Biology

Autoimmune diseases result from a breakdown of immune tolerance influenced by genetic and environmental factors. Regulatory T cells (Tregs) maintain immune homeostasis, while interferon-γ (IFNγ) has context-dependent proinflammatory and regulatory roles. In B10.S mice, mercury-induced autoimmunity (HgIA) emerges within approximately 4 weeks of Hg exposure and is marked by antinucleolar antibody (ANoA) production, polyclonal B-cell activation, and deposition of immune complexes in the kidney. We investigated whether Tregs attenuate HgIA and evaluated IFNγ’s role in this regulation. Female WT and IFNγ^−/− B10.S mice received HgCl₂ or water for 4 weeks until all mice developed ANoA. CD4⁺CD25⁺Foxp3⁺ Tregs or CD4⁺CD25⁻Foxp3⁻ cells were transferred into HgCl₂-exposed WT recipients and monitored for 13 weeks. Compared with Hg-primed non-Tregs, Hg-primed WT Tregs were statistically associated with significantly reduced autoantibody levels, lower IgG1/IgG2a, and significantly decreased glomerular IgG/C3c deposition, suggesting that Hg exposure may modulate Treg function. Conversely, both water- and Hg-primed Tregs and non-Tregs from IFNγ^−/− donors elicited profoundly diminished autoantibody production and renal pathology in recipients. IFNγ^−/− mice lacked fibrillarin-specific responses, highlighting its requirement for HgIA initiation. While non-Treg transfer failed to suppress HgIA, Treg transfer reduced HgIA and highlighted relevance for immune-regulatory therapies, especially where environmental toxicants may drive autoimmune disease.

The snailfish family (Liparidae) represents one of the most rapidly speciating and ecologically diverse lineages of marine fishes, with species distributed across a broad bathymetric range from intertidal zones to the hadal depths. Despite their ecological and evolutionary significance, phylogenetic relationships and adaptive mechanisms within Liparidae remain poorly resolved due to morphological conservatism, phenotypic plasticity, and limited genomic resources due to challenges such as sampling difficulties and a reliance on partial mtDNA markers. In this study, we sequenced, assembled, and annotated the complete mitochondrial genomes of two snailfish species, Liparis chefuensis and Liparis tanakae, collected from the Yellow Sea. The mitogenome of L. chefuensis is 18,870 bp in length, encoding 13 protein-coding genes (PCGs), 2 rRNAs, and 22 tRNAs, while that of L. tanakae spans 17,485 bp and contains 13 PCGs, 2 rRNAs, and 23 tRNAs. Phylogenetic reconstruction based on the concatenated sequences of 13 mitochondrial PCGs from 15 liparid species revealed that L. chefuensis clusters within the subgenus Lyoliparis, contradicting its previous classification under Careliparis and suggesting a need for taxonomic reassessment. Notably, we identified distinct patterns of tRNA gene rearrangement in the cluster between ND2 and COI, which suggest a link to both phylogeny and habitat depth. Shallow-water species (<30 m) possess the tRNA^Trp-tRNA^Tyr-tRNA^Ala-tRNA^Asn-tRNA^Cys (WYANC) arrangement, whereas deep-water species (>100 m) display the derived tRNA^Trp-tRNA^Asn-tRNA^Cys-tRNA^Tyr-tRNA^Ala-tRNA^Cys/tRNA^Ala (WNCYAC/A) configurations. These rearrangements are hypothesized to originate from tandem duplication events followed by random gene loss, potentially reflecting adaptive evolution to deep-sea environments. Additionally, L. tanakae exhibits a markedly higher number of non-canonical G–U and A–C base pairs in its tRNA secondary structures, indicating substantial structural divergence. Our findings not only provide essential mitogenomic resources for snailfish systematics and species identification but also propose that tRNA rearrangements in mitochondrial genomes may serve as genomic innovations facilitating deep-sea colonization. This study enhances our understanding of mitochondrial genome evolution and environmental adaptation in marine fishes.

This study sought to evaluate the neuroprotective effects of YGD in an oxidative stress-induced Alzheimer’s disease (AD)-like cellular model and to elucidate the underlying molecular pathways, with a focus on tau phosphorylation, Aβ accumulation, and antioxidant defense mechanisms. Rat primary hippocampal neurons were exposed to hydrogen peroxide to induce oxidative stress. The effects of YGD on neuronal viability, neurite outgrowth, and synaptic integrity were assessed using the immunodetection of microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD-95), and synapsin-1. Levels of phosphorylated tau and Aβ were quantified, and the involvement of extracellular signal-regulated kinase (ERK), glycogen synthase kinase 3β (GSK3β), and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways was examined. Additionally, in silico molecular docking studies targeting the ATP-binding site of GSK3β were conducted to screen major phytochemicals from the ten medicinal herbs constituting YGD. YGD markedly enhanced neuronal viability under oxidative stress, promoted neurite extension, and increased synaptic marker expression (MAP2, PSD-95, and synapsin-1). Treatment reduced phosphorylated tau by suppressing ERK and GSK3β activation and significantly decreased Aβ accumulation. YGD also upregulated antioxidant defenses via the activation of the Nrf2 pathway. Docking simulations identified oleanolic acid (from Cornus officinalis) as the most potent GSK3β binder (−9.86 ± 0.40 kcal/mol), forming stable interactions with ARG96, ASN95, and GLU97. Additional compounds, including alisol C, drypemolundein B, and friedelin, demonstrated favorable binding energies and engaged key ATP-binding site residues. YGD confers neuroprotection through the integrated modulation of tau phosphorylation, Aβ pathology, and oxidative stress, partly via the multi-target engagement of GSK3β by its constituent phytochemicals. These findings support that YGD attenuates oxidative stress-induced AD-like cellular alterations.