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扶金化积丸对Lewis肺癌荷瘤小鼠Akt/MDM2/p53信号通路的影响
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作者 付芸芸 李炜 +8 位作者 李林洲 秦大凯 任德祥 赵峻 陈露露 吕学颖 夏小军 雷旭东 单金姝 《中成药》 北大核心 2025年第9期3085-3089,共5页
目的探究扶金化积丸对Lewis肺癌荷瘤小鼠肿瘤生长的抑制作用。方法60只C57BL/6小鼠随机分为空白组、模型组、顺铂组(0.005 g/kg)和中药低、中、高剂量组(0.54、1.07、2.14 g/kg扶金化积丸),每组10只,除空白组外,其余各组小鼠均腋下接种L... 目的探究扶金化积丸对Lewis肺癌荷瘤小鼠肿瘤生长的抑制作用。方法60只C57BL/6小鼠随机分为空白组、模型组、顺铂组(0.005 g/kg)和中药低、中、高剂量组(0.54、1.07、2.14 g/kg扶金化积丸),每组10只,除空白组外,其余各组小鼠均腋下接种Lewis细胞悬液,构建Lewis肺癌移植瘤模型。各组连续给药14 d后取材,称量小鼠体质量,剥离肿瘤并称量肿瘤质量,计算抑瘤率;流式细胞仪检测肿瘤细胞周期的变化;TUNEL法检测肿瘤组织细胞凋亡情况;HE染色观察肿瘤组织病理形态变化;RT-qPCR及Western blot法检测肿瘤组织Akt、MDM2、p53、p21、Bcl-2、Bax、Bcl-2 mRNA和蛋白表达情况。结果与空白组比较,模型组小鼠毛发暗淡,精神状态差,行动迟缓,饮食量减少,大便干燥;与模型组比较,顺铂组和中药各剂量组小鼠毛发光泽,活动增加,精神状态好转,粪质状态改善,药物干预第7、14天体质量无明显变化(P>0.05)。与模型组比较,中药高剂量组和顺铂组小鼠肿瘤质量降低(P<0.05),抑瘤率均增加;肿瘤组织细胞核皱缩,少量细胞核破碎、溶解,肿瘤组织出现不同程度坏死;肿瘤组织凋亡细胞数增多,阳性表达密度较高,细胞凋亡率升高(P<0.05);肿瘤组织G_(0)/G_(1)期细胞比例增加(P<0.05),S期、G_(2)/M期细胞比例降低(P<0.05);肿瘤组织Akt、MDM2、Bcl-2 mRNA和蛋白表达降低(P<0.05),p53、p21、Bax mRNA和蛋白表达升高(P<0.05)。结论扶金化积丸可能通过调控Akt/MDM2/p53信号通路诱导肿瘤细胞凋亡,进而抑制Lewis肺癌荷瘤小鼠皮下肿瘤的生长。 展开更多
关键词 扶金化积丸 肺癌 顺铂 Akt/mdm2/p53信号通路 凋亡
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复方浙贝颗粒基于MDM2/p53信号通路调节MHC-Ⅱ逆转白血病多药耐药机制研究 被引量:1
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作者 杨茜茹 田劭丹 +6 位作者 薛程元 李光达 张雅月 张宇 李冬云 齐宇镈 侯丽 《北京中医药》 2025年第3期325-330,共6页
目的 探讨复方浙贝颗粒(CZBG)基于双微体同源基因2(MDM2)/p53信号通路调节主要组织相容性复合体Ⅱ类(MHC-Ⅱ)逆转白血病多药耐药的作用机制。方法 选取人急性髓系白血病细胞(KG-1a、MOLM-13细胞),将KG-1a、MOLM-13细胞分别分为CZBG组、... 目的 探讨复方浙贝颗粒(CZBG)基于双微体同源基因2(MDM2)/p53信号通路调节主要组织相容性复合体Ⅱ类(MHC-Ⅱ)逆转白血病多药耐药的作用机制。方法 选取人急性髓系白血病细胞(KG-1a、MOLM-13细胞),将KG-1a、MOLM-13细胞分别分为CZBG组、空白对照组。空白对照组予完全培养基培养,CZBG组予含不同浓度的CZBG完全培养基培养。CCK-8法检测细胞增殖,Western blotting法检测MDM2、p53蛋白表达,流式细胞术检测MHC-Ⅱ表达。结果 干预24、48、72 h,CZBG对KG-1a、MOLM-13细胞增殖均具有抑制作用。其中CZBG在24、48、72 h时对KG-1a细胞的半数抑制浓度(IC50)为(2.276±0.218)、(1.254±0.104)、(1.040±0.108)mg/mL,对MOLM-13细胞的IC50为(2.809±0.121)、(1.585±0.103)、(1.194±0.105)mg/mL。应用2.2 mg/mL CZBG干预KG-1a细胞24 h时,与空白对照组比较,CZBG组MDM2蛋白相对表达量低(P<0.05),p53蛋白相对表达量高(P<0.05)。用2.8 mg/mL CZBG干预MOLM-13细胞24 h时,与空白对照组比较,CZBG组MDM2蛋白表达低(P<0.05),p53蛋白相对表达量高(P<0.05)。KG-1a、MOLM-13细胞分别经CZBG处理24 h,CZBG组细胞表面的MHC-Ⅱ表达高(P<0.05)。结论 CZBG逆转白血病多药耐药的作用机制可能与通过MDM2/p53通路调节白血病细胞表面MHC-Ⅱ表达,干预免疫逃逸有关。 展开更多
关键词 复方浙贝颗粒 双微体同源基因2(mdm2)/p53信号通路 主要组织相容性复合体Ⅱ类 白血病 多药耐药 作用机制
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伴有MDM2和CDK4基因扩增的ZC3H7B::BCOR基因融合的高级别子宫内膜间质肉瘤1例并文献复习
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作者 车稳 李芹芹 +1 位作者 罗方秀 方旭前 《临床与病理杂志》 2025年第2期239-247,共9页
1例伴有双微体同源基因2(murine double minute 2,MDM2)和细胞周期蛋白依赖性激酶4(cyclindependent kinase 4,CDK4)扩增的ZC3H7B::B细胞淋巴瘤6协同抑制蛋白(B-cell lymphoma 6 corepressor,BCOR)基因融合的高级别子宫内膜间质肉瘤患者... 1例伴有双微体同源基因2(murine double minute 2,MDM2)和细胞周期蛋白依赖性激酶4(cyclindependent kinase 4,CDK4)扩增的ZC3H7B::B细胞淋巴瘤6协同抑制蛋白(B-cell lymphoma 6 corepressor,BCOR)基因融合的高级别子宫内膜间质肉瘤患者,45岁,女,因经量增多伴血块行超声检查,发现子宫占位,肿块最大径为10.3 cm,行全子宫+双附件切除术。光镜下肿瘤组织在肌壁间呈浸润性生长,有细胞致密区和稀疏区,致密区细胞呈卵圆形或胖梭形,细胞呈中度异型,核分裂象约为14个/10 HPF(HPF为高倍镜视野);稀疏区瘤细胞呈梭形,轻至中度异型,间质富于黏液,核分裂象约为8个/10 HPF,可见多灶坏死。免疫组织化学染色示肿瘤细胞的细胞周期蛋白D1(cyclin D1)、细胞周期依赖性激酶抑制蛋白2A(cyclindependent kinase inhibitor 2A,CDKN2A,又称为P16)和富含AT序列结合蛋白2(special AT-rich sequence-binding protein 2,SATB2)呈弥漫表达,BCOR)呈弱阳性表达,急性淋巴母细胞白血病共同抗原(common acute lymphoblastic leukemia antigen,CALLA,又称CD10)呈部分阳性表达,肌源性标记的平滑肌肌动蛋白(smooth muscle actin,SMA)和高分子量钙调素结合蛋白(high molecular weight caldesmon,h-Caldesmon)呈少量阳性表达。荧光原位杂交和二代测序检测存在ZC3H7B::BCOR基因融合,并伴有MDM2和CDK4基因扩增。术后随访22个月患者死亡。此类患者有望能从MDM2/CDK4共抑制剂中获益。 展开更多
关键词 ZC3H7B::BCOR基因融合 高级别子宫内膜间质肉瘤 mdm2和CDK4基因扩增 mdm2-P53相互作用 mdm2/CDK4抑制剂
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甲氧基查尔酮类化合物的合成、体外抗宫颈癌活性及其与MDM2分子对接研究
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作者 廖波儿 郭伟 木合布力·阿布力孜 《合成化学》 2025年第1期30-36,共7页
通过Claisen-Schmidt缩合反应原理,合成出4个甲氧基查尔酮类化合物,其结构均经^(1)H NMR、^(13)C NMR确证。以宫颈癌He La和Si Ha细胞作为受试细胞,测定目标化合物对细胞抑制作用及诱导凋亡作用,并通过分子对接技术研究化合物3,4,5-三... 通过Claisen-Schmidt缩合反应原理,合成出4个甲氧基查尔酮类化合物,其结构均经^(1)H NMR、^(13)C NMR确证。以宫颈癌He La和Si Ha细胞作为受试细胞,测定目标化合物对细胞抑制作用及诱导凋亡作用,并通过分子对接技术研究化合物3,4,5-三甲氧基-2′,4′-二甲氧基查尔酮(3d)与MDM2蛋白构效关系。研究结果表明:4个甲氧查尔酮化合物均对宫颈癌He La和Si Ha细胞展现出较好的抑制活性,其中化合物3d对宫颈癌He La和Si Ha细胞抑制活性最高,作用24 h,IC_(50)为26.39μmol/L。在凋亡实验中,化合物3d显著诱导细胞凋亡,作用48 h,细胞凋亡率达到77%。分子对接结果显示:化合物3d与MDM2靶标蛋白的结合自由能为-6.2 kcal/mol,此结果表明;化合物3d与MDM2蛋白具有较高的结合性。 展开更多
关键词 甲氧基查尔酮 宫颈癌 合成 分子对接 mdm2蛋白
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Study of the Transport Behavior of Multispherical Proppant in Intersecting Fracture Based on Discrete Element Method 被引量:1
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作者 Chengyong Peng JianshuWu +2 位作者 Mao Jiang Biao Yin Yishan Lou 《Energy Engineering》 EI 2025年第1期185-201,共17页
To analyze the differences in the transport and distribution of different types of proppants and to address issues such as the short effective support of proppant and poor placement in hydraulically intersecting fract... To analyze the differences in the transport and distribution of different types of proppants and to address issues such as the short effective support of proppant and poor placement in hydraulically intersecting fractures,this study considered the combined impact of geological-engineering factors on conductivity.Using reservoir production parameters and the discrete elementmethod,multispherical proppants were constructed.Additionally,a 3D fracture model,based on the specified conditions of the L block,employed coupled(Computational Fluid Dynamics)CFD-DEM(Discrete ElementMethod)for joint simulations to quantitatively analyze the transport and placement patterns of multispherical proppants in intersecting fractures.Results indicate that turbulent kinetic energy is an intrinsic factor affecting proppant transport.Moreover,the efficiency of placement and migration distance of low-sphericity quartz sand constructed by the DEM in the main fracture are significantly reduced compared to spherical ceramic proppants,with a 27.7%decrease in the volume fraction of the fracture surface,subsequently affecting the placement concentration and damaging fracture conductivity.Compared to small-angle fractures,controlling artificial and natural fractures to expand at angles of 45°to 60°increases the effective support length by approximately 20.6%.During hydraulic fracturing of gas wells,ensuring the fracture support area and post-closure conductivity can be achieved by controlling the sphericity of proppants and adjusting the perforation direction to control the direction of artificial fractures. 展开更多
关键词 Hydraulic fracturing discrete element method PROPPANT SPHERICITY CFD-DEM
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Combing the Entropy Weight Method with Fuzzy Mathematics for Assessing the Quality and Post-Ripening Mechanism of High-Temperature Daqu during Storage 被引量:1
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作者 YANG Junlin YANG Shaojuan +8 位作者 WU Cheng YIN Yanshun YOU Xiaolong ZHAO Wenyu ZHU Anran WANG Jia HU Feng HU Jianfeng WANG Diqiang 《食品科学》 北大核心 2025年第9期48-62,共15页
This study investigated the physicochemical properties,enzyme activities,volatile flavor components,microbial communities,and sensory evaluation of high-temperature Daqu(HTD)during the maturation process,and a standar... This study investigated the physicochemical properties,enzyme activities,volatile flavor components,microbial communities,and sensory evaluation of high-temperature Daqu(HTD)during the maturation process,and a standard system was established for comprehensive quality evaluation of HTD.There were obvious changes in the physicochemical properties,enzyme activities,and volatile flavor components at different storage periods,which affected the sensory evaluation of HTD to a certain extent.The results of high-throughput sequencing revealed significant microbial diversity,and showed that the bacterial community changed significantly more than did the fungal community.During the storage process,the dominant bacterial genera were Kroppenstedtia and Thermoascus.The correlation between dominant microorganisms and quality indicators highlighted their role in HTD quality.Lactococcus,Candida,Pichia,Paecilomyces,and protease activity played a crucial role in the formation of isovaleraldehyde.Acidic protease activity had the greatest impact on the microbial community.Moisture promoted isobutyric acid generation.Furthermore,the comprehensive quality evaluation standard system was established by the entropy weight method combined with multi-factor fuzzy mathematics.Consequently,this study provides innovative insights for comprehensive quality evaluation of HTD during storage and establishes a groundwork for scientific and rational storage of HTD and quality control of sauce-flavor Baijiu. 展开更多
关键词 microbial community high-temperature Daqu comprehensive quality evaluation entropy weight method maturation process
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In situ stress inversion using nonlinear stress boundaries achieved by the bubbling method 被引量:1
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作者 Xige Liu Chenchun Huang +3 位作者 Wancheng Zhu Joung Oh Chengguo Zhang Guangyao Si 《Journal of Rock Mechanics and Geotechnical Engineering》 2025年第3期1510-1527,共18页
Due to the heterogeneity of rock masses and the variability of in situ stress,the traditional linear inversion method is insufficiently accurate to achieve high accuracy of the in situ stress field.To address this cha... Due to the heterogeneity of rock masses and the variability of in situ stress,the traditional linear inversion method is insufficiently accurate to achieve high accuracy of the in situ stress field.To address this challenge,nonlinear stress boundaries for a numerical model are determined through regression analysis of a series of nonlinear coefficient matrices,which are derived from the bubbling method.Considering the randomness and flexibility of the bubbling method,a parametric study is conducted to determine recommended ranges for these parameters,including the standard deviation(σb)of bubble radii,the non-uniform coefficient matrix number(λ)for nonlinear stress boundaries,and the number(m)and positions of in situ stress measurement points.A model case study provides a reference for the selection of these parameters.Additionally,when the nonlinear in situ stress inversion method is employed,stress distortion inevitably occurs near model boundaries,aligning with the Saint Venant's principle.Two strategies are proposed accordingly:employing a systematic reduction of nonlinear coefficients to achieve high inversion accuracy while minimizing significant stress distortion,and excluding regions with severe stress distortion near the model edges while utilizing the central part of the model for subsequent simulations.These two strategies have been successfully implemented in the nonlinear in situ stress inversion of the Xincheng Gold Mine and have achieved higher inversion accuracy than the linear method.Specifically,the linear and nonlinear inversion methods yield root mean square errors(RMSE)of 4.15 and 3.2,and inversion relative errors(δAve)of 22.08%and 17.55%,respectively.Therefore,the nonlinear inversion method outperforms the traditional multiple linear regression method,even in the presence of a systematic reduction in the nonlinear stress boundaries. 展开更多
关键词 In situ stress field Inversion method The bubbling method Nonlinear stress boundary Multiple linear regression method
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MDM2通过P53/GPX4通路对结肠癌细胞铁死亡的影响
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作者 张金华 霍虹 +1 位作者 许瑞琪 李昀 《云南民族大学学报(自然科学版)》 2025年第5期557-563,共7页
探讨MDM2表达水平对人结肠癌细胞铁死亡的影响.将MDM2 siRNA质粒和MDM2过表达质粒分别转染入结肠癌HCT116细胞,设置空白对照组、MDM2干扰对照组、MDM2干扰组、空载体对照组、MDM2过表达组;CCK8检测各组细胞增殖活性,试剂盒检测亚铁离子(... 探讨MDM2表达水平对人结肠癌细胞铁死亡的影响.将MDM2 siRNA质粒和MDM2过表达质粒分别转染入结肠癌HCT116细胞,设置空白对照组、MDM2干扰对照组、MDM2干扰组、空载体对照组、MDM2过表达组;CCK8检测各组细胞增殖活性,试剂盒检测亚铁离子(Fe^(2+))、谷胱甘肽(GSH)、丙二醛(MDA)浓度,免疫荧光检测活性氧(ROS)表达水平,Western blot和RT-qPCR分别检测MDM2、P53、GPX4、PTGS2蛋白和mRNA表达水平.与对照组比较,MDM2干扰后细胞中MDA、Fe^(2+)浓度及ROS水平、P53和PTGS2 mRNA及蛋白表达均明显上升,GSH浓度、细胞增殖活性、MDM2和GPX4 mRNA及蛋白表达均明显降低;在MDM2过表达后细胞中MDA浓度、ROS水平、P53和PTGS2 mRNA及蛋白表达均明显下降,GSH浓度、细胞增殖活性、MDM2和GPX4 mRNA及蛋白表达均明显上升. MDM2可通过调控P53/GPX4信号通路,抑制人结肠癌细胞铁死亡. 展开更多
关键词 mdm2 P53/GPX4通路 结肠癌 铁死亡
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工程化OMEGA-TnpB系统的构建及体外靶向MDM2基因抑制骨肉瘤细胞恶性生物学行为的研究
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作者 王梓颖 陈泽华 +5 位作者 王振 朱庆岩 郭子轩 赵雪林 赵子仪 许猛 《解放军医学院学报》 2025年第4期315-322,328,共9页
背景传统治疗手段对晚期、复发及转移性骨肉瘤患者的治疗效果有限。基因治疗为骨肉瘤提供了新的治疗选择。然而,现有基因编辑工具(如CRISPR-Cas9)因尺寸大、免疫原性高等问题限制了其临床应用。新发现的OMEGA-TnpB系统具有紧凑的尺寸(约... 背景传统治疗手段对晚期、复发及转移性骨肉瘤患者的治疗效果有限。基因治疗为骨肉瘤提供了新的治疗选择。然而,现有基因编辑工具(如CRISPR-Cas9)因尺寸大、免疫原性高等问题限制了其临床应用。新发现的OMEGA-TnpB系统具有紧凑的尺寸(约400 aa),在肿瘤基因编辑中展现出巨大潜力。目的通过改造OMEGA-TnpB系统,开发高效、紧凑的基因编辑工具,并验证其在骨肉瘤基因治疗中的应用潜力。方法通过理性设计获取TnpB突变体。利用单链退火(single strand annealing,SSA)报告系统筛选突变体,并在HEK293T和骨肉瘤细胞系(143B)中验证其编辑效率。最后使用优化的TnpB突变体敲除骨肉瘤基因MDM2,通过RT-qPCR、流式细胞术、CCK-8、划痕实验和Transwell实验评估其对细胞增殖、凋亡、迁移及侵袭的影响。结果筛选出多个高活性TnpB突变体,其中ISYmu1-L225K在HEK293T细胞(P<0.01)和143B细胞(P<0.01)中的编辑效率显著高于enOsCas12f1,在HEK293T细胞部分位点与SpCas9比较无统计学差异。敲除MDM2基因后,骨肉瘤细胞的增殖能力下降(P<0.01),凋亡率增加(P<0.01),迁移(P<0.01)和侵袭(P<0.05)能力被抑制。结论成功获取了在哺乳动物细胞内基因编辑效率提高的TnpB突变体ISYmu1-L225K,验证了ISYmu1-L225K能够靶向敲除MDM2基因并抑制骨肉瘤细胞的恶性行为,为骨肉瘤的精准治疗提供了新思路。 展开更多
关键词 OMEGA-TnpB系统 mdm2基因 骨肉瘤 基因治疗 基因编辑
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基于MDM4/p53/GPX4信号通路探讨加味少腹逐瘀汤对子宫内膜异位症大鼠异位子宫内膜组织铁死亡的影响 被引量:4
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作者 张作良 林祥羽 +3 位作者 王婉润 王家兴 杨亚玲 武权生 《中国实验方剂学杂志》 北大核心 2025年第4期39-47,共9页
目的:探讨加味少腹逐瘀汤通过小鼠双体4/肿瘤抑制因子p53/谷胱甘肽过氧化物酶4(MDM4/p53/GPX4)信号通路诱导子宫内膜异位症大鼠异位子宫内膜组织铁死亡的作用机制。方法:将70只SPF级雌性SD大鼠随机分为空白组(n=10)、假手术组(n=10)和... 目的:探讨加味少腹逐瘀汤通过小鼠双体4/肿瘤抑制因子p53/谷胱甘肽过氧化物酶4(MDM4/p53/GPX4)信号通路诱导子宫内膜异位症大鼠异位子宫内膜组织铁死亡的作用机制。方法:将70只SPF级雌性SD大鼠随机分为空白组(n=10)、假手术组(n=10)和造模组(n=50),假手术组大鼠行剖腹探查术,造模组大鼠按照自体移植法构建子宫内膜异位症疾病模型。造模成功后随机分为模型组,孕三烯酮组(0.25 mg·kg^(-1)),加味少腹逐瘀汤高、中、低剂量组(30、15、7.5 g·kg^(-1)),每组10只。给药4周后,处死大鼠取材。透射电镜观察大鼠子宫内膜组织超微结构改变,普鲁士蓝染色观察子宫内膜组织铁离子沉积,酶联免疫吸附测定法(ELISA)检测各组大鼠血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量,比色法检测大鼠子宫内膜组织铁离子(Fe2+)、丙二醛(MDA)、谷胱甘肽(GSH)含量,免疫荧光法(IF)检测子宫内膜组织GSH、GPX4相对荧光强度,蛋白免疫印迹法(Western blot)检测子宫内膜组织中磷脂酰肌醇3-激酶(PI3K)、磷酸化(p)-PI3K、蛋白激酶B(Akt)、p-Akt、MDM4、p53、GPX4蛋白相对表达量,实时荧光定量聚合酶链式反应(Real-time PCR)检测PI3K、Akt、MDM4、p53、GPX4 mRNA表达。结果:与空白组及假手术组比较,模型组大鼠超微结构可见铁死亡损伤减轻,普鲁士蓝染色可见铁离子聚集数量减少,铁离子阳性表达面积下降,血清IL-6、IL-1β、TNF-α含量升高,子宫内膜组织Fe^(2+)、MDA相对含量降低,GSH相对含量升高,GSH、GPX4荧光相对强度增强(P<0.01),PI3K、p-PI3K、Akt、p-Akt、MDM4、GPX4蛋白及mRNA表达量上升,p53蛋白及mRNA表达量下降(P<0.01)。与模型组比较,孕三烯酮组及加味少腹逐瘀汤高、中剂量组异位子宫内膜组织,透射电镜超微结构可见铁死亡损伤不同程度加重,普鲁士蓝染色可见铁离子聚集数量增加,铁离子阳性表达面积上升,血清IL-6、IL-1β、TNF-α含量下降,子宫内膜组织Fe^(2+)、MDA相对含量升高,GSH相对含量下降,GSH、GPX4荧光相对强度减弱,PI3K、p-PI3K、Akt、p-Akt、MDM4、GPX4蛋白及mRNA表达量下降,p53蛋白及mRNA表达量上升(P<0.05,P<0.01)。结论:加味少腹逐瘀汤可能通过干预MDM4/p53/GPX4信号通路关键蛋白,诱导异位子宫内膜组织铁死亡,减轻炎性反应,从而对子宫内膜异位症起到治疗作用。 展开更多
关键词 子宫内膜异位症 铁死亡 加味少腹逐瘀汤 小鼠双体4/肿瘤抑制因子p53/谷胱甘肽过氧化物酶4(mdm4/p53/GPX4)信号通路
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Insight Into the Separation-of-Variable Methods for the Closed-Form Solutions of Free Vibration of Rectangular Thin Plates
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作者 Yufeng Xing Ye Yuan Gen Li 《Computer Modeling in Engineering & Sciences》 SCIE EI 2025年第1期329-355,共27页
The separation-of-variable(SOV)methods,such as the improved SOV method,the variational SOV method,and the extended SOV method,have been proposed by the present authors and coworkers to obtain the closed-form analytica... The separation-of-variable(SOV)methods,such as the improved SOV method,the variational SOV method,and the extended SOV method,have been proposed by the present authors and coworkers to obtain the closed-form analytical solutions for free vibration and eigenbuckling of rectangular plates and circular cylindrical shells.By taking the free vibration of rectangular thin plates as an example,this work presents the theoretical framework of the SOV methods in an instructive way,and the bisection–based solution procedures for a group of nonlinear eigenvalue equations.Besides,the explicit equations of nodal lines of the SOV methods are presented,and the relations of nodal line patterns and frequency orders are investigated.It is concluded that the highly accurate SOV methods have the same accuracy for all frequencies,the mode shapes about repeated frequencies can also be precisely captured,and the SOV methods do not have the problem of missing roots as well. 展开更多
关键词 Separation-of-variable method Rayleigh quotient nodal line eigenvalue equation bisection method
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MDM2-p53抑制剂nutlin-3对野生型p53肿瘤细胞系的抑制作用及机制的研究
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作者 马明远 刘莹莹 +2 位作者 钱宇卿 周思雨 李铭东 《药学学报》 北大核心 2025年第5期1407-1413,共7页
Nutlin-3是代表性小分子MDM2-p53拮抗剂,能通过破坏p53和MDM2的相互作用,稳定p53状态,从而诱导p53信号通路发挥抗肿瘤作用。本研究以HCT-116、H460、HepG2、MCF-7、A549、SJSA-1六种野生型p53肿瘤细胞系为研究对象,采用噻唑蓝(methyl th... Nutlin-3是代表性小分子MDM2-p53拮抗剂,能通过破坏p53和MDM2的相互作用,稳定p53状态,从而诱导p53信号通路发挥抗肿瘤作用。本研究以HCT-116、H460、HepG2、MCF-7、A549、SJSA-1六种野生型p53肿瘤细胞系为研究对象,采用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法、平板克隆实验检测nutlin-3对6种不同野生型p53癌细胞增殖的影响;通过流式细胞术检测nutlin-3对H460细胞周期和细胞凋亡的影响;通过蛋白印迹实验检测泛素特异蛋白酶7(ubiquitin-specific protease 7,USP7)、细胞死亡结构域相关蛋白(death domain-associated protein,DAXX)、鼠双微体2(murine double minute 2,MDM2)、鼠双微体4(murine double minute 4,MDMX/MDM4)、p53的表达,探讨nutlin-3的抗肿瘤作用机制;通过免疫共沉淀(co-immunoprecipitation,Co-IP)实验检测nutlin-3对MDM2与MDMX、p53相互作用的影响。结果显示,nutlin-3呈时间和浓度依赖性地抑制H460的增殖;细胞周期和凋亡结果显示,nutlin-3能阻滞H460细胞周期于G0/G1期,通过激活cleaved-PARP并诱导细胞凋亡;蛋白印迹结果显示,nutlin-3能够上调H460细胞中USP7、DAXX、MDM2、MDMX、p53蛋白的表达;Co-IP结果表明,nutlin-3抑制MDM2与p53、MDM2与MDMX的蛋白相互作用。综上所述,nutlin-3能够显著抑制野生型p53癌细胞的增殖,并诱导细胞周期阻滞和细胞凋亡,其机制可能与破坏MDM2/MDMX与p53相互作用,从而激活MDM2-p53信号通路有关。 展开更多
关键词 nutlin-3 mdm2-p53抑制剂 mdm2 野生型P53 抗肿瘤
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Improved methods,properties,applications and prospects of microbial induced carbonate precipitation(MICP)treated soil:A review 被引量:2
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作者 Xuanshuo Zhang Hongyu Wang +3 位作者 Ya Wang Jinghui Wang Jing Cao Gang Zhang 《Biogeotechnics》 2025年第1期34-54,共21页
Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vi... Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vironment and intensify carbon emissions.However,the use of microbially induced calcium carbonate pre-cipitation(MICP)to obtain bio-cement is a novel technique with the potential to induce soil stability,providing a low-carbon,environment-friendly,and sustainable integrated solution for some geotechnical engineering pro-blems in the environment.This paper presents a comprehensive review of the latest progress in soil improvement based on the MICP strategy.It systematically summarizes and overviews the mineralization mechanism,influ-encing factors,improved methods,engineering characteristics,and current field application status of the MICP.Additionally,it also explores the limitations and correspondingly proposes prospective applications via the MICP approach for soil improvement.This review indicates that the utilization of different environmental calcium-based wastes in MICP and combination of materials and MICP are conducive to meeting engineering and market demand.Furthermore,we recommend and encourage global collaborative study and practice with a view to commercializing MICP technique in the future.The current review purports to provide insights for engineers and interdisciplinary researchers,and guidance for future engineering applications. 展开更多
关键词 Soil improvement Bio-cement MICP Improved methods Field application cases
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一种基于Least Square Method算法的城轨车辆车门动作时间精准判断的研究
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作者 李宏菱 宋华杰 +3 位作者 马仲智 周辉 李晴 陈龙 《时代汽车》 2025年第3期190-192,共3页
为研究城市轨道交通车辆客室车门动作时间精准性,门的动作主要依靠直流无刷电机的驱动,所以门动作判断的根本,是对电机运动状态的判读,门运动过程中由于电机码盘线受杂波干扰,系统无法准确寻找计时点从而影响系统判断门运动时间;建立波... 为研究城市轨道交通车辆客室车门动作时间精准性,门的动作主要依靠直流无刷电机的驱动,所以门动作判断的根本,是对电机运动状态的判读,门运动过程中由于电机码盘线受杂波干扰,系统无法准确寻找计时点从而影响系统判断门运动时间;建立波形矫正模型,利用数学方法校准波形,让MCU找出最佳计时点并处理(误差不超过10ms),采用最小二乘法模型,通过最小化误差的平方和找到一组数据的最佳函数匹配,求得未知的数据,并使得这些求得的数据与实际数据之间误差的平方和为最小,可精准地得到门动作时间。模拟测试结果表明,门动作时间测算误差所示其误差为7.42ms,小于10ms。 展开更多
关键词 城轨车辆 客室车门 电机码盘 Least Square method算法 门动作时间精准
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Research on Bearing Fault Diagnosis Method Based on Deep Learning 被引量:1
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作者 Ting Zheng 《Journal of Electronic Research and Application》 2025年第1期1-6,共6页
Bearing is an indispensable key component in mechanical equipment,and its working state is directly related to the stability and safety of the whole equipment.In recent years,with the rapid development of artificial i... Bearing is an indispensable key component in mechanical equipment,and its working state is directly related to the stability and safety of the whole equipment.In recent years,with the rapid development of artificial intelligence technology,especially the breakthrough of deep learning technology,it provides a new idea for bearing fault diagnosis.Deep learning can automatically learn features from a large amount of data,has a strong nonlinear modeling ability,and can effectively solve the problems existing in traditional methods.Aiming at the key problems in bearing fault diagnosis,this paper studies the fault diagnosis method based on deep learning,which not only provides a new solution for bearing fault diagnosis but also provides a reference for the application of deep learning in other mechanical fault diagnosis fields. 展开更多
关键词 Deep learning Bearing failure Diagnostic methods
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胃腺癌中SPIN1、E2F1、MDM2的表达及临床意义
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作者 吕蓓蓓 李加美 +1 位作者 李佳 姚志刚 《临床与实验病理学杂志》 北大核心 2025年第8期1082-1088,共7页
目的探讨胃腺癌中SPIN1、E2F1、MDM2的表达及相关性,并分析其与临床病理特征及预后的关系。方法收集174例原发胃腺癌及43例癌旁正常胃黏膜组织蜡块,制作组织芯片,应用免疫组化法检测SPIN1、E2F1及MDM2在胃腺癌及正常胃黏膜组织中的表达... 目的探讨胃腺癌中SPIN1、E2F1、MDM2的表达及相关性,并分析其与临床病理特征及预后的关系。方法收集174例原发胃腺癌及43例癌旁正常胃黏膜组织蜡块,制作组织芯片,应用免疫组化法检测SPIN1、E2F1及MDM2在胃腺癌及正常胃黏膜组织中的表达,并进一步分析三者与临床病理特征的相关性。采用Kaplan-Meier进行生存分析,运用Spearman相关性分析评估三者间两两的相关性。结果174例胃腺癌组织中SPIN1、E2F1、MDM2的阳性率为70.7%、66.7%、35.1%,均明显高于癌旁正常胃黏膜组织(7.0%、16.3%、7.0%)(P均<0.001)。SPIN1表达与胃癌分化程度、TNM分期及淋巴结转移呈正相关(P<0.05);E2F1表达与胃癌患者性别及淋巴结转移有相关性(P<0.05);MDM2表达与胃癌临床病理特征均无明显相关性。生存分析显示:SPIN1、E2F1高表达组患者的预后较低表达组差;MDM2表达与预后无明显相关性。Spearman相关性分析显示:SPIN1与E2F1(r=0.3276),SPIN1与MDM2(r=0.2961)表达呈正相关(P<0.001),E2F1与MDM2表达无明显相关性。结论SPIN1和E2F1可作为胃腺癌转移及预后评估的分子标志物,评估胃腺癌患者SPIN1、E2F1的表达水平有助于精确分层及精准治疗。 展开更多
关键词 胃肿瘤 腺癌 E2F1 SPIN1 mdm2
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A dual⁃parameter method for seismic resilience assessment of buildings 被引量:1
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作者 LI Shuang HU Binbin +1 位作者 LIU Wen ZHAI Changhai 《Journal of Southeast University(English Edition)》 2025年第1期1-11,共11页
To quantify the seismic resilience of buildings,a method for evaluating functional loss from the component level to the overall building is proposed,and the dual-parameter seismic resilience assessment method based on... To quantify the seismic resilience of buildings,a method for evaluating functional loss from the component level to the overall building is proposed,and the dual-parameter seismic resilience assessment method based on postearthquake loss and recovery time is improved.A threelevel function tree model is established,which can consider the dynamic changes in weight coefficients of different category of components relative to their functional losses.Bayesian networks are utilized to quantify the impact of weather conditions,construction technology levels,and worker skill levels on component repair time.A method for determining the real-time functional recovery curve of buildings based on the component repair process is proposed.Taking a three-story teaching building as an example,the seismic resilience indices under basic earthquakes and rare earthquakes are calculated.The results show that the seismic resilience grade of the teaching building is comprehensively judged as GradeⅢ,and its resilience grade is more significantly affected by postearthquake loss.The proposed method can be used to predict the seismic resilience of buildings prior to earthquakes,identify weak components within buildings,and provide guidance for taking measures to enhance the seismic resilience of buildings. 展开更多
关键词 seismic resilience assessment dual-parameter method functional loss recovery time Bayesian networks
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A Review of the Hydrodynamic Damping Characteristics of Blade-like Structures:Focus on the Quantitative Identification Methods and Key Influencing Parameters 被引量:1
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作者 Yongshun Zeng Zhaohui Qian +1 位作者 Jiayun Zhang Zhifeng Yao 《哈尔滨工程大学学报(英文版)》 2025年第1期21-34,共14页
Ocean energy has progressively gained considerable interest due to its sufficient potential to meet the world’s energy demand,and the blade is the core component in electricity generation from the ocean current.Howev... Ocean energy has progressively gained considerable interest due to its sufficient potential to meet the world’s energy demand,and the blade is the core component in electricity generation from the ocean current.However,the widened hydraulic excitation frequency may satisfy the blade resonance due to the time variation in the velocity and angle of attack of the ocean current,even resulting in blade fatigue and destructively interfering with grid stability.A key parameter that determines the resonance amplitude of the blade is the hydrodynamic damping ratio(HDR).However,HDR is difficult to obtain due to the complex fluid-structure interaction(FSI).Therefore,a literature review was conducted on the hydrodynamic damping characteristics of blade-like structures.The experimental and simulation methods used to identify and obtain the HDR quantitatively were described,placing emphasis on the experimental processes and simulation setups.Moreover,the accuracy and efficiency of different simulation methods were compared,and the modal work approach was recommended.The effects of key typical parameters,including flow velocity,angle of attack,gap,rotational speed,and cavitation,on the HDR were then summarized,and the suggestions on operating conditions were presented from the perspective of increasing the HDR.Subsequently,considering multiple flow parameters,several theoretical derivations and semi-empirical prediction formulas for HDR were introduced,and the accuracy and application were discussed.Based on the shortcomings of the existing research,the direction of future research was finally determined.The current work offers a clear understanding of the HDR of blade-like structures,which could improve the evaluation accuracy of flow-induced vibration in the design stage. 展开更多
关键词 Blade fatigue Hydrodynamic damping ratio Identification method Affecting factors Prediction formula
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Formation mechanism of herpetrione self-assembled nanoparticles based on p H-driven method 被引量:1
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作者 Yuwen Zhu Xiang Deng +4 位作者 Yan Wu Baode Shen Lingyu Hang Yuye Xue Hailong Yuan 《Chinese Chemical Letters》 2025年第1期387-391,共5页
The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method... The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall.,and the SAN exhibited uniform particle size and demonstrated good stability.In this paper,we analyzed the interactions between the main active compound,herpetrione(Her),and its main carrier,Herpetospermum caudigerum Wall.polysaccharide(HCWP),along with their self-assembly mechanisms under different p H values.The binding constants of Her and HCWP increase with rising p H,leading to the formation of Her-HCWP SAN with a smaller particle size,higher zeta potential,and improved thermal stability.While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising p H,the hydrophobic force consistently plays a dominant role.This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by p H driven method. 展开更多
关键词 Traditional Chinese medicine NANOPARTICLES Herpetrione Interaction pH-driven method Self-assembly Isothermal titration calorimetry
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Estimation of Chloride Diffusivity in Hydrated Tricalcium Silicate Using a Hydration-Diffusion Integrated Method
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作者 WANG Xin SHEN Dejian +2 位作者 TAO Sijie LIU Ruixin WU Shengxing 《Journal of Wuhan University of Technology(Materials Science)》 SCIE EI CAS 2025年第1期49-64,共16页
This study aims to develop a chloride diffusion simulation method that considers the hydration microstructure and pore solution properties during the hydration of tricalcium silicate(C3S).The method combines the hydra... This study aims to develop a chloride diffusion simulation method that considers the hydration microstructure and pore solution properties during the hydration of tricalcium silicate(C3S).The method combines the hydration simulation,thermodynamic calculation,and finite element analysis to examine the effects of pore solution,including effect of electrochemical potential,effect of chemical activity,and effect of mechanical interactions between ions,on the chloride effective diffusion coefficient of hydrated C3S paste.The results indicate that the effect of electrochemical potential on chloride diffusion becomes stronger with increasing hydration age due to the increase in the content of hydrated calcium silicate;as the hydration age increases,the effect of chemical activity on chloride diffusion weakens when the number of diffusible elements decreases;the effect of mechanical interactions between ions on chloride diffusion decreases with the increase of hydration age. 展开更多
关键词 tricalcium silicate simulation method chloride diffusion coefficient pore solution
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