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At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand‐1 (PD‐L1) expression. Incredibly, intracellular PD‐L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD‐L1function still limits the effectiveness of radio‐immunotherapy. Therefore, better PD‐L1 regulation strategies are still urgently needed to better sensitize radio‐immunotherapy. Hence, for this purpose, TPP‐LND is synthesized by linking mitochondrial‐targeted triphenylphosphine cations (TPP+) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP‐LND is wrapped with liposomes to form TPP‐LND@Lip nanoparticles. By doing this, TPP‐LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD‐L1 via enhancing the adenosine 5′‐monophosphate‐activated protein kinase activation. As expected, these well‐designed economical TPP‐LND@Lip nanoparticles are more effective than conventional anti‐PD‐L1 antibodies to some extent. [ABSTRACT FROM AUTHOR]

Salinity is an important environmental factor that affects fish growth, development, and reproduction. As euryhaline fish, half-smooth tongue sole (Cynoglossus semilaevis) are a suitable species for deciphering the salinity adaptation mechanism of fish; however, the molecular mechanisms underlying low- and high-salinity responses remain unclear. In this study, RNA-seq was applied to characterize the genes and regulatory pathways involved in C. semilaevis gill responses to high- (32 ppt), low- (8 ppt), and control-salinity (24 ppt) water. Gills were rich in mitochondria-rich cells (MRCs) in high salinity. Compared with control, 2137 and 218 differentially expressed genes (DEGs) were identified in low and high salinity, respectively. The enriched functions of most DEGs were metabolism, ion transport, regulation of cell cycle, and immune response. The DEGs involved in oxidative phosphorylation, citrate cycle, and fatty acid metabolism were down-regulated in low salinity. For ion transport, high and low salinity significantly altered the expressions of prlr , ca12 , and cftr. In cell cycle arrest and cellular repair, gadd45b , igfbp5 , and igfbp2 were significantly upregulated in high and low salinity. For immune response, il10 , il34 , il12b , and crp increased in high and low salinity. Our findings suggested that alterations in material and energy metabolism, ions transport, cell cycle arrest, cellular repair, and immune response, are required to maintain C. semilaevis gill homeostasis under high and low salinity. This study provides insight into the divergence of C. semilaevis osmoregulation mechanisms acclimating to high and low salinity, which will serve as reference for the healthy culture of C. semilaevis. [Display omitted] • Gill transcriptome profiles revealed that C. semilaevis adapted high- and low-salinity water via adjusting material and energy metabolism, ion transport, cell cycle arrest, cellular repair, and immune response. • First revealed C. semilaevis gill adaptation mechanism to high and low salinity at the transcriptome level. [ABSTRACT FROM AUTHOR]

Abstract The African catfish, Clarias gariepinus , an important cultured freshwater species in many countries, possess the characteristic of high disease resistance. However, little genomic information for this character of the fish is available up to now. To address the shortfall and to better understand C. gariepinus immune response to pathogen infection at molecular level, C. gariepinus were challenged with potent A. veronii and the high-throughput RNA sequencing (RNA-seq) technology were employed to produce transcriptomes from spleen. In total, an average of 46,073,372 clean reads obtained were de novo assembled into 156,955 unigenes with an average length of 1082 bp. All of unigenes were annotated to seven public databases. Three comparisons were separately conducted between the infected groups at 3 h, 24 h, 48 h post-challenge and control group. A total of 2482 differentially expressed unigenes (DEGs) were identified. Among these, 114 immune-related DEGs were captured, including 88, 42, and 31 genes at 3 h, 24 h and 48 h after infection respectively, for analysis of expression pattern and enrichment. The 114 DEGs displayed four expression patterns by cluster analysis and they were significantly enriched in 38 pathways (q < 0.01) related to the immune or disease, five of which were NF-kappa B, TNF, NLR, TLR and RLR pathways. Finally, the expression levels of twelve selected immune-related DEGs involved in above five pathways were scrutinized. Seven of which were up-regulated at 3 h after infection, afterward, their expression dropped to control level. In summary, this study provides valuable transcriptome resource for understanding the defense mechanisms of C. gariepinus in resistance to pathogens from the gene expression viewpoint, which also open up the possibility to study the immune complexity and to better comprehend the interrelationships between some immune pathways in C. gariepinus. Highlights • It's the first study on spleen transcriptome of C. gariepinus infected by A. Veronii • One hundred and fourteen differentially expressed immune-related genes were captured. • Above genes were significantly enriched in 38 pathways related to immune or disease. • The expression levels of 12 genes involved in five pathways were scrutinized. [ABSTRACT FROM AUTHOR]