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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

Microstructural evolution during the progressive transformation-induced plasticity effect in a Fe-0.1C-5Mnmedium manganese steel

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 369-379页

作者： Mei Zhang Wenhao Li Yangfei Chen Yang Jiang Xiaofei guo Han Dong School of Materials Science and Engineering Shanghai UniversityShanghai 200444China State Key Laboratory of Advanced Special Steel Shanghai UniversityShanghai 200444China

The microstructural evolution of a cold-rolled and intercritical annealed medium-Mn steel(Fe-0.10C-5Mn)was investigated during uniaxial tensile ***-situ observations under scanning electron microscopy,transmission electron microscopy,and X-ray diffraction analysis were conducted to characterize the progressive transformation-induced plasticity process and associated fracture initiation *** findings were discussed with the local strain measurements via digital image *** results indicated that Lüders band formation in the steel was limited to 1.5%strain,which was mainly due to the early-stage martensitic phase transformation of a very small amount of the less stable large-sized retained austenite(RA),which led to localized stress concentrations and strain hardening and further retardation of *** small-sized RA exhibited high stability and progressively transformed into martensite and contributed to a stably extended Portevin-Le Chatelier *** volume fraction of RA gradually decreased from 26.8%to 8.2%prior to *** the late deformation stage,fracture initiation primarily occurred at the austenite/martensite and ferrite/martensite interfaces and the ferrite phase.

关键词： medium-Mn steel retained austenite progressive transformation-induced plasticity effect local strain fracture initiation

High-performance poly(aromatic pyridine) copolymers with crown ether moieties for high temperature polymer electrolyte membrane fuel cells

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Science China Chemistry 2025年

作者： Qian Wang Songhao Zhao Yunpeng guo Wei Wei Lele Wang Jingshuai Yang Department of Chemistry College of Sciences Northeastern University Institute of Metal Research Chinese Academy of Sciences

This study concentrates on the development of high temperature polymer electrolyte membranes（HT-PEMs）, which are essential components for HT-PEM fuel cells（HT-PEMFCs）. Although the phosphoric acid（PA）-doped polybenzimidazole（PBI） has been regarded as the successful HT-PEM, this system still suffers from several challenges, including the use of carcinogenic monomers, complex synthesis procedures, and poor solubility in organic solvents. To develop more cost-effective, readily synthesized and high-performance alternatives, this study employs a simply superacid-catalyzed Friedel-Crafts reaction to synthesize a series of poly（triphenyl-co-dibenzo-18-crown-6 pyridine） copolymers, denoted as P(TPx%-co-CEy%), using ptriphenyl, dibenzo-18-crown-6 and 4-acetylpyridine as monomers. The copolymerized hydrophilic and bulky crown ether unites introduce large free volumes and multiple interaction sites with PA molecules, as elucidated by theoretical *** microphase separation structures are formed as confirmed by atomic force microscope（AFM）, transmission electron microscopy（TEM） and small-angle X-ray scattering（SAXS）. Thus P(TPx%-co-CEy%) membranes exhibit excellent PA absorption and proton conduction abilities. For example, after immersing in 85 wt% PA at 30 °C, the P(TP91%-co-CE9%) membrane achieves a PA doping content of 205% and a high conductivity of 0.138 S cm-1at 180 °C, while maintaining a tensile strength of 7.5 MPa at room temperature. Without humidification and backpressure, the peak power density of an H2-O2cell equipped with P(TP91%-co-CE9%)/205%PA reaches nearly 1200 mW cm-2, representing one of the highest performances reported for PA-doped HT-PEMs to date. This work demonstrates the enormous potential of poly（triphenyl-co-crown ether pyridine） membranes in the HT-PEMFC applications.

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Modeling tactile perceived intensity for vibration from a coin eccentric rotating mass motor

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Science China Technological Sciences 2025年

作者： Yun FANG Jingchen HUANG Yujun WU Jiaqi DONG Weichao guo Xinjun SHENG State Key Laboratory of Mechanical System and Vibration School of Mechanical Engineering Shanghai Jiao Tong University Meta Robotics Institute Shanghai Jiao Tong University

Establishing the relationship between vibrotactile parameters and perceived intensity（PI） is of great significance in the regulation of desired sensations, which contribute to haptic interfaces in practical applications. Coin eccentric rotating mass（ERM） motors are routinely utilized due to their lightweight design and efficient ability to evoke strong tactile sensations. By adjusting input voltages, ERMs can yield different stimuli, but the effects of their physical properties on PI remain ***, we developed the physical model of the ERM-skin system and optimized the parameters affecting PI. Moreover, the relationship between stimulus and perception was derived based on Fechner?s law. Three experiments were conducted on fifteen subjects（ten males and five females, aged 24.40 ± 2.87 years） to identify the vibration parameters and corresponding PI to verify the proposed PI model. ERMs in this study were attached to phantom skin/forearm with slim adhesive tape to minimize the interference. Experiment 1 performed vibration calibration with ERM attached to the skin phantom to simulate the actual configuration. Then, the relative and absolute PI of subjects on specific stimuli were acquired in Experiments 2 and *** fitting reliability of the proposed PI model was evaluated on fifteen subjects with R2of 0.73 ± 0.07 and root mean squared error（RMSE） of 1.35 ± 0.28. Overall, the proposed PI model established the quantitative relationship between stimulus parameters（vibration parameters and physical parameters） and subjective PI, which provided theoretical support for ERM optimization and vibrotactile modulation.

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Unraveling the significance of cobalt on transformation kinetics,crystallography and impact toughness in high-strength steels

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 380-390页

作者： Yishuang Yu Jingxiao Zhao Xuelin Wang Hui guo Zhenjia Xie Chengjia Shang Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing 100083China School of Materials Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China

This work reveals the significant effects of cobalt(Co)on the microstructure and impact toughness of as-quenched highstrength steels by experimental characterizations and thermo-kinetic *** results show that the Co-bearing steel exhibits finer blocks and a lower ductile-brittle transition temperature than the steel without ***,the Co-bearing steel reveals higher transformation rates at the intermediate stage with bainite volume fraction ranging from around 0.1 to *** improved impact toughness of the Co-bearing steel results from the higher dense block boundaries dominated by the V1/V2 variant ***,the addition of Co induces a larger transformation driving force and a lower bainite start temperature(BS),thereby contributing to the refinement of blocks and the increase of the V1/V2 variant *** findings would be instructive for the composition,microstructure design,and property optimization of high-strength steels.

关键词： high-strength steel cobalt transformation kinetics crystallography impact toughness

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

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Neural Regeneration Research 2025年第2期20卷 533-547页

作者： Yanli Zhang Tian Li Jie Miao Zhina Zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei Zhang Haiting Li Qiang Su Junhong guo Department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina Department of Physiology Key Laboratory of Cellular PhysiologyMinistry of EducationShanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Hernia and Abdominal Wall Surgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Laboratory Medicine of Fenyang College Shanxi Medical UniversityFenyangShanxi ProvinceChina

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial ***,the functional role of GGT5 in the development of Alzheimer’s disease remains *** study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying *** observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse ***,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive ***,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 *** effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa *** findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 *** findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1

Deciphering the role of ultra-low-loaded rhodium in NiFe-MIL-53 for superior oxygen evolution reaction

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Journal of Energy Chemistry 2025年第1期100卷 77-86页

作者： Jinzhi Jia Jinhua Zhang Kailu guo Lanyue Zhang Gening Du Hao You Junfeng Huang Mudong Tu Hua Li Yong Peng Wei Dou Cailing Xu State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering School of Materials and Energy Lanzhou University College of Chemistry and Chemical Engineering Luoyang Normal University

Designing highly active and stable electrocatalysts of oxygen evolution reaction （OER） is one of the crucial *** this study,a novel OER electrocatalyst,NiFe-MIL-53 modified with ultra-low rhodium（Rh@NiFe-MIL-53）,is successfully prepared via the hydrothermal ***-situ Raman spectroscopy and electrochemical impedance spectroscopy reveal that the doped Rh accelerates the phase transformation of NiFe-MIL-53 and the in-situ formed Rh@NiFeOOH is the actual active *** importantly,the enhanced reversibility of electrochemical reconstruction between NiFeOOH and NiFe（OH）2after doping Rh is beneficial for improving the electrochemical stability of the catalyst.X-ray photoelectron spectroscopy spectra show the strong electronic interaction between single-atom Rh and Ni/Fe in Rh@***,theoretical calculations confirm that the integration of single-atom Rh into the NiFeOOH successfully reduces the band gap,regulates the d-band center （εd）,accelerates the charge transfer,and optimizes the adsorption behavior of oxygen-containing intermediates,thereby lowering the energy barrier of rate-determining ***,the optimized Rh@NiFe-MIL-53 exhibits excellent OER activity （240 mV） with a small Tafel slope of 48.2 mV dec-1and long-term durability (over1270 h at 10 m A cm-2and 110 h at 200 mA cm-2).This work presents a new perspective on designing highly efficient OER electrocatalysts.

关键词： X ray photoelectron spectroscopy

Modifying metabolic and immune hallmarks of cancer by a copper complex

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Science China Chemistry 2025年

作者： Chengyan Chu Yunhua Zhang Chengyuan Qian Xiuzhi Yang Yicun Shang Zijian guo Xiaoyong Wang State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University

Metabolic adaptation of cancer cells is a key tactic for maintaining their tumorigenicity and viability in the tumor immune microenvironment （TIME）.Concurrent modulation on the metabolic pathway and immune system could change the living condition of cancer cells and potentiate the efficacy of anticancer drugs.A copper complex （DDCu） was designed to influence the energy metabolism of cancer cells and reshape the *** restrained the production and transportation of lactate by inhibiting the expression of lactate dehydrogenase and monocarboxylate transporter 4,thereby altering the metabolic pathway of cancer cells and improving the acidic tumor ***,DDCu was reduced to Cu+by cellular glutathione to react with lipoylated proteins of the tricarboxylic acid cycle and destabilize the Fe–S cluster proteins,leading to the aggregation of dihydrolipoamide S-acetyltransferase and cuproptosis in cancer ***,DDCu promoted the polarization of macrophages from the M2 to M1 phenotype,activated CD4+and CD8+T cells,and reversed the *** a result,DDCu inhibited the tumor growth through a synergy between metabolic regulation and immunomodulation.

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circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年

作者： Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia guo Zhaoyang Zeng Can guo NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong Laboratory Cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang Key Laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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