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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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Scalable Ir-Doped NiFe₂O₄/TiO₂ Heterojunction Anode for Decentralized Saline Wastewater Treatment and H₂ Production

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NANO-MICRO LETTERS 2025年第1期17卷 1-18页

作者： hong, Sukhwa Kim, Jiseon Park, Jaebeom Im, Sunmi Hoffmann, Michael R. Cho, Kangwoo Pohang Univ Sci & Technol POSTECH Div Environm Sci & Engn Pohang 790784 South Korea CALTECH Linde Labs Pasadena CA 91125 USA Yonsei Univ Int Campus Inst Convergence Res & Educ Adv Technol I CREATE Incheon 21983 South Korea

Wastewater electrolysis cells (WECs) for decentralized wastewater treatment/reuse coupled with H-2 production can reduce the carbon footprint associated with transportation of water, waste, and energy carrier. This study reports Ir-doped NiFe2O4 (NFI, similar to 5 at% Ir) spinel layer with TiO2 overlayer (NFI/TiO2), as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment cell. In dilute (0.1 M) NaCl solutions, the NFI/TiO2 marks superior activity and selectivity for chlorine evolution reaction, outperforming the benchmark IrO2. Robust operation in near-neutral pH was confirmed. Electroanalyses including operando X-ray absorption spectroscopy unveiled crucial roles of TiO2 which serves both as the primary site for Cl- chemisorption and a protective layer for NFI as an ohmic contact. Galvanostatic electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO2 not only achieves quasi-stoichiometric NH4+-to-N-2 conversion, but also enhances H-2 generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive chlorine. The scaled-up WEC with NFI/TiO2 was demonstrated for electrolysis of toilet wastewater.

关键词： Wastewater electrolysis cell Ir-doped NiFe2O4 Reactive chlorine species Decentralized H-2 production On-site wastewater treatment

Constructing Donor–Acceptor‑Linked COFs Electrolytes to Regulate Electron Density and Accelerate the Li^(+)Migration in Quasi‑Solid‑State Battery

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Nano-Micro Letters 2025年第1期17卷 456-471页

作者： Genfu Zhao Hang Ma Conghui Zhang Yongxin Yang Shuyuan Yu Haiye Zhu Yongjiang Sun hong Guo School of Materials and Energy International Joint Research Center for Advanced Energy Materials of Yunnan ProvinceYunnan UniversityKunming 650091People’s Republic of China Yunnan Yuntianhua Co. LtdR&D CenterKunming 650228People’s Republic of China Southwest United Graduate School Kunming 650091People’s Republic of China

Regulation the electronic density of solid-state electrolyte by donor–acceptor(D–A)system can achieve highly-selective Li^(+)transportation and conduction in solid-state Li metal *** study reports a high-performance solid-state electrolyte thorough D–A-linked covalent organic frameworks(COFs)based on intramolecular charge transfer *** other reported COFbased solid-state electrolyte,the developed concept with D–A-linked COFs not only achieves electronic modulation to promote highly-selective Li^(+)migration and inhibit Li dendrite,but also offers a crucial opportunity to understand the role of electronic density in solid-state Li metal *** introduced strong electronegativity F-based ligand in COF electrolyte results in highlyselective Li^(+)(transference number 0.83),high ionic conductivity(6.7×10^(-4)S cm^(−1)),excellent cyclic ability(1000 h)in Li metal symmetric cell and high-capacity retention in Li/LiFePO_(4)cell(90.8%for 300 cycles at 5C)than substituted C-and N-based *** is ascribed to outstanding D–A interaction between donor porphyrin and acceptor F atoms,which effectively expedites electron transferring from porphyrin to F-based ligand and enhances Li^(+)***,we anticipate that this work creates insight into the strategy for accelerating Li^(+)conduction in high-performance solid-state Li metal batteries through D–A system.

关键词： Electronic modulation engineering Donor-acceptor-linked covalent organic frameworks Quasi-solid-state Li metal battery

Flexible Graphene Field‑Effect Transistors and Their Application in Flexible Biomedical Sensing

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Nano-Micro Letters 2025年第2期17卷 252-313页

作者： Mingyuan Sun Shuai Wang Yanbo Liang Chao Wang Yunhong Zhang hong Liu Yu Zhang Lin Han Institute of Marine Science and Technology Shandong UniversityQingdao 266237ShandongPeople’s Republic of China State Key Laboratory of Crystal Materials Shandong UniversityJinan 250100ShandongPeople’s Republic of China School of Integrated Circuits Shandong UniversityJinan 250100ShandongPeople’s Republic of China Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application Jinan250100ShandongPeople’s Republic of China

Flexible electronics are transforming our lives by making daily activities more *** to this innovation are field-effect transistors(FETs),valued for their efficient signal processing,nanoscale fabrication,low-power consumption,fast response times,and ***,known for its exceptional mechanical properties,high electron mobility,and biocompatibility,is an ideal material for FET channels and *** combination of graphene and FETs has given rise to flexible graphene field-effect transistors(FGFETs),driving significant advances in flexible electronics and sparked a strong interest in flexible biomedical ***,we first provide a brief overview of the basic structure,operating mechanism,and evaluation parameters of FGFETs,and delve into their material selection and patterning *** ability of FGFETs to sense strains and biomolecular charges opens up diverse application *** specifically analyze the latest strategies for integrating FGFETs into wearable and implantable flexible biomedical sensors,focusing on the key aspects of constructing high-quality flexible biomedical ***,we discuss the current challenges and prospects of FGFETs and their applications in biomedical *** review will provide valuable insights and inspiration for ongoing research to improve the quality of FGFETs and broaden their application prospects in flexible biomedical sensing.

关键词： Flexible Graphene Field-effect transistor Wearable Implantable Biosensor

Relationship between longitudinal changes in lipid composition and ischemic stroke among hypertensive patients

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World Journal of Clinical Cases 2025年第4期13卷 18-27页

作者： Cheng-Cheng Wei Yu-Qing Huang Cheng-hong Yu Department of Cardiology Tongxiang First People's HospitalTongxiang 314500Zhejiang ProvinceChina Department of Cardiology Guangdong Cardiovascular InstituteGuangzhou 510080Guangdong ProvinceChina

BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained *** To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive *** Between 2013 and 2014,6094 hypertension individuals were included in this,and ischemic stroke cases were documented to the end of *** changes of lipid were stratified into four groups:(1)Normal was transformed into normal group;(2)Abnormal was transformed into normal group;(3)Normal was transformed into abnormal group;and(4)Abnormal was transformed into abnormal *** examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke,we utilized multivariate Cox proportional hazards models with hazard ratio(HR)and 95%*** The average age of the participants was 62.32 years±13.00 years,with 329 women making up 54.0%of the *** the course of a mean follow-up of 4.8 years,143 ischemic strokes *** normal was transformed into normal group was used as a reference,after full adjustments,the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group,normal was transformed into abnormal group and abnormal was transformed into abnormal Wei CC et *** changed and ischemic stroke WJCC https://*** 2 February 6,2025 Volume 13 Issue 4 group were 1.089(95%CI:0.598-1.982;P=0.779),2.369(95%CI:1.424-3.941;P<0.001)and 1.448(95%CI:1.002-2.298;P=0.047)(P for trend was 0.233),*** In individuals with hypertension,longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.

关键词： Longitudinal change Hypertension Dyslipidemia Lipid profile Ischemic stroke

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou hongdong Zhao Ye hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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法治是中国式现代化的重要保障

新疆师范大学学报（哲学社会科学版） 2025年第2期46卷 7-16,F0002页

作者：莫纪宏中国社会科学院法学研究所北京100720

党的二十届三中全会审议通过的《中共中央关于进一步全面深化改革、推进中国式现代化的决定》明确提出“法治是中国式现代化的重要保障”,对法治与现代化之间的辩证关系从理论与实践相结合的角度作出系统阐述,对不断完善和健全法治在保... 详细信息

党的二十届三中全会审议通过的《中共中央关于进一步全面深化改革、推进中国式现代化的决定》明确提出“法治是中国式现代化的重要保障”,对法治与现代化之间的辩证关系从理论与实践相结合的角度作出系统阐述,对不断完善和健全法治在保障中国式现代化中的能力,推动法治与现代化同频共振、并肩前行发挥了政策引领作用。从法理层面准确认识法治对中国式现代化的保障机制和制度功能,要从历史维度、政治维度、理论维度、比较维度和实践维度“五个维度”有机统一的角度认识中国式现代化的具体特征和制度形态,针对不同层面的中国式现代化目标采取不同性质的法治应对和保障措施。法治在中国式现代化进程中,通过保障制度现代化推进中国式现代化。其中,法治自身也需要现代化。没有法治现代化就没有社会主义现代化。法治在推进中国式现代化过程中,通过不断提升自身效能和保障能力,逐步实现自身的现代化,成为中国式现代化事业的重要组成部分。

关键词：法治中国式现代化历史维度政治维度理论维度比较维度实践维度

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump