Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death

Hexokinase II (HK2), a key enzyme involved in glucose metabolism, is regulated by growth factor signaling and is required for initiation and maintenance of tumors. Here we show that metabolic stress triggered by perturbation of receptor tyrosine kinase FLT3 in non–acute myeloid leukemia cells sensitizes cancer cells to autophagy inhibition and leads to excessive activation of chaperone-mediated autophagy (CMA). Our data demonstrate that FLT3 is an important sensor of cellular nutritional state and elucidate the role and molecular mechanism of CMA in metabolic regulation and mediating cancer cell death. Importantly, our proteome analysis revealed that HK2 is a CMA substrate and that its degradation by CMA is regulated by glucose availability. We reveal a new mechanism by which excessive activation of CMA may be exploited pharmacologically to eliminate cancer cells by inhibiting both FLT3 and autophagy. Our study delineates a novel pharmacological strategy to promote the degradation of HK2 in cancer cells

Focus on Innovation or Focus on Sales? The Influences of the Government of China’s Demand-Side Reform during COVID-19 and Their Sustainability Consequences in the Consumer Products Industry

Affected by COVID-19, the Chinese government has implemented demand-side reform policies to stimulate consumption. In this context, should consumer goods companies focus on innovation (FOI) or focus on ales (FOS), and what impact does it have on sustainability? Based on the empirical data of listed companies in China’s A-share consumer goods industry, this paper uses a hierarchical regression model, a mediation effect test, moderation effect analysis, and a robustness test, and it finds that for consumer products industry enterprises under the background of demand-side reform: (1) FOI negatively affects enterprise sustainability, FOS positively affects enterprise sustainability, and tilting resources from FOI to FOS is conducive to improving sustainability; (2) the direct effect of FOI on sustainability is not significant, and its negative effect on sustainability is exerted exclusively indirectly through FOS; and (3) firm value can positively moderate the relationship between FOS and sustainability, but its moderating effect on the relationship between FOI and sustainability is insignificant. These conclusions are of positive significance for the study of corporate innovation, sales behavior, and sustainability performance under demand-side reform. More broadly, this paper enriches the study of corporate sustainability in the context of an unfavorable macro environment and short-term and large policy stimulus in the market

An Improved Music Algorithm for DOA Estimation of Coherent Signals

The estimation of direction of arrival (DOA) is the main study of the direction finding and location of radio signal, MUSIC algorithm is the most classic DOA estimation. MUSIC algorithm can estimate independent signals’ DOA effectively, but it is failure to coherent signals. Concerning the issue, the modified MUSIC algorithm works when the correlative signals exist. However, the estimation performance of modified MUSIC algorithm will deteriorate in the case that the signal-noise rate is low. This paper improves the modified MUSIC algorithm by using matrix decomposition. Finally, the computer simulation results prove that this proposed method has better direction finding performance than the modified MUSIC algorithm with low signal to noise ratio

Approximation operators, binary relation and basis algebra in L-fuzzy rough sets

Approximation operators play a vital role in rough set theory. Their three elements, namely, binary relation in the universe, basis algebra and properties, are fundamental in the study of approximation operators. In this paper, the interrelations among the three elements of approximation operators in L-fuzzy rough sets are discussed under the constructive approach, the axiomatic approach and the basis algebra choosing approach respectively. In the constructive approach, the properties of the approximation operators depend on the basis algebra and the binary relation. In the axiomatic approach, the induced binary relation is influenced by the axiom set and the basis algebra. In the basis algebra choosing approach, the basis algebra is constructed by properties of approximation operators and specific binary relations