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Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, children, immunocompromised adults, and elderly individuals. Currently, there are few therapeutic options available to prevent RSV infection. The present study aimed to investigate the effects of luteolin on RSV replication and the related mechanisms. Material and methods: We pretreated cells and mice with luteolin before infection with RSV, the virus titer, expressions of RSV-F, interferon (IFN)-stimulated genes (ISGs), and production of IFN-α and IFN-β were determined by plaque assay, RT-qPCR, and ELISA, respectively. The activation of Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling pathway was detected by Western blotting and luciferase assay. Proteins which negatively regulate STAT1 were determined by Western blotting. Then cells were transfected with suppressor of cytokine signaling 1 (SOCS1) plasmid and virus replication and ISGs expression were determined. Luciferase reporter assay and Western blotting were performed to detect the relationship between SOCS1 and miR-155. Results: Luteolin inhibited RSV replication, as shown by the decreased viral titer and RSV-F mRNA expression both in vitro and in vivo. The antiviral activity of luteolin was attributed to the enhanced phosphorylation of STAT1, resulting in the increased production of ISGs. Further study showed that SOCS1 was downregulated by luteolin and SOCS1 is a direct target of microRNA-155 (miR-155). Inhibition of miR-155 rescued luteolin-mediated SOCS1 downregulation, whereas upregulation of miR-155 enhanced the inhibitory effect of luteolin. Conclusion: Luteolin inhibits RSV replication by regulating the miR-155/SOCS1/STAT1 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Tc1/mariner and Zator, as two superfamilies of IS630-Tc1-mariner (ITm) group, have been well-defined. However, the molecular evolution and domestication of pogo transposons, once designated as an important family of the Tc1/mariner superfamily, are still poorly understood. Results: Here, phylogenetic analysis show that pogo transposases, together with Tc1/mariner, DD34E/Gambol, and Zator transposases form four distinct monophyletic clades with high bootstrap supports (> = 74%), suggesting that they are separate superfamilies of ITm group. The pogo superfamily represents high diversity with six distinct families (Passer, Tigger, pogoR, Lemi, Mover, and Fot/Fot-like) and wide distribution with an expansion spanning across all the kingdoms of eukaryotes. It shows widespread occurrences in animals and fungi, but restricted taxonomic distribution in land plants. It has invaded almost all lineages of animals—even mammals—and has been domesticated repeatedly in vertebrates, with 12 genes, including centromere-associated protein B (CENPB), CENPB DNA-binding domain containing 1 (CENPBD1), Jrk helix–turn–helix protein (JRK), JRK like (JRKL), pogo transposable element derived with KRAB domain (POGK), and with ZNF domain (POGZ), and Tigger transposable element-derived 2 to 7 (TIGD2–7), deduced as originating from this superfamily. Two of them (JRKL and TIGD2) seem to have been co-domesticated, and the others represent independent domestication events. Four genes (TIGD3, TIGD4, TIGD5, and POGZ) tend to represent ancient domestications in vertebrates, while the others only emerge in mammals and seem to be domesticated recently. Significant structural variations including target site duplication (TSD) types and the DDE triad signatures (DD29–56D) were observed for pogo transposons. Most domesticated genes are derived from the complete transposase genes; but CENPB, POGK, and POGZ are chimeric genes fused with additional functional domains. Conclusions: This is the first report to systematically reveal the evolutionary profiles of the pogo transposons, suggesting that pogo and Tc1/Mariner are two separate superfamilies of ITm group, and demonstrating the repeated domestications of pogo in vertebrates. These data indicate that pogo transposons have played important roles in shaping the genome and gene evolution of fungi and animals. This study expands our understanding of the diversity of pogo transposons and updates the classification of ITm group. [ABSTRACT FROM AUTHOR]

Background: Tc1/mariner and Zator, as two superfamilies of IS630-Tc1-mariner (ITm) group, have been well-defined. However, the molecular evolution and domestication of pogo transposons, once designated as an important family of the Tc1/mariner superfamily, are still poorly understood. Results: Here, phylogenetic analysis show that pogo transposases, together with Tc1/mariner, DD34E/Gambol, and Zator transposases form four distinct monophyletic clades with high bootstrap supports (> = 74%), suggesting that they are separate superfamilies of ITm group. The pogo superfamily represents high diversity with six distinct families (Passer, Tigger, pogoR, Lemi, Mover, and Fot/Fot-like) and wide distribution with an expansion spanning across all the kingdoms of eukaryotes. It shows widespread occurrences in animals and fungi, but restricted taxonomic distribution in land plants. It has invaded almost all lineages of animals—even mammals—and has been domesticated repeatedly in vertebrates, with 12 genes, including centromere-associated protein B (CENPB), CENPB DNA-binding domain containing 1 (CENPBD1), Jrk helix–turn–helix protein (JRK), JRK like (JRKL), pogo transposable element derived with KRAB domain (POGK), and with ZNF domain (POGZ), and Tigger transposable element-derived 2 to 7 (TIGD2–7), deduced as originating from this superfamily. Two of them (JRKL and TIGD2) seem to have been co-domesticated, and the others represent independent domestication events. Four genes (TIGD3, TIGD4, TIGD5, and POGZ) tend to represent ancient domestications in vertebrates, while the others only emerge in mammals and seem to be domesticated recently. Significant structural variations including target site duplication (TSD) types and the DDE triad signatures (DD29–56D) were observed for pogo transposons. Most domesticated genes are derived from the complete transposase genes; but CENPB, POGK, and POGZ are chimeric genes fused with additional functional domains. Conclusions: This is the first report to systematically reveal the evolutionary profiles of the pogo transposons, suggesting that pogo and Tc1/Mariner are two separate superfamilies of ITm group, and demonstrating the repeated domestications of pogo in vertebrates. These data indicate that pogo transposons have played important roles in shaping the genome and gene evolution of fungi and animals. This study expands our understanding of the diversity of pogo transposons and updates the classification of ITm group. [ABSTRACT FROM AUTHOR]

Background: The Tc1/mariner superfamily might represent the most diverse and widely distributed group of DNA transposons. Several families have been identified; however, exploring the diversity of this superfamily and updating its classification is still ongoing in the life sciences. Results: Here we identified a new family of Tc1/mariner transposons, named Incomer (IC), which is close to, but distinct from the known family DD34E/Tc1. ICs have a total length of about 1.2 kb, and harbor a single open reading frame encoding a ~ 346 amino acid transposase with a DD36E motif and flanked by short terminal inverted repeats (TIRs) (22–32 base pairs, bp). This family is absent from prokaryotes, and is mainly distributed among vertebrates (141 species of four classes), including Agnatha (one species of jawless fish), Actinopterygii (132 species of ray-finned fish), Amphibia (four species of frogs), and Mammalia (four species of bats), but have a restricted distribution in invertebrates (four species in Insecta and nine in Arachnida). All ICs in bats (Myotis lucifugus, Eptesicus fuscus, Myotis davidii, and Myotis brandtii) are present as truncated copies in these genomes, and most of them are flanked by relatively long TIRs (51–126 bp). High copy numbers of miniature inverted-repeat transposable elements (MITEs) derived from ICs were also identified in bat genomes. Phylogenetic analysis revealed that ICs are more closely related to DD34E/Tc1 than to other families of Tc1/mariner (e.g., DD34D/mariner and DD × D/pogo), and can be classified into four distinct clusters. The host and IC phylogenies and pairwise distance comparisons between RAG1 genes and all consensus sequences of ICs support the idea that multiple episodes of horizontal transfer (HT) of ICs have occurred in vertebrates. In addition, the discovery of intact transposases, perfect TIRs and target site duplications of ICs suggests that this family may still be active in Insecta, Arachnida, frogs, and fish. Conclusions: Exploring the diversity of Tc1/mariner transposons and revealing their evolutionary profiles will help provide a better understanding of the evolution of DNA transposons and their impact on genomic evolution. Here, a newly discovered family (DD36E/Incomer) of Tc1/mariner transposons is described in animals. It displays a similar structural organization and close relationship with the known DD34E/Tc1 elements, but has a relatively narrow distribution, indicating that DD36E/IC might have originated from the DD34E/Tc1 family. Our data also support the hypothesis of horizontal transfer of IC in vertebrates, even invading one lineage of mammals (bats). This study expands our understanding of the diversity of Tc1/mariner transposons and updates the classification of this superfamily. [ABSTRACT FROM AUTHOR]

Background: Retrotransposons are the major determinants of genome sizes and they have shaped both genes and genomes in mammalian organisms, but their overall activity, diversity, and evolution dynamics, particularly their impact on protein coding and lncRNA genes in pigs remain largely unknown. Results: In the present study, we performed de novo detection of retrotransposons in pigs by using multiple pipelines, four distinct families of pig-specific L1 s classified into 51 distinct subfamilies and representing four evolution models and three expansion waves of pig-specific SINEs represented by three distinct families were identified. ERVs were classified into 18 families and found two most "modern" subfamilies in the pig genome. The transposition activity of pig L1 was verified by experiment, the sense and antisense promoter activities of young L1 5′UTRs and ERV LTRs and expression profiles of young retrotransposons in multiple tissues and cell lines were also validated. Furthermore, retrotransposons had an extensive impact on lncRNA and protein coding genes at both the genomic and transcriptomic levels. Most protein coding and lncRNA (> 80%) genes contained retrotransposon insertions, and about half of protein coding genes (44.30%) and one-fourth (24.13%) of lncRNA genes contained the youngest retrotransposon insertions. Nearly half of protein coding genes (43.78%) could generate chimeric transcripts with retrotransposons. Significant distribution bias of retrotransposon composition, location, and orientation in lncRNA and protein coding genes, and their transcripts, were observed. Conclusions: In the current study, we characterized the classification and evolution profile of retrotransposons in pigs, experimentally proved the transposition activity of the young pig L1 subfamily, characterized the sense and antisense expression profiles and promoter activities of young retrotransposons, and investigated their impact on lncRNA and protein coding genes by defining the mobilome landscapes at the genomic and transcriptomic levels. These findings help provide a better understanding of retrotransposon evolution in mammal and their impact on the genome and transcriptome. [ABSTRACT FROM AUTHOR]

Background and Aims: Serum GP73 is a useful biomarker in assessing hepatic fibrosis degree. The aim of this study was to evaluate the predictive value of serum GP73 level for posthepatectomy short-term outcomes in hepatocellular carcinoma (HCC) patients.Methods: A total of 280 patients undergoing liver resection for HCC between October 2015 and April 2018 were included in this study. Detailed preoperative clinicopathological data were collected and GP73 levels in serum obtained the day before hepatectomy were examined. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff of GP73, and independent risk factors for postoperative outcomes was assessed by logistic regression model.Results: The mean GP73 level in patients was 111.8 ± 153.3 ng/mL. Serum GP73 levels were correlated with the METAVIR fibrosis score. Overall complications occurred in 145 patients and major complications developed in 29 patients. ROC analysis demonstrated that the predictive power of serum GP73 for postoperative outcomes was greater than the Child-Pugh score, ALBI score, FIB-4 index and APRI score. The optimal value of serum GP73 to predict overall complications and major complications was 80.9 and 79.2 respectively. Serum GP73 levels were independent factors affecting the incidence of overall complications (odds ratio [OR], 3.996; 95% CI 2.152-7.421; P < 0.001) and major complications (OR, 4.970; 95% CI 1.654-14.934; P = 0.004) by multivariate analysis.Conclusion: Serum GP73 is a useful tool to stratify HCC patients and to predict short-term outcomes after hepatectomy. [ABSTRACT FROM AUTHOR]