Investigation of artificial intelligence integrated fluorescence endoscopy image analysis with indocyanine green for interpretation of precancerous lesions in colon cancer.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Tailoring an Interface Microstructure for High-Performance Reversible Protonic Ceramic Electrochemical Cells via Soft Lithography.

Micropatterning is considered a promising strategy for improving the performance of electrochemical devices. However, micropatterning on ceramic is limited by its mechanically fragile properties. This paper reports a novel imprinting-assisted transfer technique to fabricate an interlayer structure in a protonic ceramic electrochemical cell with a micropatterned electrolyte. A dense proton-conducting electrolyte, BaCe0.7Zr0.1Y0.1Yb0.1O3-δ, is micropatterned in a chevron shape with the highest aspect ratio of patterns in electrode-supported cells to the best of our knowledge, increasing surface areas of both electrode sides more than 40%. The distribution of relaxation time analysis reveals that the chevron-patterned electrolyte layer significantly increases the electrode contact areas and active electrochemical reaction sites at the vicinity of the interfaces, contributing to enhanced performances of both the fuel cell and electrolysis operations. The patterned cell demonstrates improved fuel cell performance (>45%) and enhances electrolysis cell performance (30%) at 500 °C. This novel micropatterning technique is promising for the facile production of layered electrochemical cells, further opening a new route for the performance enhancement of ceramic-based electrochemical cells.

Spine-like Joint Link Mechanism to Design Wearable Assistive Devices.

When we develop wearable assistive devices, comfort and support are two main issues that need to be considered. In conventional design approaches, the degree of freedom of the wearer's joint movements tends to be oversimplified. Accordingly, the wearer's motion becomes restrained and bone/ligament injuries might occur in case of an unexpected fall. To mitigate these issues, this paper proposes a novel joint link mechanism inspired by a human spine structure as well as functionalities. The key feature of the proposed spine-like joint link mechanism is that hemispherical blocks are concatenated via flexible synthetic fiber lines so that their concatenation stiffness can be adjusted according to a tensile force. This feature has a great potentiality for designing a wearable assistive device that can support aged people's sit-to-stand action or augment spinal motion by regulating the concatenation stiffness. In addition, the concatenated hemispherical blocks enable the wearer to move his/her joint with full freedom, which in turn increases the wearer's mobility and prevents joint misalignment. The experimental results with a testbed and a pilot wearer substantiated that the spine-like joint link mechanism can serve as a key component in the design of wearable assistive devices for better mobility.

Biomolecular imaging of colorectal tumor lesions using a FITC-labeled scFv-Cκ fragment antibody.

For the sensitive diagnosis of colorectal cancer lesions, advanced molecular imaging techniques using cancer-specific targets have emerged. However, issues regarding the clearance of unbound probes and immunogenicity remain unresolved. To overcome these limitations, we developed a small-sized scFv antibody fragment conjugated with FITC for the real-time detection of colorectal cancer by in vivo molecular endoscopy imaging. A small-sized scFv fragment can target colon cancer secreted protein-2 (CCSP-2), highly expressed in colorectal adenocarcinoma tissues; moreover, its full-length IgG probe has been used for molecular imaging previously. To assess the efficacy of anti-CCSP-2 scFv-FITC, surgical specimens were obtained from 21 patients with colorectal cancer for ex vivo molecular fluorescence analysis, histology, and immunohistochemistry. Orthotopic mice were administered with anti-CCSP-2 scFv-FITC topically and intravenously, and distinct tumor lesions were observed by real-time fluorescence colonoscopy. The fluorescence imaging of human colon cancer specimens allowed the differentiation of malignant tissues from non-malignant tissues (p < 0.05), and the CCSP-2 expression level was found to be correlated with the fluorescence intensity. Here, we demonstrated the feasibility and safety of anti-CCSP-2 scFv-FITC for molecular imaging as well as its potential in real-time fluorescence colonoscopy for the differential diagnosis of tumor lesions.

Stimulatory effects of interleukin-1 beta on development of porcine uterine epithelial cell are mediated by activation of the ERK1/2 MAPK cell signaling cascade.

Successful establishment of pregnancy depends on timely changes in the conceptus (embryo and associated extra-embryonic membranes) and uterine endometrium orchestrated by molecules from both the conceptus and uterus. Interleukin-1 beta (IL-1ß) is an important mediator of that communication regulating development of the peri-implantation conceptus and opening the window of implantation during early pregnancy. However, little is known about IL-1ß-mediated intracellular signaling cascades and functional effects in uterine luminal epithelium (LE) during the peri-implantation period of pregnancy in pigs. Therefore, this study determined, using an immortalized porcine LE (pLE) cell line from day 12 pregnant gilts: 1) the intracellular signaling cascade responsible for activities of IL-1ß in pLE cells, and 2) the changes in cellular activities induced by IL-1ß. IL-1ß stimulated phosphorylation of ERK1/2 proteins in pLE cells in a dose-dependent manner. Ten ng/ml IL-1ß increased levels of phosphorylated (p)-ERK1/2 proteins in pLE cells within 15 min post-treatment, and this IL-1ß-induced phosphorylated status was inhibited by increasing doses of U0126 (ERK1/2 inhibitor). In addition IL-1ß increased p-P70S6K, p-P90S6K, p-S6, and p-P38 proteins in a time-dependent manner, but IL-1ß-induced activation of P70S6K and S6 proteins was significantly decreased in the presence of pharmacological inhibitors for ERK1/2 (U0126), MTOR (rapamycin), and P38 (SB203580). Moreover, IL-1ß treatment potently increased the abundance of p-ERK1/2 proteins in the nucleus and cytoplasm. Similarly cytoplasmic p-S6 proteins were localized abundantly in the pLE cells treated with IL-1ß. Furthermore, IL-1ß increased proliferation of pLE cells by approximately 200%, and pretreatment of pLE cells with U0126 significantly inhibited this stimulatory effect. Collectively, results of this study indicate that IL-1ß plays an important role in development of uterine LE by stimulating cell proliferation, and that these effects are coordinately regulated by activation of the ERK1/2 and P38 MAPK cell signaling cascades.