Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis

Obeticholic acid(OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, D-galactosamine/LPS(GalN/LPS)-treated mice and cycloheximide/TNFα(CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell(HSC)activation/proliferation and prevented fibrosis. Elevated bile acid(BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

Molecular dispersion enhances photovoltaic efficiency and thermal stability in quasi-bilayer organic solar cells

In comparison to widely adopted bulk heterojunction(BHJ)structures for organic solar cells(OSC),exploiting the sequential deposition to form planar heterojunction(PHJ)structures enables to realize the favorable vertical phase separation to facilitate charge extraction and reduce charge recombination in OSCs.However,effective tunings on the power conversion efficiency(PCE)in PHJ-OSCs are still restrained by the currently available methods.Based on a polymeric donor PBDBT-2 F(PBDBT=Poly[[4,8-bis[5-(2-ethylhexyl)-4-fluoro-2-thienyl]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl]-2,5-thiophenediyl[5,7-bis(2-ethylhexyl)-4,8-dioxo-4 H,8 H-benzo[1,2-c:4,5-c′]dithiophene-1,3-diyl]-2,5-thiophenediyl])and a non-fullerene(NF)acceptor Y6,we proposed a strategy to improve the properties of photovoltaic performances in PHJ-based OSCs through dilute dispersions of the PBDBT-2 F donor into the acceptor-dominant phase with the sequential film deposition.With the control of donor dispersions,the charge transport balance in the PHJ-OSCs is improved,leading to the expedited photocarrier sweep-out with reduced bimolecular charge recombination.As a result,a PCE of 15.4%is achieved in the PHJ-OSCs.Importantly,the PHJ solar cells with donor dispersions exhibit better thermal stability than corresponding BHJ devices,which is related to the better film morphology robustness and less affected charge sweep-out during the thermal aging.