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Di-2-ethylhexyl phthalate (DEHP), as a common endocrine disrupting chemicals, can induce toxicity to reproductive system. However, the mechanism remains to be explored. In our study, DEHP exposure induced testicular injury in rats. The high throughput transcriptional sequencing was performed to identify differentially expressed genes (DEGs) between the treatment and control groups. KEGG analysis revealed that DEGs were enriched in apoptosis, PPARα, and ER stress pathway. DEHP up-regulated the expression of PPARα, Bax, Bim, caspase-4. GRP78, PERK, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. This view has also been confirmed in TM3 and TM4 cells. In vitro, after pre-treatment with GW6471 (an inhibitor of PPARα) or GSK (an inhibitor of PERK), the apoptosis was inhibited and mitochondrial dysfunction was improved. Moreover, the improvement of mitochondrial dysfunction decreased the expression of PERK pathway by using SS-31(a protective agent for mitochondrial function). Interestingly, ER stress promoted the accumulation of ROS by ERO1L (the downstream of CHOP during ER stress), and the ROS further aggravated the ER stress, thus forming a feedback loop during the apoptosis. In this process, a vicious cycle consisting of PERK, eIF2α, ATF4, CHOP, ERO1L, ROS was involved. Taken together, our results suggested that mitochondrial dysfunction and ER stress-ROS feedback loop caused by PPARα activation played a crucial role in DEHP-induced apoptosis. This work provides insight into the mechanism of DEHP-induced reproductive toxicity. [Display omitted] • DEHP induced apoptosis in rat testis. • MEHP induced apoptosis in TM3 and TM4 cells. • PPARα was activated to induce mitochondrial dysfunction through CPT1A pathway. • Apoptosis was via PPARα regulated mitochondrial disorder and ER stress interaction. • the ER stress-ROS feedback loop was discovered during apoptosis. [ABSTRACT FROM AUTHOR]

Arsenic exposure is related to insulin resistance (IR). However, the underlying mechanism is still uncertain. NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a key driving factor of IR. We found that NaAsO 2 caused hepatic IR, activated NLRP3 inflammasome, and inhibited glycolysis pathway in vivo. We also found that tricarboxylic acid cycle (TCA cycle) was inhibited, and the content of hepatic lactate was upregulated with the treatment of arsenic. Consistent with these findings, we found that NLRP3 inflammasome and glycolysis were involved in the development of IR in L-02 cells. Besides, inhibiting NLRP3 inflammasome upregulated aerobic glycolysis and inhibited anaerobic glycolysis. Moreover, we demonstrated that NLRP3 inflammasome could bind to pyruvate kinase, liver and RBC (PKLR). Simultaneously, insulin signaling rather than NLRP3 inflammasome activation was altered by overexpressing PKLR. In summary, after treatment with NaAsO 2 , NLRP3 inflammasome blocked the glycolytic pathway via binding to PKLR, which in turn caused hepatic IR. This study shed new light on the molecular mechanism underlying arsenic-induced IR. • NLRP3 inflammasome was involved in arsenic-induced hepatic insulin resistance (IR). • NaAsO2 blocked the glycolytic pathway in hepatic insulin resistance. • NLRP3 inflammasome modulated glycolysis pathway via binding to PKLR. [ABSTRACT FROM AUTHOR]

• Propose an entropy index selection strategy for the Masi entropy thresholding. • Propose the DP framework of the multilevel Masi entropy thresholding. • Propose an adaptive efficient Masi entropy multilevel thresholding based on DP. • Verify the performance of the proposed method on different benchmark data sets. Masi entropy multilevel thresholding can utilize additive and non-extensive information in images to effectively segment a complex image. However, the entropy index of Masi entropy cannot be selected automatically, and the time complexity of the multilevel algorithm by exhaustive searching grows exponentially with the increase of the threshold numbers. To address these two problems, an adaptive entropy index selection strategy based on image histogram information is proposed first. To improve the computation efficiency, an efficient solution for the adaptive Masi entropy multilevel thresholding algorithm based on dynamic programming (DP + AMasi) is also proposed. The DP + AMasi algorithm is compared with the Masi entropy multilevel thresholding algorithm by exhaustive search and state-of-the-art metaheuristic algorithms on three benchmark datasets. The effectiveness of the DP + AMasi is verified by fitness function values, Uniformity Measure, Davies Bouldin index, and CPU run time. In addition, the Wilcoxon test is used to analyze the differences between algorithms. [ABSTRACT FROM AUTHOR]

Evidence has been demonstrated that lncRNAs are involved in a variety of immune responses in vertebrate. It has been demonstrated that immune-related lncRNAs play vital functions in immune regulation against infections in teleost. Nocardia seriolae, as one of the Gram-positive bacteria, can cause chronic systemic granulomatous disease for snakehead (Channa argus). However, how lncRNAs function in the immune regulation process once snakehead was infected with N. seriolae infection has not been studied so far. Accordingly, transcription landscapes of lncRNAs and mRNAs in snakehead were investigated. A total of 1,991 lncRNA were obtained. Totally, we predicted 57,584 co-expression and 16,047 co-location lncRNA-mRNA pairs. To further analyze the potential function of these lncRNAs, GO enrichment analysis and KEGG signal pathways were performed on the target mRNAs of these differently expressed lncRNAs, suggesting that lncRNAs may play essential roles in modulating mRNA expression levels, and subsequently trigger downstream immune signaling pathways to regulate the immune response in snakehead. In addition, 9 DEmRNA and 3 lncRNAs were randomly selected for qRT-PCR analyzed, which confirmed the accuracy of transcriptome data. These results can provide novel knowledge about lncRNAs in immune responses process in snakehead, and can serve as important resources for further investigating the roles of lncRNAs during pathogen infections in teleost. • A total of 1991 lncRNA were identified in snakehead. • 7584 co-expression and 16,047 co-location lncRNA-mRNA pairs were found in snakehead. • 13 core lncRNA-mRNAs networks were constructed in N. seriolae infected snakehead. • 9 DEmRNA and 3 lncRNAs were randomly selected for qRT-PCR analyzed. [ABSTRACT FROM AUTHOR]

MicroRNAs play crucial roles in various biological processes, including but not limited to differentiation, development, disease, and immunity. However, their immunoregulatory roles in half-smooth tongue sole are lacking. Our previous studies indicated that miR-722 could target C5aR1 to modulate the complement pathway to alleviate inflammatory response and even affect the mortality after the bacterial infection with Vibrio anguillarum. Driven by the purpose of revealing the underlying mechanisms, in this study, we investigated the effects of miR-722 on the gene expression and alternative splicing (AS) in the liver of half-smooth tongue sole after Vibrio anguillarum infection, with the approach of miR-722 overexpression/silencing and subsequent RNA-seq. Among the different comparisons, the I group (miR-722 inhibitor and V. anguillarum) versus blank control (PBS) exhibited the highest number of differentially expressed genes (DEGs), suggesting that the immune response was overactivated after inhibiting the miR-722. In addition, enrichment analyses were performed to reveal the functions of DEGs and differential AS (DAS) genes, reflecting the enrichment of RNA splicing and immune-related pathways including NF-κB and T cell receptor signaling pathway. Comparing the M group (miR-722 mimic and V. anguillarum) with the negative control (random sequence and V. anguillarum), two immune-related genes, cd48 and mapk8 , were differentially expressed, of which mapk8 was also differentially spliced, indicating their importance in the immune response. Furthermore, representative gene analysis was performed, suggesting their corresponding functional changes due to AS. To verify the RNA-seq data, quantitative real-time PCR was employed with twenty pairs of primers for DEGs and DAS events. Overall, our results demonstrated that miR-722 could mediate the transcriptome-wide changes of gene expression and AS in half-smooth tongue sole, and provided insights into the regulatory role of miR-722 in immune responses, laying the foundation for further functional analyses and practical applications in aquaculture. • miR-722 mediated the transcriptome-wide changes of gene expression and AS in tongue sole. • DAS contributed significantly to the immune response after the bacterial infection. • mapk8 was the only gene that underwent both differential expression and DAS in M vs N. [ABSTRACT FROM AUTHOR]

The complement system is essential to host defense, but its excessive activation caused by severe pathogen invasion is a driving force in adverse inflammatory. The binding of complement component 5a (C5a) and complement component 5a receptor 1 (C5aR1) is the key to trigger complement-mediated inflammatory response in mammals. However, the role of C5a-C5aR1 axis in fish immune response remains obscure. In this study, the role of C5a-C5aR1 axis of zebrafish (Danio rerio) after serious infection with Aeromonas hydrophila was investigated. C5a and C5aR1 of zebrafish were cloned, with CDS sequences of 228 and 1041 bp, respectively, and they were widely expressed in various tissues with the highest expression in the liver and spleen, respectively. The survival of zebrafish was closely correlated to the dose of A. hydrophila. The cytokine storm occurred at high concentrations of A. hydrophila infection. At 24 h post infection (hpi), the expression of C5a and C5aR1 in the spleen increased 26.8-fold and 9.9-fold in treatment group 1 (TG1, 3.0 × 107 CFU/mL) (P < 0.01), and 4.7-fold and 3.4-fold in treatment group 2 (TG2, 1.0 × 107 CFU/mL) (P < 0.05), respectively. Correspondingly, proinflammatory cytokines interleukin-1β (IL-1β), interleukin-8 (IL-8), and interleukin-17 (IL-17) were positively correlated to C5a and C5aR1 at mRNA and protein expression levels. The expression of IL-1β was significantly increased in the spleen at 6 hpi, with a 599.2-fold and 203.2-fold upregulation in TG1 and TG2 (P < 0.001), respectively. Moreover, after inhibition of C5a-C5aR1 binding treated with C5aR1 antagonist (W-54011), zebrafish showed lower expression of C5a , C5aR1 , and cytokines, less intestinal damage, and significantly enhancement of survival (P < 0.05) after A. hydrophila challenge. This study revealed that the inflammatory effect of C5a was achieved by binding to C5aR1 in zebrafish, providing novel insights into using C5a-C5aR1 axis as an effective target to reduce bacterial inflammation and disease in fish. • C5a-C5aR1 axis was activated by bacterial infection with dose effect. • Hyperactivation of C5a-C5aR1 axis triggered a "cytokine storm" at both mRNA and protein levels in zebrafish. • Inhibition of C5a-C5aR1 axis significantly reduced the inflammatory response after bacterial infection in zebrafish. • The inflammatory effect of C5a was achieved by binding to C5aR1. [ABSTRACT FROM AUTHOR]