Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer

Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity in mouse models. Clinical trials in non-small cell lung cancer (NSCLC) reveal that IL-6 targeted therapy relieves NSCLC-related anemia and cachexia, although other clinical effects require further study. We crossed IL-6-/- mice with KrasG12D mutant mice, which develop lung tumors after activation of mutant KrasG12D, to investigate whether IL-6 inhibition contributes to tumor progression and survival time in vivo. KrasG12D; IL-6-/- mice exhibited increased tumorigenesis, but slower tumor growth and longer survival, than KrasG12D mice. Further, in order to investigate whether IL-6 deletion contributes to suppression of lung cancer metastasis, we generated KrasG12D; p53flox/flox; IL-6-/- mice, which developed lung cancer with a trend for reduced metastases and longer survival than KrasG12D; p53flox/flox mice. Tumors from KrasG12D; IL-6-/- mice showed increased expression of TNFα and decreased expression of CCL-19, CCL-20 and phosphorylated STAT3 (pSTAT3) than KrasG12D mice; however, these changes were not present between tumors from KrasG12D; p53flox/flox; IL-6-/- and KrasG12D; p53flox/flox mice. Upregulation of pSTAT3 and phosphorylated AKT (pAKT) were observed in KrasG12D tumors with p53 deletion. Taken together, these results indicate that IL-6 deletion accelerates tumorigenesis but delays tumor progression and prolongs survival time in a Kras-driven mouse model of lung cancer. However, these effects can be attenuated by p53 deletion

Semilocal Convergence Analysis for Inexact Newton Method under Weak Condition

Under the hypothesis that the first derivative satisfies some kind of weak Lipschitz conditions, a new semilocal convergence theorem for inexact Newton method is presented. Unified convergence criteria ensuring the convergence of inexact Newton method are also established. Applications to some special cases such as the Kantorovich type conditions and γ-Conditions are provided and some well-known convergence theorems for Newton's method are obtained as corollaries

Porous Prussian Blue Analogs Decorated Electrospun Carbon Nanofibers as Efficient Electrocatalyst for Overall Water Splitting

Metal-organic frameworks are becoming increasingly important in electrocatalysis as the hydrogen production sector grows. However, their electrocatalytic capability is limited by their inclination to agglomerate and the insufficient exposure of active sites. In this work, a three-step strategy was used to develop a bifunctional electrocatalyst with porous Prussian blue analogs supported on carbon nanofibers. The use of electrospun carbon nanofibers as conductive substrates can successfully address the problem of easy aggregation. Moreover, the etching procedure with tannic acid creates a porous structure that effectively regulates the electrical structure and exposes additional active sites. The resulting catalyst performs well in both the hydrogen evolution reaction and the oxygen evolution reaction, and also exhibits good stability in overall water splitting. The findings of this study present new concepts for the design and fabrication of metal-organic frameworks-based materials in the realm of electrocatalysis

Hierarchical Longitudinal Control for Connected and Automated Vehicles in Mixed Traffic on a Signalized Arterial

This paper proposes a two-layer hierarchical longitudinal control approach that optimizes travel time and trajectories along multiple intersections on an arterial under mixed traffic of connected automated vehicles (CAV) and human-driven vehicles (HV). The upper layer optimizes the travel time in an optimization loop, and the lower layer formulates a longitudinal controller to optimize the movement of CAVs in each block of an urban arterial by applying optimal control. Four scenarios are considered for optimal control based on the physical constraints of vehicles and the relationship between estimated arrival times and traffic signal timing. In each scenario, the estimated minimized travel time is systematically obtained from the upper layer. As the results indicate, the proposed method significantly improves the mobility of the signalized corridor with mixed traffic by minimizing stops and smoothing trajectories, and the travel time reduction is up to 29.33% compared to the baseline when no control is applied.</jats:p

Hierarchical Longitudinal Control for Connected and Automated Vehicles in Mixed Traffic on a Signalized Arterial

This paper proposes a two-layer hierarchical longitudinal control approach that optimizes travel time and trajectories along multiple intersections on an arterial under mixed traffic of connected automated vehicles (CAV) and human-driven vehicles (HV). The upper layer optimizes the travel time in an optimization loop, and the lower layer formulates a longitudinal controller to optimize the movement of CAVs in each block of an urban arterial by applying optimal control. Four scenarios are considered for optimal control based on the physical constraints of vehicles and the relationship between estimated arrival times and traffic signal timing. In each scenario, the estimated minimized travel time is systematically obtained from the upper layer. As the results indicate, the proposed method significantly improves the mobility of the signalized corridor with mixed traffic by minimizing stops and smoothing trajectories, and the travel time reduction is up to 29.33% compared to the baseline when no control is applied

Changes in the Ecological Footprint of Rural Populations in the Taihang Mountains, China

Due to massive rural&ndash;urban migration, population size and age structure are subject to significant changes in the mountainous areas of China. This can influence the ecological pressure of the mountainous areas correspondingly. In particular, large numbers of young laborers migrate from rural areas, which may greatly decrease the intensity of local human activities. However, it is still unclear how population changes (size and age structure) affect environmental changes and how to measure these changes. We analyzed changes in the ecological footprint (EF) in the Taihang Mountain region in northern China using field survey data. From 2000 to 2016, the population size in the study area decreased by 9.7%, while the EF declined by 32.1%. The EF per capita (EF_per) decreased more rapidly with decreasing elevation, which indicated that at lower elevations, households were less dependent on local resources. For households with more elderly people, the EF_per was considerably lower than for other households in 2000. However, in 2016, this was not the case, and the households with a share of the working-age population between 50&ndash;75% had the lowest EF_per. Our study is of great practical significance for reasonably guiding population migration and rural sustainable development

Changes in the Water-Energy Coupling Relationship in Grain Production: A Case Study of the North China Plain

Water consumption and energy consumption are inevitable in grain production, but few studies have focused on the integrated assessment of these two indicators and their relationships. To address the research deficiency, taking the North China Plain (NCP) as a case study, this paper quantifies the changes in grain crop planting structure and the accompanying changes in irrigation water consumption (IWC) and energy consumption (EC) in the NCP. On this basis, the water-energy coupling index (CI) is constructed to analyze the water-energy coupling relationship in the context of grain crop planting structure change. The results revealed that the sown area of three of the four main grain crops in the NCP, namely winter wheat, summer maize, and rice, roughly increased in the south and decreased in the north, while the sown area of spring maize increased in most counties where it was planted in the NCP from 2000 to 2015. With the change of grain crop planting structure, IWC and EC of winter wheat in the NCP decreased by 19.87 &times; 106 m3 and 16.78 &times; 108 MJ, respectively, mainly distributed in the Beijing-Tianjin-Hebei region, while IWC and EC of other crops all increased. In terms of CI values, although that of spring maize increased, those of winter wheat, summer maize, and rice all decreased, and the overall CI values of grain production in the NCP decreased from 0.442 in 2000 to 0.438 in 2015, indicating that grain crop distribution has been optimized toward a less water- and energy-intensive and more sustainable layout in the NCP. This paper can add case and methodological support to the food-water-energy (FEW) nexus research and can also provide policy suggestions for regional crop optimization layout and conservation of both water and energy resources