Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown.Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of each pathway and the correlation between genes or pathways were analyzed by bioinformatic methods.Results: By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis.Conclusion: These results give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage.

BackgroundProgrammed cell death protein 1 (PD-1) receptor has two ligands,programmed death-ligand 1 (PD-L1) and PD-L2. When compared with PD-L1, PD-L2 has not received much attention, and its role remains unclear.MethodsThe expression profiles of pdcd1lg2 (PD-L2-encoding gene) mRNA and PD-L2 protein were analyzed using TCGA, ICGC, and HPA databases. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of PD-L2. We used GSEA, Spearman’s correlation analysis and PPI network to explore the biological functions of PD-L2. PD-L2-associated immune cell infiltration was evaluated using the ESTIMATE algorithm and TIMER 2.0. The expressions of PD-L2 in tumor-associated macrophages (TAMs) in human colon cancer samples, and in mice in an immunocompetent syngeneic setting were verified using scRNA-seq datasets, multiplex immunofluorescence staining, and flow cytometry. After fluorescence-activated cell sorting, flow cytometry and qRT-PCR and transwell and colony formation assays were used to evaluate the phenotype and functions of PD-L2+TAMs. Immune checkpoint inhibitors (ICIs) therapy prediction analysis was performed using TIDE and TISMO. Last, a series of targeted small-molecule drugs with promising therapeutic effects were predicted using the GSCA platform.ResultsPD-L2 was expressed in all the common human cancer types and deteriorated outcomes in multiple cancers. PPI network and Spearman’s correlation analysis revealed that PD-L2 was closely associated with many immune molecules. Moreover, both GSEA results of KEGG pathways and GSEA results for Reactome analysis indicated that PD-L2 expression played an important role in cancer immune response. Further analysis showed that PD-L2 expression was strongly associated with the infiltration of immune cells in tumor tissue in almost all cancer types, among which macrophages were the most positively associated with PD-L2 in colon cancer. According to the results mentioned above, we verified the expression of PD-L2 in TAMs in colon cancer and found that PD-L2+TAMs population was not static. Additionally, PD-L2+TAMs exhibited protumor M2 phenotype and increased the migration, invasion, and proliferative capacity of colon cancer cells. Furthermore, PD-L2 had a substantial predictive value for ICIs therapy cohorts.ConclusionPD-L2 in the TME, especially expressed on TAMs, could be applied as a potential therapeutic target.

BackgroundParkinson’s disease (PD) is a common age-related chronic neurodegenerative disease. There is currently no affordable, effective, and less invasive test for PD diagnosis. Metabolite profiling in blood and blood-based gene transcripts is thought to be an ideal method for diagnosing PD.AimIn this study, the objective is to identify the potential diagnostic biomarkers of PD by analyzing microarray gene expression data of samples from PD patients.MethodsA computational approach, namely, Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression gene networks and identify the key modules that were highly correlated with PD from the GSE99039 dataset. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to identify the hub genes in the key modules with strong association with PD. The selected hub genes were then used to construct a diagnostic model based on logistic regression analysis, and the Receiver Operating Characteristic (ROC) curves were used to evaluate the efficacy of the model using the GSE99039 dataset. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to validate the hub genes.ResultsWGCNA identified two key modules associated with inflammation and immune response. Seven hub genes, LILRB1, LSP1, SIPA1, SLC15A3, MBOAT7, RNF24, and TLE3 were identified from the two modules and used to construct diagnostic models. ROC analysis showed that the diagnostic model had a good diagnostic performance for PD in the training and testing datasets. Results of the RT-PCR experiments showed that there were significant differences in the mRNA expression of LILRB1, LSP1, and MBOAT7 among the seven hub genes.ConclusionThe 7-gene panel (LILRB1, LSP1, SIPA1, SLC15A3, MBOAT7, RNF24, and TLE3) will serve as a potential diagnostic signature for PD.

Polycystic ovary syndrome (PCOS) is a common age-related endocrinopathy that promotes the metabolic disorder of the liver. Growing evidence suggests that the pathophysiology of this disorder is closely associated with the interaction between the liver and its exosome. However, the underlying mechanism of the interactions remains unclear. In this study, we aimed to investigate the metabolite profiles of liver tissues and hepatic exosomes between normal (n = 11) and PCOS (n = 13) mice of young- and middle-age using gas chromatograph-mass spectrometry (GC-MS) based metabolomics analysis. Within the 145 identified metabolites, 7 and 48 metabolites were statistically different (p < 0.05, q < 0.05) in the liver tissue and exosomes, respectively, between PCOS and normal groups. The greater disparity in exosome indicated its potential to reflect the metabolic status of the liver. Based on hepatic exosome metabolome, the downregulations of glycolysis and TCA cycle were related to hepatic pathophysiology of PCOS independent of age. Fatty acids were the preferred substrates in young-age-PCOS liver while amino acids were the main substrates in middle-age-PCOS liver for the processes of gluconeogenesis. Overall, this study enables us to better understand the metabolic status of the PCOS liver at different ages, and exosome metabolomics shows its potential to gain the metabolic insights of parental cell or source organ.