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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

Science China Life Sciences 2024年

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 College Fudan University Department of Breast Surgery Fudan University Shanghai Cancer Center Fudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan Hospital Capital 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 Center Fudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) Institutes of Biomedical Sciences Fudan 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 siRNAs 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 AZD1775promotes 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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Hot Compressive Deformation Characteristics of Al-9.3Zn-2.4Mg-1.1Cu Alloy

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 754-765页

作者：刘鹏茹郝世明 xie Jingpei School of Physics and Engineering Henan University of Science and TechnologyLuoyang 471023China School of Materials Science and Engineering Henan University of Science and TechnologyLuoyang 471023China Provincial and Ministerial Co-Construction of Collaborative Innovation Center for Non-Ferrous Metal New Materials and Advanced Processing Technology Luoyang 471023China

To understand the hot compression deformation characteristics of the self-developed Al-9.3Zn-2.4Mg^(-1).1Cu alloy,the hot compression tests of Al-9.3Zn-2.4Mg^(-1).1Cu alloy were investigated by Gleeble 1500 thermo-mechanical simulator to determine the best hot processing *** hot deformation temperatures were 300,350,400,and 450℃,and the strain rates were 1,0.1,0.01,and 0.003 s^(-1),*** on the experimental results,the constitutive equation and hot processing maps are established,and the corresponding strain rate and temperature-sensitive index are *** results show that Al-9.3Zn-2.4Mg^(-1).1Cu alloy has a dynamic softening trend and high strain rate sensitivity during the isothermal compression *** hot deformation behavior can be described by an Arrhenius-type equation after strain *** temperature has a negligible effect on the hot processing properties,while a low strain rate is favorable for the hot working of *** processing maps and microstructure show that the optimal processing conditions were in the temperature range of 400-450℃and strain rate range of 0.003-0.005 s^(-1).

关键词： Al-Zn-Mg-Cu alloy hot working hot deformation behavior constitutive equations processing maps

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Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure:A multicenter study

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World Journal of Gastroenterology 2024年第27期30卷 3314-3325页

作者： Guang-Wen Cheng Yan Fang Li-Yun Xue Xiao-Hui Qiao Xue-Qi Li Yan Zhang Jia Guo Xiao-Yan xie Hong ding Department of Ultrasound Huashan HospitalFudan UniversityShanghai 200040China Department of Ultrasound Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Medical Ultrasonics Institute of Diagnostic and Interventional UltrasoundSun Yat-sen University First Affiliated HospitalGuangzhou 510080Guangdong ProvinceChina Institute of Ultrasound in Medicine and Engineering Shanghai Cancer CenterShanghai 200040China Department of Ultrasound Eastern Hepatobiliary Surgical HospitalSecond Military Medical UniversityShanghai 200433China Department of Ultrasound National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China

BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function *** size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/*** was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict *** prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction *** To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction *** This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March *** 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other *** absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a *** performance was validated *** diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)*** A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this *** independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total *** diagnostic performanc

关键词： Shear-wave elastography Spleen Hepatectomy Posthepatectomy liver failure Hepatocellular carcinoma

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Literature overview of basic characteristics and flotation laws of flocs

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International Journal of Minerals,Metallurgy and Materials 2024年第5期31卷 943-958页

作者： Wanzhong Yin Yu xie Zhanglei Zhu School of Resources and Civil Engineering Northeastern UniversityShenyang 110819China College of Chemistry and Chemical Engineering Xi’an University of Science and TechnologyXi’an 710054China

Flocculation flotation is the most efficient method for recovering fine-grained minerals,and its essence lies in flotation and recovery of *** physical characteristics of flocs are mainly determined by their apparent particle size and structure(density and morphology).Substantial researches have been conducted regarding the effect of floc characteristics on particle settling and water ***,the influence of floc characteristics on flotation has not been widely *** on the floc formation and flocculation flotation,this study reviews the fundamental physical characteristics of flocs from the perspectives of floc particle size and structure,summarizing the interaction between floc particle size and ***,it thoroughly discusses the effect of floc particle size and structure on floc floatability,further revealing the influence of floc characteristics on bubble collision and adhesion and elucidating the mechanisms of interaction between flocs and ***,it is observed that floc particle size is not the only factor influencing flocculation *** the appropriate apparent particle size range,flocs with a compact structure exhibit higher efficiency in bubble collision and adhesion during flotation,thereby resulting in enhanced flotation *** study aims to provide a reference for flocculation flotation,targeting the development of more efficient and refined flocculation flotation processes in the future.

关键词： flocs basic characteristics particle size and structure flotation laws bubbles

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Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第5期30卷 449-457页

作者： xie Shuang-ran MA Liang XU Xin-yu ZHOU Shu xie Hui-miao xie Chang-sheng The First Clinical Medical College Zhejiang Chinese Medical UniversityHangzhou 310053China Department of Medical Oncology Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical UniversityHangzhou 310007China Department of Dermatology the Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Famous Chinese Medicine Clinic the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310005China Department of Medical Oncology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China

Backgroup:Currently,aromatherapy is being increasingly utilized in clinical practice,particularly in managing the side effects associated with radiotherapy and ***,it remains to be established whether aromatherapy can effectively alleviate these ***:To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and ***:Seven databases were researched from inception until September 29,2023,including PubMed,Scopus,and Web of Science,Chinese National Knowledge Infrastructure,Wanfang database,China Biology Medicine disc and VIP Chinese Medical Journal *** Manager version 5.3 was utilized for data *** Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the *** quality rating was assessed using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE) approach through the GRADEpro GDT online ***:Nineteen studies involving 1,541 patients were *** can alleviate nausea [relative risk(RR)=0.64,95% confidence interval(CI):0.53 to 0.78,Pding to the GRADE ***:Aromatherapy is an efficacious,safe a

关键词： aromatherapy cancer chemoradiotherapy physical psychological

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Copy number variation of NAL23 causes narrow-leaf development in rice

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Journal of Genetics and Genomics 2024年第8期51卷 880-883页

作者： Degui Zhou Yajing Li Xianrong xie Wenyan ding Libin Chen Tie Li Jianian Tang Xiyu Tan Weizhi Liu Yueqin Heng Yongyao xie Letian Chen Qi Liu Shaochuan Zhou Jing Zhao Gong Zhang Jiantao Tan Yaoguang Liu Rongxin Shen State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources Guangdong Laboratory for Lingnan Modern AgricultureCollege of Life SciencesSouth China Agricultural UniversityGuangzhouGuangdong 510642China Guangdong Key Laboratory of New Technology in Rice Breeding Rice Research InstituteGuangdong Academy of Agricultural SciencesGuangzhouGuangdong 510640China Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology Institute of Life and Health EngineeringJinan UniversityGuangzhouGuangdong 510632China

Leaf shape is a key trait for plant architecture relating to photosynthesis and transpiration in plants(Lawson et al.,2020).Erect leaves with proper leaf length and width,particularly the upper three leaves in cereal crops,could significantly improve light absorption efficiency in canopy and ultimately increase crop yield(Jiao et al.,2010).Rice leaves initiate at the peripheral zone of shoot apical meristem,then develop along the proximal-distal,adaxial-abaxial,and mediallateral axes to form a flat symmetric architecture(Du et al.,2018).

关键词： crops cereal narrow

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Optimal Coordination of Transportable Power Sources and Repair Crews for Service Restoration of Distribution Networks Considering Uncertainty of Traffic Congestion

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Journal of Modern Power Systems and Clean Energy 2024年第1期12卷 189-201页

作者： Zhao Shi Yan Xu Dunjian xie Shiwei xie Amer M.Y.M.Ghias Nanyang Technological University Singapore the School of Electrical Engineering and Automation Fuzhou UniversityFuzhou 350108China

This paper proposes a new method for service restoration of distribution network with the support of transportable power sources(TPSs)and repair crews(RCs).Firstly,a coupling model of distribution networks and vehicle routing of TPSs and RCs is proposed,where the TPSs serve as emergency power supply sources,and the RCs are used to repair the faulted *** the uncertainty of traffic congestion,the probability distribution of the travel time spent on each road is derived based on the Nesterov user equilibrium model,and a two-stage stochastic program is formulated to determine the optimal routings of TPSs and *** efficiently solve the proposed stochastic mixed-integer linear program(MILP),a two-phase scenario reduction method is then developed to scale down the problem size,and an adaptive progressive hedging algorithm is used for an efficient *** effectiveness of the proposed methods and algorithms has been illustrated in a modified IEEE 33-bus system.

关键词： Service restoration distribution network traffic uncertainty transportable power source repair crew stochastic program

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Analysis of a class of globally divergence-free HDG methods for stationary Navier-Stokes equations

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Science China Mathematics 2024年第5期67卷 1133-1158页

作者： Gang Chen Xiaoping xie School of Mathematics Sichuan University Chengdu 610064China

In this paper,we analyze a class of globally divergence-free(and therefore pressure-robust)hybridizable discontinuous Galerkin(HDG)finite element methods for stationary Navier-Stokes *** methods use the P_(k)/P_(k-1)(k≥1)discontinuous finite element combination for the velocity and pressure approximations in the interior of elements,piecewise Pm(m=k,k-1)for the velocity gradient approximation in the interior of elements,and piecewise P_(k)/P_(k) for the trace approximations of the velocity and pressure on the inter-element *** show that the uniqueness condition for the discrete solution is guaranteed by that for the continuous solution together with a sufficiently small mesh *** on the derived discrete HDG Sobolev embedding properties,optimal error estimates are *** experiments are performed to verify the theoretical analysis.

关键词： Navier-Stokes equations HDG methods divergence-free uniqueness condition error estimates

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Method for Detecting Industrial Defects in Intelligent Manufacturing Using Deep Learning

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Computers, Materials & Continua 2024年第1期78卷 1329-1343页

作者： Bowen Yu Chunli xie College of Mechanical and Electrical Engineering Northeast Forestry UniversityHarbin150040China

With the advent of Industry 4.0,marked by a surge in intelligent manufacturing,advanced sensors embedded in smart factories now enable extensive data collection on equipment *** analysis of such data is pivotal for ensuring production safety,a critical factor in monitoring the health status of manufacturing *** defect detection techniques,typically limited to specific scenarios,often require manual feature extraction,leading to inefficiencies and limited versatility in the overall *** research presents an intelligent defect detection methodology that leverages deep learning techniques to automate feature extraction and defect localization *** proposed approach encompasses a suite of components:the high-level feature learning block(HLFLB),the multi-scale feature learning block(MSFLB),and a dynamic adaptive fusion block(DAFB),working in tandem to extract meticulously and synergistically aggregate defect-related characteristics across various scales and hierarchical *** have conducted validation of the proposed method using datasets derived from gearbox and bearing *** empirical outcomes underscore the superior defect detection capability of our *** demonstrates consistently high performance across diverse datasets and possesses the accuracy required to categorize defects,taking into account their specific locations and the extent of damage,proving the method’s effectiveness and reliability in identifying defects in industrial components.

关键词： Industrial defect detection deep learning intelligent manufacturing

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Building the toolbox for in vivo glia-to-neuron reprogramming

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Neural Regeneration Research 2024年第6期19卷 1171-1172页

作者： Ye xie Bo Chen Departments of Ophthalmology and Neuroscience Icahn School of Medicine at Mount Sinai

Unlike regenerative-competent species that possess a remarkable intrinsic capacity to replenish lost neurons and restore neurocircuits spontaneously, the central nervous system in adult mammals lacks the ability to compensate for the neuronal loss caused by neurodegenerative diseases or traumatic injuries resulting in permanent loss of functionality. Inspired by earlier discoveries that radial glia or astrocytes isolated from the postnatal cortex can generate neurons,

关键词： CONVERSION DISEASE

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