Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

Evaluating foot reflexology as a proposed treatment for sensorineural hearing loss:A critical review

This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a condition characterized by damage to the cochlea or the neural pathways that transmit auditory information to the brain.The etiology of SNHL is often complex,involving genetic mutations,prenatal factors,or perinatal insults.Reflexology,an alternative therapy involving the application of pressure to specific points on the feet,is based on the hypothesis that these points correspond to different organs and systems in the body,including the auditory system.However,the biological plausibility and clinical efficacy of foot reflexology in addressing SNHL lack empirical support.This editorial examines the pathophysiology of SNHL,assesses the clinical claims of reflexology practitioners,and emphasizes the necessity of evidence-based approaches in treating infant hearing loss.While complementary therapies may provide ancillary benefits,they should not supplant validated medical treatments in managing SNHL in infants.Further research is needed to evaluate the safety and efficacy of foot reflexology and other alternative therapies in pediatric audiology.

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Is it possible to foot reflexology for infants with sensorineural hearing loss?

Foot reflexology is a non-invasive and safe complementary therapy that works by massaging the reflex zones of the feet and exerts systemic or whole-body regulation through meridian nerve conduction.This therapy is commonly used in the treatment of various conditions such as autism and Parkinson's disease.However,there is limited reporting on the use of foot reflexology therapy for infants with sensorineural hearing loss(SNHL).Currently,there is no definitive conclusion on how foot reflexology therapy can influence hearing.This editorial holds some guiding significance regarding this clinical issue.The aim is to present physiological evidence of how foot reflexology therapy can impact infants with SNHL,thereby enhancing clinician’s awareness of foot reflexology in treating infants with SNHL.

Physical rehabilitation for sensorineural hearing loss in childhood:Progress and challenges

Early intervention for sensorineural hearing loss(SNHL)in childhood is crucial for auditory and language development.In recent years,innovative auditory stimulation techniques and speech therapy strategies,such as middle ear implants,cochlear implants,auditory brainstem implants,and midbrain implants,have provided new avenues for improving patient outcomes.Additionally,basic research advancements in cell reprogramming and regeneration,stem cell therapy,and targeted drug delivery offer promising approaches to meet the individualized needs of children with SNHL.However,many challenges and unresolved issues remain in the treatment of SNHL.This article comments on the case report,which describes a female pediatric patient with SNHL who underwent foot reflexology which led to the normalization of hearing thresholds.Reflexology is considered to have potential benefits in physical rehabilitation,but its efficacy in hearing restoration requires further scientific validation through rigorous clinical trials and large-scale prospective studies.

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

Molecular mechanisms and roles of inflammatory responses on low-frequency residual hearing after cochlear implantation

Preservation of low-frequency residual hearing is very important for combined electro-acoustic stimulation after cochlear implantation.However,in clinical practice,loss of low-frequency residual hearing often occurs after cochlear implantation and its mechanisms remain unclear.Factors affecting lowfrequency residual hearing after cochlear implantation are one of the hot spots in current research.Inflammation induced by injury associated with cochlear implantation is deemed to be significant,as it may give rise to low-frequency residual hearing loss by interfering with the blood labyrinth barrier and neural synapses.Pathological changes along the pathway for low-frequency auditory signals transmission may include latent factors such as damage to neuroepithelial structures,synapses,stria vascularis and other ultrastructures.In this review,current research on mechanisms of low-frequency residual hearing loss after cochlear implantation and possible roles of inflammatory responses are summarized.

Recovery of hearing loss in atypical Meniere’s disease after treatment with orofacial and neck massage: A case report

BACKGROUND A 48-year-old female presented with sudden-onset right-sided aural fullness,low-frequency hearing loss,and tinnitus.Medical history included right-sided tempo-romandibular joint disorder(TMJD)with crepitation,and retro-orbital headaches.The patient was diagnosed with atypical Meniere’s disease(MD)and received in-tratympanic steroids,prednisone,betahistine,and began a low-sodium diet;how-ever,the patient’s symptoms worsened.CASE SUMMARY The patient sought physical therapy for TMJD;testing revealed reduced motion and dysfunction with vertical opening,lateral excursion of the mandible to the right,and tenderness to palpation.Treatment included soft tissue mobilization of right facial structures and temporal fossa,intraoral massage of the right pterygoid musculature,and massage of right neck structures.After 4 weeks,the patient noticed subjective improvement in hearing and decreased headaches.After 11 weeks,an audiogram showed that the hearing loss had recovered.The patient has continued the daily at-home intraoral/neck massage therapy and maintained normal hearing over 4 years to date.The temporal relationship between physical therapy and recovery of hearing loss suggests muscular or inflammatory etiology as at least partially causative of this patient’s symptoms.The mechanism of healing may have been due to decreased inflammation,improved blood flow,restored function of cranial nerves,or some combination of these and other unknown factors.CONCLUSION This report suggests that orofacial physical and massage therapy may be an effective treatment for the cochlear symptoms associated with MD.

Enhancing Low-Frequency Microwave Absorption Through Structural Polarization Modulation of MXenes

Two-dimensional carbon-based materials have shown promising electromagnetic wave absorption capabilities in mid-and high-frequency ranges,but face challenges in low-frequency absorption due to limited control over polarization response mecha-nisms and ambiguous resonance behavior.In this study,we pro-pose a novel approach to enhance absorption efficiency in aligned three-dimensional(3D)MXene/CNF(cellulose nanofibers)cavities by modifying polarization properties and manipulating resonance response in the 3D MXene architecture.This controlled polarization mechanism results in a significant shift of the main absorption region from the X-band to the S-band,leading to a remarkable reflection loss value of-47.9 dB in the low-frequency range.Furthermore,our findings revealed the importance of the oriented electromagnetic coupling in influencing electromagnetic response and microwave absorption properties.The present study inspired us to develop a generic strategy for low-frequency tuned absorption in the absence of magnetic element participation,while orientation-induced polarization and the derived magnetic resonance coupling are the key controlling factors of the method.

Effect of foot reflexology on an infant with sensorineural hearing loss:A case report

BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Universal newborn hearing screening program in Saudi Arabia: Current insight

Newborn hearing screening(NHS) programs are essential to identify hearing loss early in life and to improve outcomes in children. In Saudi Arabia, the national NHS program has been operational since 2016;however, few studies have evaluated its status, and none have covered all provinces across the country. This cross-sectional retrospective study provides an overview of the program's status across all provinces, focusing on screening coverage rates, referral/fail rates, and follow-up procedures. In 2021, 199,034 newborns were screened, with a coverage rate of 92.6% and an overall referral/fail rate of 1.87%. These performance measures provide a foundation for future progress and improvements. This study highlights the importance of ongoing efforts to enhance the program's effectiveness and sustainability.

Low-frequency bandgap and vibration suppression mechanism of a novel square hierarchical honeycomb metamaterial

The suppression of low-frequency vibration and noise has always been an important issue in a wide range of engineering applications.To address this concern,a novel square hierarchical honeycomb metamaterial capable of reducing low-frequency noise has been developed.By combining Bloch’s theorem with the finite element method,the band structure is calculated.Numerical results indicate that this metamaterial can produce multiple low-frequency bandgaps within 500 Hz,with a bandgap ratio exceeding 50%.The first bandgap spans from 169.57 Hz to 216.42 Hz.To reveal the formation mechanism of the bandgap,a vibrational mode analysis is performed.Numerical analysis demonstrates that the bandgap is attributed to the suppression of elastic wave propagation by the vibrations of the structure’s two protruding corners and overall expansion vibrations.Additionally,detailed parametric analyses are conducted to investigate the effect ofθ,i.e.,the angle between the protruding corner of the structure and the horizontal direction,on the band structures and the total effective bandgap width.It is found that reducingθis conducive to obtaining lower frequency bandgaps.The propagation characteristics of elastic waves in the structure are explored by the group velocity,phase velocity,and wave propagation direction.Finally,the transmission characteristics of a finite periodic structure are investigated experimentally.The results indicate significant acceleration amplitude attenuation within the bandgap range,confirming the structure’s excellent low-frequency vibration suppression capability.

Effect analysis of unilateral deaf adults wearing bone-conduction hearing aids:A case report

The prevalence of unilateral deafness(SSD)or asymmetric hearing loss(AHL)among patients with hearing impairments ranges from 7.2%to 15.0%,indicating a relatively significant proportion.However,these individuals often overlook their hearing loss,resulting in delayed or inadequate treatment.This oversight can lead to a lack of binaural summation and squelch effect,as well as the head shadow effect,which can significantly impact their speech recognition and sound localization abilities,especially in noisy environments.Recently,a groundbreaking Sound Bite™Pinyin® Bone Conduction Hearing Aid(HA)device has been has been introduced as a viable alternative to traditional percutaneous stimulation hearing assistance devices.This innovative device harnesses bone conduction technology to convey sound vibrations directly to the inner ear via the bones of the jaw and skull,effectively bypassing the air conduction pathway that is commonly compromised in individuals with hearing loss.This report details the evaluation and adjustment process of a HA device worn by a 31-year-old female patient who suffers from a congenital ossicular chain deformity in her right ear,while maintaining normal hearing in her left ear.The report comprehensively covers the hearing thresholds of the 31-year-old female patient on the day of fitting the hearing aid and one month later.It also presents assessments of the hearing aid’s performance through the Abbreviated Profile of Hearing Aid Benefit(APHAB)questionnaire,conducted three days after adjustment,one month later,and one year later.Furthermore,the report details the evaluation of the patient’s sound localization ability,comparing her performance before and after wearing the hearing aid device.Additionally,it includes measurements of her speech recognition ability for monosyllabic words and Yang Yang Ge words,which are specific tests in the Chinese language,conducted two years after the initial fitting of the hearing aid.The discovery that bone-anchored hearing devices can significantly enhance hearing thresholds in patients with unilateral conductive hearing loss represents a significant milestone.These devices not only improve speech recognition ability but also enhance sound localization in noisy environments.This improvement is accompanied by a high level of subjective satisfaction among patients,indicating a positive impact on their overall quality of life.

Dynamic characteristics of coal specimens with varying static preloading levels under low-frequency disturbance load

The mechanical properties of residual coal pillars under the influence of upward mining disturbances significantly affect the safety of residual mining activities on working faces.This study conducted low-frequency disturbance dynamic uniaxial compression tests on coal specimens using a self-developed dynamic-static load coupling electro-hydraulic servo system,and studied the strength evolutions,surface deformations,acoustic emission(AE)characteristic parameters,and the failure modes of coal specimens with different static preloading levels were studied.The disturbance damage is positively correlated with the coal specimen static preload level.Specifically,the cumulative AE count rates of the initial accelerated damage stage for the coal specimens with static preloading level of 60%and 70%of the uniaxial compressive strength(UCS)were 2.66 and 3.19 times that of the 50%UCS specimens,respectively.Macroscopically,this behaviour manifested as a decrease in the compressive strength,and the mean strengths of the disturbance-damaged coal specimens with 60%and 70%of UCS static preloading decreased by 8.53%and 9.32%,respectively,compared to those of the specimens under pure static loading.The crack sources,such as the primary fissures,strongly control the dynamic response of the coal specimen.The difference between the dynamic responses of the coal specimens and that of dense rocks is significant.

A seismic elastic moduli module for the measurements of low-frequency wave dispersion and attenuation of fluid-saturated rocks under different pressures

Knowledge about the seismic elastic modulus dispersion,and associated attenuation,in fluid-saturated rocks is essential for better interpretation of seismic observations taken as part of hydrocarbon identification and time-lapse seismic surveillance of both conventional and unconventional reservoir and overburden performances.A Seismic Elastic Moduli Module has been developed,based on the forced-oscillations method,to experimentally investigate the frequency dependence of Young's modulus and Poisson's ratio,as well as the inferred attenuation,of cylindrical samples under different confining pressure conditions.Calibration with three standard samples showed that the measured elastic moduli were consistent with the published data,indicating that the new apparatus can operate reliably over a wide frequency range of f∈[1-2000,10^(6)]Hz.The Young's modulus and Poisson's ratio of the shale and the tight sandstone samples were measured under axial stress oscillations to assess the frequency-and pressure-dependent effects.Under dry condition,both samples appear to be nearly frequency independent,with weak pressure dependence for the shale and significant pressure dependence for the sandstone.In particular,it was found that the tight sandstone with complex pore microstructure exhibited apparent dispersion and attenuation under brine or glycerin saturation conditions,the levels of which were strongly influenced by the increased effective pressure.In addition,the measured Young's moduli results were compared with the theoretical predictions from a scaled poroelastic model with a reasonably good agreement,revealing that the combined fluid flow mechanisms at both mesoscopic and microscopic scales possibly responsible for the measured dispersion.

Low-frequency oscillation of train-network system considering traction power supply mode

The low-frequency oscillation(LFO)has occurred in the train-network system due to the introduction of the power electronics of the trains.The modeling and analyzing method in current researches based on electrified railway unilateral power supply system are not suitable for the LFO analysis in a bilateral power supply system,where the trains are supplied by two traction substations.In this work,based on the single-input and single-output impedance model of China CRH5 trains,the node admittance matrices of the train-network system both in unilateral and bilateral power supply modes are established,including three-phase power grid,traction transformers and traction network.Then the modal analysis is used to study the oscillation modes and propagation characteristics of the unilateral and bilateral power supply systems.Moreover,the influence of the equivalent inductance of the power grid,the length of the transmission line,and the length of the traction network are analyzed on the critical oscillation mode of the bilateral power supply system.Finally,the theoretical analysis results are verified by the time-domain simulation model in MATLAB/Simulink.

Suppression of low-frequency ultrasound broadband vibration using star-shaped single-phase metamaterials

In order to suppress the low-frequency ultrasound vibration in the broadband range of 20 k Hz—100 k Hz,this paper proposes and discusses an acoustic metamaterial with low-frequency ultrasound vibration attenuation properties,which is configured by hybrid arc and sharp-angle convergent star-shaped lattices.The effect of the dispersion relation and the bandgap characteristic for the scatterers in star-shaped are simulated and analyzed.The target bandgap width is extended by optimizing the geometry parameters of arc and sharp-angle convergent lattices.The proposed metamaterial configured by optimized hybrid lattices exhibits remarkable broad bandgap characteristics by bandgap complementarity,and the simulation results verify a 99%vibration attenuation amplitude can be obtained in the frequency of20 k Hz—100 k Hz.After the fabrication of the proposed hybrid configurational star-shaped metamaterial by 3D printing technique,the transmission loss experiments are performed,and the experimental results indicate that the fabricated metamaterial has the characteristics of broadband vibration attenuation and an amplitude greater than 85%attenuation for the target frequency.These results demonstrate that the hybrid configurational star-shaped metamaterials can effectively widen the bandgap and realize high efficiency attenuation,which has capability for the vibration attenuation in the application of highprecise equipment.

Ionically Imprinting-Based Copper(Ⅱ)Label-Free Detection for Preventing Hearing Loss

Copper is a microelement with important physiological functions in the body.However,the excess copper ion(Cu^(2+))may cause severe health problems,such as hair cell apoptosis and the resultant hearing loss.Therefore,the assay of Cu^(2+)is important.We integrate ionic imprinting technology(IIT)and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads(IIHBs)as a low-cost and high-specificity platform for Cu^(2+)detection.The IIHBs have a macroporous microstructure,uniform size,vivid structural color,and magnetic responsiveness.When incubated in solution,IIHBs recognize Cu^(2+)and exhibit a reflective peak change,thereby achieving label-free detection.In addition,benefiting from the IIT,the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100μmol·L^(-1).These features indicated that the developed IIHBs are promising candidates for Cu^(2+)detection,particularly for the prevention of hearing loss.

Current optimization-based control of dual three-phase PMSM for low-frequency temperature swing reduction

In this paper,a control scheme based on current optimization is proposed for dual three-phase permanent-magnet synchronous motor(DTP-PMSM)drive to reduce the low-frequency temperature swing.The reduction of temperature swing can be equivalent to reducing maximum instantaneous phase copper loss in this paper.First,a two-level optimization aiming at minimizing maximum instantaneous phase copper loss at each electrical angle is proposed.Then,the optimization is transformed to a singlelevel optimization by introducing the auxiliary variable for easy solving.Considering that singleobjective optimization trades a great total copper loss for a small reduction of maximum phase copper loss,the optimization considering both instantaneous total copper loss and maximum phase copper loss is proposed,which has the same performance of temperature swing reduction but with lower total loss.In this way,the proposed control scheme can reduce maximum junction temperature by 11%.Both simulation and experimental results are presented to prove the effectiveness and superiority of the proposed control scheme for low-frequency temperature swing reduction.