Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Biochemical Composition and Related Potential Nutritional and Health Properties of Sobrassada de Mallorca.

'Sobrassada de Mallorca' is an EU PGI (Protected Geographical Indication) -qualified traditional food with important historical, social, and gastronomical relevance. However, its nutritional features are poorly characterized. Here, we studied 15 samples of Sobrassada de Mallorca (SM) and 9 samples of 'Sobrassada de Mallorca de Porc Negre' (SMBP), which are the two types of sobrassada that are PGI-protected. Their composition was assessed under the light of the EU Regulation 1924/2006 on nutrition and health claims (NHC) made on food. Results show the notably high energetic density (588 and 561 kcal/100 g for SM and SMBP, respectively) due to the notable fatty acid (FA) content and the relatively high proportion of unsaturated FAs (≈61% of total FAs) is also noted, mainly oleic acid (39.7 and 45.7%). Moreover, analyses showed that 100 g of both types of 'Sobrassada de Mallorca' present a 'significant' content (at least 15% of the established Nutrient Reference Values) of vitamins A (241 and 232 µg), E (2.67 and 2.67 mg), B3 (3.50 and 2.43 mg), B6 (0.27 and 0.35 mg), B12 (0.65 and 0.56 µg), phosphorus (271 and 186 mg), and selenium (17.3 and 16.2 µg) as defined by the EU standards and, in essence, their associated health benefits can be claimed for both SM and SMBP or foods containing them. In principle, SM and SMBP could be associated with various health claims (HC), including those related to energy-yielding metabolism, normal functioning of the immune system, and reduction of tiredness and fatigue.

Glycosaminoglycan dermatan sulfate supplementation decreases diet-induced obesity and metabolic dysfunction in mice.

Glycosaminoglycans are complex carbohydrates used as nutraceuticals for diverse applications. We studied the potential of the glycosaminoglycan dermatan sulfate (DS) to counteract the development of diet-induced obesity (DIO) using obesity-prone mice fed a high-fat diet (HFD) as a model. Oral DS supplementation protected the animals against HFD-induced increases in whole-body adiposity, visceral fat mass, adipocyte size, blood glucose levels, insulin resistance, and pro-inflammatory lipids levels in brown adipose tissue (BAT) and the liver, where it largely counteracted the HFD-induced changes in the nonpolar metabolome. Protection against DIO in the DS-supplemented mice occurred despite higher energy intake and appeared to be associated with increased energy expenditure, higher uncoupling protein 1 expression in BAT, decreased BAT "whitening," and an enhanced channeling of fuel substrates toward skeletal muscle. This work is the first preclinical study to examine the anti-obesity activity of DS tested individually in vivo. The results support possible uses of DS as an active component in functional foods/supplements to manage obesity and associated metabolic diseases.

Dietary Sources, Sex, and rs5888 (SCARB1) as Modulators of Vitamin A's Effect on Cardiometabolic Health.

Although preclinical studies have attributed vitamin A (VA) cardiometabolic benefits, these effects are still controversial and not always supported in large human studies. Here, the outcomes associated with VA and its relationship with habitual dietary sources, sex, and genetic background have been studied. To do so, the data from an observational study (n = 455) (64% females, mean age of 36 years) showing that suboptimal VA intake (mainly from retinol rather than carotene) is associated with cardiometabolic risk (CMR) were considered. A higher odds ratio (OR) of suffering ≥ 2 simultaneous CMR factors was observed in men in the low consumption tercile of retinol (OR = 2.04; p = 0.019). In women, however, this relationship was not evident. Then, incubation of peripheral blood mononuclear cells (PBMCs) with VA-related compounds (ex vivo functional assay from 81 men and women) induced specific changes in the activity of genes involved in lipid homeostasis and inflammatory status, which were dependent on the type of compound tested and the sex of the person. In addition, the presence of the genetic variant rs5888 in SCARB1 was identified as having a high influence on VA-related metabolic response. The new evidence derived from this study could be relevant for personalized nutritional advice concerning VA and CMR.

KLB and NOX4 expression levels as potential blood-based transcriptional biomarkers of physical activity in children.

Insufficient physical activity (PA) in children is considered one of the major contributors to obesity and cardiometabolic complications later in life. Although regular exercise may contribute to disease prevention and health promotion, reliable early biomarkers are required to objectively discern people performing low PA from those who exercise enough. Here, we aimed to identify potential transcript-based biomarkers through the analysis of a whole-genome microarray in peripheral blood cells (PBC) from physically less active (n = 10) comparing with more active (n = 10) children. A set of genes differentially expressed (p < 0.01, Limma test) in less physically active children were identified, including the down-regulation of genes related to cardiometabolic benefits and improved skeletal function (KLB, NOX4, and SYPL2), and the up-regulation of genes whose elevated expression levels are associated with metabolic complications (IRX5, UBD, and MGP). The analysis of the enriched pathways significantly affected by PA levels were those associated with protein catabolism, skeletal morphogenesis, and wound healing, among others, which may suggest a differential impact of low PA on these processes. Microarray analysis comparing children according to their usual PA has revealed potential PBC transcript-based biomarkers that may be useful in early discerning children expending high sedentary time and its associated negative consequences.

Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies.

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

Supplementation with the Prebiotic High-Esterified Pectin Improves Blood Pressure and Cardiovascular Risk Biomarker Profile, Counteracting Metabolic Malprogramming.

Supplementation with the prebiotic pectin is associated with beneficial health effects. We aimed to characterize the cardioprotective actions of chronic high-esterified pectin (HEP) supplementation (10%) in a model of metabolic malprogramming in rats, prone to obesity and associated disorders: the progeny of mild calorie-restricted dams during the first half of pregnancy. Results show that pectin supplementation reverses metabolic malprogramming associated with gestational undernutrition. In this sense, HEP supplementation improved blood pressure, reduced heart lipid content, and regulated cardiac gene expression of atrial natriuretic peptide and lipid metabolism-related genes. Moreover, it caused an elevation in circulating levels of fibroblast growth factor 21 and a higher expression of its co-receptor ß-klotho in the heart. Most effects are correlated with the gut levels of beneficial bacteria promoted by HEP. Therefore, chronic HEP supplementation shows cardioprotective actions, and hence, it is worth considering as a strategy to prevent programmed cardiometabolic alterations.

Statistical Characterization of Wireless Power Transfer via Unmodulated Emission.

In the past few years, the ability to transfer power wirelessly has experienced growing interest from the research community. Because the wireless channel is subject to a large number of random phenomena, a crucial aspect is the statistical characterization of the energy that can be harvested by a given device. For this characterization to be reliable, a powerful model of the propagation channel is necessary. The recently proposed generalized-K model has proven to be very useful, as it encompasses the effects of path loss, shadowing, and fast fading for a broad set of wireless scenarios, and because it is analytically tractable. Accordingly, the purpose of this paper is to characterize, from a statistical point of view, the energy harvested by a static device from an unmodulated carrier signal generated by a dedicated source, assuming that the wireless channel obeys the generalized-K propagation model. Specifically, by using simulation-validated analytical methods, this paper provides exact closed-form expressions for the average and variance of the energy harvested over an arbitrary time period. The derived formulation can be used to determine a power transfer plan that allows multiple or even massive numbers of low-power devices to operate continuously, as expected from future network scenarios such as the Internet of things or 5G/6G.

A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study.

BACKGROUND & AIMS: Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform-which uses metabolomic and genetic information to classify individuals into different 'metabolic clusters' and create personalized dietary plans-for improving health outcomes in subjects with overweight or obesity. METHODS: A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18-65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior. RESULTS: There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: -2.1 [95% CI -2.9, -1.4] kg; control: -2.0 [95% CI -2.7, -1.3] kg) and body weight (personalized: -3.1 [95% CI -4.1, -2.1] kg; control: -3.3 [95% CI -4.2, -2.4] kg). The difference between groups in fat mass change was -0.1 kg (95% CI -1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups. CONCLUSION: Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov registry (NCT04590989).

Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations.

Coronavirus disease 2019 (COVID-19) has caused a global health crisis and the factors behind its differential impact on COVID-19 among populations are still being known. Geographical differences in nutrient profile could be a relevant factor, especially considering that scientific evidence supports that 10 micronutrients are essential for proper immune system function. This study aims to evaluate these micronutrient intakes in the territories of Spain and to analyze their relationship with epidemiological indicators of COVID-19 from the first two waves of COVID-19, when neither specific vaccines nor drugs had yet come into play. Results showed that vitamin D, A, B9, and zinc intakes were particularly insufficient in Spain. The joint intake of these four micronutrients was lower in regions with the highest COVID-19 incidence and mortality, and of particular importance, was the insufficient intake of vitamin D. A pattern of food consumption associated with lower COVID-19 impact was observed. In conclusion, the results show the relevance of the optimal consumption of foods rich in essential nutrients for the immune system. Therefore, this assessment could serve to launch specific dietary recommendations to strengthen the immune system in Spanish territories to better face potential new COVID-19 variants and/or further infectious diseases.

Absorption, Distribution, Metabolism, and Excretion of the Main Olive Tree Phenols and Polyphenols: A Literature Review.

The effects of olive tree (poly)phenols (OPs) are largely dependent upon their bioavailability and metabolization by humans. Absorption, distribution, metabolism, and excretion (ADME) are fundamental for the nutritional efficacy and toxicological impact of foods containing OPs. This review includes studies on the administration of hydroxytyrosol (HT), oleuropein (Ole), or other OPs and foods, products, or mixtures that contain them. Briefly, data from in vivo studies indicate that OPs are absorbable by intestinal cells. Both absorption and bioavailability depend upon each compound and/or the matrix in which it is contained. OPs metabolism begins in enterocytes and can also continue in the liver. Metabolic phase I mainly consists of the hydrolysis of Ole, which results in an increase in the HT content. Phase II metabolic reactions involve the conjugation of (poly)phenols mainly with glucuronide and sulfate groups. This review offers a complete perspective of the ADME processes of OPs, which could support the future nutritional and/or toxicological studies in this area.

Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework.

The pandemic caused by the new coronavirus has caused shock waves in many countries, producing a global health crisis worldwide. Lack of knowledge of the biological mechanisms of viruses, plus the absence of effective treatments against the disease (COVID-19) and/or vaccines have pulled factors that can compromise the proper functioning of the immune system to fight against infectious diseases into the spotlight. The optimal status of specific nutrients is considered crucial to keeping immune components within their normal activity, helping to avoid and overcome infections. Specifically, the European Food Safety Authority (EFSA) evaluated and deems six vitamins (D, A, C, Folate, B6, B12) and four minerals (zinc, iron, copper and selenium) to be essential for the normal functioning of the immune system, due to the scientific evidence collected so far. In this report, an update on the evidence of the contribution of nutritional factors as immune-enhancing aspects, factors that could reduce their bioavailability, and the role of the optimal status of these nutrients within the COVID-19 pandemic context was carried out. First, a non-systematic review of the current state of knowledge regarding the impact of an optimal nutritional status of these nutrients on the proper functioning of the immune system as well as their potential role in COVID-19 prevention/treatment was carried out by searching for available scientific evidence in PubMed and LitCovid databases. Second, a compilation from published sources and an analysis of nutritional data from 10 European countries was performed, and the relationship between country nutritional status and epidemiological COVID-19 data (available in the Worldometers database) was evaluated following an ecological study design. Furthermore, the potential effect of genetics was considered through the selection of genetic variants previously identified in Genome-Wide Association studies (GWAs) as influencing the nutritional status of these 10 considered nutrients. Therefore, access to genetic information in accessible databases (1000genomes, by Ensembl) of individuals from European populations enabled an approximation that countries might present a greater risk of suboptimal status of the nutrients studied. Results from the review approach show the importance of maintaining a correct nutritional status of these 10 nutrients analyzed for the health of the immune system, highlighting the importance of Vitamin D and iron in the context of COVID-19. Besides, the ecological study demonstrates that intake levels of relevant micronutrients-especially Vitamins D, C, B12, and iron-are inversely associated with higher COVID-19 incidence and/or mortality, particularly in populations genetically predisposed to show lower micronutrient status. In conclusion, nutrigenetic data provided by joint assessment of 10 essential nutrients for the functioning of the immune system and of the genetic factors that can limit their bioavailability can be a fundamental tool to help strengthen the immune system of individuals and prepare populations to fight against infectious diseases such as COVID-19.

Increased Risk of High Body Fat and Altered Lipid Metabolism Associated to Suboptimal Consumption of Vitamin A Is Modulated by Genetic Variants rs5888 (SCARB1), rs1800629 (UCP1) and rs659366 (UCP2).

Obesity is characterized by an excessive body fat percentage (BF%). Animal and cell studies have shown benefits of vitamin A (VA) on BF% and lipid metabolism, but it is still controversial in humans. Furthermore, although some genetic variants may explain heterogeneity in VA plasma levels, their role in VA metabolic response is still scarcely characterized. This study was designed as a combination of an observational study involving 158 male subjects followed by a study with a well-balanced genotype-phenotype protocol, including in the design an ex vivo intervention study performed on isolated peripheral blood mononuclear cells (PBMCs) of the 41 former males. This is a strategy to accurately identify the delivery of Precision Nutrition recommendations to targeted subjects. The study assesses the influence of rs5888 (SCARB1), rs659366 (UCP2), and rs1800629 (UCP1) variants on higher BF% associated with suboptimal VA consumption and underlines the cellular mechanisms involved by analyzing basal and retinoic acid (RA) response on PBMC gene expression. Data show that male carriers with the major allele combinations and following suboptimal-VA diet show higher BF% (adjusted ANOVA test p-value = 0.006). Genotype-BF% interaction is observed on oxidative/inflammatory gene expression and also influences lipid related gene expression in response to RA. Data indicate that under suboptimal consumption of VA, carriers of VA responsive variants and with high-BF% show a gene expression profile consistent with an impaired basal metabolic state. The results show the relevance of consuming VA within the required amounts, its impact on metabolism and energy balance, and consequently, on men's adiposity with a clear influence of genetic variants SCARB1, UCP2 and UCP1.

Carotenoids and carotenoid conversion products in adipose tissue biology and obesity: Pre-clinical and human studies.

Antiobesity activities of carotenoids and carotenoid conversion products (CCPs) have been demonstrated in pre-clinical studies, and mechanisms behind have begun to be unveiled, thus suggesting these compounds may help obesity prevention and management. The antiobesity action of carotenoids and CCPs can be traced to effects in multiple tissues, notably the adipose tissues. Key aspects of the biology of adipose tissues appear to be affected by carotenoid and CCPs, including adipogenesis, metabolic capacities for energy storage, release and inefficient oxidation, secretory function, and modulation of oxidative stress and inflammatory pathways. Here, we review the connections of carotenoids and CCPs with adipose tissue biology and obesity as revealed by cell and animal intervention studies, studies addressing the role of endogenous retinoid metabolism, and human epidemiological and intervention studies. We also consider human genetic variability influencing carotenoid and vitamin A metabolism, particularly in adipose tissues, as a potentially relevant aspect towards personalization of dietary recommendations to prevent or manage obesity and optimize metabolic health. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome.

Omega-3 rich diets have been shown to improve inflammatory status. However, in an ex vivo system of human blood cells, the efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulating lipid metabolism and cytokine response is attenuated in overweight subjects and shows high inter-individual variability. This suggests that obesity may be exerting a synergistic effect with genetic background disturbing the anti-inflammatory potential of omega-3 long-chain polyunsaturated fatty acids (PUFA). In the present work, a genetic score aiming to explore the risk associated to low grade inflammation and obesity (LGI-Ob) has been elaborated and assessed as a tool to contribute to discern population at risk for metabolic syndrome. Pro-inflammatory gene expression and cytokine production as a response to omega-3 were associated with LGI-Ob score; and lower anti-inflammatory effect of PUFA was observed in subjects with a high genetic score. Furthermore, overweight/obese individuals showed positive correlation of both plasma C-Reactive Protein and triglyceride/HDLc-index with LGI-Ob; and high LGI-Ob score was associated with greater hypertension (p = 0.047), Type 2 diabetes (p = 0.026), and metabolic risk (p = 0.021). The study shows that genetic variation can influence inflammation and omega-3 response, and that the LGI-Ob score could be a useful tool to classify subjects at inflammatory risk and more prone to suffer metabolic syndrome and associated metabolic disturbances.

Vitamin E Metabolic Effects and Genetic Variants: A Challenge for Precision Nutrition in Obesity and Associated Disturbances.

Vitamin E (VE) has a recognized leading role as a contributor to the protection of cell constituents from oxidative damage. However, evidence suggests that the health benefits of VE go far beyond that of an antioxidant acting in lipophilic environments. In humans, VE is channeled toward pathways dealing with lipoproteins and cholesterol, underlining its relevance in lipid handling and metabolism. In this context, both VE intake and status may be relevant in physiopathological conditions associated with disturbances in lipid metabolism or concomitant with oxidative stress, such as obesity. However, dietary reference values for VE in obese populations have not yet been defined, and VE supplementation trials show contradictory results. Therefore, a better understanding of the role of genetic variants in genes involved in VE metabolism may be crucial to exert dietary recommendations with a higher degree of precision. In particular, genetic variability should be taken into account in targets concerning VE bioavailability per se or concomitant with impaired lipoprotein transport. Genetic variants associated with impaired VE liver balance, and the handling/resolution of oxidative stress might also be relevant, but the core information that exists at present is insufficient to deliver precise recommendations.

Optimal Routing for Time-Driven EH-WSN under Regular Energy Sources.

The recent provision of energy-harvesting capabilities to wireless sensor networks (WSN) has entailed the redefinition of design objectives. Specifically, the traditional goal of maximizing network lifetime has been replaced by optimizing network performance, namely delay and throughput. The present paper contributes to this reformulation by considering the routing problem for the class of time-driven energy-harvesting WSN (EH-WSN) under regular or quasi-periodic energy sources. In particular, this paper shows that the minimum hop count (MHC) criterion maximizes the average duty cycle that can be sustained by nodes in this type of scenarios. This is a primary objective in EH-WSN, since large duty cycles lead to enhanced performance. Based on a previous result, a general expression is first obtained that gives mathematical form to the relationship between duty cycle and traffic load for any node in a time-driven EH-WSN fed by a regular energy source. This expression reveals that the duty cycle achievable by a node decreases as its traffic load increases. Then, it is shown that MHC minimizes the average traffic load over the network, and thus it maximizes the average duty cycle of nodes. This result is numerically validated via simulation by comparison with other well-known routing strategies. Accordingly, this paper suggests assigning top priority to the MHC criterion in the development of routing protocols for time-driven EH-WSN under regular energy sources.

Analytical Model for the Duty Cycle in Solar-Based EH-WSN for Environmental Monitoring.

A technology drift is currently taking place from traditional battery-powered sensor networks, which exhibit limited lifetime, to the new Energy-Harvesting Wireless Sensor Networks (EH-WSN), which open the way towards self-sustained operation. However, this emergent modality also brings up new challenges, especially due to the time-varying nature and unpredictability of ambient energy sources. Most proposals for implementing EH-WSN rely on heuristic approaches to redesign the duty-cycling mechanism at the MAC layer, with the ultimate goal of optimizing network performance while preserving self-sustained and continuous operation. In contrast to the common system-wide reduced duty cycle of battery-powered sensor networks, the duty cycle in EH-WSN is much larger and adapted to the energy harvesting rate and traffic load of each node in the network. In this paper, we focus on solar-based EH-WSN devoted to environmental monitoring. In contrast to current works, we follow an analytical approach, which results into closed-form expressions for the duty cycle and initial energy storage that guarantee self-sustained operation to any node in a solar-based EH-WSN. To center the analysis, we consider TinyOS sensor nodes, though we postulate that the essential components of the obtained formulation will contribute to further develop duty cycle adaptation schemes for TinyOS and other software platforms.

Nanoscale communication with molecular arrays in nanonetworks.

Molecular communication is a promising nanoscale communication paradigm that enables nanomachines to exchange information by using molecules as communication carrier. Up to now, the molecular communication channel between a transmitter nanomachine (TN) and a receiver nanomachine (RN) has been modeled as either concentration channel or timing channel. However, these channel models necessitate exact time synchronization of the nanomachines and provide a relatively low communication bandwidth. In this paper, the Molecular ARray-based COmmunication (MARCO) scheme is proposed, in which the transmission order of different molecules is used to convey molecular information without any need for time synchronization. The MARCO channel model is first theoretically derived, and the intersymbol interference and error probabilities are obtained. Based on the error probability, achievable communication rates are analytically obtained. Numerical results and performance comparisons reveal that MARCO provides significantly higher communication rate, i.e., on the scale of 100 Kbps, than the previously proposed molecular communication models without any need for synchronization. More specifically, MARCO can provide more than 250 Kbps of molecular communication rate if intersymbol time and internode distance are set to 2 µs and 2 nm, respectively.