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The inner ear of mammals includes the cochlea and vestibule, which house specialized hair cells that are responsible for hearing and balance, respectively. While cochlear hair cells fail to regenerate following damage, those of the utricle, which is part of the vestibular apparatus, show partial regeneration. In birds, the macula lagena, a unique ear structure in this clade, has the ability to regenerate hair cells similarly to the utricle. Many studies have sought to explain regeneration in terms of evolution and species differences. However, it remains unclear what the cellular and molecular basis is behind the differences in inner ear structures and between avians and mammals. In the present study, we first investigated the anatomical structures of the inner ear of both chickens and rodents. We then performed RNA sequencing (RNA‐Seq) and made cross‐species analyses of the expression of homologous genes obtained from the inner ear tissue from both chickens and mice. Finally, we focused on the lagena, the basilar papilla, and the utricle in chickens and identified differentially expressed genes between tissues and determined the expression patterns of genes involved in inner ear structure formation by single‐cell RNA sequencing and bulk RNA‐Seq. We concluded that the cellular and molecular composition of the lagena is more similar to that of the utricle than the cochlea. Taken together, our study provides a valuable resource for the study of inner ear evolution and development. [ABSTRACT FROM AUTHOR]

This paper proposes a nonelliptic extended English teaching ability evaluation algorithm based on an adaptive random matrix model. The algorithm models a nonelliptical expansion target as multiple elliptical sub-objectives, and the expansion state of each sub-target is described by an inverse Wishart distribution. The new method is combined to improve the robustness problem caused by the initialization after the algorithm expansion. This research uses the smart teacher education platform to conduct research and analysis on the evaluation of teaching practice ability of intern normal students. From the perspective of data evaluation, we explore the influence of normal students' curriculum training on the teaching practice ability of normal students. By analyzing the correlation between normal students' course grades and practice grades, this paper explores the influence of normal students' prepractice training on normal students' teaching practice ability. This paper explores the influence of the training of normal students' course learning on the teaching practice ability of normal students. The results show that the learning level of normal students' professional courses has a significant impact on the development of normal students' practice performance and teaching practice ability; the impact of normal students' pedagogical course level on normal students' practice performance and teaching practice ability is relatively low. [ABSTRACT FROM AUTHOR]

Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and β-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or β-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear. Materials and Methods: Postnatal day 1 wild‐type or neomycin‐damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high‐throughput RNA‐sequencing was used to measure gene expression levels. Results: We found that DBZ promoted SC proliferation and HC regeneration in a dose‐dependent manner in both normal and damaged cochleae. In addition, most of the newly regenerated HCs induced by DBZ had visible and relatively mature stereocilia bundle structures. Finally, RNA sequencing detected the differentially expressed genes between DBZ treatment and controls, and interaction networks were constructed for the most highly differentially expressed genes. Conclusions: Our study demonstrates that DBZ can significantly promote SC proliferation and increase the number of mitotically regenerated HCs with relatively mature stereocilia bundles in the neonatal mouse cochlea by inhibiting Notch signalling and activating Wnt signalling, suggesting the DBZ might be a new therapeutic target for stimulating HC regeneration. [ABSTRACT FROM AUTHOR]

Aim: Cinchonine (CN) and its isomer cinchonidine (CD), two of the common cinchona alkaloids, are wildly used as antimalarial drugs. However, the effects of CN and CD on the auditory system are unknown. Methods: Molecular docking and molecular dynamics (MD) simulation were used for predicting effective drugs. The CCK‐8 assay was conducted for assessing cell viability in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells. MitoSox Red staining revealed reactive oxygen species (ROS) amounts. TMRM staining was used to assess the mitochondrial membrane potential (ΔΨm). Immunofluorescence staining of myosin 7a was used to examine hair cells (HCs) in cisplatin‐treated neonatal mouse cochlear explants, while TUJ‐1 immunostaining was used for the detection of spiral ganglion neurons (SGNs). Cleaved caspase‐3 and TUNEL immunostaining were utilized for apoptosis assessment. Immunoblot was carried out to detect PI3K‐AKT signaling effectors. Results: Pretreatment with CN or CD significantly increased cell viability and reduced mitochondrial dysfunction and ROS accumulation in cisplatin‐treated HEI‐OC1 cells. Immunofluorescent staining of cochlear explants showed that CN and CD attenuated cisplatin‐induced damage to SGNs and HCs. Immunoblot revealed that CN and CD downregulated the expression of cleaved caspase‐3 and activated PI3K‐AKT signaling in cisplatin‐injured HEI‐OC1 cells. Conclusion: CD and CN can reduce ototoxicity caused by cisplatin and might help treat cisplatin‐associated hearing loss. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is one of the most common malignant tumors derived from pluripotent cells of the neural crest. Nodal is an important embryonic morphogen which can re‐express in cancer cells. The roles of Nodal in the progression of NB are not illustrated. Our present study reveals that Nodal is upregulated in NB cells and tissues. Targeted inhibition of Nodal can suppress the in vitro migration and invasion of NB cells while increase its chemo‐sensitivity to doxorubicin (Dox) treatment. Nodal positively regulates the expression of Zeb1, one well‐known transcription factors of epithelial to mesenchymal transition (EMT) of cancer cells. Knockdown of Zeb1 can attenuate Nodal‐induced malignancy of NB cells. Mechanistically, Nodal increases the protein stability of Zeb1 while has no effect on its mRNA expression. It is due to that Nodal can increase the expression of Ataxia telangiectasia mutated kinase (ATM), which can phosphorylate and stabilize Zeb1 in cancer cells. Collectively, our data revealed that Nodal can increase the malignancy of NB cells via increasing the expression of Zeb1. It suggests that targeted inhibition of Nodal might be a potential therapy approach for NB treatment. © 2019 BioFactors, 45(3):355–363, 2019 [ABSTRACT FROM AUTHOR]

Abstract: The pricing mechanism in a deregulated electricity market is consistently a critical issue to improve market operations. Along with the development of electricity market, large consumers may purchase electric power from generators directly. In this paper, with an effort to introduce McAfee’s second-price sealed auction mechanism into multi-unit electric power transaction between competitive generators and large consumers, an auction model is developed to decide electric power price between competitive generators and large consumers based on the inclusion of the transaction cost and power transmission cost in a wholesale electricity market. After the description of pricing rules in the deregulated power market, auction rules and transaction rules are discussed. In particular, auction rules can increase the probability that generators providing a large number of supply and large consumers with high demand win the auction. On the other hand, transaction rules can optimize the whole transmission cost and transaction cost under market equilibrium, and the whole system is dispatched to maximize social welfare. A numerical example with eight suppliers and eight large consumers is provided to illustrate the essential features of this method. [Copyright &y& Elsevier]

Objective: We sought to determine the biocompatibility of electrospun regenerated silk fibroin (RSF) mats with inner ear progenitors, especially their effect on the differentiation of inner ear progenitors into hair cells. Methods: Neonatal mouse cochleae (n = 20) were collected and digested and allowed to form spheres over several days. Cells digested from the spheres were then seeded onto aligned or random RSF mats, with laminin-coated coverslips serving as controls. The inner ear progenitor cell mortality was examined by TUNEL labeling, and the adhesion of cells to the RSF mats or coverslip was determined by scanning electron microscopy. Finally, the number of hair cells that differentiated from inner ear progenitors was determined by Myosin7a expression. Unpaired Student's t-tests and one-way ANOVA followed by a Dunnett's multiple comparisons test were used in this study (p < 0.05). Results: After 5 days of culture, the inner ear progenitors had good adhesion to both the aligned and random RSF mats and there was no significant difference in TUNEL+ cells between the mats compared to the coverslip (p > 0.05). After 7 days of in vitro differentiation culture, the percentage of differentiated hair cells on the control, aligned, and random RSF mats was 2.5 ± 0.5%, 2.7 ± 0.4%, and 2.4 ± 0.2%, respectively, and there was no significant difference between Myosin7a+ cells on either RSF mat compared to controls (p > 0.05). Conclusion: The aligned and random RSF mats had excellent biocompatibility with inner ear progenitors and helped the inner ear progenitors maintain their stemness. Our results thus indicate that RSF mats represent a useful scaffold for the development of new strategies for inner ear tissue engineering research. [ABSTRACT FROM AUTHOR]

The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3 ′ -iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Axin2 and β-catenin after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a primary clinical challenge for the management of small cell lung cancer. Additionally, transcriptional regulation by super enhancer (SE) has an important role in tumor evolution. The functions of SEs, a key class of noncoding DNA cis-regulatory elements, have been the subject of many recent studies in the field of cancer research. Methods: In this study, using chromatin immunoprecipitation-sequencing and RNA-sequencing (RNA-seq), we aimed to identify SEs associated with chemoresistance from H69AR cells. Through integrated bioinformatics analysis of the MEME chip, we predicted the master transcriptional factors (TFs) binding to SE sites and verified the relationships between TFs of SEs and drug resistance by RNA interference, cell counting kit 8 assays, quantitative real-time reverse transcription polymerase chain reaction. Results: In total, 108 SEs were screened from H69AR cells. When combining this analysis with RNA-seq data, 45 SEs were suggested to be closely related to drug resistance. Then, 12 master TFs were predicted to localize to regions of those SEs. Subsequently, we selected forkhead box P1 (FOXP1), interferon regulatory factor 1 (IRF1), and specificity protein 1 (SP1) to authenticate the functional relationships of master TFs with chemoresistance via SEs. Conclusions: We screened out SEs involved with drug resistance and evaluated the functions of FOXP1, IRF1, and SP1 in chemoresistance. Our findings established a large group of SEs associated with drug resistance in small cell lung cancer, revealed the drug resistance mechanisms of SEs, and provided insights into the clinical applications of SEs. [ABSTRACT FROM AUTHOR]