Personalized Nutrition Intervention Improves Health Status in Overweight/Obese Chinese Adults: A Randomized Controlled Trial.

Background: Overweight and obesity increase the risk of noncommunicable diseases (NCDs). Personalized nutrition (PN) approaches may provide tailored nutritional advice/service by focusing on individual's unique characteristics to prevent against NCDs. Objective: We aimed to compare the effect of PN intervention with the traditional "one size fits all" intervention on health status in overweight/obese Chinese adults. Methods: In this 12-week randomized controlled trial, 400 adults with BMI ≥24 kg/m2 were randomized to control group (CG, n = 200) and PN group (PNG, n = 200). The CG received conventional health guidance according to the Dietary Guidelines for Chinese Residents and Chinese DRIs Handbook, whereas the PNG experienced PN intervention that was developed by using decision trees based on the subjects' anthropometric measurements, blood samples (phenotype), buccal cells (genotype), and dietary and physical activity (PA) assessments (baseline and updated). Results: Compared with the conventional intervention, PN intervention significantly improved clinical outcomes of anthropometric (e.g., body mass index (BMI), body fat percentage, waist circumference) and blood biomarkers (e.g., blood lipids, uric acid, homocysteine). The improvement in clinical outcomes was achieved through behavior change in diet and PA. The subjects in the PNG had higher China dietary guidelines index values and PA levels. Personalized recommendations of "lose weight," "increase fiber" and "take multivitamin/mineral supplements" were the major contributors to the decrease of BMI and improvement of lipid profile. Conclusion: We provided the first evidence that PN intervention was more beneficial than conventional nutrition intervention to improve health status in overweight/obese Chinese adults. This study provides a model of framework for developing personalized advice in Chinese population.Chictr.org.cn (ChiCTR1900026226).

ABO, D blood typing and subtyping using plug-based microfluidics.

A plug-based microfluidic approach was used to perform multiple agglutination assays in parallel without cross-contamination and using only microliter volumes of blood. To perform agglutination assays on-chip, a microfluidic device was designed to combine aqueous streams of antibody, buffer, and red blood cells (RBCs) to form droplets 30-40 nL in volume surrounded by a fluorinated carrier fluid. Using this approach, proof-of-concept ABO and D (Rh) blood typing and group A subtyping were successfully performed by screening against multiple antigens without cross-contamination. On-chip subtyping distinguished common A1 and A2 RBCs by using a lectin-based dilution assay. This flexible platform was extended to differentiate rare, weakly agglutinating RBCs of A subtypes by analyzing agglutination avidity as a function of shear rate. Quantitative analysis of changes in contrast within plugs revealed subtleties in agglutination kinetics and enabled characterization of agglutination of rare blood subtypes. Finally, this platform was used to detect bacteria, demonstrating the potential usefulness of this assay in detecting sepsis and the potential for applications in agglutination-based viral detection. The speed, control, and minimal sample consumption provided by this technology present an advance for point of care applications, blood typing of newborns, and general blood assays in small model organisms.

Effects of shear rate on propagation of blood clotting determined using microfluidics and numerical simulations.

This paper describes microfluidic experiments with human blood plasma and numerical simulations to determine the role of fluid flow in the regulation of propagation of blood clotting. We demonstrate that propagation of clotting can be regulated by different mechanisms depending on the volume-to-surface ratio of a channel. In small channels, propagation of clotting can be prevented by surface-bound inhibitors of clotting present on vessel walls. In large channels, where surface-bound inhibitors are ineffective, propagation of clotting can be prevented by a shear rate above a threshold value, in agreement with predictions of a simple reaction-diffusion mechanism. We also demonstrate that propagation of clotting in a channel with a large volume-to-surface ratio and a shear rate below a threshold shear rate can be slowed by decreasing the production of thrombin, an activator of clotting. These in vitro results make two predictions, which should be experimentally tested in vivo. First, propagation of clotting from superficial veins to deep veins may be regulated by shear rate, which might explain the correlation between superficial thrombosis and the development of deep vein thrombosis (DVT). Second, nontoxic thrombin inhibitors with high binding affinities could be locally administered to prevent recurrent thrombosis after a clot has been removed. In addition, these results demonstrate the utility of simplified mechanisms and microfluidics for generating and testing predictions about the dynamics of complex biochemical networks.

Using chemistry and microfluidics to understand the spatial dynamics of complex biological networks.

Understanding the spatial dynamics of biochemical networks is both fundamentally important for understanding life at the systems level and also has practical implications for medicine, engineering, biology, and chemistry. Studies at the level of individual reactions provide essential information about the function, interactions, and localization of individual molecular species and reactions in a network. However, analyzing the spatial dynamics of complex biochemical networks at this level is difficult. Biochemical networks are nonequilibrium systems containing dozens to hundreds of reactions with nonlinear and time-dependent interactions, and these interactions are influenced by diffusion, flow, and the relative values of state-dependent kinetic parameters. To achieve an overall understanding of the spatial dynamics of a network and the global mechanisms that drive its function, networks must be analyzed as a whole, where all of the components and influential parameters of a network are simultaneously considered. Here, we describe chemical concepts and microfluidic tools developed for network-level investigations of the spatial dynamics of these networks. Modular approaches can be used to simplify these networks by separating them into modules, and simple experimental or computational models can be created by replacing each module with a single reaction. Microfluidics can be used to implement these models as well as to analyze and perturb the complex network itself with spatial control on the micrometer scale. We also describe the application of these network-level approaches to elucidate the mechanisms governing the spatial dynamics of two networkshemostasis (blood clotting) and early patterning of the Drosophila embryo. To investigate the dynamics of the complex network of hemostasis, we simplified the network by using a modular mechanism and created a chemical model based on this mechanism by using microfluidics. Then, we used the mechanism and the model to predict the dynamics of initiation and propagation of blood clotting and tested these predictions with human blood plasma by using microfluidics. We discovered that both initiation and propagation of clotting are regulated by a threshold response to the concentration of activators of clotting, and that clotting is sensitive to the spatial localization of stimuli. To understand the dynamics of patterning of the Drosophila embryo, we used microfluidics to perturb the environment around a developing embryo and observe the effects of this perturbation on the expression of Hunchback, a protein whose localization is essential to proper development. We found that the mechanism that is responsible for Hunchback positioning is asymmetric, time-dependent, and more complex than previously proposed by studies of individual reactions. Overall, these approaches provide strategies for simplifying, modeling, and probing complex networks without sacrificing the functionality of the network. Such network-level strategies may be most useful for understanding systems with nonlinear interactions where spatial dynamics is essential for function. In addition, microfluidics provides an opportunity to investigate the mechanisms responsible for robust functioning of complex networks. By creating nonideal, stressful, and perturbed environments, microfluidic experiments could reveal the function of pathways thought to be nonessential under ideal conditions.

Characterization of the threshold response of initiation of blood clotting to stimulus patch size.

This article demonstrates that the threshold response of initiation of blood clotting to the size of a patch of stimulus is a robust phenomenon under a wide range of conditions and follows a simple scaling relationship based on the Damköhler number. Human blood and plasma were exposed to surfaces patterned with patches presenting clotting stimuli using microfluidics. Perturbations of the complex network of hemostasis, including temperature, variations in the concentration of stimulus (tissue factor), and the absence or inhibition of individual components of the network (factor IIa, factor V, factor VIII, and thrombomodulin), did not affect the existence of this response. A scaling relationship between the threshold patch size and the timescale of reaction for clotting was supported in numerical simulations, a simple chemical model system, and experiments with human blood plasma. These results may be useful for understanding the spatiotemporal dynamics of other autocatalytic systems and emphasize the relevance of clustering of proteins and lipids in the regulation of signaling processes.

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis.

This article demonstrates that a simple chemical model system, built by using a modular approach, may be used to predict the spatiotemporal dynamics of initiation of blood clotting in the complex network of hemostasis. Microfluidics was used to create in vitro environments that expose both the complex network and the model system to surfaces patterned with patches presenting clotting stimuli. Both systems displayed a threshold response, with clotting initiating only on isolated patches larger than a threshold size. The magnitude of the threshold patch size for both systems was described by the Damköhler number, measuring competition of reaction and diffusion. Reaction produces activators at the patch, and diffusion removes activators from the patch. The chemical model made additional predictions that were validated experimentally with human blood plasma. These experiments show that blood can be exposed to significant amounts of clot-inducing stimuli, such as tissue factor, without initiating clotting. Overall, these results demonstrate that such chemical model systems, implemented with microfluidics, may be used to predict spatiotemporal dynamics of complex biochemical networks.