Microwave-induced thermoacoustic imaging (MTI) has the advantages of high resolution, high contrast, non-ionization, and non-invasive. Recently, MTI was used in the field of breast cancer screening. In this paper, based on the finite element method (FEM) and COMSOL Multiphysics software, a three-dimensional breast cancer model suitable for exploring the MTI process is proposed to investigate the influence of Young’s modulus (YM) of breast cancer tissue on MTI. It is found that the process of electromagnetic heating and initial pressure generation of the entire breast tissue is earlier in time than the thermal expansion process. Besides, compared with normal breast tissue, tumor tissue has a greater temperature rise, displacement, and pressure rise. In particular, YM of the tumor is related to the speed of thermal expansion. In particular, the larger the YM of the tumor is, the higher the heating and contraction frequency is, and the greater the maximum pressure is. Different Young’s moduli correspond to different thermoacoustic signal spectra. In MTI, this study can be used to judge different degrees of breast cancer based on elastic imaging. In addition, this study is helpful in exploring the possibility of microwave-induced thermoacoustic elastic imaging (MTAE).

Structured illumination microscopy (SIM) is a popular and powerful super-resolution (SR) technique in biomedical research. However, the conventional reconstruction algorithm for SIM heavily relies on the accurate prior knowledge of illumination patterns and signal-to-noise ratio (SNR) of raw images. To obtain high-quality SR images, several raw images need to be captured under high fluorescence level, which further restricts SIM’s temporal resolution and its applications. Deep learning (DL) is a data-driven technology that has been used to expand the limits of optical microscopy. In this study, we propose a deep neural network based on multi-level wavelet and attention mechanism (MWAM) for SIM. Our results show that the MWAM network can extract high-frequency information contained in SIM raw images and accurately integrate it into the output image, resulting in superior SR images compared to those generated using wide-field images as input data. We also demonstrate that the number of SIM raw images can be reduced to three, with one image in each illumination orientation, to achieve the optimal tradeoff between temporal and spatial resolution. Furthermore, our MWAM network exhibits superior reconstruction ability on low-SNR images compared to conventional SIM algorithms. We have also analyzed the adaptability of this network on other biological samples and successfully applied the pretrained model to other SIM systems.

Three-dimensional (3D) cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models. The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness. While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D, they often have limitations, such as being too harsh for fragile 3D cell cultures, requiring complex handling protocols, or inducing tissue deformation with shrinkage or expansion. To address this issue, we proposed a modified optical clearing method for 3D cell cultures, called MACS-W, which is simple, highly efficient, and morphology-preserving. In our evaluation of MACS-W, we found that it exhibits excellent clearing capability in just 10min, with minimal deformation, and helps drug evaluation on tumor spheroids. In summary, MACS-W is a fast, minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.

Structured illumination microscopy (SIM) achieves super-resolution (SR) by modulating the high-frequency information of the sample into the passband of the optical system and subsequent image reconstruction. The traditional Wiener-filtering-based reconstruction algorithm operates in the Fourier domain, it requires prior knowledge of the sinusoidal illumination patterns which makes the time-consuming procedure of parameter estimation to raw datasets necessary, besides, the parameter estimation is sensitive to noise or aberration-induced pattern distortion which leads to reconstruction artifacts. Here, we propose a spatial-domain image reconstruction method that does not require parameter estimation but calculates patterns from raw datasets, and a reconstructed image can be obtained just by calculating the spatial covariance of differential calculated patterns and differential filtered datasets (the notch filtering operation is performed to the raw datasets for attenuating and compensating the optical transfer function (OTF)). Experiments on reconstructing raw datasets including nonbiological, biological, and simulated samples demonstrate that our method has SR capability, high reconstruction speed, and high robustness to aberration and noise.

Light-sheet fluorescence microscopy (LSFM) has been widely used to image the three-dimensional (3D) structures and functions of various millimeter-size bio-specimen such as zebrafish. However, the sample adsorption and scattering cause shading of the light-sheet illumination, preventing the even 3D image of thick samples. Herein, we report a continuous-rotational light-sheet microscope (CR-LSM) that enables simultaneous 3D bright-field and fluorescence imaging. With a high-accuracy rotational stage, CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles. Then, 3D morphology and fluorescent structure were reconstructed with a developed algorithm. Using CR-LSM, zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.

Vascular-targeted photodynamic therapy (V-PDT) is an effective treatment for port wine stains (PWS). However, repeated treatment is usually needed to achieve optimal treatment outcomes, possibly due to the limited treatment light penetration depth in the PWS lesion. The optical clearing technique can increase light penetration in depth by reducing light scattering. This study aimed to investigate the V-PDT in combination with an optical clearing agent (OCA) for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model. Vascular responses were closely monitored with laser speckle contrast imaging (LSCI), optical coherence tomography angiography, and stereo microscope before, during, and after the treatment. We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature. The combination of OCA and V-PDT resulted in significant vascular damage, including vasoconstriction and the reduction of blood flow. Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases, including PWS.

Monomethyl auristatin E (MMAE) is a derivative of the marine peptide Dolastatin 10, which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials. The antibody drug conjugate (ADC) of MMAE is currently used in clinical practice. However, the safety issues of MMAE-based ADC, such as high drug toxicity and poor bioavailability, still exist when using it for anticancer therapy. A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects. Herein, PLGA-b-PEG2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy. The sustained release effect and the immunogenic cell death (ICD) effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments. The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention (EPR) effect, inducing cell apoptosis and causing a certain degree of immune response. The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC. Overall, this study provides a safe and effective chemotherapeutic approach, as well as a simple and effective synthetic process for MMAE-based nanoparticles, improving their therapeutic efficacy and safety.

Collective cell migration is a coordinated movement of multi-cell systems essential for various processes throughout life. The collective motions often occur under spatial restrictions, hallmarked by the collective rotation of epithelial cells confined in circular substrates. Here, we aim to explore how geometric shapes of confinement regulate this collective cell movement. We develop quantitative methods for cell velocity orientation analysis, and find that boundary cells exhibit stronger tangential ordering migration than inner cells in circular pattern. Furthermore, decreased tangential ordering movement capability of collective cells in triangular and square patterns are observed, due to the disturbance of cell motion at unsmooth corners of these patterns. On the other hand, the collective cell rotation is slightly affected by a convex defect of the circular pattern, while almost hindered with a concave defect, also resulting from different smoothness features of their boundaries. Numerical simulations employing cell Potts model well reproduce and extend experimental observations. Together, our results highlight the importance of boundary smoothness in the regulation of collective cell tangential ordering migration.