The loaded matrix:neurotrophin-enriched hydrogels for stem cell brain repair in Parkinson's disease

More than 200 years after Parkinson's disease was first described by the English surgeon whose name would eventually be given to the condition,available treatments remain purely symptomatic,leaving a critical unmet clinical need for a diseasemodifying therapy.

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

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

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

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

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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

Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

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.

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.

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。

Power Transformer No-Load Loss Prediction with FEM Modeling and Building Factor Optimization

Estimation of power transformer no-load loss is a critical issue in the design of distribution transformers. Any deviation in estimation of the core losses during the design stage can lead to a financial penalty for the transformer manufacturer. In this paper an effective and novel method is proposed to determine all components of the iron core losses applying a combination of the empirical and numerical techniques. In this method at the first stage all computable components of the core losses are calculated, using Finite Element Method (FEM) modeling and analysis of the transformer iron core. This method takes into account magnetic sheets anisotropy, joint losses and stacking holes. Next, a Quadratic Programming (QP) optimization technique is employed to estimate the incomputable components of the core losses. This method provides a chance for improvement of the core loss estimation over the time when more measured data become available. The optimization process handles the singular deviations caused by different manufacturing machineries and labor during the transformer manufacturing and overhaul process. Therefore, application of this method enables different companies to obtain different results for the same designs and materials employed, using their historical data. Effectiveness of this method is verified by inspection of 54 full size distribution transformer measurement data.

Simulating long-term effect of Hyrcanian forest loss on phosphorus loading at the sub-watershed level

Conversion of forest land to farmland in the Hyrcanian forest of northern Iran increases the nutrient input, especially the phosphorus（P） nutrient, thus impacting the water quality. Modeling the effect of forest loss on surface water quality provides valuable information for forest management. This study predicts the future impacts of forest loss between 2010 and 2040 on P loading in the Tajan River watershed at the sub-watershed level. To understand drivers of the land cover, we used Land Change Modeler（LCM） combining with the Soil Water Assessment Tool（SWAT） model to simulate the impacts of land use change on P loading. We characterized priority management areas for locating comprehensive and cost-effective management practices at the sub-watershed level. Results show that agricultural expansion has led to an intense deforestation. During the future period 2010–2040, forest area is expected to decrease by 34,739 hm^2. And the areas of pasture and agriculture are expected to increase by 7668 and 27,071 hm^2, respectively. In most sub-watersheds, P pollution will be intensified with the increase in deforestation by the year 2040. And the P concentration is expected to increase from 0.08 to 2.30 mg/L in all of sub-watersheds by the year 2040. It should be noted that the phosphorous concentration exceeds the American Public Health Association′s water quality standard of 0.2 mg/L for P in drinking water in both current and future scenarios in the Tajan River watershed. Only 30% of sub-watersheds will comply with the water quality standards by the year 2040. The finding of the present study highlights the importance of conserving forest area to maintain a stable water quality.

A Stator Current Vector Orientation Based Multi-objective Integrative Suppressions of Flexible Load Vibration and Torque Ripple for PMSM Considering Electrical Loss

To store energy from the grid into spiral torsion spring(STS)smoothly and efficiently via PMSM,a multi-objective control problem of flexible load’s vibration,PMSM’s torque ripple,and electrical loss is raised,where the current studies on vibration and torque ripple are mostly addressed separately,not to mention electrical loss.This research attempts to propose a multi-objective integrative control scenario that can simultaneously solve these problems satisfactorily in a unitary nonlinear control framework.Firstly,a dynamic mathematical model of PMSM is built under stator current vector orientation,and then the model of PMSM is combined with the vibration model of STS to establish the overall system model of STS driven by PMSM with considering motor’s electrical loss.Then,a backstepping control principle-based multi-objective integrative control approach is proposed to realize the suppression of flexible load’s vibration and the reduction of PMSM’s torque ripple and electrical loss concurrently.Meanwhile,this research also designs a wide range speed identification method based on the least square algorithm with a forgetting factor.Simulation and experimental results have verified that the proposed integrative control method enables the state variables to track their respective references quickly and accurately,both torque ripple and load vibration are effectively suppressed,and the operating efficiency of the whole system is improved.

Distortionless Lossy Transmission Lines Terminated by in Series Connected <i>RCL</i>-Loads

The paper deals with a lossy transmission line terminated at both ends by non-linear RCL elements. The mixed problem for the hyperbolic system, describing the transmission line, to an initial value problem for a neutral equation is reduced. Sufficient conditions for the existence and uniqueness of periodic regimes are formulated. The proof is based on the finding out of suitable operator whose fixed point is a periodic solution of the neutral equation. The method has a good rate of convergence of the successive approximations even for high frequencies.

Mechanical responses of anchoring structure under triaxial cyclic loading

Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.

Effects of Glosses and Involvement Loads on Incidental Vocabulary Acquisition

The present study aims at exploring the effects of different glosses and involvement loads on incidental vocabulary acquisition among non-English majors.It investigates whether glosses and involvement load would have an effect on the learners’immediate word gain and promote their word knowledge retention.The experiment chooses 96 non-English freshmen at a university in Si Chuan Province.Results indicate that Translation task with multiple-choice glosses is the most effective,and reading comprehension task with single glosses is the worst.

Optimal Placement of Reclosers to Minimize Power Losses during Non-Load Bearing Disturbances in a Power Distribution Using Firefly Algorithm

The research reported in this paper focuses on non-technical power loss reduction for power distribution systems. Such reduction of costs of energy not served (ENS.COST), is intelligently evaluated and optimized using a firefly algorithm, from where savings of 43.3% on energy not served are achieved.

State-of-the-art on the anchorage performance of rock bolts subjected to shear load

Rock bolts are extensively utilized in underground engineering as a means of offering support and stability to rock masses in tunnels,mines,and other underground structures.In environments of high ground stress,faults or weak zones can frequently arise in rock formations,presenting a significant challenge for engineering and potentially leading to underground engineering collapse.Rock bolts serve as a crucial structural element for the transmission of tensile stress and are capable of withstanding shear loads to prevent sliding of weak zones within rock mass.Therefore,a complete understanding of the behavior of rock bolts subjected to shear loads is essential.This paper presents a state-of-the-art review of the research progress of rock bolts subjected to shear load in three categories:experiment,numerical simulation,and analytical model.The review focuses on the research studies and developments in this area since the 1970s,providing a comprehensive overview of numerous factors that influence the anchorage performance of rock bolts.These factors include the diameter and angle of the rock bolt installation,rock strength,grouting material,bolt material,borehole diameter,rock bolt preload,normal stress,joint surface roughness and joint expansion angle.The paper reviews the improvement of mechanical parameter setting in numerical simulation of rock bolt shear.Furthermore,it delves into the optimization of the analytical model concerning rock bolt shear theory,approached from the perspectives of both Elastic foundation beam theory coupled with Elastoplasticity theory and Structural mechanic methods.The significance of this review lies in its ability to provide insights into the mechanical behavior of rock bolts.The paper also highlights the limitations of current research and guidelines for further research of rock bolts.

Prediction of Attention and Short-Term Memory Loss by EEG Workload Estimation

Mental workload plays a vital role in cognitive impairment. The impairment refers to a person’s difficulty in remembering, receiving new information, learning new things, concentrating, or making decisions that seriously affect everyday life. In this paper, the simultaneous capacity (SIMKAP) experiment-based EEG workload analysis was presented using 45 subjects for multitasking mental workload estimation with subject wise attention loss calculation as well as short term memory loss measurement. Using an open access preprocessed EEG dataset, Discrete wavelet transforms (DWT) was utilized for feature extraction and Minimum redundancy and maximum relevancy (MRMR) technique was used to select most relevance features. Wavelet decomposition technique was also used for decomposing EEG signals into five sub bands. Fourteen statistical features were calculated from each sub band signal to form a 5 × 14 window size. The Neural Network (Narrow) classification algorithm was used to classify dataset for low and high workload conditions and comparison was made using some other machine learning models. The results show the classifier’s accuracy of 86.7%, precision of 84.4%, F1 score of 86.33%, and recall of 88.37% that crosses the state-of-the art methodologies in the literature. This prediction is expected to greatly facilitate the improved way in memory and attention loss impairments assessment.

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.

Comparative Analysis between Conventional PI, Fuzzy Logic and Artificial Neural Network Based Speed Controllers of Induction Motor with Considering Core Loss and Stray Load Loss

Most of the controllers of IM （induction motor） for industrial applications have been designed based on PI controller without consideration of CL （core loss） and SLL （stray load loss）. To get the precise performances of torque as well as rotor speed and flux, the above mentioned losses should be considered. Conventional PI controller has overshoot effect at the transient period of the speed response curve. On the other hand, fuzzy logic and ANN （artificial neural network） based controllers can minimize the overshoot effect at the transient period because they have the abilities to deal with the nonlinear systems. In this paper, a comparative analysis is done between PI, fuzzy logic and ANN based speed controllers to find the suitable control strategy for IM with consideration of CL and SLL. The simulation analysis is done by using Matlab/Simulink software. The simulation results show that the fuzzy logic based speed controller gives better responses than ANN and conventional PI based speed controllers in terms of rotor speed, electromagnetic torque and rotor flux of IM.

Mechanical behavior and failure mechanisms of rock bolts subjected to static-dynamic loads

This study explores the effects of dynamic and static loading on rock bolt performance a key factor in maintaining the structural safety of coal mine roadways susceptible to coal bursts.Employing a housemade load frame to simulate various failure scenarios,pretension-impact-pull tests on rock bolts were conducted to scrutinize their dynamic responses under varied static load conditions and their failure traits under combined loads.The experimental results denote that with increased impact energy,maximum and average impact loads on rock bolts escalate significantly under pretension,initiating plastic deformation beyond a certain threshold.Despite minor reductions in the yield load due to impactinduced damage,pretension aids in constraining post-impact deformation rate and fluctuation degree of rock bolts.Moreover,impact-induced plastic deformation causes internal microstructure dislocation,fortifying the stiffness of the rock bolt support system.The magnitude of this fortification is directly related to the plastic deformation induced by the impact.These findings provide crucial guidance for designing rock bolt support in coal mine roadway excavation,emphasizing the necessity to consider both static and dynamic loads for improved safety and efficiency.