背景:E1A结合蛋白300(E1A Binding Protein 300,EP300)作为一种多功能组蛋白乙酰转移酶,广泛参与基因表达调控、细胞生长及分化等生物学过程,并与多种炎症及免疫相关疾病相关,但它在过敏性鼻炎发病中的具体功能尚不明确。目的:探究过敏...背景:E1A结合蛋白300(E1A Binding Protein 300,EP300)作为一种多功能组蛋白乙酰转移酶,广泛参与基因表达调控、细胞生长及分化等生物学过程,并与多种炎症及免疫相关疾病相关,但它在过敏性鼻炎发病中的具体功能尚不明确。目的:探究过敏性鼻炎相关基因表达变化,分析其与程序性细胞死亡的关联,寻找潜在生物标志物和治疗靶点。方法:①从GSE51392、GSE43523和GSE206149数据集中收集过敏性鼻炎患者和对照组的基因表达数据,筛选差异表达基因并进行WGCNA分析。②于2022年3月至2024年5月从新疆医科大学第五附属医院收集10例进行翼管神经切断术治疗的过敏性鼻炎患者和10例健康对照者,采集患者术前术后血液和鼻腔黏膜组织样本。③构建大鼠过敏性鼻炎模型并敲降EP300,并将大鼠分为对照组、模型组、模型+shEP300-NC组、模型+shEP300组。通过ELISA、苏木精-伊红染色、RT-qPCR和Western blot技术分别检测血清炎症因子水平、鼻黏膜组织病理变化及相关基因和蛋白表达。结果与结论:①过敏性鼻炎和对照之间鉴定出43个交集基因;WGCNA发现Green模块与过敏性鼻炎相关性强,通过与程序性细胞死亡相关基因和共同差异表达基因进行交集分析得到关键基因EP300。②与术前相比,过敏性鼻炎患者术后血清白细胞介素4、白细胞介素5、白细胞介素13水平及鼻黏膜组织EP300、LC3B、Beclin1、cleaved-Caspase的表达显著降低,鼻黏膜组织p62、Bcl2的表达显著升高。③与对照组比较,模型组大鼠血清白细胞介素4、白细胞介素5、白细胞介素13水平及鼻黏膜组织EP300、LC3B、Beclin1、cleaved-Caspase的表达显著升高,鼻黏膜组织p62、Bcl2的表达显著降低;与模型组比较,模型+shEP300组大鼠上述指标均呈现相反变化。④结论:EP300可通过调控炎症、自噬与凋亡参与过敏性鼻炎的发生发展过程。展开更多
Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely us...Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely used in fields such as injection molding,die casting,and stamping dies.Adding reinforcing particles into steel is an effective means to improve its performance.Nb/18Ni300 composites were fabricated by LPBF using two kinds of Nb powders with different particle sizes,and their microstructures and properties were studied.The results show that the unmelted Nb particles are uniformly distributed in the 18Ni300 matrix and the grains are refined,which is particularly pronounced with fine Nb particles.In addition,element diffusion occurs between the particles and the matrix.The main phases of the base alloy are α-Fe and a small amount of γ-Fe.With the addition of Nb,part of the α-Fe is transformed into γ-Fe,and unmelted Nb phases appear.The addition of Nb also enhances the hardness and wear resistance of the composites but slightly reduces their tensile properties.After aging treatment,the molten pools and grain boundaries become blurred,grains are further refined,and the interfaces around the particles are thinned.The aging treatment also promotes the formation of reverted austenite.The hardness,ultimate tensile strength,and volumetric wear rate of the base alloy reach 51.9 HRC,1704 MPa,and 17.8×10^(-6) mm^(3)/(N·m),respectively.In contrast,the sample added with fine Nb particles has the highest hardness(56.1 HRC),ultimate tensile strength(1892 MPa)and yield strength(1842 MPa),and the volume wear rate of the sample added with coarse Nb particles is reduced by 90%to 1.7×10^(-6) mm^(3)/(N·m).展开更多
文摘背景:E1A结合蛋白300(E1A Binding Protein 300,EP300)作为一种多功能组蛋白乙酰转移酶,广泛参与基因表达调控、细胞生长及分化等生物学过程,并与多种炎症及免疫相关疾病相关,但它在过敏性鼻炎发病中的具体功能尚不明确。目的:探究过敏性鼻炎相关基因表达变化,分析其与程序性细胞死亡的关联,寻找潜在生物标志物和治疗靶点。方法:①从GSE51392、GSE43523和GSE206149数据集中收集过敏性鼻炎患者和对照组的基因表达数据,筛选差异表达基因并进行WGCNA分析。②于2022年3月至2024年5月从新疆医科大学第五附属医院收集10例进行翼管神经切断术治疗的过敏性鼻炎患者和10例健康对照者,采集患者术前术后血液和鼻腔黏膜组织样本。③构建大鼠过敏性鼻炎模型并敲降EP300,并将大鼠分为对照组、模型组、模型+shEP300-NC组、模型+shEP300组。通过ELISA、苏木精-伊红染色、RT-qPCR和Western blot技术分别检测血清炎症因子水平、鼻黏膜组织病理变化及相关基因和蛋白表达。结果与结论:①过敏性鼻炎和对照之间鉴定出43个交集基因;WGCNA发现Green模块与过敏性鼻炎相关性强,通过与程序性细胞死亡相关基因和共同差异表达基因进行交集分析得到关键基因EP300。②与术前相比,过敏性鼻炎患者术后血清白细胞介素4、白细胞介素5、白细胞介素13水平及鼻黏膜组织EP300、LC3B、Beclin1、cleaved-Caspase的表达显著降低,鼻黏膜组织p62、Bcl2的表达显著升高。③与对照组比较,模型组大鼠血清白细胞介素4、白细胞介素5、白细胞介素13水平及鼻黏膜组织EP300、LC3B、Beclin1、cleaved-Caspase的表达显著升高,鼻黏膜组织p62、Bcl2的表达显著降低;与模型组比较,模型+shEP300组大鼠上述指标均呈现相反变化。④结论:EP300可通过调控炎症、自噬与凋亡参与过敏性鼻炎的发生发展过程。
基金Key-Area Research and Development Program of Guangdong Province(2023B0909020004)Project of Innovation Research Team in Zhongshan(CXTD2023006)+1 种基金Natural Science Foundation of Guangdong Province(2023A1515011573)Zhongshan Social Welfare Science and Technology Research Project(2024B2022)。
文摘Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely used in fields such as injection molding,die casting,and stamping dies.Adding reinforcing particles into steel is an effective means to improve its performance.Nb/18Ni300 composites were fabricated by LPBF using two kinds of Nb powders with different particle sizes,and their microstructures and properties were studied.The results show that the unmelted Nb particles are uniformly distributed in the 18Ni300 matrix and the grains are refined,which is particularly pronounced with fine Nb particles.In addition,element diffusion occurs between the particles and the matrix.The main phases of the base alloy are α-Fe and a small amount of γ-Fe.With the addition of Nb,part of the α-Fe is transformed into γ-Fe,and unmelted Nb phases appear.The addition of Nb also enhances the hardness and wear resistance of the composites but slightly reduces their tensile properties.After aging treatment,the molten pools and grain boundaries become blurred,grains are further refined,and the interfaces around the particles are thinned.The aging treatment also promotes the formation of reverted austenite.The hardness,ultimate tensile strength,and volumetric wear rate of the base alloy reach 51.9 HRC,1704 MPa,and 17.8×10^(-6) mm^(3)/(N·m),respectively.In contrast,the sample added with fine Nb particles has the highest hardness(56.1 HRC),ultimate tensile strength(1892 MPa)and yield strength(1842 MPa),and the volume wear rate of the sample added with coarse Nb particles is reduced by 90%to 1.7×10^(-6) mm^(3)/(N·m).
