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

MSSM Anatomy of the Polarization Puzzle in B --> phi K* Decays

We analyze the $B \to \phi K^{*}$ polarization puzzle in the Minimal Supersymmetric Standard Model (MSSM) including the neutral Higgs boson (NHB) contributions. To calculate the non-factorizable contributions to hadronic matrix elements of operators, we have used the QCD factorization framework to the $\alpha_s$ order. It is shown that the recent experimental results of the polarization fractions in $B\to \phi K^{*}$ decays, which are difficult to be explained in SM, could be explained in MSSM if there are flavor non-diagonal squark mass matrix elements of 2nd and 3rd generations, which also satisfy all relevant constraints from known experiments ($B\to X_s\gamma, B_s\to \mu^+\mu^-, B\to X_s \mu^+\mu^-, B\to X_s g, \Delta M_s$, etc.). We have shown in details that the experimental results can be accommodated with the flavor non-diagonal mass insertion of chirality RL, RL+LR, RR, or LL+ RR when the NHB contributions as well as $\mathcal{O}(\alpha_s)$ corrections of hadronic matrix elements of operators are included. However the branching ratios for the decay are smaller than the experimental measurements.Comment: 15 pages, 5 figures, minor revision and references adde

A Study Of Online Beauty Community Members\u27 Voices: EWOM Text Mining

The Internet promotes the development of the social media, these new media offer open platforms for participants to share product/service reviews with each other. This study applied the theory of conformity behavior to explain online community members’ information consumption behaviors by using text-mining techniques. NetBeans7.4 was used to conduct Chinese tokenization and data analysis. Next, factor analysis and correlation analysis were conducted to reduce the attribute size of products. Our findings demonstrate that more attributes a product/brand has more discussions found in an online community. The conformity phenomenon is seen in help to accumulate sufficient and complete eWOM to reach a sufficient quantity. Thus, brand is more likely to be mentioned. However, the few brand vendors with high product strength have the impact of conformity, in which, may result in a lower spread power with wrong marketing strategy. Therefore, we argue that the reputation bias generated by conformity will make a misleading purchase decision. Based on the conformity effect of eWOM, we establish the effectiveness of text mining technology applied to information search platform design and brand marketing strategy. Implications were proposed in the final section

The LqL_q-weighted dual programming of the linear Chebyshev approximation and an interior-point method

Given samples of a real or complex-valued function on a set of distinct nodes, the traditional linear Chebyshev approximation is to compute the best minimax approximation on a prescribed linear functional space. Lawson's iteration is a classical and well-known method for that task. However, Lawson's iteration converges linearly and in many cases, the convergence is very slow. In this paper, by the duality theory of linear programming, we first provide an elementary and self-contained proof for the well-known Alternation Theorem in the real case. Also, relying upon the Lagrange duality, we further establish an $L_q$-weighted dual programming for the linear Chebyshev approximation. In this framework, we revisit the convergence of Lawson's iteration, and moreover, propose a Newton type iteration, the interior-point method, to solve the $L_2$-weighted dual programming. Numerical experiments are reported to demonstrate its fast convergence and its capability in finding the reference points that characterize the unique minimax approximation.Comment: 29 pages, 8 figure

Biodegradation of Ammonia in Biofiltration Systems: Changes of Metabolic Products and Microbial Communities

In the first stage, the feasibility of using the waste materials from coal power plants (i.e., coal slag) and landscapes (i.e., wood chip and compost) as packing media in various biofiltration systems for ammonia (NH3) removal was investigated. In the second stage, the optimized biotrickling system packed with coal slag was employed to investigate the effects of inlet concentration on NH3 treatment performance. A complete NH3 removal was achieved at concentrations of up to 250 ppm at an empty bed retention time of as low as 8 s, which is shorter than most previously reported biofiltration systems. Results of metabolic product analysis indicated that half of introduced NH3 was oxidized to nitrate and the rest was converted to ammonium ion at low loadings, while nitrite and ammonium ions predominate at high loadings. A bacterial community shift was observed with regard to the loading rates and pH conditions. In addition, there were no common operating problems, such as clogging and compaction, in the operation for more than 1 year

Pharmacokinetic/Pharmacodynamic Profiles of Tiamulin in an Experimental Intratracheal Infection Model of Mycoplasma gallisepticum

Mycoplasma gallisepticum is the most important pathogen in poultry among four pathogenic Mycoplasma species. Tiamulin is a pleuromutilin antibiotic that shows a great activity against M. gallisepticum and has been approved for use in veterinary medicine particularly for poultry. However, the pharmacokinetic/pharmacodynamics (PK/PD) profiles of tiamulin against M. gallisepticum are not well understood. Therefore, in the current studies, we investigated the in vivo PK/PD profiles of tiamulin using a well-established experimental intratracheal infection model of M. gallisepticum. The efficacy of tiamulin against M. gallisepticum was studied in 8-day-old chickens after intramuscular (i.m.) administration at 10 doses between 0-80 mg/kg. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the PK parameters of tiamulin following i.m. administration at doses of 5, 40, and 80 mg/kg in Mycoplasma gallisepticum-infected neutropenic chickens. Real-time PCR (RT-PCR) was used for quantitative detection of M. gallisepticum. The MIC of tiamulin against M. gallisepticum strain S6 was 0.03 μg/mL. The PK/PD index, AUC24h/MIC, correlated well with the in vivo antibacterial efficacy. The in vivo data suggest that animal dosage regimens should supply AUC24h/MIC of tiamulin of 382.68 h for 2 log10 ccu equivalents M. gallisepticum reduction. To attain that goal, the administered dose is expected to be 45 mg/kg b.w. for treatment of M. gallisepticum infection with an MIC90 of 0.03 μg/mL

Rottlerin Inhibits Lonicera japonica-Induced Photokilling in Human Lung Cancer Cells through Cytoskeleton-Related Signaling Cascade

This study demonstrated that many apoptotic signaling pathways, such as Rho family, PKC family, MAP kinase family, and mitochondria-mediated apoptotic pathway, were triggered by Lonicera japonica extracts and irradiation in CH27 cells. Rottlerin, a PKCδ -selective inhibitor, reversed the photoactivated Lonicera japonica extract-induced decrease in PKCδ protein expression and change in cell morphology in this study. In addition, rottlerin inhibited the photoactivated Lonicera japonica-induced decrease in protein expression of Ras, ERK, p38, PKCα, and PKCε, which are the kinases of prosurvival signaling pathway. We also demonstrated that pretreatment with rottlerin prevented actin microfilaments and microtubules from damage during the photoactivated Lonicera japonica-induced CH27 cell death. Furthermore, the promotion of the cytoskeleton-related signaling cascade following rottlerin by upregulation of cytoskeleton-related mediators (p38, HSP27, FAK, paxillin, and tubulin) and molecules of downstream of F-actin (mitochondria-mediated apoptosis pathway) reduces CH27 cell death, indicating that cytoskeleton is the potential target in the photoactivated Lonicera japonicaextract-induced photokilling of CH27 cells