Search

Graphical abstract BRIEFS. "Monometallic NiO-Ni 3 S 2 /NF heteronanosheets" were rationally designed as highly-active bifunctional electrocatalysts for overall water splitting. The electron transfer between tightly combined metallic Ni 3 S 2 and NiO domains creates a highly active interface zone, emerging as electrocatalysts that are superior to their single-component counterparts and most of the state-of-the-art catalysts for HER or OER so far. Highlights • Monometallic NiO-Ni 3 S 2 heteronanosheets array is in situ constructed on Ni foam. • The NiO-Ni 3 S 2 /NF can act as bifunctional electrocatalysts for water splitting. • The NiO-Ni 3 S 2 /NF show a cell voltage of 1.57 V at 10 mA cm−2 for water splitting. • The role of NiO-Ni 3 S 2 interfaces for the excellent activity has been established. Abstract Developing cost-effective and stable bifunctional catalysts for overall water splitting is of enormous importance for the realization of sustainable clean-energy technologies. Herein, a monometallic NiO-Ni 3 S 2 heteronanosheets supported on Ni foam are rationally constructed as bifunctional electrocatalysts for overall water splitting. On account of the unique electronic property of the abundant interface and its 3D interconnected integration structure, NiO-Ni 3 S 2 heteronanosheets exhibit high electrocatalytic activity toward both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Utilizing NiO-Ni 3 S 2 /NF as both the anode and the cathode for overall water splitting, a current density of 10 mA cm−2 is achieved at a cell voltage of as low as 1.57 V with excellent stability, exceeding that of the integrated performance of Pt/C and RuO 2. DFT calculations further reveal that key role of the established interfaces between Ni 3 S 2 and NiO in modulating the chemisorption of hydrogen and oxygen-containing intermediates, and consequently improving the overall electrochemical water-splitting activity. [ABSTRACT FROM AUTHOR]

Recent studies have emphasized the close relationship between macrophages and tumor immunity, and the prognosis of lung adenocarcinoma (LUAD) patients is intimately linked to this. Nonetheless, the prognostic signature and classification of different immune patterns in LUAD patients based on the macrophages is largely unexplored. Two sc-RNAseq datasets of LUAD patients were collected and reprocessed. The differentially expressed genes (DEGs) related to macrophages between LUAD tissues and normal lung tissues were then identified. Based upon the above genes, three distinct immune patterns in the TCGA-LUAD cohort were identified. The ssGSEA and CIBERSORT were applied for immune profiling and characterization of different subtypes. A four-gene prognostic signature for LUAD patients was established based on the DEGs between the subtypes using stepwise multi-Cox regression. TCGA-LUAD cohort was used as training set. Five GEO-LUAD datasets and an independent cohort containing 112 LUAD samples were used for validation. TIDE (tumor immune dysfunction and exclusion) and drug sensitivity analyses were also performed. Macrophage-related differentially expressed genes were found out using the publicly available scRNA-seq data of LUAD. Three different immune patterns which were proved to have distinct immune infiltration characteristics in the TCGA-LUAD cohort were recognized based on the above macrophage-related genes. Thereafter, 174 DEGs among the above three different immune patterns were figured out; on the basis of this, a four-gene prognostic signature was constructed. This signature distinguished the prognosis of LUAD patients well in various GSE datasets as well as our independent cohort. Further analyses revealed that patients which had a higher risk score also accompanied with a lower immune infiltration level and a worse response to several immunotherapy biomarkers. This study highlighted that macrophage were significantly associated with TME diversity and complexity. The four-gene prognostic signature could be used for predicting outcomes and immune landscapes for patients with LUAD. [Display omitted] • Depicting the LUAD landscape and acquiring macrophage-related differentially expressed genes from scRNAseq data of LUAD. • Identifying and depicting 3 distinct LUAD subtypes with distinct immune landscapes which were termed as "immune-infiltrated phenotype", "immune-excluded phenotype" and "immune-desert phenotype". • Establishment of a four-gene prognostic model for LUAD patients and validation of the signature using publicly attainable LUAD cohorts and an independent cohort containing 112 LUAD samples. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were first-line treatments for NSCLC patients with EGFR-mutations. However, about 30 % of responders relapsed within six months because of acquired resistance. In this study, we used Connectivity Map (CMap) to discover a drug capable of reversing acquired EGFR-TKIs resistance. To investigate Lymecycline's ability to reverse acquired EGFR-TKIs resistance, two Icotinib resistant cell lines were constructed. Lymecycline's ability to suppress the proliferation of Icotinib resistant cells in vitro and in vivo was then evaluated. Molecular targets were predicted using network pharmacology and used to identify the molecular mechanism. Growth factor receptor-bound protein 2 (GRB2) is an EGFR-binding adaptor protein essential for EGFR phosphorylation and regulation of AKT/ERK/STAT3 signaling pathways. Lymecycline targeted GRB2 and inhibited the resistance of the cell cycle to EGFR-TKI, arresting disease progression and inducing apoptosis in cancer cells. Combined Lymecycline and Icotinib treatment produced a synergistic effect and induced apoptosis in HCC827R5 and PC9R10 cells. Cell proliferation in resistant cancer cells was significantly inhibited by the combined Lymecycline and Icotinib treatment in mouse models. Lymecycline inhibited the resistance of the cell cycle to EGFR-TKI and induced apoptosis in NSCLC by inhibiting EGFR phosphorylation and GRB2-mediated AKT/ERK/STAT3 signaling pathways. This provided strong support that Lymecycline when combined with EGFR targeting drugs, enhanced the efficacy of treatments for drug-resistant NSCLC. [ABSTRACT FROM AUTHOR]