PubMed

Diabetes Res Clin Pract. 2023 Nov;205:110986. doi: 10.1016/j.diabres.2023.110986. Epub 2023 Oct 28.ABSTRACTAIMS: To explore the clinical factors and urinary metabolites that predict biopsy-confirmed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM).METHODS: Data from the medical records of 126 patients with T2DM who underwent kidney biopsy between January 2010 and October 2020 at a single-center were retrospectively reviewed to investigate the clinical factors that predict DN. Urine samples were collected to perform urine metabolomics in patients with T2DM divided by biopsy-confirmed DN, immunoglobulin A, and membranous nephropathy, and a control group of healthy participants. Each group comprised 11 age- and sex-matched participants. A prediction model was developed using a combination of clinical factors and urinary metabolites, and a multivariate receiver operating characteristic (ROC) analysis was conducted.RESULTS: Age, presence of proliferative diabetic retinopathy, T2DM duration, and hemoglobin A1c levels were clinical factors predictive of DN. Four urinary metabolites (alanine, choline, N-phenylacetylglycine, and trigonelline) had variable importance in projection scores > 1 and were predictive of DN. When conducting multivariate ROC analysis with a combination of clinical factors and urinary metabolites, the area under the curve was 1.000.CONCLUSIONS: The combination of clinical factors and urinary metabolites is highly valuable for predicting biopsy-confirmed DN in patients with T2DM.PMID:39445434 | DOI:10.1016/j.diabres.2023.110986

Front Plant Sci. 2024 Oct 9;15:1466493. doi: 10.3389/fpls.2024.1466493. eCollection 2024.ABSTRACTINTRODUCTION: Alfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa.METHODS: In this study, we root applied 0.1, 0.5, and 1 mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes.RESULTS: The results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid.DISCUSSION: In conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress.PMID:39445141 | PMC:PMC11496139 | DOI:10.3389/fpls.2024.1466493

Front Immunol. 2024 Oct 9;15:1463078. doi: 10.3389/fimmu.2024.1463078. eCollection 2024.ABSTRACTOBJECT: Osteosarcoma is a malignant tumor originating from the bones, commonly found in children and adolescents, especially in rapidly growing bone areas such as the knees and upper arms. In this study, we aim to delineate the evolution and convergence of research themes in osteosarcoma metabolomics over the past decade, identify major contributors, and forecast emerging trends that could direct future research efforts.METHOD: The bibliometric method has been applied to systematically analyze the literature in the field of osteosarcoma metabolomics. The relevant literatures were collected from the Web of Science Core Collection, spanning from January 1, 2014, to December 31, 2023. Tools such as CiteSpace, Bibliometrix, and VOSviewer were used for the visual analysis of the collected literatures. The focused information includes institutions, journals, countries, authors, keywords, and citations.RESULT: Various aspects in the field of osteosarcoma metabolism were analyzed. Shanghai Jiao Tong University has published the most papers in the past ten years, followed by Central South University and Zhejiang University. Among the sources, the international journal of molecular sciences publishes the most articles, and oncotarget is the journal with the highest H index. According to Bradford's law, there are 34 core journals identified. A total of 5501 authors participated in the creation of papers in this field. The distribution of authors follows Lotka`s Law, and 85.3% of authors have only one article. 46% of the corresponding authors are from China, but most of these corresponding authors are not good at international cooperation. China also has the largest number of publications, followed by the United States. It can be confirmed that China dominates this field. Among the keywords, "expression" is the keyword that has received the most attention in the past ten years. All keywords can be divided into 9 clusters. Based on the explosive words and hot topics each year, we speculate that future research will focus on the tumor microenvironment, molecular mechanisms and autophagy, targeted therapies and inhibitors.CONCLUSION: In summary, this study comprehensively analyzed the current state of research in the field of osteosarcoma metabolism through bibliometric methods. The findings revealed the development trends and research hotspots in this field, which may provide valuable references for future research directions.PMID:39445018 | PMC:PMC11496093 | DOI:10.3389/fimmu.2024.1463078

JACC Basic Transl Sci. 2024 Jul 31;9(9):1144-1158. doi: 10.1016/j.jacbts.2024.04.008. eCollection 2024 Sep.ABSTRACTBoth heart failure and cardiometabolic disease are on the rise, and abnormal cardiac and peripheral metabolism are central to the syndrome of heart failure. Advances in metabolomic profiling have improved our understanding of the heart's metabolic flexibility in patients with and without heart failure. Prior studies have noted patients with heart failure display metabolomic profiles associated with marked abnormalities in the metabolism of fatty acids, branched-chain amino acids, ketones, and glucose compared with control subjects. Metabolomics can highlight specific pathways that are dysregulated; however, other metabolites beyond those related to fuel metabolism may also play a role in precision-medicine approaches. Novel approaches include metabolic flux studies, spatial and single-cell analysis, serial monitoring of treatment response, and integration with other -omics data. The goal of these innovative approaches should be to harness metabolomic technologies to affect precision care for patients with heart failure.PMID:39444924 | PMC:PMC11494393 | DOI:10.1016/j.jacbts.2024.04.008

Front Physiol. 2024 Oct 9;15:1456664. doi: 10.3389/fphys.2024.1456664. eCollection 2024.ABSTRACTINTRODUCTION: Spaghetti meat (SM) and wooden breast (WB) are emerging myopathies in the breast meat of fast-growing broiler chickens. The purpose of the study was to investigate the metabolomic differences between normal (N), SM, and WB fillets 24 h postmortem.MATERIALS AND METHODS: Eight chicken breasts for each experimental group were collected from a commercial processing plant. Supernatant from tissue homogenates were subjected to ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS) analysis.RESULTS AND METHODS: A total of 3,090 metabolites were identified in the chicken breast meat. The comparison of WB and N showed 850 differential metabolites (P < 0.05), and the comparison of SM and N displayed 617 differential metabolites. The comparison of WB and SM showed 568 differential metabolites. The principal component analysis (PCA) plots showed a distinct separation between SM and N and between WB and N except for one sample, but SM and WB were not distinctly separated. Compared to N, 15-Hydroxyeicosatetraenoic acid (15-HETE) increased, and D-inositol-4-phosphate decreased in both SM and WB, indicating that cellular homeostasis and lipid metabolism can be affected in SM and WB. The abundance of nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH) was exclusively decreased between SM and N (P < 0.05). Purine metabolism was upregulated in SM and WB compared to N with a greater degree of upregulation in WB than SM. Folic acid levels decreased in SM and WB compared to N (P < 0.05). Steroid hormone biosynthesis was downregulated in SM compared to N (P < 0.05). Carbon metabolism was downregulated in SM and WB compared to N with greater degree of downregulation in WB than SM (P < 0.05). These data suggest both shared and unique metabolic alterations in SM and WB, indicating commonalities and differences in their underlying etiologies and meat quality traits. Dietary supplementation of deficient nutrients, such as NADH, folic acids, etc. and modulation of altered pathways in SM and WB would be strategies to reduce the incidence and severity of SM and WB.PMID:39444756 | PMC:PMC11496178 | DOI:10.3389/fphys.2024.1456664

Front Vet Sci. 2024 Oct 9;11:1475564. doi: 10.3389/fvets.2024.1475564. eCollection 2024.ABSTRACTINTRODUCTION: Fatty liver disease in dairy cows is a metabolic disorder that significantly affects their health and productivity, imposing a notable economic burden on the global dairy industry. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target features, has shown unique advantages in the prevention and treatment of various diseases. Guiqi Yimu Powder, a traditional TCM formula, enhances growth, boosts production efficiency, and strengthens immune function in livestock by regulating antioxidant along with anti-inflammatory pathways. However, its specific regulatory mechanisms on fatty liver in dairy cows remain unclear. This study aims to investigate the molecular-level effects and potential regulatory mechanisms of Guiqi Yimu Powder in a Trimethylamine N-oxide (TMAO) induced fatty liver cell model of dairy cows.METHODS: We employed a comprehensive analysis integrating transcriptomics, proteomics, metabolomics, and network pharmacology. An in vitro dairy cow fatty liver cell model was established using TMAO to induce lipid accumulation. Cells were treated with the optimal TMAO concentration identified through preliminary experiments, and further divided into a lipid accumulation group and Guiqi Yimu Powder treatment groups. The treatment groups received varying concentrations of Guiqi Yimu Powder (10, 20, 30, 40, or 50 g/L). High-throughput omics sequencing technologies were utilized to perform a comprehensive analysis of the treated cells. Bioinformatics methods were applied to explore the regulatory effects, aiming to elucidate the specific impacts of Guiqi Yimu Powder on lipid metabolism, liver function, and related signaling pathways, thereby providing scientific evidence for its potential application in the prevention and treatment of fatty liver in dairy cows.RESULTS: Guiqi Yimu Powder treatment significantly affected 1,536 genes, 152 proteins, and 259 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules are involved in multiple pathways related to the pathology of fatty liver, including metabolic pathways, glutathione metabolism, hepatitis B, and AMPK signaling pathway (p < 0.05). Notably, joint analysis highlighted the regulatory mechanisms of Guiqi Yimu Powder on glutathione cycling, with L-5-Oxoproline identified as an important metabolic compound. These findings indicate its impact on oxidative stress, energy metabolism, and liver function, suggesting potential therapeutic applications for fatty liver in dairy cows.DISCUSSION: This study elucidated the regulatory mechanisms of Guiqi Yimu Powder on fatty liver cells in dairy cows, providing new scientific evidence for its potential application in the prevention and treatment of fatty liver disease.PMID:39444735 | PMC:PMC11497463 | DOI:10.3389/fvets.2024.1475564

Front Microbiol. 2024 Oct 9;15:1471732. doi: 10.3389/fmicb.2024.1471732. eCollection 2024.ABSTRACTThe rumen microbiota-a symbiont to its host and consists of critical functional substances-plays a vital role in the animal body and represents a new perspective in the study of adaptive evolution in animals. This study used Slide Viewer slicing analysis system, gas chromatography, RT-qPCR and other technologies, as well as 16S and metabolomics determination methods, to measure and analyze the microstructure of rumen epithelium, rumen fermentation parameters, rumen transport genes, rumen microbiota and metabolites in Tibetan sheep and Hu sheep. The results indicate that the rumen nipple height and cuticle thickness of Tibetan sheep are significantly greater than those of Hu sheep (p < 0.01) and that the digestion and absorption of forage are greater. The levels of carbohydrate metabolism, lipid metabolism, and protein turnover were increased in Tibetan sheep, which enabled them to ferment efficiently, utilize forage, and absorb metabolic volatile fatty acids (VFAs). Tibetan sheep rumen metabolites are related to immune function and energy metabolism, which regulate rumen growth and development and gastrointestinal homeostasis. Thus, compared with Hu sheep, Tibetan sheep have more rumen papilla and cuticle corneum, and the synergistic effect of the microbiota and its metabolites is a characteristic and strategy for adapting to high-altitude environments.PMID:39444691 | PMC:PMC11496609 | DOI:10.3389/fmicb.2024.1471732

Front Microbiol. 2024 Oct 9;15:1420922. doi: 10.3389/fmicb.2024.1420922. eCollection 2024.ABSTRACTWalnut (Juglans spp.), a significant deciduous tree of economic and ecological importance, faces substantial threats from walnut anthracnose, primarily caused by Colletotrichum gloeosporioides. Bacillus velezensis has shown promise in mitigating this fungal pathogen. To delve deeper into the induction mechanism of B. velezensis on walnut plant resistance, we conducted a metabolomic analysis on walnut leaves from six different treatment groups. Specifically, the groups were defined as follows: Group B.v. was inoculated with B. velezensis alone, Group CK served as the blank control, and Group C.g. was inoculated solely with C. gloeosporioides. Group B.v.-C.g. received B. velezensis followed by C. gloeosporioides inoculation. Group B.v.+C.g. underwent simultaneous inoculation with both B. velezensis and C. gloeosporioides, while Group C.g.-B.v. was treated first with C. gloeosporioides then B. velezensis. A total of 1,503 metabolites were detected, mainly including flavonoids, terpenoids, and steroids. The results revealed that B. velezensis spraying not only enhanced the inherent resistance of walnut plants but also significantly regulated walnut plants already infected with C. gloeosporioides. This was mainly achieved by inducing walnut plants to adjust their metabolic pathways such as salicylic acid, jasmonic acid, and abscisic acid, thereby strengthening their stress response. Transcriptomic and metabolomic correlation analyses showed that in the comparisons of B.v. vs. CK, C.g. vs. CK, and C.g.-B.v. vs. C.g., 59, 244, and 122 differential abundance metabolites were detected, along with 7860, 3677, and 5587 differential genes, respectively. Amino acid synthesis, starch and sucrose metabolism, photosynthesis, phenylpropane metabolism, purine metabolism, and glutathione metabolism played crucial roles in walnut's disease resistance mechanism. Further analysis revealed that B. velezensis induced walnut plants to regulate multiple genes, such as LOC109005403, LOC108985444 and LOC118344177, resulting in the production of defensive metabolites such as palmitic acid, coumarin and ferulic acid, thereby enhancing their resistance to C. gloeosporioides. In summary, B. velezensis induces systemic resistance in walnut plants by modulating the metabolic pathways of salicylic acid, jasmonic acid, and abscisic acid. It enhances this resistance by strengthening cell walls, synthesizing defensive secondary metabolites, and regulating energy metabolism and stress responses. These findings provide a solid theoretical foundation for the future field application of B. velezensis in controlling walnut anthracnose.PMID:39444687 | PMC:PMC11496756 | DOI:10.3389/fmicb.2024.1420922

Front Microbiol. 2024 Oct 9;15:1467841. doi: 10.3389/fmicb.2024.1467841. eCollection 2024.ABSTRACTBACKGROUND: The ability of yaks to adapt to the extreme environment of low temperatures and hypoxia at cold seasons on the Qinghai-Tibet Plateau (QTP) is related to the host genome; however, the convergent evolution of rumen microbiomes in host adaption is unknown.METHODS: Here, we conducted a multi-omics study on the rumen fluid of grazing yaks from warm (July) and cold (December) seasons on the QTP to evaluate the convergent evolution of rumen microbiomes in the adaptation of grazing yaks to cold-seasons environments.RESULTS: The results showed that grazing yaks at cold seasons had higher fibrolytic enzyme activities and volatile fatty acids (VFAs) concentrations, and the relative abundance of Firmicutes and the ratio Firmicutes to Bacteroidetes was significantly higher than that of yaks at warm seasons. Macrogenomic analyses showed that genes involved in forming VFAs and arginine were significantly enriched in cold-season yaks. Transcriptome analyses of the rumen epithelium showed that 72 genes associated with VFAs absorption and transport were significantly upregulated in cold-season yaks. Metabolomic analyses showed that the levels of ornithine, related to efficient nitrogen utilization, were significantly upregulated in cold-season yaks.CONCLUSION: The synergistic role of rumen microbiomes in the adaptation of grazing yaks to extreme environments at cold seasons was revealed by multi-omics study.PMID:39444681 | PMC:PMC11496799 | DOI:10.3389/fmicb.2024.1467841

Front Cardiovasc Med. 2024 Oct 9;11:1430477. doi: 10.3389/fcvm.2024.1430477. eCollection 2024.ABSTRACTBACKGROUND: Prior research has established a correlation between immune cell activity and heart failure (HF), but the causal nature of this relationship remains unclear. Furthermore, the potential influence of metabolite levels on this interaction has not been comprehensively explored. To address these gaps, we employed a bidirectional Mendelian randomization (MR) approach in two stages to examine whether metabolite levels can mediate the causal relationship between immune cells and HF.METHODS: Genetic information was extracted from summary data of genome-wide association studies. By applying a two-sample, two-step MR approach, we investigated the causal relationships among immune cells, metabolite levels, and HF, with a specific focus on the mediating effects of metabolites. Sensitivity analysis techniques were implemented to ensure the robustness of our findings.RESULTS: MR analysis revealed significant causal associations between HF and eight specific immune cells and five metabolites. Mediation analysis further identified three mediated relationships. Particularly, hexadecenedioate (C16:1-DC) mediated the influence of both the CD28- CD127- CD25++ CD8br%CD8br (mediation proportion: 19.2%) and CD28+ CD45RA + CD8br%T cells (mediation proportion: 11.9%) on HF. Additionally, the relationship between IgD + CD38br AC cells and HF appeared to be mediated by the phosphate to alanine ratio (mediation proportion: 16.3%). Sensitivity analyses validated that the used instrumental variables were free from pleiotropy and heterogeneity.CONCLUSION: This study provides evidence that certain immune cell levels are associated with the risk of HF and that metabolite levels may mediate these relationships. However, to strengthen these findings, further validation using MR analyses with larger sample sizes is essential.PMID:39444553 | PMC:PMC11496177 | DOI:10.3389/fcvm.2024.1430477

Front Bioeng Biotechnol. 2024 Oct 9;12:1468974. doi: 10.3389/fbioe.2024.1468974. eCollection 2024.ABSTRACTNon-proteinogenic amino acids (npAAs) are valuable building blocks for the development of advanced pharmaceuticals and agrochemicals. The surge in interest in their synthesis is primarily due to the potential to enhance and diversify existing bioactive molecules. This can be achieved by altering these bioactive molecules to improve their effectiveness, reducing resistance compared to their natural counterparts or generating molecules with novel functions. Traditional production of npAAs in native hosts requires specialized conditions and complex cultivation media. Furthermore, these compounds are often found in organisms that challenge genetic manipulation. Thus, the recombinant production of these npAAs in a model organism like Escherichia coli paves the way for groundbreaking advancements in synthetic biology. Two synthetic operons, comprising of five heterologous proteins were genomically integrated into E. coli for the synthesis of npAAs β-methylphenylalanine (BmePhe), β-hydroxyenduracididine (BhEnd), and enduracididine (End). Proteomic and metabolomic analysis confirmed production of these compounds in E. coli for the first time. Interestingly, we discovered that the exogenous addition of pathway precursors to the E. coli system enhanced the yield of BmePhe by 2.5 times, whereas it concurrently attenuated the production of BhEnd and End, signifying a selective precursor-dependent yield enhancement. The synthetic biology landscape is broadened in this study by expanding the repertoire of amino acids beyond the conventional set of 22 standard proteinogenic amino acids. The biosynthesized npAAs, End, BhEnd, and BmePhe hold promise for engineering proteins with modified functions, integrating into novel metabolites and/or enhancing biological stability and activity. Additionally, these amino acids' biological production and subsequent purification present an alternative to traditional chemical synthesis methods, paving a direct pathway for pharmacological evaluation.PMID:39444519 | PMC:PMC11496134 | DOI:10.3389/fbioe.2024.1468974

Front Endocrinol (Lausanne). 2024 Oct 9;15:1476774. doi: 10.3389/fendo.2024.1476774. eCollection 2024.ABSTRACTBACKGROUND: Recurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL.METHODS: Immune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored.RESULTS: In the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis.CONCLUSION: The study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL.PMID:39444455 | PMC:PMC11496058 | DOI:10.3389/fendo.2024.1476774

Mol Plant. 2024 Oct 23:S1674-2052(24)00331-9. doi: 10.1016/j.molp.2024.10.009. Online ahead of print.ABSTRACTBioactive compounds are playing an increasingly prominent role in breeding functional and nutritive fruit crops such as citrus. However, the genomic and metabolic basis for the selection and differentiation underlying bioactive compounds variations in citrus remain poorly understood. Here, we constructed a species-level variation atlas of genomes and metabolomes using 299 citrus accessions. A total of 19,829 significant SNPs were targeted to 653 annotated metabolites, among which multiple significant signals were identified for secondary metabolites, especially flavonoids. Significantly differential accumulation of bioactive compounds in phenylpropane pathway, mainly flavonoids and coumarins, were unveiled across ancestral citrus species during differentiation, which is likely associated with the divergent haplotype distribution and/or expression profiles of relevant genes, including p-coumaroyl coenzyme A 2'-hydroxylases, flavone synthases, cytochrome P450 enzymes, prenyltransferases and UDP-glycosyltransferases. Moreover, we elucidated the citrus varieties with excellent antioxidant and anticancer capacities, clarifying the robust associations between distinct bioactivities and specific metabolites. Thus, these findings provide citrus breeding options for enrichment of beneficial flavonoids and avoidance of the potential risk of coumarins. This study will illuminate the application of genomic and metabolic engineering strategies in developing modern healthy citrus cultivars.PMID:39444162 | DOI:10.1016/j.molp.2024.10.009

Metallomics. 2024 Oct 23:mfae048. doi: 10.1093/mtomcs/mfae048. Online ahead of print.ABSTRACTStreptomyces scabiei is the causative agents of common scab on root and tuber crops. Life in the soil imposes intense competition between soil-dwelling microorganisms and we evaluated here the antimicrobial properties of S. scabiei. Under laboratory culture conditions, increasing peptone levels correlated with increased growth inhibitory properties of S. scabiei. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin and turgichelin) increased with the quantity of peptone thereby suggesting that they participate in growth inhibition. Mass spectrometry imaging further confirmed that the zones of secreted siderophores and growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity both led to increased microbial growth. Replacement of peptone by natural nitrogen sources regularly used as fertilizers such as ammonium nitrate, ammonium sulfate, sodium nitrate, and urea also triggered siderophore production in S. scabiei. The observed effect is not mediated by alkalinization of the medium as increasing the pH without providing additional nitrogen sources did not induce siderophore production. The nitrogen-induced siderophore production also inhibited the growth of important plant pathogens. Overall, our work suggests that not only the iron availability but also the nitrogen fertilizer sources could significantly impact the competition for iron between crop-colonizing microorganisms.PMID:39444076 | DOI:10.1093/mtomcs/mfae048

Anal Bioanal Chem. 2024 Oct 24. doi: 10.1007/s00216-024-05588-z. Online ahead of print.ABSTRACTUntargeted metabolomics UHPLC-HRMS workflows typically employ narrowbore 2.1-mm inner diameter (i.d.) columns. However, the wide concentration range of the metabolome and the need to often analyze small sample amounts poses challenges to these approaches. Reducing the column diameter could be a potential solution. Herein, we evaluated the performance of a microbore 1.0-mm i.d. setup compared to the 2.1-mm i.d. benchmark for untargeted metabolomics. The 1.0-mm i.d. setup was implemented on a micro-UHPLC system, while the 2.1-mm i.d. on a standard UHPLC, both coupled to quadrupole-orbitrap HRMS. On polar standard metabolites, a sensitivity gain with an average 3.8-fold increase over the 2.1-mm i.d., along with lower LOD (LODavg 1.48 ng/mL vs. 6.18 ng/mL) and LOQ (LOQavg 4.94 ng/mL vs. 20.60 ng/mL), was observed. The microbore method detected and quantified all metabolites at LLOQ with respect to 2.1, also demonstrating good repeatability with lower CV% for retention times (0.29% vs. 0.63%) and peak areas (4.65% vs. 7.27%). The analysis of various samples, in both RP and HILIC modes, including different plasma volumes, dried blood spots (DBS), and colorectal cancer (CRC) patient-derived organoids (PDOs), in full scan-data dependent mode (FS-DDA) reported a significant increase in MS1 and MS2 features, as well as MS/MS spectral matches by 38.95%, 39.26%, and 18.23%, respectively. These findings demonstrate that 1.0-mm i.d. columns in UHPLC-HRMS could be a potential strategy to enhance coverage for low-amount samples while maintaining the same analytical throughput and robustness of 2.1-mm i.d. formats, with reduced solvent consumption.PMID:39443364 | DOI:10.1007/s00216-024-05588-z

Prostate. 2024 Oct 23. doi: 10.1002/pros.24815. Online ahead of print.ABSTRACTBACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity.METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival.RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis.CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.PMID:39442954 | DOI:10.1002/pros.24815

J Adv Res. 2024 Oct 21:S2090-1232(24)00472-7. doi: 10.1016/j.jare.2024.10.017. Online ahead of print.ABSTRACTINTRODUCTION: Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.OBJECTIVES: This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI.METHODS: We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI.RESULTS: The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing lactobacilli) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process.CONCLUSIONS: Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.PMID:39442873 | DOI:10.1016/j.jare.2024.10.017

N Biotechnol. 2024 Oct 21:S1871-6784(24)00552-1. doi: 10.1016/j.nbt.2024.10.002. Online ahead of print.ABSTRACTPlants face multiple challenges from environmental pollutants and higher emissions of atmospheric CO2. Therefore, a hydroponic-based experiment was used to explore the combined effects of elevated [CO2] (700 ppm) and exogenous cyanide (CN-) (3.0mg CN/L) on rice seedlings under nitrogen deficiency, utilizing metabonomics and transcriptomic analysis. Elevated [CO2] significantly improved the growth of CN--treated rice seedlings compared to those with ambient [CO2] (350 ppm), and it also significantly affected CN- assimilation. Transcriptome analysis revealed distinct impacts on differentially expressed genes (DEGs) across treatments and tissues. KEGG analysis showed variability in DEGs enriched in amino acid (AA) and energy metabolism pathways due to elevated [CO2] and CN-. Metabonomics indicated that higher input of [CO2] and exogenous CN- more severely impacted energy metabolism elements than the individual species of AAs. Positive synergistic effects of elevated [CO2] and CN- were observed for glutamine and asparagine in shoots, and methionine in roots, wherein negative effects were noted for phenylalanine in shoots, and phenylalanine, valine, and alanine in roots. Meanwhile, positive effects on fumarate in shoots and α-ketoglutarate and succinate in roots were also found. Overall, elevated [CO2] enhances growth in CN--treated rice seedlings under nitrogen deficiency by altering AA and energy metabolism. This is the first attempt to provide new evidence of [CO2]-based gaseous fertilization as an energy-saving strategy for rice plants fed with biodegradable N-containing pollutants as a supporting N source under N deficient conditions.PMID:39442870 | DOI:10.1016/j.nbt.2024.10.002

Biomed J. 2024 Oct 21:100802. doi: 10.1016/j.bj.2024.100802. Online ahead of print.ABSTRACTHyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-13C]pyruvate and [1-13C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.PMID:39442802 | DOI:10.1016/j.bj.2024.100802

Environ Res. 2024 Oct 22:120211. doi: 10.1016/j.envres.2024.120211. Online ahead of print.ABSTRACTThe combined pollution of polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) has attracted wide attention due to their high toxicity, mutagenicity, carcinogenicity and teratogenicity. A thorough understanding of the progress of the relevant studies about their co-toxicity and co-contamination remediation is of great importance to prevent environmental risk and develop new efficient remediation methods. This paper summarized the factors resulting in different co-toxic effects, the interaction mechanism influencing co-toxicity and the development of remediation technologies for the co-contamination. Also, the inadequacies of the previous studies related to the co-toxic effect and the remediation methods were pointed out, while the corresponding solutions were proposed. The specific type and concentration of PAHs and HMs, the specific type of their action object and environmental factors could affect their co-toxicity by influencing each other's transmembrane process, detoxification process and increasing reactive oxygen species (ROS) and some other mechanisms that need to be further studied. The specific action mechanisms of the concentration, environmental factors and the specific type of PAHs and HMs, their effect on each other's transmembrane processes, investigations at the cellular and molecular levels, non-targeted metabolomics analysis, as well as long-term ecological effects were proposed to be further explored in order to obtain more information about the co-toxicity. The combination of two or more methods, especially combining bioremediation with other methods, is a potential development field for the remediation of co-contamination. It can make full use of the advantages of each remediation method, to achieve an increase of remediation efficiency and a decrease of both remediation cost and ecological risk. This review intends to further improve the understanding on co-toxicity and provide references for the development and innovation of remediation technologies for the co-contamination of PAHs and HMs.PMID:39442665 | DOI:10.1016/j.envres.2024.120211