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Most lung cancer deaths are caused by a distant disseminated disease rather than primary tumors. Understanding the biology behind distant metastasis (DM) is crucial for the effective prediction and reduction of recurrence rates. Genome-wide analysis of the tumor provides a new way to explore the pathogenesis and molecular diagnosis of metastasis in lung adenocarcinoma. In our study, a total of 215 eligible lung adenocarcinoma patients were enrolled. The DNA was extracted from Formalin-fixed paraffin-embedded (FFPE) samples from the primary tumors of these patients. Comprehensive molecular profiling was performed using a panel covering the exome of lung cancer-associated driver genes based on targeted next-generation sequencing. Tumor gene alterations were analyzed to investigate the differences in molecular features between lung adenocarcinomas with or without DM. Patients with DM of lung adenocarcinoma had significantly more variations in overall copy number (defined as Copy Number Alteration (CNA) load and Copy Number Instability (CNI) score). Interestingly, the study of the relationship between copy number variation and other molecular features verified that the degree of copy number variation has a positive correlation with mutations of DNA damage repair pathway (DDR). Thus, the additional analysis further revealed that metastatic patients accumulated more mutations in the DDR pathway, suggesting that impaired function of the DDR pathway and copy number variations play important roles in the invasion process of cancer cells. A comprehensive genetic analysis of lung adenocarcinoma revealed significant genomic changes between DM and non-DM patients. This finding may shed new light on the elucidation of lung cancer invasion mechanisms, and provide potential predictors for metastatic lung cancer.Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding molecules that also interfere with its biological activity. However, MIF tautomerase activity assays are troubled by irregularities, thus creating a need for alternative methods. In this study, we identified a 7-hydroxycoumarin fluorophore with high affinity for the MIF tautomerase active site (Ki = 18 ± 1 nM) that binds with concomitant quenching of its fluorescence. This property enabled development of a novel competition-based assay format to quantify MIF binding. We also demonstrated that the 7-hydroxycoumarin fluorophore interfered with the MIF-CD74 interaction and inhibited proliferation of A549 cells. Thus, we provide a high-affinity MIF binder as a novel tool to advance MIF-oriented research.Analysis of subcellular organelles (e.g., a cytoplasm membrane and mitochondria) during cellular processes can provide particularly useful information for our understanding of cell chemistry and biology. For this purpose, fluorescent probes capable of dynamically imaging multiple organelles in a simultaneous and selective manner are highly demanded, yet such probes are scarcely reported due to the challenges in molecular design. In this study, we developed a dual-colored aggregation-induced emission (AIE) probe TPNPDA-C12 with twisted intramolecular charge transfer (TICT) to visualize the membrane and mitochondria of the same cells through distinct fluorescence channels simultaneously. this website We also successfully used the probe to monitor and distinguish the dynamic changes of the organelles during cell apoptosis and necrosis induced by reactive oxygen species (ROS) and cytotoxins.As increasing demand for noncontact temperature sensing, the development of a high-performance optical thermometer probe is more and more urgent. In this work, an efficient dual-mode optical thermometry strategy based on the Pr3+/Dy3+ energy transfer (ET) in some typical double-perovskite oxides is presented, which offers a promising way to design FIR/lifetime dual-mode optical thermometry with excellent temperature-measuring sensitivity and signal discrimination. According to this strategy, double-perovskite La2MgTiO6Pr3+/Dy3+ phosphors are successfully synthesized. On the basis of diverse thermal responses between Pr3+ and Dy3+, the FIR of Pr3+ to Dy3+ (four FIR mode) in this material displays outstanding optical thermometry performance from 298 to 548 K. The maximum absolute and relative sensitivities (Sa and Sr) of mode 1 are 0.09 and 2.357% K-1, being better than the current optical temperature measurement materials. For the fluorescence lifetime mode, the Sa-max and Sr-max values reach 2.85 × s 10-4 and 1.814% K-1. Furthermore, the dual-mode optical thermometry mechanism was presented and studied. It also demonstrated excellent optical thermometry performance in the other Pr3+/Dy3+ codoped double-perovskite oxides, such as LaMg0.598Nb0.402O3, NaLa(MoO4)2, NaGd(MoO4)2, and NaLa(WO4)2, proving the universality of the presented strategy. This article presents an effective Pr3+/Dy3+ ET pathway for developing new and highly sensitive FIR/lifetime dual-mode optical temperature sensing materials.Calvatia nipponica is an extremely rare mushroom with a limited number of studies on its chemical components and biological activities published. Here we report the isolation of a novel sterol, calvatianone (1), possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids (2-5) from the fruiting bodies of C. nipponica. The structure of calvatianone including its absolute configuration was determined by NMR spectroscopic analyses, HR-ESIMS, gauge-including atomic orbital NMR chemical shift calculations, and ECD calculations. Ergosterol peroxide (3) and cyathisterol (4) suppressed the cell viability increase induced by 17β-estradiol in MCF-7 breast cancer cell lines, suggesting a possible approach for these compounds to serve as ERα antagonists.A single-crystal rod with a composition of Li6.95La3Zr1.95Nb0.05O12 was grown using the floating zone method. The single-crystal rod had a diameter of 8 mm and length of 90 mm. Li6.95La3Zr1.95Nb0.05O12 crystallizes in an orthorhombic system, with space group Ibca, and the single crystal with 0.05 substitutions of niobium had the following lattice parameters a = 13.1280(3) Å, b = 12.6777(3) Å, and c = 13.1226(4) Å. The reliability values obtained were R = 1.77% and wR = 3.27% in Li6.95La3Zr1.95Nb0.05O12 for 857 independent refractions, with a shift/error for 115 parameters of less than 0.001 value in the single-crystal X-ray diffraction data. Four interspace sites were occupied by the Li ions, constructed by the framework structure. The Li1, Li2, and Li3 ions are located in the octahedral 16f site, and Li4 is in the tetrahedral 8d site. The bulk lithium-ion conductivity in Li6.95La3Zr1.95Nb0.05O12 was 3.21 × 10-4 S cm-1 at 298 K.
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