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Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Chinese Medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang weiwei deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang Department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China Department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life Sciences Westlake UniversityHangzhouZhejiang 310024China Key Laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

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Research on Partner Selection in Enterprise Innovation Ecosystem

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Proceedings of Business and Economic Studies 2024年第1期7卷 99-103页

作者： Shuang Luo Junxi Gao weiwei deng Sichuan Tourism University Chengdu 610100Sichuan ProvinceChina

In the face of fierce market competition,enterprises must ensure the competitiveness of their products or services through technological innovation.However,the complexity of technology often surpasses the capabilities of individual enterprises,leading them to deepen cooperation with other organizations.The entities within the enterprise innovation ecosystem depend on each other,collaborate closely,and rely on core enterprises to integrate resources,thereby creating system value and enhancing competitiveness.The purpose of this paper is to explore the process of selecting appropriate ecosystem partners.It begins by providing an overview of relevant concepts,characteristics,selection factors,and methods.Subsequently,it analyzes the roles,resources,and synergy evolution of the entities within the ecosystem.An evaluation system encompassing operation,core,synergy,and development capability is then established.This system comprises 16 indicators,including organization scale and reputation,and is accompanied by a hierarchical evaluation model.Finally,the validity of the evaluation system is confirmed through empirical analysis,utilizing the Analytic Hierarchy Process(AHP)and the fuzzy comprehensive evaluation method.

关键词： Enterprise innovation ecosystem Partner selection Core enterprise

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An overview for monitoring and prediction of pathogenic microorganisms in the atmosphere

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Fundamental Research 2024年第3期4卷 430-441页

作者： Jianping Huang Danfeng Wang Yongguan Zhu Zifeng Yang Maosheng Yao Xiaoming Shi Taicheng An Qiang Zhang Cunrui Huang Xinhui Bi Jiang Li Zifa Wang Yongqin Liu Guibing Zhu Siyu Chen Jian Hang Xinghua Qiu weiwei deng Huaiyu Tian Tengfei Zhang Tianmu Chen Sijin Liu Xinbo Lian Bin Chen Beidou Zhang Yingjie Zhao Rui Wang Han Li Collaborative Innovation Center for Western Ecological Safety College of Atmospheric SciencesLanzhou UniversityLanzhou 730000China Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory HealthFirst Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease(Guangzhou Medical University)Guangzhou 510230China College of Environmental Sciences and Engineering Peking UniversityBeijing 100871China China CDC Key Laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health School of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Ministry of Education Key Laboratory for Earth System Modeling Department of Earth System ScienceTsinghua UniversityBeijing 100084China Vanke School of Public Health Tsinghua UniversityBeijing 100084China State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Center for Pan-third Pole Environment Lanzhou UniversityLanzhou 730000China College of Atmospheric Sciences Lanzhou UniversityLanzhou 730000China School of Atmospheric Sciences Sun Yat-sen Universityand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 510640

Corona virus disease 2019(COVID-19)has exerted a profound adverse impact on human health.Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people.Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks.Monitoring of pathogenic microorganisms in the air,especially in densely populated areas,may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage.The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation,allocate health resources,and formulate epidemic response policies.This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission,which lays a theoretical foundation for the monitoring and prediction of epidemic development.Secondly,the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized.Subsequently,this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology,atmospheric sciences,environmental sciences,sociology,demography,etc.By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere,this review proposes suggestions for epidemic response,namely,the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.

关键词： Aerosol transmission Epidemic monitoring methods Epidemic prediction modelsEpidemic response Multidisciplinary cooperation

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Deep structure of the Southeast Asian curved subduction system and its dynamic process

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Journal of Oceanology and Limnology 2024年第3期42卷 701-704页

作者： weiwei DING Key Laboratory of Submarine Geoscience&Second Institute of Oceanography Ministry of Natural ResourcesHangzhou 310012China School of Oceanography Shanghai Jiao Tong UniversityShanghai 200030China

The deep structure,material circulation,and dynamic processes in the Southeast Asia have long been an elusive scientific puzzle due to the lack of systematic scientific observations and recognized theoretical models.Based on the deep seismic tomography using long-period natural earthquake data,in this study,the deep structure and material circulation of the curved subduction system in Southeast Asia was studied,and the dynamic processes since 100 million years ago was reconstructed.It is pointed out that challenges still exist in the precise reconstruction of deep mantle structures of the study area,the influence of multi-stage subduction on deep material exchange and shallow magma activity,as well as the spatiotemporal evolution and coupling mechanism of multi-plate convergence.Future work should focus on high-resolution land-sea joint 3-D seismic tomography imaging of the curved subduction system in the Southeast Asia,combined with geochemical analysis and geodynamic modelling works.

关键词： curved subduction system deep structure material recycling dynamic process Southeast Asia

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A Server Placement Algorithm for Reducing Risk and Improving Power Utilization in Data Centers

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Tsinghua Science and Technology 2024年第1期29卷 158-173页

作者： Rui Chen Huikang Huang Xiaoxuan Luo weiwei Lin School of Computer Science and Engineering South China University of TechnologyGuangzhou 510006China Peng Cheng Laboratory Shenzhen 518066China

As the power demand in data centers is increasing,the power capacity of the power supply system has become an essential resource to be optimized.Although many data centers use power oversubscription to make full use of the power capacity,there are unavoidable power supply risks associated with it.Therefore,how to improve the data center power capacity utilization while ensuring power supply security has become an important issue.To solve this problem,we first define it and propose a risk evaluation metric called Weighted Power Supply Risk(WPSRisk).Then,a method,named Hybrid Genetic Algorithm with Ant Colony System(HGAACS),is proposed to improve power capacity utilization and reduce power supply risks by optimizing the server placement in the power supply system.HGAACS uses historical power data of each server to find a better placement solution by population iteration.HGAACS possesses not only the remarkable local search ability of Ant Colony System(ACS),but also enhances the global search capability by incorporating genetic operators from Genetic Algorithm(GA).To verify the performance of HGAACS,we experimentally compare it with five other placement algorithms.The experimental results show that HGAACS can perform better than other algorithms in both improving power utilization and reducing the riskof powersupply system.

关键词： server placement power utilization power supply risk swarm intelligence algorithm

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Botrytis cinerea-induced F-box protein 1 enhances disease resistance by inhibiting JAO/JOX-mediated jasmonic acid catabolism in Arabidopsis

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Molecular Plant 2024年第2期17卷 297-311页

作者： Min Zhang weiwei Li Tingyu Zhang Yueyan Liu Lijing Liu The Key Laboratory of Plant Development and Environmental Adaptation Biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdao 266237China

Jasmonic acid(JA)is a crucial phytohormone that regulates plant immunity.The endogenous JA level is determined by the rates of its biosynthesis and catabolism in plants.The activation of JA biosynthesis has been well documented;however,how plants repress JA catabolism upon pathogen infection remains elusive.In this study,we identified and characterized Botrytis cinerea-induced F-box protein 1(BFP1)in Arabidopsis.The expression of BFP1 was induced by B.cinerea in a JA signaling-dependent manner,and BFP1 protein was critical for plant defense against B.cinerea and plant response to JA.In addition,BFP1 overexpression increased plant defenses against broad-spectrum pathogens without fitness costs.Further experiments demonstrated that BFP1 interacts with and mediates the ubiquitination and degrada-tion of jasmonic acid oxidases(JAOs,also known as jasmonate-induced oxygenases,JoXs),the enzymes that hydroxylate JA to 12OH-JA.Consistent with this,BFP1 affects the accumulation of JA and 12OH-JA during B.cinerea infection.Moreover,mutation of JAo2 complemented the phenotypes of the bfp1 mutant.Collectively,our results unveil a new mechanism used by plants to activate immune responses upon path-ogeninfection:suppressing JA catabolism.

关键词： plant immunity BFP1 JAO/JOXs JA catabolism ubiquitination-mediated degradation

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Microearthquake reveals the lithospheric structure at midocean ridges and oceanic transform faults

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Journal of Oceanology and Limnology 2024年第3期42卷 697-700页

作者： Zhiteng YU Jiabiao LI weiwei DING Key Laboratory of Submarine Geosciences&Second Institute of Oceanography Ministry of Natural ResourcesHangzhou 310012China

Mid-ocean ridge and oceanic transforms are among the most prominent features on the seafloor surface and are crucial for understanding seafloor spreading and plate tectonic dynamics,but the deep structure of the oceanic lithosphere remains poorly understood.The large number of microearthquakes occurring along ridges and transforms provide valuable information for gaining an indepth view of the underlying detailed seismic structures,contributing to understanding geodynamic processes within the oceanic lithosphere.Previous studies have indicated that the maximum depth of microseismicity is controlled by the 600-℃isotherm.However,this perspective is being challenged due to increasing observations of deep earthquakes that far exceed this suggested isotherm along mid-ocean ridges and oceanic transform faults.Several mechanisms have been proposed to explain these deep events,and we suggest that local geodynamic processes(e.g.,magma supply,mylonite shear zone,longlived faults,hydrothermal vents,etc.)likely play a more important role than previously thought.

关键词： microearthquake mid-ocean ridge oceanic transform fault oceanic lithosphere thermal structure earthquake location

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MCR-YOLO model for underwater target detection based on multi-color spatial features

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Optoelectronics Letters 2024年第5期20卷 313-320页

作者： LIU Peiyu XING weiwei MA Yixuan School of Software Engineering Beijing Jiaotong UniversityBeijing 100044China

Within the fields of underwater robotics and ocean information processing, computer vision-based underwater target detection is an important area of research. Underwater target detection is made more difficult by a number of problems with underwater imagery, such as low contrast, color distortion, fuzzy texture features, and noise interference, which are caused by the limitations of the unique underwater imaging environment. In order to solve the above challenges, this paper proposes a multi-color space residual you only look once(MCR-YOLO) model for underwater target detection. First, the RGB image is converted into YCb Cr space, and the brightness channel Y is used to extract the non-color features of color-biased images based on improved Res Net50. Then, the output features of three scales are combined between adjacent scales to exchange information. At the same time, the image features integrated with low-frequency information are obtained via the low-frequency feature extraction branch and the three-channel RGB image, and the features from the three scales of the two branches are fused at the corresponding scales. Finally, multi-scale fusion and target detection are accomplished utilizing the path aggregation network(PANet) framework. Experiments on relevant datasets demonstrate that the method can improve feature extraction of critical targets in underwater environments and achieve good detection accuracy.

关键词： underwater image utilizing

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Striking a growth–defense balance:Stress regulators that function in maize development

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Journal of Integrative Plant Biology 2024年第3期66卷 424-442页

作者： Shiyi Xie Hongbing Luo Wei Huang weiwei Jin Zhaobin Dong Maize Engineering and Technology Research Center of Hunan Province College of AgronomyHunan Agricultural UniversityChangsha 410128China State Key Laboratory of Maize Bio-breeding National Maize Improvement CenterFrontiers Science Center for Molecular Design BreedingChina Agricultural UniversityBeijing 100193China Tianjin Key Laboratory of Intelligent Breeding of Major Crops Fresh Corn Research Center of BTHCollege of Agronomy&Resources and EnvironmentTianjin Agricultural UniversityTianjin 300384China

Maize(Zea mays)cultivation is strongly affected by both abiotic and biotic stress,leading to reduced growth and productivity.It has recently become clear that regulators of plant stress responses,including the phytohormones abscisic acid(ABA),ethylene(ET),and jasmonic acid(JA),together with reactive oxygen species(ROS),shape plant growth and development.Beyond their well established functions in stress responses,these molecules play crucial roles in balancing growth and defense,which must be finely tuned to achieve high yields in crops while maintaining some level of defense.In this review,we provide an in-depth analysis of recent research on the developmental functions of stress regulators,focusing specifically on maize.By unraveling the contributions of these regulators to maize development,we present new avenues for enhancing maize cultivation and growth while highlighting the potential risks associated with manipulating stress regulators to enhance grain yields in the face of environmental challenges.

关键词： stress regulators maize development ABA ET JA ROS

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Gut flora in multiple sclerosis:implications for pathogenesis and treatment

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Neural Regeneration Research 2024年第7期19卷 1480-1488页

作者： weiwei Zhang Ying Wang Mingqin Zhu Kangding Liu Hong-Liang Zhang Department of Neurology the First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Department of Life Sciences National Natural Science Foundation of ChinaBeijingChina

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

关键词： gut flora gut-brain axis multiple sclerosis pathogenesis treatment

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