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Activated Drp1 regulates p62-mediated autophagic flux and aggravates inflammation in cerebral ischemia-reperfusion via the ROS-RIP1/RIP3-exosome axis

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Military Medical Research 2022年第6期9卷 668-685页

作者： Xue Zeng Yun-Dong Zhang Rui-Yan Ma Yuan-Jing Chen xin-ming xiang Dong-Yao Hou Xue-Han Li He Huang Tao Li Chen-Yang Duan Department of Anaesthesiology the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Neurology the Third Affliated Hospital of Chongqing Medical UniversityChongqing 401120China Department of Cardiovascular Surgery Xinqiao HospitalArmy Medical UniversityChongqing 400037China State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionDaping HospitalArmy Medical UniversityChongqing 400042China

Background: Cerebral ischemia-reperfusion injury(CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains ***: The 150 male C57 mice underwent middle cerebral artery occlusion(MCAO) for 1 h and reperfusion for 24 h,Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1(Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine(NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA(mtDNA) copy number, intracellular and mitochondrial reactive oxygen species(ROS),autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/I, TNF-α,IL-1β, etc., were detected under normal or Drp1 interference ***: The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI(P0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4–5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1(P<0.05). Furthermore, TNF-α and IL-1βincreased in CIRI-

关键词： Cerebral ischemia-reperfusion(CIRI) Oxygen-glucose deprivation/reoxygenation(OGD/R) Drp1 p62 LC3 II/I Reactive oxygen species(ROS) RIP1/RIP3 Autophagy Exosome Inflammatory

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： xiang LI WENKE JIN LIFENG WU HUAN WANG xin XIE WEI HUANG BO LIU State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy

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Tungsten 2025年第1期7卷 183-194页

作者： xin-Ran Sun Hao-ming Yuan Guo-Da Zhang Chao Wang Shu-Juan Sun Peng-Fei Shi Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers School of Chemistry and Chemical Engineering Linyi University

The combination of photodynamic therapy（PDT） and chemodynamic therapy（CDT） in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione（GSH） overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework（Mn-TCPP） was constructed by the one-pot method and further used for immobilizing glucose oxidase（GOx） to obtain GOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide（H2O2） and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and GSH,thus greatly enhancing ***,benefiting from GOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by GOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

关键词： Chemodynamic therapy Immobilizing enzyme Metal–organic frameworks Photodynamic therapy Starvation therapy

Preparation and study of novel mid-to-low-temperature phase-change molten salts

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Science China Technological Sciences 2025年

作者： Chenxing REN Yifan WANG xin HE Chenghang ZHENG xiang GAO State Key Laboratory of Clean Energy Utilization Zhejiang University Institute of Carbon Neutrality Zhejiang University Baima Lake Laboratory Zhejiang University

Molten salts is a promising medium for heat storage and heat transfer due to their advantages of low cost, low steam pressure, high energy storage density and wide temperature range. In this paper, a new phase change mixture of molten salts with KNO3, NaNO3, ZnCl2, NaF, Na2CO3, NaCl, and MgO as materials has been prepared through a plenty of experiments. The experimental results show that the melting point of some molten salts can be reduced to 202.9°C, and the decomposition temperature can reach 701.3°C. In addition, its thermophysical properties, including specific heat, viscosity and thermal stability, were measured and analyzed. The average specific heat of some molten salts is as high as 2.53 J/（g K）, and the average thermal conductivity is as high as 0.77 W/（m K）. In the 4-day short-term thermal stability test, the fluctuation of each parameter is minimal, and the overall thermal physical property is relatively stable. Compared with the traditional phase change molten salt, the new hybrid molten salt has a significantly lower melting point, a further improvement in the decomposition temperature, specific heat and other comprehensive thermophysical properties, and a better overall economy, which has important application value in heat transfer and energy storage.

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting xiang xiangxin xing Xuyun Hua Yuwen Zhang xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

Inter‑Skeleton Conductive Routes Tuning Multifunctional Conductive Foam for Electromagnetic Interference Shielding,Sensing and Thermal Management

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Nano-Micro Letters 2025年第3期17卷 19-36页

作者： Xufeng Li Chunyan Chen Zhenyang Li Peng Yi Haihan Zou Gao Deng ming Fang Junzhe He xin Sun Ronghai Yu Jianglan Shui Caofeng Pan Xiaofang Liu School of Materials Science and Engineering Beihang UniversityBeijing 100191People’s Republic of China Institute of Atomic Manufacturing Beihang UniversityBeijing 100191People’s Republic of China Tianmushan Laboratory Xixi Octagon CityYuhang DistrictHangzhou 310023People’s Republic of China Science and Technology On Electromagnetic Scattering Laboratory Beijing Institute of Environmental FeaturesBeijing 100854People’s Republic of China

Conductive polymer foam(CPF)with excellent compressibility and variable resistance has promising applications in electromagnetic interference(EMI)shielding and other integrated functions for wearable ***,its insufficient change amplitude of resistance with compressive strain generally leads to a degradation of shielding performance during ***,an innovative loading strategy of conductive materials on polymer foam is proposed to significantly increase the contact probability and contact area of conductive components under *** inter-skeleton conductive films are constructed by loading alginate-decorated magnetic liquid metal on the polymethacrylate films hanged between the foam skeleton(denoted as AMLM-PM foam).Traditional point contact between conductive skeletons under compression is upgraded to planar contact between conductive ***,the resistance change of AMLM-PM reaches four orders of magnitude under ***,the inter-skeleton conductive films can improve the mechanical strength of foam,prevent the leakage of liquid metal and increase the scattering area of EM ***-PM foam has strain-adaptive EMI shielding performance and shows compression-enhanced shielding effectiveness,solving the problem of traditional CPFs upon *** upgrade of resistance response also enables foam to achieve sensitive pressure sensing over a wide pressure range and compression-regulated Joule heating function.

关键词： Inter-skeleton conductive films Conductive polymer foam Liquid metal Electromagnetic interference shielding

Engineering N3C vacancies in hierarchical porous carbon nitride nanosheets for room temperature ultradeep photocatalytic aerobic oxidative desulfurization

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Science China Chemistry 2025年

作者： Yina Nie Weijie Yang xin Wang xiang Li Lele Wei Xiaolin Bai Lin Liu Feng Fu Jun Wan College of Chemistry & Chemical Engineering Research Institute of Comprehensive Energy Industrial Technology Shaanxi Key Laboratory of Chemical Reaction Engineering Yan'an University Anhui Engineering Research Center of Carbon Neutrality College of Chemistry and Materials Science Anhui Normal University

The production of ultra-low sulfur clean fuels holds global significance for improving energy efficiency and reducing environmental pollution. Photocatalytic aerobic oxidative desulfurization（PODS） offers an attractive approach to efficiently remove refractory heterocyclic aromatic sulfur compounds under mild conditions. However, the sluggish charge dynamics,insufficient molecule activation, and slow mass transfer within photocatalysts restrict the overall desulfurization efficiency,hindering the widespread application of this technology. Herein, we developed a defective g-C3N4（M1U3CN） photocatalyst with bridged N3Cvacancies and hierarchical porous structures to address these limitations. This catalyst not only demonstrates outstanding dibenzothiophene（DBT） removal efficiency of 99.6% for model oil with high conversion and selectivity but also achieves complete sulfur removal from gasoline as well as 96.7% sulfur removal for distilled diesel at room temperature,successfully achieving ultradeep aerobic oxidative desulfurization. The introduction of rich N3Cvacancies and abundant micromeso-macroporous distribution in M1U3CN enhances kinetic efficiencies by promoting charge carrier separation, mass transfer,and molecular activation simultaneously; resulting in exceptional PODS performance. This work provides a collaborative strategy to overcome kinetic challenges in aerobic oxidative desulfurization via defect and structural engineering of the catalyst.

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Gradient maturation experiment on hairs implies taphonomic changes in fossil hairs

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Science China Earth Sciences 2025年第1期68卷 62-73页

作者： xin LI Yibo ZHOU Tao ZHAO xingjian HE Yanhong PAN State Key Laboratory for Mineral Deposits Research Center for Critical Earth Material Cycling Centre for Research and Education on Biological Evolution and Environment and Frontiers Science School of Earth Sciences and Engineering Nanjing University Institute of Palaeontology Yunnan Key Laboratory of Earth System Science Yunnan Key Laboratory for PalaeobiologyYunnan University

Mammalian hair, as a key feature related to endothermy, physical protection, and camouflage, has a long geohistorical record that dates back even to the Mesozoic. However, the limited information on the taphonomy of hair hinders the understanding of its evolutionary significance in deep time. To address this, we conducted taphonomic experiments to simulate the transformation process of black hair. The changes in the morphological structure, microscopic characteristics, and chemical composition of hair during the simulated fossilization process were documented by scanning electron microscopy, Fourier transform infrared(FTIR) spectroscopy, and Raman spectroscopy. Our results revealed that damage to the morphology of hair began at a mild temperature(150–175°C), and hair transformed into a fluid-like mass at a relatively high temperature(200°C). In addition, the morphological structure of melanosomes had relatively greater preservation potential than keratins did, and the microscopic features of melanosomes were persistently stable. The Raman and FTIR spectra indicated that the characteristic melanin and keratin peaks changed as the temperature increased. Although the chemical signals were not lost completely, the variations in the characteristic amide bands in the FTIR spectra indicate that the keratins severely degraded at high temperatures(>200°C), whereas the characteristic melanin bands in the Raman spectra suggested that melanin signals were still recognizable, even at high temperatures(>200°C). These results were confirmed by principal component analysis(PCA) and principal component analysis linear discriminant analysis(PCA–LDA). In addition, the Raman signals of all the samples in the simulated experiments were distinguished from the signals of common geological carbonaceous materials(humic acid), which suggested that Raman spectroscopy can be used to detect melanin in fossils.

关键词： Mammalian hair Melanin Keratin Fossilization Experimental taphonomy