Inhibition of DHCR24 activates LXRα to ameliorate hepatic steatosis and inflammation

Liver X receptor (LXR) agonism has theoretical potential for treating NAFLD/NASH, but synthetic agonists induce hyperlipidemia in preclinical models. Desmosterol, which is converted by & UDelta;24-dehydrocholesterol reductase (DHCR24) into cholesterol, is a potent endogenous LXR agonist with anti-inflammatory properties. We aimed to investigate the effects of DHCR24 inhibition on NAFLD/NASH development. Here, by using APOE*3-Leiden. CETP mice, a well-established translational model that develops diet-induced human-like NAFLD/NASH characteristics, we report that SH42, a published DHCR24 inhibitor, markedly increases desmosterol levels in liver and plasma, reduces hepatic lipid content and the steatosis score, and decreases plasma fatty acid and cholesteryl ester concentrations. Flow cytometry showed that SH42 decreases liver inflammation by preventing Kupffer cell activation and monocyte infiltration. LXRa deficiency completely abolishes these beneficial effects of SH42. Together, the inhibition of DHCR24 by SH42 prevents diet-induced hepatic steatosis and inflammation in a strictly LXRa-dependent manner without causing hyperlipidemia. Finally, we also showed that SH42 treatment decreased liver collagen content and plasma alanine transaminase levels in an established NAFLD model. In conclusion, we anticipate that pharmacological DHCR24 inhibition may represent a novel therapeutic strategy for treatment of NAFLD/NASH.Metabolic health: pathophysiological trajectories and therap

Observation of Resonance Structures in e+e- →π+π-ψ2 (3823) and Mass Measurement of ψ2 (3823)

© 2022 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the "https://creativecommons.org/licenses/by/4.0/"Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. Funded by SCOAP3.Using a data sample corresponding to an integrated luminosity of 11.3 fb-1 collected at center-of-mass energies from 4.23 to 4.70 GeV with the BESIII detector, we measure the product of the e+e-→π+π-ψ2(3823) cross section and the branching fraction B[ψ2(3823)→γχc1]. For the first time, resonance structure is observed in the cross section line shape of e+e-→π+π-ψ2(3823) with significances exceeding 5σ. A fit to data with two coherent Breit-Wigner resonances modeling the s-dependent cross section yields M(R1)=4406.9±17.2±4.5 MeV/c2, Γ(R1)=128.1±37.2±2.3 MeV, and M(R2)=4647.9±8.6±0.8 MeV/c2, Γ(R2)=33.1±18.6±4.1 MeV. Though weakly disfavored by the data, a single resonance with M(R)=4417.5±26.2±3.5 MeV/c2, Γ(R)=245±48±13 MeV is also possible to interpret data. This observation deepens our understanding of the nature of the vector charmoniumlike states. The mass of the ψ2(3823) state is measured as (3823.12±0.43±0.13) MeV/c2, which is the most precise measurement to date

STCF Conceptual Design Report: Volume 1 -- Physics & Detector

International audienceThe Super $\tau$-Charm facility (STCF) is an electron-positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with a peak luminosity of $0.5\times 10^{35}{\rm cm}^{-2}{\rm s}^{-1}$ or higher. The STCF will produce a data sample about a factor of 100 larger than that by the present $\tau$-Charm factory -- the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies

STCF Conceptual Design Report: Volume 1 -- Physics & Detector

International audienceThe Super $\tau$-Charm facility (STCF) is an electron-positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with a peak luminosity of $0.5\times 10^{35}{\rm cm}^{-2}{\rm s}^{-1}$ or higher. The STCF will produce a data sample about a factor of 100 larger than that by the present $\tau$-Charm factory -- the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies

Search for the semi-leptonic decays Λc+→Λπ+π−e+νe and Λc+→pKS0π−e+νe

We search for the semi-leptonic decays Λc+→Λπ+π−e+νe and Λc+→pKS0π−e+νe in a sample of 4.5fb−1 of e+e− annihilation data collected in the center-of-mass energy region between 4.600GeV and 4.699GeV by the BESIII detector at the BEPCII. No significant signals are observed, and the upper limits on the decay branching fractions are set to be B(Λc+→Λπ+π−e+νe)<3.9×10−4 and B(Λc+→pKS0π−e+νe)<3.3×10−4 at the 90% confidence level, respectively