Access to Chiral β‑Boryl δ‑Lactones via NHC-Catalyzed [4 + 2] Annulation

We report a carbene-catalyzed [4 + 2] annulation of activated esters and β-borate enones, providing an efficient method to build enantioenriched organoborones with two consecutive stereogenic centers. It is worth noting that this protocol represents a new organocatalytic manner to generate chiral β-C–B bonds. Moreover, it also greatly enriches the structural diversity of the chiral organoboron compounds

Table_4_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.xlsx

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_3_Pyroptosis-Related Signatures for Predicting Prognosis in Breast Cancer.TIF

BackgroundFemale breast cancer (BC) has become the most common cancer in the world, and its mortality was considerably higher in transitioning vs. transitioned countries. Pyroptosis, an inflammation-dependent programmed cell death mediated by inflammasomes, has been observed in human colorectal tumors and gliomas. However, the characteristics of pyrolysis-related genes and their influence and mechanism on the tumorigenesis and progress of BC were unknown.MethodsBased on the global public database, we used comprehensive bioinformatics analysis to systematically analyze the expression of pyroptosis-related genes in BC and their relationship in tumor progression. In addition, BC patients were divided into two groups, and the clinical features and outcomes could be better predicted by the consistent clustering of pyroptosis-related genes. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to establish a risk score. Then, we further explored the prognostic value and clinical features of pyroptosis genes. Finally, we used the Human Protein Atlas (HPA) platform to identify the expression at protein levels of the key genes.ResultsWe confirmed that the expression of pyroptosis-related genes was different in BC and normal breast tissues. A high frequency of somatic mutations occurred in BC. In addition, 33 pyroptosis-related proteins interacted frequently. Based on univariate analysis and the LASSO Cox model, five pyroptosis-related genes [including GADMA, interleukin-6 (IL-6), NLR pyrin domain-containing protein 6 (NLRP6), caspase-1 (CASP1), and caspase-9 (CASP9)], were obtained to calculate a risk score. The risk score was identified as an independent risk factor for the prognosis of BC and might play an auxiliary role in clinical classification. The HPA platform confirmed that the expression trends of the key genes were consistent with our previous studies.ConclusionPyroptosis had an important effect on the progression of BC. And the pyroptosis-related genes could be used as new prognostic biomarkers and therapeutic targets for BC.</p

Image_8_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.jpeg

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_7_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.jpeg

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_9_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.jpeg

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_11_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.jpeg

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Table_1_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.xlsx

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_10_Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming.jpeg

BackgroundThe genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC.MethodsThis study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted.ResultsFirst, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression.ConclusionThis study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.</p

Image_2_Pyroptosis-Related Signatures for Predicting Prognosis in Breast Cancer.TIF

BackgroundFemale breast cancer (BC) has become the most common cancer in the world, and its mortality was considerably higher in transitioning vs. transitioned countries. Pyroptosis, an inflammation-dependent programmed cell death mediated by inflammasomes, has been observed in human colorectal tumors and gliomas. However, the characteristics of pyrolysis-related genes and their influence and mechanism on the tumorigenesis and progress of BC were unknown.MethodsBased on the global public database, we used comprehensive bioinformatics analysis to systematically analyze the expression of pyroptosis-related genes in BC and their relationship in tumor progression. In addition, BC patients were divided into two groups, and the clinical features and outcomes could be better predicted by the consistent clustering of pyroptosis-related genes. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to establish a risk score. Then, we further explored the prognostic value and clinical features of pyroptosis genes. Finally, we used the Human Protein Atlas (HPA) platform to identify the expression at protein levels of the key genes.ResultsWe confirmed that the expression of pyroptosis-related genes was different in BC and normal breast tissues. A high frequency of somatic mutations occurred in BC. In addition, 33 pyroptosis-related proteins interacted frequently. Based on univariate analysis and the LASSO Cox model, five pyroptosis-related genes [including GADMA, interleukin-6 (IL-6), NLR pyrin domain-containing protein 6 (NLRP6), caspase-1 (CASP1), and caspase-9 (CASP9)], were obtained to calculate a risk score. The risk score was identified as an independent risk factor for the prognosis of BC and might play an auxiliary role in clinical classification. The HPA platform confirmed that the expression trends of the key genes were consistent with our previous studies.ConclusionPyroptosis had an important effect on the progression of BC. And the pyroptosis-related genes could be used as new prognostic biomarkers and therapeutic targets for BC.</p