Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple Myeloma and Have Strong Implications for Adverse Prognosis

Background/Aims: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. Methods: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). Results: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. Conclusion: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention

New Insight on Hydrogen Evolution Reaction Activity of MoP2 from Theoretical Perspective

We systematically investigated the hydrogen evolution reaction (HER) of six facets of MoP 2 based on the periodic density functional theory (DFT). The calculated values of Gibbs free energy of hydrogen adsorption ( Δ G H ) indicated that the (111) facet has a good HER activity for a large range of hydrogen coverages. The zigzagged patterns before 75% hydrogen coverage suggest a facilitation among Mo1, P1 and Mo2 sites, which are attributed to repeat occupancy sites of H atoms. From ab initial atomistic thermodynamics analysis of hydrogen coverage, we gained that the most stable coverage of hydrogen is 18.75% at 1 atm H 2 and 298 K. Finally, the doping effects on HER activity were investigated and found that catalytic performance can be improved by substituting P with an S or N atom, as well as substituting the Mo atom with an Fe atom, respectively. We hope this work can provide new insights on further understanding of HER for MoP 2 and give instructions for the experimental design and synthesis of transition metal phosphides (TMPs)-based high-performance catalysts

Expression of NEAT1 can be used as a predictor for Dex resistance in multiple myeloma patients

Abstract Objective Multiple myeloma is a heterogeneous disorder and the intratumor genetic heterogeneity contributes to emergency of drug resistance. Dexamethasone has been used clinically for decades for MM. Nevertheless, their use is severely hampered by the risk of developing side effects and the occurrence of Dex resistance. LncRNA NEAT1 plays a oncogenic role and participates in drug resistance in many solid tumors. Therefore, we investigated a potential usefulness of this molecular as a biomarker for diagnosis of MM and possible correlations of NEAT1 expression with drug resistance and prognosis. Methods Bone marrow and peripheral blood mononuclear cells samples were collected from 60 newly diagnosed MM patients. The expression of NEAT1expression level were detected by quantitative real-time PCR analyses. The relationship about the expression levels of lncRNA with other clinical and cytogenetic features was analyzed. In addition, we measured to analysis the correlation between the expression of NEAT1 and Dex resistance in MM patients. Results It was found that the expression of NEAT1 is significantly higher in multiple myeloma patients compared to controls and does not change with other clinical features and cytogenetic features. We further discovered that overexpression of NEAT1 was associated with Dex resistance and a poor prognosis in MM patients. Conclusion LncRNA NEAT1 has a significant value that might act as a promoting factor in the development of MM and may be severed as a diagnostic factor in MM. NEAT1 invovled in Dex resistance, which provide a new interpretation during the chemotherapy for MM

Model-Independent Observation of Exotic Contributions to B0→J/ψK+π−B^0\to J/\psi K^+\pi^- Decays

International audienceAn angular analysis of B0→J/ψK+π- decays is performed, using proton-proton collision data corresponding to an integrated luminosity of 3  fb-1 collected with the LHCb detector. The m(K+π-) spectrum is divided into fine bins. In each m(K+π-) bin, the hypothesis that the three-dimensional angular distribution can be described by structures induced only by K* resonances is examined, making minimal assumptions about the K+π- system. The data reject the K*-only hypothesis with a large significance, implying the observation of exotic contributions in a model-independent fashion. Inspection of the m(J/ψπ-) vs m(K+π-) plane suggests structures near m(J/ψπ-)=4200 and 4600 MeV

Study of Υ\Upsilon production in ppPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

International audienceThe production of ϒ(nS) mesons (n = 1, 2, 3) in pPb and Pbp collisions at a centre-of-mass energy per nucleon pair $\sqrt{s_{\mathrm{NN}}}=8.16$ TeV is measured by the LHCb experiment, using a data sample corresponding to an integrated luminosity of 31.8 nb$^{−1}$. The ϒ(nS) mesons are reconstructed through their decays into two opposite-sign muons. The measurements comprise the differential production cross-sections of the ϒ(1S) and ϒ(2S) states, their forward-to-backward ratios and nuclear modification factors. The measurements are performed as a function of the transverse momentum p$_{T}$ and rapidity in the nucleon-nucleon centre-of-mass frame y$^{*}$ of the ϒ(nS) states, in the kinematic range p$_{T}$ < 25 GeV/c and 1.5 < y$^{*}$ < 4.0 (−5.0 < y$^{*}$ < −2.5) for pPb (Pbp) collisions. In addition, production cross-sections for ϒ(3S) are measured integrated over phase space and the production ratios between all three ϒ(nS) states are determined. Suppression for bottomonium in proton-lead collisions is observed, which is particularly visible in the ratios. The results are compared to theoretical models

First Measurement of Charm Production in its Fixed-Target Configuration at the LHC

International audienceThe first measurement of heavy-flavor production by the LHCb experiment in its fixed-target mode is presented. The production of J/ψ and D0 mesons is studied with beams of protons of different energies colliding with gaseous targets of helium and argon with nucleon-nucleon center-of-mass energies of sNN=86.6 and 110.4 GeV, respectively. The J/ψ and D0 production cross sections in pHe collisions in the rapidity range [2, 4.6] are found to be σJ/ψ=652±33(stat)±42(syst)   nb/nucleon and σD0=80.8±2.4(stat)±6.3(syst)  μb/nucleon, where the first uncertainty is statistical and the second is systematic. No evidence for a substantial intrinsic charm content of the nucleon is observed in the large Bjorken-x region

Measurement of the CPCP-violating phase ϕs\phi_s from Bs0→J/ψπ+π−B_{s}^{0}\to J/\psi\pi^+\pi^- decays in 13 TeV pppp collisions

International audienceDecays of Bs0 and B‾0s mesons into J/ψπ+π− final states are studied in a data sample corresponding to 1.9 fb −1 of integrated luminosity collected with the LHCb detector in 13 TeV pp collisions. A time-dependent amplitude analysis is used to determine the final-state resonance contributions, the CP -violating phase ϕs=−0.057±0.060±0.011 rad, the decay-width difference between the heavier mass Bs0 eigenstate and the B0 meson of −0.050±0.004±0.004 ps −1 , and the CP -violating parameter |λ|=1.01−0.06+0.08±0.03 , where the first uncertainty is statistical and the second systematic. These results are combined with previous LHCb measurements in the same decay channel using 7 TeV and 8 TeV pp collisions obtaining ϕs=0.002±0.044±0.012 rad, and |λ|=0.949±0.036±0.019