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Summary: Human umbilical cord mesenchymal stem cells (UC-MSCs)-derived hepatocyte-like cells (HLCs) have shown great promise in the treatment of liver diseases. However, most current induction protocols yield hepatocyte-like cells with limited function as compared with primary hepatocytes. Schisandrin B (Sch B) is one of the main components of Schisandra chinensis, which can prevent fibrosis progression and promote liver cell regeneration. Herein, we investigated the effects of Sch B on hepatic differentiation of UC-MSCs. We found that treatment with 10 μM Sch B from the second stage of the differentiation process increased hepatic marker levels and hepatic function. Additionally, RNA-seq analysis revealed that Sch B promoted hepatic differentiation via activating the JAK2/STAT3 pathway. When transplanted HLCs into mice with CCL4-induced liver fibrosis, Sch B-treated HLCs exhibited significant therapeutic effects. This study provides an optimized hepatic differentiation protocol for UC-MSCs based on Sch B, yielding functioning cells for liver disease treatment.

Although extensive studies have investigated changes in regional ecosystem services (ESs) under rapid urbanization, few analyses have used high-resolution image data to investigate urban wetlands. Taking the Xixi wetland region as a case area, this study aimed to investigate the temporal and spatial variation and influencing factors of typical ESs during 1984–2018 using high-resolution images. The results showed that the Xixi wetland region underwent substantial changes of land use as well as in different ESs. While carbon storage presented an increasing trend from 223.25 t/ha to 368.11 t/ha from 1984 to 2018, the changes of other services illustrated an overall degradation in this important urban wetland. Evident trade-off and synergy effects were observed between water yield and carbon storage and between biodiversity protection and recreation and cultural services. Redundancy analysis revealed the detrimental impacts of impervious cover on the provision of ESs in this urban wetland area. The results obtained in this study highlight the great challenges that urban wetland parks face in balancing wetland conservation and sustainable use.

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance is an important issue to be resolved for the clinical treatment of HCC. In the current study, we identified that ABCC5 is a critical regulator and a promising therapeutic target of acquired sorafenib resistance in human hepatocellular carcinoma cells. The expression of ABCC5 was dramatically induced in sorafenib-resistant HCC cells and was remarkably associated with poor clinical prognoses. The down-regulation of ABCC5 expression could significantly reduce the resistance of sorafenib to HCC cells. Importantly, activation of PI3K/AKT/NRF2 axis was essential for sorafenib to induce ABCC5 expression. ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in vitro and in vivo. These findings demonstrate a novel molecular mechanism of acquired sorafenib resistance and also suggest that ABCC5 is a new regulator of ferroptosis in HCC cells.