RCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α–XBP1s pathway

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α–XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α–XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α–XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC

China biomass-to-heat market evaluation and policy recommendations of development

This research focused on comparative analysis on the economic efficiency of biomass-to-heat with that of traditional modes of heat production by coal, oil and natural gas in a bid to determine the competitiveness, and potential for scaling up and commercialization. The research showed that BMF-to-heat is competitive and its cost is equivalent to coal in some regions in China, especially where with a higher demand for clean energy, BMF will become the best alternative. However, in regions where coal price is low, BMF is less competitive and supportive government policies are required to further promote its application. Biomass gasification and biomethane/biogas are slightly less competitive than coal, but slightly more than gas. They are relatively promising to commercialize. Based on the market evaluation research results, this paper proposes the policy recommendations for the large-scale and commercial development of biomass energy heating in China