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The ocular mucosa (OM) is an important and unique part of the vertebrate mucosal immune system. The OM plays an important role in maintaining visual function and defending against foreign antigens or microorganisms, while maintaining a balance between the two through complex regulatory mechanisms. However, the function of ocular mucosal defense against foreign pathogens and mucosal immune response in bony fish are still less studied. To acquire deeper understanding into the mucosal immunity of the OM in teleost fish, we established a study of the immune response of rainbow trout (Oncorhynchus mykiss) infected with the infectious hematopoietic necrosis virus (IHNV). Our findings revealed that IHNV could successfully infiltrate the trout's OM, indicating that the OM could be an important portal for the IHNV. Furthermore, qPCR and RNA-Seq analysis results showed that a large number of immune-related genes were significantly upregulated in the OM of trout with IHNV infection. Critically, the results of our RNA-Seq analysis demonstrated that viral infection triggered a robust immune response, as evidenced by the substantial induction of antiviral, innate, and adaptive immune-related genes in the OM of infected fish, which underscored the essential role of the OM in viral infection. Overall, our findings revealed a previously unknown function of teleost OM in antiviral defense, and provided a theoretical basis for the study of the mucosal immunity of fish. [ABSTRACT FROM AUTHOR]

Simple Summary: With the increasing demand for aquaculture, the resource of high-quality traditional protein (such as fishmeal) becomes limited, and plant ingredients are often used as substitutes for fishmeal because of their low price and wide availability. However, plant proteins are usually deficient in certain essential amino acids (EAAs), which adversely affects the growth performance of aquatic animals. Lysine is generally the first limiting amino acid in plant protein ingredients used to formulate the aquafeed, and it plays an important role in physiological processes including antioxidant, differentiation, growth, immunity, and reduction of nitrogen emission. In this study, the effects of dietary graded L-lysine concentrations on the growth, proximate composition, and AA (amino acid) profile of coho salmon alevins were evaluated by a feeding trial. The results showed that an adequate dietary lysine level significantly improved the specific growth rate (SGR), protein efficiency ratio (PER), body protein deposition (BPD), and feed conversion ratio (FCR). The dietary optimum L-lysine requirements for coho salmon alevins were 3.74%, 3.73%, 3.91%, and 3.77% of the diet or 6.80%, 6.78%, 7.11%, and 6.85% of dietary proteins against the SGR, PER, BPD, and FCR, respectively. The suitable dietary L-lysine concentration for coho salmon (Oncorhynchus kisutch) alevins was assessed by a dose response feeding trial. Six experimental diets were made with graded L-lysine concentrations of 2.29%, 2.81%, 3.32%, 3.80%, 4.27%, and 4.78% of the dry matter, respectively, each of which was fed to triplicate groups of 100 alevins (initial body weight: 0.30 ± 0.01 g) in 18 plastic baskets (water volume 240 L). The alevins were cultured in a flowing freshwater system and fed manually to apparent satiation four times a day for 12 weeks. The survival rate of alevins did not differ significantly among the dietary groups. The specific growth rate (SGR), protein efficiency ratio (PER), and body protein deposition (BPD) increased significantly (p < 0.05) with the increase in dietary lysine concentration up to 3.80% and then reduced as lysine level further increased. The feed conversion ratio (FCR) had an inverse trend to SGR. The whole-body crude protein content of the alevins increased significantly with increasing dietary lysine level, while crude lipid content showed the opposite trend. In comparison, the contents of morphological indices, whole-body moisture, and ash were not affected significantly (p > 0.05) by the different dietary lysine concentrations. The highest contents of lysine, arginine, and total essential amino acids (EAAs) were observed in the group with 4.27% dietary lysine concentration, which did not differ significantly from those in the 3.32%, 3.80%, and 4.78% groups but was significantly higher than those in the 2.29% and 2.81% groups. Similarly, valine had the highest content in the group with 4.78%. The variations in dietary lysine had no significant impacts on other EAA and non-EAA contents except glycine, which increased with increasing dietary lysine level. Second-order polynomial model analyses based on SGR, PER, BPD, and FCR evaluated the optimum L-lysine requirements of coho salmon alevins as 3.74%, 3.73%, 3.91%, and 3.77% of the diet or 6.80%, 6.78%, 7.11%, and 6.85% of dietary proteins, respectively. [ABSTRACT FROM AUTHOR]

Grass carp reovirus (GCRV), one of the most serious pathogens threatening grass carp (Ctenopharyngodon idella), can lead to grass carp hemorrhagic disease (GCHD). Currently, GCRV can be divided into three genotypes, but the comparison of their pathogenic mechanisms and the host responses remain unclear. In this study, we utilized the Ctenopharyngodon idella kidney (CIK) model infected with GCRV to conduct comparative studies on the three genotypes. We observed a cytopathic effect (CPE) in the GCRV-I and GCRV-III groups, whereas the GCRV-II group did not show any CPE. Moreover, a consistent trend in the mRNA expression levels of antiviral-related genes across all experimental groups of CIK cells was detected via qPCR and further explored through RNA-seq analysis. Importantly, GO/KEGG enrichment analysis showed that GCRV-I, -II, and -III could all activate the immune response in CIK cells, but GCRV-II induced more intense immune responses. Intriguingly, transcriptomic analysis revealed a widespread down-regulation of metabolism processes such as steroid biosynthesis, butanoate metabolism, and N-Glycan biosynthesis in infected CIK cells. Overall, our results reveal the CIK cells showed unique responses in immunity and metabolism in the three genotypes of GCRV infection. These results provide a theoretical basis for understanding the pathogenesis and prevention and control methods of GCRV. [ABSTRACT FROM AUTHOR]

Granulocytes are crucial innate immune cells that have been extensively studied in teleost fish. Studies in mammals have revealed that mechanistic target of rapamycin complex 1 (mTORC1) signaling acts as a significant immune regulatory hub, influencing granulocyte immune function. To investigate whether mTORC1 signaling also regulates the immune function of granulocytes in teleost fish, we established a model of RAPA inhibition of the mTORC1 signaling pathway using granulocytes from largemouth bass (Micropterus salmoides). Our results demonstrated that inhibition of mTORC1 signaling promoted autophagy and apoptosis of granulocytes while inhibiting cell proliferation. Moreover, inhibition of the mTORC1 signaling pathway enhanced the phagocytosis capacity of granulocytes. Collectively, our findings revealed the evolutionarily conserved role of the mTORC1 signaling pathway in regulating granulocyte responses, thus providing novel insights into the function of granulocytes in teleost fish. [ABSTRACT FROM AUTHOR]

Micellar-nanocarrier-based drug delivery systems possessing characteristics such as an excellent circulation stability, inhibited premature release and on-demand site-specific release are urgently needed for enhanced therapeutic efficacy. Therefore, a novel kind of shell-sheddable core-crosslinked polymeric micelles with pH and oxidation dual-triggered on-demand drug release behavior was facilely constructed. The multifunctional micelles were self-assembled from a carefully designed amphiphilic triblock PEGylated polyurethane (PEG-acetal-PUBr-acetal-PEG) employing an acid-labile acetal linker at the hydrophilic–hydrophobic interface and pendant reactive bromo-containing polyurethane (PU) as the hydrophobic block, followed by a post-crosslinking via oxidation-cleavable diselenide linkages. These well-defined micelles exhibited an enhanced structural stability against dilution, achieved through the incorporation of diselenide crosslinkers. As expected, they were found to possess dual pH- and oxidation-responsive dissociation behaviors when exposure to acid pH (~5.0) and 50 mM H2O2 conditions, as evidenced using dynamic light-scattering (DLS) and atomic force microscopy (AFM) analyses. An in vitro drug release investigation showed that the drug indomethacin (IND) could be efficiently encapsulated in the micelles, which demonstrated an inhibited premature release compared to the non-crosslinked ones. It is noteworthy that the resulting micelles could efficiently release entrapped drugs at a fast rate in response to either pH or oxidation stimuli. Moreover, the release could be significantly accelerated in the presence of both acid pH and oxidation conditions, relative to a single stimulus, owing to the synergetic degradation of micelles through pH-induced dePEGylation and oxidation-triggered decrosslinking processes. The proposed shell-sheddable core-crosslinked micelles with a pH and oxidation dual-response could be potential candidates as drug carriers for on-demand drug delivery. [ABSTRACT FROM AUTHOR]

The ocular mucosa (OM) is an important and unique part of the vertebrate mucosal immune system. The OM plays an important role in maintaining visual function and defending against foreign antigens or microorganisms, while maintaining a balance between the two through complex regulatory mechanisms. However, the function of ocular mucosal defense against foreign pathogens and mucosal immune response in bony fish are still less studied. To acquire deeper understanding into the mucosal immunity of the OM in teleost fish, we established a study of the immune response of rainbow trout ( Oncorhynchus mykiss ) infected with the infectious hematopoietic necrosis virus (IHNV). Our findings revealed that IHNV could successfully infiltrate the trout's OM, indicating that the OM could be an important portal for the IHNV. Furthermore, qPCR and RNA-Seq analysis results showed that a large number of immune-related genes were significantly upregulated in the OM of trout with IHNV infection. Critically, the results of our RNA-Seq analysis demonstrated that viral infection triggered a robust immune response, as evidenced by the substantial induction of antiviral, innate, and adaptive immune-related genes in the OM of infected fish, which underscored the essential role of the OM in viral infection. Overall, our findings revealed a previously unknown function of teleost OM in antiviral defense, and provided a theoretical basis for the study of the mucosal immunity of fish.