A multi-ancestry cerebral cortex transcriptome-wide association study identifies genes associated with smoking behaviors.

Transcriptome-wide association studies (TWAS) have provided valuable insight in identifying genes that may impact cigarette smoking. Most of previous studies, however, mainly focused on European ancestry. Limited TWAS studies have been conducted across multiple ancestries to explore genes that may impact smoking behaviors. In this study, we used cis-eQTL data of cerebral cortex from multiple ancestries in MetaBrain, including European, East Asian, and African samples, as reference panels to perform multi-ancestry TWAS analyses on ancestry-matched GWASs of four smoking behaviors including smoking initiation, smoking cessation, age of smoking initiation, and number of cigarettes per day in GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Multiple-ancestry fine-mapping approach was conducted to identify credible gene sets associated with these four traits. Enrichment and module network analyses were further performed to explore the potential roles of these identified gene sets. A total of 719 unique genes were identified to be associated with at least one of the four smoking traits across ancestries. Among those, 249 genes were further prioritized as putative causal genes in multiple ancestry-based fine-mapping approach. Several well-known smoking-related genes, including PSMA4, IREB2, and CHRNA3, showed high confidence across ancestries. Some novel genes, e.g., TSPAN3 and ANK2, were also identified in the credible sets. The enrichment analysis identified a series of critical pathways related to smoking such as synaptic transmission and glutamate receptor activity. Leveraging the power of the latest multi-ancestry GWAS and eQTL data sources, this study revealed hundreds of genes and relevant biological processes related to smoking behaviors. These findings provide new insights for future functional studies on smoking behaviors.

Synthesis of acridones via Ir(III)-catalyzed amination annulation of oxazoles with anthranils.

An unprecedented Ir(III)-catalyzed C-H activation/amination/annulation of 2-phenyloxazoles with anthranils for the highly selective preparation of acridone derivatives in one-pot under controlled conditions is reported. This protocol is characterized by atom economy and high regioselectivity. A wide range of anthranils with 2-phenyloxazoles were well tolerated and afforded the desired products in moderate to good yields, in which the anthranil serves as a convenient amination reagent.

Hsa_circ_0000877 facilitates the progression of diffuse large B-cell lymphoma by miR-370-3p/mitogen-activated protein kinase kinase kinase kinase 4/Hippo pathway.

Diffuse large B-cell lymphoma (DLBCL) originates from B lymphocytes and is a fatal hematological malignancy. Circular RNAs have been increasingly reported as a promising biological target for cancer therapy, but their role in DLBCL remains poorly studied. Relative expression levels of has_circ_0000877 (circ_0000877), microRNA-370-3p (miR-370-3p), and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) were assessed by quantitative real-time PCR. Western blot analysis was employed to measure protein levels. Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect the proliferation of TMD8 and U2932 cells. Cell cycle and apoptosis were investigated by flow cytometry. Transwell assay was used to analyze cell migration and invasion. Molecular interaction was determined by dual-luciferase reporter assay and RNA immunoprecipitation assay. The protein expression of Ki67 in tumor tissues of mice was detected by immunohistochemistry assay. The expression of circ_0000877 was markedly elevated in DLBCL tissues and cell lines. The decreased expression of circ_0000877 significantly inhibited proliferation, migration, and invasion of DLBCL cell lines. In addition, silencing circ_0000877 promoted cell apoptosis and induced cell cycle arrest in G0/G1 phase. Then, miR-370-3p directly interacted with circ_0000877 and MAP4K4. Circ_0000877 promoted MAP4K4 level by sponging miR-370-3p. MAP4K4 depletion inhibited the activation of Hippo pathway. Finally, circ_0000877 silencing significantly prevented the growth of DLBCL cells in vivo . Our findings revealed that circ_0000877 could regulate the malignant evolution of DLBCL by miR-370-3p/MAP4K4/Hippo pathway.

Formation of Fluorovinyl Spiro-[imidazole-indene] and α-Amino-ß-naphthalenones via Rh(III)-Catalyzed Cascade C-H Functionalization.

An efficacious method for building fluorovinyl spiro-[imidazole-indene] and α-amino-ß-naphthalenone skeletons synchronously has been shown to consist of Rh(III)-catalyzed C-H functionalization between 2H-imidazoles and difluoromethylene alkynes. This protocol demonstrates a practical and straightforward route for installing fluorine elements in the envisioned position of heterocyclic compounds.