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Guglielmina Chimienti Anna Picca Flavio Fracasso Francesco Russo Antonella Orlando Giuseppe Riezzo Christiaan Leeuwenburgh Vito Pesce Angela Maria Serena Lezza 《International journal of molecular sciences》2021,22(4)
Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement. 相似文献
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对激光选区熔化(Selective laser melting,SLM)成形马氏体时效钢进行固溶及500 ℃时效不同时间的热处理,分析时效时间对其组织性能的影响。结果表明:SLM 18Ni300钢经固溶+时效处理后,其组织为马氏体、逆转变奥氏体和Ni3(Mo, Ti)析出相,随时效时间增加,析出相数量逐渐增加并聚集长大,同时逆转变奥氏体含量增大。随时效时间的增加,其硬度和强度逐渐增加达到峰值后下降,而伸长率不断增加。SLM 18Ni300钢的最佳时效工艺为500 ℃×4 h。 相似文献
4.
对航天用紧固件TC4钛合金棒材进行固溶时效处理,对棒材不同位置进行显微组织观察、硬度和室温拉伸性能检测。结果表明:TC4钛合金棒材经固溶时效后表面至心部的组织与性能受冷却速度的影响呈现显著差异。固溶时效后的显微组织由稳定的等轴α相、弥散的马氏体α′相和亚稳定β相组成,试样端面上因冷却速度相差不大,次生α相的形态和含量没有明显差异;中部截面上边部至心部的次生α相含量逐渐增多,同时次生α相片层厚度逐渐增大并趋于等轴化。端面上不同位置显微硬度值没有明显差异,但中部截面上由边部至心部的显微硬度值呈总体降低趋势,且中部截面上边部的显微硬度值与端面相差不大。试样心部因固溶过程中冷却缓慢,整体试样的室温拉伸性能明显低于去除心部的试样。 相似文献
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针对现有的广告点击率预估模型未能精准挖掘用户历史兴趣及历史兴趣对目标广告点击与否的影响,提出了一种基于改进Transformer的广告点击率预估模型.该模型采用Transformer网络捕捉隐藏在用户点击序列背后的潜在历史兴趣;同时针对Transformer建模用户历史兴趣无法有效关联目标广告的问题,提出了一种改进的Transformer网络.改进后的Transformer不但有效建模用户历史兴趣,而且考虑了跟目标广告的关联.新模型采用辅助损失函数来监督改进的Transformer对用户历史兴趣的抽取过程,然后采用注意力机制进一步建模用户的历史兴趣和目标广告的相关性以提升模型的预估性能.实验结果表明新模型有效提升了广告点击率的预估效果. 相似文献
6.
以玉米淀粉为原料,用流变分析、食品物性分析、差示扫描量热分析、低场核磁共振成像分析等研究冷藏过程中不同含量(相对玉米淀粉干基质量的1%、3%、5%和7%)皂荚糖胶对玉米淀粉老化特性的影响。动态流变时间扫描结果表明:随着老化时间的延长,玉米淀粉的弹性模量增加,皂荚糖胶的加入使复配体系弹性模量的变化率减小,一定程度上抑制玉米淀粉的短期老化;凝胶强度实验表明:随着冷藏时间的延长,玉米淀粉凝胶体系的硬度值增加,皂荚糖胶的加入使玉米淀粉形成质地更柔软的凝胶,硬度值明显降低;差示扫描量热测定结果表明:随着皂荚糖胶含量的增加,复配体系的老化率逐渐减小。用低场核磁水分运动性实验方法,通过5%皂荚糖胶加入前后淀粉凝胶中自由水、结合水和不易流动水含量的对比证实该胶对凝胶的水分分布有较大的影响;该研究能进一步丰富植物胶体对淀粉老化性能影响的理论。 相似文献
7.
Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9
LIUCHENG WU YI WANG LILI DU GUIQING JI RUI ZHOU ZEYI ZHAO JUN CHEN SHUNXING ZHU 《Biocell》2021,45(6):1501-1507
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value. 相似文献
8.
Marc De Doncker Chloé De Graeve Dr. Jorick Franceus Dr. Koen Beerens Prof. Vladimír Křen Dr. Helena Pelantová Dr. Ronny Vercauteren Prof. Dr. Tom Desmet 《Chembiochem : a European journal of chemical biology》2021,22(23):3319-3325
The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis. 相似文献
9.
为了进一步提高Fe-15Mn-4.5Si-10Cr-5Ni系形状记忆合金的形状记忆效应,利用OM、TEM及物理相分析等试验方法,研究了直接时效及固溶+时效热处理工艺对试验合金微观组织、第二相析出及形状记忆效应的影响。结果表明,试验合金经固溶处理后,因第二相粒子大幅度回溶,导致试验合金形状记忆性能下降较为明显;同时,因直接时效处理较固溶+时效处理显著提高了试验合金中Cr碳化物第二相析出量,使试验合金形状记忆性能大幅度提升。其中,试验合金在800 ℃直接时效可获得最佳形状回复率。 相似文献
10.
随着神东煤炭老龄化速度加快退休人员数量增加,如何将退休人员管理服务方式由企业转向社会化管理服务,是神东煤炭近两年国企改革工作的重点。本文回顾了神东煤炭集团退休人员社会化管理工作探索和实践过程,以及期间存在的工作量大、缺失党员资料补齐难、档案接收标准高等问题。按照各地政策,神东煤炭提出了先易后难的移交对策;2020年12月底,基本完成了存量退休人员社会化管理移交工作,包括完成了存量退休人员管理职能、人事档案移交,完成了属地党员组织关系转接。企业、政府及退休人员三方均得到受益。 相似文献