PubMed

Food Sci Nutr. 2026 May 3;14(5):e71857. doi: 10.1002/fsn3.71857. eCollection 2026 May.ABSTRACTPulmonary fibrosis (PF) is an irreversible chronic lung disease in which dysregulation of tissue repair leads to excessive deposition of extracellular matrix (ECM). Rosa roxburghii Tratt (RRT), which has anti-inflammatory and antioxidant properties, exhibits the potential to attenuate organ fibrosis. In this study, we evaluated the bioactive content and antioxidant capacity of different polar extracts of RRT (RRTEs), and explored the multi-target mechanism of the optimal extract in alleviating PF. The ethyl acetate extract of RRT (EAE) exhibited the highest bioactive content and the strongest antioxidant capacity. EAE intervention reshaped the gut microbiota composition in PF mice by enriching beneficial bacteria and reducing pathogenic taxa. Metabolomic analysis identified 11 potential serum biomarkers associated with PF, which were involved in 7 metabolic pathways. Notably, EAE attenuated the disruption of L-tryptophan metabolism, primarily through modulation of serotonin. Moreover, EAE was found to alleviate epithelial-mesenchymal transition (EMT) and inhibit inflammatory cytokine via the JAK2/STAT3 pathway. In conclusion, EAE may exert anti-PF effects associated with the structure of the gut microbiota, correction of amino acid metabolic disorders (notably tryptophan metabolism) and modulating JAK2/STAT3 signaling pathway in the lung. These findings provide new insights into the therapeutic potential of EAE against PF.PMID:42088464 | PMC:PMC13136511 | DOI:10.1002/fsn3.71857

iScience. 2026 Apr 9;29(5):115668. doi: 10.1016/j.isci.2026.115668. eCollection 2026 May 15.ABSTRACTChordomas are ultra-rare malignancies of the axial skeleton with limited treatment options. Some tumors exhibit immunogenic features and respond to checkpoint blockade, but the biological determinants remain unclear. To investigate chordoma immunogenicity, we integrated spatial transcriptomic and metabolomic profiling. GeoMx digital spatial profiling was performed on 15 chordomas, analyzing tumor and stromal compartments and comparing inflamed versus non-inflamed tumors. Consecutive sections underwent MALDI mass spectrometry imaging. Key findings were validated by immunohistochemistry. To link transcriptional states with interferon-γ, chordoma cell lines were treated with interferon-γ. Spatial profiling revealed transcriptomic differences between inflamed and non-inflamed tumors across both compartments, and immune infiltration correlated with a broader gene expression repertoire in cancer cells. MSI identified distinct metabolic signatures, including glycogen accumulation in inflamed tumors. However, interferon-γ treatment did not induce TBXT (brachyury) expression in chordoma cells. Together, these data reveal strong associations between transcriptional states, metabolic profiles, and immune infiltration in chordomas.PMID:42088348 | PMC:PMC13137147 | DOI:10.1016/j.isci.2026.115668

Food Chem X. 2026 Apr 24;36:103914. doi: 10.1016/j.fochx.2026.103914. eCollection 2026 May.ABSTRACTGlobal consumption of poultry meat, particularly chicken, continues to rise. However, there remains a limited understanding regarding alterations in muscle metabolites during animal breeding processes. Here, we demonstrate metabolic differences between selectively bred offspring roosters and their three parental lines. The offspring exhibited superior meat quality, as evidenced by significantly elevated absolute levels of inosine monophosphate (IMP) and decreased cooking loss. Complementary LC-MS and GC-MS analyses revealed dynamic changes in the chicken skeletal muscle metabolome, identifying amino acids and their derivatives as the primary discriminatory metabolites exhibiting elevated abundance in the offspring. Furthermore, gut microbiota was found to correlate with fluctuations in muscle metabolite levels, particularly phenylalanine and IMP. This study provides novel insights for quality control and traceability of animal-derived foods, advocating a whole-industry-chain perspective to scientifically enhance meat quality and flavor attributes.PMID:42088288 | PMC:PMC13138054 | DOI:10.1016/j.fochx.2026.103914

Food Chem X. 2026 Apr 24;36:103904. doi: 10.1016/j.fochx.2026.103904. eCollection 2026 May.ABSTRACTTo elucidate the effects of lactic acid bacteria fermentation on beef jerky metabolites, gas chromatography-mass spectrometry (GC-MS) and metabolomics techniques were employed to investigate free amino acids, key flavour compounds, and metabolic products in beef jerky fermented by lactic acid bacteria strains IMAUJBP3 and IMAUJBR3. Results indicated that lactic acid fermentation increased unsaturated fatty acid content and the proportion of key flavour substances in beef jerky. Metabolomics revealed lipids and lipoid molecules, organic acids and their derivatives as the primary differential metabolites between the two beef jerky groups. KEGG differential metabolic pathway topology analysis identified nucleotide metabolism, arachidonic acid metabolism, fructose and mannose metabolism was the key pathways influencing the quality formation of fermented beef jerky. The accumulation of key flavour compounds is highly correlated with changes in peptides, lipid molecules. These findings provide a theoretical basis for the application of lactic acid bacteria starter cultures in beef jerky production.PMID:42088281 | PMC:PMC13137188 | DOI:10.1016/j.fochx.2026.103904

Front Microbiol. 2026 Apr 20;17:1803757. doi: 10.3389/fmicb.2026.1803757. eCollection 2026.ABSTRACTPanax ginseng is one of the most important medicinal and edible plants with pharmacological compounds mainly concentrated in the roots. Although chemical transformations of ginseng active compounds have been studied, their biotransformation processes by beneficial microbes are less reported. This study aimed to reveal changes in the functional components in P. ginseng roots fermented by the golden flower fungus Aspergillus cristatus. P. ginseng roots were incubated with A. cristatus, and the final product was given the name "Golden Flower Chinese Ginseng (GFCG)." A high-performance liquid chromatography (HP-LC) and liquid chromatograph mass spectrometer (LC-MS) system revealed that fermentation by A. cristatus caused metabolite changes in GFCG and promoted the production of rare ginsenosides. Transcriptomic analysis demonstrated that more than 72% of significantly differentially expressed genes in A. cristatus showed a decrease during interaction with P. ginseng. In the meantime, transcription-related genes were suppressed, while translational and post-translational events were activated, suggesting a special role of the fungal microbe when it is colonizing medical and edible plants. Therefore, this study provides detailed chemical characterization of GFCG and the potential molecular mechanism underlying the biotransformation of P. ginseng.PMID:42088274 | PMC:PMC13136136 | DOI:10.3389/fmicb.2026.1803757

Front Microbiol. 2026 Apr 20;17:1793713. doi: 10.3389/fmicb.2026.1793713. eCollection 2026.ABSTRACTSeveral Streptomyces strains were isolated from freshwater sediments collected in the Laxenburg ponds (Lower Austria). Genome sequencing and bioinformatics analyses revealed biosynthetic gene clusters (BGCs) that may specify production of chemically diverse secondary metabolites. Various culture conditions were employed to induce metabolite production, and subsequent LC-MS analyses facilitated the identification of the produced compounds and their correlation with the corresponding BGCs. These analyses of sediment-derived Streptomyces spp. highlight their extensive biosynthetic potential, revealing a diverse range of bioactive secondary metabolites, including siderophores, antibiotics, and other compounds with potential therapeutic applications. Genomes of two Streptomyces isolates, one of them representing a potentially new species, harbored several uncharacterized BGCs that may specify biosynthesis of novel secondary metabolites. Although targeted overexpression of pathway-specific regulators from these BGCs did not yield additional metabolites, whereas knockout experiments led to metabolic changes, presumably reflecting regulatory or compensatory interactions between multiple biosynthetic pathways. Continued exploration of these strains and their BGCs may lead to the discovery of new bioactive molecules with pharmaceutical and biotechnological applications.PMID:42088272 | PMC:PMC13136089 | DOI:10.3389/fmicb.2026.1793713

Front Plant Sci. 2026 Apr 20;17:1755625. doi: 10.3389/fpls.2026.1755625. eCollection 2026.ABSTRACTINTRODUCTION: Sugarcane tillering represents a complex developmental process shaped by multiple interacting molecular networks. To outline a multi-omics regulatory framework linking hormonal, ionomic, and transcriptomic variation to contrasting tillering capacities in sugarcane, we analyzed contrasting genotypes using an integrated multi-omics approach.METHODS: Four field-grown sugarcane genotypes at the peak tillering stage were analyzed using integrated transcriptomics, targeted phytohormone metabolomics, and ionomics, with three biological replicates per genotype × tissue combination.RESULTS: High-tillering plants maintained a transcriptional and metabolic state optimized for growth, including enhanced expression of photosynthetic and carbon metabolic pathways, marked accumulation of the auxin-associated metabolite tryptamine (Log2FC = 4.97), elevated auxin- and cytokinin-associated metabolites, and preferential enrichment of micronutrients in tiller tissues. In contrast, low-tillering genotypes adopted a stress-prepared phenotype characterized by activation of defense and protein synthesis pathways, reduced 1-aminocyclopropane-1-carboxylic acid (ACC) levels in high-tillering plants relative to low-tillering plants (Log2FC = -2.26), accumulation of jasmonate-, salicylic acid-, and abscisic acid (ABA)-associated metabolites, and distinct ionomic signatures associated with nutrient imbalance. Weighted Gene Co-expression Network Analysis (WGCNA) further revealed a polarized regulatory structure, with the growth-associated module positively correlated with cis-Zeatin riboside (cZR) (yellow-labelled, r = 0.71), whereas the defense-associated module showed strong negative correlations with cZR/cis-Zeatin (cZ) (brown-labelled, r = -0.74/-0.75), and another defense-associated module showed positive correlations with ACC and Salicylic acid (SA) (turquoise-labelled, r = 0.77 and 0.79, respectively) .DISCUSSION: This study provides an integrated multi-omics framework for understanding sugarcane tillering and highlights a coordinated growth-defense trade-off associated with contrasting tillering strategies.PMID:42088035 | PMC:PMC13136100 | DOI:10.3389/fpls.2026.1755625

Reprod Med Biol. 2026 May 4;25(1):e70056. doi: 10.1002/rmb2.70056. eCollection 2026 Jan-Dec.ABSTRACTBACKGROUND: With the increase in the number of patients with infertility, the number of patients requiring in vitro fertilization and embryo transfer (IVF-ET) is also increasing. No established method exists for predicting pregnancy rates under IVF-ET, and the urgent development of pregnancy predictive biomarkers is required. Follicular fluid (FF) can be collected noninvasively during oocyte retrieval and contains numerous substances indicative of follicular status, making it a strong candidate for such biomarkers.METHODS: This review summarizes the predictive potential of several biomarkers in FF for pregnancy. We focused on FF components such as hormones, proteins, growth factors, inflammatory markers, oxidative stress markers, metabolomics, and nucleic acids.MAIN FINDINGS: FF contains stem cell factors, interleukin-6, coenzyme Q10, vitamin D, cell-free deoxyribonucleic acid, and micro ribonucleic acids within extracellular vesicles, which can predict in vitro fertilization (IVF) success. Recently, omics has enabled the analysis of a wide range of constituents, contributing to the search for potential biomarkers.CONCLUSION: This review presents a comprehensive overview of relevant FF biomarkers for predicting IVF outcomes. Reliable FF predictive biomarkers are expected to improve future IVF success rates and embryo selection, thereby enhancing overall assisted reproductive technology outcomes.PMID:42087984 | PMC:PMC13137436 | DOI:10.1002/rmb2.70056

Hum Mutat. 2026 May 3;2026:7729933. doi: 10.1155/humu/7729933. eCollection 2026.ABSTRACTNucleotide metabolism significantly influences tumor cell proliferation, yet its specific profile in pancreatic cancer remains inadequately understood. This study was aimed at characterizing the nucleotide metabolic profile in pancreatic cancer and assessing the contribution of the key gene adenylate kinase (AK) 4. Multiomics data, including transcriptomic, single-cell sequencing, spatial transcriptomic, and metabolomics datasets, were obtained from publicly accessible platforms. The impact of AK4, a key gene of nucleotide metabolism, on the proliferation and migration of pancreatic cancer cells was investigated using various molecular biological techniques. Nucleotide pathway-related metabolites exhibited marked differences in abundance between pancreatic cancer tissues and normal pancreatic tissues. Single-cell sequencing analysis identified MKI67+ and myeloid cells as subsets with overactive nucleotide metabolism. Immune cells from tumor tissues had a higher score of nucleotide metabolism than those from the normal pancreas. Spatial transcriptomics revealed spatial features of nucleotide metabolism in pancreatic cancer. Pancreatic cancer patients displayed distinct clinical heterogeneity in nucleotide metabolism, with elevated nucleotide signaling correlating with poorer patient prognosis. Furthermore, tumor subtypes showed variations in immune microenvironment features and immune checkpoint expression, which may explain their differential prognoses. A nucleotide metabolic-derived prognostic panel had the potential to predict the clinical outcomes of patients with pancreatic cancer. The AK4 gene played a central role in nucleotide metabolism, and its overexpression in clinical pancreatic cancer samples was frequently linked to adverse patient outcomes. Cell-based experiments revealed that AK4 knockdown suppressed pancreatic cancer cell proliferation and migration. Abnormal nucleotide metabolism pathways are implicated in pancreatic cancer onset and progression.PMID:42087892 | PMC:PMC13136522 | DOI:10.1155/humu/7729933

J Agric Food Chem. 2026 May 6. doi: 10.1021/acs.jafc.5c15327. Online ahead of print.ABSTRACTThe biosynthesis of selenium nanoparticles (SeNPs) from selenite is a green and safe strategy, but their mechanisms in lactic acid bacteria (LAB) remain unclear. In this study, DACN818 was isolated from traditional homemade Paocai and identified via whole-genome analysis as Ligilactobacillus salivarius. It had a high conversion rate (≥70% within 24 h) of sodium selenite at a concentration of 2000 μg/mL (11.56 mM), exhibiting improved performance over currently reported LAB. Characterization by SEM-EDS, XRD, XPS, Raman, and FTIR spectroscopic techniques revealed that the synthesized SeNPs were predominantly amorphous and coated with polysaccharides and proteins. Transcriptome and metabolome analyses indicated that the conversion process involves sulfur/glutathione metabolism, the phosphotransferase system, amino acid degradation and energy metabolism, and genes such as manX, scrA, fruA, cadC, and yfeX, rather than genes encoding ABC transporter permeases, were implicated, providing a theoretical basis for its application in the green synthesis of SeNPs.PMID:42087842 | DOI:10.1021/acs.jafc.5c15327

Biomed Chromatogr. 2026 Jun;40(6):e70480. doi: 10.1002/bmc.70480.ABSTRACTCeiba insignis and Ceiba speciosa are utilized in traditional medicine for treating inflammatory diseases. The analysis of their extracts by LC-ESI-MS/MS revealed the presence of flavonoids like kaempferol hexoside and apigenin-O-deoxyhexosyl hexoside and fatty acids, namely, sterculic acid, α-linolenic acid, and dihydrosterculic acid. C. insignis extract decreased 5-lipoxygenase and tumor necrosis factor alpha (TNF-α) gene expression by 0.2908-fold and 0.3276-fold, whereas C. speciosa extract reduced their expression by 0.4392-fold and 0.2663-fold, respectively. In response to lipopolysaccharide stimulation, both extracts had anti-inflammatory effects like those of the control medication celecoxib, which decreased 5-LOX and TNF-α expression by 0.3554-fold and 0.2263-fold, respectively. Molecular docking highlighted that dihydrosterculic acid showed the tightest fit within 5-LOX center revealing binding energy (∆G = -35.09 kcal/mol). Consequently, this study highlighted the relevance of the flowers of both Ceiba species in treating inflammatory disorders that in turn confirmed the traditional medicinal uses of these plants.PMID:42087791 | DOI:10.1002/bmc.70480

J Proteome Res. 2026 May 5. doi: 10.1021/acs.jproteome.5c01150. Online ahead of print.ABSTRACTGroup 3 medulloblastoma (G3MB) is an aggressive pediatric brain tumor subtype accounting for 20-25% of cases and characterized by poor prognosis and frequent metastasis. This subgroup frequently exhibits MYC amplification, driving oncogenic transcription, biosynthesis, and metabolic reprogramming, which is crucial for the rapid growth of tumor cells. Prior proteomic analysis of G3MB samples showed disrupted glucose and pyruvate metabolism, with notable overexpression of mitochondrial phosphoenolpyruvate carboxykinase (PCK2). This links the TCA cycle and pyruvate metabolism, aiding metabolic flexibility under nutrient stress. Consistent with this observation, we observed PCK2 overexpression in two independent patient data sets. To investigate its functional role, we performed shRNA-mediated knockdown of PCK2 in HD-MB03 and G3MB cells. Quantitative proteomics using Evosep-Tims TOF revealed dysregulation of metabolic interactors along with enrichment of ribosomal and RNA processing pathways. Complementary metabolomic profiling showed alterations in phosphocholine, carnitine, and metabolites related to redox imbalance upon PCK2 loss. Together, these findings provide insights into PCK2's role in Group 3 MB cells and expose vulnerabilities for therapeutic targeting.PMID:42087405 | DOI:10.1021/acs.jproteome.5c01150

J Cell Mol Med. 2026 May;30(9):e71063. doi: 10.1111/jcmm.71063.ABSTRACTAlthough culturing cells in serum-free or low-serum media may lead to reduced cell proliferation, it is crucial to minimise the presence of foreign proteins and other impurities that could compromise the validity of experimental findings on immunomodulation. The study aimed to investigate the immunomodulatory effects of the secretome derived from the serum-free media (SFM) of stem cells obtained from human exfoliated deciduous teeth on THP-1-derived macrophage polarisation and the assessment of inflammatory and oxidative stress mediators. THP-1 cells were polarised into M0 and M1 macrophages, and their differentiation was confirmed using flow cytometry to analyse specific markers of M0 (CD14 and CD68) and M1 (CD80 and CD86). The secretome was collected from SHED-MSCs cultured for 48 h in serum-free DMEM/F12 media. After treating THP-1-derived M0/M1 macrophages with SFM-secretome from SHED-MSCs, cells and supernatants were evaluated for immunosuppressive (anti-inflammatory and antioxidant) and immunostimulatory (pro-inflammatory and pro-oxidant) indicators. Secretome treatment decreased the population of M1 macrophages, along with the expression of pro-inflammatory and pro-oxidative markers, including CD80, CD86, TNF-α, IL-12, NO, MDA and IL-6R. The immunomodulatory effect of the secretome produced by SFM, which may help reduce inflammation, is demonstrated by an increase in M2 macrophages and anti-inflammatory and antioxidant markers, including CD206, TGFβ-2, IL-10, TAC, CAT, SOD and ARG1. The secretome produced by SFM-derived SHED-MSCs may reduce the risk of introducing foreign proteins and other potentially hazardous chemicals and enhance the efficacy of cellular secretions for applications such as immunotherapy or regenerative medicine by modulating the immune system.PMID:42087360 | DOI:10.1111/jcmm.71063

Mov Disord. 2026 May 5. doi: 10.1002/mds.70353. Online ahead of print.ABSTRACTBACKGROUND: Central lipid dysregulation is implicated in spinocerebellar ataxia type 3 (SCA3), but peripheral lipid profiles remain poorly understood. Disease-associated low body mass index (BMI) may confound interpretation.OBJECTIVE: The aim was to characterize peripheral lipid profiles across SCA3 disease stages and unmask intrinsic metabolic alterations.METHODS: This cross-sectional study analyzed the lipid profiles of 37 preataxic carriers, 229 ataxic patients, and 316 controls using BMI-adjusted analysis of covariance (ANCOVA), mediation analysis, hierarchical regression, and receiver operating characteristic (ROC) analysis.RESULTS: After adjustment, ataxic patients exhibited elevated low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C). Mediation analysis revealed these alterations were substantially masked by BMI. HDL-C exhibited a stage-dependent pattern-elevated in preataxic carriers but depleted in ataxic patients. Lower HDL-C independently predicted higher Scale for the Assessment and Rating of Ataxia (SARA) (β = -2.881, P = 0.006). HDL-C improved ataxic-preataxic discrimination, achieving an area under the curve (AUC) of 0.837.CONCLUSIONS: SCA3 exhibits dyslipidemia with elevated LDL-C and reduced HDL-C, partially masked by BMI. HDL-C depletion accompanies phenoconversion and correlates with severity, representing a candidate peripheral biomarker. © 2026 International Parkinson and Movement Disorder Society.PMID:42087344 | DOI:10.1002/mds.70353

Microbiome. 2026 May 5. doi: 10.1186/s40168-026-02399-5. Online ahead of print.ABSTRACTBACKGROUND: Microplastics (MP) pollution is widespread in livestock farming environments. Exposure to MP can impair the gastrointestinal barrier, alter the structure and metabolism of the microbiota, and subsequently lead to organ damage. MP not only hinder cattle farming but also enter the food chain, posing a potential risk. Polyethylene (PE), a type of MP commonly detected in ruminant feed, has not yet been studied for its specific effects on cattle. Using calves as an animal model, this study investigates how exposure to MP induces toxicity via the rumen microbiota-gut-liver axis.RESULTS: Exposure to MP impaired weight gain and liver development in cattle, altered liver tissue pathology, increased blood lipopolysaccharide (LPS) levels, and triggered a systemic inflammatory response, identifying the liver as the primary target organ. Inflammation was closely associated with the dysbiosis of rumen microbiota and metabolites. MP exposure also damages the barrier integrity of the rumen, jejunum, and colon. The underlying mechanism involves MP altering the rumen microbial composition, which in turn triggers metabolic disorders, activates LPS synthesis pathways, and inhibits tight junction protein expression in the jejunum and colon. Although MP do not cause significant architectural damage to muscle tissue, they disrupt lipid homeostasis and nutrient composition, thereby promoting the deposition of pro-inflammatory LPS within muscle tissue. Rumen fluid metabolomics analysis revealed that differential metabolites were mainly enriched in the ATP-binding cassette transporter (ABC) pathway, with 4-fluoro-3-phenoxybenzoic acid and isovalerylglutamic acid being significantly correlated with levels of LPS, IL-6, TNF-α, and IL-1β. Notably, the concurrent increase in TNF-α and LPS in both the bloodstream and liver, alongside altered blood metabolomics, indicates that MP induce hepatic damage by disrupting the rumen microbiota-gut-liver axis. Transcriptomic analysis revealed that liver inflammatory injury was closely associated with NF-κB activation. Further mechanistic analysis supported the central role of the TLR4/MyD88/NF-κB signaling pathway.CONCLUSIONS: MP impair liver function in cattle by disrupting the rumen microbiota-gut-liver axis. This process involves the perturbation of rumen flora and intestinal barriers, triggering LPS translocation into the bloodstream, and ultimately causing liver damage. Video Abstract.PMID:42087232 | DOI:10.1186/s40168-026-02399-5

Plant Cell Environ. 2026 May 5. doi: 10.1111/pce.70581. Online ahead of print.ABSTRACTIn this study, we analyzed a unique Nicotiana tabacum BY-2 line that was gradually adapted to and subsequently maintained in 190 mM NaCl for over 15 years. Years of continuous high salinity shaped a stable "new homeostasis" in BY-2 suspension cells. Salt-adapted cells were smaller and formed tighter clusters. Metabolomics revealed constitutive enrichment of osmoprotectants and antioxidant-associated metabolites-including proline, GABA, and selected purine derivatives-and a marked increase in β-sitosterol, together pointing to osmoadaptation, membrane stabilization, and ROS buffering without broad induction of classical antioxidant enzymes. Proteomics showed modest changes dominated by information-processing layers: higher abundance of histone deacetylases, RNA-binding and splicing-related factors, and enzymes linked to mRNA polyadenylation/decapping. In contrast, many 60S ribosomal proteins were less abundant, indicating restrained translation. Despite persistent osmotic pressure, enzymes of central metabolism changed little overall, whereas lipid-associated shifts and sterol enrichment suggest ongoing membrane remodeling. Collectively, these multi-omics data indicate that long-term salt adaptation in BY-2 cells prioritizes small-molecule osmolytes and post-transcriptional control over costly protein turnover, supporting sustained function under high osmolarity. This work provides novel insights into the molecular features underlying the reprogramming of the metabolome and proteome, enabling plant cells to survive long-term in high-salinity conditions.PMID:42087178 | DOI:10.1111/pce.70581

Trials. 2026 May 5. doi: 10.1186/s13063-026-09759-4. Online ahead of print.ABSTRACTBACKGROUND: Haskap berries have great potential as a superfood due to high polyphenolic content which confers both anti-inflammatory and antioxidant activity. These health impacts are mitigated, at least in part, by the gut microbiome as most ingested polyphenols pass to the large intestine for microbial enzymatic action and conversion to secondary phenolic metabolites. These microbial actions mediate both the bioavailability and the bioefficacy of Haskap-derived phenolics. However, clinical intervention trials characterizing the impact of long-term Haskap consumption on human health and the interaction between Haskap-derived phenolics and the gut microbiome are limited. This study aims to determine the impact of Haskap consumption on gut microbiome composition, gut microbial and serum metabolites, and other health outcome metrics in a cohort of adults with both low and high risk of metabolic syndrome.METHODS: This is a four-armed, randomized, triple-blind, placebo-controlled clinical trial conducted in a cohort of adults with both low and high risk of metabolic syndrome. A total of 120 participants (60 metabolically healthy, 60 metabolically unhealthy) will be randomized in a 1:1 ratio to consume a daily dose of either Haskap or placebo juice for 8 weeks. Outcome measures will be collected before and after the intervention period to determine the health impacts of Haskap in both groups. Primary outcome measures include fasting blood markers of glucose and lipid metabolism and inflammation, fat oxidation rates during submaximal exercise, 16S rRNA fecal microbial composition data, and mass spectrometry-acquired fecal and serum metabolomic data. Secondary outcome measures include anthropometric and sleep quality measures as well as acute and habitual dietary intake data.DISCUSSION: Investigating how the gut microbiome influences the health benefits of consuming Haskap berries will help elucidate potential mechanisms of Haskap-induced metabolic health benefits and help inform the development of effective strategies to decrease metabolic disease risk through Haskap consumption.TRIAL REGISTRATION: ClinicalTrials.gov NCT06546020. Registered on 1 August 2024.PMID:42087172 | DOI:10.1186/s13063-026-09759-4

Planta. 2026 May 5;263(6):149. doi: 10.1007/s00425-026-05008-9.ABSTRACTTranscriptomic and metabolic comparisons reveal putative regulatory and metabolic differences underlying juice sac initiation in citrus fruit. The edible portion of citrus fruits consists of juice sacs-specialized structures unique among fruits-that develop shortly after anthesis from the endocarp, originating from the innermost layers of the albedo. While their physiological and biochemical properties are well studied, the regulatory mechanisms controlling juice sac initiation remain poorly understood. In this study, we compared two cultivars of citron (Citrus medica L.)-the Calabria citron, which develops juice sacs normally, and the Yemenite citron, which does not-across four developmental stages: closed flowers, flowers at anthesis, and fruitlets at one and two weeks post-anthesis. We performed a comparative transcriptomic analysis of endocarp cells, followed by Weighted Gene Co-Expression Network Analysis (WGCNA) and a metabolomic analysis of whole ovaries and fruitlets. As expected, the Calabria endocarp exhibited higher expression of genes associated with cell wall formation, DNA replication, and cell proliferation, particularly two weeks post-anthesis. In contrast, stress-related genes were more abundant in the Yemenite endocarp. Calabria ovaries and fruitlets showed an increase in amino acids, whereas those of the Yemenite citron exhibited induction of TCA cycle and energy metabolism pathways. Integrating transcriptomic and metabolomic data revealed significant enrichment of carbohydrate and energy metabolism pathways in the Yemenite citron. Additionally, we identified a transcription factor regulatory network that may contribute to juice sac initiation. These findings provide new insights into the molecular processes underlying juice sac initiation and establish a foundation for future research aimed at elucidating its regulatory mechanisms.PMID:42086970 | DOI:10.1007/s00425-026-05008-9

Pediatr Nephrol. 2026 May 6. doi: 10.1007/s00467-026-07321-7. Online ahead of print.ABSTRACTPediatric acute kidney injury (AKI) often presents insidiously and progresses rapidly. Traditional diagnostic criteria based on serum creatinine and urine output are markedly delayed and insufficient to capture injury patterns across different etiologies. This paper aims to summarize recent advances in pediatric AKI biomarker research since the release of the ADQI 23 (2020) consensus. Focusing on three major clinical scenarios-cardiac surgery, sepsis, and nephrotoxic drugs-it reviews early biomarker evidence and explores their potential applications in risk stratification. At the mechanistic level, this paper outlines key pathological pathways in pediatric AKI progression: oxygenation-perfusion imbalance after cardiac surgery, endothelium-immune dysregulation driven by sepsis, and tubular-mitochondrial injury associated with nephrotoxic exposure. In CS-AKI, uNGAL shows the earliest elevation within hours after cardiopulmonary bypass, followed by sequential changes in IL-18, L-FABP, and KIM-1. [TIMP-2] × [IGFBP7] and exosomal miRNA aid in identifying high-risk or severe AKI. In SA-AKI, suPAR and glycocalyx/endothelial injury markers (e.g., syndecan-1, Angpt-2/sTM/Tie-2), combined with urinary DKK3 and complement Ba, can be used for early risk stratification and predicting poor outcomes. In NT-AKI, uNGAL has high negative predictive value for excluding severe AKI, while uKIM-1, uCysC, uOPN, and multi-biomarker combinations can indicate subclinical tubular injury earlier after drug exposure. Overall, single biomarkers struggle to cover AKI heterogeneity. Future efforts should integrate functional dynamic assessments (e.g., FST, RRI), scenario-based multi-biomarker combinations, and AI dynamic models to propose evidence-based, scenario-stratified identification pathways. These will serve as structured references for prospective studies and clinical workflow optimization.PMID:42086806 | DOI:10.1007/s00467-026-07321-7

Cell Death Differ. 2026 May 5. doi: 10.1038/s41418-026-01750-5. Online ahead of print.ABSTRACTTo elucidate the role and regulatory mechanisms of macrophage-derived cystatin C (CST3) in Crohn's disease (CD), focusing on colonic inflammation, macrophage-epithelial interactions, and barrier dysfunction. Colonic samples from CD patients, including inflamed and non-inflamed regions, were subjected to scRNA-seq. In vitro macrophage-epithelial co-culture models and untargeted metabolomics were employed, and the findings were validated using macrophage-specific CST3 knockout (KO) and overexpression mice under TNBS-induced and IL-10 KO colitis conditions. Mechanistic investigations included Co-IP, ChIP-qPCR, ubiquitination assays, rescue experiments, and functional analyses of efferocytosis, macrophage polarization, and barrier integrity. CST3 expression was considerably reduced in macrophages from inflamed CD tissues through suppressor of SMAD5-dependent transcriptional repression and MYCBP2-mediated K48-linked ubiquitination and degradation. Loss of CST3 impaired efferocytosis and M2 polarization by inhibiting the ACVR1C/TGF-β/SMAD pathway. CST3 deficiency also disrupted intestinal epithelial proliferation, compromised barrier function, and increased apoptosis via enhanced NAMPT-INSR signaling and accumulation of the inflammatory cytokines. In mice, macrophage-specific CST3 deletion exacerbated colitis, whereas its overexpression alleviated inflammation and restored epithelial integrity. These findings establish macrophage CST3 as a key regulator of immune-metabolic-epithelial crosstalk in CD, and indicate that restoring CST3 function or targeting its regulatory axis may represent a novel therapeutic strategy for CD.PMID:42086781 | DOI:10.1038/s41418-026-01750-5