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Feedback circuits are one of the major causes underlying tumor resistance. Thus, compounds that target one oncogenic pathway with simultaneously blocking its compensatory pathway will be of great value for cancer treatment. Here, ...
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Feedback circuits are one of the major causes underlying tumor resistance. Thus, compounds that target one oncogenic pathway with simultaneously blocking its compensatory pathway will be of great value for cancer treatment. Here, we develop a new MEK inhibitor designated as KZ-02 that exhibits unexpectedly higher cytotoxicity than its starting compound AZD6244, a well-known MEK inhibitor, in colorectal cancer (CRC). Subsequent kinase selectivity study identified Pim-1 as an additional cellular target for KZ-02. Further studies showed that AZD6244 and Pim-1 1 (a Pim-1 inhibitor) have a synergistic effect on CRC suppression. Mechanistic study revealed that MEK inhibition by AZD6244 leads to increased Pim-1 expression, which could be a general mechanism behind the compromised cell-killing activity of MEK inhibitors. KZ-02, despite increasing Pim-1 mRNA expression, simultaneously promotes Pim-1 proteasomal degradation. Therefore, we uncover a new MEK inhibitor KZ-02 with significantly enhanced antitumor activity by co-targeting MEK and Pim-1.
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摘要 :AbstractAlthough differential evolution (DE) algorithms have been widely proposed for tackling various of problems, the trade-off among population diversity, global and local exploration ability, and convergence rate is hard to ma...
展开AbstractAlthough differential evolution (DE) algorithms have been widely proposed for tackling various of problems, the trade-off among population diversity, global and local exploration ability, and convergence rate is hard to maintain with the existing strategies. From this respective, this paper presents some new mutation strategies of DE by applying the clearing niche mechanism to the existing mutation strategies. Insteading of using random, best or target individuals as base vector, the niche individuals are utilized in these strategies. As the base vector is from a subpopulation, which is made up of the best individuals in each niche, the base vector can be guided by the global or local best ones. This mechanism is beneficial to the balance among population diversity, search capability, and convergence rate of DE, since it can both enhance the population diversity and search capability. Extensive experimental results indicate that the proposed strategies based on clearing niche mechanism can effectively enhance DE’s performance.Graphical Abstract]]>
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The paper is concerned with the exponential attractors for the viscoelastic wave model in Ω ⊂ R~3: u_(tt) - h_t(0)△u - ∫_0~∞ θ_sh_t(s)△u(t - s)ds + f(u) = g, with time-dependent memory kernel h_t (·) which is used to model...
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The paper is concerned with the exponential attractors for the viscoelastic wave model in Ω ⊂ R~3: u_(tt) - h_t(0)△u - ∫_0~∞ θ_sh_t(s)△u(t - s)ds + f(u) = g, with time-dependent memory kernel h_t (·) which is used to model aging phenomena of the material. Conti et al. (Am J Math 140(2):349-389, 2018a; Am J Math 140(6): 1687-1729, 2018b) recently provided the correct mathematical setting for the model and a well-posedness result within the novel theory of dynamical systems acting on time-dependent spaces, recently established by Conti et al. (J Differ Equ 255:1254-1277, 2013), and proved the existence and the regularity of the time-dependent global attractor. In this work, we further study the existence of the time-dependent exponential attractors as well as their regularity. We establish an abstract existence criterion via quasi-stability method introduced originally by Chueshov and Lasiecka (J Dyn Differ Equ 16:469-512, 2004), and on the basis of the theory and technique developed in Conti et al. (2018a, b) we further provide a new method to overcome the difficulty of the lack of further regularity to show the existence of the time-dependent exponential attractor. And these techniques can be used to tackle other hyperbolic models.
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Abstract In fuel cells, the generally low oxygen reduction reactions (ORR) rate at the cathode is a major factor limiting the overall performance of fuel cell, so the development of high‐performance, stable and inexpensive ORR el...
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Abstract In fuel cells, the generally low oxygen reduction reactions (ORR) rate at the cathode is a major factor limiting the overall performance of fuel cell, so the development of high‐performance, stable and inexpensive ORR electrocatalysts is a major researching direction. Nano‐electrocatalysts, especially one‐dimensional (1D) electrocatalysts, exhibit good catalytic behavior in fuel cell reactions due to their unique anisotropic structure, large specific surface area, high elasticity and excellent stability. To date, many advanced 1D electrocatalysts have been reported for optimizing the cathode ORR of fuel cells. Therefore, a comprehensive review of the structural design of 1D nano‐electrocatalysts and a systematic analysis of their enhanced performance still need further summarized and concluded. In this review, we firstly introduce the main synthetic methods of 1D electrocatalysts, and then discuss the recent advances and advantages of different structured 1D electrocatalysts involving nanofibers, nanotubes, nanorods, nanochains, nanowires, nanobelts, nanoneedles, nanowhiskers, and coaxial nanocables. In addition, we also introduce 1D electrocatalysts while highlighting advanced strategies and preparation methods for these different structured 1D electrocatalysts to improve ORR performance. Finally, we prospect the future development of 1D ORR electrocatalysts.
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The development of modern computational fluid dynamics (CFD) technology provides many preliminary references for experimental design. In addition, the CFD calculation results verified by experiments can display enormous microdata ...
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The development of modern computational fluid dynamics (CFD) technology provides many preliminary references for experimental design. In addition, the CFD calculation results verified by experiments can display enormous microdata in areas that are difficult to measure through experiments, as an extension. This can make measurements more reasonable and effective, shorten measurement times, and save manpower and capital significantly. Therefore, it is vital to verify the accuracy of CFD calculation results, especially in cases of complex structures and multiphase flows. The results of model tests can be utilized in a prototype experiment by properly designing a test section and selecting a working fluid if the Reynolds similarity criterion is met. Optical measurement technology is a noninvasive measurement method, and the impact on the flow field can be almost negligible. It is advised to use transparent materials and prepare a refractive index-matching (RIM) fluid to obtain a good optical path. Polymethyl methacrylate (PMMA) is widely used in flow field visualization experiments because of its good light transmission and mechanical strength. This review is aimed at introducing the current status of different flow field measurement techniques; moreover, it is intended to help the readers to become more familiar with the principles of RIM, the characteristics, applications, and usage suggestions of various RIM fluid schemes of PMMA, providing references for researchers in the design, preparation, and conducting stages of flow field visualization measurement experiments. This review is divided into five sections. In the introduction section, Chapter 1, relevant research developments and related results of flow field measurements are presented, followed by the innovations and benefits of this paper. In Chapter 2, the flow field visualization measurements are presented and a derivation is shown. In Chapter 3, some RIM fluid schemes of PMMA and their applications are given, which are very valuable for peers. In Chapter 4, the measurement and analysis of some physical properties are described. In the RIM process, it is necessary to focus on the RI, density, dynamic viscosity, compatibility, stability, safety, and cost of RIM fluids. These factors greatly impact the accuracy of experimental results, experimental progress, and safety of the experimenters. Based on the analysis and our practical experience, some suggestions are given for preparing and using RIM fluids. In the conclusion section, Chapter 5, the results and practical implications of this paper are summarized.
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Carbonaceous materials have been regarded as promising anodes for potassium-ion batteries(PIBs)due to their low cost and good conductivity.However,the larger size of K+ will unavoidably cause the electrode structure to collapse up...
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Carbonaceous materials have been regarded as promising anodes for potassium-ion batteries(PIBs)due to their low cost and good conductivity.However,the larger size of K+ will unavoidably cause the electrode structure to collapse upon repeated insertion/extraction,and meanwhile encounters slow diffusion kinetics,thus resulting in fast capacity decay and poor rate.To solve these issues,heteroatom-doping and pore-structure engineering have been proved to be effective in increasing defects,expanding the inter-layer spacing,accelerating ion migration,and accommodating volume fluctuation,etc.,and as a result the capacity,rate,and cyclability are greatly improved.Besides,electrolyte/binder optimization and electrode composition design are conducive to forming a stable and uniform solid electrolyte interphase layer,which favors ion diffusion and interfacial stability,thereby leading to enhanced rate and cyclability.Despite this,a systematic conclusion on the effect of these optimization strategies on potassium storage is still lacking,and has rarely been reported so far.Hence,this work mainly focuses on the discussion of the mechanism behind the improved potassium storage properties,starting from the structure-performance relationship based on the abovementioned strategies.The perspectives on development of carbon anodes to enable their further application in PIBs are also provided.
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Previous studies have measured urban competitiveness mainly from the perspective of cities' engine growth. Besides the cities' engine growth, this paper also emphasises cities' development resistance, city interactions and environ...
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Previous studies have measured urban competitiveness mainly from the perspective of cities' engine growth. Besides the cities' engine growth, this paper also emphasises cities' development resistance, city interactions and environment conditions, and establishes a four-level indicator system for evaluating urban competitiveness. Given that results of urban competitiveness by a single method may not be objective and comprehensive owing to the oneside view, this paper develops an integrated approach, which combines five evaluation methods and seven validity coefficients. The urban competitiveness of ten cities in Yangtze River Delta of China has been measured by the integrated approach. The ranking results indicate that during the period 2006-2009, Suzhou ranked the top among ten cities. Nanjing and Hangzhou held the second and third positions, respectively. Wuxi,Changzhou and Ningbo followed in the middle. Shaoxing, Zhoushan, Huzhou and Taizhou ranked low. Finally, some suggestions for enhancing urban competitiveness of ten cities are recommended.
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Various uncertainties exist in most urban land-use allocation systems; however, they have not been considered in most traditional urban land-use allocation methods. In this study, an interval-probabilistic urban land-use allocatio...
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Various uncertainties exist in most urban land-use allocation systems; however, they have not been considered in most traditional urban land-use allocation methods. In this study, an interval-probabilistic urban land-use allocation model is developed based on a hybrid interval-probabilistic programming method. The developed interval-probabilistic urban land-use allocation model can deal with uncertainties expressed as intervals and probability distributions; moreover, it can also help examine the reliability of satisfying (or risk of violating) system constraints under uncertainty; the interval-probabilistic urban land-use allocation model not only considers economic factors, but also involves environmental and ecological constraints, which can effectively reflect various interrelations among different aspects in the urban land-use system. The developed model is applied to a case of long-term land-use allocation planning in the city of Wuhan, China. Interval solutions associated with different risk levels of constraint violation are obtained. The desired system benefit from the land-use system will be between $ [1781.921, 2290.970] × 10~9 under the minimum violating probabilities, and in this condition, the optimized areas of industrial land, commercial land and landfill will be [35,739, 42,402] ha, [58,572, 62,450] ha, and [903, 1087] ha. Results provide the decision makers of Wuhan with desired land-use allocation patterns and environmental policies, which are related to a variety of trade-offs between system benefit and constraint-violation risk. Willingness to accept low benefit from land-use system will guarantee meeting the environmental protection objective. A strong desire to acquire high system benefit will run into the risk of violating environmental constraint.
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Recently, atomically dispersed dual-metal sites carbocatalysts (DMSCs) make a wave in the field of persulfate-based advanced oxidation processes (PS-AOPs) in light of their ≈100% atomic utilization efficiency, high density of act...
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Recently, atomically dispersed dual-metal sites carbocatalysts (DMSCs) make a wave in the field of persulfate-based advanced oxidation processes (PS-AOPs) in light of their ≈100% atomic utilization efficiency, high density of active sites, and superior catalytic activity. This review aims to provide a state-of-the-art overview on the development of DMSCs for activating PS. Initially, the types and properties of DMSCs are summarized, as well as the role of doping different heteroatoms is discussed. Subsequently, the properties of different carbon carriers and the methods for the synthesis of DMSCs are outlined. After that, the mechanism and application of DMSCs for the activation of PS toward organic contaminants degradation are revealed. Particularly, the mechanism of nonradical pathway is described, and the necessity of coupling DMSCs-based PS-AOPs to other processes for practical water treatment is emphasized. Finally, the formidable challenges and future research directions of DMSCs are proposed. This review is expected to provide insight into the preparation of DMSCs in the field of nanomaterials and to broaden the path for their environmental applications.
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Nanostructured metal oxides (MOs) have been a well-concerning focus for the development of high-performance supercapacitors due to their capability of delivering pseudocapacitive contribution. To effectively promote the potential ...
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Nanostructured metal oxides (MOs) have been a well-concerning focus for the development of high-performance supercapacitors due to their capability of delivering pseudocapacitive contribution. To effectively promote the potential of MOs for this purpose, the regulation of their electronic configuration, electrical conductivity, and active sites should be conducted where the introduction of oxygen vacancies (OVs) into MOs offers promising prospects. As a result, a comprehensive summary of the latest progress in this field is of paramount importance. After theoretically analyzing the role of OVs for boosted supercapacitive energy storage performance at the molecular/atomic levels, the possibility of controllably engineering OVs in MOs is discussed to provide valuable guides for experimental design. Then, the continuously emerged technologies for regulating OVs in MOs are classified in a simple yet clear manner, namely, direct incorporation and postregulation. Then, the typical examples of the oxygen-deficient MOs including single transition MOs, binary transition MOs, and composites with improved electrochemical performance have been discussed. Finally, the challenges and prospects of this rising field are outlooked to conclude this review.
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