57,247 research outputs found

    Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality

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    Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation

    Bimetallic Oxide of Y<sub>2</sub>Cu<sub>2</sub>O<sub>5</sub> for Electroreduction of CO<sub>2</sub> to Syngas

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    The incorporation of guest elements into Cu-based bimetallic oxides has been proven as an effective way to modify the electronic structure and reactivity of Cu active sites. Here, the Y element was chosen as the guest element to modulate the electronic structure of Cu and alter its performance for electrochemical CO2 reduction reaction (CO2RR). Y2Cu2O5, a high-crystallinity Cu-based bimetallic oxide, was synthesized via the sol–gel method. For pure-phase CuO and Y2O3 controls, the selectivity of H2 significantly exceeded that of CO. While Y and Cu combined in equal molar weights to form Y2Cu2O5, a notable enhancement in the CO selectivity was observed, resulting in a CO/H2 ratio of approximately 1:1. These results prove that under the influence of Y, the electronic structure of Cu exhibits heightened CO selectivity. When the electrolyte solution was substituted with 1 M KOH, the CO/H2 ratio achieved was about 2:1, indicating that the ratio of syngas can be adjusted by changing the concentration or type of electrolyte. This study explores the electronic modulation of a guest element in Cu-based bimetallic oxides and clarifies the beneficial influence of the Y element on the activity of Cu sites, which provides a novel approach for designing and regulating the activity of catalyst active sites

    Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC

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    International audienceUltrarelativistic nuclear collisions create a strongly interacting state of hot and dense quark-gluon matter that exhibits a remarkable collective flow behavior with minimal viscous dissipation. To gain deeper insights into its intrinsic nature and fundamental degrees of freedom, we extracted the speed of sound in this medium created using lead-lead (PbPb) collisions at a center-of-mass energy per nucleon pair of 5.02 TeV. The data were recorded by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 0.607 nb−1^{-1}. The measurement is performed by studying the multiplicity dependence of the average transverse momentum of charged particles emitted in head-on PbPb collisions. Our findings reveal that the speed of sound in this matter is nearly half the speed of light, with a squared value of 0.241 ±\pm 0.002 (stat) ±\pm 0.016 (syst) in natural units. The effective medium temperature, estimated using the mean transverse momentum, is 219 ±\pm 8 (syst) MeV. The measured squared speed of sound at this temperature aligns precisely with predictions from lattice quantum chromodynamic (QCD) calculations. This result provides a stringent constraint on the equation of state of the created medium and direct evidence for a deconfined QCD phase being attained in relativistic nuclear collisions

    Multiplicity dependence of σψ(2S)/σJ/ψ\sigma_{\psi(2S)}/\sigma_{J/\psi} in pppp collisions at s=13\sqrt{s}=13 TeV

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    International audienceThe ratio of production cross-sections of ψ(2S)\psi(2S) over J/ψJ/\psi mesons as a function of charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy s=13\sqrt{s}=13 TeV is measured with a data sample collected by the LHCb detector, corresponding to an integrated luminosity of 658 pb−1^{-1}. The ratio is measured for both prompt and non-prompt ψ(2S)\psi(2S) and J/ψJ/\psi mesons. When there is an overlap between the rapidity ranges over which multiplicity and charmonia production are measured, a multiplicity-dependent modification of the ratio is observed for prompt mesons. No significant multiplicity dependence is found when the ranges do not overlap. For non-prompt production, the ψ(2S)−to−J/ψ\psi(2S)-to-J/\psi production ratio is roughly independent of multiplicity irrespective of the rapidity range over which the multiplicity is measured. The results are compared to predictions of the co-mover model and agree well except in the low multiplicity region. The ratio of production cross-sections of ψ(2S)\psi(2S) over J/ψJ/\psi mesons are cross-checked with other measurements in di-lepton channels and found to be compatible

    Characterisation of flavourous sesame oil obtained from microwaved sesame seed by subcritical propane extraction

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    This study developed a novel and green method to produce fragrant sesame oil using microwaves and subcritical extraction (SBE). Sesame seeds were microwaved at 540 W for 0–9 min before subcritical propane extraction at 40 °C and 0.5 MPa. SBE caused less deformation to the cellular microstructure of sesame cotyledons while dramatically improving oil yield (96.7–97.1 %) compared to screw processing (SP) (53.1–58.6 %). SBE improved extraction rates for Îł-tocopherol (381.1–454.9 Όg/g) and sesame lignans (917.9–970.4 mg/100 g) in sesame oil compared to SP (360.1–443.8 Όg/g and 872.8–916.8 mg/100 g, respectively). Microwaves generated aroma-active heterocyclics and phenolics faster than hot-air roasting in sesame oil with a better sensory profile. SBE had a higher extraction rate for aroma-active terpenes, alcohols, and esters while reducing the concentrations of carcinogenic PAHs and HCAs in sesame oil. The novel combination process of microwaves and subcritical extraction is promising in producing fragrant sesame oil with superior qualities

    CEPC Technical Design Report -- Accelerator