Abstract
The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict ...cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.
Clinical Trial Registration
: The trial was registered at clinicaltrials.gov as NCT03531879.
A key capability of molecular motors is sustainable force generation by a single motor copy. Direct force characterization at the single-motor level is still missing for artificial molecular motors, ...though long reported for their biological counterparts. Here we report single-molecule detection of sustained force-generating motility for an artificial track-walking molecular motor capable of autonomous chemically fueled operation. A single motor plus its track (both made of deoxyribonucleic acids or DNA) is assembled, operated and detected under magnetic tweezers by a method designed to overcome difficulty from the motor's soft double-stranded track. The motor shows self-directed walking by ∼16 nm steps up to a distance of 120 nm (covering the entire track), yielding a stall force of ∼2-3 pN. These results imply a reasonably efficient chemomechanical conversion of the motor compared to a high-efficiency biomotor. The stall force is near the level of translational biomotors powering human muscles and allows similar force-demanding applications by their artificial counterparts. This single-motor study reveals fast subsecond steps, suggesting big room for improvement in the speed of DNA motors in general. Besides, the established single-molecule method is applicable to force measurements of many other DNA motors with soft tracks.
A key capability of molecular motors is sustainable force generation by a single motor copy.
Optically powered nanomotors are advantageous for clean nanotechnology over chemically fuelled nanomotors. The two motor types are further bounded by different physical principles. Despite the gap, ...we show here that an optically powered DNA bipedal nanomotor is readily created from a high-performing chemically fuelled counterpart by subjecting its fuel to cyclic site-specific optomechanical control - as if the fuel is optically recharged. Optimizing azobenzene-based control of the original nucleotide fuel selects a light-responsive fuel analog that replicates the different binding affinity of the fuel and reaction products. The resultant motor largely retains high-performing features of the original chemical motor, and achieves the highest directional fidelity among reported light-driven DNA nanomotors. This study thus demonstrates a novel strategy for transforming chemical nanomotors to optical ones for clean nanotechnology. The strategy is potentially applicable to many chemical nanomotors with oligomeric fuels like nucleotides, peptides and synthetic polymers, leading to a new class of light-powered nanomotors that are akin to chemical nanomotors and benefit from their generally high efficiency mechanistically. The motor from this study also provides a rare model system for studying the subtle boundary between chemical and optical nanomotors - a topic pertinent to chemomechanical and optomechanical energy conversion at the single-molecule level.
Optically powered nanomotors are advantageous for clean nanotechnology over chemically fuelled nanomotors.
Optically powered nanomotors are advantageous for clean nanotechnology over chemically fuelled nanomotors. The two motor types are further bounded by different physical principles. Despite the gap, ...we show here that an optically powered DNA bipedal nanomotor is readily created from a high-performing chemically fuelled counterpart by subjecting its fuel to cyclic site-specific optomechanical control - as if the fuel is optically recharged. Optimizing azobenzene-based control of the original nucleotide fuel selects a light-responsive fuel analog that replicates the different binding affinity of the fuel and reaction products. The resultant motor largely retains high-performing features of the original chemical motor, and achieves the highest directional fidelity among reported light-driven DNA nanomotors. This study thus demonstrates a novel strategy for transforming chemical nanomotors to optical ones for clean nanotechnology. The strategy is potentially applicable to many chemical nanomotors with oligomeric fuels like nucleotides, peptides and synthetic polymers, leading to a new class of light-powered nanomotors that are akin to chemical nanomotors and benefit from their generally high efficiency mechanistically. The motor from this study also provides a rare model system for studying the subtle boundary between chemical and optical nanomotors - a topic pertinent to chemomechanical and optomechanical energy conversion at the single-molecule level.
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