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71.
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10−6). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.  相似文献   
72.
Nickel (Ni2+) is one of the most common allergens, affecting around 10–15% of the general population. As the demand for orthopedic implant surgery rises, the number of surgical revisions due to joint implant failure also increases. There is evidence that some patients develop joint failure due to an immune response to a component of the implant, and we have found that Ni2+ is an especially important cause. Hence, understanding the mechanisms by which Ni2+ allergy induces joint implant failure becomes a critical research question. The structural basis of Ni2+ activation of pathogenic T cells is still not clear. The purpose of this study was to characterize Ni2+-reactive T cell repertoires derived from the peripheral blood of joint failure patients due to Ni2+ sensitization using single-cell sequencing techniques. We stimulated the proliferation of Ni2+ -reactive T cells from two implant failure patients in vitro, and sorted them for single-cell VDJ sequencing (10× genomics). We identified 2650 productive V-J spanning pairs. Both TCR α chains and β chains were enriched. TRBV18 usage is the highest in the P7 CD4+ population (18.1%), and TRBV5-1 usage is the highest in the P7 CD8+ population (12.1%). TRBV19 and TRBV20-1 segments are present in a high percentage of both P7 and P9 sequenced T cells. Remarkably, the alpha and beta chain combination of TRAV41-TRBV18 accounts for 13.5% of the CD4+ population of P7 patient. Compared to current Ni specific T cell repertoire studies of contact dermatitis, the Vα and Vβ usages of these joint implant failure patients were different. This could be due to the different availability of self-peptides in these two different tissues. However, TRBV19 (Vβ17) was among frequently used TCR β chains, which are common in previous reports. This implies that some pathogenic T cells could be similar in Ni2+ hypersensitivities in skin and joints. The alignment of the TCR CDR3β sequences showed a conserved glutamic acid (Glu) that could potentially interact with Ni2+. The study of these Ni2+ specific TCRs may shed light on the molecular mechanism of T cell activation by low molecular weight chemical haptens.  相似文献   
73.
Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient’s selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.  相似文献   
74.
A 3D architecture carbon fiber preform, specifically fine-woven cloth and punctured felt preform, is used to manufacture a novel advanced Cf/C-SiC-ZrC composite. The composite matrix is produced by chemical vapor infiltration (CVI) plus precursor infiltration and pyrolysis (PIP) process and finalized by using a chemical vapor deposition (CVD) of SiC coating to make the final density of the material reach 1.95 g/cm3. The organic precursors of SiC and ZrC have a weight ratio of 4:1 in a xylene solute. The composite mechanical properties, such as tensile, compression, bending, shear, and Z-direction load bearing, are introduced under analysis to find possible applications for the composite. What is more, scanning electron microscope (SEM) images are employed to illustrate the failure behavior of the ceramic composite. The results showed that the punctured filament tows will be beneficial, not only for the composite to withstand compression force up to 308.6 MPa and shear strength to 18.14 MPa but also for the alternatively stacked weave piles and short fiber layers to support the punctured bundles, as well as to hold the composite structure under mechanical forces from different orientations, which is believed to reinforce the ceramic matrix for some high pressure and severe ablation applications.  相似文献   
75.
为研究冲击速度和热处理温度对黑云母花岗岩动态力学特性的影响,利用改进的霍普金森压杆系统对25~800 ℃共9个温度等级的热处理试样分别进行3种弹速下的冲击压缩试验。试验结果表明:随着冲击速度的增加,25~700 ℃热处理试样的应力—应变曲线由“Ⅱ型”转变为“Ⅰ型”,而800 ℃热处理试样均表现出“Ⅰ型”应力—应变曲线特征。同一温度热处理下试块的峰值应力、应变和平均应变均随动荷载的升高而增大。相同的冲击速度下,300 ℃热处理试样的动力学性能有所改善,500 ℃后试样的动力学性能开始逐渐劣化。同一温度热处理试样的破碎程度随冲击速度的增加而增加;相同冲击速度下,热处理试样的破碎程度随温度的升高先减弱后增强。  相似文献   
76.
制备了两种纳米TiN改性金属陶瓷可转位铣刀片ToolA和ToolB。研究了这两种新型面铣刀在切削正火态45#钢时的铣削性能及其失效机理。试验结果表明,两种试验铣刀片在Vc=294m/min,fz=0.16mm/z,ap=0.5mm条件下铣削45#钢时,均未发现“崩刃”现象,并全都以“磨损”的形式失效,刀具寿命较长。此外,在同样切削条件下,ToolA具有良好的抗氧化磨损性能,而ToolB有更高的耐机械冲击能力;高温扩散和氧化磨损成为导致纳米TiN改性铣刀片磨损失效的主要原因。  相似文献   
77.
张丽霞 《机床电器》2003,30(6):18-19
本文对数控机床故障现象进行了简要分析并列举维修实例。  相似文献   
78.
用化学成分分析、金相组织检验、硬度测试以及对刹车鼓的宏观和微观分析等方法,对刹车鼓刹车失灵进行分析,并探讨了刹车鼓失效的原因、失效形式以及对刹车鼓铸件质量控制。  相似文献   
79.
通过金相分析及断口观察,对GCr15钢轴承套圈的磨削开裂进行了系统分析。结果表明.淬火裂纹是套圈失效的根本原因,而原材料中Cr的带状偏析、套圈表面的应力集中、淬火加热时的氧化脱碳以及不当的磨削工序则共同加剧了淬火裂纹的萌生和扩展。  相似文献   
80.
周召贵 《大氮肥》2003,26(2):100-102
综述合成氨二段转化废热锅炉失效历程分析,废热锅炉列管穿孔、管板泄漏及水压试验泄漏的原因,提出解决对策。  相似文献   
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