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USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells

Current Medical Science 2024年第4期44卷 707-717页

作者： Xiao-hui YAN yin-na zhu Yan-ting zhu Kidney Disease and Dialysis Center Shaanxi Provincial People's HospitalXi'an 710068China Department of Nephrology The Third Affiliated Hospital of Xi'an Medical UniversityXi'an 710000China Nephrology and Hemodialysis Center Shaanxi Provincial People's HospitalXi'an 710068China

Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and ***19 mRna expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation *** cycle distribution and apoptosis were detected by flow *** USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and *** In HG+FFA-challenged HK-2 cells,USP19 was highly ***19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 ***,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 ***,USP19 stabilized the TAK1 protein through ***,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 *** The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

关键词： HK-2 cells high glucose free fatty acid dysfunction USP19 deubiquitination

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Anti-breast cancer effect of quercetin nanoparticles based on MOFs for chemo-phototherapy and heat shock proteins inhibition

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nano Research 2025年第1期18卷 545-558页

作者： Rongyue zhu Shilang Liao Mengru Cai Dongge yin Tingting Fu Jing Liu Yuji Du Jiahui Kong Rongrong Chang Jian Ni Xingbin yin Beijing University of Chinese Medicine Fangshan DistrictBeijing 102488China

Phototherapy, including photodynamic therapy(PDT) and photothermal therapy (PTT), is a promisingmethod of tumor treatment, which has the advantages ofstrong specificity and small side effects. However, PDT willaggravate the hypoxic environment in tumor cells, and PTTwill lead to heat-resistant reaction, both of which will make theorganism quickly produce heat shock proteins (HSPs) toprotect itself, thus seriously hindering the therapeuticefficiency of phototherapy. As a natural HSPs inhibitor,quercetin (QR) provides a feasible way to solve this ***, a kind of metal organic framework (MOF), Fe-TCPP(FT), was used as a delivery material and photosensitizer tobuild a chemo-phototherapy platform, and QR was used as achemotherapy drug and HSPs inhibitor. On this basis, the nanoparticles (NPs) were modified with PEG-CPP30 (a cellpenetratingpeptide that specifically recognizes human breast cancer MCF-7 cells), which showed excellent targetingcapacity and biocompatibility. The combination of chemotherapy and phototherapy significantly improved the anti-cancereffect. At the same time, NPs also showed prominent anti-HSPs effect. The effective connection of the two played acomplementary role in the process of tumor treatment, which provided a new strategy for the accurate and efficienttreatment of tumors in the future.

关键词： quercetin Fe-metal organic frameworks(MOFs) phototherapy anti-cancer heat shock proteins inhibition

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CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

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Neural Regeneration Research 2025年第8期20卷 2420-2432页

作者： Lin yin Yalan Xu Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li yin Wang Peifeng Li Hai zhu Dong Wang Jing Li Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina College of Life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina Department of Urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

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Neural Regeneration Research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen zhu Tingting Guo Yiran Zhang Tingting Xing Peng yin Shihua Li Xiao-Jiang Li Su Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto *** mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy *** aggregates alter protein-protein interactions and compromise transcriptional *** this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

关键词： androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model neurodegeneration neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor

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Molecule‑Level Multiscale Design of Nonflammable Gel Polymer Electrolyte to Build Stable SEI/CEI for Lithium Metal Battery

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nano-Micro Letters 2025年第1期17卷 404-423页

作者： Qiqi Sun Zelong Gong Tao Zhang Jiafeng Li Xianli zhu Ruixiao zhu Lingxu Wang Leyuan Ma Xuehui Li Miaofa Yuan Zhiwei Zhang Luyuan Zhang Zhao Qian Longwei yin Rajeev Ahuja Chengxiang Wang Key Laboratory for Liquid‑Solid Structural Evolution and Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJinan 250061People’s Republic of China Condensed Matter Theory Department of Physics and AstronomyUppsala UniversityUppsala 75120Sweden

The risk of flammability is an unavoidable issue for gel polymer electrolytes(GPEs).Usually,flameretardant solvents are necessary to be used,but most of them would react with anode/cathode easily and cause serious interfacial instability,which is a big challenge for design and application of nonflammable ***,a nonflammable GPE(SGPE)is developed by in situ polymerizing trifluoroethyl methacrylate(TFMA)monomers with flame-retardant triethyl phosphate(TEP)solvents and LiTFSI–LiDFOB dual lithium *** is strongly anchored to PTFMA matrix via polarity interaction between-P=O and-CH_(2)CF_(3).It reduces free TEP molecules,which obviously mitigates interfacial reactions,and enhances flame-retardant performance of TEP *** TEP molecules are also inhibited in solvation of Li^(+),leading to anion-dominated solvation sheath,which creates inorganic-rich solid electrolyte interface/cathode electrolyte interface *** coordination structure changes Li^(+)transport from sluggish vehicular to fast structural transport,raising ionic conductivity to 1.03 mS cm^(-1) and transfer number to 0.41 at 30℃.The Li|SGPE|Li cell presents highly reversible Li stripping/plating performance for over 1000 h at 0.1 mA cm^(−2),and 4.2 V LiCoO_(2)|SGPE|Li battery delivers high average specific capacity>120 mAh g^(−1) over 200 *** study paves a new way to make nonflammable GPE that is compatible with Li metal anode.

关键词： Anchoring effect Nonflammable gel electrolyte In situ cross-linked Electrode-electrolyte interface Li metal battery

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Modification of Maxwell model for conductivity prediction of carbon nanotubes-filled polymer composites with tunneling effect

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 25-36页

作者： Jue zhu Longyuan LI Ningtao zhu Zhejiang Provincial Engineering Research Center for the Safety of Pressure Vessel and Pipeline Key Laboratory of Impact and Safety Engineering (Ningbo University) Ministry of Education School of Engineering Computing and Mathematics University of Plymouth Xi'an Zhanshi Testing & Engineering Co.Ltd.

Carbon nanotubes(CNTs) have garnered great attention in recent years due to their outstanding electrical, thermal, and mechanical properties. The incorporation of small amounts of CNTs in polymers can substantially improve the sensitivity of the polymer's electrical conductivity. This paper presents a modified Maxwell model to evaluate the electrical conductivity of CNTs-filled polymer composites by introducing a transition zone to account for the tunneling effect. In this modified Maxwell model, the CNTs-filled polymer composite is modeled as a three-phase composite, consisting of a matrix(polymer), inclusions(CNTs), and a transition zone(tunneling zone). The effective electrical conductivity(EEC) of the composite is calculated based on the volume fractions and electrical conductivities of the matrix, inclusions, and transition zone. The model's validity is confirmed through the use of available test data, which demonstrates its capability to accurately capture the nonlinear conductivity behavior observed in CNTs-polymer composites. This study offers valuable insights into the design of high-performance conductive polymer nanocomposites, and enhances the understanding of electrical conduction mechanisms in CNT-dispersed polymer composites.

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Impacts of the annual cycle of background SST in the tropical Pacific on the phase and amplitude of ENSO

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 12-17页

作者： Song Jiang Congwen zhu Ning Jiang State Key Laboratory of Severe Weather(LASW) Chinese Academy of Meteorological SciencesBeijingChina College of Earth and Planetary Sciences University of Chinese Academy of SciencesBeijingChina

The dominant annual cycle of sea surface temperature(SST)in the tropical Pacific exhibits an antisymmetric mode,which explains 83.4%total variance,and serves as a background of El Niño-Southern Oscillation(ENSO).However,there is no consensus yet on its anomalous impacts on the phase and amplitude of *** on data during 1982-2022,results show that anomalies of the antisymmetric mode can affect the evolution of ENSO on the interannual scale via Bjerknes feedback,in which the positive(negative)phase of the antisymmetric mode can strengthen El Niño(La Niña)in boreal winter via an earlier(delayed)seasonal cycle transition and larger(smaller)annual *** magnitude of the SST anomalies in the equatorial eastern Pacific can reach more than±0.3◦C,regulated by the changes in the antisymmetric mode based on random sensitivity *** reveal the spatial pattern of the annual cycle associated with the seasonal phase-locking of ENSO evolution and provide new insight into the impact of the annual cycle of background SST on ENSO,which possibly carries important implications for forecasting ENSO.

关键词： Annual cycle SST anomaly Antisymmetric mode ENSO

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Satellite remote sensing reveals overwhelming recovery of forest from disturbances in Asia

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 46-51页

作者： Yiying zhu Hesong Wang Anzhi Zhang School of Ecology and nature Conservation Beijing Forestry UniversityBeijingChina Key Laboratory of Regional Climate and Environment for Temperate East Asia Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina College of Forestry and Landscape Architecture Xinjiang Agricultural UniversityUrumqiChina

Forest ecosystems play key roles in mitigating human-induced climate change through enhanced carbon uptake;however,frequently occurring climate extremes and human activities have considerably threatened the stability of *** the same time,detailed accounts of disturbances and forest responses are not yet well quantified in *** study employed the Breaks For Additive Seasonal and Trend method-an abrupt-change detection method-to analyze the Enhanced Vegetation Index time series in East Asia,South Asia,and Southeast *** approach allowed us to detect forest disturbance and quantify the resilience after *** showed that 20%of forests experienced disturbance with an increasing trend from 2000 to 2022,and Southeast Asian countries were more severely affected by ***,95%of forests had robust resilience and could recover from disturbance within a few *** resilience of forests suffering from greater magnitude of disturbance tended to be stronger than forests with lower disturbance *** summary,this study investigated the resilience of forests across the low and middle latitudes of Asia over the past two *** authors found that most forests exhibited good resilience after disturbance and about two-thirds had recovered to a better state in *** findings of this study underscore the complex relationship between disturbance and resilience,contributing to comprehension of forest resilience through satellite remote sensing.

关键词： Forest ecosystem Enhanced vegetation index Breaks for additive seasonal and trend method Disturbance Resilience

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Rock fracture mechanism of buffer blasting with cushion layer at the borehole bottom

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 325-334页

作者： Xinguang zhu Chenxi Ding Zhe Sui Hong Su Xu Guo School of Civil and Resources Engineering University of Science and Technology BeijingBeijing 100083China Key Laboratory for Mechanics in Fluid Solid Coupling Systems Institute of MechanicsChinese Academy of SciencesBeijing 100190China School of Mechanics and Civil Engineering China University of Mining and Technology(Beijing)Beijing 100083China School of Chemical and Blasting Engineering Anhui University of Science and TechnologyHuainan 232001China

This study primarily investigates the rock fracture mechanism of bottom cushion layer blasting and explores the effects of the bottom cushion layer on rock *** involves analyses of the evolution patterns of blasting stress,characteristics of crack distribution,and rock fracture features in the ***,blasting model experiments were carried out using the dynamic caustics principle to investigate the influence of bottom cushion layers and initiation methods on the integrity of the bottom rock *** experimental results indicate that the combined use of bottom cushion layers and inverse initiation effectively protects the integrity of the bottom rock ***,the process of stress wave propagation and dynamic crack propagation in rocks was simulated using the continuum-discontinuum element method(CDEM)and the Landau explosion source model,with varying thicknesses of bottom cushion *** numerical simulation results indicate that with increasing cushion thickness,the absorption of energy generated by the explosion becomes more pronounced,resulting in fewer cracks in the bottom rock *** illustrates the positive role of the cushion layer in protecting the integrity of the bottom rock mass.

关键词： bottom cushion layer blasting crack propagation continuum-discontinuum element method dynamic stress intensity factor

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绿色金融支持生态旅游资源价值实现的因素及模式分析

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生态经济 2025年第1期41卷 168-175页

作者：尹国俊朱佳娴浙江农林大学经济管理学院浙江杭州311300

中国生态旅游资源丰富,但绿色金融工具支持生态旅游资源价值实现的有效模式尚不明晰。运用fsQCA方法,以42个浙江省县域样本为典型案例,从组态视角分析了绿色金融支持生态旅游资源价值实现的路径和有效模式,最终得出六条有效路径,根据主... 详细信息

中国生态旅游资源丰富,但绿色金融工具支持生态旅游资源价值实现的有效模式尚不明晰。运用fsQCA方法,以42个浙江省县域样本为典型案例,从组态视角分析了绿色金融支持生态旅游资源价值实现的路径和有效模式,最终得出六条有效路径,根据主导要素的不同,绿色金融支持生态旅游资源价值实现可以分为投资主导、融资主导、多方融合三种模式。结果发现:多个绿色金融工具互相补充、共同作用,其中节能环保发展水平在多数路径当中居于核心位置,各影响因素的作用因路径不同而存在差异。各地需要因地制宜根据影响因素分布状态采取恰当的支持模式。

关键词：绿色金融生态旅游生态资源价值模式

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