Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis.

Background: Cisplatin (CIS) is widely used to treat various cancers but can cause ototoxicity and sensory hair cell loss in the inner ear. Copper induces an excessive production of reactive oxygen species (ROS) in hair cells, leading to the development of various antioxidants. Methods and results: This study aimed to evaluate the potential antioxidant properties of curcumin (CUR) in the inner ear organ of corti-1 cells (OC1) and animal models (zebrafish and guinea pigs). Graphene oxide quantum dots (GOQDs) enabled CUR to penetrate the round window membrane (RWM) and maintain the concentration in the perilymph after inner ear administration. The results showed that CUR/GOQDs had favorable biocompatibility and strongly affected ROS generation induced by CIS in OC1 cells. DCFHDA Green staining demonstrated that CUR/GOQDs successfully reversed the decrease in mitochondrial membrane potential induced by CIS in vitro and rescued cells from early cuproptosis, which was confirmed by FDX1 staining. Additionally, the experiment found that CUR decreased the expression of cuproptosis proteins (FDX1, LIAS, and LIPT1) and increased the expression of the Bcl-2 protein. Conclusion: The results demonstrate that CUR/GOQDs is a promising therapeutic agent that can prevent CIS-induced ototoxicity by blocking the cuproptosis signal pathway.

Segregation of competing speech in adults and children with normal hearing and in children with cochlear implants.

Children with normal hearing (CNH) have greater difficulty segregating competing speech than do adults with normal hearing (ANH). Children with cochlear implants (CCI) have greater difficulty segregating competing speech than do CNH. In the present study, speech reception thresholds (SRTs) in competing speech were measured in Chinese Mandarin-speaking ANH, CNH, and CCIs. Target sentences were produced by a male Mandarin-speaking talker. Maskers were time-forward or -reversed sentences produced by a native Mandarin-speaking male (different from the target) or female or a non-native English-speaking male. The SRTs were lowest (best) for the ANH group, followed by the CNH and CCI groups. The masking release (MR) was comparable between the ANH and CNH group, but much poorer in the CCI group. The temporal properties differed between the native and non-native maskers and between forward and reversed speech. The temporal properties of the maskers were significantly associated with the SRTs for the CCI and CNH groups but not for the ANH group. Whereas the temporal properties of the maskers were significantly associated with the MR for all three groups, the association was stronger for the CCI and CNH groups than for the ANH group.

Effects of Monaural Asymmetry and Target-Masker Similarity on Binaural Advantage in Children and Adults With Normal Hearing.

Purpose For colocated targets and maskers, binaural listening typically offers a small but significant advantage over monaural listening. This study investigated how monaural asymmetry and target-masker similarity may limit binaural advantage in adults and children. Method Ten Mandarin-speaking Chinese adults (aged 22-27 years) and 12 children (aged 7-14 years) with normal hearing participated in the study. Monaural and binaural speech recognition thresholds (SRTs) were adaptively measured for colocated competing speech. The target-masker sex was the same or different. Performance was measured using headphones for three listening conditions: left ear, right ear, and both ears. Binaural advantage was calculated relative to the poorer or better ear. Results Mean SRTs were significantly lower for adults than children. When the target-masker sex was the same, SRTs were significantly lower with the better ear than with the poorer ear or both ears (p < .05). When the target-masker sex was different, SRTs were significantly lower with the better ear or both ears than with the poorer ear (p < .05). Children and adults similarly benefitted from target-masker sex differences. Substantial monaural asymmetry was observed, but the effects of asymmetry on binaural advantage were similar between adults and children. Monaural asymmetry was significantly correlated with binaural advantage relative to the poorer ear (p = .004), but not to the better ear (p = .056). Conclusions Binaural listening may offer little advantage (or even a disadvantage) over monaural listening with the better ear, especially when competing talkers have similar vocal characteristics. Monaural asymmetry appears to limit binaural advantage in listeners with normal hearing, similar to observations in listeners with hearing impairment. While language development may limit perception of competing speech, it does not appear to limit the effects of monaural asymmetry or target-masker sex on binaural advantage.

Effect of neuregulin-1 on the auditory cortex in adult C57BL/6J mice.

OBJECTIVES: We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice. MATERIALS AND METHODS: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6-8 weeks and 42-44 weeks). Three groups of 42-44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry. RESULTS: Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42-44 weeks was lower compared with 6-8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group. CONCLUSION: We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.

The development and validation of the Closed-set Mandarin Sentence (CMS) test.

Matrix-styled sentence tests offer a closed-set paradigm that may be useful when evaluating speech intelligibility. Ideally, sentence test materials should reflect the distribution of phonemes within the target language. We developed and validated the Closed-set Mandarin Sentence (CMS) test to assess Mandarin speech intelligibility in noise. CMS test materials were selected to be familiar words and to represent the natural distribution of vowels, consonants, and lexical tones found in Mandarin Chinese. Ten key words in each of five categories (Name, Verb, Number, Color, and Fruit) were produced by a native Mandarin talker, resulting in a total of 50 words that could be combined to produce 100,000 unique sentences. Normative data were collected in 10 normal-hearing, adult Mandarin-speaking Chinese listeners using a closed-set test paradigm. Two test runs were conducted for each subject, and 20 sentences per run were randomly generated while ensuring that each word was presented only twice in each run. First, the level of the words in each category were adjusted to produce equal intelligibility in noise. Test-retest reliability for word-in-sentence recognition was excellent according to Cronbach's alpha (0.952). After the category level adjustments, speech reception thresholds (SRTs) for sentences in noise, defined as the signal-to-noise ratio (SNR) that produced 50% correct whole sentence recognition, were adaptively measured by adjusting the SNR according to the correctness of response. The mean SRT was -7.9 (SE=0.41) and -8.1 (SE=0.34) dB for runs 1 and 2, respectively. The mean standard deviation across runs was 0.93 dB, and paired t-tests showed no significant difference between runs 1 and 2 (p=0.74) despite random sentences being generated for each run and each subject. The results suggest that the CMS provides large stimulus set with which to repeatedly and reliably measure Mandarin-speaking listeners' speech understanding in noise using a closed-set paradigm.

Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers.

The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6-8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected.

Effect of T-type calcium channel blockers on spiral ganglion neurons of aged C57BL/6J mice.

To explore the expression levels of T-type calcium channel receptors in spiral ganglion neurons of C57BL/6J mice and the effect of T-type calcium channel blockers on the spiral ganglion neurons of 42-44-W C57BL/6J mice. We first quantified the subunits of T-type calcium channel blockers in the spiral ganglion neurons of C57BL/6J mice in three groups (6-8 W, 24-26 W, 42-44 W) according to age via RT-PCR. Next, we administered three drugs (zonisamide, felodipine, saline) to the 42-44-W C57BL/6J mice by gavage for four weeks. We observed the changes in the hearing threshold of 42-44-W C57BL/6J mice after treatment. Meanwhile, we measured the expression of calcium-binding proteins of spiral ganglion neurons after treatment. Our results showed that three receptors were expressed in the spiral ganglion neurons of C57BL/6J mice. The expression level of α1H was stronger than that of α1G and α1I. The expression levels of three receptors especially for α1G and α1H significantly decreased with age. The hearing threshold at 24 kHz was significantly decreased after zonisamide administration. No significant difference in the expression level of calbindin in spiral ganglion neurons was noted. Interestingly, the expression level of calmodulin in spiral ganglion neurons was lower in the zonisamide-treated groups than in the felodipine- and saline-treated group. We concluded that the administration of T-type calcium channel blocker for four consecutive weeks can improve the hearing by ameliorating calcium overload on spiral ganglion neurons of 42-44-W C57BL/6J mice.

The relationship between age-related hearing loss and synaptic changes in the hippocampus of C57BL/6J mice.

To explore the relationship between age-related hearing loss (presbycusis) and synaptic degeneration in the hippocampal CA3 region of C57BL/6J mice, we investigated both cognitive performance and synaptic changes within the hippocampus of C57BL/6J mice from three age groups of 6-8, 24-26, and 42-44 weeks; CBA/CaJ mice served as controls. The auditory brainstem response was used as a measure of hearing threshold, and cognitive behavior was evaluated using the Morris water maze. The ultrastructure of synapses was observed with transmission electron microscopy, and the quantity and distribution of the synaptic markers synaptophysin and PSD-95 were observed with immunohistochemistry. The hearing threshold of C57BL/6J mice was significantly higher at 24-26 weeks than at 6-8 weeks, and hearing loss was profound at 42-44 weeks. This was accompanied by progressive degeneration of synapses within the auditory cortex. In contrast, the hearing threshold of CBA/CaJ mice was relatively unchanged at 24-26 weeks of age, and these mice developed only mild hearing loss at 42-44 weeks of age. Interestingly, C57BL/6J, but not CBA/CaJ mice clearly exhibited both decreased performance in the Morris water maze and degeneration of synapses within the hippocampus. We therefore conclude that age-related hearing loss is accompanied by the degeneration of synapses in the hippocampal CA3 region of C57BL/6J mice.

[Correlation between age-related hearing loss and impairment of cognition in C57BL/6J mice].

OBJECTIVE: To explore the correlation of age-related hearing loss and cognition impairment in C57BL/6J mice by observing hearing, cognitive function and synapses. METHODS: C57BL/6J and CBA/CaJ mice were divided into 3 groups. The hearing and cognitive functions of each animal was tested. And the ultrastructure of synapses was simultaneously observed for C57BL/6J mice. RESULTS: The 24-26-week-old C57BL/6J mice developed moderate hearing loss while the 42-44-week-old C57BL/6J counterparts suffered profound hearing loss. Whereas excellent hearing was maintained in 3 groups of CBA/CaJ mice within 44 weeks. During cognitive test, the performance of 42-44-week-old C57BL/6J mice was significantly worse than CBA/CaJ mice. During probe test, the number of platform crossing of 42-44-week-old C57BL/6J mice was smaller than that of CBA/CaJ mice (0.5 ± 0.6 vs 1.9 ± 1.6; P < 0.05). The 42-44-week-old C57BL/6J mice had a wider synaptic cleft and a thinner postsynaptic density than the 24-26-week-old C57BL/6J counterparts [synaptic cleft: (19.4 ± 0.5) nm vs (11.9 ± 0.7) nm; postsynaptic density: (15.2 ± 0.5) nm vs (27.8 ± 2.0) nm; both P < 0.05]. Furthermore, the degeneration of synapses in hippocampus CA3 area of C57BL/6J mice were clearly observed at 42 - 44 weeks of age, but not seen in CBA/CaJ mice. CONCLUSION: Age-related hearing loss might impact on the cognition impairment in C57BL/6J mice.

Use of the loud sound stimulation test in diagnosis of semicircular canal dehiscence syndrome.

Semicircular canal dehiscence (SCD) syndrome is rare, and its diagnosis is a significant challenge in clinical practice. Our aim was to explore application of the loud sound stimulation test for diagnosing SCD syndrome. Eight cases of superior semicircular canal dehiscence (SSCD), among them two patients had bilateral dehiscences and one case of lateral semicircular canal dehiscence (LSCD). A total of 11 dehiscences were studied retrospectively. Loud sounds (pure tones, 100 dB, 110 dB nHL) at frequencies of 500, 1,000, and 2,000 Hz were used to stimulate both ears for 5 s. A temporal bone computed tomography (CT) scan with semicircular canal reconstruction was performed in all patients. Vertigo was present in seven of nine cases following loud sound stimulation. In addition, the patient with LSCD demonstrated horizontal eye movement following loud sound stimulation, whereas six patients with SSCD showed rotational eye movement. Among them, two patients with bilateral superior canal dehiscence showed a positive response to the loud sound stimulation in only one ear. The diagnoses of all patients were confirmed with a high-resolution temporal bone CT with corresponding multi-planar reconstruction of the affected semicircular canals with various size dehiscences. We conclude that the characteristic eye movement following loud sound stimulation is valuable for diagnosing SCD syndrome. In addition, the loud sound stimulation test has unique advantages, especially for confirming the affected ear and the corresponding semicircular canal.