Purpose VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic RCC. However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for both patients with TKI naïve or resistant RCC. Experimental design In this study, we performed transcriptome analysis of VEGFR TKI resistant tumors in a murine model and discovered that the SPHK/S1P pathway is upregulated at the time of resistance. We tested S1P pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Results Resistant tumors expressed several hypoxia regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC suggesting that human RCC behavior could, in part, be due to over-production of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Conclusions Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment naïve RCC and also in the setting of resistance to VEGFR TKI therapy.

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Achieving high selectivity and conversion efficiency simultaneously is a challenge for visible-light-driven photocatalytic CO 2 reduction into CH 4 . Here, a facile nanofiber synthesis method and a new defect control strategy at room-temperature are reported for the fabrication of flexible mesoporous black Nb 2 O 5 nanofiber catalysts that contain abundant oxygen-vacancies and unsaturated Nb dual-sites, which are efficient towards photocatalytic production of CH 4 . The oxygen-vacancy decreases the bandgap width of Nb 2 O 5 from 3.01-2.25 eV, which broadens the light-absorption range from ultraviolet to visible-light, and the dual sites in the mesopores can easily adsorb CO 2 , so that the intermediate product of CO* can be spontaneously changed into *CHO. The formation of a highly stable NbCHO* intermediate at the dual sites is proposed to be the key feature determining selectivity. The preliminary results show that without using sacrificial agents and photosensitizers, the nanofiber catalyst achieves 64.8% selectivity for CH 4 production with a high evolution rate of 19.5 µmol g −1 h −1 under visible-light. Furthermore, the flexible catalyst film can be directly used in devices, showing appealing and broadly commercial applications.

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CuCl 2 -impregnated sorbents were employed to remove elemental mercury from flue gas. Three carriers including neutral Al 2 O 3 , artificial zeolite, and activated carbon have been investigated in this research. The performances of these prepared sorbents have been tested in a bench-scale fixed-bed reactor under different simulated flue gas atmospheres and temperatures (333−573 K). CuCl 2 -impregnated activated carbon showed the best adsorption ability. However, CuCl 2 -impregnated neutral Al 2 O 3 and zeolite have demonstrated an adsorption rate similar to that of CuCl 2 -impregnated activated carbon in the early stage of the tests (5 min), and they achieved relatively high mercury oxidation efficiencies. These non-carbon sorbents could remarkably enhance the technoeconomical properties of mercury removal in coal-fired power plants and have great potentials in industrial application. The appropriate mercury capture temperature for these sorbents is 333−473 K. The possible mechanisms of elemental mercury oxidation have been discussed.

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Interbasin water transfers and diversions are among the most controversial water-resources-planning topics worldwide. They provide supply alternatives to receiving basins and potential challenges to the donor basins within a context of changing global water problems. This study presents a bibliometric analysis of global interbasin water transfer research between 1900 and 2014. The bibliometric analysis analyzes general characteristics of publications, the national, institutional, and personal research outputs, participating regions and their research activity, and global trends and hot issues in the field of water transfers. Our results show that the rate of annual publication of interbasin water transfer research grew steadily after 1972 and is rising quickly at present. The United States produced the largest number of single-country publications (37.4 %) and international collaborative publications (46.6 %). However, China had a high growth rate of publications after 2001, and surpassed the United States and ranked 1st in 2012, with the Chinese Academy of Sciences playing a leading role in the emergence of China's research output. The global geographic distribution of publication activity shows that an increasing number of countries, agencies, and scholars have become part of the research enterprise. There is ample opportunity for cooperation between them to be strengthened in the future. The results of keyword evolution generally indicate that the research on interbasin water transfers expanded from 1991 through 2014. The hydrological and eco-environmental impacts of the South-to-North Water Transfer/Diversion Project in China and the corresponding long-term monitoring and conservation strategy have become one of the top topics of attention.