Identification and prognostic biomarkers among ZDHHC4/12/18/24, and APT2 in lung adenocarcinoma.

S-palmitoylases and S-depalmitoylases are differentially expressed in various cancers and several malignant tumors and show a strong prognostic ability. Notwithstanding, the potential clinical impact of S-palmitoylases and S-depalmitoylases, particularly in the prognosis and progression of lung adenocarcinoma (LUAD), has not been clarified. Expression levels of S-palmitoylases and S-depalmitoylases in LUAD were investigated using TCGA. GEPIA was used to evaluate the mRNA levels of S-palmitoylases and S-depalmitoylases at different pathological stages. Metascape was used to investigate the biological significance of S-palmitoylases and S-depalmitoylases. The Kaplan-Meier plotter was used to analyze the prognostic value of S-palmitoylases and S-depalmitoylases. CBioportal was used to analyze gene alterations in S-palmitoylases and S-depalmitoylases. UALCAN was used to examine DNA promoter methylation levels of S-palmitoylases and S-depalmitoylases. Finally, we investigated the relationship between S-palmitoylases, S-depalmitoylases, and tumor-infiltrating immune cells using TIMER. Correlations with immune checkpoint-related genes were determined using the R packages reshape2, ggpubr, ggplot2, and corrplot. PCR was also performed to assess the degree of ZDHHC4/12/18/24 and APT2 transcript expression in lung adenocarcinoma and adjacent normal lung tissues. HPA was utilized to investigate protein levels of S-palmitoylases and S-depalmitoylases in LUAD and normal lung tissue. Our study found that ZDHHC2/3/4/5/6/7/9/12/13/16/18/20/21/23/24, APT1/2, PPT1, LYPLAL1, ABHD4/10/11/12/13 and ABHD17C mRNA expression was significantly upregulated in LUAD, whereas ZDHHC1/8/11/11B/14/15/17/19/22, ABHD6/16A and ABHD17A mRNA expression was significantly downregulated. The functions of the differentially expressed S-palmitoylases and S-depalmitoylases were mainly associated with protein-cysteine S-palmitoyltransferase and protein-cysteine S-acyltransferase activities. Patients with high expression of ZDHHC4/12/18/24, APT2, ABHD4, ABHD11 and ABHD12 had a shorter overall survival. Infiltration of six immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) was closely associated with the expression of ZDHHC4/12/18/24 and APT2. ZDHHC4/12/18/24 and APT2 positively correlated with the immune checkpoint-related gene CD276. We assessed the mRNA levels of ZDHHC4/12/18/24 and APT2 using qRT-PCR and found increased expression of ZDHHC4/12/18/24 in LUAD compared with healty control lung tissues. ZDHHC4/12/18/24, and APT2 are potential prognostic biomarkers of LUAD. Their expression levels could be related to the tumor microenvironment in LUAD.

Epidemiological investigation of lower respiratory tract infections during influenza A (H1N1) pdm09 virus pandemic based on targeted next-generation sequencing.

Background: Co-infection has been a significant contributor to morbidity and mortality in previous influenza pandemics. However, the current influenza A (H1N1) pdm09 virus pandemic, as the first major outbreak following the SARS-CoV-2 pandemic, may differ epidemiologically. Further investigation is necessary to understand the specific features and impact of this influenza A pandemic. Study design: We conducted a retrospective cohort study at a Chinese hospital between January and April 2023, focusing on patients with lower respiratory tract infections. Pathogen detection employed targeted next-generation sequencing (tNGS) on bronchoalveolar lavage fluid (BALF) or sputum samples. Results: This study enrolled 167 patients with lower respiratory tract infections, and the overall positivity rate detected through tNGS was around 80%. Among them, 40 patients had influenza A (H1N1) pdm09 virus infection, peaking in March. In these patients, 27.5% had sole infections, and 72.5% had co-infections, commonly with bacteria. The frequently detected pathogens were Aspergillus fumigatus, SARS-CoV-2, and Streptococcus pneumoniae. For non-influenza A virus-infected patients, the co-infection rate was 36.1%, with 42.3% having SARS-CoV-2. Patients with influenza A virus infection were younger, had more females and diabetes cases. Among them, those with sole infections were older, with less fever and asthma but more smoking history. Regarding prognosis, compared to sole influenza A virus infection, co-infected patients demonstrated higher 21-day recovery rates and a higher incidence of heart failure. However, they exhibited lower proportions of respiratory failure, acute kidney failure, septic shock, and hospital stays lasting more than 10 days. Interestingly, patients with non-influenza A virus infection had a significantly lower 21-day recovery rate. Correlation analysis indicated that the 21-day recovery rate was only associated with influenza A (H1N1) pdm09 virus. Conclusion: During the current pandemic, the influenza A (H1N1) pdm09 virus may have been influenced by the SARS-CoV-2 pandemic and did not exhibit a strong pathogenicity. In fact, patients infected with influenza A virus showed better prognoses compared to those infected with other pathogens. Additionally, tNGS demonstrated excellent detection performance in this study and showed great potential, prompting clinical physicians to consider its use as an auxiliary diagnostic tool.