PubMed

Sci Transl Med. 2025 Feb 5;17(784):eadp8913. doi: 10.1126/scitranslmed.adp8913. Epub 2025 Feb 5.ABSTRACTAlthough oncogenic NRAS activates mitogen-activated protein kinase (MAPK) signaling, inhibition of the MAPK pathway is not therapeutically efficacious in NRAS-mutant (NRASMUT) tumors. Here, we report that selectively silencing the ribosomal protein S6 kinase 2 (S6K2) while preserving the activity of S6K1 perturbs lipid metabolism, enhances fatty acid unsaturation, and triggers lethal lipid peroxidation in NRASMUT melanoma cells that are resistant to MAPK inhibition. S6K2 depletion induces endoplasmic reticulum stress and peroxisome proliferator-activated receptor α (PPARα) activation, triggering cell death selectively in MAPK inhibitor-resistant melanoma. We found that combining PPARα agonists and polyunsaturated fatty acids phenocopied the effects of S6K2 abrogation, blocking tumor growth in both patient-derived xenografts and immunocompetent murine melanoma models. Collectively, our study establishes S6K2 and its effector subnetwork as promising targets for NRASMUT melanomas that are resistant to global MAPK pathway inhibitors.PMID:39908352 | DOI:10.1126/scitranslmed.adp8913

PLoS One. 2025 Feb 5;20(2):e0310786. doi: 10.1371/journal.pone.0310786. eCollection 2025.ABSTRACTAccording to the previous investigation and research of our group, it was found that Centranthera grandiflora Benth. (C. grandiflora for short) might be a root hemiparasitic plant. The experiments of mixed sowing of C. grandiflora and 9 companion plants that might be hosts were conducted, and the growth, biological yield and other indexes were observed. The results showed that Cyperus iria L. was the best host for C. grandiflora, and when they were mixed sowed, C. grandiflora had a vigorous growth above ground and the haustoria connected obviously below ground, while C. grandiflora could achieve blossoming and fruiting in the same year. Next, nontargeted metabonomics analysis methods were utilized to clarify the differences in metabolites between parasitized and non-parasitized C. grandiflora. A total of 82 metabolites with significant differences were screened. The main upregulated differential metabolites of non-parasitized plants were for plant growth, while that of parasitized plants were functional compounds such as EPA. Out of 82 differential metabolites, 32 were annotated into 37 KEGG pathways. Analysis of the 37 pathways in combination with the differential metabolites showed that in addition to being involved in the synthesis pathway of iridoid terpenes, the up-regulated metabolites of parasitized plants were involved in the synthesis pathways of several functional components, while that of non-parasitic plants were involved in the subsequent catabolism of monoterpenoid compounds, as well as the metabolic pathways of nutrients synthesis and catabolism, energy generation, and phytohormone production required for plant growth.PMID:39908286 | DOI:10.1371/journal.pone.0310786

Plant J. 2025 Feb;121(3):e70026. doi: 10.1111/tpj.70026.ABSTRACTPartial root-zone drying irrigation (PRD) has been widely employed to regulate crop root development and responses to environmental fluctuations. However, its role in reprogramming rhizospheric microorganisms and inducing plant stress tolerance remains largely unexplored. This study aimed to investigate the effects of PRD on the response of barley (Hordeum vulgare) plants to low temperatures under various irrigation regimes. Under low temperature, barley plants subjected to PRD exhibited a significantly enhanced net photosynthetic rate, stomatal conductance, and maximum quantum efficiency of photosystem II compared to fully irrigated plants. Additionally, these plants showed a reduction in relative conductance. These results suggest that PRD could be a viable strategy for enhancing crop stress tolerance through irrigation management. Metabolomic analysis revealed that PRD influenced the accumulation of glutathione and 9-octadecenamide in roots under low temperature, which was corroborated by transcriptome profiling data. Furthermore, the study highlighted the close association between this regulatory process and rhizosphere core microorganisms, such as Sphingobium and Mortierella, enriched in barley roots under PRD. This study revealed the mechanism underlying plant stress tolerance induction by PRD and the roles of rhizosphere microorganisms in this process. Also, the current study suggests that PRD is a promising strategy for enhancing crop stress tolerance through effective irrigation management.PMID:39908208 | DOI:10.1111/tpj.70026

Plant J. 2025 Feb;121(3):e17231. doi: 10.1111/tpj.17231.ABSTRACTSeeds of Brassicaceae produce a large diversity of beneficial and antinutritional specialized metabolites (SMs) that influence their quality and provide resistance to stresses. While SM distribution has been described in leaves and root tissues, limited information is available about their spatiotemporal accumulation in seeds. Camelina sativa (camelina) is an oilseed Brassicaceae cultivated for human and animal nutrition and for industrial uses. While we previously explored SM diversity and plasticity, no information is available about SM distribution and expression of related proteins and genes in camelina seeds. In this study, we used a multi-omic approach, integrating untargeted metabolomics, proteomics, and transcriptomics to investigate the synthesis, modification, and degradation of SMs accumulated in camelina seed tissues (seed coat, endosperm, embryo) at six developmental and two germination stages. Metabolomic results showed distinct patterns of SMs and their related pathways, highlighting significant contrasts in seed composition and spatial distribution for the defense-related and antinutritional glucosinolate (GSL) compounds among camelina, Arabidopsis thaliana, and Brassica napus, three closely related Brassicaceae species. Notably, thanks to metabolomic and proteomic/transcriptomic techniques the variation in GSL spatial distributions was primarily driven by differences in their structure (metabolomics data) and transport (transcriptomic and proteomic data) mechanisms. Long-chain C8-C11 methylsulfinylalkyl GSLs were predominantly accumulated in the seed coat and endosperm, while mid- and short-chain C3-C7 methylsulfinylalkyl GSLs were accumulated in the embryo. Characterizing the spatial dynamics of seed SMs provides valuable insights that can guide the development of crops with optimized distribution of beneficial and toxic metabolites, improving seed nutritional profiles.PMID:39908193 | DOI:10.1111/tpj.17231

Cell Rep. 2025 Feb 4;44(2):115265. doi: 10.1016/j.celrep.2025.115265. Online ahead of print.ABSTRACTSarcopenia significantly diminishes quality of life and increases mortality risk in older adults. While the connection between the gut microbiome and muscle health is recognized, the underlying mechanisms are poorly understood. In this study, shotgun metagenomics revealed that Bifidobacterium adolescentis is notably depleted in individuals with sarcopenia, correlating with reduced muscle mass and function. This finding was validated in aged mice. Metabolomics analysis identified nicotinic acid as a key metabolite produced by B. adolescentis, linked to improvements in muscle mass and functionality in individuals with sarcopenia. Mechanistically, nicotinic acid restores nicotinamide adenine dinucleotide (NAD+) levels in muscle, inhibits the FoxO3/Atrogin-1/Murf-1 axis, and promotes satellite cell proliferation, reducing muscle atrophy. Additionally, NAD+ activation enhances the silent-information-regulator 1 (SIRT1)/peroxisome-proliferator-activated-receptor-γ-coactivator 1-alpha (PGC-1α) axis, stimulating mitochondrial biogenesis and promoting oxidative metabolism in slow-twitch fibers, ultimately improving muscle function. Our findings suggest that B. adolescentis-derived nicotinic acid could be a promising therapeutic strategy for individuals with sarcopenia.PMID:39908139 | DOI:10.1016/j.celrep.2025.115265

Curr Nutr Rep. 2025 Feb 5;14(1):29. doi: 10.1007/s13668-025-00620-9.ABSTRACTPURPOSE OF THE REVIEW: This literature review provides examples of the influence of certain genetic variants on health outcomes after dietary polyphenol consumption or supplementation. Available evidence is organized according to the major classes of polyphenols (flavonoids, phenolic acids, stilbenes, lignans, and tannins) and their derived subgroups.RECENT FINDINGS: Nutrigenetic studies have identified mainly single nucleotide polymorphisms located within genes involved in the biotransformation of phenolic acids, stilbenes, lignans and several flavonoid molecules. These genetic variants may affect polyphenol metabolism rates and related predisposition to chronic non-communicable diseases. Moreover, differential cardiometabolic outcomes upon polyphenol supplementation as dietary sources or nutraceuticals have been modulated by specific genotypes. Although current evidence is still limited, growing gene-polyphenol interactions are contributing to systematically elucidate the biological functions of polyphenols; determine individual risk phenotypes to specific diseases or particular responses upon polyphenol exposure; and facilitate the prescription of personalized genotype-based doses of dietary polyphenols to optimize related health benefits. Additionally, the integration of genetics with other omics insights (epigenomics, transcriptomics, metagenomics, and metabolomics) trough biological systems and high-dimensional data analyses and interpretation may provide a more comprehensive understanding of polyphenol metabolism for precision nutrition applications in health and disease.PMID:39907890 | DOI:10.1007/s13668-025-00620-9

Environ Monit Assess. 2025 Feb 5;197(3):244. doi: 10.1007/s10661-025-13674-7.ABSTRACTThe pulp and paperboard industries are the major industrial sector that consumes significant amounts of fresh water and generates large volumes of wastewater. The treatment of this wastewater resulted in the production of a substantial amount of sludge, which posed serious environmental challenges. This study explored a sustainable solution by converting PBS into biochar through slow pyrolysis of temperatures up to ≤ 500 °C, offering an alternative approach to waste management and resource conservation. The physicochemical parameters of paper board sludge biochar (PBSB) exhibited a neutral pH of 7.49, electrical conductivity of 0.09 dS m-1, organic carbon of 38.12% and CaCO3 of 24.5%. Proximate analysis of PBSB revealed an increased fixed carbon of 76.43%, total organic carbon (TOC) of 7.13%, and reduced volatile matter and moisture levels. The TGA analysis of the dried paperboard sludge sample showed a 20% mass reduction when heated to 350 °C. During this process, more than 90% of the volatile components were removed.. The micro nutrients viz., Fe 5.06 mg L-1, Mn 419.3 mg L-1, Cu 26.3 mg L-1, and Zn 66.1 mg L-1 contents were observed in PBSB. FT-IR analysis identified the presence of various carbon-containing functional groups, including C-Cl, C-N, C-C, H-C = O, C-H, and -C≡C-H, indicating substantial chemical transformations during pyrolysis. SEM-EDX analysis revealed that PBSB has fine particle size and a coarse fluffy spongy porous structure ideal for water adsorption. Elemental analysis (XRD) showed high carbon and oxygen content with significant amounts of aluminosilicates, carbonates, and nutrients like phosphorus and potassium, suggesting PBSB as a potential slow-release fertilizer. This research highlights the potential of biochar derived from paperboard waste as a sustainable solution for waste management and resource recovery.PMID:39907848 | DOI:10.1007/s10661-025-13674-7

Appl Biochem Biotechnol. 2025 Feb 5. doi: 10.1007/s12010-024-05098-9. Online ahead of print.ABSTRACTEndophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential for new drug development. Their ability to address the growing issue of drug resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on a large scale to meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided the identification and characterization of fungal endophytes and their metabolites. Current estimates suggest there are approximately 1.20 million fungal endophytes globally, yet only around 16% (190,000) have been identified and studied in detail. This underscores the vast untapped potential of fungal endophytes in pharmaceutical research. Research has increasingly focused on the transformation of bioactive compounds by fungal endophytes through chemical and enzymatic processes. A notable example is the anthraquinone derivative 6-O-methylalaternin, whose cytotoxic potential is enhanced by the addition of a hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up new avenues for developing safer and more effective therapeutic agents by synthesizing targeted derivatives. Despite the immense promise, challenges remain, particularly in the large-scale cultivation of fungal endophytes and in understanding the complexities of their biosynthetic pathways. Additionally, the genetic manipulation of endophytes for optimized metabolite production is still in its infancy. Future research should aim to overcome these limitations by focusing on more efficient cultivation methods and deeper exploration of fungal endophytes' genetic and metabolic capabilities to fully harness their therapeutic potential.PMID:39907846 | DOI:10.1007/s12010-024-05098-9

Anal Bioanal Chem. 2025 Feb 5. doi: 10.1007/s00216-025-05760-z. Online ahead of print.ABSTRACTMicrosampling, especially dried blood spots (DBS), emerged in recent years as a viable alternative to conventional blood collection since it is rapid, simple, minimally invasive, and has user-friendly characteristics. Moreover, DBS are able to avoid analyte degradation thanks to their great stability. Due to their versatility, clinical applications with DBS have increased, including mass spectrometry-based metabolomics and lipidomics studies. In this work, we evaluated and optimized extraction protocols testing five different extraction solutions to perform metabolomics and lipidomics studies on the same spot considering three commercially available microsampling devices, Capitainer, Whatman, and Telimmune. Parallelly, we also evaluated the short-term stability of the three devices at room temperature for up to 5 days. Our results showed that pure methanol was the best compromise to simultaneously extract from the same spot both the lipidome and polar metabolome. However, we also propose a two-step protocol combining methanol and water extraction that improves polar metabolite extraction and shows improved reproducibility in Capitainer and Whatman. Short-term stability results highlighted that both polar metabolites and lipids were stable for up to 6 days using the Capitainer device, while with Whatman and Telimmune, some significant variations were observed after 3 days for some classes of metabolites/lipids, suggesting the need for cold-chain storage when working with these devices.PMID:39907755 | DOI:10.1007/s00216-025-05760-z

Am J Physiol Renal Physiol. 2025 Feb 5. doi: 10.1152/ajprenal.00201.2024. Online ahead of print.ABSTRACTPodocyte injury plays a critical role in the pathogenesis and progression of focal and segmental glomerulosclerosis (FSGS). Transmembrane protein 30A (TMEM30A) downregulation participates in podocyte injury. This study aimed to identify the critical pathways and molecules associated with the downregulation of TMEM30A in the context of FSGS podocyte injury. In our study, we found TMEM30A and podocyte marker Synaptopodin were significantly downregulated in kidney tissues from patients with FSGS compared to those in normal controls. Using transcriptomic and metabolomic analyses, we characterized Tmem30a knockdown (KD) and normal mouse podocytes to identify differentially expressed genes and metabolites. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) network were constructed, and the differentially expressed genes and metabolites were enriched into glycolytic pathway. Furthermore, we found the key glycolytic enzymes were downregulated in patients with FSGS, podocyte-specific Tmem30aLoxP/LoxP; NPHS2-Cre mice, and Tmem30a KD mouse podocytes. For rescue experiments, shTmem30a-resistant cDNA (resTmem30a) was created to intervene Tmem30a KD mouse podocytes. And we observed that podocyte-related molecules were downregulated in the Tmem30a KD group, along with glycolysis-related molecules, but the resTmem30a partially reversed this trend. Our findings clarified TMEM30A downregulation initiates podocyte injury by reducing glycolysis-related molecules (ALDOA, HK2, LDHA, and GAPDH) in FSGS and have implications for early diagnosis, prevention, and treatment.PMID:39907744 | DOI:10.1152/ajprenal.00201.2024

J Chem Inf Model. 2025 Feb 5. doi: 10.1021/acs.jcim.4c02040. Online ahead of print.ABSTRACTSpecificity, sensitivity, and high metabolite coverage make mass spectrometry (MS) one of the most valuable tools in metabolomics and lipidomics. However, translation of metabolomics MS methods to multiyear studies conducted across multiple batches is limited by variability in electrospray ionization response, making batch-to-batch comparisons challenging. This limitation creates an artificial divide between nontargeted discovery work that is broad in scope but limited in terms of absolute quantitation ability and targeted work that is highly accurate but limited in scope due to the need for matched isotopically labeled standards. These issues are often observed in stem cell studies using metabolomic and lipidomic MS approaches, where patient recruitment can be a years-long process and samples become available in discrete batches every few months. To bridge this gap, we developed a machine learning model that predicts electrospray ionization sensitivity for lipid classes that have shown correlation with stem cell potency. Molecular descriptors derived from these lipids' chemical structures are used as model input to predict electrospray response, enabling quantitation by MS with moderate accuracy (semiquantitation). Model performance was evaluated via internal and external validation using cultured cells from various stem cell donors, achieving global percent errors of 40% and 20% for positive and negative electrospray ion modes, respectively. Although this accuracy is typically insufficient for traditional targeted lipidomics experiments, it is sufficient for semiquantitative estimation of lipid marker concentrations across batches without the need for specific chemical standards that many times are unavailable. Furthermore, the precision for model-predicted concentrations was 16.9% for the positive mode and 7.5% for the negative mode, indicating promise for data harmonization across batches. The set of molecular descriptors used by the models described here was able to yield higher accuracy than those previously published in the literature, showing high promise toward semiquantitative lipidomics.PMID:39907635 | DOI:10.1021/acs.jcim.4c02040

Biomol Biomed. 2025 Feb 3. doi: 10.17305/bb.2025.11835. Online ahead of print.ABSTRACTThis study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.PMID:39907559 | DOI:10.17305/bb.2025.11835

Pest Manag Sci. 2025 Feb 5. doi: 10.1002/ps.8701. Online ahead of print.ABSTRACTBACKGROUND: The ascomycete Magnaporthe oryzae is a destructive phytopathogenic fungus that causes rice blast disease and can greatly reduce rice yields. Due to the widespread use of synthesized chemical fungicides and the frequent occurrence of fungicide resistance and environmental pollution as a result, it has become increasingly urgent to develop environmentally friendly biocontrol alternatives, including plant crude extracts.RESULTS: In this study, the crude extracts of the tropical plant Millettia pachyloba were screened out and exhibited excellent preventive effects against M. oryzae at 200 μg mL-1. Bio-guided isolation of M. pachyloba was conducted and three isoflavonoids, rotenolone, durmillone, and durallone, whose chemical structures were determined using spectroscopic and spectrometric analyses, were obtained. The three isoflavonoids exhibited antifungal activities on conidial germination and appressorium formation in M. oryzae. Rotenolone had the strongest effect, with EC50 values of 57.81 μg mL-1 on conidial germination and 19.14 μg mL-1 on appressorium formation. Comparative metabolomics showed that differential metabolites were enriched in ABC transporter pathways and amino acid metabolic pathways when M. oryzae conidia were treated with rotenolone, suggesting that rotenolone interferes with amino acid transportation. Moreover, the M. pachyloba crude extract also effectively inhibited the infection of other fungal pathogens on tomato, apple, wheat, and maize.CONCLUSION: The results suggest that isoflavones extracted from M. pachyloba prevent rice blast by inhibiting the infection-related morphogenesis of M. oryzae and may interfere with amino acid transport, demonstrating that M. pachyloba crude extract exhibits potential as a bio-fungicide for controlling fungal diseases in plants. © 2025 Society of Chemical Industry.PMID:39906930 | DOI:10.1002/ps.8701

Evol Lett. 2024 Nov 11;9(1):150-162. doi: 10.1093/evlett/qrae062. eCollection 2025 Feb.ABSTRACTShared developmental, physiological, and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability, and evolvability to certain axes in multivariate trait space ("variational modules" or "syndromes"). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite that links traits related to energy metabolism along a "power-endurance" axis in Drosophila melanogaster. The "power" pole of the axis is characterized by high potential for energy generation and expenditure-high expression of glycolysis and TCA cycle genes, high abundance of mitochondria, and high spontaneous locomotor activity. The opposite "endurance" pole is characterized by high triglyceride (fat) reserves, locomotor endurance, and starvation resistance (and low values of traits associated with the "power" pole). This trait suite also aligns with the first principal component of metabolome; the "power" direction is characterized by low levels of trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate "Selected" populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six "Control" populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regimes, the above traits strongly covaried along this "power-endurance" axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the "power" direction compared to Controls. Aspects of this "power-endurance" axis resemble the "pace of life" syndrome and the "thrifty phenotype"; it may have evolved as part of a coordinated organismal response to nutritional conditions.PMID:39906580 | PMC:PMC11790217 | DOI:10.1093/evlett/qrae062

Front Pharmacol. 2025 Jan 21;15:1466504. doi: 10.3389/fphar.2024.1466504. eCollection 2024.ABSTRACTBACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (nAChRs), which are expressed throughout the mammalian brain, mediate a variety of physiological functions. Despite their widespread presence, the functions of nAChRs are not yet fully understood. α-Conotoxins, which are peptides derived from the venom of marine cone snails, target different subtypes of nAChRs. Specifically, α-Conotoxins [D1G, ΔQ14] LvIC, identified from Conus lividus, have demonstrated strong activity on α6β4* nAChRs in vitro. However, the effects of [D1G, ΔQ14] LvIC have not been investigated in vivo. This study aims to examine the activities of [D1G, ΔQ14] LvIC and explore its potential mechanisms in vivo.METHODS: The study involved the injection of [D1G, ΔQ14] LvIC into the lateral cerebral ventricle (LV) of mice. Following this procedure, behavioral tests were conducted to assess changes in the mice's behavior. To investigate the molecular alterations in the mice's brains, untargeted metabolomics and label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) were employed. Subsequently, Western blot (WB) and quantitative reverse transcription PCR (RT-qPCR) techniques were utilized to detect specific molecular changes induced by [D1G, ΔQ14] LvIC.RESULTS: The injection of [D1G, ΔQ14] LvIC led to a decrease in locomotor activity in mice. This treatment also resulted in reduced expression of neuronal calcium sensor 1 (NCS-1) and neuroligin 3 (NLGN-3) in the prefrontal cortex (PFC), hippocampus (Hip), and caudate putamen (CPu). Both NCS-1 and NLGN-3 are crucial for neuronal development, synapse formation, and neuron activity, and their reduction is associated with decreased synapse strength. Despite these changes, results from the Morris water maze (MWM) indicated that [D1G, ΔQ14] LvIC did not impair the learning and memory abilities of the mice.CONCLUSION: Our findings indicate that α-conotoxin [D1G, ΔQ14] LvIC significantly decreased locomotor activity in mice. Additionally, it altered gene expression primarily in areas related to neuronal development, synapse formation, and neuron activity, while also reducing synapse strength. This study first proposed that [D1G, ΔQ14] LvIC could modulate mice's locomotor activity. However, further investigation is needed to understand the therapeutic effects of [D1G, ΔQ14] LvIC.PMID:39906393 | PMC:PMC11790622 | DOI:10.3389/fphar.2024.1466504

J Orthop Translat. 2025 Jan 22;51:37-50. doi: 10.1016/j.jot.2024.12.008. eCollection 2025 Mar.ABSTRACTBACKGROUND: Fresh osteochondral allografts (OCAs) contain numerous immunogenic components in the subchondral bone (SB). Whether high-speed centrifugation (HSC) reduces immune rejection by removing bone marrow elements (BMEs), compared to methods without HSC, remains unknown. This study aimed to validate the efficacy and safety of HSC in reducing immune rejection by removing allogeneic BMEs.METHODS: OCAs were obtained from the femoral condyles of the stifle joint in 18 pigs. Gross observations, histological staining, weight measurements, and DNA extraction were performed to assess the effects of centrifugation speed and duration on BMEs removal in OCAs. The effect of HSC on OCAs preservation was determined in vitro using microbiological testing, live/dead cell staining, and histological staining. Moreover, the co-culture effect of RAW264.7 cells and OCAs with or without HSC in vitro was evaluated using enzyme-linked immunosorbent assay (ELISA), histological staining, and immunohistochemical staining. The transplantation effect of OCAs with or without HSC was examined in vivo using a subcutaneous mouse model. Finally, the residues in the centrifuge tubes were analysed using ELISA, haematoxylin and eosin (HE) staining, and metabolomic analysis.RESULTS: Centrifugal speeds of 12000 rpm for 1 min were sufficient to reduce BMEs by over 90 %. HSC had a protective effect on chondrocytes and the extracellular matrix during the in vitro preservation of OCAs. In addition, OCAs using the HSC method exhibited reduced recognition by the host immune system compared with OCAs without HSC, thereby reducing immune rejection. Lipids were the most abundant and difficult-to-remove antigenic components and are the most likely to affect host macrophage polarisation, playing an important role in immune rejection.CONCLUSION: Our study demonstrated that HSC method significantly reduces immune rejection by removing BMEs from OCAs.THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study demonstrated that HSC is a simple, efficient, and safe physical method for removing antigenic components from OCAs, effectively reducing immune rejection and highlighting its clinical potential.PMID:39906333 | PMC:PMC11791335 | DOI:10.1016/j.jot.2024.12.008

Front Vet Sci. 2025 Jan 21;12:1527284. doi: 10.3389/fvets.2025.1527284. eCollection 2025.ABSTRACTCottonseed meal is a promising alternative to soybean meal in poultry feed, but concerns over free gossypol limit its use. Although the general toxicity of free gossypol is well-known, its specific effects on the liver-the primary site where it accumulates-are less thoroughly studied, particularly at the molecular level. This study investigated the hepatotoxic effects of gossypol acetate (GA) on goslings through a comprehensive analysis combining morphology, transcriptomics, and metabolomics. Forty-eight 7-day-old male goslings with similar body weight (BW) were randomly assigned to two groups: a control group, receiving a saline solution (0.9%, 2.5 mL/kg BW), and a GA-treated group, administered GA at 50 mg/kg BW orally for 14 days. Histological analysis revealed signs of liver damage, including granular degeneration, hepatocyte enlargement, necrosis, and mitochondrial injury. Transcriptomic analysis identified 1,137 differentially expressed genes, with 702 upregulated and 435 downregulated. Key affected pathways included carbon metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, propanoate metabolism, TCA cycle, fatty acid degradation, primary bile acid biosynthesis, tryptophan metabolism, cysteine and methionine metabolism, focal adhesion, and the PPAR signaling pathway. Metabolomic analysis revealed 109 differential metabolites, 82 upregulated and 27 downregulated, implicating disruptions in linoleic acid metabolism, arachidonic acid metabolism, cAMP signaling, and serotonergic synapse pathways. Overall, GA-induced hepatotoxicity involves impaired energy production, disrupted lipid metabolism, and abnormal liver focal adhesion, leading to liver cell dysfunction. These findings highlight the vulnerability of mitochondria and critical metabolic pathways, providing insights into the molecular mechanisms of GA toxicity and guiding future studies on mitigating GA-induced liver damage in goslings.PMID:39906302 | PMC:PMC11792171 | DOI:10.3389/fvets.2025.1527284

Front Plant Sci. 2025 Jan 21;15:1483538. doi: 10.3389/fpls.2024.1483538. eCollection 2024.ABSTRACTAstragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (AMM) is an important medicinal plant that is used for both medicine and food. It is widely used in Asia and South Asia. It is normally cultivated by transplanting the annual rhizomes. Understanding the dormancy of underground buds of AMM is essential for its harvest and transplantation. Despite thorough research on bud dormancy in perennial woody plants, perennial herbs, and especially medicinal plants, such as AMM, have rarely been studied. We analyzed the transcriptome and non-targeted metabolome of dormant buds stage-by-stage to investigate the regulatory mechanism of the transition from endo- to ecodormancy. A total of 1,069 differentially accumulated metabolites (DAMs) participated in amino acid and carbohydrate metabolism. Transcriptome analysis revealed 16,832 differentially expressed genes (DEGs). Functional enrichment analysis indicated that carbohydrate metabolism, hormone signaling pathways, and amino acid metabolism contributed to the transition from endo- to ecodormancy. Starch and sucrose metabolism and hormone signaling pathways were mainly analyzed in the transition between different dormancy states. During the transition from endo- to ecodormancy, the highest content of indole-3-acetic acid (IAA) and the highest number of DEGs enriched in the IAA signaling pathway demonstrated that IAA may play a key role in this process. We obtained candidate genes through co-expression network analysis, such as BGL, GN, glgC, and glgB, which are involved in starch and sucrose metabolism. The transcription factors MYB, ERF, bHLH, zinc finger, and MADS-box may regulate the genes involved in hormone signal transduction and starch and sucrose metabolism, which are critical for regulating the transition from endo- to ecodormancy in AMM buds. In summary, these results provide insights into the novel regulatory mechanism of the transition of endo- to ecodormancy in underground buds of AMM and offer new analytical strategies for breaking dormancy in advance and shortening breeding time.PMID:39906223 | PMC:PMC11790638 | DOI:10.3389/fpls.2024.1483538

Anal Chem. 2025 Feb 5. doi: 10.1021/acs.analchem.4c05530. Online ahead of print.ABSTRACT1H NMR spectroscopy has enabled the quantitative profiling of metabolites in various biofluids, emerging as a possible diagnostic tool for metabolic disorders and other diseases. To boost the signal-to-noise ratio and detect proton resonances near the water signal, current 1H NMR experiments require solvent suppression schemes (e.g., presaturation, jump-and-return, WATERGATE, excitation sculpting, etc.). Unfortunately, these techniques affect the quantitative assessment of analytes containing exchangeable protons. To address this issue, we introduce two new one-dimensional (1D) 1H NMR techniques that eliminate the water signal, preserving the intensities of exchangeable protons. Using GENETICS-AI, a software that combines an evolutionary algorithm and artificial intelligence, we tailored new water irradiation devoid (WADE) pulses and optimized the 1D 1H NOESY sequence for metabolomic analysis. When applied to human urine samples, kidney tissue extract, and plasma, the WADE technique allowed for accurate measurement of typical metabolites and direct quantification of urea, which is usually challenging to measure using standard NMR experiments. We anticipate that these new NMR techniques will significantly improve the accuracy and reliability of metabolite quantitative assessment for a wide range of biological fluids.PMID:39905912 | DOI:10.1021/acs.analchem.4c05530

Small. 2025 Feb 5:e2410638. doi: 10.1002/smll.202410638. Online ahead of print.ABSTRACTThe development of matrices has shown great potential for fluid metabolic analysis in disease detection. However, single-fluid metabolomic analysis has been recognized as insufficient to fully capture the complexities of diseases such as liver disease, which limits detection accuracy. To this end, the hollow dodecahedral nanocages-based analytical tool is developed, featuring four-high characteristics of speed, throughput, efficiency, and patient compliance, to enhance extraction of multifluid metabolic profiles. The cross-referencing of these profiles among different liver diseases, including hepatocellular carcinoma (HCC), chronic liver disease (CLD), and healthy controls, enhances the diagnosis of liver diseases, particularly achieving near-perfect discrimination for HCC with an AUC value of 0.990, significantly outperforming any single fluid analysis. Additionally, the dynamic changes in expression levels of the key biomarkers throughout disease progression are explored, providing insights into their temporal evolution, and highlighting their role in monitoring disease status. This work highlights that multifluid metabolic analysis can comprehensively and sensitively reflect the disease status, enabling precise identification of complex diseases and facilitating personalized treatment.PMID:39905898 | DOI:10.1002/smll.202410638