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

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun wang Xiaoxu Zhang Song Mao Yini Li Dongzhen yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

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

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu yu wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao yuan Lingqi yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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微针在皮肤间质液生物分析中的研究进展

分析化学 2022年第6期50卷 819-829页

作者：卢惠婷李金泽王夜宇葛如娇董海峰北京科技大学化学与生物工程学院生物工程与传感技术北京市重点实验室深圳大学生物医学工程学院马歇尔生物医学工程实验室

对生物样品进行采集并分析测定是疾病诊断和治疗的有效手段，其中，血液取样和分析是临床诊断中的标准方法，但血液采样具有损伤性，通常会导致皮肤组织损伤从而引起患者不适。皮肤间质液（Interstitial skin fluid, ISF）具有丰富的生... 详细信息

对生物样品进行采集并分析测定是疾病诊断和治疗的有效手段，其中，血液取样和分析是临床诊断中的标准方法，但血液采样具有损伤性，通常会导致皮肤组织损伤从而引起患者不适。皮肤间质液（Interstitial skin fluid, ISF）具有丰富的生物学信息，是一种很有前景的血液替代品，然而，以微创和非侵入性方式采集ISF中足够的标志物仍然具有很大的挑战。近年来，微针（Microneedles, MNs）技术因其具有高效、安全、方便和无痛等特点，在ISF研究中备受关注。MNs作为一种微米级别的针阵列，在医疗美容、分子递送、诊断监测以及疾病治疗等方面取得了显著的成果，但在ISF生物分析中的应用很少。本文总结了制备MNs的材料，详细描述了MNs在ISF采样、生物标志物捕获和分析以及可穿戴传感等方面的应用，展望了MNs作为一个新兴研究领域的发展前景，并总结了在技术成果转化过程中需要考虑和存在的问题。

关键词：微针生物分析体液采样微创评述

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新发展理念下高职院校高水平专业群建设研究

湖北开放职业学院学报 2024年第13期37卷 63-64,76页

作者：王妤夜冯逆水王青无锡工艺职业技术学院江苏无锡214206

专业群建设实质为打造能够精准对接区域职业岗位群的专业群。但当前高职院校在专业群建设中并未形成全新建设思路,不仅缺乏建“群”意识,还存在一定盲目性与随意性。“创新、协调、绿色、开放、共享”的新发展理念正推动着中国经济社会... 详细信息

专业群建设实质为打造能够精准对接区域职业岗位群的专业群。但当前高职院校在专业群建设中并未形成全新建设思路,不仅缺乏建“群”意识,还存在一定盲目性与随意性。“创新、协调、绿色、开放、共享”的新发展理念正推动着中国经济社会高质量发展。高职院校也应积极应用新发展理念引领专业群建设,瞄准适应产业、支撑发展、中国特色、世界水平等目标,以创新发展精准对接区域产业群、以协调发展强化专业群内部治理、以绿色发展打造高水平师资队伍、以开放发展强化专业群国际交流、以共享发展深化专业群校企合作,推动高职院校高质量发展。

关键词：新发展理念高职院校高水平专业群建设

基于超表面的太赫兹与中长波红外高效分光器件

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物理学报 2024年第19期73卷 296-303页

作者：张鸿伟蔡仁昊李吉宁钟凯王与烨徐德刚姚建铨天津大学精密仪器与光电子工程学院天津300072 天津大学光电信息技术教育部重点实验室天津300072 天津大学微光机电系统技术教育部重点实验室天津300072 天津津航技术物理研究所天津300038

多模复合成像技术结合了不同传感器的优势,具有图像质量高、信息获取能力强、目标检测和识别能力高、对复杂环境的强适应能力、系统的稳定性和鲁棒性高等优点.其中,太赫兹和红外复合成像技术结合了太赫兹波段和红外波段的特点,具有宽频... 详细信息

多模复合成像技术结合了不同传感器的优势,具有图像质量高、信息获取能力强、目标检测和识别能力高、对复杂环境的强适应能力、系统的稳定性和鲁棒性高等优点.其中,太赫兹和红外复合成像技术结合了太赫兹波段和红外波段的特点,具有宽频谱覆盖、高分辨率、穿透性强的优点,有广阔的应用前景.作为共口径复合成像系统的关键器件之一的太赫兹和红外波段的高效分光器目前仍然缺少,性能亟待提升.本文提出了一种结构简单、性能高效的双层金属加介质基底结构二向色超表面.作为分光器件使用,当入射角度为45°时,其在中心频率1.1 THz附近实现大于97%的透射系数,在中波红外3—5μm和长波红外8—14μm波长范围均实现大于98%的反射系数.该设计对层间结构错位、结构倒圆角、小倍率缩放等结构失配和加工误差都具有很好的鲁棒性,并且具有偏振不敏感特性.而当入射角度在0°—60°内变化时,器件依然保持优异的分光特性.基于巴比涅定理和等效电路模型,对该超表面的电磁响应特性进行理论分析,分析结果与模拟仿真结果相吻合.该研究结果证明了超表面作为分光器件应用于太赫兹与红外波段的多波长复合成像系统中的可行性,并为未来新型复合成像探测技术的研究提供了支撑.

关键词：超表面二向色镜等效电路模型巴比涅定理

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毛细管辐射采暖热源方案技术经济分析

流体机械 2010年第1期38卷 81-85页

作者：傅允准蔡颖玲李晶王烨玉上海工程技术大学上海201620

首先介绍毛细管辐射采暖地面和顶棚构造，并采用试验方法分析热泵机组供热性能，然后采用BIN法计算不同热源方案毛细管采暖系统能耗，分析其节能性；最后分析各热源方案的初投资和运行费用以及其对环境影响。通过研究得出：（1）地源热... 详细信息

首先介绍毛细管辐射采暖地面和顶棚构造，并采用试验方法分析热泵机组供热性能，然后采用BIN法计算不同热源方案毛细管采暖系统能耗，分析其节能性；最后分析各热源方案的初投资和运行费用以及其对环境影响。通过研究得出：（1）地源热泵机组提供28～35℃的低温热水时的COP值与制取40～50℃热水相比大大提高，节能效果显著；（2）在冬季采暖总耗煤量方面，地源热泵系统最小，与风冷热泵、天然气燃气炉相比分别节省了32．9％、129％的耗煤量；（3）采用天燃气采暖炉为热源时，污染物排放量最少，对环境破坏最小；（4）从经济方面分析，风冷热泵冷热水机组是最优的热源方案。

关键词：毛细管辐射采暖热源方案经济性环境影响

[Current advances in the analysis of free RNA modified nucleosides by high performance liquid chromatography-tandem mass spectrometry]

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Se pu = Chinese journal of chromatography 2025年第1期43卷 3-12页

作者： Lyu-ye Zhang Wei-Bing Zhang Hai-Lin wang State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China. Shanghai Key Laboratory of Functional Materials Chemistry School of Chemistry & Molecular Engineering East China University of Science and Technology Shanghai 200237 China. State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China 3. University of Chinese Academy of Sciences Beijing 100049 China. University of Chinese Academy of Sciences Beijing 100049 China.

Post-transcriptional ribonucleic acid (RNA) modifications play crucial roles in regulating gene expression, with both eukaryotic and prokaryotic RNA exhibiting more than 170 distinct and ubiquitous modifications. RNA turnover generates numerous free nucleosides, including unmodified nucleosides and a variety of modified ones. Unlike unmodified nucleosides, modified nucleosides are not further degraded or used in the salvage-synthesis pathway owing to a lack of specific enzymes, which leads to the cytosolic accumulation or cellular efflux of modified nucleosides. These modified nucleosides can act as signaling molecules that regulate downstream pathways once transported to the extracellular space; alternatively, they are metabolized in the bloodstream and excreted in urine. Metabolized modified nucleosides are altered by cellular stress responses and mediate abnormal physiological states. Changes in the urinary and blood levels of modified nucleosides associated with cancer can serve as biomarkers for disease. Therefore, identifying and accurately quantifying nucleosides is vital for understanding RNA degradation and associated patterns of nucleoside metabolism. Such analyses are helpful when studying the biological functions and potential clinical applications of modified nucleosides. In this regard, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) offers significant advantages in terms of sensitivity, selectivity, and efficiency, and has been widely used to analyze DNA and RNA nucleosides/nucleotides and their analogues. Multiple MS detection patterns and quantification methods have been established to detect nucleosides in biological samples, including cultured cells, urine, blood, and tissue samples. However, the development of an accurate HPLC-MS/MS method faces several challenges. Firstly, the presence of a complex biological matrix that contains macromolecules, small molecules, and salts can interfere with analysis. Salts and co-elu

关键词： RNA modifications high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) metabolite analysis methylated nucleosides

An Iterated Greedy Algorithm with Memory and Learning Mechanisms for the Distributed Permutation Flow Shop Scheduling Problem

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Computers, Materials & Continua 2025年第1期82卷 371-388页

作者： Binhui wang Hongfeng wang College of Information Science and Engineering Northeastern UniversityShenyang110819China

The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent *** iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution ***,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale *** a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the ***,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous *** addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory ***,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom *** last,a discrete adaptive learning rate is employed to enhance the stability of the memory and *** ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large ***,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale *** indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.

关键词： Distributed permutation flow shop scheduling makespan iterated greedy algorithm memory mechanism cooperative reinforcement learning