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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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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong huang Weixuan Chen Ying huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration Research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Critical Care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

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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

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Solar flare forecasting based on a Fusion Model

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Earth and Planetary Physics 2025年第1期9卷 171-181页

作者： YiYang Li ShiYong huang SiBo Xu ZhiGang Yuan Kui Jiang QiYang Xiong RenTong Lin School of Earth and Space Science Technology Hubei Luojia LaboratoryWuhan UniversityWuhan 430072China

Solar flare prediction is an important subject in the field of space *** learning technology has greatly promoted the development of this *** this study,we propose a novel solar flare forecasting model integrating Deep Residual Network(ResNet)and Support Vector Machine(SVM)for both≥C-class(C,M,and X classes)and≥M-class(M and X classes)*** collected samples of magnetograms from May 1,2010 to September 13,2018 from Space-weather Helioseismic and Magnetic Imager(HMI)Active Region Patches and then used a cross-validation method to obtain seven independent data *** then utilized five metrics to evaluate our fusion model,based on intermediate-output extracted by ResNet and SVM using the Gaussian kernel *** results show that the primary metric true skill statistics(TSS)achieves a value of 0.708±0.027 for≥C-class prediction,and of 0.758±0.042 for≥M-class prediction;these values indicate that our approach performs significantly better than those of previous *** metrics of our fusion model’s performance on the seven datasets indicate that the model is quite stable and robust,suggesting that fusion models that integrate an excellent baseline network with SVM can achieve improved performance in solar flare ***,we also discuss the performance impact of architectural innovation in our fusion model.

关键词： solar flare pace weather deep learning Fusion Model

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Accurate manipulation of anthropomorphic robotic arm based on 3D human eye gazing with posture error compensation

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Science China Technological Sciences 2025年

作者： Quanlin LI Xianzong WANG Jiaji MA Qianjun huang Qizhi JIANG Wenbin CHEN Caihua XIONG State Key Laboratory of Intelligent Manufacturing Equipment and Technology School of Mechanical Science and Engineering Huazhong University of Science and Technology Institute of Medical Equipment Science and Engineering Huazhong University of Science and Technology

As humans and robots work closer together than ever, anthropomorphic robotic arms with intuitive human-robot interaction interfaces have drawn massive attention to improving the quality of robot-assisted manipulation. In pursuit of this,we designed a dedicated 7-degrees-of-freedom (DoF) anthropomorphic robotic arm having three compact differential joints and a head-mounted gaze tracker enabling head-pose-tracked 3D gaze estimation. Moreover, two key challenges were addressed to achieve accurate robot-assisted manipulation of the object indicated by the direction of human gaze. First, a novel predictive pupil feature was proposed for 3D gaze estimation. Differing from most existing features subjected to the common paraxial approximation assumption, the proposed novel predictive pupil feature considered the light refraction at two corneal surfaces with a more realistic eye model, significantly improving the 3D gaze estimation accuracy when the eyeball rotates at large angles. Second, a novel optimization-based approach was developed to efficiently compensate for the posture errors of the designed 7-DoF anthropomorphic robotic arm for accurate manipulation. Compared with the existing Jacobian-based or optimization-based approaches with nominal joint values as iteration initial, the proposed approach computed the optimal iteration initial and realized faster convergence for real-time posture error compensation. With the posture error compensation in real time and 3D gaze estimated accurately, the human can command accurate robot-assisted manipulation using his eyes intuitively. The proposed system was successfully tested on five healthy subjects.

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Moment Redistribution Effect of the Continuous Glass Fiber Reinforced Polymer-Concrete Composite Slabs Based on Static Loading Experiment

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Structural Durability & Health Monitoring 2025年第1期19卷 105-123页

作者： Zhao-Jun Zhang Wen-Wei Wang Jing-Shui Zhen Bo-Cheng Li De-Cheng Cai Yang-Yang Du Hui huang Offshore Oil Engineering Co.Ltd. Tianjin300461China Department of Bridge Engineering School of TransportationSoutheast UniversityNanjing211189China

This study aimed to investigate the moment redistribution in continuous glass fiber reinforced polymer(GFRP)-concrete composite slabs caused by concrete cracking and steel bar yielding in the negative bending moment *** experimental bending moment redistribution test was conducted on continuous GFRP-concrete composite slabs,and a calculation method based on the conjugate beam method was *** composite slabs were formed by combining GFRP profiles with a concrete layer and supported on steel beams to create two-span continuous composite slab *** methods,epoxy resin bonding,and stud connection,were used to connect the composite slabs with the steel *** experimental findings showed that the specimen connected with epoxy resin exhibited two moments redistribution phenomena during the loading process:concrete cracking and steel bar yielding at the internal *** contrast,the composite slab connected with steel beams by studs exhibited only one-moment redistribution phenomenon throughout the loading *** the concrete at the internal support cracked,the bending moment decreased in the internal support section and increased in the midspan *** the steel bars yielded,the bending moment further decreased in the internal support section and increased in the mid-span *** GFRP profiles do not experience cracking,there was no significant decrease in the bending moment of the mid-span *** test specimens experienced compressive failure of concrete at the mid-span *** results showed good agreement between the calculated and experimental values of bending moments in the mid-span section and internal support *** proposed model can effectively predict the moment redistribution behavior of continuous GFRP-concrete composite slabs.

关键词： Moment redistribution GFRP-concrete composite slabs bending moment experimental study analysis model

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