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Density functional theory (DFT), atoms in molecules (AIM) theory, natural bond orbital (NBO) analysis, and Wiberg bond index (WBI) are employed to investigate the mechanism of lignin dissolution and regeneration in 1-allyl-3methylimidazolium chloride (AmimCl). Lignin is modeled with 1-(4-methoxyphenyl)-2-methoxyethanol (LigOH). From the theoretical results, it is observed that AmimCl interacts with LigOH mainly by hydrogen bonds (H bonds), and the interaction of AmimCl with LigOH is stronger than that of LigOH with LigOH; thus, it can be speculated that lignin can be dissolved in AmimCl. In addition, the H bonds between LigOH and AmimCl are weakened or even destroyed by the addition of water. The experimental results also reveal that lignin can be easily regenerated from the AmimCl−lignin solution by the addition of water. The regenerated lignin is characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetry (TG), and scanning electron microscopy (SEM) compared to the original lignin.

Staphylococcus epidermidis (S. epidermidis) plays a critical role in modulating cutaneous inflammatory responses in skin. Although S. epidermidis has been shown to co-colonize with Propionibacterium acnes (P. acnes) in acne lesions, it is unclear whether S. epidermidis is involved in the regulation of P. acnes-induced inflammatory responses. In this study, we demonstrated that S. epidermidis inhibited P. acnes-induced inflammation in skin. P. acnes induced the expression of interleukin-6 and tumor necrosis factor-α via the activation of toll-like receptor (TLR) 2 in both keratinocytes and mouse ears. Staphylococcal lipoteichoic acid activated TLR2 to induce miR-143 in keratinocytes, and miR-143, in turn, directly targeted 3' UTR of TLR2 to decrease the stability of TLR2 mRNA and then decreased TLR2 protein, thus inhibiting P. acnes-induced proinflammatory cytokines. The inhibitory effect of miR-143 was further confirmed in vivo as the administration of miR-143 antagomir into mouse ears abrogated the inhibitory effect of lipoteichoic acid on P. acnes-induced inflammation in skin. Taken together, these observations demonstrate that staphylococcal lipoteichoic acid inhibits P. acnes-induced inflammation via the induction of miR-143, and suggest that local modulation of inflammatory responses by S. epidermidis at the site of acne vulgaris might be a beneficial therapeutic strategy for management of P. acnes-induced inflammation.

BackgroundImmune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.MethodsWe performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), in vitro functional studies, and in vivo transposon-based mouse models.ResultsIntegrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with KRAS mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity.ConclusionsOur study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.