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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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Overexpression of microRNA-124 promotes the neuronal differentiation of bone marrow-derived mesenchymal stem cells

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Neural Regeneration Research 2014年第12期9卷 1241-1248页

作者： defeng Zou Yi chen Yaxin Han chen Lv Guanjun Tu Department of Orthopedics First Affiliated Hospital of China Medical University Department of Orthopedics Jinhua Central Hospital of Zhejiang University

microRNAs （miRNAs） play an important regulatory role in the self-renewal and differentiation of stem cells. In this study, we examined the effects of miRNA-124 （miR-124） overexpression in bone marrow-derived mesenchymal stem cells. In particular, we focused on the effect of overexpression on the differentiation of bone marrow-derived mesenchymal stem cells into neurons. First, we used GeneChip technology to analyze the expression of miRNAs in bone marrow-derived mesen- chymal stem cells, neural stem cells and neurons, miR-124 expression was substantially reduced in bone marrow-derived mesenchymal stem cells compared with the other cell types. We con- structed a lentiviral vector overexpressing miR-124 and transfected it into bone marrow-derived mesenchymal stem cells. Intracellular expression levels of the neuronal early markers [3-III tu- bulin and microtubule-associated protein-2 were significantly increased, and apoptosis induced by oxygen and glucose deprivation was reduced in transfected cells. After miR-124-transfected bone marrow-derived mesenchymal stem cells were transplanted into the injured rat spinal cord, a large number of cells positive for the neuronal marker neurofilament-200 were observed in the transplanted region. The Basso-Beattie-Bresnahan locomotion scores showed that the motor function of the hind limb of rats with spinal cord injury was substantially improved. These re- sults suggest that miR-124 plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells into neurons. Our findings should facilitate the development of novel strategies for enhancing the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for spinal cord injury.

关键词： nerve regeneration microRNA-124 lentivirus overexpression bone marrow-de-rived mesenchymal stem cells neural stern cells spinal cord injury neurogenesis GeneChip motor function NSFC grant neural regeneration

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Vector meson's spin alignments in high energy reactions

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 5-20页

作者： Jin-Hui chen Zuo-Tang Liang Yu-Gang Ma Xin-Li Sheng Qun Wang Key Laboratory of Nuclear Physics and Ion-beam Application (MoE) Institute of Modern PhysicsFudan University Institute of Frontier and Interdisciplinary Science Key Laboratory of Particle Physics and Particle Irradiation (MOE)Shandong University INFN-Firenze Department of Modern Physics University of Science and Technology of China School of Mechanics and Physics Anhui University of Science and Technology

The global spin alignment of vector mesons has been observed by the STAR collaboration at the Relativistic Heavy Ion Collider （RHIC） at Brookhaven National Laboratory （BNL）.It provides a unique opportunity to probe the correlation between the polarized quark and antiquark in the strongly coupled quark-gluon plasma （sQGP） produced in relativistic heavy ion collisions,opening a new window to explore the properties of s *** addition,spin alignments of vector mesons have also been observed in other high-energy particle collisions such as e+e-annihilations at high energies where hadron production is dominated by quark fragmentation *** results obtained are quite different from those obtained in heavy ion collisions where quark coalescence/combination mechanism dominates suggesting strong dependence on hadronization *** comprehensive studies in different hadronization processes are *** this article,we present a brief review of theoretical and experimental advances in the study of vector meson’s spin alignments in a variety of high-energy particle collisions,with emphasis on hadronization mechanisms.

关键词： vector meson spin alignment global polarization relativistic heavy ion collisions fragmentation

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker chen chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Mutual-structure weighted guided image filtering for depth map restoration

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Optoelectronics Letters 2025年第1期21卷 51-56页

作者： LIU Zijian SONG Jian chen Quanmin XU Jiangtao Tianjin Key Laboratory of Imaging and Sensing Microelectronic Technology School of Microelectronics Tianjin University Spikesee Technology Co. Ltd.

Although guided image filtering(GIF) is known for preserving edges and fast computation, it may produce inaccurate outputs in depth map restoration. In this paper, a novel confidence-weighted GIF called mutual-structure weighted GIF(MSWGIF) is proposed, which replaces the mean filtering strategy in GIF during handling overlapping windows. The confidence value is composed of a depth term and a mutual-structure term, where the depth term is utilized to protect the edges of the output, and the mutual-structure term helps to select accurate windows during the structure characteristics of the guidance image are transferred to the output. Experimental results show that MSWGIF reduces the root mean square error(RMSE) by an average of 12.37%, and the average growth rate of correlation(CORR) is 0.07% on average. Additionally, the average growth rate of structure similarity index measure(SSIM) is 0.34%.

关键词： Wiener filtering

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Adaptive-basis decomposition-based low-rank network for efficient non-uniform motion deblurring

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Optoelectronics Letters 2025年第1期21卷 43-50页

作者： chen Lei XIONG Qingbo ZHANG Wei LI Runde School of Software Henan University School of Applied Technology China University of Labor Relations

In this study, we present a unified sparsity-driven framework that significantly enhances motion deblurring performance by integrating two key components: a custom-designed dataset and a low-rank module(LRM). This framework leverages the inherent sparsity of per-pixel blur kernels to bolster both deblurring accuracy and model interpretability. Firstly, we propose an adaptive-basis decomposition-based deblurring(ADD) approach, which constructs a tailored training dataset to enhance the generalization capacity of the deblurring network. The ADD framework adaptively decomposes motion blur into sparse basis elements, effectively addressing the intricacies associated with non-uniform blurs. Secondly, an LRM is proposed to improve the interpretability of deblurring models as a plug-and-play module, primarily designed to identify and harness the intrinsic sparse features in sharp images. A series of ablation studies have been conducted to substantiate the synergistic advantages of combining the proposed ADD with the LRM for overall improvement in deblurring efficacy. Subsequently, we empirically demonstrate through rigorous experimentation that incorporating the LRM into an existing Uformer network leads to substantial enhancement in reconstruction performance. This integration yields a sparsity-guided low-rank network(SGLRN). Operating under the overarching principle of sparsity, SGLRN consistently outperforms state-of-the-art methods across multiple standard deblurring benchmarks. Comprehensive experimental results, assessed through quantitative metrics and qualitative visual evaluations, provide compelling evidence of its effectiveness. The overall deblurring results are available at Google Drive.

关键词： Image enhancement

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Research Progress on Heat Stress of Rice at Flowering Stage

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Rice science 2019年第1期26卷 1-10页

作者： WANG Yaliang WANG Lei ZHOU Jianxia HU Shengbo chen Huizhe XIANG Jing ZHANG Yikai ZENG Yongjun SHI Qinghua ZHU defeng ZHANG Yuping College of Agronomy Jiangxi Agricultural University/Key Laboratory of Crop Physiology Ecology and Genetics BreedingMinistry of Education China National Rice Research Institute/State Key Laboratory of Rice Biology Jinhua Municipal Institute of Agricultural Sciences

Global warming has caused frequent occurrence of heat stress at the flowering stage of single-season rice in the Yangtze River region of China, which results in declines of spikelet fertility and yield in rice. Rice flowering stage is the most sensitive period to high temperatures, and therefore, the key for heat stress happening is the flowering stage coinciding with high temperature, which causes spikelet fertility decreasing in heat-sensitive varieties, and is the major factor for heat injury differences among various rice planting regions. With the development of rice breeding, temperature indexes for heat stress has been converted from daily maximum temperature of 35 oC to 38 oC with the stress duration of more than 3 d. During the flowering stage, anther dehiscence inhibition and low pollen shedding onto the stigma are two main reasons for spikelet fertility reduction under high temperatures. At panicle initiation stage, high temperatures aggravate spikelet degeneration, and destroy floral organ development. Various types of rice varieties coexist in production, and indica-japonica hybrid rice demonstrates the highest heat resistance in general, followed by indica and japonica rice varieties. In production, avoiding high temperature is the main strategy of preventing heat stress, and planting suitable cultivars and adjustment of sowing date are the most effective measures. Irrigation is an effective real-time cultivation measure to decline the canopy temperature during the rice flowering stage. We suggested that further study should be focused on exploring heat injury differences among different rice variety types, and innovating rice-planting methods according to planting system changes in rice planting regions with extreme heat stress. Meanwhile, high temperature monitor and warning systems should be improved to achieve optimal heat stress management efficiencies.

关键词： flowering stage heat stress spikelet fertility high temperature yield variety

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Alternative Strategy for Development of Dielectric Calcium Copper Titanate‑Based Electrolytes for Low‑Temperature Solid Oxide Fuel Cells

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Nano-Micro Letters 2025年第1期17卷 310-332页

作者： Sajid Rauf Muhammad Bilal Hanif Zuhra Tayyab Matej Veis MAKYousaf Shah Naveed Mushtaq Dmitry Medvedev Yibin Tian chen Xia Martin Motola Bin Zhu College of Mechatronics and Control Engineering Shenzhen UniversityShenzhen 518060People’s Republic of China Department of Inorganic Chemistry Faculty of Natural SciencesComenius University BratislavaIlkovicova684215 BratislavaSlovakia Energy Storage Joint Research Center School of Energy and EnvironmentSoutheast UniversityNanjing 210096People’s Republic of China Hydrogen Energy Laboratory Ural Federal University620002 EkaterinburgRussia Laboratory of Electrochemical Devices Based on Solid Oxide Proton Electrolytes Institute of High Temperature Electrochemistry620066 EkaterinburgRussia School of Microelectronics Hubei UniversityWuhan 430062People’s Republic of China

The development of low-temperature solid oxide fuel cells(LT-SOFCs)is of significant importance for realizing the widespread application of *** has stimulated a substantial materials research effort in developing high oxide-ion conductivity in the electrolyte layer of *** this context,for the first time,a dielectric material,CaCu_(3)Ti_(4)O_(12)(CCTO)is designed for LT-SOFCs electrolyte application in this *** individual CCTO and its heterostructure materials with a p-type Ni_(0.8)Co_(0.15)Al_(0.05)LiO_(2−δ)(NCAL)semiconductor are evaluated as alternative electrolytes in LT-SOFC at 450–550℃.The single cell with the individual CCTO electrolyte exhibits a power output of approximately 263 mW cm^(-2) and an open-circuit voltage(OCV)of 0.95 V at 550℃,while the cell with the CCTO–NCAL heterostructure electrolyte capably delivers an improved power output of approximately 605 mW cm^(-2) along with a higher OCV over 1.0 V,which indicates the introduction of high hole-conducting NCAL into the CCTO could enhance the cell performance rather than inducing any potential short-circuiting *** is found that these promising outcomes are due to the interplay of the dielectric material,its structure,and overall properties that led to improve electrochemical mechanism in CCTO–***,density functional theory calculations provide the detailed information about the electronic and structural properties of the CCTO and NCAL and their heterostructure CCTO–*** study thus provides a new approach for developing new advanced electrolytes for LT-SOFCs.

关键词： LT-SOFCs Dielectric CaCu_(3)Ti_(4)O_(12) Semiconductor Ni_(0.8)Co_(0.15)Al_(0.05)LiO_(2−δ) Ionic conductivity Heterostructure electrolyte

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Observation of topological charge transformations in acoustic vortex using passive periodic systems

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 140-147页

作者： Di-Chao chen Xie Liu Changqing Xu Da-Jian Wu Ying cheng Xiao-Jun Liu School of Physics and Technology Nanjing Normal University Key Laboratory of Modern Acoustics School of Physics Nanjing University

Vortex transmutation utilizes a periodic system, which not only enables the alteration of the topological charge(TC) of unstable input vortices but also facilitates their transformation into stable structures. This approach is crucial for investigating the characteristics of vortices in various wave systems. Here, we achieve acoustic vortex TC transmutation by employing a welldesigned dual-structured plate external system(DPES). The interactions between the acoustic vortex and the finite-order discrete rotational symmetry lead to the transformation of its topological charge when complete rotational symmetry is broken to Nthorder discrete symmetry. Our results experimentally demonstrate the acoustic vortex TC transmutation based on passive artificial structures, enabling numerous applications in particle manipulation and information multiplexing as well as advancing our understanding and control over free-space acoustic vortices.

关键词： acoustic vortex topological charge transformation artificial structure

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang Department of Spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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