Background and Objectives:The perception of sound in the vertical plane supports spatial hearing by enabling listeners to detect sources located above and below.Sounds originating from both the front and back elevatio...Background and Objectives:The perception of sound in the vertical plane supports spatial hearing by enabling listeners to detect sources located above and below.Sounds originating from both the front and back elevations along the mid-sagittal plane further contribute to a three-dimensional auditory experience.This study aimed to characterize the variability in vertical sound localization abilities among normal-hearing(NH)individuals using spatialized audio.Materials and Methods:Fifty-one NH participants(aged 18 to 35 years)completed three vertical localization tasks under headphones as part of a single-group,within-subject experimental study.These tasks included two-plane identification:(1)top-down localization,(2)front-back localization,and one discrimination task in the front plane.Hierarchical Cluster Analysis(HCA)was employed to identify distinct patterns in spatial localization profiles specific to the vertical-median plane.Fisher's Discriminant Function Analysis(FDA)was used to validate the accuracy of HCA and estimate classification error.Results:HCA revealed three distinct listener clusters:(1)cluster 1 with good performance across all three tasks,(2)cluster 2 with selective impairment in top-bottom identification,and(3)cluster 3 with selective deficits in front-back identification.FDA validated group membership of the clusters identified by the HCA,with a prediction accuracy of 98%.Conclusions:Individuals with clinically NH exhibited three distinct vertical localization profiles:uniform performers,those impaired in top-bottom identification,and those impaired in front-back identification.These profiles may be linked to the interplay between acoustic and non-acoustic perceptual factors.展开更多
Objective:To investigate subjective and objective listening abilities in noise in young adults,older adults with normal hearing,and adults with listening difficulties(LiD).Methods:This study examined 20 young adults,2...Objective:To investigate subjective and objective listening abilities in noise in young adults,older adults with normal hearing,and adults with listening difficulties(LiD).Methods:This study examined 20 young adults,20 older adults with normal hearing,and 20 adults with LiD.All participants underwent pure-tone audiometry and the Hearing in Noise Test-Japanese version(HINT-J)and completed the Speech,Spatial and Qualities of Hearing Scale(SSQ).Results:All groups had normal hearing thresholds(125-8,000 Hz).Older adults with normal hearing performed worse on the HINT-J than young adults,while adults with LiD reported greater subjective LiD on the SSQ.No significant correlations were found between HINTJ and SSQ scores with any group.Significant differences were found between groups in terms of both the HINT-J(χ^(2)(2)=17.9,p<0.01)and SSQ(χ^(2)(2)=38.7,p<0.01).Conclusion:Despite normal audiometric thresholds,older adults with normal hearing and adults with LiD experience distinct LiD in noisy environments,highlighting the need for comprehensive assessment beyond traditional audiometry.Future research should focus on developing more sensitive diagnostic tools.展开更多
Studies conducted on neurodegenerative diseases diversely report on changes in the cerebral microvasculature:Fundamental hallmarks of prevalent neurodegenerative diseases,such as Alzheimer’s disease(AD),dementia with...Studies conducted on neurodegenerative diseases diversely report on changes in the cerebral microvasculature:Fundamental hallmarks of prevalent neurodegenerative diseases,such as Alzheimer’s disease(AD),dementia with Lewy bodies,Parkinson’s disease,Huntington’s disease,include region-specific neuronal loss and neuroinflammation eventually leading to brain atrophy.Numerous studies have also demonstrated that neurodegeneration and changes in the microvasculature are interconnected.For example,in AD,changes in vessel density have been reported to vary-increasing,remaining unchanged,or decreasing-in brain regions most affected by neurodegeneration.展开更多
Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,w...Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.展开更多
Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevate...Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.展开更多
Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although th...Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.展开更多
Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identify...Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.展开更多
Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databa...Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.展开更多
Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with W...Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with Williams syndrome and provide references for future clinical management.Method Between January 2007 and March 2022,families with at least 1 WS patient was recruited from the Newborn Cohort Study of Hearing Loss.Audiological tests were performed,and then appropriate medical management was offered.Furthermore,an overview of the hearing loss phenotype in Williams syndrome in different locations was reviewed.Results A total of two families with at least 1 Williams syndrome patient were recruited from the Newborn Cohort Study of Hearing Loss(ChiCTR2100049765).We identified moderately severe sensorineural or conductive hearing loss that emerged as early as the infancy period in Williams syndrome subjects in Chinese children.Our results extended the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period.We also found that with early diagnosis,proper management,and regular monitoring,children with Williams syndrome could return to a normal or near-normal school life.Conclusions Our study demonstrated the distinct hearing profile in Chinese children with Williams syndrome for the first time.This cohort of WS subjects extends the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period,indicating the importance of clinicians screening and monitoring the hearing status of individuals with WS as early as possible.These data provide references for otolaryngologists and paediatricians to inform the clinical understanding and management of hearing loss in Williams syndrome.展开更多
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.Her...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.展开更多
Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down ...Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down the decline in SPiN performance associated with aging.Objectives:Therefore,we assessed SPiN performances in a continuum of age groups comprising musicians and non-musicians.The goal was to compare how the aging process affected SPiN performances of musicians and non-musicians.Method:A cross-sectional descriptive mixed design was used,involving 150 participants divided into 75 musicians and 75 non-musicians.Each age group(10-19,20-29,30-39,40-49,and 50-59)consisted of15 musicians and 15 non-musicians.Six Kannada sentence lists were combined with four-talker babble.At+5,0,and-5 dB signal-to-noise ratios(SNRs),the percent correct Speech Identification Scores were calculated.Results:The repeated measure ANOVA(RM ANOVA)revealed significant main effects and interaction effects between SNR,musicianship,and age groups(p<0.05).A small to large effect size was noted(ηp2=0.05 to0.17).A significant interaction effect and follow-up post hoc tests showed that SPiN abilities deteriorated more rapidly with increasing age in nonmusicians compared to musicians,especially at difficult SNRs.Conclusions:Musicians had better SPiN abilities than non-musicians across all age groups.Also,age-related deterioration in SPiN abilities was faster in non-musicians compared to musicians.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound e...Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound efficacy of brainwave entrainment using binaural beats, comparing it to a standard tinnitus masker over a three-month duration. Method: Sixty-three individuals having tinnitus with normal hearing sensitivity were enrolled in the study. The participants were categorized into groups Ⅰ, Ⅱ, and Ⅲ. They were provided with delta(4 Hz) and alpha(10 Hz) frequency binaural beats and standard tinnitus masker, respectively, for a duration of three months. The tinnitus handicap inventory(THI) scores, Visual analogue scale(VAS) rating for tinnitus distress, and quality of life parameters were measured. The reductions obtained for each measure during the end of the first, second and third month were measured and compared across the groups. Results: All three groups showed considerable reductions in THI and VAS scores and improvements in the quality of life domains, focusing on physical and psychological health. However, groups Ⅰ and Ⅱ, who received binaural beats stimuli, showed higher benefits than those who received standard tinnitus masker. Conclusion: The results of the current study indicated that binaural beats can be an effective treatment technique for individuals with tinnitus having normal hearing sensitivity. Clinicians and otology/audiology practitioners shall adopt this innovative treatment after further validating these findings.展开更多
Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (m...Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.展开更多
BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optim...BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optimization and validation of programming parameters.ObjectiveThe study has attempted to describe the changes in behavioral responses with modification of T and M levels.MethodsTwenty-five participants in the age range 5 to 12 years using HR90K/HiFocus1J or HR90KAdvantage/HiFocus1J with Harmony speech processors participated in the study.A decrease in T levels,a rise in T levels,or a decrease in M levels in the everyday program were used to create experimental programs.Sound field thresholds and speech perception were measured at 50 dBHL for three experimental and everyday programs.ConclusionThe results indicated that only reductions of M levels resulted in significantly(p<0.01)poor aided thresholds and speech perception.On the other hand,variation in T levels did not have significant changes in either sound field thresholds or speech perception.The results highlight that M levels must be correctly established in order to prevent decreased speech perception and audibility.展开更多
Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore...Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.展开更多
Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).Wit...Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).With a prevalence of 3.8/100,000(Barisic et al.,2014),CFM is the second most common congenital craniofacial abnormality(Li et al.,2022;Luo et al.,2023).Most cases are sporadic,but familial ones suggest autosomal dominant(AD)or autosomal recessive(AR)(Beleza-Meireles et al.,2014).In 2023,Quiat et al.and Mao et al.successively identified FOXI3 variants in 16 pedigrees and 10 sporadic cases,respectively,accounting for 3.1%of CFM cases(Mao et al.,2023;Quiat et al.,2023).FOX/3 has surpassed SF3B2 as the most frequently identified pathogenic gene for CFM to date(Timberlake et al.,2021;Mao et al.,2023;Quiat et al.,2023).In this study,we performed whole-exome sequencing(WES)on 201 CFM pedigrees and detected FOX/3 variants in 8 AD-inherited pedigrees with 24 patients and 28 unaffected individuals(Fig.1A).展开更多
Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologie...Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.展开更多
The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential p...The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential platform for studying hearing mechanics and are crucial for developing next-generation auditory prostheses and artificial hearing systems for sensorineural hearing restoration.Recent advances in additive manufacturing,organ-on-a-chip models,drug delivery platforms,and artificial intelligence have provided valuable insights into how to manufacture artificial cochlea models that more accurately replicate the complex anatomy and physiology of the inner ear.This paper reviews recent advancements in the applications of advanced manufacturing techniques in reproducing the physical,biological,and intelligent functions of the cochlea.It also outlines the current challenges to developing mechanically,electrically,and anatomically accurate functional models of the inner ear.Finally,this review identifies the major requirements and outlook for impactful research in this field going forward.Through interdisciplinary collaboration and innovation,these functional cochlea models are poised to drive significant advancements in hearing treatments,and ultimately enhance the quality of life for individuals with hearing loss.展开更多
This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumora...This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.展开更多
文摘Background and Objectives:The perception of sound in the vertical plane supports spatial hearing by enabling listeners to detect sources located above and below.Sounds originating from both the front and back elevations along the mid-sagittal plane further contribute to a three-dimensional auditory experience.This study aimed to characterize the variability in vertical sound localization abilities among normal-hearing(NH)individuals using spatialized audio.Materials and Methods:Fifty-one NH participants(aged 18 to 35 years)completed three vertical localization tasks under headphones as part of a single-group,within-subject experimental study.These tasks included two-plane identification:(1)top-down localization,(2)front-back localization,and one discrimination task in the front plane.Hierarchical Cluster Analysis(HCA)was employed to identify distinct patterns in spatial localization profiles specific to the vertical-median plane.Fisher's Discriminant Function Analysis(FDA)was used to validate the accuracy of HCA and estimate classification error.Results:HCA revealed three distinct listener clusters:(1)cluster 1 with good performance across all three tasks,(2)cluster 2 with selective impairment in top-bottom identification,and(3)cluster 3 with selective deficits in front-back identification.FDA validated group membership of the clusters identified by the HCA,with a prediction accuracy of 98%.Conclusions:Individuals with clinically NH exhibited three distinct vertical localization profiles:uniform performers,those impaired in top-bottom identification,and those impaired in front-back identification.These profiles may be linked to the interplay between acoustic and non-acoustic perceptual factors.
基金supported by the Japan Society for the Promotion of Science(JSPS)Grants in Aids for Scientific Research(KAKENHI)[grant number 21K20238].
文摘Objective:To investigate subjective and objective listening abilities in noise in young adults,older adults with normal hearing,and adults with listening difficulties(LiD).Methods:This study examined 20 young adults,20 older adults with normal hearing,and 20 adults with LiD.All participants underwent pure-tone audiometry and the Hearing in Noise Test-Japanese version(HINT-J)and completed the Speech,Spatial and Qualities of Hearing Scale(SSQ).Results:All groups had normal hearing thresholds(125-8,000 Hz).Older adults with normal hearing performed worse on the HINT-J than young adults,while adults with LiD reported greater subjective LiD on the SSQ.No significant correlations were found between HINTJ and SSQ scores with any group.Significant differences were found between groups in terms of both the HINT-J(χ^(2)(2)=17.9,p<0.01)and SSQ(χ^(2)(2)=38.7,p<0.01).Conclusion:Despite normal audiometric thresholds,older adults with normal hearing and adults with LiD experience distinct LiD in noisy environments,highlighting the need for comprehensive assessment beyond traditional audiometry.Future research should focus on developing more sensitive diagnostic tools.
文摘Studies conducted on neurodegenerative diseases diversely report on changes in the cerebral microvasculature:Fundamental hallmarks of prevalent neurodegenerative diseases,such as Alzheimer’s disease(AD),dementia with Lewy bodies,Parkinson’s disease,Huntington’s disease,include region-specific neuronal loss and neuroinflammation eventually leading to brain atrophy.Numerous studies have also demonstrated that neurodegeneration and changes in the microvasculature are interconnected.For example,in AD,changes in vessel density have been reported to vary-increasing,remaining unchanged,or decreasing-in brain regions most affected by neurodegeneration.
基金supported by the National Natural Science Foundation of China(82271159,82071049,82425018,and 82101219)the STI2030-Major Projects(2022ZD0205400).
文摘Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.
基金supported by the National Natural Science Foundation of China(82271159,82425018,82071049,81830029,82192860,81922018,82201283,82101219,and 82192861)Shanghai Clinical Medical Research Center for Otolaryngology Diseases(20MC1920200)the STI2030-Major Projects(2022ZD0205400).
文摘Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.
基金supported by the National Natural Science Foundation of China(No.82271889,82572117,82371173,and 82172105)the National Key Research and Development Program of China(No.2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400)。
文摘Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.
基金supported by the Scientific and Innovative Action Plan of Shanghai(CN)(22Y11902000)the National Natural Science Foundation of China(82371144 and 82201273)+2 种基金the Cross-Disciplinary Research Fund of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202231)the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)We extend our gratitude to Prof.Hao Wu and the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases for providing essential resources and laboratory facilities,and to Prof.Lei Song and Prof.Zhiyong Liu for valuable insights and guidance.
文摘Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.
文摘Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.
基金supported by the grants of the National Key Research and Development Program of China(Grant No.2023YFC2508400)the National Natural Science Foundation of China(Grant No.82350005).
文摘Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with Williams syndrome and provide references for future clinical management.Method Between January 2007 and March 2022,families with at least 1 WS patient was recruited from the Newborn Cohort Study of Hearing Loss.Audiological tests were performed,and then appropriate medical management was offered.Furthermore,an overview of the hearing loss phenotype in Williams syndrome in different locations was reviewed.Results A total of two families with at least 1 Williams syndrome patient were recruited from the Newborn Cohort Study of Hearing Loss(ChiCTR2100049765).We identified moderately severe sensorineural or conductive hearing loss that emerged as early as the infancy period in Williams syndrome subjects in Chinese children.Our results extended the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period.We also found that with early diagnosis,proper management,and regular monitoring,children with Williams syndrome could return to a normal or near-normal school life.Conclusions Our study demonstrated the distinct hearing profile in Chinese children with Williams syndrome for the first time.This cohort of WS subjects extends the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period,indicating the importance of clinicians screening and monitoring the hearing status of individuals with WS as early as possible.These data provide references for otolaryngologists and paediatricians to inform the clinical understanding and management of hearing loss in Williams syndrome.
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘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.
文摘Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down the decline in SPiN performance associated with aging.Objectives:Therefore,we assessed SPiN performances in a continuum of age groups comprising musicians and non-musicians.The goal was to compare how the aging process affected SPiN performances of musicians and non-musicians.Method:A cross-sectional descriptive mixed design was used,involving 150 participants divided into 75 musicians and 75 non-musicians.Each age group(10-19,20-29,30-39,40-49,and 50-59)consisted of15 musicians and 15 non-musicians.Six Kannada sentence lists were combined with four-talker babble.At+5,0,and-5 dB signal-to-noise ratios(SNRs),the percent correct Speech Identification Scores were calculated.Results:The repeated measure ANOVA(RM ANOVA)revealed significant main effects and interaction effects between SNR,musicianship,and age groups(p<0.05).A small to large effect size was noted(ηp2=0.05 to0.17).A significant interaction effect and follow-up post hoc tests showed that SPiN abilities deteriorated more rapidly with increasing age in nonmusicians compared to musicians,especially at difficult SNRs.Conclusions:Musicians had better SPiN abilities than non-musicians across all age groups.Also,age-related deterioration in SPiN abilities was faster in non-musicians compared to musicians.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
文摘Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound efficacy of brainwave entrainment using binaural beats, comparing it to a standard tinnitus masker over a three-month duration. Method: Sixty-three individuals having tinnitus with normal hearing sensitivity were enrolled in the study. The participants were categorized into groups Ⅰ, Ⅱ, and Ⅲ. They were provided with delta(4 Hz) and alpha(10 Hz) frequency binaural beats and standard tinnitus masker, respectively, for a duration of three months. The tinnitus handicap inventory(THI) scores, Visual analogue scale(VAS) rating for tinnitus distress, and quality of life parameters were measured. The reductions obtained for each measure during the end of the first, second and third month were measured and compared across the groups. Results: All three groups showed considerable reductions in THI and VAS scores and improvements in the quality of life domains, focusing on physical and psychological health. However, groups Ⅰ and Ⅱ, who received binaural beats stimuli, showed higher benefits than those who received standard tinnitus masker. Conclusion: The results of the current study indicated that binaural beats can be an effective treatment technique for individuals with tinnitus having normal hearing sensitivity. Clinicians and otology/audiology practitioners shall adopt this innovative treatment after further validating these findings.
文摘Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.
文摘BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optimization and validation of programming parameters.ObjectiveThe study has attempted to describe the changes in behavioral responses with modification of T and M levels.MethodsTwenty-five participants in the age range 5 to 12 years using HR90K/HiFocus1J or HR90KAdvantage/HiFocus1J with Harmony speech processors participated in the study.A decrease in T levels,a rise in T levels,or a decrease in M levels in the everyday program were used to create experimental programs.Sound field thresholds and speech perception were measured at 50 dBHL for three experimental and everyday programs.ConclusionThe results indicated that only reductions of M levels resulted in significantly(p<0.01)poor aided thresholds and speech perception.On the other hand,variation in T levels did not have significant changes in either sound field thresholds or speech perception.The results highlight that M levels must be correctly established in order to prevent decreased speech perception and audibility.
基金supported by the Beijing Natural Science Foundation of China under Grant 7222185。
文摘Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.
基金support in this study.This work was supported by the National Natural Science Foundation of China(82271889,82172105)the National Key Research and Development Program of China(2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400).
文摘Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).With a prevalence of 3.8/100,000(Barisic et al.,2014),CFM is the second most common congenital craniofacial abnormality(Li et al.,2022;Luo et al.,2023).Most cases are sporadic,but familial ones suggest autosomal dominant(AD)or autosomal recessive(AR)(Beleza-Meireles et al.,2014).In 2023,Quiat et al.and Mao et al.successively identified FOXI3 variants in 16 pedigrees and 10 sporadic cases,respectively,accounting for 3.1%of CFM cases(Mao et al.,2023;Quiat et al.,2023).FOX/3 has surpassed SF3B2 as the most frequently identified pathogenic gene for CFM to date(Timberlake et al.,2021;Mao et al.,2023;Quiat et al.,2023).In this study,we performed whole-exome sequencing(WES)on 201 CFM pedigrees and detected FOX/3 variants in 8 AD-inherited pedigrees with 24 patients and 28 unaffected individuals(Fig.1A).
基金supported by the National Natural Science Foundation of China(Nos.82271158,82301312,82071045,82101219,82071048).
文摘Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.
基金support from the UCL GRS/ORS scholarshipUCL Fellowship Incubator Award+9 种基金supported by the NIHR Cambridge Biomedical Research Centre(NIHR203312)funded by the Royal National Institute for Deaf People(RNID,G100138)funded by the Rosetrees Trust Enterprise Fellowship(EF2020100099)RNID Flexigrant(F112)Wellcome Trust Developing Concept Fund(RG93172/BANCE/40181)by the Evelyn Trustfunded by the Woolf Fisher Trust,New Zealandthe Cambridge Commonwealth,European,&International Trustby Trinity CollegeUniversity of Cambridge。
文摘The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential platform for studying hearing mechanics and are crucial for developing next-generation auditory prostheses and artificial hearing systems for sensorineural hearing restoration.Recent advances in additive manufacturing,organ-on-a-chip models,drug delivery platforms,and artificial intelligence have provided valuable insights into how to manufacture artificial cochlea models that more accurately replicate the complex anatomy and physiology of the inner ear.This paper reviews recent advancements in the applications of advanced manufacturing techniques in reproducing the physical,biological,and intelligent functions of the cochlea.It also outlines the current challenges to developing mechanically,electrically,and anatomically accurate functional models of the inner ear.Finally,this review identifies the major requirements and outlook for impactful research in this field going forward.Through interdisciplinary collaboration and innovation,these functional cochlea models are poised to drive significant advancements in hearing treatments,and ultimately enhance the quality of life for individuals with hearing loss.
基金Supported by National Natural Science Foundation of China,No.82404058Shanghai Municipal Commission of Health and Family Planning,No.2024ZZ2049Beijing Xisike Clinical Oncology Research Foundation,No.Y-HS202401-0011.
文摘This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.
