: Mycobacterium tuberculosis, the pathogen of tuberculosis (TB), can survive in host macrophages and induce macrophages to M2 phenotype might result in latent MTB infection. During the latent phase, the expression of MTB heat-shock protein 16.3 (Hsp16.3) is markedly increased among most of bacterial proteins, but the role of Hsp16.3 in macrophage M2 polarization is not clear. In this work, we found that macrophages incubated with 100 ng/ml MTB Hsp16.3 increased the production of Arg-1, IL-10, TGF-beta, and CD206. These results showed that MTB Hsp16.3 may induce macrophage M2 phenotype. And the interaction of Hsp16.3 with macrophages was found to depend on chemokine receptors CCRL2 and CX3CR1. Additionally, we used overexpression and silencing techniques to further verify the effect of CCRL2 and CX3CR1 on MTB Hsp16.3-induced M2 polarization macrophages. Furthermore, we explored the downstream signaling molecules of CCRL2 and CX3CR1 and we found MTB Hsp16.3 altered the signal transduction of the AKT/ERK/p38-MAPK. Taken together, this study provides evidence that MTB Hsp16.3 promotes macrophages to M2 phenotype and explores its underlying mechanism.

Microwave-induced thermoacoustic imaging (MTAI) is a promising alternative for breast tumor detection due to its deep imaging depth, high resolution, and minimal biological hazards. However, due to the bulky size and complicated system configuration of conventional benchtop MTAI, it is limited to imaging various anatomical sites and its application in different clinical scenarios. In this study, a handheld MTAI system equipped with a compact impedance matching microwave-sono and an ergonomically designed probe was presented and evaluated. The probe integrates a flexible coaxial cable for microwave delivery, a miniaturized microwave antenna, a linear transducer array, and wedge-shaped polystyrene blocks for efficient acoustic coupling, achieving microwave illumination and ultrasonic detection coaxially, and enabling high signal-to-noise ratio (SNR). Phantom experiments demonstrated that the maximum imaging depth is 5 cm (SNR = 8 dB), and the lateral and axial resolutions are 1.5 mm and 0.9 mm, respectively. Finally, three healthy female volunteers of different ages were subjected to breast thermoacoustic tomography and ultrasound imaging. The results showed that the h-MTAI data are correlated with the data of ultrasound imaging, indicating the safety and effectiveness of the system. Thus, the proposed h-MTAI system might contribute to breast tumor screening.

Microwave-induced thermoacoustic imaging (MTAI) has been widely used in biomedical science, and has the potential as an auxiliary measure for clinical diagnosis and treatment. Recently, there are increasing interests in using ultrashort microwave-pumped thermoacoustic imaging techniques to obtain high-efficiency, high-resolution images. However, the traditional imaging system can only provide uniform radiation in a relatively small area, which limits their large field of view in clinical applications (such as whole-breast imaging, brain imaging). To address this problem, we propose an ultrashort pulse microwave thermoacoustic imaging device with a large size aperture antenna. The system can provide a microwave radiation area of 40 cm × 27 cm and a uniform imaging view of 14 cm × 14 cm. With 7 cm imaging depth and a 290 μm resolution. The practical feasibility of the system for breast tumor screening is tested in phantoms with different shapes and in an ex vivo human breast tumor which is embedded in the excised breast of an ewe (π × 5 cm × 5 cm). The tumor can be identified with a contrast of about 1:2. The results demonstrate that the dedicated MTAI system with the uniform large field of view, high imaging resolution, and large imaging depth have the potential for clinical routine breast screening.

Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.

In situ image guidance is one of the key techniques for accurate diagnosis and treatment in clinical medicine. Conventional imaging techniques such as CT, MRI provide critical information for diagnosis and treatment planning, but are less practical due to either technical complexity or ionizing radiation-related safety. Microwave-pumped thermoacoustic imaging (MTAI) is a promising alternative to real-time bioimaging due to its deep imaging depth, high resolution and minimal biological hazards. More importantly, by mapping the distribution of microwave absorbers, this method can also provide a new perspective for noninvasively observing the anatomy and functional structure of the target. In this work, we introduce a concept of in situ MTAI guidance by combining MTAI and an accurate spatial definition of invasive apparatus used in potential procedures. By mounting tiny MTAI beacons on the apparatus, it is possible to accurately reconstruct the relative position of the device to the target tissue for either real time visual guidance or as the foundation for potential automated procedures. The image quality including its applicable depth and resolution, the accuracy of the device localization is analyzed and tested with simulated breast tumor to demonstrate the capacity of the proposed technique. With refined adaptation for potential applications, this technique may provide a novel approach for a broad range of medical and biological applications.