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Objectives To analyze the evolution pattern of matrix (M) gene and amino acid site variation of M2 protein of influenza A (H1N1) pdm09 viruses in Hainnan province during the influenza epidemic season 2019-2020 (April 1, 2019 - March 29, 2020). Methods A total of 14 strains of influenza A (H1N1) pdm09 subtype virus was selected for sequencing. The phylogenetic trees were constructed by neighbor-jointing method, and the differences between the prevalent and vaccine strains in Hainan were compared by gene evolutionary trees. The sequencing results were analyzed by MEGA 10.1.8 and DNASTAR 7.0.1 software. Results During 2019-2020 influenza season influenza A (H1N1) pdm09 virus accounted for 4.9% of total influenza viruses detected in Hainan province. Phylogenetic analysis showed that M gene of influenza A (H1N1) pdm09 virus isolates in Hainan province from 2019 to 2020 could be divide into 6B.1 clade, be same with the international vaccine strain A/Brisbane/02/2018. The nucleotide and amino acid similarities were 98.7%-100.0%, 98.8%-100.0% respectively. And 12 isolates had mutations in amino acid S23N in the coding region of the extracellular region of the protein; all 14 isolates had mutations in the S31N site in the transmembrane region, and the mutation rate was 100.0%. There was 1 isolate with amino acid variation at the I39V locus and 9 isolates with amino acid variation at the E70D locus in the cytoplasmic region. Conclusions These data suggest that the activity of influenza A (H1N1) pdm09 virus was low level in Hainan province during 2019-2020 influenza season. The strains isolated in Hainan province have remained resistant to amantadine, and the circulating viruses were matched by current influenza vaccine. Special attention should be paid to the amino acid variation of M2 protein in future work to provide a scientific basis for the use of clinical anti-influenza virus drugs. [ABSTRACT FROM AUTHOR]

Background: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited., Aim: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer., Methods: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model., Results: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes ( SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL ) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma., Conclusion: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)