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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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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei wang Zhizhong Guan Xiaolan Qi wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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Synthesis of chiral phosphine derivatives through a copper（I）-catalyzed desymmetric SNAr reaction

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Science China Chemistry 2025年

作者： Shuai Zhang Pei-Zhi Liu Yan-Bo Li Qi Zhang Jun-Zhao Xiao Yi-Fan wang Tian-Yu wei Jia-wei Jiang Ye wang Qian Peng Liang Yin Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials Shanghai Institute of Organic Chemistry University of Chinese Academy of Sciences Chinese Academy of Sciences State Key Laboratory of Elemento-Organic Chemistry and Tianjin Key Laboratory of Biosensing and Molecular Recognition College of Chemistry Frontiers Science Center for New Organic Matter Nankai University Haihe Laboratory of Sustainable Chemical Transformations

Axially chiral phosphines are a class of extremely important ligands in asymmetric catalysis. Herein, an unprecedented copper（I）-catalyzed asymmetric SNAr reaction with HP（S）R2is uncovered, which delivers a series of axially chiral phosphine derivatives in high yields with excellent enantioselectivity. Furthermore, the diastereoselective reaction with the kinetic resolution of racemic HP（S）ArR proceeds smoothly, providing the products with moderate diastereoselectivity and excellent enantioselectivity. Control experiments indicate that HP（S）Ph2is much more active than HPPh2and HP（O）Ph2as the pronucleophile in the present reaction. It is found that the SNAr reaction （the first SNAr） proceeds in a desymmetric manner, providing the desired chiral products while a continued SNAr reaction （the second SNAr） slightly occurs in a kinetic resolution manner in the present catalytic system, which enhances the ee of the desired chiral products. DFTcalculations support a concerted reaction pathway rather than a step-wise mechanism. Finally, axially chiral olefin-phosphines produced by the present method work as suitable ligands in Pdcatalyzed asymmetric allylic substitution with C-, N-, and O-nucleophiles and Rh-catalyzed asymmetric addition of arylboronic acid to benzil.

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关于光学成象的谱项分析及信息传递

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物理学报 1960年第6期 305-315页

作者：谭维翰王之江

本文从衍射理论与信息传送观点,导出物体结构谱项表示式,并分析了光学成象的物理实质,指出分辨本领这一概念与信息传送能力的联系,最后给出逐项量度谱项的机构来。

关键词：信息传递谱项情报传递位相板光学成象多光束干涉

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High-performance transparent graphene-based antennas

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Science China Technological Sciences 2025年

作者： Chaoye HONG Lusong wei weijia wang Youmei TANG Qinghai ZHU Jiangtao HUANGFU Mingsheng XU College of Integrated Circuits State Key Laboratory of Silicon and Advanced Semiconductor Materials Zhejiang University College of Information Science and Electronic Engineering Zhejiang University

With the continuous development of wireless communication technology, applications in the military, aerospace,and vehicle wireless communication sectors have demanded miniaturized and aesthetically pleasing antennas. Transparent antennas, which combine the advantages of optical and radio-frequency(RF) technologies, have become a popular research topic. However, existing transparent antennas often suffer from complex preparation processes, fragile materials, poor conductivity, and low optical transmittance. Here, we develop hybrid conductive thin films using graphene and silver nanowires,achieving a transmittance of 86% and a sheet resistance of 7.8 Ω/sq with high environmental stability. We demonstrate the suitability of this nanocomposite in two applications: a transparent ultrahigh-frequency RF-identification tag folded dipole antenna and a transparent X-band microwave half-wave dipole antenna. These antennas offer high gain, high radiation efficiency, and small size, indicating that transparent graphene-based antennas have remarkable potential for intelligent information sensor systems.

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Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang Jie Chen Hai-Di Fan Wan wang Bin wang Ju-Yun Ma Peng-Peng Li Hai-wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua Qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

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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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An Iterated Greedy Algorithm with Memory and Learning Mechanisms for the Distributed Permutation Flow Shop Scheduling Problem

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Computers, Materials & Continua 2025年第1期82卷 371-388页

作者： Binhui wang Hongfeng wang College of Information Science and Engineering Northeastern UniversityShenyang110819China

The distributed permutation flow shop scheduling problem(DPFSP)has received increasing attention in recent *** iterated greedy algorithm(IGA)serves as a powerful optimizer for addressing such a problem because of its straightforward,single-solution evolution ***,a potential draw-back of IGA is the lack of utilization of historical information,which could lead to an imbalance between exploration and exploitation,especially in large-scale *** a consequence,this paper develops an IGA with memory and learning mechanisms(MLIGA)to efficiently solve the DPFSP targeted at the ***,we incorporate a memory mechanism to make a more informed selection of the initial solution at each stage of the search,by extending,reconstructing,and reinforcing the information from previous *** addition,we design a twolayer cooperative reinforcement learning approach to intelligently determine the key parameters of IGA and the operations of the memory ***,to ensure that the experience generated by each perturbation operator is fully learned and to reduce the prior parameters of MLIGA,a probability curve-based acceptance criterion is proposed by combining a cube root function with custom *** last,a discrete adaptive learning rate is employed to enhance the stability of the memory and *** ablation experiments are utilized to verify the effectiveness of the memory mechanism,and the results show that this mechanism is capable of improving the performance of IGA to a large ***,through comparative experiments involving MLIGA and five state-of-the-art algorithms on 720 benchmarks,we have discovered that MLI-GA demonstrates significant potential for solving large-scale *** indicates that MLIGA is well-suited for real-world distributed flow shop scheduling.

关键词： Distributed permutation flow shop scheduling makespan iterated greedy algorithm memory mechanism cooperative reinforcement learning

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刺激膈下迷走神经外周端对血浆自由脂肪酸浓度的影响

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生理学报 1964年第3期 210-218页

作者：林坤伟王志均北京医学院生理教研组北京医学院生理教研组大连医学院进修教师

本工作主要用兎做急性实驗,用强直感应电流刺激腹侧和背侧膈下迷走神經外周端,观察血浆自由脂肪酸濃度的变化,結果如下: (一)兎在麻醉情况下不进行刺激时,血浆自由脂肪酸濃度是比較稳定的;刺激膈下迷走神經后,血浆自由脂肪酸濃度卽显著... 详细信息

本工作主要用兎做急性实驗,用强直感应电流刺激腹侧和背侧膈下迷走神經外周端,观察血浆自由脂肪酸濃度的变化,結果如下: (一)兎在麻醉情况下不进行刺激时,血浆自由脂肪酸濃度是比較稳定的;刺激膈下迷走神經后,血浆自由脂肪酸濃度卽显著升高;注射阿托品后,此反应卽消失。这說明兴奋迷走神經有使血浆自由脂肪酸濃度升高的作用。 (二)切除两侧腎上腺后刺激膈下迷走神經,血浆自由脂肪酸濃度仍表現明显的升高;而当切除胰腺后,此反应卽消失。这說明兴奋迷走神經所引起的血浆自由脂肪酸濃度的增高性变化,主要是通过胰腺而实現的。 (三)为了探討胰腺中那一因素与上述現象的产生有关,曾以注射氯化钴以及四氧嘧啶方法分別破坏胰島α和β細胞。初步結果指出,破坏α細胞后,再刺激膈下迷走神經,血浆自由脂肪酸濃度仍表現升高反应;而当破坏β細胞后,此反应卽基本消失。又結扎胰导管16—23天后,在胰腺腺泡細胞萎縮的基础上,刺激膈下迷走神經,血浆自由脂肪酸濃度不仅不表現升高,反呈明显下降。总結以上結果,可以认为:兴奋迷走神經可通过对于胰腺(可能与胰島β細胞以及胰腺外分泌系統有关)的作用明显地增高血浆自由脂肪酸的水平,这对于进一步闡明在正常机体中脂类代謝的神經体液性調节机制,似有重要的意义。

关键词：脂肪酸胰腺周端血浆

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