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Abstract The porcine epidemic diarrhea virus (PEDV) causes diarrhea in piglets, thereby causing very significant economic losses for the global swine industry. In previous studies, it has been confirmed that microRNAs (miRNAs) play an important role in the infection caused by PEDV. However, the precise molecular mechanism of miRNAs in the regulation of PEDV infection is still not fully understood. In the present study, we utilized miRNA-seq analysis to identify ssc-miR-1343 with differential expression between PEDV-infected and normal piglets. The expression of ssc-miR-1343 was detected in isolated exosomes, and it was found to be significantly higher than that in the controls following PEDV infection. The ssc-miR-1343 mimic was found to decrease PEDV replication, whereas the ssc-miR-1343 inhibitor was observed to increase PEDV replication, and ssc-miR-1343 was delivered by exosomes during PEDV infection. Mechanistically, ssc-miR-1343 binds to the 3′UTR region of FAM131C, down-regulating its expression, and FAM131C has been shown to enhance PEDV replication through simultaneously suppressing pathways associated with innate immunity. The ssc-miR-1343/FAM131C axis was found to upregulate the host immune response against PEDV infection. In conclusion, our findings indicate that the transport of ssc-miR-1343 in exosomes is involved in PEDV infection. This discovery presents a new potential target for the development of drugs to treat PEDV.

As the most abundant class of transcription factors in eukaryotes, C2H2-type zinc finger proteins (C2H2-ZFPs) play critical roles in various biological processes. Despite being extensively studied in mammals, C2H2-ZFPs remain poorly characterized in birds. Recent accumulation of multi-omics data for chicken enables the genome-wide investigation of C2H2-ZFPs in birds. The purpose of this study is to reveal the genomic occurrence and evolutionary signature of chicken C2H2-ZFPs, and further depict their expression profiles across diverse chicken tissues. Here, we annotated 301 C2H2-ZFPs in chicken genome, which are associated with different effector domains, including KRAB, BTB, HOMEO, PHD, SCAN, and SET. Among them, most KRAB-ZFPs lack orthologues in mammals and tend to form clusters by duplication, supporting their fast evolution in chicken. We also annotated a unique and previously unidentified SCAN-ZFP, which is lineage-specific and highly expressed in ovary and testis. By integrating 101 RNA-seq datasets for 32 tissues, we found that most C2H2-ZFPs have tissue-specific expression. Particularly, 74 C2H2-ZFPs—including 27 KRAB-ZFPs—show blastoderm-enriched expression, indicating their association with early embryo development. Overall, this study performs comprehensive annotation and expression profiling of C2H2 ZFPs in diverse chicken tissues, which gives new insights into the evolution and potential function of C2H2-ZFPs in avian species.

Dysregulation of metabolism plays an important role in the onset and progression of multiple pathogenic diseases, including viral hepatitis. However, a model to predict viral hepatitis risk by metabolic pathways is still lacking. Thus, we developed two risk assessment models for viral hepatitis based on metabolic pathways identified through univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The first model is designed to assess the progression of the disease by evaluating changes in the Child–Pugh class, hepatic decompensation, and the development of hepatocellular carcinoma. The second model is focused on determining the prognosis of the illness, taking into account the patient’s cancer status. Our models were further validated by Kaplan–Meier plots of survival curves. In addition, we investigated the contribution of immune cells in metabolic processes and identified three distinct subsets of immune cells—CD8+ T cells, macrophages, and NK cells—that have significantly affected metabolic pathways. Specifically, our findings suggest that resting or inactive macrophages and NK cells contribute to maintaining metabolic homeostasis, particularly with regard to lipid and α-amino acid metabolism, thereby potentially reducing the risk of viral hepatitis progression. Moreover, maintaining metabolic homeostasis ensures a balance between killer-proliferative and exhausted CD8+ T cells, which helps in mitigating CD8+ T cell-mediated liver damage while preserving energy reserves. In conclusion, our study offers a useful tool for early disease detection in viral hepatitis patients through metabolic pathway analysis and sheds light on the immunological understanding of the disease through the examination of immune cell metabolic disorders.

Fumonisin B1 (FB1) is a mycotoxin that poses a great threat to agricultural production and the health of humans and animals. Pterostilbene (PTE) is a natural plant polyphenolic compound with good anti-inflammatory, antioxidant and cell regeneration effects, yet its effectiveness in treating FB1-induced cytotoxicity remains to be explored. In this study, we used porcine alveolar macrophages (3D4/21) as a model to characterize the cytotoxicity induced by FB1, and to investigate the potential alleviating effect of PTE on FB1-induced cytotoxicity. We demonstrate that FB1 induces cytotoxicity, apoptosis, pro-inflammatory cytokine production and mitochondrial damage, which can be largely recovered by PTE treatment, suggesting the promising application of PTE to treat FB1-induced damage. Mechanistically, FB1 activates the JAK/STAT signaling pathway, while PTE attenuates FB1-induced cytotoxicity through the inhibition of key JAK/STAT genes such as JAK2 and STAT3. Overall, our study characterized the molecular mechanism for FB1-induced cytotoxicity and found PTE to be a promising component which can alleviate FB1-induced cytotoxicity by interfering in the activation of JAK/STAT pathway.

Porcine epidemic diarrhea virus (PEDV) is a burdensome coronavirus for the global pig industry. Although its fecal-oral route has been well-recognized, increasing evidence suggests that PEDV can also spread through airborne routes, indicating that the infection may also occur in the respiratory tract. N6-methyladenosine (m6A) has been known to regulate viral replication and host immunity, yet its regulatory role and molecular mechanism regarding PEDV infection outside the gastrointestinal tract remain unexplored. In this study, we demonstrate that PEDV can infect porcine lung tissue and the 3D4/21 alveolar macrophage cell line, and the key m6A demethylase ALKBH5 is remarkably induced after PEDV infection. Interestingly, the disruption of ALKBH5 expression remarkably increases the infection’s capacity for PEDV. Transcriptome profiling identified dozens of putative targets of ALKBH5, including GAS6, which is known to regulate virus infectivity. Further, MeRIP-qPCR and mRNA stability analyses suggest that ALKBH5 regulates the expression of GAS6 via an m6A-YTHDF2-dependent mechanism. Overall, our study demonstrates that PEDV can infect porcine lung tissue and 3D4/21 cells and reveals the crucial role of ALKBH5 in restraining PEDV infections, at least partly, by influencing GAS6 through an m6A-YTHDF2-dependent mechanism.

Melatonin is an important endogenous hormone that shows antioxidant functions and pleiotropic effects, playing a crucial role in animal reproduction. Ovary granulosa cells (GCs) surround the oocyte, which play an important role in regulating oocytes development. Deoxynivalenol (DON) is a common fusarium mycotoxin contaminant of feedstuff and food, posing a serious threat to human and animal reproductive systems. Herein, murine ovary GCs were studied as a reproduction cell model, aimed to assess the protective effect of melatonin on DON-induced toxicity in murine ovary GCs. The results showed that DON adversely affected the viability and growth of murine ovary GCs and increased the apoptosis rate, while melatonin administration ameliorated these toxic effects. We further reveal that DON exposure increased the intracellular reactive oxygen species level, reduced the mitochondrial membrane potential and ATP, and upregulated Tnfα (tumor necrosis factor α), Il6 (interleukin 6), and Il1β (interleukin 1 β) gene expression. Moreover, DON exposure downregulated reproductive hormone gene expression and significantly increased nuclear factor kappa B (p65) activation and mitogen-activated protein kinase phosphorylation. Melatonin treatment attenuated all these effects, suggesting that melatonin protects GCs from the adverse effects of DON by ameliorating oxidative stress, mitochondrial dysfunction, and inflammation. Overall, these results reveal the mechanisms of DON and melatonin in GCs and provide a theoretical basis for melatonin as a drug to improve mycotoxin contamination.

Many computational methods have been widely used to identify transcription regulatory interactions based on gene expression profiles. The selection of dependency measure is very important for successful regulatory network inference. In this paper, we develop a new method-DBoMM (Difference in BIC of Mixture Models)-for estimating dependency of gene by fitting the gene expression profiles into mixture Gaussian models. We show that DBoMM out-performs 4 other existing methods, including Kendall's tau correlation (TAU), Pearson Correlation (COR), Euclidean distance (EUC) and Mutual information (MI) using Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Arabidopsis thaliana data and synthetic data. DBoMM can also identify condition-dependent regulatory interactions and is robust to noisy data. Of the 741 Escherichia coli regulatory interactions inferred by DBoMM at a 60% true positive rate, 65 are previously known interactions and 676 are novel predictions. To validate the new prediction, the promoter sequences of target genes regulated by the same transcription factors were analyzed and significant motifs were identified.