[Spatial-temporal Characteristics and Driving Factors of Greenhouse Gas Emissions from Rivers in a Rapidly Urbanizing Area].

Rivers play an important role in greenhouse gas emissions. Over the past decade, because of global urbanization trends, rapid land use changes have led to changes in river ecosystems that have had a stimulating effect on the greenhouse gas production and emissions. Presently, there is an urgent need for assessments of the greenhouse gas concentrations and emissions in watersheds. Therefore, this study was designed to evaluate river-based greenhouse gas emissions and their spatial-temporal features as well as possible impact factors in a rapidly urbanizing area. The specific objectives were to investigate how river greenhouse gas concentrations and emission fluxes are responding to urbanization in the Liangtan River, which is not only the largest sub-basin but also the most polluted one in Chongqing City. The thin layer diffusion model method was used to monitor year-round concentrations of pCO2, CH4, and N2O in September and December 2014, and March and June 2015. The pCO2 range was (23.38±34.89)-(1395.33±55.45) Pa, and the concentration ranges of CH4 and N2O were (65.09±28.09)-(6021.36±94.36) nmol·L-1 and (29.47±5.16)-(510.28±18.34) nmol·L-1, respectively. The emission fluxes of CO2, CH4, and N2O, which were calculated based on the method of wind speed model estimations, were -6.1-786.9, 0.31-27.62, and 0.06-1.08 mmol·(m2·d)-1, respectively. Moreover, the CO2 and CH4 emissions displayed significant spatial differences, and these were roughly consistent with the pollution load gradient. The greenhouse gas concentrations and fluxes of trunk streams increased and then decreased from upstream to downstream, and the highest value was detected at the middle reaches where the urbanization rate is higher than in other areas and the river is seriously polluted. As for branches, the greenhouse gas concentrations and fluxes increased significantly from the upstream agricultural areas to the downstream urban areas. The CO2 fluxes followed a seasonal pattern, with the highest CO2 emission values observed in autumn, then successively winter, summer, and spring. The CH4 fluxes were the highest in spring and the lowest in summer, while N2O flux seasonal patterns were not significant. Because of the high carbon and nitrogen loads in the basin, the CO2 products and emissions were not restricted by biogenic elements, but levels were found to be related to important biological metabolic factors such as the water temperature, pH, DO, and chlorophyll a. The carbon, nitrogen, and phosphorus content of the water combined with sewage input influenced the CH4 products and emissions. Meanwhile, N2O production and emissions were mainly found to be driven by urban sewage discharge with high N2O concentrations. Rapid urbanization accelerated greenhouse gas emissions from the urban rivers, so that in the urban reaches, CO2/CH4 fluxes were twice those of the non-urban reaches, and all over the basin N2O fluxes were at a high level. These findings illustrate how river basin urbanization can change aquatic environments and aggravate allochthonous pollution inputs such as carbon, nitrogen, and phosphorus, which in turn can dramatically stimulate river-based greenhouse gas production and emissions; meanwhile, spatial and temporal differences in greenhouse gas emissions in rivers can lead to the formation of emission hotspots.

Quantitative Proteomics of Th-MYCN Transgenic Mice Reveals Aurora Kinase Inhibitor Altered Metabolic Pathways and Enhanced ACADM To Suppress Neuroblastoma Progression.

Neuroblastoma is a neural crest-derived embryonal tumor and accounts for about 15% of all cancer deaths in children. MYCN amplification is associated with aggressive and advanced stage of high-risk neuroblastoma, which remains difficult to treat and exhibits poor survival under current multimodality treatment. Here, we analyzed the transcriptomic profiles of neuroblastoma patients and showed that aurora kinases lead to poor survival and had positive correlation with MYCN amplification and high-risk disease. Further, pan-aurora kinase inhibitor (tozasertib) treatment not only induces cell-cycle arrest and suppresses cell proliferation, migration, and invasion ability in MYCN-amplified (MNA) neuroblastoma cell lines, but also inhibits tumor growth and prolongs animal survival in Th-MYCN transgenic mice. Moreover, we performed quantitative proteomics and identified 150 differentially expressed proteins after tozasertib treatment in the Th-MYCN mouse model. The functional and network-based enrichment revealed that tozasertib alters metabolic processes and identified a mitochondrial flavoenzyme in fatty acid ß-oxidation, ACADM, which is correlated with aurora kinases and neuroblastoma patient survival. Our findings indicate that the aurora kinase inhibitor could cause metabolic imbalance, possibly by disturbing carbohydrate and fatty acid metabolic pathways, and ACADM may be a potential target in MNA neuroblastoma.

A novel dressing seeded with embryonic artery CD133+ cells and loaded with the Sirt1 agonist SRT1720 accelerates the healing of diabetic ischemic ulcers.

Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133+ cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology. EACCs were seeded onto the PCSS dressing and this was used to treat diabetic ulcers. The results indicated that SRT1720 promotes the proliferation of EACCs, enhances the secretion of vascular endothelial growth factor A, interluekin 8 and basic fibroblast growth factor, and inhibits the secretion of tumor necrosis factor α. Furthermore, SRT1720 promoted the paracrine function of EACCs and promoted the proliferation and migration of human umbilical vein endothelial cells. PCSS induced the steady release of SRT1720 over a 15-day period and PCSS seeded with EACCs (PCSS-EACCs) were transplanted into the diabetic ischemic ulcers of mice with diabetes. The results of these experiments indicated that angiogenesis and the healing of diabetic ischemic ulcers was significantly improved following the transplantation of PCSS-EACCs. Therefore, PCSS-EACCs may be a novel and effective treatment for diabetic ischemic ulcers.

Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells.

Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.