o8G Site-Specifically Modified tRF-1-AspGTC: A Novel Therapeutic Target and Biomarker for Pulmonary Hypertension.

BACKGROUND: Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. We aimed to gain insight into the mechanistic contribution of oxidative stress-induced 8-oxoguanine in pulmonary vascular remodeling. METHODS: Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine -modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH. RESULTS: This modification occurs at the position 5 of the tRF-1-AspGTC (5o8G tRF). Inhibition of the 5o8G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o8G tRF retargeted mRNA of WNT5A (Wingless-type MMTV integration site family, member 5A) and CASP3 (Caspase3) and inhibited their expression. Ultimately, BMPR2 (Bone morphogenetic protein receptor 2) -reactive oxygen species/5o8G tRF/WNT5A signaling pathway exacerbated the progression of PH. CONCLUSIONS: Our study highlights the role of site-specific 8-oxoguanine-modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o8G tRF as a potential innovative marker for diagnosing this disease.

[Effect of Characteristic Variable Extraction on Accuracy of Cu in Navel Orange Peel by LIBS].

Heavy metals pollution in foodstuffs is more and more serious. It is impossible to satisfy the modern agricultural development by conventional chemical analysis. Laser induced breakdown spectroscopy (LIBS) is an emerging technology with the characteristic of rapid and nondestructive detection. But LIBS' s repeatability, sensitivity and accuracy has much room to improve. In this work, heavy metal Cu in Gannan Navel Orange which is the Jiangxi specialty fruit will be predicted by LIBS. Firstly, the navel orange samples were contaminated in our lab. The spectra of samples were collected by irradiating the peel by optimized LIBS parameters. The laser energy was set as 20 mJ, delay time of Spectral Data Gathering was set as 1.2 micros, the integration time of Spectral data gathering was set as 2 ms. The real concentration in samples was obtained by AAS (atom absorption spectroscopy). The characteristic variables Cu I 324.7 and Cu I 327.4 were extracted. And the calibration model was constructed between LIBS spectra and real concentration about Cu. The results show that relative error of the predicted concentrations of three relational model were 7.01% or less, reached a minimum of 0.02%, 0.01% and 0.02% respectively. The average relative errors were 2.33%, 3.10% and 26.3%. Tests showed that different characteristic variables decided different accuracy. It is very important to choose suitable characteristic variable. At the same time, this work is helpful to explore the distribution of heavy metals between pulp and peel.

ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Associations Between Serum Soluble α-Klotho and the Prevalence of Specific Cardiovascular Disease.

Objective: Accumulating experimental evidence has identified the beneficial effects of the anti-aging protein, serum soluble α-Klotho, on longevity, and the cardiovascular system. Although a previous study has revealed the predictive value of α-Klotho on total cardiovascular disease (CVD), the associations between α-Klotho and specific CVDs, including congestive heart failure (CHF), coronary heart disease (CHD), myocardial infarction (MI), and stroke, remains to be fully elucidated in humans. Methods: For 8,615 adults in the 2007 to 2016 National Health and Nutrition Examination Survey, stratified multivariable logistic regression models, restricted cubic spline curves, and subgroup analyses were used to evaluate the associations between α-Klotho and the four specific CVDs. Results: In the quartile analyses, compared to those in the highest quartile, participants in the lowest level of α-Klotho were significantly associated with CHF [odds ratio (OR) = 1.46, 95% CI: 1.09-1.97] and MI (1.33, 1.02-1.74), which was not the case for CHD (1.12, 0.91-1.38) or stroke (0.96, 0.73-1.25). Each unit increment in the ln-transformed α-Klotho concentrations was only positively associated with a 38 and 24% reduction in the prevalence of CHF and MI, respectively. Restricted cubic spline curves indicated that the α-Klotho was correlated with CHF and MI in linear-inverse relationships. Conclusion: The present findings suggested that the serum soluble α-Klotho is significantly associated with the prevalence of CHF and MI. To better determine whether α-Klotho is a specific biomarker of CVD, particularly for CHD and stroke, further research in humans is needed.