Screening biomarkers for Sjogren’s Syndrome by computer analysis and evaluating the expression correlations with the levels of immune cells

BackgroundSjögren’s syndrome (SS) is a systemic autoimmune disease that affects about 0.04-0.1% of the general population. SS diagnosis depends on symptoms, clinical signs, autoimmune serology, and even invasive histopathological examination. This study explored biomarkers for SS diagnosis.MethodsWe downloaded three datasets of SS patients’ and healthy pepole’s whole blood (GSE51092, GSE66795, and GSE140161) from the Gene Expression Omnibus (GEO) database. We used machine learning algorithm to mine possible diagnostic biomarkers for SS patients. Additionally, we assessed the biomarkers’ diagnostic value using the receiver operating characteristic (ROC) curve. Moreover, we confirmed the expression of the biomarkers through the reverse transcription quantitative polymerase chain reaction (RT-qPCR) using our own Chinese cohort. Eventually, the proportions of 22 immune cells in SS patients were calculated by CIBERSORT, and connections between the expression of the biomarkers and immune cell ratios were studied.ResultsWe obtained 43 DEGs that were mainly involved in immune-related pathways. Next, 11 candidate biomarkers were selected and validated by the validation cohort data set. Besides, the area under curves (AUC) of XAF1, STAT1, IFI27, HES4, TTC21A, and OTOF in the discovery and validation datasets were 0.903 and 0.877, respectively. Subsequently, eight genes, including HES4, IFI27, LY6E, OTOF, STAT1, TTC21A, XAF1, and ZCCHC2, were selected as prospective biomarkers and verified by RT-qPCR. Finally, we revealed the most relevant immune cells with the expression of HES4, IFI27, LY6E, OTOF, TTC21A, XAF1, and ZCCHC2.ConclusionIn this paper, we identified seven key biomarkers that have potential value for diagnosing Chinese SS patients

Effects of Grout Compactness on the Tensile Behavior of Grouted Splice Sleeve Connectors

The quality of grouted sleeve has a significant influence on the performance of the sleeve splice. Incompactness of the infilled grout is inevitable in sleeve grouting. To investigate the tensile behavior of grouted splice sleeves due to different grout compactness, monotonic tensile tests on grouted splice sleeve connectors were performed at grout compactness of 100%, 90%, 70%, and 50%, respectively. The bond-slip analytical model of rebar-grout was deduced by fitting the tensile test data, and the formula for the tensile capacity of the grouted splice sleeve was proposed in the paper. The results show that the tensile strength of the splice sleeve reduces as the grout compactness decreases. It was found from the experiment that the calculated values of tensile capacity are in good agreement with the experimental values. The proposed formula can be adopted in determining whether reinforcing remedies or re-grouting should be taken in the case of incompact grout in grouted splice sleeve connectors

Effects of Grout Compactness on the Tensile Behavior of Grouted Splice Sleeve Connectors

The quality of grouted sleeve has a significant influence on the performance of the sleeve splice. Incompactness of the infilled grout is inevitable in sleeve grouting. To investigate the tensile behavior of grouted splice sleeves due to different grout compactness, monotonic tensile tests on grouted splice sleeve connectors were performed at grout compactness of 100%, 90%, 70%, and 50%, respectively. The bond-slip analytical model of rebar-grout was deduced by fitting the tensile test data, and the formula for the tensile capacity of the grouted splice sleeve was proposed in the paper. The results show that the tensile strength of the splice sleeve reduces as the grout compactness decreases. It was found from the experiment that the calculated values of tensile capacity are in good agreement with the experimental values. The proposed formula can be adopted in determining whether reinforcing remedies or re-grouting should be taken in the case of incompact grout in grouted splice sleeve connectors

The novel putative methyltransferase METTL7A as one prognostic biomarker potentially associated with immune infiltration in human renal cancer

Among urological cancers, renal cancer has the highest fatality rate. In a previous pan-cancer study of the METTL family, we observed a stronger association between the METTL family members and the risk of renal cancer compared to other cancers. Among these members, METTL7A, a potential methyltransferase, was identified as a protective factor, although its role and mechanism in renal cancer remain unclear. In this study, we utilized public databases to examine the expression of METTL7A in renal cancer tissues and normal tissues and found that METTL7A expression was much lower in renal cancer tissues. We also noticed a link between low METTL7A expression and poor prognosis for patients. According to the results of our functional enrichment analysis, METTL7A may have a role in immunological functions in renal cancer. METTL7A expression was strongly linked with the degrees of immune cell infiltration and expression of numerous immunological components. METTL7A had significantly different effects on the survival times of renal cancer patients with high or low immune infiltration. Our findings suggest that METTL7A may be used as both a prognostic biomarker and an immunological target for kidney cancer. In conclusion, our study sheds light on the importance of METTL7A in renal cancer and emphasizes the potential of targeting METTL7A as a novel therapeutic strategy for kidney cancer

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma

Abstract Purpose Oral adenoid cystic carcinoma (OACC) has high rates of both local–regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. Experimental design We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC–MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein–protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. Results Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. Conclusions and clinical relevance Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC

Integrated proteome and malonylome analyses reveal the potential meaning of TLN1 and ACTB in end-stage renal disease

Abstract Background End-stage renal disease (ESRD) is a condition that is characterized by the loss of kidney function. ESRD patients suffer from various endothelial dysfunctions, inflammation, and immune system defects. Lysine malonylation (Kmal) is a recently discovered post-translational modification (PTM). Although Kmal has the ability to regulate a wide range of biological processes in various organisms, its specific role in ESRD is limited. Methods In this study, the affinity enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have been used to create the first global proteome and malonyl proteome (malonylome) profiles of peripheral blood mononuclear cells (PBMCs) from twenty patients with ESRD and eighty-one controls. Results On analysis, 793 differentially expressed proteins (DEPs) and 12 differentially malonylated proteins (DMPs) with 16 Kmal sites were identified. The Rap1 signaling pathway and platelet activation pathway were found to be important in the development of chronic kidney disease (CKD), as were DMPs TLN1 and ACTB, as well as one malonylated site. One conserved Kmal motif was also discovered. Conclusions These findings provided the first report on the Kmal profile in ESRD, which could be useful in understanding the potential role of lysine malonylation modification in the development of ESRD

Spatial metabolomics on liver cirrhosis to hepatocellular carcinoma progression

Abstract Background Hepatocellular carcinoma (HCC) is one of the deadliest cancers and is mainly developed from chronic liver diseases such as hepatitis-B infection-associated liver cirrhosis (LC). The progression from LC to HCC makes the detection of diagnostic biomarkers to be challenging. Hence, there have been constant efforts to improve on identifying the critical and predictive changes accompanying the disease progression. Methods In this study, we looked to using the mass spectrometry mediated spatial metabolomics technique to simultaneous examine hundreds of metabolites in an untargeted fashion. Additionally, metabolic profiles were compared between six subregions within the HCC tissue to collect spatial information. Results Through those metabolites, altered metabolic pathways in LC and HCC were identified. Specifically, the amino acid metabolisms and the glycerophospholipid metabolisms experienced the most changes. Many of the altered metabolites and metabolic pathways were able to be connected through the urea cycle. Conclusions The identification of the key metabolites and pathways can expand our knowledge on HCC metabolic reprogramming and help us exam potential biomarkers for earlier detection of the malignant disease progression

Additional file 1 of Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma

Additional file 1: Supplementary text. Detailed research methods. Supplementary Fig. 1. PPI and cluster of hyper-modified DHMPs. Supplementary Fig. 2. PPI and cluster of hypo-modified DHMPs. Supplementary Table 1. Statistics of Mass Spectrometry Data. Supplementary Table 2. Clinical characteristics of OACC patients. Supplementary Table 3. Go enrichment analyses of differentially expressed proteins. Supplementary Table 4. KEGG pathway enrichment of differentially expressed proteins. Supplementary Table 5. Go enrichment analyses of differentially expressed and 2-hydroxyisobutyrylated modified proteins. Supplementary Table 6. KEGG pathway enrichment of differentially expressed and 2-hydroxyisobutyrylated modified proteins. Supplementary Table 7. Top 10 hub proteins in hyper-and hypo modified DHMPs based on degree. Supplementary Table 8. KEGG enrichment in up cluster 1–6. Supplementary Table 9. KEGG enrichment in down cluster 1–2. Supplementary Table 10. The Khib of glycolysis pathway enzyme