In-Situ Spontaneous Electropolymerization Enables Robust Hydrogel Electrolyte Interfaces in Aqueous Batteries.

Hydrogels hold great promise as electrolytes for emerging aqueous batteries, for which establishing a robust electrode-hydrogel interface is crucial for mitigating side reactions. Conventional hydrogel electrolytes fabricated by ex situ polymerization through either thermal stimulation or photo exposure cannot ensure complete interfacial contact with electrodes. Herein, we introduce an in situ electropolymerization approach for constructing hydrogel electrolytes. The hydrogel is spontaneously generated during the initial cycling of the battery, eliminating the need of additional initiators for polymerization. The involvement of electrodes during the hydrogel synthesis yields well-bonded and deep infiltrated electrode-electrolyte interfaces. As a case study, we attest that, the in situ-formed polyanionic hydrogel in Zn-MnO2 battery substantially improves the stability and kinetics of both Zn anode and porous MnO2 cathode owing to the robust interfaces. This research provides insight to the function of hydrogel electrolyte interfaces and constitutes a critical advancement in designing highly durable aqueous batteries.

ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1.

Zinc finger CCHC-type containing 4 (ZCCHC4), RNA binding protein, has been reported to mediate rRNA methylation and affect tumor cell proliferation. However, the role of ZCCHC4 in the regulation of osteosarcoma (OS) remains unknown. ZCCHC4 was highly expressed in OS tissues and cell lines. Overexpression or silencing of ZCCHC4 promoted or inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and motility. Additionally, we proved that ZCCHC4 facilitates OS progression through upregulating integrin ß1 (ITGB1). In the animal model, ZCCHC4 knockdown reduced OS tumor growth and metastases in vivo. Our findings showed that ZCCHC4 promoted the progression of OS through upregulating ITGB1 and suggested that inhibition of ZCCHC4 could be a novel therapeutic strategy for OS.

Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

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.

Cancer/testis antigen LDHC promotes proliferation and metastasis by activating the PI3K/Akt/GSK-3ß-signaling pathway and the in lung adenocarcinoma.

The cancer/testis antigen lactate dehydrogenase-C4 (LDHC) is a specific isoenzyme of the LDH family that regulates invasion and metastasis in some malignancies; however, little is known regarding its role in progression of lung adenocarcinoma (LUAD). Thus, we investigated LDHC expression by immunohistochemistry, and analyzed its clinical significance in 88 LUAD specimens. The role and molecular mechanisms subserving LDHC in cellular proliferation, migration, and invasion were explored both in vitro and in vivo. As a result, we found that high LDHC expression was significantly correlated with clinicopathological features of aggressive LUAD and a poor prognosis. Overexpression of LDHC induced LUAD cells to produce lactate and ATP, increased their metastatic and invasive potential-, and accelerated xenograft tumor growth. We further demonstrated that overexpression of LDHC affected the expression of cell proliferation-related proteins (cyclin D1 and c-Myc) and epithelial-mesenchymal transition (EMT)-related proteins (MMP-2, MMP-9, E-cadherin, Vimentin, Twist, Slug, and Snail) both in vitro and in vivo. Finally, excessive activation of LDHC enhanced the phosphorylation levels of AKT and GSK-3ß, revealing activation of the PI3K/Akt/GSK-3ß oncogenic-signaling pathways. Treatment with a PI3K inhibitor reversed the effects of LDHC overexpression by inhibiting cellular proliferation, migration, and invasion, with diminished levels of p-Akt and p-GSK3ß. PI3K inhibition also reversed cell proliferation-related and EMT-related proteins in LDHC-overexpressing A549 cells. In conclusion, LDHC promotes proliferation, migration, invasion, and EMT in LUAD cells via activation of the PI3K/Akt/GSK-3ß pathway.

Plasma Exosomal CXCL7 is a Potential Biomarker for Lung Adenocarcinoma.

BACKGROUND: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. METHODS: The differential expression profile of plasma exosomal mRNA was established by high-throughput sequencing, and the expression and diagnostic value of plasma exosomal CXCL7 mRNA and protein in LUAD were studied to evaluate their diagnostic value as tumor biomarkers. RESULTS: The expression of plasma exosomal CXCL7 mRNA in patients with LUAD was significantly increased (p < 0.01), which had no significant correlation with age, gender, and stage. ROC was used to evaluate the diagnostic value of plasma exosomal CXCL7 mRNA in LUAD patients with AUC = 0.7171. Further analysis signified that the CXCL7 protein of plasma exosomes in LUAD patients was overexpressed, and it was positively correlated with TNM stage and age. The diagnostic value of plasma exosomal CXCL7 in LUAD is better than serum CEA, with an AUC of 0.785, which has higher sensitivity and specificity. CONCLUSIONS: This research suggests that plasma exosomal CXCL7 may become an effective biomarker for early diagnosis of LUAD.

High expression of DARS2 indicates poor prognosis in lung adenocarcinoma.

BACKGROUND: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated. METHODS: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro. RESULTS: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result. CONCLUSION: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.

Identification of a RNA-Seq Based Prognostic Signature with Seven Immune-Related lncRNAs for Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is still a worldwide challenge. Accumulated evidence demonstrates that the superiority of immune-related long noncoding RNAs (lncRNAs) are closely connected with tumorigenesis and prognosis of cancer. However, no detailed studies have been conducted to present a reliable signature for predicting prognosis in LUAD patients from the perspective of tumor immunology. The aim of this study was to con-struct a risk score model based on the signature of the group of seven immune-related lncRNAs to predict the prognosis of patients with LUAD. METHODS: We performed a genome-wide analysis of expression profiles in 522 LUAD patients from The Cancer Genome Atlas (TCGA) project to explore the prognostic ability of immune-related lncRNAs. By using Kaplan-Meier analysis, univariate/multivariate Cox regression, receiver operating characteristic curve (ROC), and principal components analysis (PCA), a risk score model was constructed based on the signature of the group of seven immune-related lncRNAs to predict the prognosis of patients with LUAD. RESULTS: Using survival analysis and Cox regression model, we identified a set of seven lncRNAs (LINC00941, FAM83A-AS1, AC026355.1, AC068338.3, AC010980.2, AL365181.2, and AC079949.2) demonstrating an ability to stratify patients into high and low risk groups with significantly different survival outcomes. Moreover, the signature was identified as an independent prognostic factor and significantly associated with the overall survival (OS) of LUAD. The area under curve (AUC) of a ROC curve for the signature of the group of seven immune-related lncRNAs in predicting OS was 0.757. In addition, low-risk and high-risk groups displayed different immune statuses based on PCA. CONCLUSIONS: This study suggested a promising seven prognostic immune-related lncRNAs risk scoring system and may provide new information for immunological treatment in LUAD.

Serum exosomal miR-7977 as a novel biomarker for lung adenocarcinoma.

Exosomal microRNAs (miRNAs) have great potentials as a novel biomarker to predict lung cancer. We applied a miRNA microarray to identify aberrantly expressed serum exosomal miRNAs as candidate biomarkers for patients with lung adenocarcinoma (LUAD). Compared with the normal control, 31 exosomal miRNAs were found to be upregulated and 29 exosomal miRNAs were downregulated in the serum of LUAD respectively. Then, 10 dysregulated exosomal miRNAs expression levels in serum were further validated via qRT-polymerase chain reaction. Notably, exosomal miR-7977 was highest expressed and miR-98-3p was lowest expressed in the patients with LUAD, and exosomal miR-7977 showed significant correlation with the N stage and TNM stage with patients with LUAD (P < .05). Receiver operating characteristic curve showed that the abundant level of exosomal miR-7977 may predict LUAD with an area of under the curve (AUC) of 0.787. In comparison with exosomal miR-7977, exosomal miR-98-3p had a smaller area (0.719). The combination of exosomal miR-7977 and miR-98-3p improved the AUC to 0.816. Furthermore, in vitro experiments revealed that inhibition of miR-7977 enhanced the proliferation, invasion, and inhibited apoptosis in A549 cells, the opposite results were performed by miR-7977 mimics. In conclusion, exosomal miR-7977 was identified as a novel biomarker for patients with LUAD and may play as a tumor suppressor in lung cancer.

Circular RNAs expression profiles in plasma exosomes from early-stage lung adenocarcinoma and the potential biomarkers.

This study aimed to identify differential circular RNA (circRNA) in the plasma exosomes of patients with lung adenocarcinoma (LUAD) using high-throughput sequencing. First, exosomes were isolated using an exosome isolation kit and confirmed by Western blotting, transmission electron microscopy, and NanoSight Assay. Subsequently, plasma circRNA expression profiles were screened by high-throughput sequencing and confirmed by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Finally, the circRNA-miRNA-mRNA network was performed to forecast the potential function of circRNAs. The result of high-throughput sequencing data documented that 182 differentially expressed exosomal circRNAs in all were screened, which included 105 that were upregulated and 78 that were downregulated in LUAD patients plasma compared with controls. The four upregulated circRNAs including circ_0001492, circ_0001346, circ_0000690, and circ_0001439 were identical to the sequencing data by qRT-PCR, and their latent circRNA-miRNA-mRNA interactions were exhibited. Taken together, our study firstly revealed the altered exosomal circRNA expression from plasma samples in patients with LUAD and supports the need for exploring their potential as biomarkers and the pathological effects of lung cancer.

Overexpression of LncRNA-UCA1 Correlates with Lung Adenocarcinoma Progression and Poor Prognosis.

BACKGROUND: Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been predicted to play a critical role in various biological processes including tumorigenesis. However, the clinical significance of UCA1 in lung adenocarcinoma (LUAD) is still not understood in detail. The aim of this study was to assess the clinical significance of the UCA1 expression levels in LUAD based on publicly available data and to evaluate its potential signaling pathways. METHODS: The RNA-sequencing (RNA-seq) dataset and clinical information of all LUAD patients were downloaded from The Cancer Genome Atlas (TCGA). Kaplan-Meier plot and log-rank test were performed for survival analysis; Cox proportional hazards regression model were used to assess the relative factors. Furthermore, Starbase, Cbioportal, and Multi Experiment Matrix starbases were used to identify UCA1-related genes in LUAD. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of UCA1-related genes were performed using DAVID. RESULTS: The expression level of UCA1 in LUAD tissues (n = 468) was significantly increased compared with the adjacent non-tumor lung tissues (n = 52) (p < 0.0001). In addition, UCA1 level was significantly correlated with TNM stage and lymph node metastasis. Survival analysis showed that UCA1 over-expression was significantly associated with poor overall survival (OS) (p = 0.0098) and poor recurrence-free survival (RFS) (p = 0.0298) in LUAD patients. Multivariate analysis confirmed that high expression of lncRNA-UCA1 was an independent prognostic factor of poor OS (HR = 1.353, 95% CI: 1.005 - 1.822, p = 0.046). Finally, KEGG analysis for UCA1-related genes indicated that UCA1 might be enriched with the microRNAs in cancer, pathways in cancer, endocytosis, focal adhesion, and proteoglycans in cancer. CONCLUSIONS: This study showed that UCA1 may be involved in lung carcinogenesis, which could act as a biomarker of prognosis and therapeutic target in LUAD patients.

[Quality evaluation of Desmodium styracifolium by fingerprint, pattern recognition combined with quantitative analysis of multi-components by single marker].

HPLC analysis was performed on a Phenomenex PS C18（4.6 mm×250 mm, 5 µm）column using methanol -0.2% formic acid (30:70) at a flow rate of 0.8 mL·min⁻¹. The column temperature was 30 °C and the detection wavelength was set at 335 nm. The injection volume was 10 µL. The HPLC fingerprint of Desmodium styracifolium was established with 10 common peaks, and 5 of them were identified as vicenin-1, schaftoside, isoorientin, isoschaftoside and isovitexin, respecivetly. The fingerprints of 21 batches of D. styracifolium samples were analyzed with similarity evaluation, cluster analysis, principal component analysis and partial least squares discriminant analysis. There was no significant difference among the quantitative results of these five ingredients verified by external standard method (ESM) and quantitative analysis of multi-components by single marker (QAMS) method. The application of fingerprint, pattern recognition combined with QAMS can provide more comprehensive references for the quality control and evaluation of D. styracifolium.

Improvement and Evaluation of a Staining Method for Measuring Sperm Lactate Dehydrogenase C4 Activity.

BACKGROUND: This study sought to improve and evaluate a 2-hydroxyvaleric acid based staining method for detection of lactate dehydrogenase C4 (LDH-C4) activity in human spermatozoa. METHODS: A staining method for measuring sperm LDH-C4 activity with the substrate 2-hydroxyvaleric acid was improved. Expression level of LDH-C4 was assessed by Western blotting. The diagnostic performance was evaluated by plotting the receiver operating characteristic (ROC) curve. RESULTS: The positive products were black purple lumps concentrated in the neck segment of spermatozoa. Expression level of LDH-C4 was significantly reduced in the low activity infertile cases as compared to the matched contrasts. Decreased LDH-C4 level was significantly correlated with the declined enzyme activity (r = 0.702, p = 0.000). The ROC curve allowed for the discrimination between low and normal LDH-C4 activity cases with a sensitivity of 0.912 and specificity of 0.895, corresponding to an area under curve (AUC) of 0.941. CONCLUSIONS: The improved method hallmarks a promising accuracy in evaluating sperm LDH-C4 activity. Down-regulated LDH-C4 level is a culprit for the decreased LDH-C4 activity in spermatozoa.

Pathological Effects of the FMR1 CGG-Repeat Polymorphism (5-55 Repeat Numbers): Systematic Review and Meta-Analysis.

The fragile X mental retardation 1 (FMR1) gene contains a highly polymorphic trinucleotide (CGG) repeat and consists of various allelic forms. Traditionally, 55-200 repeats and over 200 CGG repeats have been highlighted to be associated with ovarian dysfunction and neuro-psychiatric risks. However, previous studies had paid little attention to the allelic forms of 5-55 CGG repeats. Herein, we sought to evaluate the pathological features of FMR1 allelic category with a range of 5-55 CGG repeats. We further classified the spectrum of CGG sizes (5-55 repeats) into three sub-groups as low numbers of CGG repeat (< 26 repeats), normal CGG count (26-34 repeats), and small CGG expansion (35-54 repeats). Our systematic review documented that low numbers of CGG repeat (< 26 repeats) revealed a close relationship with premature ovarian failure. Correspondingly, the meta-analysis showed that small CGG expansion, involving allelic sizes with 35-54 (n = 8, OR = 1.22, 95% CI: 0.75-2.00, P > 0.05) and 41-54 (n = 7, OR = 1.62, 95% CI: 1.14-2.30, P < 0.05), was both linked to the risk of ovarian dysfunction. Additionally, small CGG expansion exerts significant influence on male Parkinsonism cohorts (OR = 2.17, 95% CI: 1.50-3.14, P < 0.05), mental retardation, and repeat instability. Our data provide evidence that the CGG-repeat numbers below 26 or above 34 of FMR1 gene are also associated with disease risks and thus should be regarded as pathological genotypes for a routine test.

MicroRNAs as Biomarkers for the Diagnostics of Bladder Cancer: a Meta-Analysis.

BACKGROUND: Bladder cancer (BCa) is the fifth most common cancer with significant morbidity and mortality. Recently, numerous studies demonstrated that microRNAs (miRNAs) are emerging as diagnostic biomarkers for BCa. However, the findings in these studies are inconsistent. To systematically assess the potential diagnostic value of miRNAs for BCa, a meta-analysis was performed in this study. METHODS: Relevant literature was researched in PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to September 1, 2014. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and area under the SROC curve (AUC) value were analyzed by the random-effects model, whose parameters reflected the overall diagnostic performance of miRNAs. RESULTS: Thirty studies from 10 individual publications, including 1019 BCa patients and 690 controls, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.80 (95% CI: 0.78 - 0.81), 0.74 (95% CI: 0.72 - 0.76), 3.22 (95% CI: 2.68 - 3.87), 0.26 (95% CI: 0.21 - 0.32), 15.20 (95% CI: 10.25 - 22.53) and 0.85, respectively, indicating a moderate diagnostic accuracy for BCa. Moreover, our subgroup analyses showed that analysis of multiple miRNAs (AUC, sensitivity, and specificity of 0.913, 0.86, and 0.80, respectively) yielded a higher diagnostic accuracy than of single miRNAs (AUC, sensitivity, and specificity of 0.84, 0.78, and 0.73, respectively) in BCa diagnosis. In addition, as biomarkers, miRNAs are more suitable for the diagnosis of non-muscle-invasive BCa (NMIBCa) with AUC of 0.84, sensitivity of 0.74, and specificity of 0.77 than muscle-invasive BCa (MIBCa) with AUC of 0.79, sensitivity of 0.73, and specificity of 0.73. CONCLUSIONS: The present meta-analysis suggests that miRNAs are potential novel biomarkers for detection of BCa. However, further validation studies are still needed to confirm our findings.

Diagnostic Accuracies of the TUNEL, SCD, and Comet Based Sperm DNA Fragmentation Assays for Male Infertility: a Meta-analysis Study.

BACKGROUND: Recent studies have provided new insights into the diagnostic value of sperm DNA fragmentation (SDF) for male factor sterility. This study aimed to systematically evaluate the diagnostic accuracy of the SDF test for male infertility. METHODS: Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria tool. The bivariate metaanalysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve by using Meta-disc 1.4 software. Influence analysis, meta-regression, and publication bias assay were all conducted through Stata 12.0 software. RESULTS: Our bivariate random effect meta-analysis yielded an AUC (area under curve) value of 0.9211 with a sensitivity (95% confidence interval) of 0.80 (0.78 - 0.82) and specificity of 0.83 (0.80 - 0.86) for the use of the SDF test in differentiating infertile males from normal fertile controls. Moreover, our subgroup analysis suggested that SDF analysis with a single TUNEL test resulted in an AUC value of 0.9506, with a pooled sensitivity of 0.77 (0.74 - 0.80) and specificity of 0.91 (0.87 - 0.94), while SCD and Comet assays displayed a combined sensitivity of 0.77 (0.67 - 0.81) or 0.91 (0.88 - 0.94), and specificity of 0.84 (0.75 - 0.91) or 0.63 (0.54 - 0.70), accompanied by an AUC value of 0.8408 or 0.9473. CONCLUSIONS: The SDF assay confers a relatively high diagnostic accuracy for infertility detection, among which the TUNEL based methodology seems to achieve higher accuracy than the SCD and Comet assays.

Molecular photoelectron holography by an attosecond XUV pulse in a strong infrared laser field.

We have investigated the photoelectron spectra from ionization of diatomic molecules by an attosecond XUV pulse in a strong infrared laser field by quantum calculations. A clear holographic interference structure is observed in the two-dimensional photoelectron momentum spectrum. Moreover, this holographic structure depends sensitively on the electron orbitals and internuclear distance of diatomic molecules. Based on the orbital dependence of the holographic structure, one can identify the symmetries and electron density distributions of molecular orbitals. This indicates that the photoelectron holography by an attosecond XUV pulse in a strong infrared field can be used as an efficient tool for molecular imaging.

Cancer testis antigen MAGEA3 in serum and serum-derived exosomes serves as a promising biomarker in lung adenocarcinoma.

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.

Serum AXL is a potential molecular marker for predicting COVID-19 progression.

Background: The 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. Methods: A 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. Results: Compared 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. Conclusions: The 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.

The immune inflammation factors associated with disease severity and poor prognosis in patients with COVID-19: A retrospective cohort study.

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-1ß, 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.