Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis

Background: Atrial fibrillation (AF) is the most common arrhythmia. We aimed to construct competing endogenous RNA (ceRNA) networks associated with the susceptibility and persistence of AF by applying the weighted gene co-expression network analysis (WGCNA) and prioritize key genes using the random walk with restart on multiplex networks (RWR-M) algorithm.Methods: RNA sequencing results from 235 left atrial appendage samples were downloaded from the GEO database. The top 5,000 lncRNAs/mRNAs with the highest variance were used to construct a gene co-expression network using the WGCNA method. AF susceptibility- or persistence-associated modules were identified by correlating the module eigengene with the atrial rhythm phenotype. Using a module-specific manner, ceRNA pairs of lncRNA–mRNA were predicted. The RWR-M algorithm was applied to calculate the proximity between lncRNAs and known AF protein-coding genes. Random forest classifiers, based on the expression value of key lncRNA-associated ceRNA pairs, were constructed and validated against an independent data set.Results: From the 21 identified modules, magenta and tan modules were associated with AF susceptibility, whereas turquoise and yellow modules were associated with AF persistence. ceRNA networks in magenta and tan modules were primarily involved in the inflammatory process, whereas ceRNA networks in turquoise and yellow modules were primarily associated with electrical remodeling. A total of 106 previously identified AF-associated protein-coding genes were found in the ceRNA networks, including 16 that were previously implicated in the genome-wide association study. Myocardial infarction–associated transcript (MIAT) and LINC00964 were prioritized as key lncRNAs through RWR-M. The classifiers based on their associated ceRNA pairs were able to distinguish AF from sinus rhythm with respective AUC values of 0.810 and 0.940 in the training set and 0.870 and 0.922 in the independent test set. The AF-related single-nucleotide polymorphism rs35006907 was found in the intronic region of LINC00964 and negatively regulated the LINC00964 expression.Conclusion: Our study constructed AF susceptibility- and persistence-associated ceRNA networks, linked genetics with epigenetics, identified MIAT and LINC00964 as key lncRNAs, and constructed random forest classifiers based on their associated ceRNA pairs. These results will help us to better understand the mechanisms underlying AF from the ceRNA perspective and provide candidate therapeutic and diagnostic tools

Utilizing differences in bTH tolerance between the parents of two-line hybrid rice to improve the purity of hybrid rice seed

IntroductionTwo-line hybrid rice based on Photoperiod/thermo-sensitive genic male sterile (P/TGMS) lines has been developed and applied widely in agriculture due to the freedom in making hybrid combinations, less difficulty in breeding sterile lines, and simpler procedures for breeding and producing hybrid seed. However, there are certain risks associated with hybrid seed production; if the temperature during the P/TGMS fertility-sensitive period is lower than the critical temperature, seed production will fail due to self-pollination. In a previous study, we found that the issue of insufficient purity of two-line hybrid rice seed could be initially addressed by using the difference in tolerance to β-triketone herbicides (bTHs) between the female parent and the hybrid seeds.MethodsIn this study, we further investigated the types of applicable herbicides, application methods, application time, and the effects on physiological and biochemical indexes and yield in rice.ResultsThe results showed that this method could be used for hybrid purification by soaking seeds and spraying plants with the bTH benzobicylon (BBC) at safe concentrations in the range of 37.5-112.5 mg/L, and the seeds could be soaked in BBC at a treatment rate of 75.0 mg/L for 36-55 h without significant negative effects. The safe concentration for spraying in the field is 50.0-400.0 mg/L BBC at the three-leaf stage. Unlike BBC, Mesotrione (MST) can only be sprayed to achieve hybrid purification at concentrations between 10.0 and 70.0 mg/L without affecting yield. The three methods of hybrid seed purification can reach 100% efficiency without compromising the nutritional growth and yield of hybrid rice. Moreover, transcriptome sequencing revealed that 299 up-regulated significant differentially expressed genes (DEGs) in the resistant material (Huazhan) poisoned by BBC, were mainly enriched in phenylalanine metabolism and phenylpropanoid biosynthesis pathway, it may eliminate the toxic effects of herbicides through this way.DiscussionOur study establishes a foundation for the application of the bTH seed purification strategy and the three methods provide an effective mechanism for improving the purity of two-line hybrid rice seeds

7-Ketocholesterol Induces Cell Apoptosis by Activation of Nuclear Factor kappa B in Mouse Macrophages

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC). Cell apoptosis was detected by Annexin V-propidium iodide (PI) staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.</p