The complement system plays a pivotal role in the body’s immune defense mechanism. Its key effector molecule C5a and its primary receptor C5aR1 exhibit complex “double-edged sword” effects in various disease processes, including infectious diseases, inflammatory conditions, tumors, and metabolic disorders. Under normal physiological conditions, moderate levels of C5a bind to the C5aR1 receptor, recruiting immune cells to the site of infection to participate in immune defense and enhancing the body’s ability to clear pathogens. However, in various disease states, the C5a-C5aR1 pathway primarily shapes the disease microenvironment through regulating cellular pro-inflammatory and immune functions, angiogenesis processes, and tissue repair processes. It also promotes tumor immune escape through a novel mechanism through modulating the polarization of myeloid-derived suppressor cells (MDSCs) and regulating T cell function. The C5a-mediated “inflammation–fibrosis–metabolic reprogramming” vicious cycle has become a key molecular basis driving disease progression, maintaining pathological states, and promoting abnormal tissue damage repair in chronic inflammatory diseases. Through elucidating the structural biology of C5aR1 and designing allosteric modulators, nanobodies, and bifunctional molecules as new targeted intervention strategies, we aim to accelerate research progress in related medical fields. This article reviewed the molecular mechanisms of the complement system in tumor immune escape, chronic inflammation, fibrosis, and cardiovascular diseases, and explored the translational potential of targeted interventions. These discussions provide a solid theoretical foundation and new research perspectives for the medical field, aiding in the advancement of further discoveries.

Grass carp (Ctenopharyngodon idella) and barbel chub (Squaliobarbus curriculus)—both Leuciscinae subfamily species—demonstrate differences in grass carp reovirus (GCRV) infection resistance. We infected barbel chubs with type II GCRV and subjected their liver, spleen, head kidney, and trunk kidney samples to investigate anti-GCRV immune mechanisms via RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). We identified 139, 970, 867, and 2374 differentially expressed genes (DEGs) in the liver, spleen, head kidney, and trunk kidney, respectively. Across all four tissues, gene ontology analysis revealed significant immune response-related DEG enrichment, and the Kyoto Encyclopedia of Genes and Genomes analysis revealed pattern recognition receptor (PRR) and cytokine-related pathway enrichment. We noted autophagy pathway enrichment in the spleen, head kidney, and trunk kidney; apoptosis pathway enrichment in the spleen and trunk kidney; and complement- and coagulation-cascade pathway enrichment in only the spleen. Comparative transcriptome analysis between GCRV-infected barbel chubs and uninfected barbel chubs comprehensively revealed that PRR, cytokine-related, complement- and coagulation-cascade, apoptosis, and autophagy pathways are potential key factors influencing barbel chub resistance to GCRV infection. qRT-PCR validation of 11 immune-related DEGs confirmed our RNA-seq data’s accuracy. These findings provide a theoretical foundation and empirical evidence for the understanding of GCRV infection resistance in barbel chub and hybrid grass carp–barbel chub breeding.

In this work, we reported the complete mitochondrial genome of Corydoras duplicareus. The total length of the mitochondrial genome is 16,667 bp, with the base composition of 32.90% A, 26.55% T, 25.94% C, and 14.61% G. It contains two ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes, and a major non-coding control region (D-loop region). The arrangement of these genes is the same as that found in the Siluriformes. All the protein initiation codons are ATG, except for cox1 that begins with GTG. The cytochrome c oxidase subunit I (COX1) amino acid sequence of C. duplicareus and other 27 species from 8 genera were used for phylogenetic analysis by maximum likelihood method. The topology demonstrated that all species are divided into two groups (Callichthyidae and Cyprinidae), and the C. duplicareus was clustered with C.nattereri.

To investigate the effects of feeding frequency on the growth, intestinal health, and metabolism of larval red-tailed catfish (Hemibagrus wyckioides) cultured in land-based circular tanks, a 56-day feeding trial was conducted. A total of 450 fish (8.47 ± 0.36 g) were randomly allocated to three feeding frequencies: twice (F2), three times (F3), and four times (F4) daily. The results revealed that the F3 group had a significantly better feed conversion rate, specific growth rate, and weight gain rate compared to the F4 group (p < 0.05). Lipase activity and villus height were also significantly greater in the F3 group compared to the other groups (p < 0.05). The transcriptome of the F3 group showed significant enrichment in immune- and metabolism-related pathways. Additionally, the F3 group had a higher abundance of beneficial Clostridium compared to the other groups. Plesiomonas was identified as the main contributor in the F3 group, and its abundance was significantly decreased in the F4 group (p < 0.05). These findings indicated that a feeding frequency of three times per day improves the growth performance of H. wyckioides in aquaculture by increasing the abundance of beneficial Clostridium and Plesiomonas, activating multiple immune pathways, and enhancing amino acid metabolism.

Complement factor I (CFI), a complement inhibitor, is well known for regulating the complement system activation by degrading complement component 3b (C3b) in animal serum, thus becoming involved in innate defense. Nevertheless, the functional mechanisms of CFI in the complement system and in host-pathogen interactions are far from being clarified in teleost fish. In the present study, we cloned and characterized the CFI gene, CiCFI, from grass carp (Ctenopharyngodon idella) and analyzed its function in degrading serum C3b and expression changes after grass carp reovirus (GCRV) infection. The open reading frame of CiCFI was found to be 2121 bp, encoding 706 amino acids with a molecular mass of 79.06 kDa. The pairwise alignments showed that CiCFI shared the highest identity (66.9%) with CFI from Carassius gibelio and the highest similarity (78.7%) with CFI from Danio rerio. The CiCFI protein was characterized by a conserved functional core Tryp_SPc domain with the catalytic triad and substrate binding sites. Phylogenetic analysis indicated that CiCFI and the homologs CFIs from other teleost fish formed a distinct evolutionary branch. Similar with the CFIs reported in mammals, the recombinant CiCFI protein could significantly reduce the C3b content in the serum, demonstrating the conserved function of CiCFI in the complement system in the grass carp. CiCFI mRNA and protein showed the highest expression level in the liver. After GCRV infection, the mRNA expressions of CiCFI were first down-regulated, then up-regulated, and then down-regulated to the initial level, while the protein expression levels maintained an overall downward trend to the late stage of infection in the liver of grass carps. Unexpectedly, the protein levels of CiCFI were also continuously down-regulated in the serum of grass carps during GCRV infection, while the content of serum C3b proteins first increases and then returns to the initial level, suggesting a distinct role of CiCFI in regulating complement activation and fish-virus interaction. Combining our previous results that complement factor D, a complement enhancer, shows continuously up-regulated expression levels in grass carps during GCRV infection, and this study may provide the further essential data for the full picture of complex complement regulation mechanism mediated by Df and CFI of the grass carp during pathogen infection.