. De novo drug design is a computational approach that generates novel molecular structures from atomic building blocks with no a priori relationships. Conventional methods include structure-based and ligand-based design, which depend on the properties of the active site of a biological target or its known active binders, respectively. Artificial intelligence, including machine learning, is an emerging field that has positively impacted the drug discovery process. Deep reinforcement learning is a subdivision of machine learning that combines artificial neural networks with reinforcement-learning architectures. This method has successfully been employed to develop novel de novo drug design approaches using a variety of artificial networks including recurrent neural networks, convolutional neural networks, generative adversarial networks, and autoencoders. This review article summarizes advances in de novo drug design, from conventional growth algorithms to advanced machine-learning methodologies and highlights hot topics for further development.Thrombomodulin is a molecule with anti-coagulant and anti-inflammatory properties. Recently, thrombomodulin was reported to be able to bind extracellular matrix proteins, such as fibronectin and collagen; however, whether thrombomodulin regulates the binding of human breast cancer-derived cell lines to the extracellular matrix remains unknown. To investigate this, we created an extracellular domain of thrombomodulin, TMD123-Fc, or domain deletion TM-Fc proteins (TM domain 12-Fc, TM domain 23-Fc) and examined their bindings to fibronectin in vitro by ELISA. The lectin-like domain of thrombomodulin was found to be essential for the binding of the extracellular domain of thrombomodulin to fibronectin. Using a V-well cell adhesion assay or flow cytometry analysis with fluorescent beads, we found that both TMD123-Fc and TMD12-Fc inhibited the binding between β1 integrin of human breast cancer-derived cell lines and fibronectin. Furthermore, TMD123-Fc and TMD12-Fc inhibited the binding of activated integrins to fibronectin under shear stress in the presence of Ca2+ and Mg2+ but not under strong integrin-activation conditions in the presence of Mg2+ without Ca2+. This suggests that thrombomodulin Fc fusion protein administered exogenously at a relatively early stage of inflammation may be applied to the development of new therapies that inhibit the binding of β1 integrin of breast cancer cell lines to fibronectin.Previous studies suggest that factors related to smoking cessation may vary with age. This study examined the factors affecting smoking cessation by age among Korean adult male smokers using data from the Korea National Health and Nutrition Examination Survey from 2007 to 2018 (excluding 2013). Logistic regression analyses were used to investigate various factors associated with smoking cessation in three different age groups. Out of a total of 15,492 individuals, 31.5% of the 3523 individuals aged 19-39 years (young adult), 54.7% of the 7390 individuals aged 40-64 years (middle-aged), and 78.6% of the 4589 individuals aged ≥65 years (older adults) succeeded in quitting. In the young adult and middle-aged groups, being married was associated with successful quitting, and lifetime smoking was associated with unsuccessful quitting. Willpower and several comorbidities were related to successful cessation in the middle-aged and older adult groups. Skipping any meal, which suggests unhealthy behavior, was negatively related to quitting in the young adult group. We observed that factors associated with smoking cessation success or failure differed by age, which should be considered when developing smoking cessation policies and programs.We demonstrated spectral reflectometers for two types of reflectances, absolute and relative, of diffusely reflecting surfaces in directional-hemispherical geometry. Both are built based on the integrating sphere method with a Fourier-transform infrared spectrometer operating in a vacuum. The third Taylor method is dedicated to the reflectometer for absolute reflectance, by which absolute spectral diffuse reflectance scales of homemade reference plates are realized. With the reflectometer for relative reflectance, we achieved spectral diffuse reflectance scales of various samples including concrete, polystyrene, and salt plates by comparing against the reference standards. We conducted ray-tracing simulations to quantify systematic uncertainties and evaluated the overall standard uncertainty to be 2.18% (k = 1) and 2.99% (k = 1) for the absolute and relative reflectance measurements, respectively.It is predicted that by 2025, all devices will be connected to the Internet, subsequently causing the number of devices connected with the Internet to rise [...].Sensory feedback from wearables can be effective to learn better movement through enhanced information and engagement. Facilitating greater user cognition during movement practice is critical to accelerate gains in motor function during rehabilitation following brain or spinal cord trauma. This preliminary study presents an approach using an instrumented glove to leverage sense of agency, or perception of control, to provide training feedback for functional grasp. Seventeen able-bodied subjects underwent training and testing with a custom-built sensor glove prototype from our laboratory.  https://www.selleckchem.com/products/bromodeoxyuridine-brdu.html  The glove utilizes onboard force and flex sensors to provide inputs to an artificial neural network that predicts achievement of "secure" grasp. Onboard visual and audio feedback was provided during training with progressively shorter time delay to induce greater agency by intentional binding, or perceived compression in time between an action (grasp) and sensory consequence (feedback). After training, subjects demonstrated a significant reduction (p less then 0.05) in movement pathlength and completion time for a functional task involving grasp-move-place of a small object. Future work will include a model-based algorithm to compute secure grasp, virtual reality immersion, and testing with clinical populations.Pre-clinical studies have demonstrated that tart cherries, rich in hydroxycinnamic acids and anthocyanins, protect against age-related and inflammation-induced bone loss. This study examined how daily consumption of Montmorency tart cherry juice (TC) alters biomarkers of bone metabolism in older women. Healthy women, aged 65-80 years (n = 27), were randomly assigned to consume ~240 mL (8 fl. oz.) of juice once (TC1X) or twice (TC2X) per day for 90 d. Dual-energy x-ray absorptiometry (DXA) scans were performed to determine bone density at baseline, and pre- and post-treatment serum biomarkers of bone formation and resorption, vitamin D, inflammation, and oxidative stress were assessed. Irrespective of osteoporosis risk, the bone resorption marker, tartrate resistant acid phosphatase type 5b, was significantly reduced with the TC2X dose compared to baseline, but not with the TC1X dose. In terms of indicators of bone formation and turnover, neither serum bone-specific alkaline phosphatase nor osteocalcin were altered.