[en] Highlights: • CXCR4/IL-35 expression in BMSCs enhances their protective effects on colitis. • CXCR4/IL-35 expression promotes migration of BMSCs to inflamed colons. • CXCR4/IL-35 expression expands regulatory T cells and suppresses T helper 17 cells. Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for the treatment of inflammatory bowel disease owing to their immunosuppressive property and tissue healing potential. The balance between regulatory T cells (Tregs) and T helper (Th)17 cells plays a crucial role in BMSC-mediated immunosuppression. Interleukin (IL)-35 is a newly identified anti-inflammatory cytokine required for the expansion of Tregs and suppression of Th17 cell differentiation. IL-35 can amplify the immunosuppressive property of BMSCs when overexpressed in these cells. However, the reparative capability of BMSCs in vivo is limited, partly due to the poor homing efficiency of BMSCs to inflamed colons. Up-regulation of CXC chemokine receptor 4 (CXCR4) expression in BMSCs may affect the directional homing of implanted BMSCs via stromal-derived factor-1. In this study, by lentivirus-mediated introduction of CXCR4 and IL-35 genes to modify rat BMSCs, we observed enhanced migration and strengthened immunomodulatory activities of the genetically engineering BMSCs. These results suggest that modification of BMSCs by dual expression of CXCR4 and IL-35 may provide an effective therapeutic strategy for inflammatory bowel disease.

[en] Highlights: • Water is scarce in the nine coal-fired energy bases of the north and west China. • The water footprint of coal and power production in the nine bases is evaluated. • The virtual water flow along with the energy products transfer is also analyzed. • Water stress in the energy bases is keeping increasing in the past and future. • The comprehensive countermeasures are proposed to ensure water and energy security. -- Abstract: In the past decades, the nine major energy bases in north and west China produced increasing amounts of coal and coal-fired power to meet rapidly growing energy demand. However, the poor water resources condition has become a bottleneck for sustainable development. In this study, the water footprint of coal and power production is evaluated, and the flow of virtual water arising from the transport of energy products is quantified. The results show that total coal and power production increased continuously from 2006 to 2015. The annual total water footprint was as much as 1.29 billion m³; it showed an initially increasing trend that peaked in 2013, after which it decreased. After 2013, the water footprint decreased primarily as a result of improvements in water-saving technologies. The results also indicate that increasing amounts of virtual water (as much as 0.87 billion m³ in 2015) embedded in energy products flowed from the north and west water deficient areas to the southeast water-rich areas of China, causing severe water scarcity in the major energy producing regions. Unfortunately, based on our estimates, water stress will continuously increase during the 13th Five-Year Plan period (2016–2020). This study finds that water-saving measures alone are not sufficient to relieve the water shortage and to guarantee water security. Comprehensive countermeasures, including an adjustment to the industrial structure, the physical transfer of water, regulation of the virtual water trade and policy and planning changes, are also necessary.