Comprehensive Integrative Analysis Reveals the Association of KLF4 with Macrophage Infiltration and Polarization in Lung Cancer Microenvironment

Macrophage polarization and infiltration to the tumor microenvironment (TME) is a critical determining factor for tumor progression. Macrophages are polarized into two states—M1 (pro-inflammatory, anti-tumorigenic and stimulated by LPS or IFN-γ) and M2 (anti-inflammatory pro-tumorigenic and stimulated by IL-4) phenotypes. Specifically, M2 macrophages enhance tumor cell growth and survival. Recent evidences suggest the pivotal role of microRNAs in macrophage polarization during the development of Non-small cell lung cancer (NSCLC), thus proposing a new therapeutic option to target lung cancer. In silico analysis determined cogent upregulation of KLF4, downregulation of IL-1β and miR-34a-5p in NSCLC tissues, consequently worsening the overall survival of NSCLC patients. We observed a significant association of KLF4 with macrophage infiltration and polarization in NSCLC. We found that KLF4 is critically implicated in M2 polarization of macrophages, which, in turn, promotes tumorigenesis. KLF4 expression correlated with miR-34a-5p and IL-1β in a feed-forward loop (FFL), both of which are implicated in immune regulation. Mechanistic overexpression of miR-34a-5p in macrophages (IL-4 stimulated) inhibits KLF4, along with downregulation of ARG1, REL-1MB (M2 macrophage specific markers), and upregulation of IL-1β, IL-6, (M1 macrophage specific markers), demonstrating macrophage polarization switch from M2 to M1 phenotype. Moreover, co-culture of these macrophages with NSCLC cells reduces their proliferation, wound healing, clonogenic capacity and enhanced NO-mediated apoptosis. Further, transfection of miR-34a-5p in NSCLC cells, also degrades KLF4, but enhances the expression of KLF4 regulated genes—IL-1β, IL-6 (pro-inflammatory mediators), which is further enhanced upon co-culture with IL-4 stimulated macrophages. Additionally, we observed a significant increase in i-NOS/NO content upon co-culture, suggesting polarization reversion of macrophages from M2 to M1, and eventually leading to anti-tumor effects. Our findings thus show a significant role of KLF4 in tumorigenesis and TAM polarization of NSCLC. However, miR-34a-5p mediated targeting of these molecular networks will provide a better therapeutic intervention for NSCLC.

A polarization-switch effect of silicon crystals under multiple-beam diffraction geometry

On the basis of rigorous dynamical-theory calculations, a complete X-ray polarization-switch effect of silicon crystals at the exact multiple-beam diffraction condition is demonstrated. The underlying physical mechanism of this unique phenomenon can be revealed using a simple multiple-wave propagation and interference model. The constructive and destructive interference of the multiple detoured-diffraction beams along the direction of the primary diffracted beam directly leads to the complete polarization switch. This phenomenon can be realized using both synchrotron and laboratory X-ray sources at many discrete wavelengths, and used to design a novel crystal-based polarizer to achieve a 90° polarization rotation.

Dielectric Relaxation Behavior of BTO/LSMO Heterojunction

The BaTiO3 (BTO)/La0.7Sr0.3MnO3 (LSMO) magnetoelectric composite films were prepared by sol-gel method on STO (001) substrates. The heterojunction has highly preferred orientation and exhibits well ferroelectric properties with perfect hysteresis loops and microscopic polarization switch behaviors. The most interesting thing is the abnormal dielectric relaxation phenomenon in the dielectric spectra at high frequency range and around the phase transition temperature of LSMO. By analyzing the resistance properties of LSMO films, it is indicated that charge-based interfacial coupling, Maxwell-Wagner effect due to the JT polaron and fast resistivity rise in LSMO layer is the main reason. This work emphasizes the crucial role of resistivity exchanges and of carrier accumulation at interfaces for the application of magnetoelectric heterojunction.

All-Optical Switching and Logic-Gates Design Using Mode (Polarization)-Conversion in Micro-Ring Resonator

The realization of all-optical polarization switch and all-optical logic gates based on polarization-conversion on single silicon micro-ring resonator (MRR) is demonstrated. By adjusting the mode state of the input source as well as the pump light, the all-optical polarization switch, and hence, all-optical NOT, OR/NOR. AND-NAND logic gates are realized. The design is ultra-compact, ultrafast, and less optical power is required for all-optical polarization-conversion-based switch and logic gates, respectively. The MRR also shows outstanding performance as its Q (quality) factor is very high. The design is robust, simple, stable, easy-to-fabricate, and silicon-on-insulator (SOI) compatible. The structure is compatible for interconnects and capable for integrating in electronics as well as in plasmonics circuits.