Epigenetic mechanism of RBM15 in affecting cisplatin resistance in laryngeal carcinoma cells by regulating ferroptosis.

Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.

Sensory intelligence for extraction of abstract auditory rules from a speech sound stream in children with cochlear implants.

OBJECTIVE: Sensory intelligence in the brain helps listeners automatically extract abstract auditory rules formed by invariant acoustic features from complex speech sound streams, presumably serving as the neural basis for speech comprehension. However, whether this intelligence is deficient in children with cochlear implants (CIs) remains unclear. METHODS: Mandarin Chinese monosyllables shared a flat lexical tone contour to form an abstract auditory rule but differed in other acoustic features to construct a complex speech sound stream. The abstract rule was occasionally violated by monosyllables with a rising or falling lexical tone. RESULTS: In normal hearing (NH) children, the abstract auditory rule could be extracted, as revealed by a mismatch negativity (MMN) and a late discriminative negativity (LDN). However, the MMN and LDN were only evoked in CI children with good hearing and speech performance. NH children with a higher speech perception or spatial hearing score had a greater MMN. The LDN was attenuated with increasing age in NH children. CONCLUSIONS: The sensory intelligence for extraction of auditory abstract rules, associated with speech perception, is deficient in CI children. This intelligence may gradually develop during childhood and adolescence. SIGNIFICANCE: Deficient sensory intelligence in CI children may aid in understanding poor speech comprehension in complex environments.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Electrically evoked auditory brainstem responses in deaf children with cochlear nerve canal stenosis.

BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Effects of yeast extract supplemented in diet on growth performance, digestibility, intestinal histology, and the antioxidant capacity of the juvenile turbot (Scophthalmus maximus).

An 8-week feeding experiment was conducted on the juvenile turbot (Scophthalmus maximus) to evaluate the influence of yeast extract (YE) supplementation in the diet on growth performance, feed utilization, body composition, nutrient digestibility, intestinal histology, and antioxidant capacity. Four experimental diets were formulated with graded levels of yeast extract 0 (YE0), 1% (YE1), 3% (YE3), and 5% (YE5) and fed to turbots (initial body weight: 4.2 ± 0.1 g) with three replicates per diet and 200 fish in each replicate, respectively. The results showed that turbots fed with diets YE1 and YE3 displayed a significantly higher specific growth rate and protein efficiency rate than those fed with diets YE0 and YE5, while the feed conversion ratios in YE1 and YE3 groups were lower than those in YE0 and YE5. Fish fed with diets YE3 and YE5 showed higher body crude protein contents than those in groups YE0 and YE1. The highest apparent digestibility coefficients for dry matter and crude protein, digestive enzyme activities (trypsin, lipase, and amylase), and the height of the intestinal fold were observed in the YE3 group. YE3 treatment displayed a significantly higher superoxide dismutase (SOD) activity than the YE0 group, while the malondialdehyde (MDA) content in YE1 was significantly lower than those in YE0 and YE5. No significant difference was observed in serum physiological and biochemical parameters among all treatments. Overall, appropriate dietary supplementation of the yeast extract could improve the growth performance, digestibility, and antioxidant capacity of the juvenile turbot, and the recommended yeast extract level in the feed is 2.47%.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Downregulation of KCNMA1 in mice accelerates auditory hair cells senescence via ferroptosis.

KCNMA1 encodes the K+ potassium channel α-subunit that plays a significant role in the auditory system. Our previous studies indicated that KCNMA1 is associated with age-related hearing loss(AHL). However, the detailed mechanism of KCNMA1 involvement in auditory age-related degradation has not been fully clarified. Therefore, we explored the expression of KCNMA1 in the peripheral auditory of 2-month-old and 12-month-old mice by Western blotting and immunofluorescence. The results of animal experiments showed that KCNMA1 expression was decreased in 12-month-old mice compared with 2-month-old mice, whereas the ferroptosis level was increased. To verify the role of KCNMA1 in AHL, we downregulated KCNMA1 in HEI-OC1 cells by transfecting shRNA. After downregulation, the ferroptosis level was increased and the aging process was accelerated. Furthermore, the aging process was affected by the expression of ferroptosis. In conclusion, these results revealed that KCNMA1 is associated with the aging process in auditory hair cells by regulating ferroptosis, which deepens our understanding of age-related hearing loss.

Incidence and characteristics of otitis media with effusion in adults before, during, and after the COVID-19 pandemic.

OBJECTIVES: To investigate the incidence and characteristics of adult otitis media with effusion (OME) before, during, and after the COVID-19 pandemic. METHODS: A retrospective descriptive study was conducted. The incidence, age, sex, affected ear side, time of OME onset according to COVID-19 and days of improvement after conservative treatment were determined to assess the clinical features of adult OME in different periods of the COVID-19 pandemic. RESULTS: The incidence of adult OME during these periods was 3.17%, 2.30%, 6.18%, and 3.68%, respectively. Unilateral ear involvement and male sex were more common. The onset of adult OME occurred 7.80 ± 3.97 days after COVID-19 diagnosis, and improvement was observed after 12.24 ± 5.08 days of conservative treatment. Patients in the post-pandemic period were older than those in the non-pandemic period. CONCLUSION: The incidence of adult OME in China showed a tendency to decrease, recover, and decrease again following the COVID-19 outbreak. Pandemic prevention and control measures have had a certain impact on reducing the incidence, but the elderly are more prone to this disease.

Stem cells as potential therapeutics for hearing loss.

Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy's technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.

[Evaluation of the efficacy of endoscopic posterior nasal neurectomy with pharyngeal neurectomy of allergic rhinitis combined with chronic rhinosinusitis with nasal polyps].

Objective:To investigate the effect of posterior nasal neurectomy（PNN） with pharyngeal neurectomy （PN） on chronic sinusitis with nasal polyps （CRSwNP）complicated with perennial allergic rhinitis （PAR）. Methods:83 patients with perennial allergic rhinitis combined with chronic group-wide sinusitis with nasal polyps who attended our hospital from July 2020 to July 2021 were selected. All patients underwent conventional functional endoscopic sinusitis surgery（FESS）+ nasal polypectomy. Patients were divided according to whether they underwent PNN+PN. 38 cases in the experimental group underwent FESS combined with PNN+PN; 44 cases in the control group underwent conventional FESS alone. All patients underwent the VAS, RQLQ, and MLK before treatment, and at 6 months and 1 year after surgery. Meanwhile, other relevant data were collected and the preoperative and postoperative follow-up data were collected and analyzed to assess the differences between the two groups. Results:The total postoperative follow-up period was 1 year. The recurrence rate of nasal polyps at 1 year postoperatively and the nasal congestion VAS score at 6 months postoperatively were not statistically significant in the two groups（P>0.05）. However, the patients in the experimental group had statistically significantly lower effusion and sneezing VAS scores, MLK endoscopy scores and RQLQ scores at 6 months and 1 year postoperatively, and nasal congestion VAS scores at 1 year postoperatively compared to the control group（P<0.05）. Conclusion:For patients with perennial AR complicated with CRSwNP, the combination of the PNN+PN in FESS can significantly improve the short-term curative effect, and PNN+PN is a safe and effective surgical treatment.

The effect of cochlear size on electrically evoked auditory brainstem responses in deaf children.

Objectives: To investigate the relationship between auditory pathway function and cochlear size in deaf children with a radiologically normal inner ear or Mondini malformation. Methods: Thirty-five deaf children without inner ear malformations (IEMs) and forty cases with Mondini malformation were included in this study. The electrically evoked auditory brainstem responses (EABRs) evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded during cochlear implantation (CI) surgery. The anatomical parameters of the cochlea were assessed by high-resolution computed tomography and OTOPLAN 3-D construction software. Correlations between EABRs and cochlear sizes were analyzed. Results: The EABR thresholds and/or latencies were negatively correlated with the basal cochlear diameter, cochlear width and/or cochlear duct length in both patients without IEMs and those with Mondini malformation. Conclusion: The physiological function of the peripheral auditory system depends on the anatomical structure of the cochlea to an extent. A larger cochlear size appears to be associated with better auditory conduction function. Our findings may be beneficial to selection of the proper electrode type and prediction of postoperative auditory rehabilitation. Level of Evidence: Level 4.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Basic fibroblast growth factor-loaded methacrylate gelatin hydrogel microspheres for spinal nerve regeneration.

Spinal cord injury is a severe central nervous system injury, and developing appropriate drug delivery platforms for spinal nerve regeneration is highly anticipated. Here, we propose a basic fibroblast growth factor (bFGF)-loaded methacrylate gelatin (GelMA) hydrogel microsphere with ideal performances for spinal cord injury repair. Benefitting from the precise droplet manipulation capability of the microfluidic technology, the GelMA microspheres possess uniform and satisfactory size and good stability. More importantly, by taking advantage of the porous structures and facile chemical modification of the GelMA microspheres, bFGF could be easily loaded and gradually released. By co-culturing with neural stem cells, it is validated that the bFGF-loaded GelMA microspheres could effectively promote the proliferation and differentiation of neural stem cells. We also confirm the effective role of the bFGF-loaded GelMA microspheres in nerve repair of spinal cord injury in rats. Our results demonstrate the potential value of the microspheres for applications in repairing central nervous system injuries.

Evidence for predictions established by phantom sound.

Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs.

Increased expression of ST2 on regulatory T cells is associated with cancer associated fibroblast-derived IL-33 in laryngeal cancer.

Interleukin (IL)- 33 plays an essential role in regulatory T cell (Treg)-mediated immunosuppression in cancers and underlies the crosstalk between Tregs and the tumor microenvironment. However, the phenotypic characteristics of subset Tregs modulated by IL-33 and its association with the tumor microenvironment are not fully understood. This study aimed to examine the expression of ST2, the receptor of IL-33, on Tregs in tumors and to evaluate their association with cancer associated fibroblasts (CAFs) and reciprocal influences on the prognosis of laryngeal cancer. Our results showed that increased numbers of Tregs were found in laryngeal tumor tissues. Tregs in stromal IL-33-positive tumor tissues demonstrated significantly higher expression of ST2 than those in IL-33- or adjacent nontumor tissues. ST2-expressing Tregs exhibited upregulation of Ki67 and CTLA4 compared with their ST2- negative counterparts. Furthermore, IL-33 in the tumor microenvironment was mainly derived from fibroblasts. ST2 expression on Tregs was correlated with the number of IL-33-positive CAFs. High ST2 expression on Tregs, combined high ST2 on Tregs and the presence of IL-33 expressing CAFs was associated with worse survival outcomes in laryngeal cancer. This study indicated that increased expression of ST2 on Tregs is associated with microenvironmental IL-33 signaling derived from CAFs in laryngeal cancer, unraveling the special role of Tregs and fibroblasts in modulating IL-33/ST2 involved immune-evasive tumor microenvironment.

Event-Related Potential Evidence for Involuntary Consciousness During Implicit Memory Retrieval.

Classical notion claims that a memory is implicit if has nothing to do with consciousness during the information retrieval from storage, or is otherwise explicit. Here, we demonstrate event-related potential evidence for involuntary consciousness during implicit memory retrieval. We designed a passive oddball paradigm for retrieval of implicit memory in which an auditory stream of Shepard tones with musical pitch interval contrasts were delivered to the subjects. These contrasts evoked a mismatch negativity response, which is an event-related potential and a neural marker of implicit memory, in the subjects with long-term musical training, but not in the subjects without. Notably, this response was followed by a salient P3 component which implies involvement of involuntary consciousness in the implicit memory retrieval. Finally, source analysis of the P3 revealed moving dipoles from the frontal lobe to the insula, a brain region closely related to conscious attention. Our study presents a case of involvement of involuntary consciousness in the implicit memory retrieval and suggests a potential challenge to the classical definition of implicit memory.