We first constructed functionally complementary synthetic communities (SynC) based on functional traits and phylogenetic similarity to core taxa enriched under silica nanoparticles (SiO2 NPs) treatment. Then, we evaluated their combined effects with SiO2 NPs in alleviating soybean salt stress. In a 37-day pot experiment under 200 mM NaCl, combined application reduced the shoot Na+/K+ ratio by 24.7%-33.2% compared to either treatment alone. Furthermore, the rhizosphere microbiome was markedly restructured, with an enrichment of Sphingomonas, which was identified as a major contributor to salt tolerance through ion homeostasis and niacin and nicotinamide metabolism. Notably, 5-aminovaleric acid (5-AVA) was significantly positively correlated to the abundance of Sphingomonas. Exogenous application of 5-AVA enriched Sphingomonas populations by 33.9% and enhanced soybean growth under salt stress. Our findings demonstrate that the combined application enhances soybean salt tolerance by altering the root exudate composition and enriching beneficial bacteria, providing a promising strategy for advancing sustainable agriculture under salt stress.

Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is a rare autosomal recessive neurometabolic disorder caused by pathogenic variants in NAXD, in which febrile illness or infection triggers rapid clinical deterioration. We describe nine new cases that expand the clinical and molecular spectrum. Four children showed the typical presentation of severe neurological decline following fever or illness and carried variants affecting the enzyme domain. Four cases presented with illness-triggered cardiac dysfunction associated with variants in the mitochondrial targeting sequence. One case showed severe prenatal neurodegeneration resulting in stillbirth. In two patients, disease onset followed COVID-19 infection. Functional analysis of five missense variants demonstrated impaired NAXD protein solubility, reduced NADHX dehydratase activity and/or decreased thermostability. Patient fibroblasts confirmed accumulation of damaged cofactors (S-, R- and cyclic NADHX) and reduced NAXD protein levels. Comparative proteomic analysis revealed distinct molecular profiles in atypical cardiac and prenatal cases compared with typical neurological presentations. Four patients received high-dose niacin (vitamin B3) and survived repeated febrile episodes. These findings support early recognition and suggest that niacin therapy may improve outcomes across the clinical spectrum of PEBEL2.

Yarrowia lipolytica is a food-compatible yeast with strong potential for sustainable B-vitamin enrichment of functional food ingredients. This study evaluated the effects of glucose, xylose, mixed, and lignocellulosic sugars, as well as diverse nitrogen sources, on yeast growth and B-vitamin yields in controlled fermentations. Glucose with yeast extract led to the highest biomass and intracellular accumulation of thiamine (B1), niacin (B3), and pyridoxine (B6), while mixed sugars supported maximal intracellular folate (B9) content. Intracellular B-vitamin levels were consistently higher with yeast extract than with defined nitrogen sources. Cobalamin (B12) was detected in biomass under all substrate and nitrogen conditions; based on current knowledge of Y. lipolytica metabolism and the presence of trace B12 in yeast extract, these observations are consistent with uptake and retention from the medium rather than de novo biosynthesis. Results indicate that nutrient formulation, particularly the use of renewable sugars and organic nitrogen, can be strategically tuned to generate Y. lipolytica biomass with distinct B-vitamin profiles suited to different food fortification scenarios. The demonstrated use of commercial lignocellulosic sugar streams underscores the compatibility of this process with food-grade industrial substrates and circular-economy concepts, providing a practical basis for deploying B-vitamin-enriched yeast as a functional ingredient in plant-based beverages, cereal products and other fortified foods.

B vitamins are essential water-soluble cofactors involved in metabolic regulation and neurological function. In plant-based diets, maintaining adequate B vitamin status is challenging because nutritional value depends not only on vitamin content but also on bioavailability. Although many plant foods contain substantial quantities of B vitamins, their absorption is generally lower than that from animal-derived sources due to differences in chemical form, matrix associations, and conjugation state. Thiamine and niacin often require liberation from bound forms; folates must undergo enzymatic deconjugation; vitamin B6 frequently occurs in glycosylated forms with reduced biological activity; and vitamin B12 is absent from unfortified plant foods. Bioavailability is further modulated by dietary composition, gastrointestinal conditions, and host genetic variability. Assessment approaches, such as in vitro models, cellular transport systems, and in vivo biomarkers, provide complementary but incomplete perspectives on physiological availability. Fermentation has emerged as a promising strategy to enhance B vitamin bioavailability in plant foods through microbial synthesis, matrix modification, and reduction of antinutritional factors. Applications in cereals, legumes, vegetables, and fruits demonstrate substantial improvements in vitamin content and accessibility. This chapter emphasizes the disconnect between analytical vitamin content and physiological impact and positions fermentation as a scalable approach to optimize B-vitamin nutrition in plant-based dietary patterns.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in both men and women with T1DM and T2DM. In patients with T1DM in good glycemic control, the lipid profile is very similar to the general population. In contrast, in patients with T2DM, even with good glycemic control, there are frequently lipid abnormalities (elevated TG and non-HDL-C, decreased HDL-C, and an increase in small dense LDL). In both T1DM and T2DM, poor glycemic control increases TG levels and decreases HDL-C levels with modest effects on LDL-C levels. Extensive studies have demonstrated that statins decrease ASCVD in patients with diabetes. Treatment with high doses of potent statins reduces ASCVD events to a greater extent than low dose statin therapy. Adding fibrates or niacin to statin therapy has not been shown to further decrease ASCVD events. In contrast, studies have shown that the combination of a statin and ezetimibe or a statin and a PCSK9 inhibitor result in a greater decrease in ASCVD events than statins alone. Studies have suggested that EPA, an omega-3-fatty acid, when added to statins also reduces ASCVD events but this result is controversial. In statin intolerant patients with T2DM bempedoic acid decreases ASCVD events. Current recommendations state that most patients with diabetes should be on statin therapy. In certain patients with diabetes ezetimibe, PCSK9 inhibitors, and bempedoic acid can play a role in reducing ASCVD. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

While substantial research has examined the role of infant nutrition in early brain and cognitive development, the links between later childhood nutrition, brain development, and cognitive and academic skills remain less explored. In this work, we investigated for the first time the direct and indirect associations between nutrition intake, white matter microstructure and structural connectivity, and cognitive and academic outcomes. Using longitudinal data from typically developing children aged 2 to 14 years, we combined neuroimaging, dietary, and cognitive measures to test direct associations between nutrition and brain structure and connectivity, as well as cognitive and learning outcomes, and to assess whether brain development mediated these relationships. We found that specific nutrients, including DHA, sphingomyelin, iron, niacin, choline, and palmitoleic acid (omega-7), were associated with improved brain structure and connectivity, as well as better cognitive and learning outcomes. We also found that brain development partly mediated the association between childhood nutrition and learning outcomes. To our knowledge, this is the first study to show such a pathway in school-age children. These results add to the growing literature demonstrating the ongoing importance of nutrition beyond infancy in supporting childhood brain and cognitive development.

Metabolic psychiatry has recently achieved unprecedented clinical rescue in treatment-resistant Schizophrenia (SCZ) utilizing targeted ketogenic interventions. However, the field has operated without a defined genomic anchor, leaving the biophysical mechanism of these therapies largely unexplained. Here, we report the discovery of the definitive metabolic sensor array driving this pathology. By integrating high-resolution topological mapping of SCZ GWAS summary statistics, 3D chromatin conformation (Hi-C), and multi-tissue transcriptomics, we identify massive, non-coding structural variances flanking the HCAR2/HCAR1 tandem locus-the brain's master thermodynamic governor. We demonstrate that while the protein-coding hardware of these receptors remains intact, their shared 3D Topologically Associating Domain (TAD) is fundamentally fractured. This structural collapse drives a perfect transcriptomic double dissociation in the human cortex: the 3' mutational "skyscraper" severely downregulates the HCAR1 lactate emergency brake, while the 5' mutational cluster selectively paralyzes the HCAR2 β-hydroxybutyrate (BHB) and niacin cooling switch. This dual-flank enhancer failure elegantly provides a definitive genomic etiology for historical SCZ biomarkers, physically explaining both chronic cerebrospinal fluid lactate pooling and the infamous "absent niacin flush." Furthermore, peripheral eQTL mapping reveals profound antagonistic pleiotropy, characterized by a hyper-activation of the HCAR1 lactate shuttle in the testis, explaining the evolutionary conservation of this metabolically catastrophic architecture. Ultimately, we reframe Schizophrenia not as an intrinsic neurological defect, but as an evolutionary "fuel mismatch." The high-performance cognitive architecture of the hominid brain, evolved for ancestral ketogenic environments, experiences a catastrophic thermodynamic crash when deprived of its requisite BHB coolant by modern, high-glycemic diets.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in both men and women with T1D and T2D. In this chapter we review studies that determined the effect of improving glycemic control on ASCVD in both T1D and T2D. In patients with T1D, intensive glycemic control results in a reduction in ASCVD. However, intensive glycemic control does not have a major impact in reducing ASCVD in patients with T2D. We also discuss the results of the cardiovascular outcomes studies using glucose lowering drugs. Metformin, pioglitazone, SGLT2 inhibitors, GLP-1 receptor agonists, and GLP-1/GIP dual receptor agonists have been shown to decrease cardiovascular events in patients with T2D to a greater extent than other glucose lowering drugs. Many cardiovascular risk factors in addition to glucose increase the risk of ASCVD and this chapter focuses on the important role of lipids/lipoproteins. It is widely accepted that LDL-C and non-HDL-C are causative factors for ASCVD while low HDL-C levels are associated with ASCVD. There is evidence that TG may be a causative factor for ASCVD, but randomized cardiovascular outcome studies have not definitively demonstrated a benefit of lowering TG levels. In patients with T1D in good glycemic control, the lipid profile is very similar to the general population. In contrast, in patients with T2D, even with good glycemic control, there are frequently lipid abnormalities (elevated TG and non-HDL-C, decreased HDL-C, and an increase in small dense LDL). In both T1D and T2D, poor glycemic control increases TG levels and decreases HDL-C levels with modest effects on LDL-C levels. Many glucose lowering drugs used to treat diabetes, such as bile acid sequestrants, thiazolidinediones, and GLP1 receptor agonists, alter lipid/lipoprotein levels and these effects are presented. Extensive studies have demonstrated that statins decrease ASCVD in patients with diabetes. Treatment with high doses of potent statins reduces ASCVD events to a greater extent than low dose statin therapy. Adding fibrates or niacin to statin therapy has not been shown to further decrease ASCVD events. In contrast, studies have shown that the combination of a statin and ezetimibe or a statin and a PCSK9 inhibitor result in a greater decrease in ASCVD events than statins alone. Studies have suggested that icosapent ethyl (EPA), an omega-3-fatty acid, when added to statins also reduces ASCVD events in patients with T2D. In contrast, adding EPA and DHA to statin therapy does not decrease ASCVD events. In statin intolerant patients with T2D bempedoic acid decreases ASCVD events. These outcome studies form the basis of treatment recommendations, and the 2026 American Diabetes Association, 2026 American College of Cardiology/American Heart Association, and current European Society of Cardiology/European Atherosclerosis Society guidelines are discussed. Finally, how to evaluate and treat lipids/lipoproteins in patients with diabetes to reduce the risk of ASCVD is discussed in detail.For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.