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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 B O Liu State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical Technology Chengdu University of Traditional Chinese Medicine Chengdu 611137 China. Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China.

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 therapies. Autophagy is an important process for maintaining cellular homeostasis, and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors. In contrast to targeting protein activity, intervention with protein-protein interaction (PPI) can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods: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 targets. Meanwhile, 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 intersection. Colony 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 PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets, we identified 3733 previously unknown autophagy-related PPIs. Our network analysis revealed the central role of Beclin 2 in autophagy regulation, uncovering its interactions with 39 newly identified proteins. Notably, 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 results. Subsequently, investigations showed that overexpressing Beclin 2 increased Ubiquilin 1, promoted autophagy-dependent cell death, and inhibited proliferation and metastasis in MDA-MB-231 cells.

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

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： xin Yang Yu-Wen Alvin huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Research status and prospects of the fractal analysis of metal material surfaces and interfaces

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 20-38页

作者： Qinjin Dai Xuefeng Liu xin Ma Shaojie Tian Qinghe Cui Beijing Advanced Innovation Center for Materials Genome Engineering University of Science and Technology BeijingBeijing 100083China Beijing Laboratory of Metallic Materials and Processing for Modern Transportation University of Science and Technology BeijingBeijing 100083China Laboratory for Advanced Materials Processing of Ministry of Education University of Science and Technology BeijingBeijing 100083China School of Mechanical and Electrical Engineering Xinjiang Institute of EngineeringUrumqi 830023China

As a mathematical analysis method,fractal analysis can be used to quantitatively describe irregular shapes with self-similar or self-affine *** analysis has been used to characterize the shapes of metal materials at various scales and *** methods make it difficult to quantitatively describe the relationship between the regular characteristics and properties of metal material surfaces and ***,fractal analysis can be used to quantitatively describe the shape characteristics of metal materials and to establish the quantitative relationships between the shape characteristics and various properties of metal *** the perspective of two-dimensional planes and three-dimensional curved surfaces,this paper reviews the current research status of the fractal analysis of metal precipitate interfaces,metal grain boundary interfaces,metal-deposited film surfaces,metal fracture surfaces,metal machined surfaces,and metal wear *** relationship between the fractal dimensions and properties of metal material surfaces and interfaces is *** from three perspectives of fractal analysis,namely,research scope,image acquisition methods,and calculation methods,this paper identifies the direction of research on fractal analysis of metal material surfaces and interfaces that need to be *** is believed that revealing the deep influence mechanism between the fractal dimensions and properties of metal material surfaces and interfaces will be the key research direction of the fractal analysis of metal materials in the future.

关键词： metal material surfaces and interfaces fractal analysis fractal dimension homogeneity

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Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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Traditional Medicine Research 2025年第2期10卷 65-76页

作者： huan Pei Ren-Lin Li xin-Ran Song Qian-Qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu Jia-Bao Liao Wei-Bo Wen Jing Miao huan-Tian Cui School of Basic Medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical College Yunnan University of Chinese MedicineKunming 650599China First School of Clinical Medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative Chinese and Western Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

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Estimation of Chloride Diffusivity in Hydrated Tricalcium Silicate Using a Hydration-Diffusion Integrated Method

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 49-64页

作者： WANG xin SHEN Dejian TAO Sijie LIU Ruixin WU Shengxing College of Civil and Transportation Engineering Hohai UniversityNanjing 210098China

This study aims to develop a chloride diffusion simulation method that considers the hydration microstructure and pore solution properties during the hydration of tricalcium silicate(C3S).The method combines the hydration simulation,thermodynamic calculation,and finite element analysis to examine the effects of pore solution,including effect of electrochemical potential,effect of chemical activity,and effect of mechanical interactions between ions,on the chloride effective diffusion coefficient of hydrated C3S *** results indicate that the effect of electrochemical potential on chloride diffusion becomes stronger with increasing hydration age due to the increase in the content of hydrated calcium silicate;as the hydration age increases,the effect of chemical activity on chloride diffusion weakens when the number of diffusible elements decreases;the effect of mechanical interactions between ions on chloride diffusion decreases with the increase of hydration age.

关键词： tricalcium silicate simulation method chloride diffusion coefficient pore solution

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Defect Engineering:Can it Mitigate Strong Coulomb Effect of Mg^(2+)in Cathode Materials for Rechargeable Magnesium Batteries?

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Nano-Micro Letters 2025年第1期17卷 135-159页

作者： Zhengqing Fan Ruimin Li xin Zhang Wanyu Zhao Zhenghui Pan Xiaowei Yang School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240People’s Republic of China School of Chemistry and Chemical Engineering Taiyuan University of TechnologyTaiyuan 030024People’s Republic of China School of Materials Science and Engineering Tongji UniversityShanghai 201804People’s Republic of China

Rechargeable magnesium batteries(RMBs)have been considered a promising“post lithium-ion battery”system to meet the rapidly increasing demand of the emerging electric vehicle and grid energy storage ***,the sluggish diffusion kinetics of bivalent Mg^(2+)in the host material,related to the strong Coulomb effect between Mg^(2+)and host anion lattices,hinders their further development toward practical *** engineering,regarded as an effective strategy to break through the slow migration puzzle,has been validated in various cathode materials for *** this review,we first thoroughly understand the intrinsic mechanism of Mg^(2+)diffusion in cathode materials,from which the key factors affecting ion diffusion are further ***,the positive effects of purposely introduced defects,including vacancy and doping,and the corresponding strategies for introducing various defects are *** applications of defect engineering in cathode materials for RMBs with advanced electrochemical properties are also ***,the existing challenges and future perspectives of defect engineering in cathode materials for the overall high-performance RMBs are described.

关键词： Rechargeable magnesium battery Sluggish diffusion kinetic Defect engineering Cathode materials Ion migration

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Wafer‑Scale Vertical 1D GaN Nanorods/2D MoS_(2)/PEDOT:PSS for Piezophototronic Effect‑Enhanced Self‑Powered Flexible Photodetectors

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Nano-Micro Letters 2025年第3期17卷 102-116页

作者： xin Tang Hongsheng Jiang Zhengliang Lin Xuan Wang Wenliang Wang Guoqiang Li State Key Laboratory of Luminescent Materials and Devices South China University of TechnologyGuangzhou 510640People’s Republic of China Department of Electronic Materials School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou 510640People’s Republic of China

van der Waals(vdW)heterostructures constructed by lowdimensional(0D,1D,and 2D)materials are emerging as one of the most appealing systems in next-generation flexible ***,hand-stacked vdW-type photodetectors are not compatible with large-areaarray fabrication and show unimpressive performance in self-powered ***,vertical 1D GaN nanorods arrays(NRAs)/2D MoS_(2)/PEDOT:PSS in wafer scale have been proposed for self-powered flexible photodetectors arrays *** as-integrated device without external bias under weak UV illumination exhibits a competitive responsivity of 1.47 A W^(−1)and a high detectivity of 1.2×10^(11)Jones,as well as a fast response speed of 54/71μs,thanks to the strong light absorption of GaN NRAs and the efficient photogenerated carrier separation in type-II ***,the strain-tunable photodetection performances of device have been ***,the device at−0.78%strain and zero bias reveals a significantly enhanced photoresponse with a responsivity of 2.47 A W^(−1),a detectivity of 2.6×10^(11)Jones,and response times of 40/45μs,which are superior to the state-of-the-art self-powered flexible *** work presents a valuable avenue to prepare tunable vdWs heterostructures for self-powered flexible photodetection,which performs well in flexible sensors.

关键词： Vertical nanorod arrays van der Waals heterostructure Piezophototronic effect Self-powered photodetection Flexible sensors

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Vector meson's spin alignments in high energy reactions

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 5-20页

作者： Jin-Hui Chen Zuo-Tang Liang Yu-Gang Ma xin-Li Sheng Qun Wang Key Laboratory of Nuclear Physics and Ion-beam Application (MoE) Institute of Modern PhysicsFudan University Institute of Frontier and Interdisciplinary Science Key Laboratory of Particle Physics and Particle Irradiation (MOE)Shandong University INFN-Firenze Department of Modern Physics University of Science and Technology of China School of Mechanics and Physics Anhui University of Science and Technology

The global spin alignment of vector mesons has been observed by the STAR collaboration at the Relativistic Heavy Ion Collider （RHIC） at Brookhaven National Laboratory （BNL）.It provides a unique opportunity to probe the correlation between the polarized quark and antiquark in the strongly coupled quark-gluon plasma （sQGP） produced in relativistic heavy ion collisions,opening a new window to explore the properties of s *** addition,spin alignments of vector mesons have also been observed in other high-energy particle collisions such as e+e-annihilations at high energies where hadron production is dominated by quark fragmentation *** results obtained are quite different from those obtained in heavy ion collisions where quark coalescence/combination mechanism dominates suggesting strong dependence on hadronization *** comprehensive studies in different hadronization processes are *** this article,we present a brief review of theoretical and experimental advances in the study of vector meson’s spin alignments in a variety of high-energy particle collisions,with emphasis on hadronization mechanisms.

关键词： vector meson spin alignment global polarization relativistic heavy ion collisions fragmentation

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Non-existence of Shimura curves of Mumford type generically in the non-hyperelliptic locus

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Science China Mathematics 2025年

作者： xin Lü Shengli Tan Kang Zuo School of Mathematical Sciences Key Laboratory of Mathematics and Engineering Applications(Ministry of Education) Shanghai Key Laboratory of Pure Mathematics and Mathematical PracticeEast China Normal University School of Mathematics and Statistics Wuhan University Institut für Mathematik Universit?t Mainz

We show that there does not exist any Shimura curve with a strictly maximal Higgs field generically in the Torelli locus of non-hyperelliptic curves of genus g≥4. In particular, Shimura curves of Mumford type are not...

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Bilevel Optimal Scheduling of Island Integrated Energy System Considering Multifactor Pricing

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Energy Engineering 2025年第1期122卷 349-378页

作者： xin Zhang Mingming Yao Daiwen He Jihong Zhang Peihong Yang Xiaoming Zhang School of Automation and Electrical Engineering Inner Mongolia University of Science and TechnologyBaotou014010China

In this paper,a bilevel optimization model of an integrated energy operator(IEO)–load aggregator(LA)is constructed to address the coordinate optimization challenge of multiple stakeholder island integrated energy system(IIES).The upper level represents the integrated energy operator,and the lower level is the electricity-heatgas load *** to the benefit conflict between the upper and lower levels of the IIES,a dynamic pricing mechanism for coordinating the interests of the upper and lower levels is proposed,combined with factors such as the carbon emissions of the IIES,as well as the lower load interruption *** price of selling energy can be dynamically adjusted to the lower LA in the mechanism,according to the information on carbon emissions and load interruption *** benefits and win-win situations are achieved between the upper and lower ***,CPLEX is used to iteratively solve the bilevel optimization *** optimal solution is selected according to the joint optimal discrimination *** results indicate that the sourceload coordinate operation can reduce the upper and lower operation *** the proposed pricingmechanism,the carbon emissions and load interruption power of IEO-LA are reduced by 9.78%and 70.19%,respectively,and the capture power of the carbon capture equipment is improved by 36.24%.The validity of the proposed model and method is verified.

关键词： Bilevel optimal scheduling load aggregator integrated energy operator carbon emission dynamic pricing mechanism

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