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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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吸入高浓度H_(2)对高脂饮食大鼠血浆和肝脏中磷脂和鞘脂分子的影响

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山东第一医科大学（山东省医学科学院）学报 2022年第4期43卷 241-247页

作者：谢云博刘伯言陈军张驰赵敏秦树存王义围承德医学院附属医院全科医疗科神经内科河北承德067000 山东第一医科大学第二附属医院泰山氢生物医学研究院山东泰安271000

目的H_(2)吸入对脂质代谢有一定的调节作用,但对磷脂、鞘脂分子的具体影响尚无研究。本研究通过靶向脂质组学方法检测了66.7%的H_(2)吸入干预后高脂饮食大鼠血浆及肝脏中的磷脂、鞘脂分子的变化,为研究H_(2)改善脂代谢的机制研究提供依... 详细信息

目的H_(2)吸入对脂质代谢有一定的调节作用,但对磷脂、鞘脂分子的具体影响尚无研究。本研究通过靶向脂质组学方法检测了66.7%的H_(2)吸入干预后高脂饮食大鼠血浆及肝脏中的磷脂、鞘脂分子的变化,为研究H_(2)改善脂代谢的机制研究提供依据。方法选取雄性SD大鼠分为对照组、高脂饮食模型组,高脂饮食+66.7%H_(2)干预组。干预10周后,对血浆和肝脏中的不同种类的磷脂和鞘脂进行分析。结果主成分分析及聚类热图表明高脂饮食模型组与对照组之间的磷脂、鞘脂谱存在明显差异,在血浆中检测出差异磷脂分子17种,差异鞘脂分子16种;在肝脏中检测出差异磷脂分子50种,鞘脂分子18种。66.7%H_(2)干预后对血浆的磷脂和鞘脂均有影响,共计5种磷脂酰胆碱、2种溶血磷脂酰乙醇胺、1种鞘磷脂分子含量降低,差异有统计学意义(P<0.05);66.7%H_(2)干预后对肝脏磷脂影响较大,共12种磷脂酰胆碱、6种磷脂酰乙醇胺、3种溶血磷脂酰胆碱、4种溶血磷脂酰乙醇胺分子含量降低,差异有统计学意义(P<0.05),而对神经酰胺、鞘磷脂等鞘脂无显著影响。结论66.7%的H_(2)吸入可影响高脂饮食大鼠磷脂、鞘脂代谢,降低血浆及肝脏中多种磷脂的含量,改善高脂饮食导致的血浆、肝脏中多种磷脂、鞘脂分子水平的异常。H_(2)可作为一种改善脂质代谢的有效辅助手段。H_(2)改善脂质代谢的分子机制值得进一步研究。

关键词：氢气高脂饮食磷脂鞘脂

Observation of topological charge transformations in acoustic vortex using passive periodic systems

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 140-147页

作者： Di-Chao Chen xie Liu Changqing Xu Da-Jian Wu Ying Cheng Xiao-Jun Liu School of Physics and Technology Nanjing Normal University Key Laboratory of Modern Acoustics School of Physics Nanjing University

Vortex transmutation utilizes a periodic system, which not only enables the alteration of the topological charge(TC) of unstable input vortices but also facilitates their transformation into stable structures. This approach is crucial for investigating the characteristics of vortices in various wave systems. Here, we achieve acoustic vortex TC transmutation by employing a welldesigned dual-structured plate external system(DPES). The interactions between the acoustic vortex and the finite-order discrete rotational symmetry lead to the transformation of its topological charge when complete rotational symmetry is broken to Nthorder discrete symmetry. Our results experimentally demonstrate the acoustic vortex TC transmutation based on passive artificial structures, enabling numerous applications in particle manipulation and information multiplexing as well as advancing our understanding and control over free-space acoustic vortices.

关键词： acoustic vortex topological charge transformation artificial structure

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi Department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of General Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

Study on the hydrogen absorption properties of a YGdTbDyHo rare-earth high-entropy alloy

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 127-135页

作者： Tongyue Li Ziliang xie Wenjiao Zhou Huan Tong Dawen Yang Anjia Zhang Yuan Wu Xiping Song State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China Whole Win(Beijing)Materials Sci.&Tech.Co. Ltd.Beijing 100083China

This study investigated the microstructure and hydrogen absorption properties of a rare-earth high-entropy alloy(HEA),*** indicated that the YGdTbDyHo alloy had a microstructure of equiaxed grains,with the alloy elements distributed *** hydrogen absorption,the phase structure of the HEA changed from a solid solution with an hexagonal-close-packed(HCP)structure to a high-entropy hydride with an faced-centered-cubic(FCC)structure without any secondary phase *** alloy demonstrated a maximum hydrogen storage capacity of 2.33 H/M(hydrogen atom/metal atom)at 723 K,with an enthalpy change(ΔH)of-141.09 kJ·mol^(-1)and an entropy change(ΔS)of-119.14 J·mol^(-1)·K^(-1).The kinetic mechanism of hydrogen absorption was hydride nucleation and growth,with an apparent activation energy(E_(a))of 20.90 kJ·mol^(-1).Without any activation,the YGdTbDyHo alloy could absorb hydrogen quickly(180 s at 923 K)with nearly no incubation period *** reason for the obtained value of 2.33 H/M was that the hydrogen atoms occupied both tetrahedral and octahedral *** results demonstrate the potential application of HEAs as a high-capacity hydrogen storage material with a large H/M ratio,which can be used in the deuterium storage field.

关键词： rare-earth high-entropy alloy hydrogen absorption capacity pressure–composition–temperature curves kinetics

Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun xie Department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian Key Laboratory of Toxicant and Drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central Laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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不同烘烤工艺对上部叶带茎烘烤质量的影响

天津农业科学 2017年第3期23卷 35-38页

作者：赵晖吴飞跃赵锦超李峥顾勇张永辉夏建华谢强谢云波河北中烟工业有限责任公司技术中心河北石家庄050051 河南农业大学烟草学院河南郑州450002 四川省烟草公司泸州市公司四川泸州646600

为提高上部叶的质量和可用性,开展了不同烘烤工艺对上部叶带茎烘烤质量的试验。结果表明:与常规的烘烤工艺相比,烤后烟叶的颜色以橘黄为主,外观质量改善;烤后中上等烟比例增加了4.48%;感官质量评吸效果有较明显的改善,降低了刺激性和杂... 详细信息

为提高上部叶的质量和可用性,开展了不同烘烤工艺对上部叶带茎烘烤质量的试验。结果表明:与常规的烘烤工艺相比,烤后烟叶的颜色以橘黄为主,外观质量改善;烤后中上等烟比例增加了4.48%;感官质量评吸效果有较明显的改善,降低了刺激性和杂气等;且烘烤耗时整体降低了11.1%。因此,改进后上部叶带茎烘烤工艺对提高烟叶的烘烤质量和可用性有显著作用。

关键词：烤烟带茎烘烤工艺烘烤质量

Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第1期 249-256页

作者： Qing-Yun Fang Chengyihan Gu Yinghan Chen Wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin xie State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State Key Laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

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Advances in Graphene‑Based Electrode for Triboelectric Nanogenerator

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Nano-Micro Letters 2025年第1期17卷 378-403页

作者： Bin xie Yuanhui Guo Yun Chen Hao Zhang Jiawei Xiao Maoxiang Hou Huilong Liu Li Ma Xin Chen Chingping Wong State Key Laboratory of Precision Electronic Manufacturing Technology and Equipment Guangdong University of TechnologyGuangzhou 510006People’s Republic of China School of Electromechanical Engineering Guangdong University of TechnologyGuangzhou 510006People’s Republic of China School of Materials Science and Engineering Georgia Institute of TechnologyAtlantaGA 30332USA

With the continuous development of wearable electronics,wireless sensor networks and other micro-electronic devices,there is an increasingly urgent need for miniature,flexible and efficient nanopower generation *** nanogenerator(TENG)technology can convert small mechanical energy into electricity,which is expected to address this *** the core component of TENG,the choice of electrode materials significantly affects its *** metal electrode materials often suffer from problems such as durability,which limits the further application of ***,as a novel electrode material,shows excellent prospects for application in TENG owing to its unique structure and excellent electrical *** review systematically summarizes the recent research progress and application prospects of TENGs based on graphene *** precision processing methods of graphene electrodes are introduced,and the applications of graphene electrode-based TENGs in various scenarios as well as the enhancement of graphene electrodes for TENG performance are *** addition,the future development of graphene electrode-based TENGs is also prospectively discussed,aiming to promote the continuous advancement of graphene electrode-based TENGs.

关键词： Triboelectric nanogenerator Precision processing Graphene electrode Self-powered sensor