The polymorphic membrane protein D (PmpD) is a highly conserved outer membrane protein which plays an important role in pathogenesis during Chlamydia psittaci infection. In this study, we evaluated the ability of the N-terminus of PmpD (PmpD-N) to modulate the functions of chicken macrophages and the signaling pathway(s) involved in PmpD-N-induced Toll-like receptors (TLRs), as well as interleukin (IL)-6 and IL-10 cytokine secretions. Thus, HD11 macrophages were treated with exogenous and intracellular PmpD-N of C. psittaci. The chlamydial growth was evaluated by enumeration of chlamydial loads in the infected macrophages. The phagocytic function of macrophages following PmpD-N treatment was detected by fluorescein-labeled Escherichia coli (E. coli). The concentration of nitric oxide (NO) secreted by HD11 macrophages was measured by the amount of NO₂^- in the culture supernatant using the Griess method. The cytokine secretions were assessed using multiplex cytokine ELISA kits. Expression levels of TLRs, myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) were analyzed by a Western blotting assay, as well as a luciferase assay, while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The nuclear translocation of the transcription factor NF-κB was confirmed by evaluating its ability to combine with the corresponding promoter using the electrophoretic mobility shift assay (EMSA). After treatment with exogenous or endogenous PmpD-N, chlamydial loads and phagocytic functions were reduced significantly compared with those of the plasmid vector group, while NO secretions were reduced significantly compared with those of the lipopolysaccharide (LPS) treatment. Stimulation of HD11 cells with PmpD-N provoked the secretion of the Th2 cytokines, IL-6, and IL-10 and upregulated the expression of TLR2, TLR4, MyD88, and NF-κB. Furthermore, inhibition of TLR2, MyD88, and NF-κB in HD11 cells significantly decreased IL-6 and IL-10 cytokine levels, while NO production and phagocytosis increased significantly, strongly suggesting their involvement in PmpD-N-induced Th2 cytokine secretion and macrophage dysfunction. Our data indicate that C. psittaci PmpD-N inhibited macrophage functions by activating the Th2 immune response and the TLR2/MyD88/NF-κB signaling pathway.

Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis B (CHB), with macrophage M2 polarization playing a critical role in shaping the tumor-promoting hepatic immune microenvironment. Sirtuin 1 (SIRT1) has been implicated in immune modulation and liver carcinogenesis. This study investigates the potential of Mimetic Nanoparticles (MNPs) for delivering SIRT1 inhibitors to regulate macrophage polarization and remodel the hepatic immune microenvironment, aiming to prevent HCC development post-CHB. A transgenic mouse model of CHB was established, and RNA sequencing (RNA-seq) and proteomics analyses revealed significant dysregulation of genes associated with M2 macrophage polarization, particularly SIRT1. Functional enrichment analysis highlighted key pathways, including PI3K-Akt and NF-κB, that contribute to CHB-driven immune alterations. Synthesized and characterized MNPs successfully delivered SIRT1 inhibitors, effectively inhibiting M2 macrophage polarization in vitro. In vivo administration of MNPs-SIRT1-FN significantly reduced M2 macrophage infiltration and suppressed tumor growth. These findings suggest that nanoparticle-mediated SIRT1 inhibition is a promising strategy for immunomodulation and HCC prevention in CHB patients. This study provides novel insights into nanoparticle-based immunotherapy for CHB-related HCC and highlights a potential therapeutic avenue for liver cancer prevention.

The authors would like to make the following corrections to their paper, published in the International Journal of Molecular Sciences

Clostridium perfringens is an anaerobic, toxin-producing pathogen responsible for enteric and systemic disease in livestock, yet its ecology in high-altitude yaks remains poorly understood. We conducted a comprehensive investigation covering eight counties of the Xizang Autonomous Region between July 2021 and October 2024. Serological screening of 922 unvaccinated yaks revealed an individual-level antibody prevalence of 0.76% (95% CI: 0.4–1.6) and a herd-level prevalence of 25% (95% CI: 12.7–43.4). Multivariable logistic regression identified residence below 4000 m as the sole significant risk factor (adjusted OR = 8.75; 95%CI: 1.3–56.8; P = 0.04). From seven seropositive animals, one representative isolate CPTibet-Y1 was obtained and subjected to detailed phenotypic, genomic and virulence analyses. Phenotypic profiling confirmed classic biochemical traits of C. perfringens, while 16 S rRNA, Toxin gene PCR typing and whole-genome sequencing classified the strain as toxin type A, harboring Toxin gene cpa, but lacking cpb, etx, iap, cpe and netB. Antimicrobial resistance profiling revealed broad-spectrum resistance encompassing sulfonamides, lincosamides and fluoroquinolones, underpinned by six acquired resistance determinants. In a murine infection model, intraperitoneal challenge with 5 × 10⁷ CFU resulted in 100% lethality within 48 h accompanied by severe intestinal necrosis, hemorrhage and systemic pathology. This study provides unequivocal evidence for the presence of multidrug-resistant, hypervirulent type A strains on the Qinghai-Tibet Plateau, underscoring the need for enhanced surveillance and targeted control strategies in yak-farming communities.