Gefitinib has been widely used in the first‐line treatment of advanced EGFR‐mutated non‐small‐cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9‐14 months of treatment. This study revealed that Krüppel‐like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c‐Met‐overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib‐resistant NSCLC cell lines without c‐Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib‐resistant NSCLC cells with c‐Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib‐sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells by inhibiting the expression of apoptosis‐related proteins under gefitinib treatment and activating the c‐Met/Akt signaling pathway by decreasing the inhibition of β‐catenin on phosphorylation of c‐Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c‐Met overexpression.

Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases. Elevated palmitate (PA) is an independent risk factor of cardiovascular diseases, but its role in endothelial cell senescence is currently unknown. During the course of studying the prosenescent role of PA, we discovered a key role of dsRNA-dependent protein kinase [protein kinase R (PKR)] in endothelial senescence. Exposure of human umbilical vein endothelial cells (HUVECs) to PA-induced cell senescence is characterized by increased levels of senescence-associated β-galactose glucosidase activity, excessive production of reactive oxygen species production, impaired cellular proliferation, and G phase arrest. This phenomenon is associated with an increase of PKR autophosphorylation and decreased activity of sirtuin 1 (Sirt1), a pivotal antisenescent factor. PKR inactivation by PKR siRNA or its phosphorylation inhibitor 2-aminopurine significantly attenuated PA-induced HUVEC senescence by reversing Sirt1 activity and its downstream signaling. Moreover, to study the regulatory mechanism between PKR and Sirt1, we found that PKR promotes JNK activation to inhibit Sirt1 activity and that this effect could be reversed by the JNK inhibitor SP600125. These findings provide evidence that PKR mediates PA-induced HUVEC senescence by inhibiting Sirt1 signaling. Our study provides novel insights into the actions and mechanisms of PKR in endothelial senescence. NEW & NOTEWORTHY This study first provides a novel observation that dsRNA-dependent protein kinase (PKR) mediates palmitate-induced sirtuin 1 inactivation and subsequent human umbilical vein endothelial cell senescence. Most importantly, these new findings will provide a potential therapeutic strategy to improve free fatty acid-induced endothelial senescence by targeting PKR in cardiovascular diseases.

In this article, a modified four-component decomposition method with refined volume scattering models is proposed for polarimetric synthetic aperture radar (SAR) image processing. In the new decomposition method, after the orientation angle compensation, the orientation angle is placed in the probability density functions. General forms of the volume scattering models and branch conditions can be obtained. Similar to the four-component scattering power decomposition with extended volume scattering model (S4R) proposed by Sato et al., refined volume scattering models can be used for various land covers based on the criteria. Since the orientation angles are contained in the refined volume scattering models, the oriented buildings can be discriminated from the vegetation areas and the overestimation problem of volume scattering is substantially overcome. In this article, the performance of the proposed method is evaluated by the spaceborne C-band Gaofen-3 data and airborne L-band E-SAR data. Several approaches are employed as a comparison of the proposed methods. Experimental results show that, compared with the existing decomposition methods, the proposed method can effectively represent the scattering characteristics of the ambiguous regions, and the double-bounce scattering contributions over the urban areas can be substantially enhanced.

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An analytical bistatic point target reference spectrum (BPTRS) is proposed. The BPTRS is derived from the one-to-one relationship between slow time and Doppler frequency with no Taylor series expansions. Based on the BPTRS, a twodimensional frequency-domain focusing algorithm for spaceborne/airborne bistatic synthetic aperture radar is developed. The algorithm exploits a range-dependent sub-blocks processing method to perform range cell migration correction and quadratic Doppler term compensation, and then a scaled inverse Fourier transformation and a sinc interpolation are used to correct the geometric distortions in azimuth and range, respectively. Some simulation experiments are also presented to verify their performance.

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We propose a unified dynamic tracking algorithmic framework (PLAY-CS) to reconstruct signal sequences with their intrinsic structured dynamic sparsity. By capitalizing on specific statistical assumptions concerning the dynamic filter of the signal sequences, the proposed framework exhibits versatility by encompassing various existing dynamic compressive sensing (DCS) algorithms. This is achieved through the incorporation of a newly proposed Partial-Laplacian filtering sparsity model, tailored to capture a more sophisticated dynamic sparsity. In practical scenarios such as dynamic channel tracking in wireless communications, the framework demonstrates enhanced performance compared to existing DCS algorithms.

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