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Study of organ of Corti motion in the guinea pig base including differential analysis of internal motion 豚鼠基底Corti运动器官的研究,包括内部运动的差异分析。
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-08 DOI: 10.1016/j.heares.2025.109449
Lauren A. Chiriboga , C. Elliott Strimbu , Elika Fallah , Elizabeth S. Olson
The sensation of hearing arises from the interplay of micromechanical motion within the organ of Corti (OC). Optical coherence tomography (OCT) vibrometry has been used to examine the simultaneous motions of OC structures, including the basilar membrane (BM), outer hair cells (OHCs) and reticular lamina (RL), with gerbil and guinea pig (GP) as common animal models. Boosting (motion responses larger than passive motion), and nonlinearity at frequencies below the best frequency (sub-BF) are a robust observation within the gerbil OHC-region. Fallah et al. (2021) compared basal OC mechanics between gerbil and GP and found that GP OC motions at sub-BF frequencies were generally less boosted and showed less nonlinearity than those in gerbil. In the present work, we expand upon the GP measurements by measuring intra-OC motion through both the round window (RW) and a basal cochleostomy in the same experiment. We found substantial differences in the motions when measured through the RW versus the cochleostomy. In the OHC/Deiters Cell(DC) region, sub-BF nonlinearity and boosting were present in measurements through a cochleostomy, but not through the RW. A mild degree of sub-BF nonlinearity was present in the RL region in RW measurements, but not through the cochleostomy. The discussion proposes hypotheses for these differences, including optical angle dependency and mechanical perturbation. Finally, a complex difference analysis was used to extract the internal motion of OC structures riding on the BM motion. The stimulus-level-dependence of the internal OC motions was reduced in the phase responses and increased in the amplitude responses compared to the directly measured OC motion, and irregularities such as nonmonotonic scaling in the measured motion were not present in the extracted internal motion.
听觉是由听觉器官内部的微机械运动相互作用产生的。光学相干断层扫描(OCT)振动测量技术已被用于检测基底膜(BM)、外毛细胞(OHCs)和网状层(RL)等OC结构的同步运动,并以沙鼠和豚鼠(GP)为常见动物模型。在沙鼠ohc区域内,增强(运动响应大于被动运动)和低于最佳频率(次bf)频率的非线性是一个可靠的观察结果。Fallah等人(2021)比较了沙鼠和GP的基本OC力学,发现GP在次bf频率下的OC运动通常比沙鼠的运动增强更少,非线性也更小。在目前的工作中,我们在同一实验中通过圆窗(RW)和基础耳蜗造口术测量耳蜗内运动来扩展GP测量。我们发现通过RW和耳蜗造口术测量的运动有很大的不同。在OHC/ deiter细胞(DC)区域,通过耳蜗造口术测量存在亚bf非线性和增强,但通过RW不存在。在RW测量中,RL区域存在轻度的亚bf非线性,但在耳蜗造口术中没有。讨论提出了这些差异的假设,包括光学角度依赖和机械摄动。最后,采用复差分析方法提取基于基底运动的基底结构的内部运动。与直接测量的OC运动相比,内部OC运动的刺激水平依赖性在相位响应中降低,在幅度响应中增加,并且在提取的内部OC运动中不存在测量运动中的非单调标度等不规则性。
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引用次数: 0
Extended high-frequency hearing sensitivity facilitates predictive speech perception 扩展的高频听力灵敏度有助于预测语音感知。
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.heares.2025.109453
Tugba Lulaci , Pelle Söderström , Mikael Roll
Speech signal decoding relies on both cognitive performance and the ability to perceive the acoustic signal in sufficient detail. In everyday communication, natural speech is often rapid, spatially and spectrally complex, and accompanied by noise. The brain generates predictions to cope with the complex nature of the auditory signal in speech perception. Anticipatory coarticulation is a natural part of the speech signal. Acoustic traces of upcoming speech sounds provide valuable information that can support auditory prediction, especially when the input is limited or degraded. This study analyzed the relation between individual extended high-frequency hearing threshold differences and word recognition performance in an auditory gating task. Using an adapted gating paradigm with fricative onset (/f/ and /s/) words, we investigated listeners’ extended high-frequency hearing sensitivity in relation to their ability to use early coarticulatory cues predictively for spoken-word recognition. Listeners with better extended high-frequency thresholds were more accurate in predicting the identity of spoken words, using coarticulatory cues as early as 15 ms for words beginning with /s/. In contrast, /f/, which has lower energy in high-frequency energy bands, did not show this pattern. These findings highlight the perceptual role of extended high-frequency hearing in speech perception in natural speech, where input is often limited and variable, showing that extended high-frequency hearing can facilitate predictive processing by enhancing access to subtle early cues in the speech signal.
语音信号解码依赖于认知能力和足够详细地感知声信号的能力。在日常交流中,自然语言往往是快速的,空间和频谱复杂的,并伴随着噪音。大脑产生预测来应对语音感知中听觉信号的复杂性。预期协同发音是语音信号的一个自然组成部分。即将到来的语音的声学痕迹提供了有价值的信息,可以支持听觉预测,特别是当输入有限或退化时。本研究分析了听觉门控任务中个体扩展高频听阈差异与单词识别表现的关系。我们采用带有摩擦音起音(/f/和/s/)单词的适应性门控范式,研究了听者扩展的高频听力灵敏度与他们使用早期协同发音线索预测口语单词识别的能力之间的关系。高频阈值越高的听者在预测口语单词时越准确,对以/s/开头的单词使用协同发音线索的时间早为15毫秒。相比之下,高频能带能量较低的/f/没有表现出这种模式。这些发现强调了扩展高频听力在自然语音感知中的感知作用,其中输入通常是有限和可变的,表明扩展高频听力可以通过增强对语音信号中微妙的早期线索的获取来促进预测处理。
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引用次数: 0
Examining the relationship between difficulties with emotion regulation and misophonia and hyperacusis symptom severity in adults with clinically significant misophonia 临床有明显恐音症的成人情绪调节困难与恐音症及听觉亢进症状严重程度的关系
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-19 DOI: 10.1016/j.heares.2025.109457
Sajana Aryal , Ashley Moskovich , Prashanth Prabhu , M. Zachary Rosenthal
Misophonia is a prevalent and impairing sound intolerance condition that shares symptom overlap and high rates of co-morbidity with hyperacusis. Research demarcating these sound intolerance conditions is critical for the development of accurate diagnostic tools and treatment matching. Previous research suggests difficulties with emotion regulation may be a core feature of misophonia, but its relationship to hyperacusis is unknown. As a first step in exploring whether emotion regulation may be a clinical feature that differentiates misophonia from hyperacusis, the current study examined the relationship between difficulties with emotion regulation and both misophonia and hyperacusis symptom severity in a sample of adults with clinically significant misophonia.
Participants (N=143) completed the Misophonia Questionnaire, the Hyperacusis Questionnaire, and the Difficulties in Emotion Regulation Scale. Stepwise hierarchical regression analyses were conducted to examine whether difficulties with emotion regulation predicted misophonia (Model 1) and hyperacusis (Model 2) symptom severity, after controlling for age and hyperacusis severity or misophonia severity respectively. Partial correlation and Fisher’s Z analyses were subsequently conducted to examine whether domains of emotion regulation were differentially related to symptom severity.
Results indicated that greater difficulties with emotion regulation were significantly associated with misophonia but not hyperacusis severity. Additionally, misophonia symptom severity was specifically related to difficulties with goal-directed behavior, impulse control, access to strategies and nonacceptance. Findings provide preliminary evidence that difficulties with emotion regulation may be a clinical feature that differentiates misophonia from hyperacusis that should be further tested in samples of individuals with hyperacusis without misophonia.
恐音症是一种普遍的、损害性的声音不耐受状况,与听觉亢进有相同的症状重叠和高发病率。划定这些声音不耐受条件的研究对于开发准确的诊断工具和治疗匹配至关重要。先前的研究表明,情绪调节困难可能是恐音症的一个核心特征,但它与听觉亢进的关系尚不清楚。作为探索情绪调节是否可能是区分恐音症和听觉亢进的临床特征的第一步,本研究在临床有明显恐音症的成人样本中检查了情绪调节困难与恐音症和听觉亢进症状严重程度之间的关系。143名被试完成了恐音症问卷、听觉亢进问卷和情绪调节困难量表。采用逐步层次回归分析,在分别控制了年龄和听觉亢进严重程度或恐音严重程度后,检验情绪调节困难是否能预测恐音症(模型1)和听觉亢进(模型2)症状严重程度。随后进行了偏相关分析和Fisher’s Z分析,以检验情绪调节领域是否与症状严重程度存在差异。结果表明,情绪调节困难与恐音症显著相关,但与听觉亢进的严重程度无关。此外,恐音症症状的严重程度与目标导向行为、冲动控制、获取策略和不被接受的困难特别相关。研究结果提供了初步的证据,表明情绪调节困难可能是区分恐音症和听觉亢进的一个临床特征,这应该在有听觉亢进但没有恐音症的个体样本中进一步测试。
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引用次数: 0
METTL3-mediated N6-methyladenosine modification regulates NLRP3 inflammasome activation in chronic suppurative otitis media mettl3介导的n6 -甲基腺苷修饰调节慢性化脓性中耳炎NLRP3炎性体的激活
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-04 DOI: 10.1016/j.heares.2025.109439
Yuanyuan Yang , Jianxin Qiu

Background

Chronic suppurative otitis media (CSOM) is a common inflammatory condition characterized by persistent ear discharge and hearing loss. Recent studies have highlighted the importance of the NLRP3 inflammasome in the pathogenesis of various inflammatory diseases, including CSOM. Here, we investigated the role of METTL3 and N6-methyladenosine (m6A) modification in the regulation of NLRP3 inflammasome activation in CSOM.

Methods

CSOM model mice were established by intraperitoneally injected with lipopolysaccharide (LPS) and middle ear tissues were collected for analysis. Inflammatory cytokines including TNF-α, IL-1β, IFN-γ, and IL-6 were evaluated, as well as the levels of m6A related genes. The potential regulatory effects of METTL3 mediated m6A modification of NLRP3 was further studied to explain the inflammatory response in CSOM.

Results

We found that METTL3 overexpression increased the m6A level and mRNA stability of NLRP3, leading to enhanced inflammasome activation and production of inflammatory cytokines. Conversely, silencing METTL3 reduced NLRP3 expression and inflammasome activity. Rescue experiments with NLRP3 overexpression confirmed that the effects of METTL3 on inflammation were mediated through NLRP3. Additionally, the NLRP3 inhibitor MCC950 reversed the pro-inflammatory effects of METTL3 overexpression.

Conclusions

Our findings suggest that METTL3-mediated m6A modification plays a critical role in NLRP3 inflammasome activation and the inflammatory response in CSOM. Targeting the METTL3/NLRP3 axis may provide a novel therapeutic strategy for the treatment of CSOM.
慢性化脓性中耳炎(CSOM)是一种常见的炎症性疾病,其特征是持续的耳部分泌物和听力丧失。最近的研究强调了NLRP3炎性小体在包括CSOM在内的各种炎症性疾病发病机制中的重要性。在这里,我们研究了METTL3和n6 -甲基腺苷(m6A)修饰在CSOM中调节NLRP3炎性体激活中的作用。方法通过腹腔注射脂多糖(LPS)建立小鼠scsom模型,收集小鼠中耳组织进行分析。评估炎症因子包括TNF-α、IL-1β、IFN-γ和IL-6,以及m6A相关基因的水平。我们进一步研究了METTL3介导的m6A修饰NLRP3的潜在调节作用,以解释CSOM中的炎症反应。结果METTL3过表达增加了NLRP3的m6A水平和mRNA稳定性,导致炎症小体活化和炎症细胞因子的产生增强。相反,沉默METTL3会降低NLRP3的表达和炎症小体的活性。NLRP3过表达的抢救实验证实了METTL3对炎症的作用是通过NLRP3介导的。此外,NLRP3抑制剂MCC950逆转了METTL3过表达的促炎作用。结论mettl3介导的m6A修饰在CSOM NLRP3炎症小体激活和炎症反应中起关键作用。靶向METTL3/NLRP3轴可能为CSOM的治疗提供一种新的治疗策略。
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引用次数: 0
Integrative multi-dataset analysis identifies immune-inflammatory hub genes as diagnostic biomarkers and therapeutic targets for age-related hearing loss 综合多数据集分析确定免疫炎症中心基因作为年龄相关性听力损失的诊断生物标志物和治疗靶点。
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.heares.2025.109448
Xiaoqin Luo , Wei Yuan , Jun Liu , Chanyuan Zhang , Chao Li , Gang Qin
Age-related hearing loss (ARHL) is a common neurodegenerative disorder in the elderly, but its molecular mechanisms and diagnostic biomarkers remain unclear. Here, by using the GSE49543 dataset (n = 40, Affymetrix microarray) from the Gene Expression Omnibus (GEO) with limma, 17 ARHL-associated differentially expressed genes were identified, which were enriched in immune effector functions and the IL-17 signaling pathway. Weighted gene co-expression network analysis (WGCNA) further revealed that 168 genes were associated with hearing loss (module significance > 0.3). Intersecting DEGs with this module yielded 15 candidates, which were prioritized via protein-protein interaction (PPI) network (STRING) and CytoHubba algorithms to 7 core genes. Machine learning refined these to 5 hub genes: Fcgr3, Cd68, Lgals3, Laptm5, and Mpeg1, showing excellent diagnostic performance. Validation in five independent transcriptomic datasets (GSE49543, GSE6045, GSE153882, GSE154833, and GSE233798) confirmed their upregulation in ARHL samples, and experimental verification via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) further validated elevated mRNA (FCGR3, CD68, LGALS3, MPEG1) and protein (FCGR3, CD68, LGALS3) levels in aged mouse cochleae. Additionally, single-nucleus RNA sequencing (snRNA-seq) dataset GSE274279 was integrated to validate hub gene expression at single-cell resolution. These findings identify Fcgr3, Cd68, Lgals3, Laptm5, and Mpeg1 as immune-inflammatory hub genes with potential as diagnostic biomarkers and therapeutic targets for ARHL.
年龄相关性听力损失(ARHL)是老年人常见的神经退行性疾病,但其分子机制和诊断生物标志物尚不清楚。本研究利用来自Gene Expression Omnibus (GEO)与limma的GSE49543数据集(n = 40, Affymetrix微阵列),鉴定了17个与arhl相关的差异表达基因,这些基因在免疫效应功能和IL-17信号通路中富集。加权基因共表达网络分析(WGCNA)进一步揭示了168个与听力损失相关的基因(模块显著性> 0.3)。与该模块相交的deg产生15个候选基因,通过蛋白蛋白相互作用(PPI)网络(STRING)和CytoHubba算法对7个核心基因进行优先排序。机器学习将这些基因提炼为5个枢纽基因:Fcgr3、Cd68、Lgals3、Laptm5和Mpeg1,表现出出色的诊断性能。在5个独立的转录组数据集(GSE49543、GSE6045、GSE153882、GSE154833和GSE233798)中验证了它们在ARHL样本中的上调,并通过实时荧光定量PCR (qRT-PCR)和免疫组化(IHC)进一步验证了衰老小鼠耳蜗中mRNA (FCGR3、CD68、LGALS3、MPEG1)和蛋白(FCGR3、CD68、LGALS3)水平升高。此外,还整合了单核RNA测序(snRNA-seq)数据集GSE274279,以验证单细胞分辨率下枢纽基因的表达。这些发现确定Fcgr3、Cd68、Lgals3、Laptm5和Mpeg1是免疫炎症中心基因,具有作为ARHL诊断生物标志物和治疗靶点的潜力。
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引用次数: 0
Suitability of one-axis measurements for quantifying complex cochlear motion under bone conduction stimulation 骨传导刺激下单轴测量量化复杂耳蜗运动的适用性。
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.heares.2025.109441
Antonio G. Bustos , Ivo Dobrev , Guy Fierens , Christof Röösli
Bone Conduction (BC) refers to the transmission of sound vibrations through the bones of the skull, producing a similar hearing sensation to that of the conventional air-conduction pathway, which transmits sound from the eardrum to the auditory nerve. Clinically, bone conduction hearing aids represent an important resource in the treatment of various middle and outer ear pathologies. Since cochlear motion is considered a good estimation of hearing sensation under BC, accurate motion measurements are essential. Traditionally, single-beam Laser Doppler Vibrometers (LDV) have been used, however, their reliability is limited when the motion deviates from the measurement direction. This study analyses published data of promontory spatial motion, from three-dimensional accelerometers and three-dimensional LDV, to assess the suitability of one-dimensional measurement systems. A literature review of bone conduction studies was conducted, where three-dimensional promontory motion data was analyzed for directional motion influences. The findings presented in this work indicate that motion direction of the ipsilateral promontory is greatly influenced by factors such as distance from stimulation, site and direction of stimulation. Based on the conducted analysis, it was concluded that relying solely on one-dimensional measurements, typically in the ear canal direction, could result in underestimation of the magnitude of the promontory’s motion in the range of 4 to 16 dB at frequencies below 1 kHz, and 1 to 8 dB at higher frequencies, with the largest underestimation occurring when stimulation and measurement are not aligned in the same direction. Hence, clinically relevant metrics, such as transcranial attenuation, are highly dependent on reliable motion measurements. Given the spatial complexity of the promontory motion, three-dimensional measurements are recommended to fully capture skull bone motion and consequently make a better approximation of hearing sensation.
骨传导(Bone Conduction, BC)是指声音振动通过颅骨传递,产生与传统的空气传导途径类似的听觉,后者将声音从鼓膜传递到听神经。在临床上,骨传导助听器是治疗各种中外耳病变的重要资源。由于耳蜗运动被认为是BC下听力感觉的一个很好的估计,准确的运动测量是必不可少的。传统上使用的是单光束激光多普勒测振仪(LDV),但当运动偏离测量方向时,其可靠性受到限制。本研究分析了来自三维加速度计和三维LDV的已发表的海岬空间运动数据,以评估一维测量系统的适用性。我们回顾了骨传导研究的文献,分析了三维海岬运动数据对定向运动的影响。研究结果表明,同侧海岬的运动方向受刺激距离、刺激位置和刺激方向等因素的影响较大。根据所进行的分析,得出的结论是,仅依靠一维测量,通常是在耳道方向,可能导致海岬的运动幅度低估,在1 kHz以下的频率范围内为4至16 dB,在更高的频率范围内为1至8 dB,其中最大的低估发生在刺激和测量不在同一方向时。因此,临床相关指标,如经颅衰减,高度依赖于可靠的运动测量。考虑到海岬运动的空间复杂性,建议采用三维测量来充分捕捉颅骨运动,从而更好地近似听觉。
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引用次数: 0
Eye movements of younger and older adults decrease during story listening in background noise 在背景噪音下听故事时,年轻人和老年人的眼球运动减少
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.heares.2025.109447
Björn Herrmann , Florian Scharf , Andreas Widmann
Assessments of listening effort are increasingly relevant to understanding the speech-comprehension difficulties experienced by older adults. Pupillometry is the most common tool to assess listening effort but has limitations. Recent research has shown that eye movements decrease when listening is effortful and proposed indicators of eye movements as alternative measures. However, much of the work was conducted in younger adults in trial-based sentence-listening paradigms during concurrent visual stimulation. The extent to which eye movements index listening effort during continuous speech listening, independently of visual stimuli, and in older adults, is unknown. In the current study, younger and older adults listened to continuous stories with varying degrees of background noise under free and moving-dots viewing conditions. Eye movements decreased (as indexed by fixation duration, gaze dispersion, and saccade rate) with increasing speech masking. The reduction in eye movements did not depend on age group or viewing conditions, indicating that eye movements can be used to assess effects of speech masking in different visual situations and in people of different ages. The pupil size was only sensitive to speech masking early in the experiment. In sum, the current study suggests that eye movements are a potential tool to assess listening effort during continuous speech listening.
听力努力的评估与理解老年人所经历的语言理解困难越来越相关。瞳孔测量法是评估听力努力程度的最常用工具,但也有局限性。最近的研究表明,当努力倾听时,眼球运动减少,并提出了眼球运动指标作为替代措施。然而,大部分的研究是在年轻的成年人中进行的,在并行视觉刺激下,以句子-听力为基础的试验范式。在独立于视觉刺激的情况下,在老年人中,眼球运动在多大程度上反映了连续语音听力的努力程度,目前尚不清楚。在目前的研究中,年轻人和老年人在自由和移动点观看条件下听不同程度背景噪音的连续故事。随着言语掩蔽的增加,眼球运动减少(以注视时间、凝视分散和扫视率为指标)。眼球运动的减少并不取决于年龄组或观看条件,这表明眼球运动可以用来评估不同视觉情况和不同年龄人群的语音掩蔽效果。在实验早期,瞳孔大小只对语音掩蔽敏感。总而言之,目前的研究表明,眼球运动是评估连续语音听力过程中听力努力程度的潜在工具。
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引用次数: 0
Deciphering the ototoxic effects of six organochlorine pesticides on HEI-OC1 cells and mouse cochlear organotypic cultures 六种有机氯农药对HEI-OC1细胞和小鼠耳蜗器官型培养物的耳毒性作用
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-02 DOI: 10.1016/j.heares.2025.109443
Shuangshuang Mao , Ziying Zhang , Can Zhang, Zihong Zhou, Xiaohua Tan, Dandan Song, Jianyun Zhang, Yang Song, Yu Hong, Rong Chen
Organochlorine pesticides (OCPs), persistent pollutants with mutagenic and carcinogenic risks, that threatens humans, have received limited scientific attention despite their well-documented toxicity. Our study examined the ototoxicity of six prevalent OCPs (p,p’-DDT, p,p’-DDE, p,p’-DDD, Hexachlorocyclohexane, Endosulfan, Heptachlor) that are frequently identified in human biological samples, including blood and breast milk. Our findings revealed that OCPs caused cochlear damage in postnatal day 3 (P3) mice, and exhibited a dose-dependent toxicological response in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells. OCPs exposure led to the generation of ROS (H₂O₂, O₂⁻, mtROS), calcium overload, mitochondrial membrane potential (MMP) decrease, and endoplasmic reticulum (ER) stress activation. Western blot showed a marked reduction in the Bcl-2/Bax ratio, an elevated level of cleaved caspase-9/3, and four increased ER stress markers (p-eIF2α, ATF6, GRP78, CHOP). These results suggest that OCPs induce auditory cell apoptosis through interconnected pathways: oxidative stress, mitochondrial dysfunction, calcium dysregulation, and ER stress. This study provides mechanistic insights into OCP-related ototoxicity, emphasizing the need for stringent regulation of these pervasive environmental toxins.
有机氯农药(ocp)是一种具有致突变和致癌风险的持久性污染物,对人类构成威胁,尽管其毒性已得到充分证明,但科学关注有限。我们的研究检查了六种常见的ocp (p,p ' -DDT, p,p ' -DDE, p,p ' -DDD,六氯环己烷,硫丹,七氯)的耳毒性,这些ocp经常在人类生物样本中被发现,包括血液和母乳。我们的研究结果表明,OCPs可引起出生第3天(P3)小鼠的耳蜗损伤,并在House Ear Institute-Organ of Corti 1 (HEI-OC1)细胞中表现出剂量依赖性的毒理学反应。OCPs暴露导致ROS (h2o2₂,O₂⁻,mtROS)的产生,钙超载,线粒体膜电位(MMP)降低,内质网(ER)应激激活。Western blot结果显示Bcl-2/Bax比值明显降低,cleaved caspase-9/3水平升高,内质网应激标志物(p-eIF2α、ATF6、GRP78、CHOP)升高。这些结果表明OCPs通过相互关联的途径诱导听觉细胞凋亡:氧化应激、线粒体功能障碍、钙调节失调和内质网应激。这项研究提供了ocp相关耳毒性的机制见解,强调了对这些普遍存在的环境毒素进行严格监管的必要性。
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引用次数: 0
Effect of cognitive load on cervical vestibular evoked myogenic potentials 认知负荷对颈前庭诱发肌生成电位的影响。
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-29 DOI: 10.1016/j.heares.2025.109466
Rahina Abubacker , Aravind Kumar Rajasekaran , Anannya Adhikari , Muralidharan Kesavan , Pradeep Yuvaraj
While vestibular responses have traditionally been viewed as reflexive and brainstem-mediated, emerging evidence suggests they are susceptible to modulation by higher-order cognitive processes. This study aimed to investigate the influence of cognitive load, induced by the Stroop task, on Cervical Vestibular Evoked Myogenic Potentials (cVEMPs) in healthy young adults. Thirty healthy right-handed participants (aged 20–25 years) with no history of audio-vestibular, neurological, or musculoskeletal conditions underwent baseline and dual-task cVEMP recordings. The dual-task condition involved the visual Stroop task presented concurrently with acoustic stimulation. Latency (P1, N1) and amplitude (P1–N1) parameters were extracted from the cVEMP waveforms and compared across conditions. All participants exhibited identifiable cVEMP responses under both conditions. A statistically significant reduction in P1–N1 amplitude was observed during the Stroop task compared to baseline (p < 0.02), while P1 and N1 latencies remained unchanged. The asymmetry ratio did not differ significantly between conditions. These findings suggest that cognitive state should be considered during vestibular testing and support the growing recognition of central cognitive influences on vestibular processing. Cognitive load significantly attenuates cVEMP amplitude without affecting latency, suggesting top-down modulation of vestibular reflex strength.
虽然前庭反应传统上被认为是反射性的和脑干介导的,但新出现的证据表明,它们容易受到高阶认知过程的调节。本研究旨在探讨Stroop任务诱导的认知负荷对健康青年颈前庭诱发肌源性电位(cemps)的影响。30名健康的右撇子参与者(年龄20-25岁),无前庭、神经或肌肉骨骼病史,接受基线和双任务cemp记录。双任务条件包括视觉Stroop任务与声刺激同时出现。从cemp波形中提取潜伏期(P1, N1)和振幅(P1-N1)参数,并在不同条件下进行比较。在两种情况下,所有参与者都表现出可识别的cemp反应。与基线相比,在Stroop任务期间观察到P1-N1振幅的统计学显著降低(p < 0.02),而P1和N1潜伏期保持不变。不对称比例在不同条件下无显著差异。这些发现表明,在前庭测试中应考虑认知状态,并支持对前庭加工中枢认知影响的日益认识。认知负荷显著减弱cemp振幅,但不影响潜伏期,提示前庭反射强度自上而下调节。
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引用次数: 0
Promotion of a new gap junction gene Cx46 (GJA3) expression in the cochlea after Cx26 (GJB2) deficiency Cx26 (GJB2)缺乏后耳蜗新间隙连接基因Cx46 (GJA3)表达的促进
IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/j.heares.2025.109454
Tian-Ying Zhai , Jin Chen , Yong Kong , Chun Liang , Hong-Bo Zhao
Gap junction GJB2 (connexin 26, Cx26) gene mutations are responsible for >50 % of nonsyndromic hearing loss. The pathological changes mainly locate in the cochlea. However, little is known about genetic changes in the cochlea after Cx26 deficiency. In this study, we employed bulk Poly(A) RNA-Seq technique and found that Cx26 deficiency could cause many genes up- and down-regulated in the cochlea. One of the unexpected findings is significant upregulation of a gap junctional gene GJA3 (Cx46), which normally expresses in the eye rather than the ear. Quantitative PCR and digital droplet PCR further confirmed the promotion of Cx46 expression in the cochlea after Cx26 deficiency. Immunofluorescent staining showed that the promoted Cx46 was expressed at the same location as Cx26 expression in the cochlea and integrated into the same gap junctional plaques. This promotion is Cx26-specific; there was no promotion of Cx46 expression in the cochlea after knockout (KO) of Cx30 (GJB6), which is another predominant connexin co-expressed in the cochlea. Gene Set Enrichment Analysis (GSEA) revealed that Cx26 deficiency but not Cx30 KO upregulated a phototransduction pathway to promote the eye-specific gene Cx46 expression in the cochlea. This may present a natural compensation to the loss of Cx26 function, since both Cx26 and Cx46 have similar channel properties. Our findings also provide a new cue for developing a genetic approach to treat this common hereditary deafness.
间隙连接GJB2(连接蛋白26,Cx26)基因突变导致50%的非综合征性听力损失。病理改变主要发生在耳蜗。然而,对Cx26缺乏后耳蜗的遗传变化知之甚少。在本研究中,我们采用了bulk Poly(A) RNA-Seq技术,发现Cx26缺乏会导致耳蜗中许多基因的上调和下调。其中一个意想不到的发现是间隙连接基因GJA3 (Cx46)的显著上调,该基因通常在眼睛而不是耳朵中表达。定量PCR和数字液滴PCR进一步证实了Cx26缺乏后耳蜗中Cx46表达的促进作用。免疫荧光染色显示,促进的Cx46与Cx26在耳蜗中的表达位置相同,并整合到相同的间隙连接斑块中。这个促销是cx26特有的;Cx30 (GJB6)是耳蜗中另一种主要的共表达连接蛋白,敲除(KO) Cx30 (GJB6)后,耳蜗中Cx46的表达未得到促进。基因集富集分析(GSEA)显示,Cx26缺乏而非Cx30 KO上调了一条光导通路,促进了耳蜗中眼睛特异性基因Cx46的表达。这可能是对Cx26功能损失的自然补偿,因为Cx26和Cx46都具有相似的通道属性。我们的发现也为开发一种治疗这种常见遗传性耳聋的遗传方法提供了新的线索。
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Hearing Research
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