Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 μM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration. Finally, the phosphorylation levels of key kinases in the Akt/mechanistic target of rapamycin (mTOR)/mitogen-activated protein kinase (MAPK) pathway, and expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were detected by western blot analysis. Stimulation with IL-27 or sorafenib repressed proliferation, migration and invasion but promoted apoptosis, and the effects were all enhanced by the combination of these two drugs in HTB-9 cells. The effect of the combined treatment on bladder cancer cells was verified in T24 cells. Additionally, the phosphorylation levels of AKT, mTOR and MAPK as well as the expression levels of MMP-2 and MMP-9 were all decreased by a single treatment of IL-27 or sorafenib, and further decreased by the combined treatment of these two drugs. The combination of IL-27 and sorafenib inhibited proliferation, migration and invasion and promoted apoptosis of bladder cancer cells compared with mono-drug treatment. Additionally, the AKT/mTOR/MAPK pathway might be implicated in the functional effects by down-regulations of MMP-2 and MMP-9.

Phosphorus is an essential macronutrient for all living plants and plant production. Simultaneously, atmospheric nitrogen deposition also affects plant productivity at a global scale. However, few studies have investigated how plants respond to P addition while simultaneously considering N deposition. We investigated plant biomass, nutrient status and stoichiometric ratios on Potentilla tanacetifolia in response to P fertilization under contrasting N addition rates in a typical meadow steppe in Inner Mongol ia, China. Aboveground biomass of P. tanacetifolia increased under increasing levels of P fertilization under conditions of N addition. However, there was no significant change in biomass when only phosphorus was added. Plant leaf and stem P concentrations increased linearly with P addition when there was no N addition. Our results suggest that increased plant P nutrition under P addition will not turn into plant growth enhancement unless N demands are also satisfied. Nitrogen addition significantly increased leaf N concentrations, and leaf and seed N:P ratios, when there was no P fertilization. Nevertheless, the effects of N addition were weakened, and eventually disappeared when P fertilization rates increased. This indicates that N-induced alterations of the plant nutrition status and stoichiometric ratios were P availability-dependent. Overall, our results suggest that multiple-nutrient constraints and their interactions must be considered when assessing plant nutrient and growth responses to nutrient enrichment.

El fósforo es un macronutriente esencial para todas las plantas vivas y la producción vegetal. Simultáneamente, la deposición atmosférica de nitrógeno también afecta la productividad de las plantas a una escala global. Sin embargo, pocos estudios han investigado como responden las plantas a la adición de P mientras se considera la deposición atmosférica de N al mismo tiempo. Se investigaron la biomasa vegetal, el nivel de nutrientes y relaciones estequiométricas en Potentilla tanacetifolia en respuesta a la fertilización fosforada bajo varias tasas de adición de N en una estepa de pradera típica en el interior de Mongolia, China. La biomasa aérea de P. tanacetifolia se incrementó con mayores niveles de fertilización fosforada bajo condiciones de adición de N. Sin embargo, no hubo un cambio significativo en la biomasa cuando solo se agregó P. Las concentraciones de P en hoja y tallo se incrementaron linealmente con el agregado de P cuando no hubo adición de N. Nuestros resultados sugieren que una mayor nutrición fosforada a la planta bajo agregado de P no determinará un mejor crecimiento vegetal a menos que también sean satisfechas las demandas de N. El agregado de N incrementó significativamente las concentraciones de N foliares, y las relaciones N:P de la semilla y de las hojas, cuando no hubo fertilización fosforada. De todas maneras, los efectos de la adición de N fueron debilitados, y eventualmente desaparecieron, cuando se incrementaron las tasas de fertilización con P. Esto indica que las alteraciones inducidas por el N en el nivel de nutrición vegetal y las relaciones estequiométricas fueron dependientes de la disponibilidad de P. Nuestros resultados sugieren que limitaciones de varios nutrientes al mismo tiempo y sus interacciones deben ser consideradas cuando se estudian las respuestas de los nutrientes y del crecimiento de las plantas a un aumento en el nivel de nutrientes.

The influence of long-term application of pig manure combined with chemical fertilizer (MCF) or chemical fertilizer (CF) on free-living nematodes was evaluated in this study. The application model of fertilizers lasted 14 years in Mollisols, and treatments included MCF, CF and no fertilizer (NF). A total of 26 free-living nematode genera belonging to seven functional guilds were found in maize fields, and the community structure of free-living nematodes was different in MCF, CF and NF. Pig manure increased the abundance of bacterivores, especially those belonging to c-p1 (Ba1) and c-p2 (Ba2) guilds. Channel index (CI) was higher in NF than in MCF and CF, but enrichment index (EI) was higher in MCF and CF compared to NF. The structure index (SI) was highest in NF among three treatments. Total bacterivores, Ba1 and Ba2 guilds were positively correlated to organic C, total N, available N, total P and available P, but fungivores only had correlation with organic C and soil moisture. The SI index was negatively related to organic C, total N, available N, total P and available P. Collectively, these results indicate that the pig manure or chemical fertilizer normally applied to increase soil nutrition also induce negative influence on soil food web structure as reflected from biological aspect, and that soil nematodes can enhance agroecological assessments of changes induced by long-term fertilizer application in maize field in Mollisols.

Relative growth rate (RGR) of plants is a key component of fitness. Theoretically, the RGR of plants would be closely related with biomass allocation. Our mechanistic understanding of the relationship between RGR and biomass allocation under global change scenarios is still limited. We examined the responses of RGR and biomass allocation of Leymus chinensis, a dominant grass in the temperate steppe of northern China, to a wide range of N addition. We found that N addition increased RGR of L. chinensis up to a threshold of 10 g N/m². While leaf and stem weight ratios were positively correlated with N addition rates, root weight ratio showed a negative correlation. The RGR of total biomass was positively correlated with both leaf and stem weight ratios, but negatively correlated with root weight ratios. The positive responses of leaf and stem biomass allocation, or the negative responses of root biomass allocation to N addition determined enhancements or reductions, respectively, of RGR on L. chinensis. The increased RGR of L. chinensis to N addition gave a direct and robust explanation for the increased of dominance of this species under field N-addition studies. Our results have important implications for projecting the growth status of L. chinensis under scenarios of increased N deposition in northern China.

La tasa relativa de crecimiento (RGR) de las plantas es un componente clave en la adaptación de las plantas al ambiente. Teóricamente, la RGR de las plantas estaría muy relacionada con la distribución de biomasa. Nuestro entendimiento de los mecanismos de la relación entre RGR y la distribución de biomasa todavía es limitado en relación al cambio global. Las respuestas de la RGR y la distribución de biomasa a un amplio rango de adición de N se examinaron en Leymus chinensis, una gramínea dominante en la estepa templada del norte de China. La adición de N incrementó la RGR de L. chinensis hasta un límite de 10 g N/m². Mientras las relaciones del peso de hojas y tallos se correlacionaron positivamente con las tasas de adición de N, la relación del peso de raíz mostró una correlación negativa. La RGR de la biomasa total se correlacionó positivamente con las relaciones del peso de hojas y tallos, pero negativamente con las relaciones del peso de raíz. Las respuestas positivas de la distribución de biomasa a hojas y tallos, o la respuesta negativa de distribución de biomasa a las raíces, a la adición de N determinó incrementos o reducciones, respectivamente, de la RGR en L. chinensis. La mayor RGR de L. chinensis a la adición de N dio una explicación directa y robusta por la mayor dominancia de esta especie en estudios de adición nitrogenada a campo. Nuestros resultados tienen importantes implicancias para proyectar el nivel de crecimiento de L. chinensis bajo un escenario de una mayor deposición de N en el norte de China.