Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that Izb reverses β-catenin-mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP response element-luciferase activity in osteoblasts. Izb increases active forms of β-catenin and promotes β-catenin translocation, thereby dissociating β-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates PTH-stimulated GSK3β phosphorylation and β-catenin phosphorylation. Thus Izb enhances PTH stimulation of β-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating β-catenin from the PTHR. These findings provide evidence that Izb may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases

Probing dark particles indirectly at the CEPC

When dark matter candidate and its parent particles are nearly degenerate, it would be difficult to probe them at the Large Hadron Collider directly. We propose to explore their quantum loop effects at the CEPC through the golden channel process $e^+e^-\to \mu^+\mu^-$. We use a renormalizable toy model consisting of a new scalar and a fermion to describe new physics beyond the Standard Model. The new scalar and fermion are general multiplets of the $SU(2)_L\times U(1)_Y$ symmetry, and couple to the muon lepton through Yukawa interaction. We calculate their loop contributions to anomalous $\gamma\mu^+\mu^-$ and $Z\mu^+\mu^-$ couplings which can be applied to many new physics models. The prospects of their effects at the CEPC are also examined assuming a 0.002 accuracy in the cross section measurement

N-[2-(2-Chloro­phen­yl)-2-hy­droxy­eth­yl]propan-2-aminium benzoate

In the title compound, C11H17ClNO+·C7H5O2 −, obtained by the reaction of chlorprenaline {or 1-(2-chlorophenyl)-2-[(1-methylethyl)amino]ethanol} and benzoic acid, the chlorprenaline is twisted moderately [C—C—C—C torsion angle = −76.00 (17)°] compared with related compounds. The mol­ecules as usual form dimers. In the crystal structure, the two components are connected by classical O—H⋯O and N—H⋯O hydrogen bonds

Porous cerium dioxide hollow spheres and their photocatalytic performance

Uniform-sized and monodiperse cerium dioxide porous hollow spheres (CeO2-PH) based on the Ostwald ripening process were fabricated by a simple solvothermal method in the absence of any templates. The structure and morphology of CeO2-PH and CeO2-NP (cerium dioxide nanoparticles) were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and Brunauer–Emmett–Teller (BET) surface area analysis. The average diameter of face-centered cubic (fcc) phase CeO2-PH was ca. 160 nm with a high specific surface area, and it is composed of small crystal grain particles (ca. 10 nm). Furthermore, CeO2-PH has high activity for the evaluation of acetaldehyde decomposition. Optical, defect, and chemical state properties were characterized by Raman spectra, ultraviolet-visible absorption spectroscopy (UV-vis), and X-ray photoelectron spectroscopy (XPS). The presence of Ce3+ ions narrowed the band gap of CeO2-PH, resulting in the high light harvesting. The large amount of oxygen vacancy defects provided many activity sites on CeO2-PH in the photocatalytic process. The formation scheme and photocatalyic mechanism will be discussed in this paper

Superconductivity Induced by Site-Selective Arsenic Doping in Mo5_5Si3_3

Arsenic doping in silicides has been much less studied compared with phosphorus. In this study, superconductivity is successfully induced by As doping in Mo$_5$Si$_3$. The superconducting transition temperature ($T_c$) reaches 7.7 K, which is higher than those in previously known W$_5$Si$_3$-type superconductors. Mo$_5$Si$_2$As is a type-II BCS superconductor with upper and lower critical fields of 6.65 T and 22.4 mT, respectively. In addition, As atoms are found to selectively take the 8$h$ sites in Mo$_5$Si$_2$As. The emergence of superconductivity is possibly due to the shift of Fermi level as a consequence of As doping, as revealed by the specific heat measurements and first-principles calculations. Our work provides not only another example of As doping, but also a practical strategy to achieve superconductivity in silicides through Fermi level engineering.Comment: Supporting Information available at the corresponding DO

Fully Automated Detection of Corticospinal Tract Damage in Chronic Stroke Patients

Structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. However, current methods for measurement of fractional atrophy (FA) of CST based on region of interest (ROI) are time-consuming and open to bias. Here, we used tract-based spatial statistics (TBSS) together with a CST template with healthy volunteers to quantify structural integrity of CST automatically. Two groups of patients after ischemic stroke were enrolled, group 1 (10 patients, 7 men, and Fugl-Meyer assessment (FMA) scores ⩽ 50) and group 2 (12 patients, 12 men, and FMA scores = 100). CST of FAipsi, FAcontra, and FAratio was compared between the two groups. Relative to group 2, FA was decreased in group 1 in the ipsilesional CST (P<0.01), as well as the FAratio (P<0.01). There was no significant difference between the two subgroups in the contralesional CST (P=0.23). Compared with contralesional CST, FA of ipsilesional CST decreased in group 1 (P<0.01). These results suggest that the automated method used in our study could detect a surrogate biomarker to quantify the CST after stroke, which would facilitate implementation of clinical practice