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Background Osimertinib is the first-line therapy for patients with non-small cell lung cancer harboring epidermal growth factor receptor–activating alterations. Although osimertinib has been shown to elicit profound patient responses, cancer cells frequently develop additional alterations that sustain their proliferation capacity. This acquired resistance represents a substantial hurdle in precision medicine for patients with lung cancer. Methods The biological and cellular properties of the G-quadruplex ligand BMVC-8C3O and its anticancer activities were evaluated in non-small cell lung carcinomas. In addition, combined treatment with BMVC-8C3O and osimertinib was evaluated for its effects on the growth of osimertinib-resistant tumors in vivo. Results We demonstrate that BMVC-8C3O effectively suppresses c-FOS expression by stabilizing G-rich sequences located at the c-FOS promoter. The suppression c-FOS expression by BMVC-8C3O increases the sensitivity of acquired resistant cancer cells to osimertinib. Combining BMVC-8C3O and osimertinib has a synergistic effect in inhibiting the growth of acquired resistant cancers both in vitro and in mouse models. The combined inhibitory effect is not limited to BMVC-8C3O, either: several G-quadruplex ligands show varying levels of inhibition activity. We also show that simultaneous inhibition of both the c-FOS and PI3K/AKT pathways by BMVC-8C3O and osimertinib synergistically inhibits the growth of acquired resistant cancer cells. Conclusion These findings unveil a synthetic lethal strategy to prevent and inhibit epidermal growth factor receptor–altered lung cancers with acquired osimertinib resistance. G-quadruplex ligands have the potential to be integrated into current osimertinib-based treatment regimens. [ABSTRACT FROM AUTHOR]

Featured Application: Our theoretical studies report the anomalous and spin Hall conductivities of Co3−xCrxAl Heusler compounds in the L21 crystal structure. Based on density functional theory, we studied the electronic, magnetic, and mechanical properties of Co3−xCrxAl (x = 0, 1, 2, 3) Heusler compounds with the generalized gradient approximation (GGA) for the exchange-correlation potential. In this study, we report two principal spin-related phenomena, namely, the anomalous Hall effect and current spin polarization of the Co3−xCrxAl Heusler compounds in the L21 crystal structure. Heusler compounds, both ideally and inversely ordered, were considered. We found that the calculated magnetic moment of Co3−xCrxAl decreased with an increase in the Cr concentration for both ideally and inversely ordered structures, except for Cr3Al. We also found that the spin polarization for all Co3−xCrxAl was larger than 50%, except for Cr2CoAl in the inverse structure. All the considered Heusler compounds were mechanically stable except for the regular Cr2CoAl. The Hall current spin polarization was also calculated. We found that Co2CrAl in the XA structure had the largest spin Hall conductivity of 370 ( ℏ S / e   cm ), and the spin polarization of the induced Hall current was high. [ABSTRACT FROM AUTHOR]

Featured Application: This work provides a detailed analysis on the gas-sensing performance of Pd-doped ZnGa2O4-based sensors for detecting CO gas. We performed first-principles calculations to study the adsorption of the CO molecules on both clean and Pd-doped ZnGa2O4(111) surfaces. The adsorption reaction and work function of the CO adsorption models were examined. The CO molecules on the clean and Pd-doped ZnGa2O4(111) surfaces exhibit maximum work function changes of −0.55 eV and −0.79 eV, respectively. The work function change of Pd-doped ZnGa2O4(111) for detecting CO is 1.43 times higher than that of the clean ZnGa2O4(111). In addition, the adsorption energy is also significantly reduced from −1.88 eV to −3.36 eV without and with Pd atoms, respectively. The results demonstrate ZnGa2O4-based gas sensors doped by palladium can improve the sensitivity of detecting CO molecules. [ABSTRACT FROM AUTHOR]

Different G-quadruplex structures for the human telomeric sequence d([[T.sub.2]A[G.sub.3].sub.4] in vitro have been documented in the presence of sodium and potassium. Verification of the G-quadruplex structures in human telomeres in vivo is the main issue in establishing the biological function of the G-quadruplex structures in telomeres as well as the development of anticancer agents. Here we have applied two-photon excitation fluorescence lifetime imaging microscopy to measure the fluorescence lifetime of the BMVC molecule upon interaction with various DNA structures. The distinction in lifetime measured with submicrometer spatial resolution in two-photon excitation fluorescence lifetime imaging microscopy provides a powerful approach not only to verify the existence of the antiparallel G-quadruplex structure in human telomeres but also to map its localizations in metaphase chromosomes.