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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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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泊马度胺原料药杂质来源及其合成研究

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中国药物化学杂志 2015年第3期25卷 202-206页

作者：聂鲁周辛波魏朝蔡旭郝伯钧郑志兵李松军事医学科学院毒物药物研究所北京100850 沈阳药科大学制药工程学院辽宁沈阳110016

目的研究泊马度胺原料药的杂质来源与合成方法,为产品质量控制提供依据和杂质对照品。方法通过对泊马度胺原料药生产过程和存储过程的分析推测可能产生的杂质;以3-硝基邻苯二甲酸酐、3-氨基-2,6-哌啶二酮盐酸盐、2-氨基戊二酸等为原料... 详细信息

目的研究泊马度胺原料药的杂质来源与合成方法,为产品质量控制提供依据和杂质对照品。方法通过对泊马度胺原料药生产过程和存储过程的分析推测可能产生的杂质;以3-硝基邻苯二甲酸酐、3-氨基-2,6-哌啶二酮盐酸盐、2-氨基戊二酸等为原料合成有关杂质;根据对泊马度胺的杂质谱分析及合成的主要杂质对照品,建立了泊马度胺原料药杂质检测的高效液相色谱法。结果与结论合成了泊马度胺的7个相关杂质,其中一个为新结构杂质。7个杂质对照品的结构经1H-NMR、MS谱确证;建立了专属性好、灵敏度高的泊马度胺杂质分析的HPLC法,为泊马度胺原料药制备过程中的杂质控制提供帮助。

关键词：泊马度胺杂质合成高效液相色谱法

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Defects‑Rich Heterostructures Trigger Strong Polarization Coupling in Sulfides/Carbon Composites with Robust Electromagnetic Wave Absorption

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Nano-Micro Letters 2025年第1期17卷 528-547页

作者： Jiaolong Liu Siyu Zhang Dan Qu Xuejiao zhou Moxuan Yin Chenxuan Wang Xuelin Zhang Sichen Li Peijun Zhang Yuqi zhou Kai Tao Mengyang Li Bing Wei Hongjing Wu Mengyang Li Bing Wei Hongjing Wu School of Physics Xidian UniversityXi’an 710071People’s Republic of China School of Advanced Materials and Nanotechnology State Key Discipline Laboratory of Wide Band Gap Semiconductor TechnologyXidian UniversityXi’an 710071People’s Republic of China School of Microelectronics Xidian UniversityXi’an 710071People’s Republic of China School of Telecommunication Engineering Xidian UniversityXi’an 710071People’s Republic of China MOE Key Laboratory of Material Physics and Chemistry Under Extraordinary School of Physical Science and TechnologyNorthwestern Polytechnical UniversityXi’an 710072People’s Republic of China The Ministry of Education Key Laboratory of Micro and Nano Systems forAerospace School of Mechanical EngineeringNorthwestern PolytechnicalUniversityXi’an 710072People’s Republic of China

Defects-rich heterointerfaces integrated with adjustable crystalline phases and atom vacancies,as well as veiled dielectric-responsive character,are instrumental in electromagnetic *** methods,however,constrain their delicate ***,an innovative alternative is proposed:carrageenan-assistant cations-regulated(CACR)strategy,which induces a series of sulfides nanoparticles rooted in situ on the surface of carbon *** unique configuration originates from strategic vacancy formation energy of sulfides and strong sulfides-carbon support interaction,benefiting the delicate construction of defects-rich heterostructures in M_(x)S_(y)/carbon composites(M-CAs).Impressively,these generated sulfur vacancies are firstly found to strengthen electron accumulation/consumption ability at heterointerfaces and,simultaneously,induct local asymmetry of electronic structure to evoke large dipole moment,ultimately leading to polarization coupling,i.e.,defect-type interfacial ***“Janus effect”(Janus effect means versatility,as in the Greek two-headed Janus)of interfacial sulfur vacancies is intuitively confirmed by both theoretical and experimental investigations for the first ***,the sulfur vacancies-rich heterostructured Co/Ni-CAs displays broad absorption bandwidth of 6.76 GHz at only 1.8 mm,compared to sulfur vacancies-free CAs without any dielectric *** defects-rich heterostructures,this one-pot CACR strategy may steer the design and development of advanced nanomaterials,boosting functionality across diverse application domains beyond electromagnetic response.

关键词： Defects-rich heterointerfaces Sulfides Polarization coupling Electromagnetic wave absorption

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The effect of noise exposure on sleep quality of urban residents:A comparative study in Shanghai,China

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Building Simulation 2023年第4期16卷 603-613页

作者： xinbo Xu Li Lan Yuxiang Sun Zhiwei Lian School of Design Shanghai Jiao Tong UniversityShanghai 200240China China Institute of Urban Governance Shanghai Jiao Tong UniversityShanghai 200030China

Noise exposure is becoming extremely common in urban area,but its specific impact on sleep remains *** the limitations of previous researches,a field study which can conduct both horizontal and longitudinal analysis was *** participants were tested during two weeks in their homes,and the noise level of bedroom was artificially regulated by changing the status of window and *** the 1050 test nights in 75 households,noise exposure was reflected from both instrument monitoring at night and perception questionnaire in the morning,and sleep quality was accessed from actigraphy and *** analysis results showed that,92.3%of the bedroom acoustic environment did not meet the minimum requirements of Chinese standards,and 87.9%of subjects had ever experienced harmful noise during the test ***,sleep quality was affected by noise exposure from the perspective of both physiological and psychological;the duration of rapid eye movement(REM)sleep was significantly(p<0.05)shortened with the increase of sound intensity,the duration of deep sleep shortened and subjective sleep quality worsened significantly(p<0.05)with the increase of acoustic sensation *** addition,females were more sensitive to noise exposure and their subjective sleep quality was more likely to be influenced by *** study has important implications for acoustic environment design of bedrooms in cities,and suggested more attention should be paid to the anxiety caused by noise exposure.

关键词： noise exposure sleep quality sound intensity subjective perception urban governance

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Optimizing bedroom thermal environment:A review of human body temperature,sleeping thermal comfort and sleep quality

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Energy and Built Environment 2024年第6期5卷 829-839页

作者： xinbo Xu Zhiwei Lian Department of Architecture Shanghai Jiao Tong UniversityShanghai 200240China

Thermal environment may affect sleep quality and sleeping thermal comfort at the same *** to now,there is no direct evidence or physiological theory can prove the idea that thermal comfort equal to good sleep quality,but how to balance the relationship between them is often ignored when designing thermal *** review took body temperature distribution as a bridge for the connection of sleep quality and sleeping thermal *** first,we reviewed the quantitative relationships among thermal environment,body temperature,sleep quality and sleeping thermal comfort,and then based on the idea of reverse derivation,a recommended design process for bedroom thermal environment was *** step of the process corresponded to the impact mechanism described *** review results showed that,body temperature distribution was closely related to both sleep quality and thermal comfort,and thus it was suitable to be used as a bridge between them;body temperatures fluctuated dynamically during sleep,and thus heat transfer and thermal regulation models should be used to describe them;most current sleep researches regarded skin temperature as the representative value of body temperature distribution,yet core body temperature needs to be paid more attention on in the future because it was more closely related to sleep rhythm;furthermore,in addition to young people,subjects of more age groups should be tested to enrich China’s sleep research *** general,it’s theoretically possible to guarantee both sleep quality and sleeping thermal comfort,and this review can be used as a reliable reference for bedroom thermal environment design.

关键词： Sleep health Sleep quality Thermal comfort Thermal environment Body temperature distribution

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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

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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

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Bioinspired Polarized Skylight Orientation Determination Artificial Neural Network

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Journal of Bionic Engineering 2023年第3期20卷 1141-1152页

作者： Huaju Liang Hongyang Bai Ke Hu xinbo Lv School of Energy and Power Engineering Nanjing University of Science and TechnologyNanjing210094China Neuromorphic Computing Laboratory China Nanhu Academy of Electronics and Information TechnologyJiaxing314001China Guidance Radar General Department Xi’an Electronic Engineering Research InstituteXi’an710100China School of Automation Nanjing University of Science and TechnologyNanjing210094China

This paper proposes an artificial neural network to determine orientation using polarized skylight. This neural network has specific dilated convolution, which can extract light intensity information of different polarization directions. Then, the degree of polarization (DOP) and angle of polarization (AOP) are directly extracted in the network. In addition, the exponential function encoding of orientation is designed as the network output, which can better reflect the insect’s encoding of polarization information and improve the accuracy of orientation determination. Finally, training and testing were conducted on a public polarized skylight navigation dataset, and the experimental results proved the stability and effectiveness of the network.

关键词： Polarized light navigation Orientation determination Artificial neural network

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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

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调肾通督健脑法推拿联合3D矫形鞋垫对痉挛型双瘫患儿下肢生物力学及三维步态时-空参数的影响

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山东中医杂志 2024年第2期43卷 153-159,216页

作者：黄绍雄马竞周信波王琛琰宋伟王子聪罗秋刘海婷成都医学院附属第二医院核工业四一六医院四川成都610057 成都福尔泰矫形康复器材有限公司四川成都610021 成都中医药大学附属医院四川成都610075

目的:观察调肾通督健脑法推拿联合3D矫形鞋垫对痉挛型双瘫患儿下肢生物力学及三维步态时-空参数的影响。方法:将162例痉挛型双瘫患儿按随机数字表法分为对照组、观察1组和观察2组各54例。对照组采用常规康复治疗,观察1组在对照组基础上... 详细信息

目的:观察调肾通督健脑法推拿联合3D矫形鞋垫对痉挛型双瘫患儿下肢生物力学及三维步态时-空参数的影响。方法:将162例痉挛型双瘫患儿按随机数字表法分为对照组、观察1组和观察2组各54例。对照组采用常规康复治疗,观察1组在对照组基础上加用3D矫形鞋垫,观察2组在观察1组基础上加用调肾通督健脑法推拿。治疗前和治疗8周后,对三组患儿进行Berg平衡量表(BBS)评分、粗大运动功能评定量表(GMFM)中的D功能区、E功能区评分和下肢生物力学评估[包括立姿跟骨休息位(RCSP)角度、腓肠肌平均肌电信号均方根值(RMS)和超声剪切波弹性成像(SWE)],检测三组患儿三维步态时-空参数(包括步行周期、步速、步长、单支撑时间及髋、膝、踝关节最大屈曲度)。结果:量表评分方面,观察2组GMFM的D功能区和E功能区评分均高于其他两组(P<0.05);观察2组BBS评分高于对照组(P<0.05)。生物力学方面,观察2组左、右侧RCSP角度、腓肠肌RMS以及SWE腓肠肌Emean值均低于其他两组(P<0.05)。三维步态时-空参数方面,观察2组步长以及髋关节、膝关节、踝关节最大屈曲度均大于其他两组(P<0.05),单支撑时间短于其他两组(P<0.05);步速高于对照组(P<0.05)。结论:调肾通督健脑法推拿联合3D矫形鞋垫可以通过纠正下肢力学分布、缓解痉挛改善痉挛型双瘫患儿的平衡功能和下肢运动功能。

关键词：调肾通督健脑法推拿 3D矫形鞋垫脑瘫痉挛型下肢生物力学三维步态时-空参数

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