LncRNA TUG1 Regulates Proliferation of Cardiac Fibroblast via the miR-29b-3p/TGF-ß1 Axis.

Background: Atrial fibrillation (AF) is a very common clinical arrhythmia, accompanied by the overproliferation of cardiac fibroblasts (CFs). This study aimed to investigate the role of the long non-coding RNA(lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation of CFs and further investigated its underlying mechanism. Methods: One hundred four paroxysmal AF patients and 94 healthy controls were recruited. Human cardiac fibroblasts (HCFs) were applied to establish an AF cell model through treatment with angiotensin II (AngII). qRT-PCR was used for the measurement of gene levels. The cell proliferation was detected by cell counting kit-8 (CCK-8). Luciferase reporter assay was performed for target gene analysis. Results: Elevated levels of TUG1 and low expression of miR-29b-3p were detected in the serum of AF patients compared with the healthy controls. Pearson's correlation analysis exhibited an inverse relationship between TUG1 and miR-29b-3p expression in AF patients (r = -7.106, p < 0.001). Knockdown of TUG1 inhibited AngII-induced CF proliferation. Taurine upregulated gene 1 (TUG1) functions as a competing endogenous RNA (ceRNA) for miR-29b-3p, and downregulation of miR-29b-3p reversed the role of TUG1 in CF proliferation. TGF-ß1 is a direct target gene of miR-29b-3p. Conclusions: Long non-coding RNA taurine upregulated gene 1 is a key regulator in the occurrence of AF. Slicing TUG1 inhibits CF proliferation by regulating the miR-29b-3p/TGF-ß1 axis.

Long non-coding RNA SENCR alleviates hypoxia/reoxygenation-induced cardiomyocyte apoptosis and inflammatory response by sponging miR-1.

BACKGROUND: Myocardial cell apoptosis is one of the main reasons for the occurrence of acute myocardial infarction (AMI). The role of smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA (SENCR) in the cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) injury and its potential mechanism were investigated in this study to provide a novel biomarker for the development of AMI. METHODS: The expression levels of SENCR in the serum of AMI patients and non-AMI patients with chest pain (control) were detected by qRT-PCR. The function of SENCR in the cardiomyocyte apoptosis and inflammatory response induced by H/R injury was evaluated by MTT, cell apoptosis, and ELISA assay, respectively. The mechanism underlying the function of SENCR was investigated with the luciferase reporter assay. RESULTS: SENCR was significantly downregulated in AMI compared with the control volunteers, which showed negative correlations with the cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) level of patients. The H/R injury-induced cell apoptosis and inflammatory response in cardiomyocytes, which were attenuated by the overexpression of SENCR. The expression of miR-1 was suppressed by the overexpression of SENCR, while the overexpression of miR-1 could alleviate the cell apoptosis, enhance cell viability, and attenuate inflammatory response in cardiomyocyte. SENCR reversed H/R-induced myocardial cell injury by regulating the expression of miR-1. CONCLUSIONS: SENCR was correlated with the clinicopathological features of patients and was revealed to alleviate the cardiomyocyte apoptosis and inflammatory response induced by H/R injury via sponging miR-1.

Mechanisms and microstructures of 2A97 Al-Li alloy under the hot forming with synchronous quenching process.

Aluminum-lithium alloy is regarded as the most promising light material in the aircraft and aerospace industries. For the production of complex and high-precision parts, the hot forming with synchronous quenching (HFSQ) process has become an effective and attractive forming method. In order to achieve the performance and microstructure evolution of the 2A97 Al-Li alloy under the HFSQ process, the specimens were subjected to solution treatment at 520°C and held at 90 min in the Gleeble 3,500 thermal simulator. Then the hot tensile test with simultaneous quenching was conducted directly at a temperature of 300-500°C and a strain rate of 0.1-0.001 s-1 with the same equipment. Through analyzing the macroscopic stress-strain curves and microscopic fractures, it was concluded that the optimal forming temperature was 450°C with the strain rate being 0.1 s-1 and its forming mechanism under the process was presented. To obtain the microstructure evolution of 2A97 Al-Li alloy under the HFSQ process, the material was subjected to constant strain tensile test with synchronous quenching and then treated with two-stage artificial aging 200°C and 6 hr + 165°C and 6 hr. The microstructure of the alloy was observed by means of electron backscattering diffraction (EBSD). And its evolution process and the influence of temperature, strain rate, and strain on the microstructure under the process were attained.

Experimental Investigation of the Blanked Surface of C5191 Phosphor Bronze Sheet over a Wide Range of Blanking Speeds.

The influence of blanking speed on the blanked surface quality of C5191 bronze phosphorus sheets, with a thickness of 0.12 mm, was systematically studied to demonstrate the mechanism under high speed blanking. The morphology and microstructure of the blanked edge were observed by using a variety of techniques, including optical microscopy (OM), scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and transmission electron microscope (TEM). The results revealed that the local temperature and microhardness of the shear zone increased with the increase in blanking speed. Moreover, the quality of blanked edge significantly improved with the increase in blanking speed due to the combined influence of strain rate hardening and thermal softening. In addition, the blanked edge grains were elongated along the blanking direction and formed dislocation cells and sub-grains in some areas. The blanked edge is dominated by {000} <100> cubic texture at higher blanking speeds, and {112} <111> texture at lower blanking speeds. When punched at an ultra-high speed of 3000 strokes per minute (SPM 3000), the local area of the blanked edge exhibited distinct microstructural features, including low dislocation density, nanocrystals with high-angle grain boundaries, and significant differences in grain orientation. Additionally, the selected area electron diffraction (SAED) pattern exhibited a discontinuous ring-like structure, indicating the occurrence of adiabatic shearing with dynamic recrystallization.

Effect of different temperatures on the metallographic structure and tensile property of 2024-T4 alloy in integral heating single point incremental forming.

To study the tensile property and metallographic structure evolution of 2024-T4 high-strength aluminum alloy in integral heating single point incremental forming (IHSPIF), the warm tensile tests were carried out at 120-240°C with the strain rates of 0.1-0.001 s-1 . Its results could provide a certain theoretical reference to the IHSPIF. The integral heating was different from the local heating, which was to heat the overall sheet to be deformed. It was found in the tensile tests that at the strain rate of 0.01 s-1 , the optimum forming temperature was determined to be 210°C at which the ductility was the best. The material dynamically recovered at 240°C. The following IHSPIF tests were conducted at different temperatures. By observing the organization of the sidewall of the square tapered parts, the alloy dynamically recovered appeared at 210°C and its grains coarsened at 240°C. Considering the temperature interval of 30 and below the recrystallizing temperature of aluminum alloy, it was concluded that the optimal temperature for the integral heating IHSPIF was about 150°C.

Proteomic comparison of Entamoeba histolytica and Entamoeba dispar and the role of E. histolytica alcohol dehydrogenase 3 in virulence.

The protozoan intestinal parasite Entamoeba histolytica infects millions of people worldwide and is capable of causing amebic dysentery and amebic liver abscess. The closely related species Entamoeba dispar colonizes many more individuals, but this organism does not induce disease. To identify molecular differences between these two organisms that may account for their differential ability to cause disease in humans, we used two-dimensional gel-based (DIGE) proteomic analysis to compare whole cell lysates of E. histolytica and E. dispar. We observed 141 spots expressed at a substantially (>5-fold) higher level in E. histolytica HM-1:IMSS than E. dispar and 189 spots showing the opposite pattern. Strikingly, 3 of 4 proteins consistently identified as different at a greater than 5-fold level between E. histolytica HM-1:IMSS and E. dispar were identical to proteins recently identified as differentially expressed between E. histolytica HM-1:IMSS and the reduced virulence strain E. histolytica Rahman. One of these was E. histolytica alcohol dehydrogenase 3 (EhADH3). We found that E. histolytica possesses a higher level of NADP-dependent alcohol dehydrogenase activity than E. dispar and that some EhADH3 can be localized to the surface of E. histolytica. Episomal overexpression of EhADH3 in E. histolytica trophozoites resulted in only subtle phenotypic differences in E. histolytica virulence in animal models of amebic colitis and amebic liver abscess, making it difficult to directly link EhADH3 levels to virulence differences between E. histolytica and less-pathogenic Entamoeba.

Differences in complement-mediated killing of Entamoeba histolytica between men and women--an explanation for the increased susceptibility of men to invasive amebiasis?

Men are more than 7 times more likely to develop amebic liver abscess or amebic dysentery caused by Entamoeba histolytica than women. Because the complement system could play a key role in controlling amebiasis, we determined whether serum from men and women differ in the ability to kill amebic trophozoites. We found that serum from women was significantly more effective in killing E. histolytica trophozoites than serum from men, and this killing was complement dependent. Our results provide a possible explanation for the differential susceptibility of men and women to amebic liver abscess and amebic colitis.

The RXRalpha C-terminus T462 is a NMR sensor for coactivator peptide binding.

The C-terminal activation function-2 (AF-2) helix plays a crucial role in retinoid X receptor alpha (RXRalpha)-mediated gene expression. Here, we report a nuclear magnetic resonance (NMR) study of the RXRalpha ligand-binding domain complexed with 9-cis-retinoic acid and a glucocorticoid receptor-interacting protein 1 peptide. The AF-2 helix and most of the C-terminal residues were undetectable due to a severe line-broadening effect. Due to its outstanding signal-to-noise ratio, the C-terminus residue, threonine 462 (T462) exhibited two distinct crosspeaks during peptide titration, suggesting that peptide binding was in a slow exchange regime on the chemical shift timescale. Consistently, the K(d) derived from T462 intensity decay agreed with that derived from isothermal titration calorimetry. Furthermore, the exchange contribution to the (15)N transverse relaxation rate was measurable in either T462 or the bound peptide. These results suggest that T462 is a sensor for coactivator binding and is a potential probe for AF-2 helix mobility.

Effect of heterodimer partner RXRalpha on PPARgamma activation function-2 helix in solution.

The structural mechanism of allosteric communication between retinoid X receptor (RXR) and its heterodimer partners remains controversial. As a first step towards addressing this question, we report a nuclear magnetic resonance (NMR) study on the GW1929-bound peroxisome proliferator-activated receptor gamma (PPARgamma) ligand-binding domain (LBD) with and without the 9-cis-retinoic acid (9cRA)-bound RXRalpha LBD. Sequence-specific 13C(alpha), 13C(beta), and 13CO resonance assignments have been established for over 95% of the 275 residues in the PPARgamma LBD monomer. The 1HN, 15N, and 13CO chemical shift perturbations induced by the RXRalpha LBD binding are located at not only the heterodimer interface that includes the C-terminal residue Y477 but also residues Y473 and K474 in the activation function-2 (AF-2) helix. This result suggests that 9cRA-bound RXRalpha can affect the PPARgamma AF-2 helix in solution and demonstrates that NMR is a powerful new tool for studying the mechanism of allosteric ligand activation in RXR heterodimers.

Structural analysis of the acetaldehyde dehydrogenase activity of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a member of the ADHE enzyme family.

The ADHE family of enzymes are bifunctional acetaldehyde dehydrogenase (ALDH)/alcohol dehydrogenase (ADH) enzymes that probably arose from the fusion of genes encoding separate ALDH and ADH enzymes. Here we have used the Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) enzyme as a prototype to analyze the structure and function of the ALDH domain of ADHE enzymes. We find that the N-terminal domain of EhADH2, encompassing amino acids 1-446, is sufficient for ALDH activity, consistent with the concept that EhADH2, and other members of the ADHE family comprise fusion peptides. In addition, we show, using site directed mutagenesis, that the catalytic mechanism for the ALDH activity appears to be similar to that described for other members of the ALDH extended family.