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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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

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Quantum public-key crypto via EPR pairs

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 58-63页

作者： xiang-Qun Fu Hong-Wei Li Jian-Hong Shi Tan Li Wan-Su Bao Henan Key Laboratory of Quantum Information and Cryptography Information Engineering University Synergetic Innovation Center of Quantum Information and Quantum Physics University of Science and Technology of China

With the development of quantum computing technology, quantum public-key cryptography is gradually becoming an alternative to the existing classical public-key cryptography. This paper designs a quantum trapdoor one-way function via EPR pairs and quantum measurements. Based on this, a new quantum public-key cryptosystem is presented, which offers forward security,and can resist the chosen-plaintext attack and chosen-ciphertext attack. Compared with the existing quantum public-key cryptos,eavesdropping can be automatically detected in this new quantum public-key cryptosystem under a necessary condition, which is also detailed in the paper.

关键词： quantum public-key crypto trapdoor one-way function EPR pairs

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Observation of acoustic hybrid topological phases induced by the p-d orbital interactions

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 132-139页

作者： Xiao xiang Feng Gao Yu-Gui Peng Peng Wu Zong-Lin Li Xue-Feng Zhu School of Physics and Innovation Institute Huazhong University of Science and Technology

In spinless systems,growing attention has recently been attracted to synthetic gauge fields,which redefine the fundamental crystal symmetries by utilizing the projective algebraic ***,synthetic gauge fields have been commonly investigated in single orbital systems,and explorations on hybrid orbitals remain elusive in ***,we report the experimental observation of hybrid topological phases induced by hybrid synthetic gauge flux,which is formed by the interaction between p and d orbitals embedded in acoustic *** breaking the translation symmetries of Lxand/or Ly,we unambiguously demonstrate the first-order M?bius edge states and higher-order corner *** work establishes a platform for seeking exotic topological phases induced by hybrid-orbitals interactions and initializing the framework of hybrid-orbitalsrelated topological *** applications can be anticipated in scenarios such as high-quality sensing and robust wave trapping due to the stepwise energy distribution of the hybrid topological phase.

关键词： topological insulator synthetic gauge field projective symmetry corner states

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Dispatchable Capability of Aggregated Electric Vehicle Charging in Distribution Systems

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Energy Engineering 2025年第1期122卷 129-152页

作者： ShiqianWang Bo Liu Yuanpeng Hua Qiuyan Li Binhua Tang Jianshu Zhou Yue xiang Economic and Technology Research Institute State Grid Henan Electric Power CompanyZhengzhou450052China College of Electrical Engineering Sichuan UniversityChengdu610065China

This paper introduces a method for modeling the entire aggregated electric vehicle(EV)charging process and analyzing its dispatchable *** methodology involves developing a model for aggregated EV charging at the charging station level,estimating its physical dispatchable capability,determining its economic dispatchable capability under economic incentives,modeling its participation in the grid,and investigating the effects of different scenarios and EV penetration on the aggregated load dispatch and dispatchable *** results indicate that using economic dispatchable capability reduces charging prices by 9.7%compared to physical dispatchable capability and 9.3%compared to disorderly ***,the peak-to-valley difference is reduced by 64.6%when applying economic dispatchable capability with 20%EV penetration and residential base load,compared to disorderly charging.

关键词： Aggregated charging dispatchable capability peak shaving and valley filling the economics of charging demand response

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu Department of Orthopedic Surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： xiang LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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Thickness and sp3 bond modulation of（Ti/tetrahedral amorphous carbon）_n multilayer coatings

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Tungsten 2025年第1期7卷 152-160页

作者： Zhi-Jun Xie Jia-Lin Li Ling Gong xiang-Li Zhong Hong-Jia Song Jin-Bin Wang National-Provincial Laboratory of Special Function Thin Film Materials School of Materials Science and Engineering Xiangtan University

The durability of wear-resistant tetrahedral amorphous carbon（ta-C） coatings is intimately linked to their thickness and the concentration of *** enhance the lifespan of the coatings,we have prepared a multilayer coating consisting of alternating layers of Ti and ta-C,denoted as（Ti/ta-C）_n,using arc ion plating.A multi-layer structure in conjunction with stage cooling is employed to enhance the thickness and promote *** results indicate that the ID/IGvalue,representing the ratio of the intensity of the D peak to that of the G peak in Raman spectroscopy,decreases from 0.85 when no stage cooling is applied to 0.35 when stage cooling is employed,suggesting an enhancement in the fraction of sp3bonds within the *** obtained（Ti/ta-C）_n multilayer coating without peeling off has a maximum thickness of 1.14 μm,which is almost double that of the ta-C coating single layer *** the same time,the coating has a low coefficient of friction,down to 0.069,and maintains excellent friction properties with a wear rate of 3.4×10-6mm3·N-1·*** results conclusively show that the preparation technology can enhance both thickness and sp3bonding in ta-C coatings,significantly expanding their utility across tools,molds,and precision engineering components.

关键词： Arc ion plating Multilayer structure sp3 bond Ta-C coating Wear resistance

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Visualization of the protective role of estrogen against female liver fibrosis via an ER viscosity NIR fluorescent probe

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Science China Chemistry 2025年第1期68卷 360-368页

作者： Zheng Liu Changyu Zhang Zipeng Li Wanying Ma Jia Liu xiang Xia Ning Xu Wen Sun Jianjun Du Jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Dalian University of Technology Ningbo Institute of Dalian University of Technology

Endoplasmic reticulum(ER) viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF). Herein, we report the first ER-targeting viscosity-responsive near-infrared(NIR) fluorescent probe HBT-PP for investigations of HF *** twisted intramolecular charge transfer(TICT) and the excited state intramolecular proton transfer(EsiPT) are combined to endow HBT-PP with the selective response towards viscosity(～62-fold) and a super large stokes shift(～320 nm). HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells. significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression. Of note, after 10 min of stain with HBT-PP, HF lesions showed a stage-based response, indicating the potential of this probe in fast and early diagnosis of HF. These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.

关键词： NIR fluorescent probe ER viscosity hepatic fibrosis gender difference estrogen

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Cross-subcarrier precoder design for massive MIMO-OFDM downlink with symplectic optimization

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Science China(Information Sciences) 2025年

作者： Yu-Xuan ZHANG An-An LU xiang-Gen XIA Xi-Qi GAO National Mobile Communications Research Laboratory Southeast University Purple Mountain Laboratories Department of Electrical and Computer Engineering University of Delaware

We propose a cross-subcarrier precoder design(CSPD) for massive multiple-input multiple-output(MIMO) orthogonal frequency division multiplexing(OFDM) downlink. This work aims to significantly improve the channel estimation and signal detection performance by enhancing the smoothness of the frequency domain effective channel. This is accomplished by designing a few vectors known as the transform domain precoding vectors(TDPVs), which are then transformed into the frequency domain to generate the precoders for a set of subcarriers. To combat the effect of channel aging, the TDPVs are optimized under imperfect channel state information(Csi). The optimal precoder structure is derived by maximizing an upper bound of the ergodic weighted sum-rate(WSR) and utilizing the a posteriori beam-based statistical channel model(BSCM). To avoid the large-dimensional matrix inversion, we propose an algorithm with symplectic optimization. simulation results indicate that the proposed cross-subcarrier precoder design significantly outperforms conventional methods.

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Gut microbiota in cancer initiation,development and therapy

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Science China Life Sciences 2025年

作者： Ruyi Zhang xiang Zhang Harry Cheuk Hay Lau Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong Kong

Cancer has long been associated with genetic and environmental factors,but recent studies reveal the important role of gut microbiota in its initiation and *** 13%of cancers are linked to infectious agents,highlighting the need to identify the specific microorganisms *** microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune *** can lead to cancer,while certain probiotics and their metabolites may help reestablish microecological balance and improve anti-tumor immune *** into targeted approaches that enhance therapy with probiotics is ***,the effects of probiotics in humans are complex and not yet fully ***,methods to counteract harmful bacteria are still in *** clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer *** research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

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