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Abstract Background FANCA mutations have been detected in a variety of cancers and found to be pro-carcinogenic. However, no functional studies have been identified regarding the involvement of FANCA in the occurrence and the immune response of LUAD. Methods The mRNA expression and overall survival rates of FANCA were evaluated by the TIMER, PrognoScan and TCGA database in LUAD tissues, and FANCA expression was further validated by clinical serum samples using ELISA. The correlation between FANCA and immune infiltration level was investigated via TISIDB database and CIBERSORT algorithm. The Kaplan–Meier plotter was used to further evaluate the prognostic value based on the expression levels of FANCA in related immune cells. Then, the influence of FANCA knockout on the proliferation, migration, and invasion of A549 and H1299 cells was validated using CCK8, cloning formation, and Transwell assays. Subsequently, HLA-A2-restricted FANCA antigenic peptides were predicted and synthesized by NetMHC4.0 and SYFPEITHI, and DCs were induced and cultured in vitro. Finally, DCs loaded with HLA-A2-restricted FANCA antigenic peptides were co-cultured with autologous peripheral blood lymphocyte to generate specific CTLs. The killing effects of different CTLs on LUAD cells were studied. Results The results showed that high levels of FANCA in patients with LUAD were significantly correlated with worse OS survival, which was correlated with age, clinical stage, pathological T stage, M stage, and N stage in LUAD. Knockdown of FANCA in A549 and H1299 cells significantly inhibited proliferation, metastasis, and invasion in vitro. In addition, FANCA was significantly related to immune infiltrate, genomic alterations and TMB. FANCA expression infuenced the prognosis of LUAD patients by directly affecting immune cell infltration. Finally, HLA-A2-restricted FANCA antigenic peptides were synthesized. And FANCA 146–154 (SLLEFAQYL) antigenic peptide exhibit a stronger affinity for DCs, and induce CTLs to produce stronger targeted killing ability for LUAD cells at an effector-to-target ratio of 40:1. Conclusion These results demonstrated that the elevation of FANCA promotes malignant phenotype of LUAD, and the potential peptide P2 (SLLEFAQYL) derived from FANCA may be used as an epitope vaccine for the treatment of LUAD.

Amino-cured epoxy resins are widely used in the electrical and electronic industry for their excellent properties. To investigate the mechanism of the effect of O2 and H2O on the pyrolysis behavior of epoxy resin, in this paper, the cross-linked structure of bisphenol A type epoxy resin cured by adducts of diethylenetriamine and butyl glycidyl ether is modeled based on the ReaxFF force field, and the thermal decomposition processes at different temperatures and gas atmospheres were simulated and the pathways of the small molecule products were clarified. The results show that epoxy resin will produce small molecule gas products, such as H2, CO, H2O, OH, CH2O, and free radicals, in the process of pyrolysis; the presence of amino groups also generates nitrogen-containing radicals, such as CN, CH2N, and C2H4N; as the reaction temperature increases, the rate of pyrolysis reaction will be accelerated. The same temperature in oxygen and water atmospheres can accelerate the breakage of epoxy resin main chain by promoting the breakage of carbon and oxygen bonds and, at the same time, promote the generation of small molecule gases, such as H2 and CO.

Abstract Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers’ and 289 LUAD patients’ serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.

BackgroundThe severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19.MethodsA control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored.ResultsCompared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8–15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group.ConclusionsThe levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. It is essential to explore the immune response characteristics of peripheral circulation in COVID-19 patients to reveal pathogenesis and predict disease progression. In this study, the levels of total immunoglobulins (IgG, IgM, IgA), complement (C3, C4)，lymphocyte subsets (CD3+ cell，CD4+ cell，CD8+ cell, NK cell, CD19+ cell and CD45+ cell) and cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-12p, IL-1β, TNF-α, IFN-α and IFN-γ) were retrospectively analyzed in COVID-19 patients. A total of 513 patients were enrolled in this study, cases were distributed according to clinical status as mild or moderate (n = 212), severe survivors (n = 197) and severe non-survivors (n = 104). IL-6, IL-8, IL-10 and IFN-γ were increased in severe patients compared with non-severe patients, despite decreased CD45+ cell, CD3+ cell, CD4+ cell, CD8+ cell, CD19+ cell, and NK cell. Compared with severe survivors, the levels of L-6, IL-8 and IL-10 in non-survivors increased significantly, and levels of C3, CD45+ cell, CD3+ cell，CD4+ cell，CD8+ cell, and NK cell decreased. Moreover, age, IL-8, IL-10, CD8+cells and NK cell were independent risk factors for the severity of COVID-19. Multivariable regression showed increasing odds ratio of in-hospital death associated with tumor, older age, higher IL-8 level, and decreasing odds ratio of in-hospital death associated with increased levels of CD8+cell and NK cell. Finally, patients with tumor, or high IL-6 or high IL-10 expression and lower CD8+ or lower NK levels exhibited a significantly shorter survival time. In conclusion, our study provides findings of the immunological characteristics associated with disease severity to predict the progression of COVID-19. The immune inflammation factors, such as IL-6, IL-8, IL-10, CD8+ cell and NK cell, could serve as excellent biomarkers for monitoring or predicting COVID-19 progression therapeutic to COVID-19 patients.