Predicting potential therapeutic targets and small molecule drugs for early-stage lung adenocarcinoma.

Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting the majority, and its main subtype being lung adenocarcinoma (LUAD). Despite substantial advances in LUAD diagnosis and treatment, early diagnostic biomarkers inadequately fulfill clinical requirements. Thus, we conducted bioinformatics analysis to identify potential biomarkers and corresponding therapeutic drugs for early-stage LUAD patients. Here we identified a total of 10 differentially expressed genes (DEGs) with survival significance through the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Subsequently, we identified a promising small molecule drug, Aminopurvalanol A, based on the 10 key genes using the L1000FWD application, which was validated by molecular docking followed by in vivo and in vitro experiments. The results highlighted TOP2A, CDH3, ASPM, CENPF, SLC2A1, and PRC1 as potential detection biomarkers for early LUAD. We confirmed the efficacy and safety of Aminopurvalanol A, providing valuable insights for the clinical management of LUAD.

YAP1 as a Novel Negative Biomarker of Immune Checkpoint Inhibitors for EGFR-Mutant Non-Small-Cell Lung Cancer.

Background: Immune checkpoint inhibitors (ICIs) have become a standard care in non-small-cell lung cancer (NSCLC). However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population. Methods: All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1_High and YAP1_Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren's research data (NCT03513666). Results: YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1_High showed an immune-"cold" and immunosuppressive phenotype, whereas those with YAP1_Low demonstrated an immune-"hot" and immunoactive phenotype. More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial. Conclusions: YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials. This trial is registered with NCT03513666.

3,3',5,5'-Tetra-tert-butyl-2'-hy-droxy-[1,1'-biphen-yl]-2-yl 4-methyl-benzene-sulfonate.

In the title mol-ecule, C(37)H(48)O(4)S, the benzene rings in the biphenyl fragment are inclined to each other at 61.1 (1)°. The hy-droxy group is involved in a weak intra-molecular O-H⋯O(sulfonate) hydrogen bond. One tert-butyl group is disodered over two orientations in a 0.682 (17):0.318 (17) ratio. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into columns in direction [100].

Synthesis and characterization of multi-alkali-metal tetraphenolates and application in ring-opening polymerization of lactide.

A series of alkali metal complexes supported by two bulky tetraphenols were synthesized and characterized. The reactions of α,α,α',α'-tetra(3,5-di-tert-butyl-2-hydroxyphenyl)-p-xylene(para-tetraphenol) with (n)BuLi, sodium, and KSi(NMe(2))(3) gave bimetallic complexes 1, 2, and 3, respectively. Treatments of the α,α,α',α'-tetra(3,5-di-tert-butyl-2-hydroxyphenyl)-m-xylene(meta-tetraphenol) with 2 or 4 equiv of (n)BuLi afforded complexes 4 or 5, while the reactions of meta-tetraphenol with sodium and KSi(NMe(2))(3) gave only trimetallic complexes 6 and 7 for the additional p-π interaction. Complexes 1-7 were all characterized by single-crystal X-ray diffraction techniques. In the presence of benzyl alcohol, all complexes are active catalysts for the ring-opening polymerization of L-lactide. Comparatively, bimetallic complexes 1, 2, and 3 are more efficient catalysts because of their symmetric structures, in which complex 3 presents as a rare highly active potassium catalyst for the ring-opening polymerization of lactide, leading to polymers with good molecular weight control and narrow molecular weight distributions.