Arkansas Children's Nutrition Center

Osteocytes, the most abundant bone cells, are central regulators of bone remodeling that also exert endocrine control over systemic metabolism. Among the factors they produce, Lipocalin-2 (LCN2) has emerged as a cytokine linking bone and energy homeostasis, yet its local role within the skeleton remains elusive. Here, we identify that LCN2 promotes intracellular iron accumulation, mitochondrial dysfunction, and lipid peroxidation through its receptor SLC22A17, and drives ferroptotic cell death. Dmp1-Cre–mediated deletion of Lcn2 preserves mitochondrial integrity, reduces intracellular iron and lipid peroxidation, and enhances osteocyte dendricity and lacunocanalicular connectivity. Mechanistically, loss of Lcn2 suppresses Wnt antagonists DKK1 and SOST, thereby promoting Wnt/β-catenin signaling and stimulating osteoblast-mediated bone formation. Notably, Dmp1-Cre-mediated deletion of Lcn2 does not alter systemic energy balance, underscoring LCN2’s local skeletal function. These findings define the LCN2–SLC22A17 axis as a local regulator of osteocyte ferroptosis, Wnt/β-catenin signaling, and skeletal fragility.

Short- and medium-chain fatty acids (SCFAs/MCFAs) modulate metabolic and inflammatory pathways. This study examined associations between maternal plasma SCFAs/MCFAs in the first (T1) and third (T3) trimesters and maternal and infant metabolic–inflammatory indices, maternal energy metabolism, and infant anthropometrics and body composition at 2 weeks and 6 months postpartum. Data were retrieved from the Growing Life, Optimizing Wellness Study. SCFAs/MCFAs were derivatized with 3-NPH and quantified by LC–MS in Time-of-Flight mass spectrometry with elevated energy mode., while metabolic–inflammatory indices were computed from standardized biomarkers (e.g., cholesterol, insulin, leptin). Sample sizes included up to 231 participants at T1, 156 at T3, 80 infants at 2 weeks, and 55 at 6 months. Generalized linear models adjusted for covariates and multiple comparisons. At T3, higher butyric, caproic, propionic, isobutyric, and isovaleric acids were linked to a lower maternal metabolic–inflammatory index, whereas higher acetate-to-propionate, acetate-to-butyrate, and propionate-to-butyrate ratios were linked to a higher index. Maternal acetic acid and total SCFA/MCFA concentrations were inversely associated with respiratory exchange ratio at T1 and T3. Limited associations were observed with infant indices or body composition. Overall, third-trimester SCFAs were associated with maternal metabolic–inflammatory pathways with minimal downstream infant effects.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-39010-8.

ABSTRACTBackgroundYouth with obesity are at risk for accumulating liver fat, even below the threshold for metabolic dysfunction‐associated steatotic liver disease (MASLD), defined as ≥ 5% by MRI. While prior studies suggest that sub‐threshold liver fat may carry metabolic risk, the role of fibroblast growth factor‐21 (FGF21)—a liver‐derived hormone responsive to metabolic stress—has not been well characterised in this context.ObjectivesTo examine the association between liver fat < 5% and metabolic markers in pubertal youth with obesity, with a focus on FGF21.MethodsThis secondary cross‐sectional analysis included 58 pubertal adolescents with obesity (62% female; mean age 14.7 ± 1.7 years) and liver fat < 5% by MRI‐proton density fat fraction (PDFF). Fasting glucose, insulin, lipids, leptin, adiponectin and FGF21 were measured. Insulin sensitivity was estimated by homeostatic model assessment of insulin resistance (HOMA‐IR). Associations between PDFF and metabolic markers were analysed using Spearman correlations and multivariable regression, adjusted for age, sex, race, ethnicity and body mass index standard deviation score (BMI SDS).ResultsThe median PDFF was 2.68%. PDFF correlated positively with BMI SDS, waist circumference, glucose, triglyceride‐to‐high‐density lipoprotein cholesterol ratio (TG/HDL‐C) and FGF21. In adjusted models, PDFF remained independently associated with FGF21 (Beta = 52 pg/mL per 1% increase; p = 0.02), even after log transformation. No associations were observed with HOMA‐IR, leptin, or adiponectin.ConclusionsAmong pubertal youth with obesity and liver fat below the MASLD threshold, modest increases in PDFF were independently associated with higher FGF21. These findings support the potential utility of FGF21 as a biomarker of early hepatic‐metabolic stress in the framework of ‘pre‐MASLD’ state—similar to pre‐diabetes before the development of overt steatosis.

BackgroundThe African American population is disproportionately impacted by congestive heart failure (CHF). The impact includes a hospitalization rate that is 2.5 times higher and a hospital stay that is, on average, a quarter of a day longer compared with Caucasians. Notably, nursing care has been associated with nearly a 30% decrease in hospitalizations and readmissions. Previous studies have demonstrated that registered nurses (RNs), working in conjunction with electronic health record systems to conduct care tasks, may optimize length of stay in African Americans with CHF.ObjectiveThis study aimed to identify the needs of RNs who performed sociotechnical tasks, the perceived importance of these sociotechnical tasks, and the perceived performance of these tasks by RNs, in relation to the length of stay of their African American patients with CHF.MethodsThe study used an observational, cross-sectional survey design in RNs who were randomly selected from a total population of 3498 RNs who provided care to 22,703 African American patients with CHF within 113,543 heart failure hospitalizations between January 1, 2015, and January 1, 2024. The RNs were retrospectively stratified into 2 groups based on EHR data: those whose African American patients had a mean length of stay of 10 days or less (Group A) and those whose mean length of stay was greater than 10 days (Group B). Descriptive statistics, Cohen d, and a 2-sided unpaired t test were used to analyze the data.ResultsThe total sample of 200 RNs responded to the survey (100% survey completion rate). Group A (100 RNs) reported the least important task as drawing conclusions about how to use the EHR to care for African American patients (mean 4.66, SD 1.82). The least important task in Group B (100 RNs) was reading published research on African American patients (mean 4.88, SD 1.70). Group A reported performing best in caring for African American patients (mean 5.61, SD 1.44). Group B reported performing best at caring for all patients (mean 5.86, SD 1.04). A total of 17 significant sociotechnical needs were identified among groups. In total, 2 sociotechnical needs were unique to group B: caring for patients (ie, the full scope of social and technological processes in nursing care; Cohen d=0.32, 95% CI 0.04-0.59; P=.04) and working with information related to a patient’s CHF in the EHR (eg, laboratory results, discharge summaries, or radiographic images) to care for the patient (Cohen d=0.33, 95% CI 0.05-0.61; P=.03).ConclusionsLengths of patient stay may be reduced by identifying and addressing sociotechnical needs through targeted training, nursing care interventions, and RN-led risk stratification guidelines for working with EHRs to reduce lengths of stay in those who are disproportionately impacted by CHF.

Aging research relies on varied statistical methods, and applying these methods appropriately is important for scientific rigor. However, proper use of these statistical techniques is a challenge. We discuss two categories of statistical methods in aging research: (a) emerging methods requiring further validation, including techniques to examine compression of morbidity, maximum lifespan, immortal time bias, molecular aging clocks, and treatment response heterogeneity, and (b) classic and existing methods needing reconsideration and improvement, such as stepwise regression, generalized linear models, methods for accounting for clustering and nesting effects, methods for testing for group differences, methods for mediation and moderation analyses, and nonlinear models. For each method, we review its relevance to aging research, highlight statistical issues, and suggest improvements or alternatives with examples from aging research. We urge researchers to refine traditional approaches and embrace emerging methods tailored to the unique challenges of aging research. This review will help researchers identify and apply sound statistical methods, thereby improving statistical rigor in aging research.

This protocol describes a streamlined method for phenolic and polyphenolic extractions from plant material and subsequent preparation for analysis by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Previously optimized extraction solvents, sample disruption techniques (e.g. sonication), and the use of internal standards primarily targeted at flavonoids are covered in detail. A workflow for diluting, filtering, and otherwise preparing samples for analysis is also included. This approach enables sensitive, reproducible profiling and quantification of diverse phenolic and polyphenolic compounds across plant matrices.

Several studies have indicated the benefits of human milk feeding to infants however, mechanisms behind positive health outcomes have not been investigated. The study aimed to characterize circulating immune cell subpopulation gene expression in human milk-fed (HMF) compared with cow milk formula-fed (FF) infants using single-cell transcriptomics. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy HMF (n = 6), and FF (n = 3) infants who were 3-3.5 mo old and enrolled in a nonrandomized clinical trial. Single-cell RNA sequencing was used to generate a PBMC atlas and evaluate gene expression in immune cell subsets. Differential expression analysis was performed on each cell type independently after clustering the cells by similar marker gene expression using the scGEAToolbox. Differentially expressed genes were subjected to pathway analyses using an online functional enrichment analysis program. The relative abundance (%) of T and B lymphocytes, natural killer (NK) cells, and plasmacytoid dendritic cells were similar, whereas monocytes were higher in FF infants than in HMF infants (22.6 ± 10.7 compared with 8.3 ± 5.6; P = 0.0314). In addition, innate and adaptive immune cells from FF infants exhibited a higher activation state compared with HMF infants. We identified 16 distinct cell subsets from the major immune cell types: 3 monocyte subsets, 4 NK subsets, 2 B cell subsets, and 7 T cell subsets. Transcriptional profiles of each peripheral innate and adaptive immune cell subtype varied between HMF and FF infants. Pathway enrichment analysis of cell-specific transcriptional changes within subsets of major cell types revealed that the interleukin (IL)-4/IL-13 signaling pathways were upregulated in FF infants relative to HMF infants. These findings suggest that human milk downregulates peripheral immune cell cytokine transcriptional signatures linked to allergic inflammation and infection relative to formula feeding.