PubMed

Mol Psychiatry. 2025 Jan 7. doi: 10.1038/s41380-024-02862-5. Online ahead of print.ABSTRACTA major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression. We report a sex-specific deficiency in free-carnitine levels in women with aMCI and early-AD compared to cognitively healthy controls; no change was observed in men. We also replicated the prior finding of decreased LAC levels in both women and men with AD, supporting the robustness of the study samples assayed in our new study. The magnitude of the sex-specific free-carnitine deficiency reflected the severity of cognitive dysfunction and held in two study cohorts. Furthermore, patients with the lower free-carnitine levels showed higher β-amyloid(Aβ) accumulation and t-Tau levels assayed in cerebrospinal fluid (CSF). Computational analyses showed that the mitochondrial markers assayed in plasma are at least as accurate as CSF measures to classify disease status. Together with the mechanistic platform in rodents, these translational findings lay the groundwork to create preventive individualized treatments targeting sex-specific changes in mitochondrial metabolism that may be subtle to early cognitive dysfunction of AD risk.PMID:39774493 | DOI:10.1038/s41380-024-02862-5

Sci Rep. 2025 Jan 7;15(1):1144. doi: 10.1038/s41598-025-85252-3.ABSTRACTMaternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable. We hypothesized that elevated pre-pregnancy BMI compared to a normal BMI referent group, is associated with increased circulating short and long-chain acylcarnitines and subsequent development of BPD. This was a retrospective study with linkage of maternal pre-pregnancy BMI, with newborn screen metabolites obtained from the California Newborn Screening Program and further linked with neonatal outcomes. Results demonstrated elevated levels of phenylalanine and proline associated with an increased risk for BPD (OR 5.3, 95% CI 1.2-23.8 and OR 5.4, 95% CI 1.3-22.3) in the obesity group compared to the referent group. Short- and long-chain acylcarnitines demonstrated a mildly increased risk for BPD in neonates of mothers with severe obesity compared to controls. The findings suggest that specific metabolites may influence the molecular conditioning that increases susceptibility to BPD.PMID:39774255 | DOI:10.1038/s41598-025-85252-3

Sci Rep. 2025 Jan 8;15(1):1248. doi: 10.1038/s41598-025-85354-y.ABSTRACTAcute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration of genetic variants across the genome in a study population of 10,630 AP cases and 844,679 non-AP individuals revealed multiple lipidome entities significantly associated with AP risk. The study identified 23 lipid species with unidirectional causal effects on AP after accounting for heterogeneity, pleiotropy, and potential reverse causation. Additionally, five inflammatory factors (CD5, IL-13, MMP-1, STAMBP, TNFRSF9) showed significant potential causal relationship with AP. Further analysis elucidated the intricate interplay between specific lipid species and inflammatory mediators in influencing AP incidence. Notably, Sterol ester (27:1/20:4) and several phosphatidylcholine species, including PC (17:0_20:4), PC (18:0_20:4), PC (18:0_20:5), and PC (O-18:2_20:4), were negatively associated with AP risk. This protective effect was partially mediated through decreased levels of inflammatory markers, particularly STAMBP and MMP-1. The study found that these phosphatidylcholines and sterol esters significantly reduced the levels of these pro-inflammatory factors, thereby potentially mitigating AP risk. Conversely, Phosphatidylinositol (16:0_18:1) demonstrated a positive association with AP risk. This detrimental effect was partially mediated by increased levels of MMP-1 and STAMBP, suggesting a pro-inflammatory mechanism. The study provides evidence that this specific phosphatidylinositol species may exacerbate AP risk by promoting inflammatory pathways. These findings elucidate the complex interplay between lipid metabolites, inflammation, and AP pathogenesis, potentially informing novel therapeutic strategies. The study highlights the utility of Mendelian randomization in uncovering potential causal relationship in AP. It underscores the requirement for further study into the molecular mechanisms underlying lipid-mediated inflammation in AP, particularly the roles of phosphatidylcholines and sterol esters in modulating inflammatory responses. Further studies are warranted to confirm our observations in laboratory models and assess their translational value in developing AP preventive and therapeutic strategies.PMID:39774240 | DOI:10.1038/s41598-025-85354-y

Curr Opin HIV AIDS. 2024 Dec 17. doi: 10.1097/COH.0000000000000907. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To summarize the heterogeneity in the elite controllers population with the aim to identify a compatible profile with a persistent HIV remission, making distinction between persistent elite controllers, people with HIV (PWHIV) who permanently maintain virological control in the absence of antiretroviral treatment (ART), and transient elite controllers, PWHIV who eventually lose virological control. For this purpose, it is important to consider the mechanisms and biomarkers that have previously been associated with the maintenance and loss of the natural virological control.RECENT FINDINGS: Transient elite controllers, before losing virological control, exhibit a distinct metabolomic, proteomic, microRNAs (miRNA), immunological and virological profile compared to persistent elite controllers. In addition to a reduced and less polyfunctional HIV-specific T-cell response, transient elite controllers show a greater proportion of intact proviruses integrated into genic regions. In contrast, persistent elite controllers display a privileged HIV-1 reservoir profile with absence of detected intact proviruses or low proportion of clonal intact proviruses preferentially integrated into genomic features associated with HIV-1 transcriptional repression.SUMMARY: According to previous studies, the comprehensive characterization of persistent elite controllers might be crucial to identify other PWHIV with this distinct profile as spontaneously cured.PMID:39773856 | DOI:10.1097/COH.0000000000000907

J Biomed Sci. 2025 Jan 8;32(1):6. doi: 10.1186/s12929-024-01098-3.ABSTRACTBACKGROUND: Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective and safe clinical treatment strategies still need to be deeply explored. Increased number and volume of adipocytes lead to overweight and obesity. The aim of our work is to identify lncRNAs that have important regulatory in differentiation of human mesenchymal stem cells (MSCs) into adipocytes, and to provide effective targets for clinical prevention and treatment of obesity and related metabolic disorders.METHODS: We extracted primary MSCs from human adipose tissue, and conducted expression profile analysis of lncRNAs during adipogenic differentiation of MSCs to screen changed lncRNAs. Characteristics of lncRNA were revealed mainly by RACE and RNA FISH. Loss- and gain-of function experiments in vivo and in vitro were used to analyze effects of lncRNA. Targeted metabolomics was utilized to detect levels of free fatty acids. RNA pull-down, mRNA stability tests, etc. were employed to explore mechanisms of lncRNA.RESULTS: Human-specific lncRNA, we named it MEK6-AS1, was the most up-regulated transcript during adipogenic differentiation of MSCs. MEK6-AS1 was highly expressed in adipose tissue samples from individuals with BMI ≥ 25 and positively correlated with adipogenic marker genes in these samples. Knocking down lncRNA inhibited expression of adipogenic differentiation markers and ectopic adipogenesis, reducing contents of various free fatty acids, as well as promoting osteogenic differentiation. Overexpression of lncRNA had the opposite effects to the above processes. We also found that MEK6-AS1 was elevated during hepatic steatosis organoid generation. Mechanistically, MEK6-AS1 worked partially through stabilization of MEK6 mRNA by NAT10.CONCLUSIONS: We have identified a human-specific lncRNA (MEK6-AS1) with position information in the genomic database but has not been extensively reported. We demonstrated that MEK6-AS1 as a novel lncRNA involved in adipogenic differentiation and adipogenesis, fatty acid metabolism, and osteogenic differentiation. We found that MEK6-AS1 may exert its effect by enhancing MEK6 mRNA stability through NAT10. Our study may provide insights into implication of lncRNAs in stem cell biology and offer a new potential therapeutic target for the prevention and treatment of obesity and other related disease.PMID:39773638 | DOI:10.1186/s12929-024-01098-3

Aging (Albany NY). 2025 Jan 6;16. doi: 10.18632/aging.206187. Online ahead of print.ABSTRACTSo far, it has been proven that benign prostatic hyperplasia (BPH) is strongly associated with inflammation resulting from, i.a. the presence of infectious agent, autoimmune disease, aging process and lipid disorders associated with metabolic syndrome (MetS). We analyzed the association between serum eicosanoides (HETE, HODE, lipoxins, prostaglandin, and leucotrien) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 219 men (with BPH, n = 144; healthy controls, n = 75). We assessed the content arachidonic and linoleic acid derivatives in the serum samples of the study participants using liquid chromatography (HPLC). The levels of: RvE1 (p < 0.001); LXA4 5S,6R,15R (p = 0.001); 10S,17R-DiDHA (p < 0.001); MaR1 (p = 0.002); 9S-HODE (p < 0.05); 15S-HETE (p < 0.05); 12S-HETE (p < 0.001); 5-oxoETE (p < 0.05) and 5-HETE (p < 0.001) were significantly higher in patients with BPH than in the control group. PGE2 (p = 0.007), LTB4 (p < 0.001), and 18RS-HEPE (p < 0.001) were significantly higher in control group. We also analyzed the relationship between LXA4 5S,6R,15R serum levels of oxidative stress markers and concomitance of MetS. We noticed a relationship between levels and MetS (F1216 = 6.114965, p = 0.01). Our research results suggest that pro-inflammatory mediators and suppressors of inflammation are involved in the development of BPH, but their exact contribution has yet to be investigated.PMID:39773533 | DOI:10.18632/aging.206187

Eur J Med Res. 2025 Jan 7;30(1):10. doi: 10.1186/s40001-024-02245-0.ABSTRACTBACKGROUND: Burn-hemorrhagic shock combined injury, a severe condition causing complex stress responses and metabolic disturbances that significantly affect clinical outcomes in both military and civilian settings, was modeled in swine to investigate the associated metabolomic and proteomic changes and identify potential biomarkers for disease prognosis.METHODS: Eight clean-grade adult male Landrace pigs (4-5 months, average weight 60-70 kg) were used to model burn-hemorrhagic shock combined injury. Serum samples collected at 0 h and 2 h post-injury were analyzed using metabolomic and proteomic measurements. The metabolomic and proteomic data were processed through partial least squares-discriminant analysis (PLS-DA) and the KEGG enrichment etc. Furthermore, the integrate analysis of the metabolomic and proteomic data was generalized by canonical correlation discriminant analysis, and the correlation between metabolites and mortality of the swine model was predicted using a multiple linear regression model by Pearson analysis.RESULTS: PLS-DA revealed a global shift in each of the metabolomic and proteomic profiles following injury. The levels of 87 signature metabolites including various types of amino acids, fatty acids and acyl-carnitines of different lengths, and many metabolites in the gluconeogenesis, glycolysis, and tricarboxylic acid (TCA) cycle are generally increased (P < 0.05) after injury and can be used as biomarkers. Pathways related to amino acids metabolism and TCA cycle were significantly enriched (P < 0.01). In proteome analysis, we found dramatically altered (P < 0.05) levels of matrix and red blood cell-related proteins, such as type I collagen and hemoglobin. Most importantly, we found that the markedly elevated (P < 0.01) succinic acid, glutaric acid, and malic acid are closely associated (r = 0.863, 0.861, and 0.821, respectively) with injury severity by Pearson analysis, and can predict mortality using a multiple linear regression model.CONCLUSIONS: The study provides compelling observations that burn-shock swine model undergoes dramatic changes in the acute phase and present a valuable panel for clinical use of prognosis.PMID:39773520 | DOI:10.1186/s40001-024-02245-0

Microb Cell Fact. 2025 Jan 7;24(1):9. doi: 10.1186/s12934-024-02636-2.ABSTRACTBACKGROUND: Sporobolomyces pararoseus is a well-studied oleaginous red yeast that can synthesize a variety of high value-added bioactive compounds. Biofilm is one of the important biological barriers for microbial cells to resist environmental stresses and maintain stable fermentation process. Here, the effect of acidic conditions on the biosynthesis of biofilms in S. pararoseus NGR was investigated through the combination of morphology, biochemistry, and multi-omics approaches.RESULTS: The results showed that the acidic environment was the key factor to trigger the biofilm formation of S. pararoseus NGR. When S. pararoseus NGR was cultured under pH 4.7, the colony morphology was wrinkled, the cells were wrapped by a large amount of extracellular matrix, and the hydrophobicity and anti-oxidative stress ability were significantly improved, and the yield of intracellular carotenoids was significantly increased. Transcriptome and metabolome profiling indicated that carbohydrate metabolism, amino acid metabolism, lipid metabolism, and nucleic acid metabolism in S. pararoseus NGR cells were significantly enriched in biofilm cells under pH 4.7 culture conditions, including 56 differentially expressed genes and 341 differential metabolites.CONCLUSIONS: These differential genes and metabolites may play an important role in the formation of biofilms by S. pararoseus NGR in response to acidic stress. The results will provide strategies for the development and utilization of beneficial microbial biofilms, and provide theoretical support for the industrial fermentation production of microorganisms to improve their resistance and maintain stable growth.PMID:39773469 | DOI:10.1186/s12934-024-02636-2

BMC Plant Biol. 2025 Jan 8;25(1):28. doi: 10.1186/s12870-024-06035-y.ABSTRACTEffective Microorganism (EM) is widely employed as a growth promoter in agricultural practices. The aging of oat seeds not only directly impairs agricultural production but also exerts adverse effects on biodiversity. The mechanism through which EM influence the germination of aging seeds remains unclear. In this experiment, the EM bacterial solution underwent pretreatment, which included the original-solution treatment (OrT), supernatant treatment (SuT), and sterile treatment (StT). Aging of oat seeds was induced using the pretreated EM bacterial solution. In this study, the EM bacterial solution facilitated the enhancement of the germination rate, germination index, and vitality index of aged seeds, with SuT demonstrating the most pronounced effects. Specifically, SuT resulted in a significant increase in APX and POD activities, while significantly reducing the malondialdehyde content. In addition, metabolic profiling highlighted the significance of 5-phosphoribosylamine in the purine metabolic pathway. Particularly in the SuT, the upregulation of 5-phosphoribosylamine facilitated the synthesis of (R)-Allantoin, consequently augmenting antioxidant enzyme activity.PMID:39773191 | DOI:10.1186/s12870-024-06035-y

Physiol Genomics. 2025 Jan 7. doi: 10.1152/physiolgenomics.00106.2024. Online ahead of print.ABSTRACTPreeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE three-fold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short chain fatty acids (SCFA) compared to controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 compared to C57 controls was different using PERMANOVA with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared to controls. Alistipes and Helicobacter were increased while Bacteroides, Lactobacillus, Parasulterrella, and Parabacteroides were decreased compared to controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acid were decreased while isobutyric and isovaleric acid were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, GPR41. In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype.PMID:39773069 | DOI:10.1152/physiolgenomics.00106.2024

Microbiol Spectr. 2025 Jan 8:e0190124. doi: 10.1128/spectrum.01901-24. Online ahead of print.ABSTRACTLimnospira can colonize a wide variety of environments (e.g., freshwater, brackish, alkaline, or alkaline-saline water) and develop dominant and even permanent blooms that overshadow and limit the diversity of adjacent phototrophs, especially in alkaline and saline environments. Previous phylogenomic analysis of Limnospira allowed us to distinguish two major phylogenetic clades (I and II) but failed to clearly segregate strains according to their respective habitats in terms of salinity or biogeography. In the present work, we attempted to determine whether Limnospira displays metabolic signatures specific to its different habitats, particularly brackish and alkaline-saline ecosystems. The impact of accessory gene repertoires on respective chemical adaptations was also determined. In complement of our previous phylogenomic investigation of Limnospira (Roussel et al., 2023), we develop a specific analysis of the metabolomic diversity of 93 strains of Limnospira, grown under standardized lab culture conditions. Overall, this original work showed distinct chemical fingerprints that were correlated with the respective biogeographic origins of the strains. The molecules that most distinguished the different Limnospira geographic groups were sugars, lipids, peptides, photosynthetic pigments, and antioxidants. Interestingly, these molecular enrichments might represent consequent adaptations to conditions of salinity, light, and oxidative stress in their respective sampling environments. Although the genes specifically involved in the production of these components remain unknown, we hypothesized that within extreme environments, such as those colonized by Limnospira, a large set of flexible genes could support the production of peculiar metabolite sets providing remarkable adaptations to specific local environmental conditions.IMPORTANCE: Limnospira are ubiquitous cyanobacteria with remarkable adaptive strategies allowing them to colonize and dominate a wide range of alkaline-saline environments worldwide. Phylogenomic analysis of Limnospira revealed two distinct major phylogenetic clades but failed to clearly segregate strains according to their habitats in terms of salinity or biogeography. We hypothesized that the genes found within this variable portion of the genome of these clades could be involved in the adaptation of Limnospira to local environmental conditions. In the present paper, we attempted to determine whether Limnospira displayed metabolic signatures specific to its different habitats. We also sought to understand the impact of the accessory gene repertoire on respective chemical adaptations.PMID:39772964 | DOI:10.1128/spectrum.01901-24

J Proteome Res. 2025 Jan 8. doi: 10.1021/acs.jproteome.4c00939. Online ahead of print.ABSTRACTSkeletal muscle aging poses a major threat to the health and quality of life of elderly individuals. Fisetin, a natural polyphenolic compound, exhibits various biological activities; however, its role in preventing skeletal muscle cell aging is still unclear. This study aimed to elucidate the effects of fisetin on skeletal muscle aging using a d-galactose-induced C2C12 myoblast senescence model. Fisetin treatment effectively ameliorated d-galactose-induced aging damage and restored cellular functionality by improving cell viability, reducing the accumulation of the senescence marker enzyme SA-β-gal, and decreasing the expression of key aging marker proteins, p16 and p53. NMR-based metabolomics and RNA-seq transcriptomics analyses revealed that fisetin regulates several critical metabolic pathways, including glutathione metabolism, glycine, serine and threonine metabolism, as well as taurine and hypotaurine metabolism. This regulation led to the restoration of amino acid metabolism, stabilization of cellular energy homeostasis, and the preservation of membrane integrity. In addition, fisetin inhibited calcium signaling and JAK-STAT pathways, reduced cellular stress responses and reversed senescence-induced cell cycle arrest. Together, these findings highlight the potential of fisetin as a therapeutic agent to combat skeletal muscle aging and restore cellular homeostasis, offering a promising avenue for the development of antiaging treatments for skeletal muscle degeneration.PMID:39772754 | DOI:10.1021/acs.jproteome.4c00939

mSystems. 2025 Jan 7:e0003824. doi: 10.1128/msystems.00038-24. Online ahead of print.ABSTRACTInfectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms. Parasite drug resistance and persistence, drug pharmacokinetics and dynamics, as well as persistently altered host immune responses and tissue damage are the most common reasons for Chagas disease treatment failure. We discuss the therapeutics that failed before regulatory approval, limitations of current therapeutic options and new treatment strategies to overcome persistent parasites, inflammatory responses, and metabolic alterations. Large-scale omics analyses were critical in generating these insights and will continue to play a prominent role in addressing the challenges still facing Chagas disease drug treatment.PMID:39772644 | DOI:10.1128/msystems.00038-24

Anal Chem. 2025 Jan 7. doi: 10.1021/acs.analchem.4c04421. Online ahead of print.ABSTRACTThe integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels. Together, this study presents a methodology that enables sequential extraction and profiling of metabolomics, lipidomics, genomics, transcriptomics, proteomics, and phosphoproteomics using biopsy tissue specimens.PMID:39772508 | DOI:10.1021/acs.analchem.4c04421

Chem Res Toxicol. 2025 Jan 8. doi: 10.1021/acs.chemrestox.4c00449. Online ahead of print.ABSTRACTDeficiency of the V-domain immunoglobulin suppressor of T-cell activation (VISTA) accelerates disease progression in lupus-prone mice, and activation of VISTA shows therapeutic effects in mouse models of a lupus-like disease. Metabolic reprogramming of T cells in systemic lupus erythematosus (SLE) patients is important in regulating T-cell function and disease progression. However, the mechanism by which VISTA affects the immunometabolism in SLE remains unclear. Here, we demonstrated that the deficiency of VISTA promoted the synthesis of the metabolite lysophosphatidylcholine (LPC) using untargeted metabolomics and increased the protein expression of the CD40 ligand (CD40L). Furthermore, baloxavir marboxil (BXM), a small molecule agonist of VISTA, significantly ameliorated autoantibody production, renal damage, and imbalance of immune cell subpopulations in the models of a lupus-like disease in mice (chronic graft-versus-host disease and MRL/MpJ-Faslpr/J mice) possibly by inhibiting LPC synthesis to downregulate CD40L protein expression and inhibiting aberrant activation of noncanonical nuclear factor-κB pathway. Our results indicated that BXM targeting VISTA ameliorated lupus-like symptoms by altering lipid metabolism and CD40L expression, which offers novel mechanisms and a promising therapy for SLE.PMID:39772456 | DOI:10.1021/acs.chemrestox.4c00449

ACS Appl Mater Interfaces. 2025 Jan 8. doi: 10.1021/acsami.4c20503. Online ahead of print.ABSTRACTThyroid nodules are a very common entity. The overall prevalence in the populace is estimated to be around 65-68%, among which a small portion (less than 5%) is malignant (cancerous). Therefore, it is important to discriminate benign thyroid nodules from malignant thyroid nodules. In this study, an equal number of participants with benign and malignant thyroid nodules (N = 10/group) were recruited. Saliva samples were collected from each participant, and SERS spectra were acquired, followed by validation using a metabolomics approach. An additional equal number of patients (N = 40/group) were recruited to construct diagnostic models. The performance of various machine learning (ML) algorithms was assessed using multiple evaluation metrics. Finally, the reliability of the optimal model was tested using blind test data (N = 10/group for benign and malignant thyroid nodules). The results showed a consistent trend between the SERS metabolic profile and the metabolites identified through MS analysis. The Multi-ResNet algorithm was optimal, achieving a 95% accuracy in sample discrimination. Additionally, blind test data sets yielded an overall accuracy of 83%. In summary, the deep-learning-guided SERS technique holds great potential in the accurate discrimination of benign and malignant thyroid nodules via human saliva samples, which facilitates the noninvasive diagnosis of malignant thyroid nodules in clinical settings.PMID:39772412 | DOI:10.1021/acsami.4c20503

Vaccines (Basel). 2024 Dec 17;12(12):1421. doi: 10.3390/vaccines12121421.ABSTRACTFollowing the publication of paper [...].PMID:39772114 | DOI:10.3390/vaccines12121421

Plants (Basel). 2024 Dec 19;13(24):3554. doi: 10.3390/plants13243554.ABSTRACTRice sheath blight (RSB), caused by the pathogenic fungus Rhizoctonia solani, poses a significant threat to global food security. The defense mechanisms employed by rice against RSB are not well understood. In our study, we analyzed the interactions between rice and R. solani by comparing the phenotypic changes, ROS content, and metabolite variations in both tolerant and susceptible rice varieties during the early stages of fungal infection. Notably, there were distinct phenotypic differences in the response to R. solani between the tolerant cultivar Zhengdao22 (ZD) and the susceptible cultivar Xinzhi No.1 (XZ). We observed that the activities of five defense-related enzymes in both tolerant and susceptible cultivars changed dynamically from 0 to 72 h post-infection with R. solani. In particular, the activities of superoxide dismutase and peroxidase were closely associated with resistance to RSB. Metabolomic analysis revealed 825 differentially accumulated metabolites (DAMs) between the tolerant and susceptible varieties, with 493 DAMs responding to R. solani infection. Among these, lipids and lipid-like molecules, organic oxygen compounds, phenylpropanoids and polyketides, organoheterocyclic compounds, and organic acids and their derivatives were the most significantly enriched. One DAM, P-coumaraldehyde, which responded to R. solani infection, was found to effectively inhibit the growth of R. solani, Magnaporthe grisea, and Ustilaginoidea virens. Additionally, multiple metabolic pathways, including amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and metabolism of terpenoids and polyketides, are likely involved in RSB resistance. Our research provides valuable insights into the molecular mechanisms underlying the interaction between rice and R. solani.PMID:39771252 | DOI:10.3390/plants13243554

Plants (Basel). 2024 Dec 17;13(24):3528. doi: 10.3390/plants13243528.ABSTRACTBlueberry plants are among the most important fruit-bearing shrubs, but they have shallow, hairless roots that are not conducive to water and nutrient uptake, especially under drought conditions. Therefore, the mechanism underlying blueberry root drought tolerance should be clarified. Hence, we established a yeast expression library comprising blueberry genes associated with root responses to drought stress. High-throughput sequencing technology enabled the identification of 1475 genes potentially related to drought tolerance. A subsequent KEGG enrichment analysis revealed 77 key genes associated with six pathways: carbon and energy metabolism, biosynthesis of secondary metabolites, nucleotide and amino acid metabolism, genetic information processing, signal transduction, and material transport and catabolism. Metabolomic profiling of drought-tolerant yeast strains under drought conditions detected 1749 differentially abundant metabolites (DAMs), including several up-regulated metabolites (organic acids, amino acids and derivatives, alkaloids, and phenylpropanoids). An integrative analysis indicated that genes encoding several enzymes, including GALM, PK, PGLS, and PIP5K, modulate key carbon metabolism-related metabolites, including D-glucose 6-phosphate and β-D-fructose 6-phosphate. Additionally, genes encoding FDPS and CCR were implicated in terpenoid and phenylalanine biosynthesis, which affected metabolite contents (e.g., farnesylcysteine and tyrosine). Furthermore, genes for GST and GLT1, along with eight DAMs, including L-γ-glutamylcysteine and L-ornithine, contributed to amino acid metabolism, while genes encoding NDPK and APRT were linked to purine metabolism, thereby affecting certain metabolites (e.g., inosine and 3',5'-cyclic GMP). Overall, the yeast functional screening system used in this study effectively identified genes and metabolites influencing blueberry root drought tolerance, offering new insights into the associated molecular mechanisms.PMID:39771226 | DOI:10.3390/plants13243528

Plants (Basel). 2024 Dec 14;13(24):3495. doi: 10.3390/plants13243495.ABSTRACTTo investigate the effects of different light qualities on the growth, photosynthesis, transcriptome, and metabolome of mint, three treatments were designed: (1) 7R3B (70% red light and 30% blue light, CK); (2) 7R3B+ far-red light (FR); (3) 7R3B+ ultraviolet light A (UVA). The results showed that supplemental FR significantly promoted the growth and photosynthesis of mint, as evidenced by the increase in plant height, plant width, biomass, effective quantum yield of PSII photochemistry (Fv'/Fm'), maximal quantum yield of PSII (Fv/Fm), and performance index (PI). UVA and CK exhibited minimal differences. Transcriptomic and metabolomic analysis indicated that a total of 788 differentially expressed genes (DEGs) and 2291 differential accumulated metabolites (DAMs) were identified under FR treatment, mainly related to plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis. FR also promoted the accumulation of phenylalanine, sinapyl alcohol, methylchavicol, and anethole in the phenylpropanoid biosynthesis pathway, and increased the levels of luteolin and leucocyanidin in the flavonoid biosynthesis pathway, which may perhaps be applied in practical production to promote the natural antibacterial and antioxidant properties of mint. An appropriate increase in FR radiation might alter transcript reprogramming and redirect metabolic flux in mint, subsequently regulating its growth and secondary metabolism. Our study uncovered the regulation of FR and UVA treatments on mint in terms of growth, physiology, transcriptome, and metabolome, providing reference for the cultivation of mint and other horticultural plants.PMID:39771193 | DOI:10.3390/plants13243495