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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68卷 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.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua huang Di Zhao Lemei Zhu Zheyu Zhang min Yi Weijun Peng Department of Integrated Traditional Chinese&Western Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Metabolic Diseases ChangshaHunan ProvinceChina Hunan Academy of Chinese Medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

Synergistically enhanced ORR and HER performance on Co-N-C coupled in-situ generated PtCo intermetallic

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Journal of Energy Chemistry 2025年第1期100卷 721-729页

作者： Guanyu Luo min Song Lulu An Xiao huang Qian Zhang Chenhao Zhang Tao Shen Shuang Wang Deli Wang Key Laboratory of Material Chemistry for Energy Conversion and Storage (Huazhong University of Science and Technology) ministry of Education School of Chemistry and Chemical Engineering Huazhong University of Science and Technology

Integrating multi-scale sites in a composite catalyst is vital to realize efficient ***,a synergistic composite catalyst consisting of Co atomic sites and in-situ generated PtCo intermetallic compounds （IMCs）(o-PtCo@CoNC) is proposed through Co pre-anchoring and subsequent impregnation-reduction *** loading of Co atoms provides a chance for in-situ generating PtCo ordered intermetallic *** remaining Co single atoms and PtCo IMCs construct synergistic electrocatalytic *** from the ordered structure,synergistic effect of Pt Co IMCs and Co single atoms,o-PtCo@CoNC exhibits excellent electrocatalytic performance for oxygen reduction reaction （ORR） and hydrogen evolution reaction （HER） with mass activity of 1.21 A mgPt-1（at 0.9 V） and5.70 A mgPt-1（at an overpotential of 100 mV）,***,o-PtCo@CoNC delivers negligible loss of half-wave potential and overpotential during long-term stability test in acid solutions,with 13 mV decay after 50,000 potential cycles for ORR and a 2.7 mV decay after 20,000 potential cycles for *** integration strategy of single-atomic sites coupled IMCs paves the way for enhancing the activity and durability of Pt-based electrocatalysts.

关键词： Synergistic effect Intermetallics Single atomic sites Oxygen reduction reaction Hydrogen evolution reaction

低温和赤霉素对亚洲百合开花及鳞茎繁殖的效应

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吉林农业大学学报 2007年第5期29卷 511-517页

作者：陈诗林黄敏玲福建省农业科学院生物技术研究所福州350003 福建省农业科学院花卉研究中心福州350013

以亚州百合为试材，探讨了低温冷藏、设施栽培和赤霉素结合低温处理对亚洲百合开花及新球繁殖的效应。结果表明：亚洲百合鳞茎在适宜温度5℃下冷藏56d，周径12cm以上的种球开花率达到95％以上；设施栽培（遮荫、保温及补光）比对照（露... 详细信息

以亚州百合为试材，探讨了低温冷藏、设施栽培和赤霉素结合低温处理对亚洲百合开花及新球繁殖的效应。结果表明：亚洲百合鳞茎在适宜温度5℃下冷藏56d，周径12cm以上的种球开花率达到95％以上；设施栽培（遮荫、保温及补光）比对照（露地栽培）花期提早31d，开花率98．5％；低温（5℃，56d）冷藏处理结合设施栽培，花期提早82d，开花率96．5％；赤霉素200mg／L处理加低温冷藏，花期提早92d，比冷藏处理提早10d，开花率97．3％；低温冷藏后用赤霉素200～300meCL处理，可显著提高花茎长，但对花期没有影响；低温或低温结合赤霉素处理，新球周径比常规栽培显著提高，而新球繁殖数显著降低；二次开花显著影响新球发育，籽球退化，需复壮栽培。

关键词：亚洲百合赤霉素低温处理开花种球繁殖

新型冠状病毒感染患者在抗病毒药物联用时的安全性分析

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中国临床药理学杂志 2020年第10期36卷 1397-1403页

作者：张杰黄敏玲王颖彦广州中医药大学第二附属医院药学部广东广州510120 广州中医药大学第二附属医院呼吸与危重症医学科广东广州510120

新型冠状病毒肺炎(COVID-19)患者特别是重症患者,多高龄合并慢性病,采用抗病毒药物联合治疗的安全性与疗效尚不明确。本文从临床药理学、相互作用及药物不良反应的维度,对抗病毒药物联合治疗时的安全性予以分析与建议。

关键词：法匹那韦氯喹洛匹那韦/利托那韦药代动力学 2019新型冠状病毒抗病毒药药学监护

鹤望兰ζ–胡萝卜素脱氢酶基因SrZDS的克隆及表达分析

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园艺学报 2016年第5期43卷 957-965页

作者：樊荣辉黄敏玲钟淮钦林兵福建省农业科学院作物研究所福建省农业科学院花卉研究中心福建省特色花卉工程技术研究中心福州350013

采用RT-PCR和RACE方法从鹤望兰(Strelitzia reginae Banks)黄色花萼中克隆到1个ζ–胡萝卜素脱氢酶基因(Sr ZDS)。其c DNA全长2 111 bp(Gen Bank收录号:KT428724),具有完整的开放阅读框,共1 710个碱基。与其他物种的氨基酸序列都有一定... 详细信息

采用RT-PCR和RACE方法从鹤望兰(Strelitzia reginae Banks)黄色花萼中克隆到1个ζ–胡萝卜素脱氢酶基因(Sr ZDS)。其c DNA全长2 111 bp(Gen Bank收录号:KT428724),具有完整的开放阅读框,共1 710个碱基。与其他物种的氨基酸序列都有一定的同源性,其中与玉米的ZDS同源性最高,达到86%。系统进化树分析显示,Sr ZDS与水仙蛋白亲缘关系较近。荧光定量PCR分析表明:Sr ZDS在鹤望兰黄色花萼中高表达,且在花发育的始花期和盛花期表达量最高。应用UPLC对其类胡萝卜素含量进行分析,其总量在黄色花萼中最高,且在盛花期最高,表明Sr ZDS的表达与类胡萝卜素含量成正相关。

关键词：鹤望兰 ζ–胡萝卜素脱氢酶类胡萝卜素生物合成基因克隆 UPLC

Highly mass activity electrocatalysts with ultralow Pt loading on carbon black for hydrogen evolution reaction

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International Journal of minerals,Metallurgy and Materials 2025年第1期32卷 182-190页

作者： Shaorou Ke Yajing Zhao Xin min Yanghong Li Ruiyu Mi Yangai Liu Xiaowen Wu minghao Fang Zhaohui huang Engineering Research Center of ministry of Education for Geological Carbon Storage and Low Carbon Utilization of Resources Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid WastersNational Laboratory of Mineral MaterialsSchool of Materials Science and TechnologyChina University of Geosciences(Beijing)Beijing 100083China

Pt-based nanocatalysts offer excellent prospects for various ***,the low loading of Pt with excellent performance for efficient and stable nanocatalysts still presents a considerable *** this study,nanocatalysts with ultralow Pt content,excellent performance,and carbon black as support were prepared through in-situ ***~2-nm particles uniformly and stably dispersed on carbon black because of the strong s-p-d orbital hybridizations between carbon black and Pt,which suppressed the agglomeration of Pt *** unique structure is beneficial for the hydrogen evolution *** catalysts exhibited remarkable catalytic activity for hydrogen evolution reaction,exhibiting a potential of 100 mV at 100 mA·cm^(-2),which is comparable to those of commercial Pt/C *** activity(1.61 A/mg)was four times that of a commercial Pt/C catalyst(0.37 A/mg).The ultralow Pt loading(6.84wt%)paves the way for the development of next-generation electrocatalysts.

关键词： hydrogen evolution reaction ultralow platinum in-situ synthesis ultrasound

腹腔镜下全子宫切除术与经腹全子宫切除术治疗子宫疾病的效果对比分析

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世界复合医学 2020年第5期6卷 83-85页

作者：黄敏玲广西南宁市上林县妇幼保健院妇产科广西南宁530500

目的研究腹腔镜下全子宫切除术与经腹全子宫切除术治疗子宫疾病的效果对比分析。方法选取该院在2017年7月—2019年6月期间接收全子宫切除术的90例子宫疾病患者作为该次研究对象。将以上患者随机分成两组进行对比实验。观察两组患者对手... 详细信息

目的研究腹腔镜下全子宫切除术与经腹全子宫切除术治疗子宫疾病的效果对比分析。方法选取该院在2017年7月—2019年6月期间接收全子宫切除术的90例子宫疾病患者作为该次研究对象。将以上患者随机分成两组进行对比实验。观察两组患者对手术治疗方案的评价,将评价分为非常满意、满意、一般、不满意4个等级。观察两组患者术后并发症的比例。观察两组患者手术时间、术中出血量、肛门排气时间、术后体温、住院时间等。结果采用观察组手术治疗方案的患者的总满意度为97.78%,采用对照组手术治疗方案患者的总满意度为82.22%,有此可见,观察组的手术治疗方案满意度高(χ2=4.444,P=0.035);采用观察组的手术治疗方案的患者共有2例出现并发症,所占比例为4.44%,采用对照组的手术治疗方案的患者共有10例出现并发症,所占比例为22.22%,由此可见,观察组的手术治疗方案的并发症比例更低(P0.05)。但观察组的术后肛门排气时间比对照组要短,术后体温也比对照组低,住院时间比对照组短,由此可以看出,观察组的手术治疗方案更佳,差异有统计学意义(P<0.05)。结论经研究发现,腹腔镜下全子宫切除术具有损伤小、病人痛苦少、手术效果好、住院时间短,治疗费用低,术后并发症发生低恢复快等优点,值得在临床中推广使用。

关键词：腹腔镜全子宫切除术经腹全子宫切除术子宫疾病

Systematic Acupuncture Explains Acupuncture at Baihui(GV20) and Fengchi(GB20) Targeting the Inflammatory Response to Regulate Migraine

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Journal of Traditional Chinese Medicine 2025年

作者： min Yu ZHENG Meifeng SUN Ju PENG Zetong CAO Zhixian huang Xiaohua Medical College of Acu-Moxi and Rehabilitation， Guangzhou University of Chinese Medicine Department of Rehabilitation Medicine， the Affiliated Panyu Central Hospital of Guangzhou Medical University

Objective: To take Baihui (GV20) and Fengchi (GB20) targeting inflammatory response to regulate migraine as an example to describe a new method for studying the mechanism of stimulating ***: The target information of Baihui (GV20) and Fengchi (GB20) was retrieved， and after intersection with migraine， Kyoto Encyclopedia of Genes and Genomes (KEGG)， Reactome， and UniProt Keywords were used for functional enrichment. After selecting the main pathway， rats were selected and nitroglycerin was used for modeling， and the behavioral scores， inflammatory factors， heme oxygenase 1 (HMOX1)， protein kinase B (AKT1)， signal transducer and activator of transcription 3 (STAT3)， phosphorylated extracellular signal-regulated kinase 1/2 (P-ERK1/ERK2) and other states of the rats in the acupuncture， twisting， and electroacupuncture groups were ***: A total of 135 Baihui (GV20) targets and 27 Fengchi (GB20) targets were collected. A total of 73 target information were obtained after the intersection of these targets in migraine. These 73 targets have three main pathways: hypoxia-inducible factor 1 (HIF-1) signaling pathway， signaling by interleukins and inflammatory response. The main targets in the pathway were verified and found that interleukin-1 beta (IL-1β)， interleukin-6 (IL-6)， tumor necrosis factor-alpha (TNF-α) and HMOX1， AKT1， STAT3， P-ERK1/ERK2 can be regulated by Baihui (GV20) and Fengchi (GB20).Conclusion: Baihui (GV20) and Fengchi (GB20) can regulate migraine by regulating inflammatory factors and HMOX1， AKT1， STAT3， P-ERK1/ERK2 and other changes in HIF-1 signaling pathway， Signaling by Interleukins and Inflammatory response pathways. Based on systems biology and network pharmacology， and with the model of "acupoint-target-disease"， explore the research methods of systematic acupuncture and moxibustion. We believe this is a usable research direction for exploring the mechanism of acupuncture stimulation.

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