Neuroprotective Effects of Chemical Constituents of Leaves of Euonymus hamiltonianus Wall.

Euonymus hamiltonianus Wall. is considered a medicinal plant and is used to treat pain, cough, dysuria, and cancer, but a clear phytochemical investigation of its biological activities has yet to be performed. Investigation of chemical constituents of the leaves of Euonymus hamiltonianus Wall. led to the isolation of three new compounds by chromatography techniques, euonymusins A-C (1, 10, and 11), and the acquisition of new spectroscopic data for euonymusin D (2), along with the identification of ten known compounds. The chemical structures of the compounds were established using extensive spectroscopic techniques, including NMR, MS, and hydrolysis, and compared with the published data. These compounds were tested in vitro for their inhibitory effects on beta amyloid production (Aß42). Compounds 13 and 14 displayed weak inhibition, with IC50 values ranging from 53.15 to 65.43 µM. Moreover, these compounds were also assessed for their inhibitory effects on nitric oxide production. Of these compounds, 3, 4, and 14 displayed inhibitory effects on NO production, with IC50 values ranging from 14.38 to 17.44 µM. Compounds 3, 4, and 14 also suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein.

A Monocular Variable Magnifications 3D Laparoscope System Using Double Liquid Lenses.

During minimal invasive surgery (MIS), the laparoscope only provides a single viewpoint to the surgeon, leaving a lack of 3D perception. Many works have been proposed to obtain depth and 3D reconstruction by designing a new optical structure or by depending on the camera pose and image sequences. Most of these works modify the structure of the conventional laparoscopes and cannot provide 3D reconstruction of different magnification views. In this study, we propose a laparoscopic system based on double liquid lenses, which provide doctors with variable magnification rates, near observation, and real-time monocular 3D reconstruction. Our system composes of an optical structure that can obtain auto magnification change and autofocus without any physically moving element, and a deep learning network based on the Depth from Defocus (DFD) method, trained to suit inconsistent camera intrinsic situations and estimate depth from images of different focal lengths. The optical structure is portable and can be mounted on conventional laparoscopes. The depth estimation network estimates depth in real-time from monocular images of different focal lengths and magnification rates. Experiments show that our system provides a 0.68-1.44x zoom rate and can estimate depth from different magnification rates at 6fps. Monocular 3D reconstruction reaches at least 6mm accuracy. The system also provides a clear view even under 1mm close working distance. Ex-vivo experiments and implementation on clinical images prove that our system provides doctors with a magnified clear view of the lesion, as well as quick monocular depth perception during laparoscopy, which help surgeons get better detection and size diagnosis of the abdomen during laparoscope surgeries.

Combined Ultrasensitive Detection of Renal Cancer Proteins and Cells Using an Optical Microfiber Functionalized with Ti3C2 MXene and Gold Nanorod-Nanosensitized Interfaces.

The ultrasensitive and quantitative detection of renal cancer protein biomarkers present at ultralow concentrations for early-stage cancer diagnosis requires a biosensing probe possessing ultrahigh detection sensitivity and remarkable biosensing selectivity. Here, we report an optical microfiber integrated with Ti3C2-supported gold nanorod hybrid nanointerfaces for implementation in ultrasensitive sensing of the carbonic anhydrase IX (CAIX) protein and renal cancer cells. Because the evanescent field of the fiber is strongly coupled with nanointerfaces in the near-infrared region, the proposed optical microfiber biosensor achieves ultrahigh-sensitivity detection of the CAIX protein biomarker with ultralow limits of detection (LODs) of 13.8 zM in pure buffer solution and 0.19 aM in 30% serum solution. In addition, the proposed sensor also successfully and specifically recognizes living renal cancer cells in cell culture media with a LOD of 180 cells/mL. This strategy may serves as a powerful biosensing platform that combines the quantification of protein biomarkers and cancer cells, resulting in a higher accuracy of early-stage renal cancer diagnosis and screenings.

Circ_0027470 promotes cadmium exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and stimulating SHH signaling pathway.

Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.

Sinapic Acid Attenuates the Neuroinflammatory Response by Targeting AKT and MAPK in LPS-Activated Microglial Models.

Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammation-related cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.

Visualization, registration and tracking techniques for augmented reality guided surgery: a review.

Augmented reality (AR) surgical navigation has developed rapidly in recent years. This paper reviews and analyzes the visualization, registration, and tracking techniques used in AR surgical navigation systems, as well as the application of these AR systems in different surgical fields. The types of AR visualization are divided into two categories ofin situvisualization and nonin situvisualization. The rendering contents of AR visualization are various. The registration methods include manual registration, point-based registration, surface registration, marker-based registration, and calibration-based registration. The tracking methods consist of self-localization, tracking with integrated cameras, external tracking, and hybrid tracking. Moreover, we describe the applications of AR in surgical fields. However, most AR applications were evaluated through model experiments and animal experiments, and there are relatively few clinical experiments, indicating that the current AR navigation methods are still in the early stage of development. Finally, we summarize the contributions and challenges of AR in the surgical fields, as well as the future development trend. Despite the fact that AR-guided surgery has not yet reached clinical maturity, we believe that if the current development trend continues, it will soon reveal its clinical utility.

Ultrasensitive Detection of Exosomes Using an Optical Microfiber Decorated with Plasmonic MoSe2-Supported Gold Nanorod Nanointerfaces.

Exosomes are potential and promising natural noninvasive biomarkers for liquid biopsies and can be involved in various biological and pathological processes in early-stage cancer. Thus, there is an urgent demand to develop low-cost, small-size, remarkable-specificity, and ultrasensitive exosome biosensors for early clinical point-of-care (POC) testing. Although various conventional tumor exosome detection methods have been generally proposed, the low detection sensitivity and specificity significantly hinder their use in cancer clinical diagnosis and prognosis. To address the above challenges, an optical microfiber integrated with MoSe2-supported gold nanorods is proposed. To tune the strong localized surface plasmon resonance (LSPR) of the nanointerfaces on the optical microfiber to be in accordance with the operating wavelength of the silica optical microfiber in the telecommunication band, gold nanorods with a high aspect ratio of approximately 10:1 are proposed. Due to the interaction between the excited LSPR effect and the evanescent field of the optical microfiber, the sensor can detect clear cell renal cancer exosomes within a wide concentration range from 100 particles/mL to 108 particles/mL, with an extremely low limit of detection (LOD) of 9.32 particles/mL, which is lower than that of current various state of the art methods. More importantly, the microfiber with high specificity can successfully differentiate pathological plasma and healthy controls, exhibiting very promising clinical applications in renal cancer diagnosis and prognosis. This work opens up a new approach for the in situ detection and quantification of exosomes with ultrahigh sensitivity in early clinical screening and diagnosis.

COVID-19 vaccine development: milestones, lessons and prospects.

With the constantly mutating of SARS-CoV-2 and the emergence of Variants of Concern (VOC), the implementation of vaccination is critically important. Existing SARS-CoV-2 vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, and virus-like particle (VLP) vaccines. Viral vector vaccines, protein subunit vaccines, and mRNA vaccines may induce additional cellular or humoral immune regulations, including Th cell responses and germinal center responses, and form relevant memory cells, greatly improving their efficiency. However, some viral vector or mRNA vaccines may be associated with complications like thrombocytopenia and myocarditis, raising concerns about the safety of these COVID-19 vaccines. Here, we systemically assess the safety and efficacy of COVID-19 vaccines, including the possible complications and different effects on pregnant women, the elderly, people with immune diseases and acquired immunodeficiency syndrome (AIDS), transplant recipients, and cancer patients. Based on the current analysis, governments and relevant agencies are recommended to continue to advance the vaccine immunization process. Simultaneously, special attention should be paid to the health status of the vaccines, timely treatment of complications, vaccine development, and ensuring the lives and health of patients. In addition, available measures such as mix-and-match vaccination, developing new vaccines like nanoparticle vaccines, and optimizing immune adjuvant to improve vaccine safety and efficacy could be considered.

Statistical and individual characteristics-based reconstruction for craniomaxillofacial surgery.

PURPOSE: In craniomaxillofacial (CMF) surgery planning, a preoperative reconstruction of the CMF reference model is crucial for surgical restoration, especially the reconstruction of bilateral defects. Current reconstruction algorithms mainly generate reference models from the image analysis aspect, however, clinical indicators of the CMF reference model mostly consider the distribution of anatomical landmarks. Generating a reference model with optimal clinical evaluation helps promote the feasibility of an algorithm. METHODS: We first build a dataset with 100 normal skull models and then calculate a statistical shape model (SSM) and the distribution of normal cephalometric values, which indicate the statistical features of a population. To further generate personalized reference models, we apply non-rigid registration to align the SSM with the defect skull model. An evaluation standard to select the optimal reference model considers both global performance and anatomical evaluation. Moreover, we develop a landmark detection network to improve the automatic level of the algorithm. RESULTS: The proposed method performs better than methods including Iterative Closest Point and SSM. From a global evaluation aspect, the results show that the RMSE between the reference model and the ground truth is [Formula: see text] mm, the percentage of vertices with error below 2 mm is [Formula: see text]% and the average faces distance is [Formula: see text] mm (better than the state-of-the-art method). From the anatomical evaluation aspect, the target registration error between the landmark pairs is [Formula: see text] mm. In addition, the clinical application confirms that the reference model can meet clinical requirements. CONCLUSION: To the best of our knowledge, we propose the first CMF reconstruction method considering the global performance of reconstruction and anatomically local evaluation from clinical experience. Simulated experiments and clinical cases prove the general applicability and strength of the method.

An accurate 3D augmented reality navigation system with enhanced autostereoscopic display for oral and maxillofacial surgery.

BACKGROUND: Oral and maxillofacial surgery demands high precision navigation to achieve optimal surgical outcomes. Augmented reality (AR) has been a promising solution for intuitive and accurate guidance, whereas existing systems have room for improvement. METHODS: We propose a high quality and accurate in situ AR navigation system. Enhanced image quality is achieved by deploying eye tracking in lenticular-based autostereoscopic display. Viewpoint tracking and optical tracking are integrated to assure accurate in situ images. RESULTS: The proposed system can provide in situ AR images in real-time, with a viewing angle of 59.5° × 49.1°, 3D image resolution of 0.35 × 0.21 mm, and image accuracy of 0.99 ± 0.70 mm. A maxillary drilling experiment obtains average position error of 1.12 ± 0.30 mm and localization time of 8.7 ± 3.9 s, significantly better than conventional 2D navigation system. CONCLUSIONS: The proposed system can display high-quality AR images and therefore reduce positioning error and operating time.

Augmented reality-based autostereoscopic surgical visualization system for telesurgery.

PURPOSE: The visualization of remote surgical scenes is the key to realizing the remote operation of surgical robots. However, current non-endoscopic surgical robot systems lack an effective visualization tool to offer sufficient surgical scene information and depth perception. METHODS: We propose a novel autostereoscopic surgical visualization system integrating 3D intraoperative scene reconstruction, autostereoscopic 3D display, and augmented reality-based image fusion. The preoperative organ structure and the intraoperative surface point cloud are obtained from medical imaging and the RGB-D camera, respectively, and aligned by an automatic marker-free intraoperative registration algorithm. After registration, preoperative meshes with precalculated illumination and intraoperative textured point cloud are blended in real time. Finally, the fused image is shown on a 3D autostereoscopic display device to achieve depth perception. RESULTS: A prototype of the autostereoscopic surgical visualization system was built. The system had a horizontal image resolution of 1.31 mm, a vertical image resolution of 0.82 mm, an average rendering rate of 33.1 FPS, an average registration rate of 20.5 FPS, and average registration errors of approximately 3 mm. A telesurgical robot prototype based on 3D autostereoscopic display was built. The quantitative evaluation experiments showed that our system achieved similar operational accuracy (1.79 ± 0.87 mm) as the conventional system (1.95 ± 0.71 mm), while having advantages in terms of completion time (with 34.11% reduction) and path length (with 35.87% reduction). Post-experimental questionnaires indicated that the system was user-friendly for novices and experts. CONCLUSION: We propose a 3D surgical visualization system with augmented instruction and depth perception for telesurgery. The qualitative and quantitative evaluation results illustrate the accuracy and efficiency of the proposed system. Therefore, it shows great prospects in robotic surgery and telesurgery.

Dew inspired breathing-based detection of genetic point mutation visualized by naked eye.

A novel label-free method based on breathing-induced vapor condensation was developed for detection of genetic point mutation. The dew-inspired detection was realized by integration of target-induced DNA ligation with rolling circle amplification (RCA). The vapor condensation induced by breathing transduced the RCA-amplified variances in DNA contents into visible contrast. The image could be recorded by a cell phone for further or even remote analysis. This green assay offers a naked-eye-reading method potentially applied for point-of-care liver cancer diagnosis in resource-limited regions.