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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie qi Jinrong Lin Yaying Sun Jiebin huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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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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静电场对强激光场非序列双电子电离的影响

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物理学报 2008年第1期57卷 124-131页

作者：李洪云王兵兵蒋红兵陈京李晓峰刘杰龚旗煌傅盘铭北京大学物理学院人工微结构和介观物理国家重点实验室北京100871 中国科学院物理研究所光物理实验室北京100080 应用物理与计算数学研究所非线性研究中心北京100088

利用半经典重碰模型计算并研究了He原子在强激光场与静电场的混合场下的非序列双电子电离过程.由于静电场破坏了激光场电场的反演对称性,在平行于激光场偏振方向的He2+离子动量分布不再具有对称双峰结构.由于超短脉冲具有相似的非对称性... 详细信息

利用半经典重碰模型计算并研究了He原子在强激光场与静电场的混合场下的非序列双电子电离过程.由于静电场破坏了激光场电场的反演对称性,在平行于激光场偏振方向的He2+离子动量分布不再具有对称双峰结构.由于超短脉冲具有相似的非对称性,研究静电场对原子在强场中非序列电离的影响,有助于分析超短脉冲非序列电离的过程,进一步了解非序列双电子电离的机理.

关键词：非序列双电离静电场重碰非对称性场

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Phrase-based hashtag recommendation for microblog posts

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Science China(Information Sciences) 2017年第1期60卷 132-144页

作者： Yeyun gong qi ZHANG Xiaoying HAN Xuanjing huang Shanghai Key Laboratory of Intelligent Information Processing School of Computer Science Fudan University

In microblogs, authors use hashtags to mark keywords or topics. These manually labeled tags can be used to benefit various live social media applications(e.g., microblog retrieval, classification). However,because only a small portion of microblogs contain hashtags, recommending hashtags for use in microblogs are a worthwhile exercise. In addition, human inference often relies on the intrinsic grouping of words into ***, existing work uses only unigrams to model corpora. In this work, we propose a novel phrase-based topical translation model to address this problem. We use the bag-of-phrases model to better capture the underlying topics of posted microblogs. We regard the phrases and hashtags in a microblog as two different languages that are talking about the same thing. Thus, the hashtag recommendation task can be viewed as a translation process from phrases to hashtags. To handle the topical information of microblogs, the proposed model regards translation probability as being topic specific. We test the methods on data collected from realworld microblogging services. The results demonstrate that the proposed method outperforms state-of-the-art methods that use the unigram model.

关键词： recommendation topic model translation phrase extraction hashtag

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FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation

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Science China Life Sciences 2025年

作者： Dake Xiao Haowen Ran Lishu Chen Yuanyuan Li Yan Cai Songyang Zhang qinghui qi Huiran Wu Cheng Zhang Shuailiang Cao Lanjuan Mi Haohao huang Ji qi qiuying Han Haiqing Tu Huiyan Li Tao Zhou Fangye Li Ailing Li Jianghong Man Nanhu Laboratory National Center of Biomedical Analysis School of Traditional Chinese Medicine Capital Medical University Department of Neurosurgery General Hospital of Central Theater Command of Chinese PLA School of Life and Health Sciences Huzhou College Department of Neurosurgery Beijing Fengtai Hospital Department of Neurosurgery First Medical Center of PLA General Hospital

The infiltration of glioblastoma multiforme(GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6(HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng huang Zhijun Wu Baitao Liu Hongjie huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Enhanced subacute ischemic stroke treatment via multistage drug delivery system design for combination therapy

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Science China Chemistry 2025年

作者： Xihan Xu Juan-Juan Li Jiamin Li Hui-Yan Zhang Yilin qi Bing-Sen Shi Tianqi Li Shan-Shan Su Weitao Zhao Chang Chen Zhongying gong Huiyu Liu Ke-Rang Wang Dong-Sheng Guo Xue Xue State Key Laboratory of Medicinal Chemical Biology College of Pharmacy Nankai University College of Chemistry State Key Laboratory of Elemento-Organic Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Frontiers Science Center for New Organic Matter Collaborative Innovation Center of Chemical Science and EngineeringNankai University College of Chemistry and Materials Science State Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education) Key Laboratory of Chemical Biology of Hebei Province Hebei Research Center of the Basic Discipline of Synthetic Chemistry Hebei University Department of Neurology Tianjin First Central Hospital School of Medicine Nankai University Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic-Inorganic Composites Beijing Laboratory of Biomedical Materials Bionanomaterials & Translational Engineering Laboratory Beijing Key Laboratory of BioprocessBeijing University of Chemical Technology

The management of acute ischemic stroke remains challenging due to its abrupt onset and the narrow treatment window,resulting in high rates of disability and *** therapy for neuroprotection and neurorepair strategies provided new hopes for subacute stroke *** we designed a multistage nanodelivery system that matches the unique microenvironment of the subacute phase of stroke,which utilizes calixarene as a building block to effectively load the neuroprotective drug *** calixarene is designed with glycosidic linkages targeting the glucose transporter 1 (GLUT1)on the blood-brain barrier (BBB) and azo bonds that are responsive to hypoxic ***,the decomposed calixarene molecules themselves possess intrinsic bio-activation to modulate inflammatory responses,achieving a multistage therapeutic approach that transitions from targeting to release and finally to *** approach combines anti-inflammation and neuroprotection,providing a multi-level treatment *** system was validated in a rat model of permanent middle cerebral artery occlusion (pMCAO),demonstrating that intravenous administration of the nanodelivery system repairs brain damage and improves motor function 24 h post-pMCAO *** work offers a precise and integrative strategy for stroke patients missing the acute therapy window to improve functional recovery and enhance the effect of comprehensive treatment.

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A novel reliability analysis method for engineering problems:Expanded learning intelligent back propagation neural network

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Chinese Journal of Aeronautics 2024年第12期37卷 212-230页

作者： Ying huang Jianguo ZHANG Xiaoduo FAN qi gong Lukai SONG School of Reliability and Systems Engineering Beihang UniversityBeijing 100191China AVIC Aero Polytechnology Establishment Beijing 100028China Department of Mechanical Engineering The Hong Kong Polytechnic UniversityHong Kong 100872China Research Institute of Aero-Engine Beihang UniversityBeijing 102206China

Estimating the failure probability of highly reliable structures in practice engineering,such as aeronautical components,is challenging because of the strong-coupling and the small failure probability *** this paper,an Expanded Learning Intelligent Back Propagation(EL-IBP)neural network approach is developed:firstly,to accurately characterize the engineering response coupling relationships,a high-fidelity Intelligent-optimized Back Propagation(IBP)neural network metamodel is developed;furthermore,to elevate the analysis efficacy for small failure assessment,a novel expanded learning strategy for adaptive IBP metamodeling is *** numerical examples and one typical practice engineering case are analyzed,to validate the effectiveness and engineering application value of the proposed *** comparison shows that the ELIBP method holds significant efficiency and accuracy superiorities in engineering *** current study may shed a light on pushing the adaptive metamodeling technique deeply toward complex engineering reliability analysis.

关键词： Reliability analysis Back propagation neural network Adaptive metamodel Variance expansion Small failure probability Strong-coupling

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Extra-narrowband metallic filters with an ultrathin single-layer metallic grating

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Chinese Physics B 2020年第6期29卷 242-248页

作者： Ran Wang qi-huang gong Jian-Jun Chen State Key Laboratory for Mesoscopic Physics School of PhysicsPeking UniversityBeijing 100871China Microelectronics Instruments and Equipments R&D Center Institude of Microelectronics of Chinese Academy of SciencesBeijing 100029China Nano-optoelectronics Frontier Center of Ministry of Education(NFC-MOE)&Collaborative Innovation Center of Quantum Matter Peking UniversityBeijing 100871China Collaborative Innovation Center of Extreme Optics Shanxi UniversityTaiyuan 030006China

Narrowband and high-transmission optical filters are extensively used in color display technology, optical information processing, and high-sensitive sensing. Because of large ohmic losses in metallic nanostructures, metallic filters usually exhibit low transmittances and broad bandwidths. By employing both strong field enhancements in metallic nano-slits and the Wood’s anomaly in a periodic metallic grating, an extra-narrowband and high-transmission metallic filter is numerically predicted in an ultrathin single-layer metallic grating. Simulation results show that the Wood’s anomaly in the ultrathin(thickness H = 60 nm) single-layer metallic grating results in large field enhancements in the substrate and low losses in the metallic grating. As a result, the transmission bandwidth(transmittance T > 60%) at λ = 1200 nm is as small as △λFWHM=1.6 nm, which is smaller than 4% of that in the previous thin dielectric and metallic filters. The corresponding quality factor is as high as Q = λ/△λFWHM= 750, which is 40 times greater than that in the previous reports. Moreover, the thickness of our metallic filter(H = 60 nm) is smaller than 40% of that in the previous reports, and its maximum transmittance can reach up to 80%. In experiments, a narrowband metallic filter with a bandwidth of about △λFWHM = 10 nm, which is smaller than 25% of that in the previous metallic filters, is demonstrated.

关键词： metallic filter extra-narrowband field enhancement Wood’s anomaly

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飞秒激光在三维微细体系中的应用

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物理 2000年第12期29卷 719-723页

作者：李承德王丹翎罗乐杨宏龚旗煌北京大学物理系人工微结构与介观物理国家重点实验室北京100871

飞秒激光的超快特性使其能以极低的脉冲能量获得超强光场 ,并且激光辐照区淀积的能量难以通过热扩散途径逸出辐照区域 ,其与透明物质相互作用是通过双光子或多光子吸收过程实现 ,故作用区限域于焦点核心很小体积内 ,因而在三维微制备及... 详细信息

飞秒激光的超快特性使其能以极低的脉冲能量获得超强光场 ,并且激光辐照区淀积的能量难以通过热扩散途径逸出辐照区域 ,其与透明物质相互作用是通过双光子或多光子吸收过程实现 ,故作用区限域于焦点核心很小体积内 ,因而在三维微制备及生物医学领域有着独到优势 .文章介绍了飞秒激光应用于微爆炸、高密度三维光学数据存储、直写光波导及三维光子晶体制备、生物医学工程等方面的最新进展 .飞秒激光三维微制备技术在微电子、计算机、光通信。

关键词：飞秒激光三维激光微制备光聚合三维微细体系

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