Background:
Metabolic disorder increases the risk of abdominal aortic aneurysm (AAA). NRs (nuclear receptors) have been increasingly recognized as important regulators of cell metabolism. However, the role of NRs in AAA development remains largely unknown.
Methods:
We analyzed the expression profile of the NR superfamily in AAA tissues and identified NR1D1 (NR subfamily 1 group D member 1) as the most highly upregulated NR in AAA tissues. To examine the role of NR1D1 in AAA formation, we used vascular smooth muscle cell (VSMC)–specific, endothelial cell–specific, and myeloid cell–specific conditional
Nr1d1
knockout mice in both AngII (angiotensin II)– and CaPO
4
-induced AAA models.
Results:
Nr1d1
gene expression exhibited the highest fold change among all 49 NRs in AAA tissues, and NR1D1 protein was upregulated in both human and murine VSMCs from AAA tissues. The knockout of
Nr1d1
in VSMCs but not endothelial cells and myeloid cells inhibited AAA formation in both AngII- and CaPO
4
-induced AAA models. Mechanistic studies identified ACO2 (aconitase-2), a key enzyme of the mitochondrial tricarboxylic acid cycle, as a direct target trans-repressed by NR1D1 that mediated the regulatory effects of NR1D1 on mitochondrial metabolism. NR1D1 deficiency restored the ACO2 dysregulation and mitochondrial dysfunction at the early stage of AngII infusion before AAA formation. Supplementation with αKG (α-ketoglutarate, a downstream metabolite of ACO2) was beneficial in preventing and treating AAA in mice in a manner that required NR1D1 in VSMCs.
Conclusions:
Our data define a previously unrecognized role of nuclear receptor NR1D1 in AAA pathogenesis and an undescribed NR1D1-ACO2 axis involved in regulating mitochondrial metabolism in VSMCs. It is important that our findings suggest αKG supplementation as an effective therapeutic approach for AAA treatment.
We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios
Microfiltration is widely used in fine filtration operations, with dead-end filtration and cross-flow filtration. The microfiltration filter element or the microfiltration membrane is easy to be polluted by impurities in the water and causes fouling, resulting in flux attenuation. The flux can be expressed by Darcy's law and attenuation model. In this paper, two industrial titanium rod sintered filter elements (Ø60 × 960 mm and Ø60 × 960 mm) of different specifications are selected, and tap water (1.0 NTU) is used for constant pressure dead-end filtration. The amount tends to be the same, about 0.435 m 3 •m −2 •h −1 , which has nothing to do with the filtration accuracy of the filter element but only depends on the characteristics of the filter cake and the filter membrane. Through the analysis of the two models, it is found that the two filtration flux models are not universal and difficult to be applied in engineering.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.