Optimizing tomato waste hydrolysate for enhanced fucoxanthin biosynthesis in mixotrophic cultivation of Isochrysis galbana.

Vegetable waste, rich in bioactive compounds, offers a promising resource for producing value-added products. This study explored the use of tomato waste, containing glucose (40 mg/g), lycopene (95.12 µg/g), and ß-carotene (24.31 µg/g), for cultivating fucoxanthin-rich Isochrysis galbana. Water-soluble lycopene (2.0 µg/mL) and ß-carotene (0.4 µg/mL) effectively upregulated key carotenoid synthesis genes and boosted cell growth and fucoxanthin production (3.64 and 3.60 pg/cell, respectively) within 10 days in a mixotrophic culture. Optimized tomato waste hydrolysate achieved a high cell density of 1.21 × 107 cells/mL, 2.13 g/L biomass, and 21.02 mg/g fucoxanthin. This study highlights the potential of combining tomato waste with microalgae for a novel and innovative approach towards waste management and resource utilization.

Mapping QTLs with additive and epistatic effects for awn length and their effects on kernel-related traits in common wheat.

Introduction: Wheat awns are crucial determinants of wheat yield due to their capacity to photosynthesize and exchange gas. Understanding the genetic basis of awn length (AL) is essential for improving wheat yield in molecular breeding programs. Methods: In this study, quantitative trait loci (QTLs) of AL were analyzed using recombinant inbred line (RIL) mapping population referred to as YY-RILs, which was derived from a cross between Yannong 15 (YN15) and Yannong 1212 (YN1212). Results and discussion: Seven putative additive QTLs and 30 pairwise epistatic QTLs for AL were identified. Among them, five novel additive QTLs (except qAl-2A and qAl-5A.2) and 30 novel pairwise epistatic QTLs were identified. qAl-5A.1 was repeatedly identified in all five environment datasets, which was considered to be one novel stable QTL for AL with minor additive effects. eqAl-2B.2-2 significantly interacted with eight loci and could be of great importance in regulating awn development. The genes associated with the major stable QTL of qAl-5A.2 and the minor stable QTL of qAl-2A were B1 and WFZP-A, respectively. Awn lengths exhibited significant genetic correlations with kernel weight and kernels per spike, which could affect grain protein content to a lesser extent. This study enhances our understanding of the genetic basis of awn development and identifies novel genes as well as markers for future genetic improvement of wheat yield.

Deciphering the roles of attached and suspended sludges in simultaneous nitrogen and phosphorus removal in an IFAS system based on metagenomic analysis.

Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO3--N reduction, endogenous NO3--N reduction, and endogenous NO2--N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance.

EMS-induced missense mutation in TaCHLI-7D affects leaf color and yield-related traits in wheat.

KEY MESSAGE: Mutations in TaCHLI impact chlorophyll levels and yield-related traits in wheat. Natural variations in TaCHLI-7A/B influence plant productivity, offering potential for molecular breeding. Chlorophyll is essential for plant growth and productivity. The CHLI subunit of the magnesium chelatase protein plays a key role inserting magnesium into protoporphyrin IX during chlorophyll biosynthesis. Here, we identify a novel wheat mutant chlorophyll (chl) that exhibits yellow-green leaves, reduced chlorophyll levels, and increased carotenoid content, leading to an overall decline in yield-related traits. Map-based cloning reveals that the chl phenotype is caused by a point mutation (Asp186Asn) in the TaCHLI-7D gene, which encodes subunit I of magnesium chelatase. Furthermore, the three TaCHLI mutants: chl-7b-1 (Pro82Ser), chl-7b-2 (Ala291Thr), and chl-7d-1 (Gly357Glu), also showed significant reductions in chlorophyll content and yield-related traits. However, TaCHLI-7D overexpression in rice significantly decreased thousand kernel weight, yield per plant, and germination. Additionally, natural variations in TaCHLI-7A/B are significantly associated with flag leaf, spike exsertion length, and yield per plant. Notably, the favorable haplotype, TaCHLI-7B-HapII, which displayed higher thousand kernel weight and yield per plant, is positively selected in wheat breeding. Our study provides insights on the regulatory molecular mechanisms underpinning leaf color and chlorophyll biosynthesis, and highlights TaCHLI functions, which provide useful molecular markers and genetic resources for wheat breeding.

Nutritional Value and Productivity Potential of the Marine Microalgae Nitzschia laevis, Phaeodactylum tricornutum and Isochrysis galbana.

Microalgae are considered promising sustainable feedstocks for the production of food, food additives, feeds, chemicals and various high-value products. Marine microalgae Phaeodactylum tricornutum, Isochrysis galbana and Nitzschia laevis are rich in fucoxanthin, which is effective for weight loss and metabolic diseases. The selection of microalgae species with outstanding nutritional profiles is fundamental for novel foods development, and the nutritional value of P. tricornutum, I. galbana and N. laevis are not yet fully understood. Hence, this study investigates and analyzes the nutritional components of the microalgae by chromatography and mass spectrometry, to explore their nutritional and industrial application potential. The results indicate that the three microalgae possess high nutritional value. Among them, P. tricornutum shows significantly higher levels of proteins (43.29%) and amino acids, while I. galbana has the highest content of carbohydrates (25.40%) and lipids (10.95%). Notwithstanding that P. tricornutum and I. galbana have higher fucoxanthin contents, N. laevis achieves the highest fucoxanthin productivity (6.21 mg/L/day) and polyunsaturated fatty acids (PUFAs) productivity (26.13 mg/L/day) because of the competitive cell density (2.89 g/L) and the advantageous specific growth rate (0.42/day). Thus, compared with P. tricornutum and I. galbana, N. laevis is a more promising candidate for co-production of fucoxanthin and PUFAs.

Tannic Acid-Based Self-Assembling Nanocarriers with Antiphotobleaching and Controlled Releasing Properties for Collaborative Near-Infrared Photothermal/Photodynamic Therapy.

Near-infrared (NIR) organic materials have been widely developed for tumor phototherapy due to their deep tumor penetration, good biodegradability, and high photothermal conversion (PCE). However, most of the NIR organic dyes are easily destroyed by photooxidation due to their big and long conjugated structures, such as cyanine dyes. Under light irradiation, the reactive oxygen species (ROS) produced by these NIR dyes can easily break their conjugated skeleton, resulting in a dramatic decrease in phototherapeutic efficiency. Herein, an NIR organic dye cyanine dye (CyS) and a photosensitizer methylene blue (MB) were chosen to prepare nanocarrier CMTNPs by facile self-assembling with a natural antioxidant, tannic acid (TA). TA can greatly enhance the stability of NIR cyanine dyes by scavenging ROS. Furthermore, CMTNPs have a character of pH/thermal dual response, allowing for controlled release of MB in the slightly acidic tumor environment during photothermal therapy. The released MB can turn on both fluorescence and photodynamic therapy effects. In vitro and in vivo experiments demonstrated the remarkable tumor ablation ability of CMTNPs. Thus, our study provided an antiphotobleaching and controlled release photosensitizer strategy through the introduction of antioxidant TA into the nanocarrier for efficient collaborative photothermal/photodynamic therapy.

Structurally diverse ent-clerodanoids from the aerial parts of Isodon scoparius.

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans.

Silvaticusins A-D: ent-kaurane diterpenoids and a cyclobutane-containing ent-kaurane dimer from Isodon silvaticus.

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 µM.

An Innovative Virtual Reality System for Measuring Refractive Error.

In this study, we aimed to validate a novel light field virtual reality (LFVR) system for estimating refractive errors in the human eye. Fifty participants with an average age of 22.12 ± 2.2 years (range 20-30 years) were enrolled. The present study compared spherical equivalent (SE) and focal line measurements (F1 and F2) obtained by the LFVR system with those obtained by established methods, including closed-field and open-field autorefractors, retinoscopy, and subjective refraction. The results showed substantial agreement between the LFVR system and the traditional methods, with intraclass correlation coefficients (ICC) for SE ranging from 82.7% to 86.7% (p < 0.01), and for F1 and F2 from 80.7% to 86.4% (p < 0.01). Intra-repeatability for F1 and F2 demonstrated strong agreement, with ICC values of 88.8% and 97.5%, respectively. These findings suggest that the LFVR system holds potential as a primary tool for refractive error measurement in optical care, offering high agreement and repeatability compared to conventional methods.

Microalgal metabolic engineering facilitates precision nutrition and dietary regulation.

Microalgae have gained considerable attention as promising candidates for precision nutrition and dietary regulation due to their versatile metabolic capabilities. This review innovatively applies system metabolic engineering to utilize microalgae for precision nutrition and sustainable diets, encompassing the construction of microalgal cell factories, cell cultivation and practical application of microalgae. Manipulating the metabolic pathways and key metabolites of microalgae through multi-omics analysis and employing advanced metabolic engineering strategies, including ZFNs, TALENs, and the CRISPR/Cas system, enhances the production of valuable bioactive compounds, such as omega-3 fatty acids, antioxidants, and essential amino acids. This work begins by providing an overview of the metabolic diversity of microalgae and their ability to thrive in diverse environmental conditions. It then delves into the principles and strategies of metabolic engineering, emphasizing the genetic modifications employed to optimize microalgal strains for enhanced nutritional content. Enhancing PSY, BKT, and CHYB benefits carotenoid synthesis, whereas boosting ACCase, fatty acid desaturases, and elongases promotes polyunsaturated fatty acid production. Here, advancements in synthetic biology, evolutionary biology and machine learning are discussed, offering insights into the precision and efficiency of metabolic pathway manipulation. Also, this review highlights the potential impact of microalgal precision nutrition on human health and aquaculture. The optimized microalgal strains could serve as sustainable and cost-effective sources of nutrition for both human consumption and aquaculture feed, addressing the growing demand for functional foods and environmentally friendly feed alternatives. The tailored microalgal strains are anticipated to play a crucial role in meeting the nutritional needs of diverse populations and contributing to sustainable food production systems.

A modified arthroscopic en masse suture bridge repair is effective for delaminated rotator cuff tears.

PURPOSE: This study aimed to clarify the characteristics of delaminated rotator cuff tears (RCTs) and evaluate the clinical outcomes of a modified arthroscopic en masse suture bridge repair for delaminated RCTs. METHODS: Patients with full-thickness RCTs, who underwent arthroscopic suture bridge repair with a minimum 2-year follow-up, were retrospectively reviewed. Patients were categorized into two groups based on the presence of delamination. Delaminated RCTs were treated using a modified en masse suture bridge technique, while nondelaminated RCTs received a conventional suture bridge technique. Preoperative and postoperative Constant scores and American Shoulder and Elbow Surgeons (ASES) scores were determined to evaluate clinical outcomes. Postoperative magnetic resonance imaging (MRI) was carried out to identify the integrity and retear of the repaired rotator cuff. RESULTS: A total of 172 patients were included in our study cohort, in which 67 (39%) delaminated RCTs were confirmed intraoperatively. The prevalence of delamination was significantly higher in large tears (53/102, 52%) compared to medium tears (14/70, 20%) (p < 0.001). No significant differences in age (n.s.) or gender (n.s.) were observed between the two groups. Both groups showed significant improvements in Constant and ASES scores postoperatively (both p < 0.001), with no significant differences between the groups (n.s.). The retear rates were 2/67 (3.0%) in the delamination group and 3/105 (2.9%) in the nondelamination group, showing no significant difference (n.s.). CONCLUSIONS: The modified arthroscopic en masse suture bridge technique was effective for repairing delaminated RCTs, yielding favourable clinical outcomes comparable to those of nondelaminated tears. LEVEL OF EVIDENCE: Level IV.

Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the Ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss in vivo remains unknown. Here, we show that male and female global heterozygous knockout (Rreb1 +/-) mice have reduced body length, weight, and fat mass on high-fat diet. Rreb1+/- mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated with Rreb1 +/- mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.

The value of synthetic magnetic resonance imaging in the diagnosis and assessment of prostate cancer aggressiveness.

Background: Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA). Methods: We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples). Results: The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001). Conclusions: Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy.

Mendelian randomization did not support the causal effect of diabetes on aortic diseases.

Observational studies revealed paradoxically inverse associations between diabetes and aortic diseases (aortic aneurysm or aortic dissection), yet the causality remains to be determined. To investigate the causal associations between diabetes and aortic diseases using Mendelian randomization (MR) analyses. Summary-level data for exposures (type 1 diabetes, type 2 diabetes, fasting glucose, fasting insulin, glycated hemoglobin) and outcomes (aortic dissection and aortic aneurysm) were obtained from public genome-wide association study data. The principal analysis was the inverse-variance weighted (IVW) method. Sensitivity analyses were also carried out, including weighted median, MR-Egger, and multivariable MR methods. According to IVW results, type 1 diabetes (odds ratio [OR]: 0.99; 95% confidence interval [CI] 0.93-1.07; P = 0.87), type 2 diabetes (OR: 0.97; 95% CI 0.77-1.20; P = 0.75), fasting glucose (OR: 1.16; 95% CI 0.48-2.84; P = 0.74), fasting insulin (OR: 2.75; 95% CI 0.53-14.26; P = 0.23), or glycated hemoglobin (OR: 0.33; 95% CI 0.09-1.17; P = 0.09) had no causal effect on aortic dissection. Similarly, type 1 diabetes, type 2 diabetes, fasting glucose, fasting insulin, or glycated hemoglobin had no causal effect on aortic aneurysm. Sensitivity analyses revealed consistent results. MR-Egger method and funnel plot yielded no indication of directional pleiotropy. Diabetes had no causal associations with aortic dissection or aortic aneurysm. The observed inverse associations in previous cohort studies may be explained by confounding factors or reverse causation.

Optically Tunable Many-Body Exciton-Phonon Quantum Interference.

This study introduces a novel paradigm for achieving widely tunable many-body Fano quantum interference in low-dimensional semiconducting nanostructures, beyond the conventional requirement of closely matched energy levels between discrete and continuum states observed in atomic Fano systems. Leveraging Floquet engineering, the remarkable tunability of Fano lineshapes is demonstrated, even when the original discrete and continuum states are separated by over 1 eV. Specifically, by controlling the quantum pathways of discrete phonon Raman scattering using femtosecond laser pulses, the Raman intermediate states across the excitonic Floquet band are tuned. This manipulation yields continuous transitions of Fano lineshapes from antiresonance to dispersive and to symmetric Lorentzian profiles, accompanied by significant variations in Fano parameter q and Raman intensity spanning 2 orders of magnitude. A subtle shift in the excitonic Floquet resonance is further shown, achieved by controlling the intensity of the femtosecond laser, which profoundly modifies quantum interference strength from destructive to constructive interference. The study reveals the crucial roles of Floquet engineering in coherent light-matter interactions and opens up new avenues for coherent control of Fano quantum interference over a broad energy spectrum in low-dimensional semiconducting nanostructures.

Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice.

Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1ß expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis.

HumanIslets: An integrated platform for human islet data access and analysis.

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca2+-ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

An investigation of association between human milk mineral patterns and infant growth.

Introduction: Human milk is widely acknowledged as the optimal food for infant aged 0 ~ 6 months. While there has been extensive documentation on the mineral and trace element composition of human milk, results on the relationship between mineral content and infant growth remain mixed. This cross-sectional study aims to explore human milk mineral patterns and to investigate associations between human milk mineral patterns, human milk metabolomic profile and infant growth. Methods: A total of 200 breast milk samples from seven cities in China was included. Human milk mineral and trace elements was detected by inductively coupled plasma mass spectrometer (ICP-MS). K-means cluster analysis was utilized to derived human milk mineral patterns. Untargeted human milk metabolomic profiles was determined using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differences of infant growth rate and metabolomic profiles were then compared across patterns identified. Results: Three human milk mineral patterns were identified. Cluster I was characterized as the highest levels of potassium, magnesium and calcium, while the lowest levels of copper, zinc, manganese and selenium. Cluster II showed the most abundant sodium, iron, zinc, manganese and selenium. Cluster III had the lowest levels of sodium, potassium, magnesium, iron and calcium. Infants of cluster I showed significantly higher length-for-age z score (0.60 ± 2.03, p = 0.03). Compared with other clusters, samples of cluster I showed lower expression of metabolites of arachidonic acid (ARA) and nicotinate and nicotinamide metabolism pathway. Discussion: A human milk mineral pattern was identified which is related to increased infant growth rate and altered metabolic signature. Future work is needed to understand these human milk patterns in terms of biologic mechanisms and generalization to other populations.

Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.

Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors' islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors' islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein-potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.