PubMed

Food Chem X. 2025 Mar 15;27:102375. doi: 10.1016/j.fochx.2025.102375. eCollection 2025 Apr.ABSTRACTIn this study, we used biomass banana peel (BP) as the precursor to synthesize CDs (defined as BP-CDs). The average sizes of BP-CDs were found to be around 5.9 nm. The prepared BP-CDs presented blue fluorescence under ultraviolet irradiation at 365 nm and exhibited excitation-wavelength-dependent fluorescence properties. Furthermore, the nitrogen-containing, oxygen-containing and sulfur-containing functionalities on/in the surface of carbon structure were observed in the resulting CDs. The antioxidant assays in vitro suggested that BP-CDs displayed strong free-radical scavenging abilities. The results of antimicrobial experiments revealed that BP-CDs exhibited noteworthy antimicrobial effects against spoilage bacteria of aquatic products. Metabolomics analysis revealed that BP-CDs exerted antibacterial activity mainly by impeding normal cell metabolism, disrupting cell wall integrity, affecting substance transport and signal transduction. Taken together, these data suggest that BP-CDs could be used as an antioxidant and antibacterial agent for the development of new preservation technologies for aquatic products.PMID:40206053 | PMC:PMC11981805 | DOI:10.1016/j.fochx.2025.102375

Food Chem X. 2025 Mar 17;27:102367. doi: 10.1016/j.fochx.2025.102367. eCollection 2025 Apr.ABSTRACTThis study aimed to investigate metabolic differences between mixed- and single-culture fermentation in black mulberry juice (BMJ). Using E-nose, E-tongue, and metabolomics, we analyzed metabolic profile variations and flavor compounds in BMJ fermented with different lactic acid bacteria (LAB). Results demonstrated that BMJ is an excellent fermentation substrate, with both cultures achieving colony counts exceeding 8 log CFU/mL after fermentation. Volcano plot and cluster analyses revealed that single-culture fermentation exhibited higher efficiency in biotransforming and degrading specific compounds, yet its metabolic profile was less diverse. In contrast, mixed-culture fermentation enhanced metabolic diversity through complementary pathways among strains, improving complex molecule production, optimizing flavors, reducing bitterness/astringency, and minimizing vitamin loss. This research provides a foundation for fermented mulberry beverage development. Future studies could integrate multi-omics analyses to advance industrial applications.PMID:40206051 | PMC:PMC11979912 | DOI:10.1016/j.fochx.2025.102367

Expert Rev Proteomics. 2025 Apr 9. doi: 10.1080/14789450.2025.2491356. Online ahead of print.ABSTRACTINTRODUCTION: The emergence of personalized medicine (PM) has shifted the focus of healthcare from the traditional 'one-size-fits-all' approach to strategies tailored to individual patients, accounting for genetic, environmental, and lifestyle factors. Acoustic ejection mass spectrometry (AEMS) is a novel technology that offers a robust and scalable platform for high-throughput MS readout. AEMS achieves analytical speeds of one sample per second while maintaining high data quality, broad compound coverage, and minimal sample preparation, making it an invaluable tool for PM.Areas covered: This article explores the potential of AEMS in critical PM applications, including therapeutic drug monitoring (TDM), proteomics, metabolomics, and mass spectrometry imaging. AEMS simplifies conventional workflows by minimizing sample preparation, enhancing automation compatibility, and enabling direct analysis of complex biological matrices.EXPERT OPINION: Integrating AEMS with orthogonal separation techniques such as differential mobility spectrometry (DMS) further addresses challenges in isomer discrimination, expanding the platform's analytical capabilities. Additionally, the development of high-throughput data processing tools could further enable AEMS to accelerate the development of personalized medicine.PMID:40205846 | DOI:10.1080/14789450.2025.2491356

CNS Neurosci Ther. 2025 Apr;31(4):e70338. doi: 10.1111/cns.70338.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuroinflammation. Astrocytes play a key role in the neuroinflammatory environment of AD, especially through lipid metabolism regulation. However, the mechanisms by which astrocytes, particularly through the triggering receptor expressed on myeloid cells 2 (Trem2) receptor, contribute to lipid dysregulation and neuroinflammation in AD remain inadequately understood.METHODS: We employed an AD mouse model and integrated single-cell RNA sequencing (scRNA-seq), transcriptomics, and high-throughput metabolomics to analyze lipid metabolism and inflammatory profiles in astrocytes. Differential gene expression was further validated with the GEO database, and in vitro and in vivo experiments were conducted to assess the impact of Trem2 modulation on astrocytic inflammation and lipid composition.RESULTS: Our findings demonstrate that Trem2 modulates lipid metabolism in astrocytes, affecting fatty acid and phospholipid pathways. In the AD model, Trem2 expression was suppressed, enhancing nuclear factor-κB (NF-κB) signaling and promoting the secretion of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Trem2 overexpression reduced astrocytic inflammation and altered lipid composition, attenuating neuroinflammation both in vitro and in vivo. These results underscore Trem2's regulatory role in lipid metabolism and its significant impact on neuroinflammation in AD.CONCLUSIONS: This study identifies Trem2 as a pivotal regulator of astrocytic lipid metabolism and neuroinflammation in AD, providing potential molecular targets for early intervention and therapeutic strategies aimed at mitigating AD progression.PMID:40205810 | DOI:10.1111/cns.70338

J Proteome Res. 2025 Apr 9. doi: 10.1021/acs.jproteome.4c00987. Online ahead of print.ABSTRACTWe used metadata to explore the metabolic interplay between culture medium from in vitro-produced bovine embryos transferred fresh or frozen, recipient blood plasma, and calf fitness, alongside gene expression and methylation in calf lymphocytes. Principal component (PC) analysis (PCA) identified covariates that were depicted in Debiased Sparse Partial Correlation networks and analyzed as enriched pathways. Four PCs explained 13.77, 9.58, 7.73 and 5.84% variability. PC1 clustered only mother weight and two embryonic metabolites. PC2, PC3 and PC4 associated 10, 17, and 5 calf features with 10, 6, and 16 embryonic and 2, 20, and 5 recipient metabolites, respectively. Subsequently, gene methylation and expression, and calf fitness were analyzed by PCA. Three PCs covered 100% variability. PC1 associated acid-base balance, protein metabolism, Cl-, and Ca2+ with IGF2 and IL1R1 expression, and IL4 and IL12B methylation. PC2 linked H19 expression and methylation with growth and biochemical traits. PC3 clustered growth, hydration, and redox balance, with IGF2, IGF2R, IL1R1 and IL3 methylation, and H19, IGF2, IGF2R and IL12B expression. Gene methylation connected with embryo metabolites through networks via K+, Cl-, HCO3- and TCO2. Calf fitness parallels the early metabolic fingerprints of the embryo and recipient, allowing embryo transfer decision-making based on calf health.PMID:40205722 | DOI:10.1021/acs.jproteome.4c00987

Gut Microbes. 2025 Dec;17(1):2489072. doi: 10.1080/19490976.2025.2489072. Epub 2025 Apr 9.ABSTRACTIonizing radiation-induced intestinal injury (IRIII) is a catastrophic disease lack of sufficient medical countermeasures currently. Regulation of the gut microbiota through dietary adjustments is a potential strategy to mitigate IRIII. Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention with pleiotropic health benefits. Whether this dietary pattern influences the pathogenesis of IRIII remains vague. We evaluated the impact of TRF on intestinal radiosensitivity in this study and discovered that only daytime TRF (DTRF), not nighttime TRF, could ameliorate intestinal damage in mice that received a high dose of IR. Faecal metagenomic and metabolomic studies revealed that the intestinal creatine level was increased by approximate 9 times by DTRF, to which the Bifidobacterium pseudolongum enrichment contribute. Further investigations showed that creatine could activate the energy sensor AMP-activated protein kinase in irradiated enterocytes and induce phosphorylation of acetyl-CoA carboxylase, resulting in reduced production of polyunsaturated fatty acids and reduced ferroptosis after IR. The administration of creatine mitigated IRIII and reduced bacteremia and proinflammatory responses. Blockade of creatine import compromised the ferroptosis inhibition and mitigation of DTRF on IRIII. Our study demonstrates a radioprotective dietary mode that can reshape the gut microbiota and increase intestinal creatine, which can suppress IR-induced ferroptosis, thereby providing effective countermeasures for IRIII prevention.PMID:40205678 | DOI:10.1080/19490976.2025.2489072

BMC Urol. 2025 Apr 9;25(1):82. doi: 10.1186/s12894-025-01767-x.ABSTRACTClear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. To investigate the underlying metabolite changes in the occurrence of ccRCC, we analyzed untargeted metabolomics of 15 ccRCC samples and paired adjacent non-malignant renal tissues by UHPLC-MS/MS analyses. In this study, 511 differential metabolites were screened, of which the top ten up-regulated metabolites in ccRCC were histamine, 1-methylnicotinamide, L-kynurenine, cortisol, tetrahydrocorticosterone, calcitriol, D-erythrose 4-phosphate, citric acid, sedoheptulose 1,7-bisphosphate, and UDP-alpha-D-galactose, and the top down-regulated metabolites were D-cysteine, acetylcholine, pantothenic acid, cytosine, UMP, biocytin, dUMP, 5-phosphoribosyl 1-pyrophosphate, cytidine-5'-monophosphate, and 16α-hydroxyestrone. KEGG pathways enrichment analysis further demonstrated several highlighted pathways: steroid hormone biosynthesis, pyrimidine metabolism, and vitamin digestion and absorption. Our study reveals metabolic patterns of ccRCC and provides insight into the potential biomarker panel to diagnose ccRCC.PMID:40205595 | DOI:10.1186/s12894-025-01767-x

Cancer Metab. 2025 Apr 9;13(1):18. doi: 10.1186/s40170-025-00385-3.ABSTRACTBACKGROUND: While the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decipher the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body-rich, low glucose) nutrient medium can engineer the glycocalyx and metabolic signature of BC cells, to further maneuver their response to therapy.METHODS: Doxorubicin (DOX) has been used as a model chemotherapeutic in this study. Bioorthogonal imaging was used to assess the degree of sialylation of the glycocalyx along with measurements of drug-induced cytotoxicity and drug internalization. Single cell label-free metabolic imaging has been performed, coupled with measurement of cellular proliferative and migratory abilities, and MS-based metabolomic screens. Transcriptomic analysis of crucial enzymes was performed using total RNA extraction and rt-qPCR.RESULTS: We found an inverse correlation of glycocalyx sialylation with drug-induced cytotoxicity and drug internalization, where ketomimetic media enhanced sialylation and protected BC cells from DOX. These hypersialylated cells proliferated slower and migrated faster as compared to their counterparts receiving a high glucose media, while exhibiting a preference for glycolysis. These cells also showed pronounced lipid droplet accumulation coupled with an inversion in their metabolomic profile. Enzymatic removal of sialic acid moieties at the glycocalyx revealed for the first time, a direct role of sialic acids as defense guards, blocking DOX entry at the cellular membrane to curtail internalization. Interestingly, the non-cancerous mammary epithelial cells exhibited opposite trends and this differential pattern in cancer vs. normal cells was traced to its biochemical roots, i.e. the expression levels of key enzymes involved in sialylation and fatty acid synthesis.CONCLUSIONS: Our findings revealed that a ketomimetic medium enhances chemoresistance and invasive disposition of BC cells via two main oncogenic pathways: hypersialylation and lipid synthesis. We propose that the crosstalk between these pathways, juxtaposed at the synthesis of the glycan precursor UDP-GlcNAc, furthers advancement of a metastatic phenotype in BC cells under ketomimetic conditions. Non-cancerous cells lack this dual defense machinery and end up being sensitized to DOX under ketomimetic conditions.PMID:40205476 | DOI:10.1186/s40170-025-00385-3

Cell Mol Life Sci. 2025 Apr 9;82(1):152. doi: 10.1007/s00018-025-05670-4.ABSTRACTRichter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into a high-grade lymphoma with previously unknown metabolic features. Transcriptomic data from primary CLL and RS samples, as well as RS-patient-derived xenografts, highlighted cellular metabolism as one of the most significant differentially expressed processes. Activity assays of key enzymes confirmed the intense metabolic rewiring of RS cells, which is characterized by an elevated rate of Krebs cycle, oxidative phosphorylation, and glutamine metabolism. These pathways were sustained by increased uptake of glucose and glutamine, two critical substrates for these cells. Moreover, RS cells showed activation of anabolic processes that resulted in the synthesis of nucleotides and lipids necessary to support their high proliferation. Exposure to drugs targeting PI3K and NF-kB, two master regulators of cellular metabolism, resulted in the shutdown of ATP production and glycolysis. Overall, these data suggest that metabolic rewiring characterizes the transformation of CLL into RS, presenting new translational opportunities.PMID:40204982 | DOI:10.1007/s00018-025-05670-4

Sci Rep. 2025 Apr 9;15(1):12179. doi: 10.1038/s41598-025-91281-9.ABSTRACTThis study aims to identify biomarkers for reliably predicting diabetic kidney disease (DKD), systematically characterize serum metabolites and gut microbiota in DKD patients, and investigate the correlation between differential serum metabolites and gut microbiota. From September 2021 to January 2023, 90 subjects were recruited: 30 with DKD, 30 with type 2 diabetes mellitus (T2DM), and 30 normal controls (NCs). Serum metabolites, including 180 different metabolites, were analyzed using untargeted metabolomics UPLC-MS/MS, and gut microbiota were assessed via 16S rRNA sequencing. Differential metabolites were identified through univariate (t-test or Mann-Whitney U-test, P < 0.05) and multivariate analyses (OPLS-DA model, VIP > 1, P < 0.05), followed by selection using the least absolute shrinkage and selection operator (LASSO). The selected overlapping serum metabolites, along with DKD-associated differential gut microbiota, were used to develop a logistic regression prediction model for DKD based on six markers. In the DKD group compared to the DM and NC groups, 39 and 60 differential serum metabolites were identified, respectively (VIP > 1, P < 0.01). Among these, 36 serum metabolites, including alpha-Hydroxyisobutyric acid, were significantly elevated in DKD patients compared to those with DM. Of these, 28 metabolites showed a negative correlation with estimated glomerular filtration rate (eGFR), while 29 showed a positive correlation with urine albumin creatinine ratio (UACR). Patients with DKD were further categorized into subgroups (DKD middle and DKD early) based on eGFR (eGFR < 90 ml/min/1.73m2, eGFR ≥ 90 ml/min/1.73m2), revealing 23 differential metabolites. Dysbiosis of the gut microbiota was evident in DKD patients, with lower relative abundances of g_Prevotella and g_Faecalibacterium compared to the DM and NC groups. Subgroup analysis indicated decreased relative abundances of g_Prevotella and g_Faecalibacterium in the DKD middle group, along with a decrease in g_Klebsiella compared to the DKD early group, which correlated positively with DKD patients' eGFR. There were 11 common metabolites among the three groups of differential metabolites. Among these, three serum metabolites-imidazolepropionic acid, adipoylcarnitine, and 1-methylhistidine-were identified as predictive serum metabolic markers. Disease prediction models (logistic regression models) were constructed based on these three metabolites combined with three genera of bacteria. These models demonstrated strong discriminatory power for diagnosing patients with DKD compared to patients with DM (area under the receiver operating characteristic curve (AUROC) = 0.939 and precision-recall curve (AUPR) = 0.940). The models also effectively discriminated between patients with DKD and NCs (0.976, 0.973). This study revealed distinctive serum metabolites and gut microbiota in patients with DKD. It demonstrated the potential utility of three specific serum metabolites and three genera of bacteria in diagnosing patients with DKD and assessing their renal dysfunction.PMID:40204798 | DOI:10.1038/s41598-025-91281-9

Plant Sci. 2025 Apr 7:112500. doi: 10.1016/j.plantsci.2025.112500. Online ahead of print.ABSTRACTLight is a key factor for inducing anthocyanin biosynthesis; however, its regulatory mode in potato anthocyanin biosynthesis remains unclear. Previous research identified a specific genotype that causes the tuber skin to gradually turn purple when exposed to light of different wavelengths. In the present study, we conducted metabolome and transcriptome analyses on tuber samples during anthocyanin accumulation. The metabolome data showed that the contents of naringenin chalcone, naringenin, dihydrokaempferol, and cyanidin gradually increased during anthocyanin accumulation. The transcriptome data showed that the expression levels of most structural genes increased gradually during anthocyanin accumulation, especially the StF3'H gene that promotes cyanidin formation. Moreover, the photo-responsive transcription factor StHY5 was specifically expressed at high levels before anthocyanin accumulation, occurring 2h after light induction. Establishment of transgenic lines demonstrated that StHY5 overexpression could promote the accumulation of anthocyanin in potato tubers, along with a parallel increase in the transcription levels of StAN2, StMYBA1, StCHI, StF3H, StF3'H, and StDFR. Electrophoretic mobility shift and dual luciferase assays showed that StHY5 can enhance the promoter activity of the MYB transcription factors StAN2 and StMYBA1 as well as the structural genes StCHI and StF3H through binding to the G-box motif. StAN2 activated the expression of StF3'H (a newly identified purple gene locus in potato) and StDFR by binding to the MYB-binding site in the promoters, thereby promoting anthocyanin biosynthesis. This study provides a theoretical basis for revealing the molecular mechanism of light-regulated anthocyanin biosynthesis in potatoes.PMID:40204193 | DOI:10.1016/j.plantsci.2025.112500

Neurochem Int. 2025 Apr 7:105977. doi: 10.1016/j.neuint.2025.105977. Online ahead of print.ABSTRACTNuciferine has been widely used in traditional Chinese medicine compound preparations and natural edible resources. Most current studies have concentrated on its lipid-lowering and weight-loss effects, while relatively few have explored its impact on central nervous system disorders. To investigate the effects of nuciferine on the nervous system and its potential pharmacological mechanisms, we mapped the distribution of nuciferine and its key metabolites in brain microregions and major organs of mice using air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). Nuciferine was found to be distributed throughout the brain, particularly in the prefrontal cortex and hippocampus. Additionally, nuciferine was detected in several peripheral organs, including the heart, liver, kidneys, and spleen. We also identified the distribution of a major demethylated metabolite (M1), which correlated with the localization of the CYP1A2 enzyme. Metabolomic analysis revealed that nuciferine significantly alters purine metabolism, specifically increasing adenosine levels while decreasing xanthine and hypoxanthine. This metabolic shift suggests a potential enhancement of neuroinhibitory effects, contributing to nuciferine's sedative, hypnotic, and analgesic properties. These findings provide novel insights into the neuropharmacological mechanisms of nuciferine.PMID:40204158 | DOI:10.1016/j.neuint.2025.105977

Brain Res. 2025 Apr 7:149625. doi: 10.1016/j.brainres.2025.149625. Online ahead of print.ABSTRACTParkinson's disease (PD) is marked by alpha-synuclein accumulation and progressive dopaminergic neuron loss. Using Nuclear Magnetic Resonance (NMR)-based metabolomics, we uncovered metabolic disturbances in idiopathic PD (iPD) and PD linked to LRRK2, GBA1, and PRKN variants in a Brazilian ethnically diverse cohort, free of comorbidities, in comparison to healthy, age-matched controls. In plasma, significant PD-associated metabolites included histidine, acetate, acetoacetate, glutamine, glucose, lipids and lipoproteins, N-acetyl-glycoproteins, and sarcosine. Urine samples revealed alterations in creatine, creatinine, L-asparagine, trimethylamine, 3-beta-hydroxybutyrate, isovaleric acid, glutamine, urea, glycine, choline, arginine, and cysteine were observed in association with PD. Notably, creatine, creatinine, acetate, glucose, and histidine showed pathway influences from LRRK2, GBA1, and PRKN variants. Enrichment analyses highlighted disruptions in glyoxylate and dicarboxylate metabolism (plasma) as well as serine, threonine, and glycine metabolism (urine). Additionally, a metabolite-gene-disease interaction network identified 14 genes associated with PD that interact with key metabolites, highlighting MAPT, SNCA, RERE, and KCNN3 as key players in both plasmaandurine. NMR in saliva samples did not show significant differences between PD groups and controls. Our findings underscore PD-associated metabolites, particularly related to arginine metabolism, the urea cycle, glutamate metabolism, glucose metabolism, and gut microbiota. These pathways and gene interactions may serve as potential biomarkers for PD diagnosis and precision medicine strategies.PMID:40204143 | DOI:10.1016/j.brainres.2025.149625

Bioresour Technol. 2025 Apr 7:132501. doi: 10.1016/j.biortech.2025.132501. Online ahead of print.ABSTRACTPolyunsaturated fatty acids (PUFAs), such as γ- linolenic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, are highly valued in the global market due to their physiological effects and health benefits. Concerns related to overfishing and marine ecosystem degradation have driven interest in microalgal lipids as a sustainable and eco-friendly alternative for PUFA production. Despite some success in commercializing microalgal lipid products, they still fail to meet global demand. Advances in high-throughput omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have deepened the understanding of lipid biosynthesis in microalgae. This review explores the potential of multi-omics approaches to elucidate PUFA biosynthesis pathways, identify key regulatory genes, and optimize metabolic engineering strategies for enhanced lipid production. Additionally, this review discusses how multi-omics technologies address challenges in large-scale cultivation, promoting the industrialization of microalgal lipid productions. These insights provide a foundation for improving microalgal PUFA yields to meet growing global demand.PMID:40204027 | DOI:10.1016/j.biortech.2025.132501

Mol Metab. 2025 Apr 7:102136. doi: 10.1016/j.molmet.2025.102136. Online ahead of print.ABSTRACTRecent modifications to glucagon-like peptide 1 (GLP-1), known for its insulinotropic and satiety-inducing effects, have focused on conjugating small molecules to enable selective delivery into GLP-1R+ tissues to achieve targeted synergy and improved metabolic outcomes. Despite continued advancements in GLP-1/small molecule conjugate strategies, the intracellular mechanisms facilitating concurrent GLP-1R signaling and small molecule cargo release remain poorly understood. We evaluate an estradiol (E2)-conjugated GLP-1 (GLP-1-CEX/E2) for relative differences in GLP-1R signaling and trafficking, and elucidate endolysosomal dynamics that lead to estrogenic activity using various live-cell, reporter, imaging, and mass-spectrometry techniques. We find GLP-1-CEX/E2 does not differentially activate or traffic the GLP-1R relative to its unconjugated GLP-1 backbone (GLP-1-CEX), but uniquely internalizes the E2 moiety and stimulates estrogenic signaling. Endolysosomal pH-dependent proteolytic activity likely mediates E2 moiety liberation, as evidenced by clear amplification in estrogenic activity following co-administration with lysosomal VATPase activator EN6. The hypothesized liberated metabolite from GLP-1-CEX/E2, E2-3-ether, exhibits partial estrogenic efficacy through ERα, and is predisposed toward estrone-3-sulfate conversion. Finally, we identify relative increases in intracellular E2, estrone, and estrone-3-sulfate following GLP-1-CEX/E2 incubation in GLP-1R+ cells, demonstrating proof-of-principle for desired cargo release. Together, our data suggest that GLP-1-CEX/E2 depends on GLP-1R trafficking and lysosome acidification for estrogenic efficacy, with a likely conversion of the liberated E2-3-ether metabolite into estrone-3-sulfate, resulting in residual downstream flux into active estradiol. Our current findings aim to improve the understanding of small molecule targeting and the efficacy behind GLP-1/small molecule conjugates.PMID:40204014 | DOI:10.1016/j.molmet.2025.102136

J Allergy Clin Immunol. 2025 Apr 7:S0091-6749(25)00375-6. doi: 10.1016/j.jaci.2025.03.025. Online ahead of print.ABSTRACTDifferences in host susceptibility and environmental exposures result in significant heterogeneity in asthma clinical expression, natural evolution and response to treatment. These differences are influenced by many factors including genomics, epigenomics, transcriptomics, proteomics and metabolomics, many of which are modified by environmental and allergic exposures. The complex and multiple characteristics that interact in asthma development and progression pose significant challenges for personalized management. This review aims to guide the clinician in its management decisions by reviewing each of the components important in developing this therapeutic paradigm and by providing several integrated goals for precision or personalized medicine for asthma. Biologic characteristics of asthma in relation to the genomics, exposome and hypersensitivity reactions (allergic responsiveness) resulting in the asthma diathesis are discussed. Further insights including the use of targeted biologics and allergen immunotherapy are provided, while discussing the importance of targeting the epithelium, mucus production, airway smooth muscle and the small airways. We examine the value of multivariate cluster analyses as a new paradigm that can inform treatment decisions and the potential of adaptive trial design to evaluate known and novel predictive biomarkers and characterize disease heterogeneity.PMID:40203996 | DOI:10.1016/j.jaci.2025.03.025

Environ Res. 2025 Apr 7:121541. doi: 10.1016/j.envres.2025.121541. Online ahead of print.ABSTRACTEnvironmental noise is a major environmental risk factor for public health. According to the noise reaction model the release of stress hormones like cortisol in response to noise exposure, plays a key role in the development of noise-induced health effects. We aimed to study the association between environmental noise with both acute (UCC) and cumulative (HCC) cortisol levels in children 5-12 years of age. To do so, we analysed data from the HELIX cohort -with spot UCC data- and from the Generation R and INMA cohorts (Gipuzkoa and Sabadell) -with HCC data. The analytical sample involved: 750 HELIX children (mean age=7.75), 1326 Generation R children (mean age=6.06), 111 INMA-Sabadell children (mean age=8.75) and 288 INMA-Gipuzkoa children (mean age=7.85). Day-evening-night equivalent (Lden) environmental noise exposure during the year of the follow-up was estimated in the addresses of participants, using existing noise maps. Directed acyclic graphs (DAGs) were used to identify appropriate covariates and reduce the chance for biased estimation. We used mixed-effects modelling and linear modelling to examine the association between Lden and cortisol concentration using complete case analyses. None of the models reached the statistical significance. We observed no correlation between HCC and UCC in INMA-Sabadell participants, for whom both urinary and hair cortisol data were available. Future research should prioritize investigating the effects of environmental noise on HCC, as it may serve as a more reliable indicator for assessing associations with chronic exposures. Additionally, future studies on noise-induced health effects in children should incorporate other biomarkers of stress and chronic inflammation to provide a more comprehensive understanding of these associations.PMID:40203977 | DOI:10.1016/j.envres.2025.121541

Int J Biol Macromol. 2025 Apr 7:142915. doi: 10.1016/j.ijbiomac.2025.142915. Online ahead of print.ABSTRACTOne of the vital functional biopolymers produced by lactic acid bacteria (LAB) is exopolysaccharide (EPS) that has been extensively studied, but less research has been done on the EPS production by pediococci. In this study, the EPS synthesis in Pediococcus acidilactici BCB1H regulated by Fe2+ was investigated by a multi-omics method. Adding Fe2+ (0.6 g/L) in a semi-defined medium was shown to significantly increase the EPS production from 225.5 to 271.5 mg/L by BCB1H. Joint transcriptomics and proteomics analyses on BCB1H under Fe2+ interference revealed upregulation of phosphotransferase systems (PTS), the key pathway to synthesizing EPSs. Further joint transcriptomics and metabolomics analyses showed a total of 22 differential metabolic pathways, including overall metabolic pathways, biosynthesis of secondary metabolites, metabolism of microorganisms in different environments. Integrated multi-omics analysis for the key differentially expressed genes, proteins and metabolites with synergistic effects revealed decarboxylating 6-phosphogluconate dehydrogenase (Gnd), acetyl-CoA carboxylase biotin carboxylase subunit (AccD) and EII sugar-specific permease (EIIs) genes that were upregulated, while glycerol kinase (GlpK) and alcohol dehydrogenase (AdhP) downregulated. Therefore, Fe2+ enhanced the EPS synthesis in BCB1H by promoting accumulation of fructose-6-phosphate, glycerate and malate, and reducing production of d-fructose-1,6-diphosphate and glycerone-phosphate, mainly by regulation of the pentose phosphate pathway, tricarboxylic acid cycle, glycolysis and gluconeogenesis pathways, and glycerolipid metabolism pathways. The present study was significant for further understanding the regulatory mechanism of EPS biosynthesis in LAB.PMID:40203930 | DOI:10.1016/j.ijbiomac.2025.142915

Phytopathology. 2025 Apr 9. doi: 10.1094/PHYTO-11-24-0357-R. Online ahead of print.ABSTRACTTea foliar disease caused by the fungal pathogen Pestalotiopsis trachicarpicola poses a significant threat to tea production and quality in China. The disease, which includes tea leaf spot and gray blight, severely impacts both tea yield and quality, partly due to the lack of effective epidemiological data and control strategies. Fluoxastrobin, a strobilurin fungicide, has shown promise in controlling various fungal diseases. This study evaluated the inhibitory activity of fluoxastrobin against multiple phytopathogenic fungi, revealing a half-maximal effective concentration of 13.64 μg/ml for P. trachicarpicola in vitro and a maximum in vivo curative activity of 81.63% against tea leaf spot caused by P. trachicarpicola. Observations from optical, scanning electron, and transmission electron microscopy revealed that fluoxastrobin induces severe hyphal deformation, including hyphal swelling, malformation, and rough hyphal surfaces. Integrated transcriptomic, metabolomic, and bioinformatic analyses indicated that fluoxastrobin affects electron transfer process, therefore disturbing the energy metabolism of hyphae. Biochemical assays indicated fluoxastrobin can inhibit ATP production in hyphae and increase the membrane potential of hyphae, with these effects being dose-dependent. Molecular docking and molecular dynamics simulations demonstrated that fluoxastrobin binds stably to NAD-dependent epimerase/dehydratase, a key enzyme in energy metabolism, with binding energies of -12.9 kcal/mol, suggesting these may be potential target protein in the fungus. Overall, this study demonstrates that fluoxastrobin disrupts electron transfer, reduces ATP production, and inhibits hyphal growth, likely by binding NAD-dependent epimerase/dehydratase. It shows potential for controlling tea foliar diseases in the future.PMID:40203857 | DOI:10.1094/PHYTO-11-24-0357-R

Food Chem. 2025 Apr 2;482:144183. doi: 10.1016/j.foodchem.2025.144183. Online ahead of print.ABSTRACTFertilization is important for tea garden management and tea flavor improvement; however, the effects of different ratios of organic and chemical fertilizer on fresh tea leaf quality and finished tea flavor remain unclear. Therefore, four fertilization treatments were used to elucidate the underlying mechanisms. Fertilization treatments increased tea yield, and organic fertilizer increased bud density. Organic fertilizer reduced bitter rutin and γ-aminobutyric acid content and phenol-to-ammonia ratio, and increased theanine, glutamic acid, quercetin-3-O-glucoside, kaempferol-3-O-rutinoside, and (-)-epicatechin-3-O-gallate content, resulting in umami taste and bright green color of green tea. Nine key differential volatiles were screened, and organic fertilizer markedly increased the levels of floral and fruity volatiles, including indole, decanal, linalool, geraniol, and cis-jasmone, resulting in lasting orchid aroma. Transcriptome analysis showed that organic fertilizer upregulated genes related to phenylalanine conversion and fatty acid metabolism, resulting in excellent tea quality. The results provide robust support for precise quality improvement in tea production.PMID:40203691 | DOI:10.1016/j.foodchem.2025.144183