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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,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 *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment Prevention and Treatment BeijingChina department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,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 *** 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 *** 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 *** 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 *** 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 ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** 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 *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Regression analysis of squeezing-induced hybrid nanofluid flow in Darcy-Forchheimer porous medium

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 193-208页

作者： K.MUHAMMAD M.SARFRAZ department of Humanities and sciences School of Electrical Engineering and Computer Science National University of Sciences and Technology department of Mathematics Quaid-i-Azam University

This article presents a mathematical model addressing a scenario involving a hybrid nanofluid flow between two infinite parallel plates. One plate remains stationary, while the other moves downward at a squeezing velocity. The space between these plates contains a Darcy-Forchheimer porous medium. A mixture of water-based fluid with gold(Au) and silicon dioxide(Si O2) nanoparticles is formulated. In contrast to the conventional Fourier's heat flux equation, this study employs the Cattaneo-Christov heat flux equation. A uniform magnetic field is applied perpendicular to the flow direction, invoking magnetohydrodynamic(MHD) effects. Further, the model accounts for Joule heating, which is the heat generated when an electric current passes through the fluid. The problem is solved via NDSolve in MATHEMATICA. Numerical and statistical analyses are conducted to provide insights into the behavior of the nanomaterials between the parallel plates with respect to the flow, energy transport, and skin *** findings of this study have potential applications in enhancing cooling systems and optimizing thermal management strategies. It is observed that the squeezing motion generates additional pressure gradients within the fluid, which enhances the flow rate but reduces the frictional drag. Consequently, the fluid is pushed more vigorously between the plates, increasing the flow velocity. As the fluid experiences higher flow rates due to the increased squeezing effect, it spends less time in the region between the plates. The thermal relaxation, however, abruptly changes the temperature, leading to a decrease in the temperature fluctuations.

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Crosstalk between degradation and bioenergetics: how autophagy and endolysosomal processes regulate energy production

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Neural Regeneration Research 2025年第3期20卷 671-681页

作者： Angelid Pabon Jagannatham Naidu Bhupana Ching-On Wong department of Biological sciences Rutgers UniversityNewarkNJUSA

Cells undergo metabolic reprogramming to adapt to changes in nutrient availability, cellular activity, and transitions in cell states. The balance between glycolysis and mitochondrial respiration is crucial for energy production, and metabolic reprogramming stipulates a shift in such balance to optimize both bioenergetic efficiency and anabolic requirements. Failure in switching bioenergetic dependence can lead to maladaptation and pathogenesis. While cellular degradation is known to recycle precursor molecules for anabolism, its potential role in regulating energy production remains less explored. The bioenergetic switch between glycolysis and mitochondrial respiration involves transcription factors and organelle homeostasis, which are both regulated by the cellular degradation pathways. A growing body of studies has demonstrated that both stem cells and differentiated cells exhibit bioenergetic switch upon perturbations of autophagic activity or endolysosomal processes. Here, we highlighted the current understanding of the interplay between degradation processes, specifically autophagy and endolysosomes, transcription factors, endolysosomal signaling, and mitochondrial homeostasis in shaping cellular bioenergetics. This review aims to summarize the relationship between degradation processes and bioenergetics, providing a foundation for future research to unveil deeper mechanistic insights into bioenergetic regulation.

关键词： autophagy bioenergetics endolysosome energy production glycolysis metabolic reprogramming mitochondria

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Binaural integration abilities in bilateral cochlear implant user

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Journal of Otology 2015年第4期10卷 150-153页

作者： Chie Obuchi Masae Shiroma Sayaka Ogane Kimitaka Kaga department of speech and hearing sciences International University of Health and Welfare

Bilateral Cochlear implants (CIs) improved speech intelligibility, speech perception in background noise, and sound localization in quiet and noisy situations. However, it is unclear whether these advantages essentially result in binaural integration of acoustic stimuli from each ear. In this study, we investigated the effectiveness of binaural integration by bilateral CIs placement using binaural hearing tests and subjective auditory perceptual assessment. A 61-year-old bilateral CIs subject underwent the following four tests:the Japanese hearing in Noise Test (HINT-J), the dichotic listening test (DLT), the Rapidly Alternating speech Perception (RASP) test, and subjective auditory perceptual assessment. The HINT-J score was significantly higher for bilateral CIs than for a unilateral CI. However, DLT and the RASP test revealed contradictory results. Subjective auditory perceptual assessment revealed active and bright impressions for bilateral hearing, which were also noisy and strong compared with those for unilateral hearing. The results of this study revealed that bilateral CIs improved speech perception in background noise and an improved auditory impression, although the bilateral integration abilities were not improved. This was probably because the patient was required to combine information from the two ears into a single perception in DLT and the RASP test. More longitudinal data should be collected and analyzed in future studies to evaluate the long-term effects of bilateral CIs. Copyright ? 2016, PLA General Hospital department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Bilateral cochlear implants Binaural integration ability Subjective auditory perceptual assessment

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Gain adjustment at tinnitus pitch to manage both tinnitus and speech perception in noise

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Journal of Otology 2019年第4期14卷 141-148页

作者： Hemanth Narayan Shetty Jijo Mathai Pottackal department of Audiology All India Institute of Speech and HearingMysuru570006India department of speech and hearing JSS Institute of Speech and HearingDharwad580007India

To investigate how much gain variation is required from prescription to effect tinnitus percept,and if this revised prescription affects speech *** participants who experienced catastrophic tinnitus even after fitted with hearing aid were *** were grouped based on their tinnitus pitch and the prescriptive formula used to fit hearing *** were evaluated for handicap from tinnitus using Tinnitus Handicap Inventory(THI).hearing aid was programmed using either NAL-NL2 or DSL(I/o)v5 prescriptive formula and gain at tinnitus pitch was adjusted till the tinnitus get *** 50 was determined soon after fitted with hearing aid and 30 days of hearing aid ***,THI and international outcome inventory for hearing aid(IOI-HA)were determined after 30 days of hearing aid use.A significant higher gain adjustment was needed at tinnitus pitch to reduce tinnitus precept using NAL-NL2 than DSL(I/o)v5 prescriptive ***,SNR 50 was not affected by either tinnitus pitch or revised prescription ***,SNR 50 improved after 30 days of hearing aid use.A 76% of the participants’experienced habituation to perception after 30 days of hearing aid use,10% had slight,10% had mild,and 4% had a moderate degree of tinnitus on *** IOA-HA,96%(N=19)of participants have reported satisfactory,and 4%(N=1)reported moderate benefit from hearing *** of prescriptive formula adjusting gain at tinnitus pitch is an efficient method to reduce tinnitus symptoms and improve speech perception.

关键词： Amplification hearing loss Tinnitus speech perception hearing aid

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Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda Zhang Weimin Yuan Zhixing Ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng Wang Lei Yang Bing Zhang Chen Zhang Shuang-Nan Zhang Yonghe Zhang Jie An David Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris Zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis Galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong Li Bifang Liu Mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng Wang Song Wang Tinggui Wang Zhongxiang Wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian Zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai Dongwei Fan Ju Guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen Jiang Ge Jin Chengkui Li Junfei Li Longhui Li Maoshun Li Wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu Fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao Wang Juan Wang Lei Wang Wenxin Wang Yilong Wang Yusa Wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang Juan Zhang Mo Zhang Wenjie Zhang Zhen Zhang Zhen Zhang Ziliang Zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of sciences School of Astronomy and Space sciences University of Chinese Academy of sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of sciences Institute of Space sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of sciences department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of sciences Physics department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory department of Astronomy University of Cape Town department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM department of Astronomy Guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University department of Astronomy University of Science and Technology School of Astronomy and Space sciences University of Science and Technology of China Institute of Deep Space sciences Deep Space Exploration Laboratory department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,GROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

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Enhanced auditory evoked potentials in musicians:A review of recent findings

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Journal of Otology 2016年第2期11卷 63-72页

作者： Himanshu Kumar Sanju Prawin Kumar All India Institute of speech and hearing department of Audiology All India Institute of Speech and Hearing

Auditory evoked potentials serve as an objective mode for assessment to check the functioning of the auditory system and *** has reported enhanced electrophysiological responses in musicians, which shows neuroplasticity in musicians. Various databases including Pub Med, Google, Google Scholar and Medline were searched for references related to auditory evoked potentials in musicians from 1994 till date. Different auditory evoked potentials in musicians have been summarized in the present article. The findings of various studies may support as evidences for music-induced neuroplasticity which can be used for the treatment of various clinical disorders. The search results showed enhanced auditory evoked potentials in musicians compared to non-musicians from brainstem to cortical levels. Also, the present review showed enhanced attentive and pre-attentive skills in musicians compared to non-musicians.

关键词： Neuroplasticity Auditory evoked potential Review Musicians Electrophysiological

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Apolipoprotein E elicits targetdirected miRNA degradation to maintain neuronal integrity

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Neural Regeneration Research 2025年第9期20卷 2577-2578页

作者： Jiazi Tan Chin-Tong Ong Temasek Life sciences Laboratory National University of SingaporeSingapore department of Biological sciences National University of SingaporeSingapore

Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous *** are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.

关键词： metabolism glycoprotein maintain

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Pre-attentive auditory discrimination skill in Indian classical vocal musicians and non-musicians

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Journal of Otology 2016年第3期11卷 102-110页

作者： Himanshu Kumar Sanju Prawin Kumar All India Institute of speech and hearing department of Audiology All India Institute of Speech and Hearing

Objective:To test for pre-attentive auditory discrimination skills in Indian classical vocal musicians and ***:Mismatch negativity(MMN) was recorded to test for pre-attentive auditory discrimination skills with a pair of stimuli of /1000 Hz/ and/1100 Hz/,with /1000 Hz/ as the frequent stimulus and /1100 Hz/ as the infrequent ***,offset and peak latencies were the considered latency parameters,whereas peak amplitude and area under the curve were considered for amplitude *** sample:Exactly 50 participants,out of which the experimental group had 25 adult Indian classical vocal musicians and 25 age-matched non-musicians served as the control group,were included in the *** group participants had a minimum professional music experience in Indian classic vocal music of 10 ***,control group participants did not have any formal training in ***:Descriptive statistics showed better waveform morphology in the experimental group as compared to the *** showed significantly better onset latency,peak amplitude and area under the curve in the experimental group but no significant difference in the offset and peak latencies between the two ***:The present study probably points towards the enhancement of pre-attentive auditory discrimination skills in Indian classical vocal musicians compared to *** indicates that Indian classical musical training enhances pre-attentive auditory discrimination skills in musicians,leading to higher peak amplitude and a greater area under the curve compared to non-musicians.

关键词： Neuronal plasticity Event-related potentials Music

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