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.

Bidirectional rotating direct-current triboelectric nanogenerator with self-adaptive mechanical switching for harvesting reciprocating motion

Amid the growing interest in triboelectric nanogenerators(TENGs)as novel energy-harvesting devices,several studies have focused on direct current(DC)TENGs to generate a stable DC output for operating electronic devices.However,owing to the working mechanisms of conventional DC TENGs,generating a stable DC output from reciprocating motion remains a challenge.Accordingly,we propose a bidirectional rotating DC TENG(BiR-TENG),which can generate DC outputs,regardless of the direction of rotation,from reciprocating motions.The distinct design of the BiR-TENG enables the mechanical rectification of the alternating current output into a rotational-direction-dependent DC output.Furthermore,it allows the conversion of the rotational-direction-dependent DC output into a unidirectional DC output by adapting the configurations depending on the rotational direction.Owing to these tailored design strategies and subsequent optimizations,the BiR-TENG could generate an effective unidirectional DC output.Applications of the BiR-TENG for the reciprocating motions of swinging doors and waves were demonstrated by harnessing this output.This study demonstrates the potential of the BiR-TENG design strategy as an effective and versatile solution for energy harvesting from reciprocating motions,highlighting the suitability of DC outputs as an energy source for electronic devices.

Analyses of nonequilibrium transport in atmospheric-pressure direct-current argon discharge under different modes

The key plasma parameters under different discharge modes, such as heavy-particle and electron temperatures, electron number density, and nonequilibrium volume of plasmas, play important roles in various applications of gas discharge plasmas. In this study, a self-consistent two-dimensional nonequilibrium fluid model coupled with an external circuit model is established to reveal the mechanisms related to the discharge modes, including the normal glow, abnormal glow,arc, and glow-to-arc transition modes, with an atmospheric-pressure direct-current(DC) argon discharge as a model plasma system. The modeling results show that, under different discharge modes, the most significant difference between the preceding four discharge modes lies in the current and energy transfer processes on the cathode side. On one hand, the current to the cathode surface is mainly delivered by the ions coming from the plasma column under the glow discharge mode due to the low temperature of the solid cathode, whereas the thermionic and secondary electrons emitted from the hot cathode surface play a very important role under the arc mode with a higher cathode surface temperature and higher ion flux toward the cathode. On the other hand, the energy transfer channel on the cathode side changes from mainly heating the solid cathode under the glow mode to simultaneously heating both the solid cathode and plasma column under the arc mode with an increase in the discharge current. Consequently, the power density in the cathode sheath(P_c) was used as a key parameter for judging different discharge modes, and the range of(0.28–1.2) × 10^(12) W m^(-3) was determined as a critical window of P_c corresponding to the glow-to-arc-mode transition for the atmospheric-pressure DC argon discharge, which was also verified by comparison with the experimental results in this study and the data in the previous literature.

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.

Integration of Electrical Properties and Polarization Loss Modulation on Atomic Fe–N‑RGO for Boosting Electromagnetic Wave Absorption

Developing effective strategies to regulate graphene’s conduction loss and polarization has become a key to expanding its application in the electromagnetic wave absorption(EMWA)field.Based on the unique energy band structure of graphene,regulating its bandgap and electrical properties by introducing heteroatoms is considered a feasible solution.Herein,metal-nitrogen doping reduced graphene oxide(M–N-RGO)was prepared by embedding a series of single metal atoms M–N_(4) sites(M=Mn,Fe,Co,Ni,Cu,Zn,Nb,Cd,and Sn)in RGO using an N-coordination atom-assisted strategy.These composites had adjustable conductivity and polarization to optimize dielectric loss and impedance matching for efficient EMWA performance.The results showed that the minimum reflection loss(RL_(min))of Fe–N-RGO reaches−74.05 dB(2.0 mm)and the maximum effective absorption bandwidth(EAB_(max))is 7.05 GHz(1.89 mm)even with a low filler loading of only 1 wt%.Combined with X-ray absorption spectra(XAFS),atomic force microscopy,and density functional theory calculation analysis,the Fe–N_(4) can be used as the polarization center to increase dipole polarization,interface polarization and defect-induced polarization due to d-p orbital hybridization and structural distortion.Moreover,electron migration within the Fe further leads to conduction loss,thereby synergistically promoting energy attenuation.This study demonstrates the effectiveness of metal-nitrogen doping in regulating the graphene′s dielectric properties,which provides an important basis for further investigation of the loss mechanism.

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.

Therapeutic potential of Carum carvi in depression,memory loss,and hippocampal sclerosis reversal in temporal lobe epilepsy

Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy with Hippocampal Sclerosis(TLE-HS)is the most drug-resistant form of epilepsy,and it also impacts physical,mental,and psychological well-being of patients.Carum carvi extract has demonstrated anti-convulsant,anti-depressant,and anxiolytic properties.This study was designed to investigate if Carum carvi extract can alleviate depression and memory loss symptoms in a TLE-HS animal model.Methods:Male Sprague Dawley rats were used to create a model of TLE-HS and Carum carvi extract treatment,along with appropriate controls,was used to test the efficacy of this herbal extract in reducing the symptoms of depression and memory loss.Results:Forced swim test showed that Carum carvi extract treated TLE-HS rats resulted in significant improvement of the symptoms of depression.However,novel object recognition test showed that memory improvement did not occur.Conclusion:Depression significantly impacts the quality of life in TLE-HS patients,and this study has shown that Carum carvi extract should be explored further as an adjuvant treatment for TLE-HS patients to improve their quality of life.

Convolutional Graph Neural Network with Novel Loss Strategies for Daily Temperature and Precipitation Statistical Downscaling over South China

Traditional meteorological downscaling methods face limitations due to the complex distribution of meteorological variables,which can lead to unstable forecasting results,especially in extreme scenarios.To overcome this issue,we propose a convolutional graph neural network(CGNN)model,which we enhance with multilayer feature fusion and a squeeze-and-excitation block.Additionally,we introduce a spatially balanced mean squared error(SBMSE)loss function to address the imbalanced distribution and spatial variability of meteorological variables.The CGNN is capable of extracting essential spatial features and aggregating them from a global perspective,thereby improving the accuracy of prediction and enhancing the model's generalization ability.Based on the experimental results,CGNN has certain advantages in terms of bias distribution,exhibiting a smaller variance.When it comes to precipitation,both UNet and AE also demonstrate relatively small biases.As for temperature,AE and CNNdense perform outstandingly during the winter.The time correlation coefficients show an improvement of at least 10%at daily and monthly scales for both temperature and precipitation.Furthermore,the SBMSE loss function displays an advantage over existing loss functions in predicting the98th percentile and identifying areas where extreme events occur.However,the SBMSE tends to overestimate the distribution of extreme precipitation,which may be due to the theoretical assumptions about the posterior distribution of data that partially limit the effectiveness of the loss function.In future work,we will further optimize the SBMSE to improve prediction accuracy.

基于Focal Loss改进LightGBM的供水管网毛刺数据检测

针对数据不平衡导致的管网毛刺数据检测召回率偏低问题,提出一种Focal Loss改进LightGBM的管网毛刺数据检测方法。首先,结合管网毛刺数据的特点,针对性构造邻域相关特征。其次,将Focal Loss函数引入LightGBM,提高模型对难以检测的毛刺样本的权重,并对Focal Loss不同的参数取值进行实验,以平衡精确率与召回率。最后,选择不同参数的Focal Loss进行模型融合,进一步提升模型对不平衡毛刺数据的检测性能。在某市供水管网的真实数据上进行实验,结果表明,对比基于交叉熵损失函数的单一模型,本文提出的Focal Loss改进后的融合模型在毛刺数据上召回率和F1值的提升幅度达33.3和18个百分点,但毛刺数据的精确率还有待进一步提升。本文所提方法从损失函数入手,动态调整难易样本的权重,有效地提升了不平衡数据下的毛刺数据的检测性能。

Constructions and Preliminary HV Conditioning of a Photocathode Direct-Current Electron Gun at IHEP

As one of the most important key technologies for future advanced light source based on the energy recovery linac, a photocathode dc electron gun is supported by Institute of High Energy Physics （IHEP） to address the technical challenges of producing very low ernittance beams at high average current. Construction of the dc gun is completed and a preliminary high voltage conditioning is carried out up to 440 k V. The design, construction and preliminary HV conditioning results for the dc gun are described.

Anomalous Direct-Current Josephson Effect in Semiconductor Nanowire Junctions

We investigate the dc Josephson effect in one-dimensional junctions where a ring conductor is sandwiched between two semiconductor nanowires with proximity-induced superconductivity. Peculiar features of the Josephson effect arise due to the interplay of spin-orbit interaction and external Zeenmn field. By tuning the Zeeman field orientation, the device can vary from 0 to π junction. Afore importantly, nonzero ,losephson current is possible at zero phase difference across the junction. Although this anomalous Josephson current is not relevant to the topological phase transition, its magnitude can be significantly enhanced whe, n the nanowire, s become topological superconductors where Majorana bound states emerge. Distinct modulation patterns are obtained for the semiconductor nanowires in the topologically trivial and non-trivial phases. These results are useful to probe the topological phase transition in semiconductor nanowire junctions via the dc Josephson effect.

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.

Modeling of Pulsed Direct-Current Glow Discharge

A self-consistent model was adopted to study the time evolution of low-voltage pulsed DC glow discharge. The distributions of electric field, ion density and electron density in nitrogen were investigated in our simulation, and the temporal shape of the discharge current was also obtained. Our results show that the dynamic behaviors of the discharge depends strongly on the applied pulse voltage, and the use of higher pulse voltages results in a significantly increase of discharge current and a decrease of discharge delay time. The current-voltage characteristic cMculated by adjusting secondary electron emission coefficient for different applied pulse voltage under the gas pressure of 1 Torr is found in a reasonable agreement with the experimental results.

Effects of the sputtering power on the crystalline structure and optical properties of the silver oxide films deposited using direct-current reactive magnetron sputtering

This paper reports that a series of silver oxide （AgzO） films are deposited on glass substrates by direct-current reactive magnetron sputtering at a substrate temperature of 250 ℃ and an oxygen flux ratio of 15：18 by modifying the sputtering power （SP）. The AgxO films deposited apparently show a structural evolution from cubic biphased （AgO ＋ Ag20） to cubic single-phased （Ag20）, and to biphased （Ag20 ＋ AgO） structure. Notably, the cubic single-phased Ag20 fihn is deposited at the SP = 105 W and an AgO phase with （220） orientation discerned in the Ag^O films deposited using the SP 〉 105 W. The transmissivity and refiectivity of the AgxO films in transparent region decrease with the increase the SP, whereas the absorptivity inversely increases with the increase of the SP. These results may be due to the structural evolution and the increasing film thickness. A redshift of the films＇ absorption edges determined in terms of Tauc formula clearly occurs from 3.1 eV to 2.73 eV with the increase of the SP.

Research on corona discharge suppression of high-voltage direct-current transmission lines based on dielectric-film-covered conductor

Corona discharge suppression for high-voltage direct-current(HVDC)transmission lines at line terminals such as converter stations is a subject that requires attention.In this paper,a method based on a conductor covered with dielectric film is proposed and implemented through a bench-scale setup.Compared with the bare conductor,the corona discharge suppression effect of the dielectric-film-covered conductor under positive polarity is studied from the composite field strength and ion current density using a line-plate experimental device.The influences of film thickness and film material on the corona discharge suppression effect are investigated.The charge accumulation and dissipation characteristics of different film materials are also studied.The results show that the conductor covered with dielectric film has excellent ability to inhibit corona discharge.The ground-level composite field strength of the conductor covered with dielectric film is lower than its nominal field strength,and its ion current density is at the nA m^(−2) level.The corona threshold voltage can be promoted by increasing the film thickness,but the ability to inhibit corona discharge becomes weak.The larger the surface electric field strength,the more charge accumulated,but the faster the charge dissipation rate.Compared with polyvinyl chloride film,cross-linked polyethylene film has stronger charge accumulation ability and slower charge dissipation rate,which can better restrain the corona discharge of HVDC transmission lines.

A crosstalk-free dual-mode sweat sensing system for naked-eye sweat loss quantification via changes in structural reflectance

Sweat loss monitoring is important for understanding the body’s thermoregulation and hydration status,as well as for comprehensive sweat analysis.Despite recent advances,developing a low-cost,scalable,and universal method for the fabrication of colorimetric microfluidics designed for sweat loss monitoring remains challenging.In this study,we propose a novel laserengraved surface roughening strategy for various flexible substrates.This process permits the construction of microchannels that show distinct structural reflectance changes before and after sweat filling.By leveraging these unique optical properties,we have developed a fully laser-engraved microfluidic device for the quantification of naked-eye sweat loss.This sweat loss sensor is capable of a volume resolution of 0.5µL and a total volume capacity of 11µL,and can be customized to meet different performance requirements.Moreover,we report the development of a crosstalk-free dual-mode sweat microfluidic system that integrates an Ag/AgCl chloride sensor and a matching wireless measurement flexible printed circuit board.This integrated system enables the real-time monitoring of colorimetric sweat loss signals and potential ion concentration signals without crosstalk.Finally,we demonstrate the potential practical use of this microfluidic sweat loss sensor and its integrated system for sports medicine via on-body studies.

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.