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灰兜巴抑制高糖培养HK-2细胞的铁死亡减轻细胞纤维化
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作者 姚顺华 黄彩丁 +3 位作者 张梦玉 张可馨 尹长江 杨坤宝 《中国组织工程研究》 北大核心 2026年第11期2774-2783,共10页
背景:糖尿病肾病与铁死亡密切相关,既往研究发现灰兜巴具有显著的降糖作用,对糖尿病肾病引起的肾脏氧化应激损伤及纤维化具有保护作用,还可降低高糖诱导的HK-2细胞纤维化水平。目的:探究灰兜巴调控谷胱甘肽过氧化物酶4(Glutathione Pero... 背景:糖尿病肾病与铁死亡密切相关,既往研究发现灰兜巴具有显著的降糖作用,对糖尿病肾病引起的肾脏氧化应激损伤及纤维化具有保护作用,还可降低高糖诱导的HK-2细胞纤维化水平。目的:探究灰兜巴调控谷胱甘肽过氧化物酶4(Glutathione Peroxidase 4,GPX4)抑制高糖培养人肾皮质近曲小管上皮细胞(HK-2)铁死亡减轻细胞纤维化作用。方法:①为探究灰兜巴对高糖培养HK-2细胞铁死亡及纤维化的干预作用,将细胞分为6组:对照组、模型组、灰兜巴低、中、高剂量组、罗格列酮组;观察HK-2细胞形态,检测细胞存活率及氧化应激相关指标丙二醛含量、谷胱甘肽水平,检测铁死亡相关指标GPX4、铁蛋白重链1、核因子E2相关因2、转铁蛋白受体及纤维化相关指标转化生长因子β1、肾损伤分子1的蛋白和mRNA表达。②为观察siRNA干扰HK-2细胞GPX4表达效果,将细胞分为NC组(阴性对照)、si-GPX4组;检测GPX4蛋白和mRNA表达。③为观察siRNA干扰GPX4对灰兜巴抑制高糖培养HK-2细胞铁死亡减轻细胞纤维化作用效果的影响,将细胞分为4组:NC组(阴性对照)、高糖组(30 mmol/L葡萄糖处理)、高糖+灰兜巴组(30 mmol/L葡萄糖+400μg/mL灰兜巴水提物处理)、高糖+灰兜巴+si-GPX4组(经GPX4-siRNA处理后,再30 mmol/L葡萄糖+400μg/mL灰兜巴水提物处理);检测丙二醛含量、谷胱甘肽水平、GPX4、铁蛋白重链1、核因子E2相关因2、转铁蛋白受体、转化生长因子β1、肾损伤分子1的蛋白和mRNA表达。结果与结论:①与对照组相比,模型组细胞存活率、谷胱甘肽水平、GPX4、铁蛋白重链1、核因子E2相关因2蛋白和mRNA表达显著降低,丙二醛含量、转铁蛋白受体、转化生长因子β1、肾损伤分子1蛋白和mRNA表达显著升高;与模型组相比,灰兜巴各剂量及罗格列酮组可不同程度改善上述指标变化。②与NC组相比,si-GPX4组GPX4蛋白和mRNA表达显著降低;与高糖+灰兜巴组相比,高糖+灰兜巴+si-GPX4组谷胱甘肽水平、GPX4、铁蛋白重链1、核因子E2相关因2蛋白和mRNA表达显著降低,丙二醛含量、转铁蛋白受体、转化生长因子β1、肾损伤分子1蛋白和mRNA表达显著升高。③结果说明,灰兜巴可通过上调GPX4抑制高糖培养HK-2细胞铁死亡减轻细胞纤维化。 展开更多
关键词 糖尿病肾病 纤维化 hk-2细胞 铁死亡 灰兜巴 GPX4
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LLM-KE: An Ontology-Aware LLM Methodology for Military Domain Knowledge Extraction
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作者 Yu Tao Ruopeng Yang +3 位作者 Yongqi Wen Yihao Zhong Kaige Jiao Xiaolei Gu 《Computers, Materials & Continua》 2026年第1期2045-2061,共17页
Since Google introduced the concept of Knowledge Graphs(KGs)in 2012,their construction technologies have evolved into a comprehensive methodological framework encompassing knowledge acquisition,extraction,representati... Since Google introduced the concept of Knowledge Graphs(KGs)in 2012,their construction technologies have evolved into a comprehensive methodological framework encompassing knowledge acquisition,extraction,representation,modeling,fusion,computation,and storage.Within this framework,knowledge extraction,as the core component,directly determines KG quality.In military domains,traditional manual curation models face efficiency constraints due to data fragmentation,complex knowledge architectures,and confidentiality protocols.Meanwhile,crowdsourced ontology construction approaches from general domains prove non-transferable,while human-crafted ontologies struggle with generalization deficiencies.To address these challenges,this study proposes an OntologyAware LLM Methodology for Military Domain Knowledge Extraction(LLM-KE).This approach leverages the deep semantic comprehension capabilities of Large Language Models(LLMs)to simulate human experts’cognitive processes in crowdsourced ontology construction,enabling automated extraction of military textual knowledge.It concurrently enhances knowledge processing efficiency and improves KG completeness.Empirical analysis demonstrates that this method effectively resolves scalability and dynamic adaptation challenges in military KG construction,establishing a novel technological pathway for advancing military intelligence development. 展开更多
关键词 knowledge extraction natural language processing knowledge graph large language model
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Defect Identification Method of Power Grid Secondary Equipment Based on Coordination of Knowledge Graph and Bayesian Network Fusion
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作者 Jun Xiong Peng Yang +1 位作者 Bohan Chen Zeming Chen 《Energy Engineering》 2026年第1期296-313,共18页
The reliable operation of power grid secondary equipment is an important guarantee for the safety and stability of the power system.However,various defects could be produced in the secondary equipment during longtermo... The reliable operation of power grid secondary equipment is an important guarantee for the safety and stability of the power system.However,various defects could be produced in the secondary equipment during longtermoperation.The complex relationship between the defect phenomenon andmulti-layer causes and the probabilistic influence of secondary equipment cannot be described through knowledge extraction and fusion technology by existing methods,which limits the real-time and accuracy of defect identification.Therefore,a defect recognition method based on the Bayesian network and knowledge graph fusion is proposed.The defect data of secondary equipment is transformed into the structured knowledge graph through knowledge extraction and fusion technology.The knowledge graph of power grid secondary equipment is mapped to the Bayesian network framework,combined with historical defect data,and introduced Noisy-OR nodes.The prior and conditional probabilities of the Bayesian network are then reasonably assigned to build a model that reflects the probability dependence between defect phenomena and potential causes in power grid secondary equipment.Defect identification of power grid secondary equipment is achieved by defect subgraph search based on the knowledge graph,and defect inference based on the Bayesian network.Practical application cases prove this method’s effectiveness in identifying secondary equipment defect causes,improving identification accuracy and efficiency. 展开更多
关键词 knowledge graph Bayesian network secondary equipment defect identification
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Automatic Detection of Health-Related Rumors: A Dual-Graph Collaborative Reasoning Framework Based on Causal Logic and Knowledge Graph
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作者 Ning Wang Haoran Lyu Yuchen Fu 《Computers, Materials & Continua》 2026年第1期2163-2193,共31页
With the widespread use of social media,the propagation of health-related rumors has become a significant public health threat.Existing methods for detecting health rumors predominantly rely on external knowledge or p... With the widespread use of social media,the propagation of health-related rumors has become a significant public health threat.Existing methods for detecting health rumors predominantly rely on external knowledge or propagation structures,with only a few recent approaches attempting causal inference;however,these have not yet effectively integrated causal discovery with domain-specific knowledge graphs for detecting health rumors.In this study,we found that the combined use of causal discovery and domain-specific knowledge graphs can effectively identify implicit pseudo-causal logic embedded within texts,holding significant potential for health rumor detection.To this end,we propose CKDG—a dual-graph fusion framework based on causal logic and medical knowledge graphs.CKDG constructs a weighted causal graph to capture the implicit causal relationships in the text and introduces a medical knowledge graph to verify semantic consistency,thereby enhancing the ability to identify the misuse of professional terminology and pseudoscientific claims.In experiments conducted on a dataset comprising 8430 health rumors,CKDG achieved an accuracy of 91.28%and an F1 score of 90.38%,representing improvements of 5.11%and 3.29%over the best baseline,respectively.Our results indicate that the integrated use of causal discovery and domainspecific knowledge graphs offers significant advantages for health rumor detection systems.This method not only improves detection performance but also enhances the transparency and credibility of model decisions by tracing causal chains and sources of knowledge conflicts.We anticipate that this work will provide key technological support for the development of trustworthy health-information filtering systems,thereby improving the reliability of public health information on social media. 展开更多
关键词 Health rumor detection causal graph knowledge graph dual-graph fusion
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m6A RNA甲基化酶METTL14调节YAP1对HK-2细胞缺血再灌注损伤的影响
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作者 李兰梅 白伟伟 +4 位作者 陈娜 孙绍婷 王萌 张明 李亚芬 《中西医结合心脑血管病杂志》 2026年第2期220-226,共7页
目的:探讨N6-甲基腺苷(m6A)RNA甲基化酶甲基转移酶14(METTL14)调节Yes关联蛋白1(YAP1)对HK-2细胞缺血再灌注(IR)损伤的影响。方法:体外培养HK-2细胞,并将细胞分为CK组、IR组、IR+si-NC组(转染si-NC)、IR+si-METTL14组(转染si-METTL14)、... 目的:探讨N6-甲基腺苷(m6A)RNA甲基化酶甲基转移酶14(METTL14)调节Yes关联蛋白1(YAP1)对HK-2细胞缺血再灌注(IR)损伤的影响。方法:体外培养HK-2细胞,并将细胞分为CK组、IR组、IR+si-NC组(转染si-NC)、IR+si-METTL14组(转染si-METTL14)、IR+si-METTL14+sh-NC组(转染si-METTL14+sh-NC)、IR+si-METTL14+sh-YAP1组(转染si-METTL14+sh-YAP1)。采用噻唑蓝溴化四唑(MTT)检测细胞活力;酶联免疫吸附法(ELISA)检测乳酸脱氢酶(LDH)、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β水平;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)含量;流式细胞术检测细胞凋亡;实时荧光定量逆转录聚合酶链式反应(RT-q PCR)检测细胞中METTL14和Yes关联蛋白1(YAP1)基因表达;蛋白免疫印迹法(Western Blot)检测Bax、Bcl-2、METTL14、YAP1蛋白表达。结果:与CK组比较,IR组HK-2细胞METTL14 mRNA表达、细胞LDH、IL-6、TNF-α、IL-1β水平、MDA含量、凋亡率、细胞中总mRNA的m6A修饰水平、Bax和METTL14蛋白表达水平升高,YAP1 mRNA表达、细胞增殖率、SOD和CAT活性、Bcl-2、Ki-67和YAP1蛋白表达水平降低(P<0.05)。与IR+si-NC组比较,IR+si-METTL14组HK-2细胞METTL14 mRNA表达、细胞LDH、IL-6、TNF-α、IL-1β水平、MDA含量、凋亡率、细胞中总mRNA的m6A修饰水平、Bax和METTL14蛋白表达水平降低,YAP1 mRNA表达、细胞增殖率、SOD和CAT活性、Bcl-2、Ki-67和YAP1蛋白表达水平升高(P<0.05)。与IR+si-METTL14+sh-NC组比较,IR+si-METTL14+sh-YAP1组HK-2细胞LDH、IL-6、TNF-α、IL-1β水平、MDA含量、凋亡率、细胞中总mRNA的m6A修饰水平、Bax表达水平升高,YAP1 mRNA表达、细胞增殖率、SOD和CAT活性、Bcl-2、Ki-67和YAP1蛋白表达水平降低(P<0.05)。结论:沉默METTL14表达可降低IR诱导的HK-2细胞炎症、氧化应激和细胞凋亡,可能与提高YAP1表达和降低m6A修饰水平有关。 展开更多
关键词 缺血再灌注 hk-2细胞 N6-甲基腺苷RNA甲基化酶 甲基转移酶14 Yes关联蛋白1 实验研究
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基于Drp1/HK1/NLRP3和线粒体凋亡信号通路研究香草酸改善异丙肾上腺素致小鼠心脏纤维化的作用机制 被引量:3
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作者 贺海波 吴勉 +8 位作者 许杰 许倩倩 万芳竹 钟华桥 张继红 周刚 覃慧林 李浩然 唐海明 《中国中药杂志》 北大核心 2025年第8期2193-2208,共16页
研究香草酸(VA)对异丙肾上腺素(ISO)致小鼠心脏纤维化(CF)的影响及作用机制。将雄性C57BL/6J小鼠随机分为空白组、VA(100 mg·kg^(-1),ig)组、ISO(10 mg·kg^(-1),sc)组、ISO+VA(10 mg·kg^(-1),sc+100 mg·kg^(-1),ig... 研究香草酸(VA)对异丙肾上腺素(ISO)致小鼠心脏纤维化(CF)的影响及作用机制。将雄性C57BL/6J小鼠随机分为空白组、VA(100 mg·kg^(-1),ig)组、ISO(10 mg·kg^(-1),sc)组、ISO+VA(10 mg·kg^(-1),sc+100 mg·kg^(-1),ig)组、ISO+动力学相关蛋白1(Drp1)抑制剂(Mdivi-1)(10 mg·kg^(-1),sc+50 mg·kg^(-1),ip)组和ISO+VA+Mdivi-1(10 mg·kg^(-1),sc+100 mg·kg^(-1),ig+50 mg·kg^(-1),ip)组。给药组每天给予相应药物,每天1次,连续14 d。末次给药次日,检测完心脏功能后,收集小鼠血清和心脏组织测定血清中天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶同工酶MB(CK-MB)、心肌肌钙蛋白I(cTnI)、活性氧(ROS)、白细胞介素(IL)-1β、IL-4、IL-6、IL-10、IL-18、肿瘤坏死因子-α(TNF-α),心脏组织中过氧化氢酶(CAT)、谷胱甘肽(GSH)、丙二醛(MDA)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC),线粒体和细胞质中cytochrome C水平;苏木精-伊红(HE)、Masson及醋酸铀和柠檬酸铅染色观察心脏组织形态学及线粒体超微结构改变,计算心肌损伤面积和胶原容积分数;流式细胞术检测心脏中巨噬细胞相对含量及M1/M2极化状态,实时定量PCR法测定心脏组织中巨噬细胞极化标志物[CD86、CD206、精氨酸酶1(Arg-1)、诱导型一氧化氮合成酶(iNOS)]、心脏纤维化标志物[Ⅰ型胶原纤维(CollⅠ)、CollⅢ、α-平滑肌肌动蛋白(α-SMA)]、细胞因子(IL-1β、IL-4、IL-6、IL-10、IL-18、TNF-α)mRNA表达,Western blot法测定心脏组织中CollⅠ、CollⅢ、α-SMA、Drp1、p-Drp1、电压依赖性阴离子通道(VDAC)、己糖激酶1(HK1)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱天冬酶-1(caspase-1)、裂解型半胱天冬酶-1(cleaved-caspase-1)、焦孔素D(GSDMD)、GSDMD-N、IL-1β、IL-18、B淋巴细胞瘤-2(Bcl-2)、B淋巴细胞瘤-xl(Bcl-xl)、Bcl-2关联死亡启动子(Bad)、Bcl-2相关X蛋白(Bax)、凋亡蛋白酶激活因子-1(Apaf-1)、半胱天冬酶-3前体(pro-caspase-3)、cleaved-caspase-3、pro-caspase-9、cleaved-caspase-9、多聚腺苷二磷酸核糖聚合酶-1(PARP-1)、cleaved-PARP-1蛋白表达。结果显示,VA可显著改善CF小鼠心功能;降低心脏损伤面积、心脏指数,血清中AST、CK-MB、cTnI、LDH、ROS、IL-1β、IL-6、IL-18、TNF-α含量,心脏组织中MDA、MPO水平,心脏组织中IL-1β、IL-6、IL-18、TNF-αmRNA表达及CollⅠ、CollⅢ和α-SMA mRNA和蛋白表达;升高血清中IL-4、IL-10和心脏组织中CAT、GSH、SOD、T-AOC含量,心脏组织中IL-4、IL-10 mRNA表达;改善心脏病理损伤程度,抑制心肌细胞凋亡、炎性浸润和胶原纤维沉积,降低胶原容积分数,减轻线粒体损伤;降低心脏组织中F4/80+CD86+M1细胞比值和CD86、iNOS mRNA表达,升高F4/80+CD206+M2细胞比值和CD206、Arg-1 mRNA表达;降低心脏组织中p-Drp1、VDAC、NLRP3、ASC、caspase-1、cleaved-caspase-1、GSDMD、GSDMD-N、IL-1β、IL-18、Bad、Bax、Apaf-1、cleaved-caspase-3、cleaved-caspase-9、cleaved-PARP-1蛋白表达和细胞质中cytochrome C含量,升高HK1、Bcl-2、Bcl-xl、pro-caspase-3、pro-caspase-9蛋白表达和Bcl-2/Bax、Bcl-xl/Bad比值及线粒体中cytochrome C含量。以上结果表明,VA对ISO致小鼠CF有显著的改善作用,可减轻ISO引起的氧化损伤和炎症反应,其机制与抑制Drp1/HK1/NLRP3和线粒体凋亡信号通路激活,抑制心肌细胞炎性浸润和胶原纤维沉积,降低胶原容积分数及ColⅠ、ColⅢ和α-SMA表达和抑制CF密切相关。 展开更多
关键词 香草酸 异丙肾上腺素 心脏纤维化 炎症反应 Drp1/hk1/NLRP3信号通路 线粒体凋亡信号通路
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RIP3参与的线粒体DNA-cGAS-STING信号通路在HK-2细胞缺氧-复氧模型中的作用
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作者 孔亚坤 王焕 +4 位作者 尹俊杰 熊承云 吴苏豫 张莹 赵建林 《郑州大学学报(医学版)》 北大核心 2025年第5期603-608,共6页
目的:探究RIP3参与的线粒体DNA(mtDNA)-cGAS-STING信号通路在HK-2缺氧-复氧(H-R)细胞模型中的作用机制。方法:构建H-R细胞模型,取对数生长期HK-2细胞,于无葡萄糖和血清的特殊培养基中缺氧培养3、6和12 h后复氧,同时设置对照组,采用MTT... 目的:探究RIP3参与的线粒体DNA(mtDNA)-cGAS-STING信号通路在HK-2缺氧-复氧(H-R)细胞模型中的作用机制。方法:构建H-R细胞模型,取对数生长期HK-2细胞,于无葡萄糖和血清的特殊培养基中缺氧培养3、6和12 h后复氧,同时设置对照组,采用MTT法检测细胞存活率,Western blot检测RIP3、cGAS、STING、TBK1、IRF3、IFN-α、IFN-β、TNF-α、IL-1β、NF-κB蛋白表达水平,RT-qPCR检测RIP3、cGAS、STING mRNA表达水平。细胞转染及加入RU.521(cGAS抑制剂)、Mito-TEMPO(线粒体ROS特异性清除剂)和溴化乙锭(EtBr)验证cGAS-STING信号通路激活机制,免疫荧光染色法测定mtDNA水平。结果:与对照组相比,H-R 3、6、12组细胞存活率均降低,mtDNA-cGAS-STING信号通路中相关蛋白RIP3、cGAS、STING、TBK1、IRF3、IFN-α、IFN-β、TNF-α、IL-1β、NF-κB及RIP3、STING mRNA表达水平均上升,H-R 6、12组cGAS mRNA表达水平均上升(P<0.05)。与H-R 12+si-NC组相比,H-R 12+si-cGAS组细胞存活率升高,RIP3、cGAS、STING mRNA表达水平均降低;与H-R 12组相比,H-R 12+RU.521组与H-R 12+Mito-TEMPO组RIP3、cGAS、STING、TBK1、IRF3、IFN-β和IL-1β蛋白表达水平均降低(P<0.05)。H-R处理12 h可增加胞质双链DNA且其与线粒体共定位,而EtBr处理可减少胞质mtDNA(P<0.05)。结论:H-R可影响HK-2细胞活力及mtDNA-cGAS-STING信号通路,cGAS在其中起重要作用,且胞质mtDNA对cGAS-STING轴有调节作用。 展开更多
关键词 缺氧-复氧 hk-2细胞 RIP3 线粒体DNA-cGAS-STING信号通路
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二至丸含药血清对D-gal诱导HK-2细胞衰老的相关机制研究
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作者 单思 洪伟 +2 位作者 王沐晨 严小军 刘红宁 《时珍国医国药》 北大核心 2025年第9期1633-1638,共6页
目的探讨二至丸含药血清对D-gal诱导HK-2细胞衰老的影响及作用机制。方法随机将HK-2细胞分为5组,二至丸高、中、低浓度组、D-gal诱导衰老模型对照组和空白对照组。利用SA-β-gal染色法测定细胞衰老率,流式细胞术观察细胞凋亡率及细胞膜... 目的探讨二至丸含药血清对D-gal诱导HK-2细胞衰老的影响及作用机制。方法随机将HK-2细胞分为5组,二至丸高、中、低浓度组、D-gal诱导衰老模型对照组和空白对照组。利用SA-β-gal染色法测定细胞衰老率,流式细胞术观察细胞凋亡率及细胞膜通透性,ELISA检测SOD、MDA水平,Western blot检测AQP1、AQP2表达水平。结果与模型对照组比较,二至丸中、高浓度组HK-2细胞β-gal染色阳性率显著降低(P<0.01);低、中、高浓度组总凋亡率显著降低(P<0.01),且呈剂量依赖型;高浓度组MDA含量显著下降(P<0.01),SOD活力升高(P>0.05);二至丸各给药组细胞通透性下降(P>0.05),二至丸各组AQP1及低、高浓度AQP2表达上调(P>0.05)。结论二至丸含药血清对D-gal诱导HK-2细胞衰老有保护作用,其保护机制可能涉及调节水液代谢。 展开更多
关键词 二至丸 衰老 hk-2细胞 水通道蛋白 细胞膜通透性
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升清降浊胶囊通过抑制铁死亡改善高糖诱导的HK2细胞损伤的机制研究
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作者 余燕娜 董鑫 +1 位作者 王亮亮 汤水福 《中国中西医结合肾病杂志》 2025年第6期487-492,I0003,共7页
目的:探讨升清降浊胶囊(shengqing jiangzhuo capsules, SQJZC)改善高糖诱导的HK2细胞损伤的作用及机制。方法:制备SQJZC含药血清;将HK2细胞分为对照组(对照血清)、模型组(30 mM葡萄糖培养基)、SQJZC低剂量组、SQJZC中剂量组、SQJZC高... 目的:探讨升清降浊胶囊(shengqing jiangzhuo capsules, SQJZC)改善高糖诱导的HK2细胞损伤的作用及机制。方法:制备SQJZC含药血清;将HK2细胞分为对照组(对照血清)、模型组(30 mM葡萄糖培养基)、SQJZC低剂量组、SQJZC中剂量组、SQJZC高剂量组、模型+铁死亡抑制剂组;检测各组细胞的Fe^(2+)、GSH和MDA含量;qPCR、Western Blot、免疫荧光法检测铁死亡相关指标的表达。结果:与对照组相比,模型组Fe^(2+)和MDA水平显著上升,GSH水平减少,SQJZC处理后Fe^(2+)和MDA水平下降,GSH显著上升;与对照组相比,模型组Kim-1表达上调,SQJZC处理后Kim-1表达下降;与对照组相比,模型组TFR-1 mRNA及蛋白表达上升,GPX4、FTH-1、SLC7A11 mRNA及蛋白表达显著下降,给予SQJZC后TFR-1 mRNA及蛋白表达下降,GPX4、FTH-1、SLC7A11 mRNA及蛋白表达上升;免疫荧光显示GPX4、FTH-1的表达与qPCR、Western Blot一致。结论:升清降浊胶囊能够改善高糖诱导的HK2细胞损伤,这种作用可能通过抑制铁死亡实现。 展开更多
关键词 升清降浊胶囊 铁死亡 hk2细胞
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基于细胞培养基中血清水平优化探索赭曲霉毒素A对HK-2细胞的毒性作用 被引量:1
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作者 董芳 张志岐 +5 位作者 聂冬霞 范楷 娄秀萍 朱雪婷 韩铮 赵志辉 《南京农业大学学报》 CAS 北大核心 2025年第1期220-229,共10页
[目的]本文旨在探讨细胞培养基中添加不同水平血清对赭曲霉毒素A(ochratoxin A,OTA)毒性的影响,以期更深入了解OTA的毒性,同时为其他OTA体外毒性研究提供重要参考。[方法]测定OTA对人肾皮质近曲小管上皮细胞(human proximal tubule-deri... [目的]本文旨在探讨细胞培养基中添加不同水平血清对赭曲霉毒素A(ochratoxin A,OTA)毒性的影响,以期更深入了解OTA的毒性,同时为其他OTA体外毒性研究提供重要参考。[方法]测定OTA对人肾皮质近曲小管上皮细胞(human proximal tubule-derived epithelial cells,HK-2)细胞活力的影响,同时利用超高效液相色谱-串联质谱技术检测细胞上清液中OTA浓度以间接反应细胞对OTA的摄入量,分析培养基中不同水平血清对OTA毒性的影响。[结果]细胞培养基中添加5%的血清在48 h内不会影响细胞活力,可以作为细胞正常培养条件;添加2%的血清在36 h不会影响细胞活力,可以作为配制OTA工作液的细胞处理条件。基于优化的细胞培养及处理条件,OTA对HK-2细胞活力的影响结果表明,OTA抑制细胞活力呈现时间和剂量依赖性,OTA处理HK-2细胞12、24、36 h的IC50分别为39.29、6.28和2.72 μmol·L^(-1)。同时OTA可以时间依赖性极显著提高细胞释放乳酸脱氢酶水平,并损伤细胞膜的完整性(P<0.01)。[结论]细胞培养基中添加不同水平的血清会影响OTA的毒性,且血清水平越高,对OTA毒性影响越大。当使用2%血清的培养基配制OTA工作液时,可在不影响细胞活力的前提下最大限度降低血清水平对OTA毒性的影响。 展开更多
关键词 赭曲霉毒素A 血清水平 hk-2细胞 超高效液相色谱-串联质谱技术
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六味地黄汤下调NF-κB/NLRP3信号通路抑制HK-2细胞焦亡延缓肾纤维化 被引量:1
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作者 马秀英 黄娜 +4 位作者 杨成 汪涵俪 裴刚 孟斌(指导) 唐群 《中药药理与临床》 北大核心 2025年第1期28-32,共5页
目的:探讨六味地黄汤对转化生长因子β1(TGF-β1)诱导肾小管上皮细胞(HK-2)的肾纤维化模型的治疗效果及作用机制。方法:体外培养HK-2细胞并随机分为:正常对照血清组、模型对照组、六味地黄汤含药血清5%、10%、20%组和MCC9501μmol/L组... 目的:探讨六味地黄汤对转化生长因子β1(TGF-β1)诱导肾小管上皮细胞(HK-2)的肾纤维化模型的治疗效果及作用机制。方法:体外培养HK-2细胞并随机分为:正常对照血清组、模型对照组、六味地黄汤含药血清5%、10%、20%组和MCC9501μmol/L组。除正常对照血清组外,其余各组细胞给予10 ng/m L TGF-β1诱导肾纤维化,并予以相应药物干预。给药24 h后收集细胞,以RT-q PCR法、Western blot法、免疫荧光法测定NF-κB/NLRP3信号通路及焦亡、肾纤维化相关指标表达。结果:与正常对照组相比,模型对照组HK-2细胞Nfkb、Nlrp3、Caspase1、Il18 mRNA表达上调(P<0.05),NF-κB、Caspase-1、IL-1β、IL-18、Vimentin蛋白表达上调(P<0.05),E-cadherin蛋白表达下调(P<0.05);与模型对照组相比,六味地黄汤含药血清10%、20%组和MCC9501μmol/L组HK-2细胞Nfkb、Nlrp3、Caspase1、Il18 mRNA表达下调(P<0.05),NF-κB、Caspase-1、IL-1β、IL-18、Vimentin蛋白表达下调(P<0.05),Ecadherin蛋白表达上调(P<0.05)。结论:六味地黄汤能抑制肾小管上皮细胞焦亡,延缓肾纤维化,其机制可能与下调NF-κB/NLRP3信号通路相关。 展开更多
关键词 六味地黄汤 细胞焦亡 肾纤维化 hk-2细胞 核因子κB/核苷酸结合寡聚化结构域样受体蛋白3信号通路
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一种基于HKS新结构的高优值氧化镓二极管
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作者 蒋典兵 程骏骥 +2 位作者 刘一锴 周浩 杨洪强 《微电子学》 北大核心 2025年第6期1063-1068,共6页
聚焦氧化镓功率器件领域,提出一种在阳极端同时具有高介(High-k,HK)区和肖特基(Schottky,S)接触的HKS二极管。相比目前主流的结势垒肖特基(Junction Barrier Schottky,JBS)二极管,新结构利用耐压时HK区可在表面形成高剂量束缚电荷的物... 聚焦氧化镓功率器件领域,提出一种在阳极端同时具有高介(High-k,HK)区和肖特基(Schottky,S)接触的HKS二极管。相比目前主流的结势垒肖特基(Junction Barrier Schottky,JBS)二极管,新结构利用耐压时HK区可在表面形成高剂量束缚电荷的物理机制,对漂移区发出的电力线进行更有效地牵引,从而进一步优化电场分布,获得显著的反向性能提升。基于校准模型的仿真结果表明,在不同参数的各个对照组中,HKS均较JBS表现出更优的性能,尤其当区间距为1.5μm时,击穿电压相对提升20.2%,而比导通电阻仅增加9.4%,令功率优值提升了32.2%。进一步研究表明,在1×10^(12) cm^(-2)的界面电荷的影响下,HKS二极管的性能未出现明显退化,体现出充分的工艺鲁棒性。 展开更多
关键词 氧化镓 hk材料 JBS二极管
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双氢青蒿素通过FOXO1/HK2/G6PC和My D88/NF-κB通路改善2型糖尿病小鼠肝脏糖代谢紊乱和炎症反应
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作者 张雨 杨源民 +4 位作者 李玉 陈利娜 刘拓 汪坤 李玉洁 《中草药》 北大核心 2025年第20期7395-7406,共12页
目的 探讨双氢青蒿素(dihydroartemisinin,DHA)治疗2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠肝脏糖代谢紊乱、炎症反应的作用及作用机制。方法 利用高糖高脂饲料喂养联合ip链脲佐菌素(40 mg/kg)诱导建立T2DM小鼠模型,设置对照组... 目的 探讨双氢青蒿素(dihydroartemisinin,DHA)治疗2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠肝脏糖代谢紊乱、炎症反应的作用及作用机制。方法 利用高糖高脂饲料喂养联合ip链脲佐菌素(40 mg/kg)诱导建立T2DM小鼠模型,设置对照组、模型组、二甲双胍(200 mg/kg)组和DHA低、中、高剂量(30、60、120 mg/kg)组,每组6只。给予药物干预4周后,检测小鼠体质量、空腹血糖(fasting blood glucose,FBG)、胰岛素抵抗指数(homeostatic model assessment for insulin resistance,HOMA-IR)、血脂四项、肝功能指标;采用ELISA法检测肝组织白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;采用苏木素-伊红(hematoxylin-eosin,HE)、PAS、油红O染色观察胰岛、肝脏组织病理变化;采用免疫组化法检测肝组织F4/80阳性表达;采用Western blotting检测肝组织糖代谢和炎症通路相关蛋白表达。采用高浓度胰岛素诱导建立肝细胞胰岛素抵抗(insulin resistance-human hepatocellular carcinoma,IRHepG2)模型,给予DHA和己糖激酶(hexokinase,HK)抑制剂3-溴丙酮酸(3-bromopyruvic acid,3-BrPA)干预后,检测细胞存活率和葡萄糖消耗量。结果 与模型组比较,DHA显著降低小鼠FBG(P<0.05、0.01),改善糖耐量损伤(P<0.05、0.01),减少HOMA-IR(P<0.01、0.001),升高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平(P<0.05、0.01),降低三酰甘油(triglyceride,TG)水平(P<0.001),降低丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性(P<0.05),减少肝脏炎症因子水平(P<0.05、0.01、0.001)。病理染色结果显示,DHA能够增加小鼠胰岛面积(P<0.001),改善β细胞损伤和肝细胞萎缩,减少肝脏脂质堆积,增加肝糖原含量。免疫组化结果显示,DHA能够减少肝脏F4/80阳性表达。Western blotting结果显示,DHA显著下调肝脏叉头框蛋白1(forkhead box O1,FOXO1)、葡萄糖-6-磷酸酶(glucose-6-phosphatase,G6PC)、髓样分化因子88(myeloid differentiation factor 88,MyD88)、核因子-κB(nuclear factor-κB,NF-κB)、F4/80蛋白表达(P<0.05、0.01、0.001),上调HK2蛋白表达(P<0.01)。细胞实验结果显示,1μmol/L胰岛素处理HepG2细胞36 h,可成功构建IR-HepG2模型;给予DHA干预后,葡萄糖消耗量显著增加(P<0.05、0.01);给予DHA和3-BrPA同时干预后,3-BrPA可部分抑制DHA对葡萄糖消耗量上调的作用。结论 DHA通过调节FOXO1/HK2/G6PC和MyD88/NF-κB通路降低FBG,改善胰岛素抵抗和糖耐量,保护胰岛和肝细胞,进而改善T2DM小鼠肝脏糖代谢紊乱和炎症反应。 展开更多
关键词 双氢青蒿素 2型糖尿病 HepG2细胞 FOXO1/hk2/G6PC通路 MyD88/NF-κB通路
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Construction of a Maritime Knowledge Graph Using GraphRAG for Entity and Relationship Extraction from Maritime Documents 被引量:1
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作者 Yi Han Tao Yang +2 位作者 Meng Yuan Pinghua Hu Chen Li 《Journal of Computer and Communications》 2025年第2期68-93,共26页
In the international shipping industry, digital intelligence transformation has become essential, with both governments and enterprises actively working to integrate diverse datasets. The domain of maritime and shippi... In the international shipping industry, digital intelligence transformation has become essential, with both governments and enterprises actively working to integrate diverse datasets. The domain of maritime and shipping is characterized by a vast array of document types, filled with complex, large-scale, and often chaotic knowledge and relationships. Effectively managing these documents is crucial for developing a Large Language Model (LLM) in the maritime domain, enabling practitioners to access and leverage valuable information. A Knowledge Graph (KG) offers a state-of-the-art solution for enhancing knowledge retrieval, providing more accurate responses and enabling context-aware reasoning. This paper presents a framework for utilizing maritime and shipping documents to construct a knowledge graph using GraphRAG, a hybrid tool combining graph-based retrieval and generation capabilities. The extraction of entities and relationships from these documents and the KG construction process are detailed. Furthermore, the KG is integrated with an LLM to develop a Q&A system, demonstrating that the system significantly improves answer accuracy compared to traditional LLMs. Additionally, the KG construction process is up to 50% faster than conventional LLM-based approaches, underscoring the efficiency of our method. This study provides a promising approach to digital intelligence in shipping, advancing knowledge accessibility and decision-making. 展开更多
关键词 Maritime knowledge Graph GraphRAG Entity and Relationship Extraction Document Management
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Impact of family history of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females 被引量:1
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作者 Melaku Mekonnen Agidew Niguss Cherie +2 位作者 Zemene Damtie Bezawit Adane Girma Derso 《World Journal of Clinical Oncology》 2025年第4期109-118,共10页
BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on ... BACKGROUND Breast cancer is one of the most prevalent causes of morbidity and mortality worldwide,presenting an increasing public health challenge,particularly in lowincome and middle-income countries.However,data on the knowledge,attitudes,and preventive practices regarding breast cancer and the associated factors among females in Wollo,Ethiopia,remain limited.AIM To assess the impact of family history(FH)of breast disease on knowledge,attitudes,and breast cancer preventive practices among reproductive-age females.METHODS A community-based cross-sectional study was conducted in May and June 2022 in Northeast Ethiopia and involved 143 reproductive-age females with FH of breast diseases and 209 without such a history.We selected participants using the systematic random sampling technique.We analyzed the data using Statistical Package for Social Science version 25 software,and logistic regression analysis was employed to determine odds ratios for variable associations,with statistical significance set at P<0.05.RESULTS Among participants with FH of breast diseases,the levels of knowledge,attitudes,and preventive practices were found to be 83.9%[95%confidence interval(CI):77.9-89.9],49.0%(95%CI:40.8-57.1),and 74.1%(95%CI:66.9-81.3),respectively.In contrast,among those without FH of breast diseases,these levels were significantly decreased to 10.5%(95%CI:6.4-14.7),32.1%(95%CI:25.7-38.4),and 16.7%(95%CI:11.7-21.8),respectively.This study also indicated that knowledge,attitudes,and preventive practices related to breast cancer are significantly higher among participants with FH of breast diseases compared to those without HF breast diseases.CONCLUSION Educational status,monthly income,and community health insurance were identified as significant factors associated with the levels of knowledge,attitudes,and preventive practices regarding breast cancer among reproductive-age females. 展开更多
关键词 Breast cancer Reproductive age knowledge ATTITUDE Practice Ethiopia
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芍药苷通过调控PI3K/AKT/NF-κB通路减轻LPS/Nig诱导的HK-2细胞焦亡
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作者 李若男 谢菁 +2 位作者 孟照宇 王朝阳 马玉清 《中国病理生理杂志》 北大核心 2025年第12期2399-2407,共9页
目的:探究芍药苷(paeoniflorin,PF)对脂多糖(lipopolysaccharide,LPS)/尼日利亚菌素(nigericin,Nig)诱导的肾小管上皮细胞(HK-2)焦亡的影响及其作用机制。方法:选择对数生长期且生长状态良好的3~5代HK-2细胞。采用10 mg/L LPS联合10μmo... 目的:探究芍药苷(paeoniflorin,PF)对脂多糖(lipopolysaccharide,LPS)/尼日利亚菌素(nigericin,Nig)诱导的肾小管上皮细胞(HK-2)焦亡的影响及其作用机制。方法:选择对数生长期且生长状态良好的3~5代HK-2细胞。采用10 mg/L LPS联合10μmol/L Nig刺激HK-2细胞,建立细胞焦亡模型。设置4个实验组进行对比研究:(1)对照(control,Con)组:细胞正常培养,不做处理;(2)模型组(LPS组):10 mg/L LPS+10μmol/L Nig处理细胞;(3)PF组:50μmol/L PF预处理细胞4 h后加入10 mg/L LPS和10μmol/L Nig继续孵育细胞24 h;(4)PI3K激动剂740Y-P组:50μmol/L PF及20μmol/L 740Y-P预处理细胞4 h后加入10 mg/L LPS和10μmol/L Nig继续孵育细胞24 h。造模24 h后收集细胞与上清液,显微镜观察细胞形态变化;ELISA测定上清液中白细胞介素1β(interleukin-1β,IL-1β)和IL-18水平;Western blot检测焦亡相关蛋白核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)、cleaved caspase-1及消皮素D的N端片段(N-terminal fragment of gasdermin D,GSDMD-N)表达水平,通路蛋白磷脂酰肌醇3-激酶(phosphatidylinositiol 3-kinase,PI3K)、蛋白激酶B(protein kinase B,PKB/AKT)和核因子κB(nuclear factor-κB,NF-κB)p65磷酸化及总蛋白表达;免疫荧光检测细胞核p-p65表达水平。结果:光镜下Con组细胞形态正常,呈上皮样排列;LPS组细胞肿胀,有伪足样突起;PF组较LPS组细胞肿胀减轻;740Y-P组较PF组细胞肿胀加重。电镜下Con组细胞形态规则,胞膜完整;LPS组细胞肿胀明显,膜泡及焦亡孔道形成;PF组较LPS组细胞肿胀减轻,细胞膜完整性改善。ELISA、Western blot及免疫荧光示LPS组较Con组IL-1β和IL-18,焦亡相关蛋白(NLRP3、cleaved caspase-1和GSDMD-N),通路蛋白(p-PI3K、p-AKT和pp65),及细胞核p-p65表达均显著升高(P<0.01);PF组较LPS组上述炎症因子、焦亡及通路蛋白及细胞核p-p65表达均显著降低(P<0.01);740Y-P组较PF组上述指标表达显著升高(P<0.05或P<0.01)。结论:芍药苷通过抑制PI3K/AKT/NF-κB通路减轻LPS/Nig诱导的HK-2细胞焦亡。 展开更多
关键词 脓毒症相关急性肾损伤 hk-2细胞 细胞焦亡 PI3K/AKT/NF-κB信号通路
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Methodology,progress and challenges of geoscience knowledge graph in International Big Science Program of Deep-Time Digital Earth 被引量:2
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作者 ZHU Yunqiang WANG Qiang +9 位作者 WANG Shu SUN Kai WANG Xinbing LV Hairong HU Xiumian ZHANG Jie WANG Bin QIU Qinjun YANG Jie ZHOU Chenghu 《Journal of Geographical Sciences》 2025年第5期1132-1156,共25页
Deep-time Earth research plays a pivotal role in deciphering the rates,patterns,and mechanisms of Earth's evolutionary processes throughout geological history,providing essential scientific foundations for climate... Deep-time Earth research plays a pivotal role in deciphering the rates,patterns,and mechanisms of Earth's evolutionary processes throughout geological history,providing essential scientific foundations for climate prediction,natural resource exploration,and sustainable planetary stewardship.To advance Deep-time Earth research in the era of big data and artificial intelligence,the International Union of Geological Sciences initiated the“Deeptime Digital Earth International Big Science Program”(DDE)in 2019.At the core of this ambitious program lies the development of geoscience knowledge graphs,serving as a transformative knowledge infrastructure that enables the integration,sharing,mining,and analysis of heterogeneous geoscience big data.The DDE knowledge graph initiative has made significant strides in three critical dimensions:(1)establishing a unified knowledge structure across geoscience disciplines that ensures consistent representation of geological entities and their interrelationships through standardized ontologies and semantic frameworks;(2)developing a robust and scalable software infrastructure capable of supporting both expert-driven and machine-assisted knowledge engineering for large-scale graph construction and management;(3)implementing a comprehensive three-tiered architecture encompassing basic,discipline-specific,and application-oriented knowledge graphs,spanning approximately 20 geoscience disciplines.Through its open knowledge framework and international collaborative network,this initiative has fostered multinational research collaborations,establishing a robust foundation for next-generation geoscience research while propelling the discipline toward FAIR(Findable,Accessible,Interoperable,Reusable)data practices in deep-time Earth systems research. 展开更多
关键词 deep-time Earth geoscience knowledge graph Deep-time Digital Earth International Big Science Program
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外泌体环状RNA诱导HK-2细胞凋亡在感染性休克AKI中的研究
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作者 李秀君 李岩 +1 位作者 张春媚 杨海玲 《中国实验诊断学》 2025年第2期210-214,共5页
目的探究外泌体环状RNA诱导HK-2细胞凋亡在感染性休克相关性急性肾损伤的作用机制。方法分为感染性休克相关性急性肾损伤患者组和健康人对照组,采集血标本。检测外泌体标记蛋白,鉴定出两组外泌体,对外泌体环状RNA进行实时PCR分析。对两... 目的探究外泌体环状RNA诱导HK-2细胞凋亡在感染性休克相关性急性肾损伤的作用机制。方法分为感染性休克相关性急性肾损伤患者组和健康人对照组,采集血标本。检测外泌体标记蛋白,鉴定出两组外泌体,对外泌体环状RNA进行实时PCR分析。对两组的HK-2细胞进行凋亡检测。结果10例感染性休克AKI入院患者,10例健康人对照。鉴定表面外泌体标记蛋白包括HSP70和TSG101。两组均鉴定出外泌体。与对照组相比,感染性休克AKI组circ-Ttc3(P<0.05)、circ-Fryl(P<0.01)表达明显下调。感染性休克AKI外泌体可抑制HK-2细胞活性,促进细胞凋亡。结论感染性休克AKI可诱导HK-2细胞凋亡,其分子机制可能与circ-Ttc3和circ-Fryl这两种环状RNA有关。 展开更多
关键词 感染性休克相关急性肾损伤 外泌体 环状RNA hk-2细胞
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TCMKD: From ancient wisdom to modern insights-A comprehensive platform for traditional Chinese medicine knowledge discovery 被引量:1
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作者 Wenke Xiao Mengqing Zhang +12 位作者 Danni Zhao Fanbo Meng Qiang Tang Lianjiang Hu Hongguo Chen Yixi Xu Qianqian Tian Mingrui Li Guiyang Zhang Liang Leng Shilin Chen Chi Song Wei Chen 《Journal of Pharmaceutical Analysis》 2025年第6期1390-1402,共13页
Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challeng... Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM. 展开更多
关键词 Traditional Chinese medicine Data mining knowledge graph Network visualization Network analysis
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A Deep-Learning-Based Method for Interpreting Distribution and Difference Knowledge from Raster Topographic Maps 被引量:1
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作者 PAN Yalan TI Peng +1 位作者 LI Mingyao LI Zhilin 《Journal of Geodesy and Geoinformation Science》 2025年第2期21-36,共16页
Topographic maps,as essential tools and sources of information for geographic research,contain precise spatial locations and rich map features,and they illustrate spatio-temporal information on the distribution and di... Topographic maps,as essential tools and sources of information for geographic research,contain precise spatial locations and rich map features,and they illustrate spatio-temporal information on the distribution and differences of various surface features.Currently,topographic maps are mainly stored in raster and vector formats.Extraction of the spatio-temporal knowledge in the maps—such as spatial distribution patterns,feature relationships,and dynamic evolution—still primarily relies on manual interpretation.However,manual interpretation is time-consuming and laborious,especially for large-scale,long-term map knowledge extraction and application.With the development of artificial intelligence technology,it is possible to improve the automation level of map knowledge interpretation.Therefore,the present study proposes an automatic interpretation method for raster topographic map knowledge based on deep learning.To address the limitations of current data-driven intelligent technology in learning map spatial relations and cognitive logic,we establish a formal description of map knowledge by mapping the relationship between map knowledge and features,thereby ensuring interpretation accuracy.Subsequently,deep learning techniques are employed to extract map features automatically,and the spatio-temporal knowledge is constructed by combining formal descriptions of geographic feature knowledge.Validation experiments demonstrate that the proposed method effectively achieves automatic interpretation of spatio-temporal knowledge of geographic features in maps,with an accuracy exceeding 80%.The findings of the present study contribute to machine understanding of spatio-temporal differences in map knowledge and advances the intelligent interpretation and utilization of cartographic information. 展开更多
关键词 raster topographic maps geographic feature knowledge intelligent interpretation deep learning
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