Background Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC. Methods Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors. Results Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation. Conclusions The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.

along two orthogonal directions, single type of nanostructures have been tailored to convert linear polarization to circular polarization and even any polarizations through transmission, reflection, or scattering. [25][26][27][28][29] And two basic subunits that produce two orthogonal polarization components have also been applied to a similar metasurface polarization generator. [30,31] Recently, metasurfaces have been reported as various nonlinear light generation platforms [32] and the concept of wavefront control on metasurfaces has been successfully extended to the nonlinear regime. For example, a continuous control over the nonlinear phase change from 0 to 2π is recently realized by changing the size and shape of nanostructures, or rotating the elements with respect to the laboratory frame. Based on these mechanisms, nonlinear planar optical devices have been achieved with simultaneous harmonic generation and wavefront control. [33][34][35][36][37][38][39][40][41][42] However, so far, few works on polarization state control of nonlinear signals produced from nonlinear metasurfaces have been reported. The key issue is to find two orthogonal polarizations of harmonic components and introduce proper phase difference between them.Here, we demonstrate a nonlinear plasmonic metasurface to realize second harmonic generation (SHG) and polarization control of SH simultaneously. Split-ring resonators (SRRs) and complementary split-ring resonators (CSRRs) rotated by 90° are selected to generate orthogonal polarizations of SH components under the same linear polarized fundamental wave (FW), respectively. We find that phase difference and amplitude ratio between SH components can be tailored by adjusting the arm length of SRRs and CSRRs. By introducing spatial offset between adjacent basic supercells, we can achieve phase difference between two orthogonal components and thus realize polarization control of output SH emission and beam splitting at the same time. We then experimentally demonstrate a nonlinear metasurface that can simultaneously generate two separated SH beams with orthogonal circular polarizations under linearly polarized FW and two orthogonal linearly polarized SH beams under circularly polarized FW. Acting like a quarter-wave plate (QWP) in linear regime, the nonlinear metasurface is called an SH quarter-wave plate, which exhibits powerful capability of nonlinear polarization manipulation. Finally, we show various elliptical polarization generations for SH with proper design.Polarization is one of the most important properties of light, which is also a typical dimension for light field manipulation. With specially designed meta-atoms and tailorable phase distribution, metasurfaces have been employed to achieve arbitrary polarization state in linear regime. Moreover, metasurface is also a platform for various types of nonlinear light generation, which can be used to realize an integrated polarized light source combined with its powerful capability of polarization manipulation. Here, a nonlinear plasmonic ...

Light beams with helical wave fronts, also called optical vortices, have attracted great interest in the community of optics and photonics. They provide an additional degree of freedom for light manipulation, leading to wide-ranging potential applications in micro-particle trapping, optical microscopy, and even quantum information processing. Recently, metallic microstructures are introduced to confine the plasmonic vortices into deep subwavelength dimension, which benefits photonic integration on chip. In this Letter, exploiting the excitation of spoof surface plasmon, we experimentally demonstrate the near-field optical vortices with tunable topological charges supported by a single metaparticle in the microwave regime. These microwave plasmonic-like vortices are excited by surface waves with a spatial asymmetric distribution of electromagnetic field, which are launched by a metallic comb-shaped waveguide. Experimental characterization of highly localized and controllable near-field vortices with the nature of deep subwavelength confirms the numerical simulation. In addition, an equivalent physical model based on the coupled mode theory is proposed to understand the generation mechanism of these spoof plasmonic vortices. Our approach offers an efficient way to generate deterministic subwavelength optical vortices, which provides the potential for critical vortex elements on photonic integrated chip.