Table1_Prediction of prognosis and immunotherapy response in breast cancer based on neutrophil extracellular traps-related classification.XLSX

Neutrophil extracellular traps (NETs), a network of DNA histone complexes and proteins released by activated neutrophils, have been demonstrated to be associated with inflammation, infection related immune response and tumorigenesis in previous reports. However, the relationship between NETs related genes and breast cancer remains controversial. In the study, we retrieved transcriptome data and clinical information of BRCA patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. The expression matrix of neutrophil extracellular traps (NETs) related genes was generated and consensus clustering was performed by Partitioning Around Medoid (PAM) to classify BRCA patients into two subgroups (NETs high group and NETs low group). Subsequently, we focus on the differentially expressed genes (DEGs) between the two NETs-related subgroups and further explored NETs enrichment related signaling pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, we constructed a risk signature model by LASSO Cox regression analysis to evaluate the association between riskscore and prognosis. Even more, we explored the landscape of the tumor immune microenvironment and the expression of immune checkpoints related genes as well as HLA genes between two NETs subtypes in breast cancer patients. Moreover, we found and validated the correlation of different immune cells with risk score, as well as the response to immunotherapy in different subgroups of patients was detected by Tumor Immune Dysfunction and Exclusion (TIDE) database. Ultimately, a nomogram prognostic prediction model was established to speculate on the prognosis of breast cancer patients. The results suggest that high riskscore is associated with poor immunotherapy response and adverse clinical outcomes in breast cancer patients. In conclusion, we established a NETs-related stratification system that is beneficial for guiding the clinical treatment and predicting prognosis of BRCA.</p

Table2_Prediction of prognosis and immunotherapy response in breast cancer based on neutrophil extracellular traps-related classification.DOCX

Neutrophil extracellular traps (NETs), a network of DNA histone complexes and proteins released by activated neutrophils, have been demonstrated to be associated with inflammation, infection related immune response and tumorigenesis in previous reports. However, the relationship between NETs related genes and breast cancer remains controversial. In the study, we retrieved transcriptome data and clinical information of BRCA patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. The expression matrix of neutrophil extracellular traps (NETs) related genes was generated and consensus clustering was performed by Partitioning Around Medoid (PAM) to classify BRCA patients into two subgroups (NETs high group and NETs low group). Subsequently, we focus on the differentially expressed genes (DEGs) between the two NETs-related subgroups and further explored NETs enrichment related signaling pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, we constructed a risk signature model by LASSO Cox regression analysis to evaluate the association between riskscore and prognosis. Even more, we explored the landscape of the tumor immune microenvironment and the expression of immune checkpoints related genes as well as HLA genes between two NETs subtypes in breast cancer patients. Moreover, we found and validated the correlation of different immune cells with risk score, as well as the response to immunotherapy in different subgroups of patients was detected by Tumor Immune Dysfunction and Exclusion (TIDE) database. Ultimately, a nomogram prognostic prediction model was established to speculate on the prognosis of breast cancer patients. The results suggest that high riskscore is associated with poor immunotherapy response and adverse clinical outcomes in breast cancer patients. In conclusion, we established a NETs-related stratification system that is beneficial for guiding the clinical treatment and predicting prognosis of BRCA.</p

Additional file 4 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 4: Table S4. Polyploidy-responsive genes in Isatidis Radix

Additional file 8 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 8: Figure S1. The morphological characterization of I. indigotica autotetraploid seedling and its diploid progenitor. A The I. indigotica seedling of autotetraploid (4x) and its diploid (2x). B Chromosomes of I. indigotica autotetraploid and diploid root tips. C The comparison of stomata between autotetraploid and diploid leaf. D Isatidis Radix autotetraploid and diploid

Indole derivative XCR-5a alleviates LPS-induced inflammation <i>in vitro</i> and <i>in vivo</i>

Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed. Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases.</p

Structural Insights into the Mechanism of High-Affinity Binding of Ochratoxin A by a DNA Aptamer

A 36-mer guanine (G)-rich DNA aptamer (OBA36) is able to distinguish one atomic difference between ochratoxin analogues A (OTA) and B (OTB), showing prominent recognition specificity and affinity among hundreds of aptamers for small molecules. Why OBA36 has >100-fold higher binding affinity to OTA than OTB remains a long-standing question due to the lack of high-resolution structure. Here we report the solution NMR structure of the aptamer–OTA complex. It was found that OTA binding induces the aptamer to fold into a well-defined unique duplex–quadruplex structural scaffold stabilized by Mg2+ and Na+ ions. OTA does not directly interact with the G-quadruplex, but specifically binds at the junction between the double helix and G-quadruplex through π–π stacking, halogen bonding (X-bond), and hydrophobic interaction. OTB has the same binding site as OTA but lacks the X-bond. The strong X-bond formed between the chlorine atom of OTA and the aromatic ring of C5 is the key to discriminating the strong binding toward OTA. The present research contributes to a deeper insight of aptamer molecular recognition, reveals structural basis of the high-affinity binding of aptamers, and provides a foundation for further aptamer engineering and applications

Additional file 5 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 5: Table S5. Correlation analysis of polyploidy-responsive genes and metabolites in Isatidis Radix

Additional file 7 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 7: Table S7. I. indigotica transcriptional factors acted as key regulators of lignan synthesis in Isatidis Radix

Additional file 6 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 6: Table S6. Correlation analysis of transcriptional factors and metabolites in Isatidis Radix

Additional file 3 of Integrative analyses of targeted metabolome and transcriptome of Isatidis Radix autotetraploids highlighted key polyploidization-responsive regulators

Additional file 3:Table S3. Metabolomic profiling of Isatidis Radix