Atherosclerosis (AS) is the leading cause of death for humans worldwide, and some circular RNAs (circRNAs) have been demonstrated to play important roles in its progression. In this study, we mainly ...investigated the functions and molecular mechanisms of circRNA-PTPRA (circPTPRA) in AS.
The expressions of circPTPRA and miR-636 were detected in serum samples of AS patients (n=30) and healthy controls (n=30) by RT-PCR. Then levels of circPTPRA were detected after ox-LDL treatment into vascular smooth muscle cell (VSMCs), macrophage and endothelial cells. LV-sh circPTPRAs were constructed and infected into VSMCs. CCK-8 assay was performed to measure cell proliferation abilities, flow cytometry (FACS) was performed to measure cell-cycle distribution and TUNEL staining was performed to detect cell apoptosis. Western blot (WB) was performed to detect protein levels of SP1, Cyclin D1, Cyclin E, Bax, Bad, Cleaved Caspase3. Luciferase reporter assay was performed to verify the potential binding sites of circPTPRA and miR-636, miR-636 and SP1.
RT-PCR showed that circPTPRA was upregulated in serum samples of AS patients, which was increased by ox-LDL in VSMCs. CircPTPRA inhibition repressed cell proliferation, improved cell-cycle distribution in G0/G1 phase and promoted cell apoptosis. MiR-636, a potential target for circPTPRA, was reduced in serum samples of AS patients and Luciferase reporter assay confirmed that circPTPRA could directly sponge with miR-636 in VSMCs. Furthermore, miR-636 inhibition promoted proliferation and repressed apoptosis of VSMCs, while miR-636 overexpression reversed these results. SP1, a transcription factor that played some roles in the progression of AS, was predicted to be a target of miR-636. MiR-636 inhibition increased SP1 while miR-636 overexpression repressed SP1 expression, Luciferase reporter assay proved that miR-636 could target at SP1 in VSMCs. Moreover, the repressed cell proliferation and promoted cell apoptosis abilities in LV-sh SP1 were reversed following with miR-636 inhibitor transfection. In addition, the repressed cell proliferation and promoted cell apoptosis abilities in VSMCs with LV-sh circPTPRAs were reversed following with miR-636 inhibitor transfection, which suggested that circPTPRA regulated cell proliferation and apoptosis through miR-636/SP1 axis in AS.
According to the results, we found that circPTPRA was upregulated in serum samples of AS patients, which promoted cell proliferation and inhibited cell apoptosis through repressing miR-636 and upregulating SP1 signaling axis. Our results uncovered a potential role of circPTPRA, which might be a marker and therapeutic target for AS patients.
A second-order phase transition in a physical system is associated with the emergence of an "order parameter" and a spontaneous symmetry breaking. The heavy fermion superconductor URu2Si2 has a ..."hidden order" (HO) phase below the temperature of 17.5 kelvin; the symmetry of the associated order parameter has remained ambiguous. Here we use polarization-resolved Raman spectroscopy to specify the symmetry of the low-energy excitations above and below the HO transition. We determine that the HO parameter breaks local vertical and diagonal reflection symmetries at the uranium sites, resulting in crystal field states with distinct chiral properties, which order to a commensurate chirality density wave ground state.
This paper investigates the effect of in-plane forces on the vibration behavior of carbon nanotube (CNT) reinforced composite skew plates. The analysis is performed by implementing the first-order ...shear deformation theory (FSDT) with the element-free/mesh-free Improved Moving Least Square-Ritz (IMLS-Ritz) method for solution to the problem. Two varieties of carbon nanotube-reinforced composite skew plates, namely uniformly distributed and functionally graded reinforcement are considered. A micromechanical model is employed to estimate the material properties of CNT-reinforced composite plates. Comparison studies are implemented to validate the accuracy of the proposed method. The frequency parameters and mode shapes for the skew plates are presented. A detailed parametric study is carried out to reveal many complicated effect on the frequency parameters of the plate. These effects include in-plane stress ratio, boundary conditions, CNT-volume fraction and geometric size. The obtained results will be references of future research and corresponding engineering project.
Batch and semi-continuous experiments were carried out to determine the effect of pH on hydrolysis and acidogenesis of kitchen wastes in the two-phase anaerobic digestion. The results of the batch ...experiment showed pH adjustment could improve both hydrolysis and acidogenesis rates of kitchen wastes. Compared with pH at 5, 9 and 11, pH 7 provided an optimum working condition for anaerobic digestion of kitchen wastes. At pH 7, about 86% of the total organic carbon (TOC) and 82% of chemical oxygen demand (COD) were solubilized and the maximum volatile fatty acid (VFA) concentration of 36g l
−1
was achieved on the fourth day. The total VFA yield was 0.27 g (g total solid (TS))
−1
, which almost doubled the yield without pH adjustment (0.15 g (g TS)
−1
). The acidified products with lower concentration of lactic acid were more favorable to the subsequent methanogenesis. At pH 7, most of the protein was degraded into ammonia nitrogen (NH
4
+
-N), resulting in additional buffer of acidified liquid. According to this, a novel method of pH adjustment applying NH
4
+
-N buffer was established. The semi-continuous experiment indicated that adjusting pH to 7 in the acidogenic stage in the two-phase anaerobic digestion process would increase both TS loading rate (16g l
−1
d
−1
) and recovery of biological energy (520 ml methane (CH
4
) (g TS)
−1
).
Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in ...behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1
knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1
mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1
mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.
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