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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

A mild, configurable, flexible CoNi-LDH（v）/Zn battery based on H-vacancy-induced reversible Zn2+ intercalation

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Journal of Energy Chemistry 2025年第1期100卷 498-508页

作者： Xinyue Cheng Dingsheng Wu Hao Gao Qingqing Wang Pengfei Lv Sam S.Yoon Qufu wei Key Laboratory of Eco-textiles Ministry of Education Jiangnan University School of Mechanical Engineering Korea University

Flexible Zn-based batteries have attracted increasing research interest as essential components of wearable energy storage ***,the advancement of flexible aqueous Zn-based batteries based on Co-Ni layered double hydroxide （CoNi-LDH） as the cathode material is hampered by their poor cycling stability and the corrosiveness of alkaline ***,CoNi-LDH nanosheets enriched with H vacancies (CoNi-LDH（v）) were constructed on a flexible carbon cloth （CC） substrate via electrochemical deposition and *** Zn-based battery comprising CoNi-LDH（v）@CC as the cathode exhibited highly reversible conversion reactions and stable operation in 3 M ZnSO4electrolyte （pH=4）.The battery delivered an excellent specific capacity (225 mA h g-1,0.26 mA h cm-2),acceptable cycling stability（53.9%,900 cycles）,and high discharging *** abundant H vacancies served as active sites for the reversible intercalation of Zn2+and the extravasation of NO3-generated channels and space for Zn2+transport and storage,together enabling an excellent Zn2+storage ***,a sandwich-structured solid-state CoNi-LDH（v）@CC//Zn@CC battery was fabricated and was found to exhibit a noteworthy electrochemical performance and mechanical *** a proof of concept,the unencapsulated battery powered a digital watch under various deformation conditions and operated stably for 80 ***,the flexible battery displayed outstanding customizability,maintaining an open-circuit voltage of 1.42 V even after being cut *** proposed engineering strategy contributes to the realization of textiles with truly wearable energy-storage devices.

关键词： CoNi/Zn battery H vacancies Mild aqueous electrolyte Tailorable battery Wearable energy storage device

GPS: graph contrastive learning via multi-scale augmented views from adversarial pooling

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Science China(Information Sciences) 2025年第1期68卷 145-158页

作者： wei JU Yiyang GU Zhengyang MAO Ziyue QIAO Yifang QIN Xiao LUO Hui XIONG Ming ZHANG School of Computer Science National Key Laboratory for Multimedia Information ProcessingPeking University Artificial Intelligence Thrust The Hong Kong University of Science and Technology Department of Computer Science University of California

Self-supervised graph representation learning has recently shown considerable promise in a range of fields, including bioinformatics and social networks. A large number of graph contrastive learning approaches have shown promising performance for representation learning on graphs, which train models by maximizing agreement between original graphs and their augmented views(i.e., positive views). Unfortunately, these methods usually involve pre-defined augmentation strategies based on the knowledge of human experts. Moreover, these strategies may fail to generate challenging positive views to provide sufficient supervision signals. In this paper, we present a novel approach named graph pooling contrast(GPS) to address these *** by the fact that graph pooling can adaptively coarsen the graph with the removal of redundancy, we rethink graph pooling and leverage it to automatically generate multi-scale positive views with varying emphasis on providing challenging positives and preserving semantics, i.e., strongly-augmented view and weakly-augmented view. Then, we incorporate both views into a joint contrastive learning framework with similarity learning and consistency learning, where our pooling module is adversarially trained with respect to the encoder for adversarial robustness. Experiments on twelve datasets on both graph classification and transfer learning tasks verify the superiority of the proposed method over its counterparts.

关键词： graph representation learning graph neural networks graph contrastive learning graph augmentations graph pooling

One Step Positive Approach for Sheet Metal Forming simulation Based on Quasi-conjugate-gradient Method

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Chinese Journal of Mechanical Engineering 2013年第4期26卷 730-736页

作者： na Jingxin CHEN wei State Key Laboratory of Automotive simulation and Control Jilin University

In one step inverse finite element approach, an initial blank shape is normally predicted from the final deformed shape. The final deformed shape needs to be trimmed into a final part after stamping, the trimmed area, therefore, needs to be compensated manually before using one step inverse approach, which causes low efficiency and in consistency with the real situation. To solve this problem, one step positive approach is proposed to simulate the sheet metal stamping process. Firstly the spatial initial solution of one step positive method is preliminarily obtained by using the mapping relationship and area coordinates, then based on the deformation theory the iterative solving is carried out in three-dimensional coordinate system by using quasi-conjugate-gradient method. During iterative process the contact judgment method is introduced to ensure that the nodes on the spatial initial solution are not separated from die surface. The predicted results of sheet metal forming process that include the shape and thickness of the stamped part can be obtained after the iterative solving process. The validity of the proposed approach is verified by comparing the predicted results obtained through the proposed approach with those obtained through the module of one step inverse approach in Autoform and the real stamped part. In one step positive method, the stamped shape of regular sheet can be calculated fast and effectively. During the iterative solution, the quasi-conjugate-gradient method is proposed to take the place of solving system of equations, and it can improve the stability and precision of the algorithm.

关键词： positive approach deformation theory quasi-conjugate-gradient method

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

SensFL:Privacy-Preserving Vertical Federated Learning with Sensitive Regularization

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 385-404页

作者： Chongzhen Zhang Zhichen Liu Xiangrui Xu Fuqiang Hu Jiao Dai Baigen Cai wei Wang School of Automation and Intelligence Beijing Jiaotong UniversityBeijing100044China Shuohuang Railway Development Co. Ltd.National Energy GroupCangzhou062350China Beijing Key Laboratory of Security and Privacy in Intelligent Transportation School of Computer Science and TechnologyBeijing Jiaotong UniversityBeijing100044China

In the realm of Intelligent Railway Transportation Systems,effective multi-party collaboration is crucial due to concerns over privacy and data *** Federated Learning(VFL)has emerged as a promising approach to facilitate such collaboration,allowing diverse entities to collectively enhance machine learning models without the need to share sensitive training ***,existing works have highlighted VFL’s susceptibility to privacy inference attacks,where an honest but curious server could potentially reconstruct a client’s raw data from embeddings uploaded by the *** vulnerability poses a significant threat to VFL-based intelligent railway transportation *** this paper,we introduce SensFL,a novel privacy-enhancing method to against privacy inference attacks in ***,SensFL integrates regularization of the sensitivity of embeddings to the original data into the model training process,effectively limiting the information contained in shared *** reducing the sensitivity of embeddings to the original data,SensFL can effectively resist reverse privacy attacks and prevent the reconstruction of the original data from the *** experiments were conducted on four distinct datasets and three different models to demonstrate the efficacy of *** results show that SensFL can effectively mitigate privacy inference attacks while maintaining the accuracy of the primary learning *** results underscore SensFL’s potential to advance privacy protection technologies within VFL-based intelligent railway systems,addressing critical security concerns in collaborative learning environments.

关键词： Vertical federated learning privacy defenses

Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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Oncology Research 2025年第1期33卷 225-234页

作者： wei ZHANG weiCHENG WANG RUI WANG XIAO HAN LIJUN ZHU WENJIE GUO YANHONG GU Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

Microstress cycle and contact fatigue of spiral bevel gears by rolling-sliding of asperity contact

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Friction 2020年第6期8卷 1083-1101页

作者： wei CAO si REN wei PU Ke XIAO School of Construction Machinery Chang'an UniversityXi'an 710064China School of Aeronautics and Astronautics Sichuan UniversityChengdu 610065China Department of Mechanical Engineering Massachusetts Institute of TechnologyCambridgeMassachusetts 02139USA College of Mechanical Engineering Chongqing UniversityChongqing 400044China

The rolling contact fatigue(RCF)model is commonly used to predict the contact fatigue life when the sliding is insignificant in contact ***,many studies reveal that the sliding,compared to the rolling state,can lead to a considerable reduction of the fatigue life and an excessive increase of the pitting area,which result from the microscopic stress cycle growth caused by the sliding of the asperity *** suggests that fatigue life in the rolling-sliding condition can be overestimated based only on the RCF *** rubbing surfaces of spiral bevel gears are subject to typical rolling-sliding *** paper aims to study the mechanism of the micro stress cycle along the meshing path and provide a reasonable method for predicting the fatigue life in spiral bevel *** microscopic stress cycle equation is derived with the consideration of gear meshing *** combination of the RCF model and asperity stress cycle is developed to calculate the fatigue life in spiral bevel *** find that the contact fatigue life decreases significantly compared with that obtained from the RCF *** is strong evidence that the microscopic stress cycle is remarkably increased by the rolling-sliding motion of the asperity contact,which is consistent with the experimental data in previous *** addition,the fatigue life under different assembling misalignments are investigated and the results demonstrate the important role of misalignments on fatigue life.

关键词： rolling/sliding contact fatigue stress cycle spiral bevel gear mixed elasto-hydrodynamic lubrication assembling misalignment

CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

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Neural Regeneration Research 2024年第6期19卷 1169-1170页

作者： Li-na wei Department of Pharmacology University of Minnesota Medical SchoolMinneapolisMNUSA

Retinoic acid(RA),the active metabolite of vitamin A(the retinoids),elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al.,2002).The effects of RA are mediated by two very distinct pathways;the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs)to regulate proper expression of RAtargeted genes.

关键词： canonical spectrum critical