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Using regional Global Positioning System (GPS) networks, we studied three‐dimensional spatial structure of ionospheric total electron content (TEC) anomalies preceding three recent large earthquakes in Chile, South America, i.e., the 2010 Maule (Mw 8.8), the 2014 Iquique (Mw 8.2), and the 2015 Illapel (Mw 8.3) earthquakes. Both positive and negative TEC anomalies, with areal extent dependent on the earthquake magnitudes, appeared simultaneously 20–40 min before the earthquakes. For the two midlatitude earthquakes (2010 Maule and 2015 Illapel), positive anomalies occurred to the north of the epicenters at altitudes 150–250 km. The negative anomalies occurred farther to the north at higher altitudes 200–500 km. This lets the epicenter, the positive and negative anomalies align parallel with the local geomagnetic field, which is a typical structure of ionospheric anomalies occurring in response to positive surface electric charges.

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The geometries, electronic, and magnetic properties of the 3d transition-metal-doped gold cluster: M@Au 6 clusters (M ) Sc, Ti, V, Cr, Mn, Fe, Co, Ni) have been systematically investigated by using relativistic all-electron density functional theory with generalized gradient approximation. It is found that all the ground states of the M@Au 6 clusters doped with an open d shells transition-metal atom are planar structures, in which the transition metal atom is located in the center of an Au 6 ring. All doped clusters show larger relative binding energies compared with pure Au 7 cluster, indicating doping by 3d transition-metal atoms could stabilize the Au 6 ring and promote the formation of a new binary alloy cluster. The magnetism calculations demonstrate that the magnetic moments of M@Au 6 clusters vary from 0 to 4 µ B by doping different transition-metal atoms into Au 6 ring, suggesting that M@Au 6 could have potential utility in new nanomaterials with tunable magnetic properties.

Background Colorectal cancer (CRC) is one of the most malignant tumors with high incidence, yet its molecular mechanism is not fully understood, hindering the development of targeted therapy. Metabolic abnormalities are a hallmark of cancer. Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy. In this study, we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms. Methods We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC. Squalene epoxidase (SQLE) was identified to be highly upregulated in CRC patients. The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability, colony and organoid formation, intracellular cholesterol concentration and xenograft tumor growth. The molecular mechanism of SQLE function was explored by combining transcriptome and untargeted metabolomics analysis. Western blotting and real‐time PCR were used to assess MAPK signaling activation by SQLE. Results SQLE‐related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis. SQLE promoted CRC growth in vitro and in vivo. Inhibition of SQLE reduced the levels of calcitriol (active form of vitamin D3) and CYP24A1, followed by an increase in intracellular Ca2+ concentration. Subsequently, MAPK signaling was suppressed, resulting in the inhibition of CRC cell growth. Consistently, terbinafine, an SQLE inhibitor, suppressed CRC cell proliferation and organoid and xenograft tumor growth. Conclusions Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1‐mediated MAPK signaling, highlighting SQLE as a potential therapeutic target for CRC treatment.

Background: VDAC1 functions in both cellular metabolism and mitochondria-mediated apoptosis. Results: New compounds were identified that induce apoptosis by promoting VDAC1 oligomerization and apoptosis in a Bakand Bak-independent manner. Conclusion: Bax and Bak are dispensable for VDAC1-mediated apoptosis, revealing a novel mechanism of apoptosis involving VDAC1 oligomerization. Significance: In cancers with Bax/Bak down-regulated, VDAC1-induced apoptosis offers a novel approach for tumor therapies.

Using ionospheric total electron contents residual data from 146 Global Navigation Satellite System stations in South America, we conducted three-dimensional tomography of ionospheric electron density anomalies immediately before the 2015 Illapel M w 8.3 earthquake, Central Chile. We used five GPS and five GLONASS satellites and applied continuity constraints to regularize the linear least squares inversion. The reconstructed anomalies are composed of positive and negative regions, at altitudes of~200 km and 400 km, respectively, distributed roughly along the geomagnetic field. This feature suggests that the observed anomalies occurred by the downward E × B drift of electrons due to electric fields within ionosphere, possibly caused by surface positive electric charges. We also discuss the existence of the mirror image anomalies near the geomagnetic conjugate point of the epicenter using stations in Colombia.Two physical models have been proposed to explain the preseismic ionospheric anomalies. Kuo et al. (2014Kuo et al. ( , 2015 considered upward electric current from crust to lower ionosphere made westward electric field within ionosphere and redistributed ionospheric electrons. Kelley et al. (2017), on the other hand, considered that the surface positive charges directly drove the redistribution of ionospheric electrons. In either of the hypotheses, surface positive electric charge makes electric fields within ionosphere, and electron redistributions by downward E × B drifts. Although the origin of the surface electric charges is not clear, we consider it likely that positive electric charges diffused from stressed rocks play an important role (e.g., Freund, 2011). HE AND HEKI4015

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