide a potential therapeutic strategy.

Mutations in the mitochondrial tRNAs have been reported to be the important cause of hearing loss. However, only a few cases have been identified thus far and the prevalence of mitochondrial tRNA mutations in hearing-impaired patients remain unclear. Here we performed the mutational analysis of 22 mitochondrial tRNA genes in a large cohort of 887 Han Chinese subjects with hearing loss by Sanger sequencing. The systemic evaluation of putative pathogenic variants was further carried out by frequency in controls (<1%), phylogenetic analysis, structural analysisandfunctionalprediction. As a result, a total of 147 variants on 22 tRNA genes were identified. Among these, 39 tRNA mutations (10 pathogenic and 29 likely pathogenic) which absent or present <1% in 773 Chinese controls, localized at highly conserved nucleotides, or changed the modified nucleotides, could have potential structural alterations and functional significance, thereby considered to be deafness-associated mutations. Furthermore, 44 subjects carried one of these 39 pathogenic/likely pathogenic tRNA mutations with a total prevalence of 4.96%. However, the phenotypic variability and incomplete penetrance of hearing loss in pedigrees carrying these tRNA mutations indicate the involvement of modifier factors, such as nuclear encoded genes associated with mitochondrion biogenesis, mitochondrial haplotypes, epigenetic and environmental factors. Thus, our data provide the evidence that mitochondrial tRNA mutations are the important causes of hearing loss among Chinese population. These findings further increase our knowledge on the clinical relevance of tRNA mutations in the mitochondrial genome, and should be helpful to elucidate the pathogenesis of maternal hearing loss.