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ABSTRACT Background Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium‐binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article. Methods The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT‐PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual‐luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit‐8 (CCK‐8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E‐cadherin expression, and a western blot was used to detect the expression of MMP‐2, MMP‐9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α‐KG, and glutamate. Results S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis. Conclusion In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.

Background & Aims: Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. Methods: We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. Results: APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. Conclusions: APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

Concerns persist about attentional engagement in online learning. The inter-subject correlation of eye movements (ISC) has shown promise as an accessible and effective method for attention assessment in online learning. This study extends previous studies investigating ISC of eye movements in online learning by addressing two research questions. Firstly, can ISC predict students’ attentional states at a finer level beyond a simple dichotomy of attention states (e.g., attending and distracted states)? Secondly, whether learners’ learning styles affect ISC’s prediction rate of attention assessment in video learning? Previous studies have shown that learners of different learning styles have different eye movement patterns when viewing static materials. However, limited research has explored the impact of learning styles on viewing patterns in video learning. An eye tracking experiment with participants watching lecture videos demonstrated a connection between ISC and self-reported attention states at a finer level. We also demonstrated that learning styles did not significantly affect ISC’s prediction rate of attention assessment in video learning, suggesting that ISC of eye movements can be effectively used without considering learners’ learning styles. These findings contribute to the ongoing discourse on optimizing attention assessment in the evolving landscape of online education.

The largemouth bass is a freshwater aquacultured fish species of great economic importance in China. With the rapid development of aquaculture industry and the increase in the aquaculture density of the fish, various infectious pathogens, including parasites, bacteria, and viruses, have been widely spread, which have caused huge losses to the aquaculture industry. Among them, largemouth bass iridovirus (LMBV) is one of the most harmful pathogens. In the present study, a virus strain named LMBV-GDSD was isolated from cultured largemouth bass and was successfully proliferated in FHM and EPC cells, with numerous viral particles observed in the infected cells under transmission electron microscopy analysis. The annotated complete genome of LMBV-GDSD was 99,285 bp and contained 102 ORFs. Based on genomic sequence alignment and phylogenetic analysis, the identified LMBV-GDSD belonged to the genus Ranavirus of Iridoviridae and was pathogenic to largemouth bass under regression infection experiments. In addition, the infection of LMBV-GDSD in largemouth bass could significantly up-regulate the expression of antiviral immune-related genes such as IRF3, IRF7, and Mx. It is thus providing valuable genetic data for a deeper understanding of the pathogenic mechanism of iridovirus in largemouth bass.