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Immune checkpoint blockade (ICB) therapy, while promising for cancer treatment, faces challenges like unexpected side effects and limited objective responses. Here, we develop an in vivo gene-editing strategy for improving ICB cancer therapy in a lastingly effective manner. The approach uses a conductive hydrogel-based electroporation system to enable nucleofection of programmed cell death protein 1 (PD1) targeted CRISPR-Cas9 DNAs into T-cells directly within the lymph nodes, and subsequently produces PD1-deficient T-cells to combat tumor growth, metastasis and recurrence in different melanoma models in mice. Following in vivo gene editing, animals show enhanced cellular and humoral immune responses along with multi-fold increases of effector T-cells infiltration to the solid tumors, preventing tumor recurrence and prolonging their survival. These findings provide a proof-of-concept for direct in vivo T-cell engineering via localized gene-editing for enhanced cancer immunotherapy, and also unlock the possibilities of using this method to treat more complex human diseases. As an alternative to the systemic delivery of immune checkpoint inhibitors, here the authors develop an in vivo gene-edit strategy using a conductive hydrogel-based electroporation system to enable nucleofection of PD1-targeted CRISPR-Cas9 DNAs into lymph node T-cells, resulting in suppression of PD1 expression and promotion of anti-tumor immune responses in preclinical cancer models.

The purpose of this study is to quantitatively evaluate the differences in corneal biomechanics after SMILE and FLEx surgery using an acoustic radiation force optical coherence elastography system (ARF-OCE) and to analyze the effect of the corneal cap on the integrity of corneal biomechanical properties. A custom ring array ultrasound transducer is used to excite corneal tissue to produce Lamb waves. Depth-resolved elastic modulus images of the in vivo cornea after refractive surgery were obtained based on the phase velocity of the Lamb wave. After refractive surgery, the average elastic modulus of the corneal flap decreased (71.7 ± 24.6 kPa), while the elastic modulus of the corneal cap increased (219.5 ± 54.9 kPa). The average elastic modulus of residual stromal bed (RSB) was increased after surgery, and the value after FLEx (305.8 ± 48.5 kPa) was significantly higher than that of SMILE (221.3 ± 43.2 kPa). Compared with FLEx, SMILE preserved most of the anterior stroma with less change in corneal biomechanics, which indicated that SMILE has an advantage in preserving the integrity of the corneal biomechanical properties. Therefore, the biomechanical properties of the cornea obtained by the ARF-OCE system may be one of the essential indicators for evaluating the safety of refractive surgery.

Optical microresonators supporting whispering-gallery modes (WGMs) have become a versatile platform for achieving electromagnetically induced transparency-like (EIT-like) phenomena. We theoretically and experimentally demonstrated the tunable coupled-mode induced transparency based on the surface nanoscale axial photonics (SNAP) microresonator. Single-EIT-like and double-EIT-like (DEIT-like) effects with one or more transparent windows are achieved due to dense mode families and tunable resonant frequencies. The experimental results can be well-fitted by the coupled mode theory. An automatically adjustable EIT-like effect is discovered by immersing the sensing region of the SNAP microresonator into an aqueous environment. The sharp lineshape and high slope of the transparent window allow us to achieve a liquid refractive index sensitivity of 2058.8 pm/RIU. Furthermore, we investigated a displacement sensing phenomenon by monitoring changes in the slope of the transparent window. We believe that the above results pave the way for multi-channel all-optical switching devices, multi-channel optical communications, and biochemical sensing processing.

The measurement accuracy of Brillouin scattering spectra is crucial for ocean remote sensing by Brillouin scattering lidar. Due to the limited resolution of ICCD cameras, the traditional processing methods remain at the pixel or partial sub-pixel level, which cannot meet the requirements of high-performance lidar. In this paper, to extract the frequency shift with high precision from stimulated Brillouin scattering (SBS) lidar, a novel spectral processing method with sub-pixel recognition accuracy is proposed based on the Hessian matrix and Steger algorithm combined with the least square fitting method. Firstly, the Hessian matrix and Frangi filter are used for signal denoising. Then, the center points of SBS spectra at the sub-pixel level are extracted using the Steger algorithm and are connected and classified according to the signal type. On that basis, the frequency shifts of Brillouin scattering are calculated by using the center and radii of interference spectra after through fitting by the least squares method. Finally, the water temperatures are inverted by using the frequency shifts of Brillouin scattering. The results show that the processing method proposed in this paper can accurately calculate the frequency shift of Brillouin scattering. The measured errors of frequency shift are generally at an order of MHz, and the inversion accuracy of water temperature can be as low as 0.14 °C. This work is essential to the application for remote sensing the seawater parameters by using the Brillouin lidar technique.

Biomechanical properties of the tongue play a significant role in maintaining its normal physiological state. Although some techniques have been used to evaluate the tongue’s elasticity, they are limited in clinical detection because of low-resolution and invasive injuries. Here, a shaker-based optical coherence elastography technique that possesses features of high resolution, high sensitivity, and non-destructive imaging was designed and applied to the elastic detection of the tongue for the first time. Repeated experiments were conducted on the in vivo beagle tongue whose shear modulus and Young’s modulus were quantified by visualization of the shear wave propagation, which indicates that our technique is reliable and operable, and may be potentially utilized in clinical fields with further refinement.

Despite the rapidly growing popularity of laser vision correction (LVC) in the correction of myopia, its quantitative evaluation has not been thoroughly investigated. In this paper, an acoustic radiation force–optical coherence elastography (ARF-OCE) system was proposed to evaluate LVC by measuring the residual stromal bed (RSB) elasticity, because it is directly relevant to the RSB thickness that is critical to maintaining normal corneal function. As expected, the Young’s modulus of the RSB was calculated, then its relationship with the RSB thickness was determined. More significantly, a specific thickness was revealed in which the Young’s modulus changed dramatically, which may imply that there is a high risk of complication caused by over-cutting of the cornea. To the best of our knowledge, this is the first ARF-OCE imaging of the RSB, which may help to determine the safe RSB thickness and thus may help us to quantitatively assess LVC surgery.

This work aims to depth-resolved quantitatively analyze the effect of different stromal ablation amounts on the corneal biomechanical properties during small incision lenticule extraction (SMILE) using optical coherence elastography (OCE). A 4.5-MHz ultrasonic transducer was used to excite elastic waves in the corneal tissue. The OCE system combined with the antisymmetric Lamb wave model was employed to achieve a high-resolution, high-sensitivity, and depth-resolved quantitative detection of the corneal Young’s modulus. Eighteen rabbits were randomly divided into three groups; each group had six rabbits. The first and second groups underwent -3D and -6D SMILE surgeries, and the third group was the control group, respectively. Young’s modulus of the corneal cap and residual stromal bed (RSB) were both increased after SMILE, which shared the stress under intraocular pressure (IOP). Furthermore, the Young’s modulus of both the corneal cap and RSB after 3D SMILE group were significantly lower than that in the -6D group, which indicated that the increases in the post-operative corneal Young’s modulus were positively correlated with the amount of stromal ablation. The OCE system for quantitative spatial characterization of corneal biomechanical properties can provide useful information on the extent of safe ablation for SMILE procedures.

We studied the effects of the aspheric transition zone on the optical wavefront aberrations, corneal surface displacement, and stress induced by the biomechanical properties of the cornea after conventional laser in situ keratomileusis (LASIK) refractive surgery. The findings in this study can help improve visual quality after refractive surgery. Hyperopia correction in 1-5D was simulated using five types of aspheric transition zones with finite element modeling. The algorithm for the simulations was designed according to the optical path difference. Wavefront aberrations were calculated from the displacements on the anterior and posterior corneal surfaces. The vertex displacements and stress on the corneal surface were also evaluated. The results showed that the aspheric transition zone has an effect on the postoperative visual quality. The main wavefront aberrations on the anterior corneal surface are defocus, y-primary astigmatism, x-coma, and spherical aberrations. The wavefront aberrations on the corneal posterior surface were relatively small and vertex displacements on the posterior corneal surface were not significantly affected by the aspheric transition zone. Stress analysis revealed that the stress on the cutting edge of the anterior corneal surface decreased with the number of aspheric transition zone increased, and profile #1 resulted in the maximum stress. The stress on the posterior surface of the cornea was more concentrated in the central region and was less than that on the anterior corneal surface overall. The results showed that the aspheric transition zone has an effect on postoperative aberrations, but wavefront aberrations cannot be eliminated. In addition, the aspheric transition zone influences the postoperative biomechanical properties of the cornea, which significantly affect the postoperative visual quality.

Temperature dependence of threshold and gain coefficient of stimulated Brillouin scattering (SBS) was investigated. It was found that the threshold of SBS decreases with the increase of temperature. Based on the definition of the threshold, a new method was proposed for determining the gain coefficient of SBS of the material experimentally by measuring the threshold. It reveals that the threshold and the gain coefficient of SBS of a material are strongly related to temperature.

Optical coherence elastography (OCE) is a noninvasive imaging technique with high sensitivity and resolution that can be used for mucocutaneous imaging. Oral submucous fibrosis (OSF) is a chronic disease that has a tendency to become cancerous. Nevertheless, there are a few noninvasive methods for early detection of OSF. A piezoelectric transducer-based (PZT) OCE technique was devised to noninvasively assess the structural and mechanical properties of mucosa in healthy and fibrotic oral diseases. We first validated the accuracy and reliability of the OCE system for tissue elasticity detection by means of a heterogeneous agar model. The structural and biomechanical characteristics of the regional tissues were then evaluated by examining the oral mucosa of both healthy and fibrotic SD rats. Normal and fibrotic tissue stiffness differed significantly ( ). The elastic wave velocity was in the normal group and in the fibrotic group. After converting the results to Young's modulus, the stiffness of the healthy buccal tissues and the fibrotic buccal tissues were and , respectively ( ). OCE can differentiate between normal and fibrotic tissue based on elasticity and optical properties. Healthy buccal tissues were softer than diseased tissues.