Cohort profile of an early life observational cohort in China: Bone and MicroBiOme onset (BAMBOO) study.

PURPOSE: The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process. PARTICIPANTS: The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively. FINDINGS TO DATE: The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study. FUTURE PLANS: Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process. TRIAL REGISTRATION NUMBER: ChiCTR2100049972.

Transcriptome Analysis on the Quality of Epimedium koreanum in Different Soil Moisture Conditions at Harvesting Stage.

Epimedium koreanum is a traditional Chinese tonic herb. Its main medicinal components are secondary metabolites such as flavonoids and flavonol glycosides, but the biosynthetic mechanism is still unclear. Moisture conditions are a key environmental factor affecting E. koreanum medicinal components during harvesting. Different stages of E. koreanum under natural conditions after rainfall were selected to study changes in physiological properties, herb quality, and transcriptome. Malondialdehyde (MDA) content increased significantly in the D3 stage after rainfall, and protective enzyme levels also rose. Additionally, the flavonol glycoside content was relatively high. We sequenced the transcriptomes of D1, D3, and D9 (R) and identified differentially expressed genes (DEGs) related to flavonoid synthesis. This analysis allowed us to predict the roadmap and key genes involved in flavonoid biosynthesis for E. koreanum. These results suggest that the E. koreanum quality can be enhanced by natural drought conditions in the soil after precipitation during harvest. The harvesting period of E. koreanum is optimal when soil moisture naturally dries to a relative water content of 26% after precipitation. These conditions help E. koreanum tolerate a certain level of water scarcity, resulting in increased expression of flavonoid-related genes and ultimately enhancing the quality of the herb.

Insight into the potential mechanism of bicarbonate assimilation promoted by mixotrophic in CO2 absorption and microalgae conversion system.

CO2 absorption-microalgae conversion (CAMC) system is a promising carbon capture and utilization technology. However, the use of HCO3- as a carbon source often led to a slower growth rate of microalgae, which also limited the application of CAMC system. In this study, the assimilation efficiency of HCO3- in CAMC system was improved through mixotrophic, and the potential mechanism was investigated. The HCO3- assimilation efficiency and biomass under mixotrophic were 34.79% and 31.76% higher than that of control. Mixotrophic increased chlorophyll and phycocyanin content, which were beneficial to capture more light energy. The content of ATP and NADPH reached 566.86 µmol/gprot and 672.86 nmol/mgprot, which increased by 31.83% and 27.67% compared to autotrophic. The activity of carbonic anhydrase and Rubisco increased by 18.52% and 22.08%, respectively. Transcriptome showed that genes related to photosynthetic and respiratory electron transport were up-regulated. The synergy of photophosphorylation and oxidative phosphorylation greatly improved energy metabolism efficiency, thus accelerating the assimilation of HCO3-. These results revealed a potential mechanism of promoting the HCO3- assimilation under mixotrophic, it also provided a guidance for using CAMC system to serve carbon neutrality.

Modeling early treatment response in AML from cell-free tumor DNA.

Monitoring disease response after intensive chemotherapy for acute myeloid leukemia (AML) currently requires invasive bone marrow biopsies, imposing a significant burden on patients. In contrast, cell-free tumor DNA (ctDNA) in peripheral blood, carrying tumor-specific mutations, offers a less-invasive assessment of residual disease. However, the relationship between ctDNA levels and bone marrow blast kinetics remains unclear. We explored this in 10 AML patients with NPM1 and IDH2 mutations undergoing initial chemotherapy. Comparison of mathematical mixed-effect models showed that (1) inclusion of blast cell death in the bone marrow, (2) transition of ctDNA to peripheral blood, and (3) ctDNA decay in peripheral blood describes kinetics of blast cells and ctDNA best. The fitted model allows prediction of residual bone marrow blast content from ctDNA, and its scaling factor, representing clonal heterogeneity, correlates with relapse risk. Our study provides precise insights into blast and ctDNA kinetics, offering novel avenues for AML disease monitoring.

pyPESTO: a modular and scalable tool for parameter estimation for dynamic models.

SUMMARY: Mechanistic models are important tools to describe and understand biological processes. However, they typically rely on unknown parameters, the estimation of which can be challenging for large and complex systems. pyPESTO is a modular framework for systematic parameter estimation, with scalable algorithms for optimization and uncertainty quantification. While tailored to ordinary differential equation problems, pyPESTO is broadly applicable to black-box parameter estimation problems. Besides own implementations, it provides a unified interface to various popular simulation and inference methods. AVAILABILITY AND IMPLEMENTATION: pyPESTO is implemented in Python, open-source under a 3-Clause BSD license. Code and documentation are available on GitHub (https://github.com/icb-dcm/pypesto).

Corrigendum: Micronutrient intake inadequacies in different types of milk consumers in Indonesian children 1-5 years: dietary modeling with young child milk improved nutrient intakes.

[This corrects the article DOI: 10.3389/fnut.2023.1169904.].

Micronutrient intake inadequacies in different types of milk consumers in Indonesian children 1­5 years: dietary modeling with young child milk improved nutrient intakes

Background: Indonesian children under-five have a high prevalence of micronutrient deficiencies. Improving young child feeding practices may be the solution. Increasing the consumption of appropriate milk products could help to reduce nutrient inadequacy. Methods: The objective of this study was to assess nutrient inadequacy in Indonesian children to evaluate the potential improvement using dietary modeling analysis. Data from children aged 1-5 years from the Indonesian Individual Dietary Consumption Survey in 2014 were used in this analysis (n = 11,020). Diet modeling was conducted in two scenarios, substitution volume to volume and calories to calories. Results: The proportion of children consuming young child milk (YCM) was the highest compared to other milk types across all age groups, followed by condensed milk and cow's milk. YCM, also called "Growing-Up Milk" (GUM), are marketed as a product specifically formulated for the nutritional needs of young children. YCM consumers had lower prevalence of inadequate intakes in iron, zinc, vitamins A, C and D across age groups when compared to condensed milk consumers. The prevalence of inadequate intakes of nutrients in condensed milk consumers was Vitamin A (67, 64%), folate (92, 91%), Vitamin D (87, 84%), iron (84, 76%), and zinc (76, 76%) in 1-2y and 3-4y, respectively. The substitution of condensed milk with a YCM reduced the prevalence of inadequate intakes of micronutrients, such as Vitamin A, vitamin D, folate, iron and zinc, which are important for immune function. YCM reduced the prevalence of inadequate intakes of micronutrients by 20-40% (Vit A and folate) and 40-50% (Vit D and zinc). The reduction of prevalence of inadequate iron intake was 31% in 1-2y and 63% in 3-4y. Conclusion: The prevalence of inadequate micronutrient intakes was high among children aged 1-5 years old in Indonesia. YCM consumers had better nutrient intake. The substitution of condensed milk with a YCM reduced the prevalence of inadequate of micronutrient intake. Thus, nutrient intakes could be improved by YCM consumption in 1-5 years old children in Indonesia, along with nutrition education on feeding practices.

Progressive disruption of hematopoietic architecture from clonal hematopoiesis to MDS.

Clonal hematopoiesis of indeterminate potential (CHIP) describes the age-related acquisition of somatic mutations in hematopoietic stem/progenitor cells (HSPC) leading to clonal blood cell expansion. Although CHIP mutations drive myeloid malignancies like myelodysplastic syndromes (MDS) it is unknown if clonal expansion is attributable to changes in cell type kinetics, or involves reorganization of the hematopoietic hierarchy. Using computational modeling we analyzed differentiation and proliferation kinetics of cultured hematopoietic stem cells (HSC) from 8 healthy individuals, 7 CHIP, and 10 MDS patients. While the standard hematopoietic hierarchy explained HSPC kinetics in healthy samples, 57% of CHIP and 70% of MDS samples were best described with alternative hierarchies. Deregulated kinetics were found at various HSPC compartments with high inter-individual heterogeneity in CHIP and MDS, while altered HSC rates were most relevant in MDS. Quantifying kinetic heterogeneity in detail, we show that reorganization of the HSPC compartment is already detectable in the premalignant CHIP state.

An Open-Access Data Platform: Global Nutrition and Health Atlas (GNHA).

The rapid development of nutrition science is embracing digital transformation to generate large amounts of data. Precision nutrition and "Big Data" place increasing demand for data repositories and visualization, which enhances the digital transformation. We defined the need for an integrated nutrition data platform as a web-based platform that can collect, store, track, analyze, monitor, and visually display key metrics in nutrition and health while allowing users to interact with visuals and download data provided in the platform. Interactive dashboards create new opportunities for scholars and practitioners to generate and test hypotheses. We present the development and implementation of the Global Nutrition and Health Atlas (GNHA; https://sites.tufts.edu/gnha/), an open-access online platform covering nutrition and health data with 26 themes and 500+ indicators from 190+ countries up to 30 y. We view GNHA as an interactive tool aiming to share information and perspectives and foster collaborations and innovations.

Food and Nutrition Systems Dashboards: A Systematic Review.

The rapid expansion of food and nutrition information requires new ways of data sharing and dissemination. Interactive platforms integrating data portals and visualization dashboards have been effectively utilized to describe, monitor, and track information related to food and nutrition; however, a comprehensive evaluation of emerging interactive systems is lacking. We conducted a systematic review on publicly available dashboards using a set of 48 evaluation metrics for data integrity, completeness, granularity, visualization quality, and interactivity based on 4 major principles: evidence, efficiency, emphasis, and ethics. We evaluated 13 dashboards, summarized their characteristics, strengths, and limitations, and provided guidelines for developing nutrition dashboards. We applied mixed effects models to summarize evaluation results adjusted for interrater variability. The proposed metrics and evaluation principles help to improve data standardization and harmonization, dashboard performance and usability, broaden information and knowledge sharing among researchers, practitioners, and decision makers in the field of food and nutrition, and accelerate data literacy and communication.

Knowledge search, knowledge integration and enterprise breakthrough innovation under the characteristics of innovation ecosystem network: The empirical evidence from enterprises in Beijing-Tianjin-Hebei region.

Enterprises acquire heterogeneous knowledge through external knowledge search and adapt to the change of external environment, which is of great significance to enterprise breakthrough innovation. This paper takes the innovation ecosystem as the boundary of the research paradigm. Based on innovation ecosystem theory, knowledge management theory and enterprise innovation theory, this paper constructs a moderated mediation model of the enterprise knowledge search, knowledge integration and breakthrough innovation under the characteristics of innovation ecosystem network. This model is tested on the survey data of 344 technology enterprise and manufacturing industries including R&D departments in the Beijing-Tianjin-Hebei region. The research results show that: knowledge integration plays part of the intermediary role between knowledge search and enterprise breakthrough innovation; the larger the network scale, the stronger the network connection, the stronger the intermediary role of knowledge integration on the relationship between knowledge search and enterprise breakthrough innovation. The research results reveal the important role of the innovation ecosystem in enterprise breakthrough innovation. At the same time, the research on knowledge search and enterprise breakthrough innovation should consider the network characteristics of innovation ecosystem and the ability of enterprise knowledge integration.

Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health.

Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and 'Mother Nature' provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship.

Cell-to-cell variability in JAK2/STAT5 pathway components and cytoplasmic volumes defines survival threshold in erythroid progenitor cells.

Survival or apoptosis is a binary decision in individual cells. However, at the cell-population level, a graded increase in survival of colony-forming unit-erythroid (CFU-E) cells is observed upon stimulation with erythropoietin (Epo). To identify components of Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signal transduction that contribute to the graded population response, we extended a cell-population-level model calibrated with experimental data to study the behavior in single cells. The single-cell model shows that the high cell-to-cell variability in nuclear phosphorylated STAT5 is caused by variability in the amount of Epo receptor (EpoR):JAK2 complexes and of SHP1, as well as the extent of nuclear import because of the large variance in the cytoplasmic volume of CFU-E cells. 24-118 pSTAT5 molecules in the nucleus for 120 min are sufficient to ensure cell survival. Thus, variability in membrane-associated processes is sufficient to convert a switch-like behavior at the single-cell level to a graded population-level response.

Nutrient Intake in Children 4-13 Years Old in Ibadan, Nigeria.

The paucity of adequate data on dietary and nutrient intakes of school-age children is a barrier to addressing malnutrition and associated risks in Nigeria. This study included 955 children aged 4-13 years from Ibadan, Nigeria, using a stratified random sampling design. Information on family socio-demographic characteristics was reported, and child anthropometrics were measured. Dietary intake data were collected using a multi-pass 24 h dietary recall method; 20% of subjects completed a second 24 h recall to estimate usual nutrient intakes. Means and distributions of usual intakes of energy and nutrients as well as prevalence of inadequacy were estimated. Usual energy intake (kcal/day) was 1345 and 1590 for younger (4-8 years) and older (9-13 years) age groups, respectively. The macronutrient intakes of most children did not conform to Adequate Macronutrient Distribution Ranges (AMDRs), which were characterized by a higher proportion of energy from carbohydrates and lower proportion from total fats. Protein intake was largely within the AMDR. Compared to recommendations, over 60% of 4-8-year-old children had inadequate intakes of calcium, copper, iron, folate, and vitamins A, D, and E. There were more micronutrient inadequacies in the older children. This study identifies nutrition gaps and suggests future research and education to improve child nutrition in Nigeria.

Analysis of dietary patterns and nutritional adequacy in lactating women: a multicentre European cohort (ATLAS study).

Eating habits of lactating women can influence the nutrient composition of human milk, which in turn influences nutrient intake of breastfed infants. The aim of the present study was to identify food patterns and nutritional adequacy among lactating women in Europe. Data from a multicentre European longitudinal cohort (ATLAS study) were analysed to identify dietary patterns using cluster analysis. Dietary information from 180 lactating women was obtained using 3-d food diaries over the first 4 months of lactation. Four dietary patterns were identified: 'vege-oils', 'fish-poultry', 'confectionery-salads' and 'mixed dishes'. Nutrition adequacy was not significantly different between clusters, but the 'vege-oils' cluster tended to yield the highest nutrition adequacy measured by Mean Adequacy Ratio. Compared with European dietary reference values (DRVs) for lactating women, women in all clusters had inadequate intakes of energy, pantothenic acid, folate, vitamin C, vitamin A, vitamin D, zinc, iodine, potassium and linoleic acid. Adequate intake for fibre and α-linolenic acid was only achieved in the 'vege-oils' cluster. Overall, fat intake was above DRVs. The present study showed that various dietary patterns do not adequately supply all nutrients, indicating a need to promote overall healthy dietary habits for European lactating women.

PEtab-Interoperable specification of parameter estimation problems in systems biology.

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been-so far-no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.

Food Sources of Key Nutrients, Meal and Dietary Patterns among Children Aged 4-13 Years in Ibadan, Nigeria: Findings from the 2019 Kids Nutrition and Health Study.

This study examined the contribution of food to nutrient intake, meal and dietary patterns among children aged 4-8 and 9-13 years in the city of Ibadan, Nigeria. Multi-pass 24-hour dietary recalls were used to assess intakes. Prudent and traditional Southwestern Nigerian dietary patterns were identified among children. The top foods and beverages were defined by frequency and amount consumed. Meal patterns were described by the eating occasions, while cluster analysis probed dietary patterns. About 88% of children had at least three meals including breakfast (95%), lunch (85%), dinner (92%) and midmorning meals (48%), while about 60% ate snacks at least once daily. Sources of energy and key nutrients were limited (yam, cassava, rice, maize, bread and beans/peas/legumes). The amount consumed per consumer of cassava products (192.2, 256.0 g), yam (169.7, 256.0 g), legumes (115.3, 150.7 g), corn/maize (160.4, 195.2), and rice (138.4, 182.3 g) were high, while beef (15.2, 17.9 g), eggs (50.6, 49.2 g), fish (27.5, 30.6 g), milk (24.2, 27.0 g) and nuts and seeds (18.2, 19.7 g) were low for children ages 4-8 and 9-13 years, respectively. In conclusion, while the frequency of meals suggests a healthy pattern, the top foods could not provide adequate nutrient (especially micronutrient) intake, which is key to the development of the target population.

Patterns of the Consumption of Young Children Formula in Chinese Children Aged 1-3 Years and Implications for Nutrient Intake.

The consumption of young children formula (YCF) is associated with reduced risk of inadequacies of nutrients that are frequently lacking in the diets of young children. In this study, we assessed the role of YCF in children's diets and whether meeting dairy intake recommendations would improve nutrient intake in young Chinese children aged 12-36 months. Dietary intake data for children from the 2012 China Maternal and Infant Nutrition and Growth study were analyzed (n = 910). Nutrient intake was compared between YCF consumers and non-consumers, and the theoretical impact of meeting dairy intake recommendations by adding cow's milk or YCF to children's diets was assessed using diet modelling. The percent of children consuming YCF was 64.5% and was positively associated with family income and mother's education level. Compared to non-consumers, YCF consumers had higher intakes of minerals (e.g., calcium, iron) and vitamins (e.g., C, D, B6) that are important for growth and immune function, and lower intakes of saturated fat. To meet dairy intake recommendations by adding either cow's milk or YCF to children's diets would improve intakes of vitamins and minerals in young Chinese children. YCF consumption contributes to the improvement of nutrient intakes in children aged 12-36 months in China.

Dairy Intake Would Reduce Nutrient Gaps in Chinese Young Children Aged 3-8 Years: A Modelling Study.

Dairy foods are under-consumed among Chinese children. We modeled the impact of increased dairy consumption on nutrient inadequacy and assessed whether the consumption of formulated milk powder for children ≥3 years (FMP3+) is useful for reducing nutrient gaps. Data from 3-8-year-old children, with completed socio-demographic and dietary measurements from the China Health and Nutrition Survey 2015, were used (n = 1122). Dietary intakes were modeled in two scenarios: Scenario 1 added FMP3+ or cow's milk to reported diet to reach recommended dairy intakes; Scenario 2 replaced the currently consumed milk with an equal volume of FMP3+. Reported nutrient intakes were compared with each model. Only 32.5% of children consumed dairy products; the average intake amount in total was 48.6 g/day. Most children (97.6%) did not meet dairy intake recommendation. Inadequate nutrient intakes were observed for calcium, potassium, thiamin, riboflavin, vitamin C and selenium. In Scenario 1, both FMP3+ and cow's milk improved the intake of all analyzed nutrients. In Scenario 2, FMP3+ substitution increased the intake of most nutrients, and reduced the proportion of children with an inadequate intake of vitamin C, thiamin, vitamin A, iron, zinc and potassium. Thus, increasing dairy consumption would reduce nutrient gaps, and FMP3+ is a good food source to help children meet nutrient requirements.

Silica-Lipid Hybrid Microparticles as Efficient Vehicles for Enhanced Stability and Bioaccessibility of Curcumin.

Curcumin is an active ingredient with multiple functions, but its application is often restricted due to its poor water solubility, weak stability, and consequently low bioaccessibility. Based on this, the aim of this work is to develop a new vehicle to overcome these restrictions. Here we developed a curcumin-loaded nanoemulsion and then curcumin-loaded silica-lipid hybrid microparticles through emulsification and vacuum drying, respectively. The loading of curcumin in the nanoemulsion and microparticles was (0.30±0.02) and (0.67±0.02) %, respectively. FTIR and XRD analyses of microparticles revealed that curcumin was encapsulated in porous, amorphous silica. In vitro antioxidant activities showed that the encapsulation would not affect the antioxidant activity of curcumin. In vitro simulated digestion indicated that nanoemulsion and microparticles had higher curcumin bioaccessibility than the control group. The storage stability of microparticles remained the same during 6 weeks in the dark at 4, 25 and 40 °C. Moreover, the microparticles had a better chemical stability than nanoemulsion under the light. The cell viability was over 80% when the concentration of nanocarriers was less than 45 µg/mL. Hence, the microparticles could be a promising means to load curcumin and improve its solubility, light stability and bioaccessibility.