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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.

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.

Abstract Background Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. Results The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. Conclusions In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

BackgroundCircular RNAs (circRNAs) play an important role in tumorigenesis and several circulating circRNA signatures are closely associated with tumor diagnosis. However, the expression and clinical significance of the two forms of circulating circRNAs, serum and serum exosomal, in patients with lung adenocarcinoma (LUAD), have not been characterized.MethodsThree differentially expressed exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were selected based on previous exosomal circRNA sequencing data analyses of LUAD patients. The expression of these circRNAs in serum and serum-derived exosomes of LUAD patients was assessed using quantitative real-time PCR (qRT-PCR), and correlations between circRNA expression and clinicopathological characteristics were analyzed. The reliability of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 to diagnose LUAD was evaluated using receiver operating characteristic (ROC) analysis.ResultsExpression of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 were significantly higher in LUAD patients than in healthy donors, and significantly lower after surgery. These three serum exosomal circRNAs were also associated with a higher cancer stage. Exosomal hsa_circ_0001492 expression was positively correlated with carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) levels. An association between the expression of the three serum circRNAs and clinical characteristics was not observed. In addition, the three serum exosomal circRNAs had higher diagnostic sensitivity and specificity than the serum circRNAs, and the area under the curve (AUC) of all three serum exosomal circRNAs was >0.75. The combination of exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 had better diagnostic sensitivity and specificity than that of a single marker, with an AUC value of 0.805.ConclusionsThe serum and serum exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were upregulated in LUAD patients. Serum exosomal circRNAs may serve as more effective biomarkers than serum circRNAs for LUAD diagnosis and may further aid the detection of this disease.

(1) Background: Toluene gas is widely used in indoor decoration and industrial production, and it not only pollutes the environment but also poses serious health risks. (2) Methods: In this work, TiO2−CoFe2O4−Ag quaternary composite gas-sensing material was prepared using a hydrothermal method to detect toluene. (3) Results: The recombination of electron–hole pairs was suppressed, and the light absorption range was expanded after constructing a heterojunction and doping with Ag, according to ultraviolet–visible (UV–vis) diffuse reflectance spectra and photoluminescence spectroscopy. Moreover, in the detection range of toluene gas (3 ppm–50 ppm), the response value of TiO2−CoFe2O4−Ag increased from 2 to 15, which was much higher than that of TiO2−Ag (1.7) and CoFe2O4−Ag (1.7). In addition, the working temperature was reduced from 360 °C to 263 °C. Furthermore, its response/recovery time was 40 s/51 s, its limit of detection was as low as 10 ppb, and its response value to toluene gas was 3–7 times greater than that of other interfering gases under the same test conditions. In addition, the response value to 5 ppm toluene was increased from 3 to 5.5 with the UV wavelength of 395 nm–405 nm. (4) Conclusions: This is primarily due to charge flow caused by heterojunction construction, as well as metal sensitization and chemical sensitization of novel metal doping. This work is a good starting point for improving gas-sensing capabilities for the detection of toluene gas.

It is of great significance to develop ethanol sensors with high sensitivity and low detection temperature. Hence, we prepared Au-supported material on mesoporous ZnO composites derived from a metal-organic framework ZIF-8 for the detection of ethanol gas. The obtained Au/ZnO materials were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (SEM), field emission transmission electron microscopy (TEM) and nitrogen adsorption and desorption isotherms. The results showed that the Au/ZnO-1.0 sample maintains a three-dimensional (3D) dodecahedron structure with a larger specific surface area (22.79 m2 g−1) and has more oxygen vacancies. Because of the unique ZIF structure, abundant surface defects and the formation of Au-ZnO Schottky junctions, an Au/ZnO-1.0 sensor has a response factor of 37.74 for 100 ppm ethanol at 250 °C, which is about 6 times that of pure ZnO material. In addition, the Au/ZnO-1.0 sensor has good selectivity for ethanol. According to density functional theory (DFT) calculations, the adsorption energy of Au/ZnO for ethanol (−1.813 eV) is significantly greater than that of pure ZnO (−0.217 eV). Furthermore, the adsorption energy for ethanol is greater than that of other gases.

Abstract Background Human papillomavirus (HPV) infection is the main etiological factor for the development of cervical cancer. Here we assessed the prevalence and distribution of HPV genotypes in Fujian population. Methods A total of 8678 women aging from 17 to 84 years olds were recruited from the Fujian Medical University Union Hospital in Fujian Province. Every woman had a face-to-face interview. Cervical samples were collected from each participant and HPV screening was conducted using microarray hybridization. Results Our study showed that the HPV prevalence in Fujian province was 38.3%. Among the positive individuals, 70.6% were detected for single HPV infection, 29.4% for multiple HPV infections. Further analysis showed that the prevalence of HPV infection significantly increased from 2009 to 2015. The four most common high risk human papillomavirus (HR-HPV) genotypes were HPV16 (8.5%), HPV52 (7.9%), HPV58 (6.2%), HPV 53 (3.5%), collectively accounting for 60.5% of all detected HPV infection. Age subgroup analysis showed two peaks for the frequencies of overall and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 55 years old. Conclusions HPV infection is becoming serious in Fujian province, which indicates the imperative to implement a HPV vaccination and screening program for this region.