PubMed

Mol Cancer Ther. 2025 May 16:OF1-OF10. doi: 10.1158/1535-7163.MCT-24-1091. Online ahead of print.ABSTRACTThe bromodomain-containing protein, transcription factor IID subunit 1 (TAF1; transcription factor II-250), is the largest component of the multiprotein assembly transcription factor IID, a dynamic complex that serves as a general factor for transcription initiation. CRISPR and RNAi screens of pan-cancer cell lines revealed that TAF1 is broadly required for optimal cell growth and survival, but a subset of cell lines showed enhanced TAF1 dependence. These observations suggest that TAF1 has the potential to serve as a therapeutic target in sensitive tumors. Current approaches employed to target TAF1 are limited to monovalent small-molecule inhibitors of the bromodomain. However, recent studies showed that such inhibitors lack cancer cell kill potential. We applied a structure-guided approach to generate cereblon recruiting Proteolysis Targeting Chimera (PROTAC) degraders of TAF1 using the chemical scaffolds of ceralasertib and GNE371. We present evidence that GNE371-based PROTACs are effective in degradation of TAF1 at concentrations as low as 1 nmol/L. TAF1 depletion activated p53 and induced apoptosis in acute myeloid leukemia (AML) cell lines and certain solid tumor cells. An in vivo active TAF1 PROTAC inhibited the growth of AML tumor xenografts. The results showed that inhibition of the bromodomain is not sufficient to inactivate TAF1 functions, whereas a PROTAC approach induces strong biological effects. Furthermore, TAF1 PROTACs have therapeutic potential against AML and other sensitive tumors.PMID:40376796 | DOI:10.1158/1535-7163.MCT-24-1091

Front Microbiol. 2025 May 1;15:1437056. doi: 10.3389/fmicb.2024.1437056. eCollection 2024.ABSTRACTAmmonia is the primary component of malodorous substances in chicken farms. Currently, the microbial ammonia reduction is considered a potential method due to its low cost, high safety, and environmental friendliness. Sphingomonas sp. Z392 can significantly reduce the ammonia level in broiler coops. However, the mechanisms of ammonia nitrogen reduction by Sphingomonas sp. Z392 remain unclear. To explore the mechanisms of ammonia reduction by Sphingomonas sp. Z392, the transcriptome and metabolome analysis of Sphingomonas sp. Z392 under high ammonium sulfate level were conducted. It was found that the transcription levels of genes related to purine metabolism (RS01720, RS07605, purM, purC, purO) and arginine metabolism (glsA, argB, argD, aguA, aguB) were decreased under high ammonium sulfate environment, and the levels of intermediate products such as ornithine, arginine, IMP, and GMP also were also decreased. In addition, the ncd2 gene in nitrogen metabolism was upregulated, and intracellular nitrite content increased by 2.27 times than that without ammonium sulfate. These results suggested that under high ammonium sulfate level, the flux of purine and arginine metabolism pathways in Sphingomonas sp. Z392 might decrease, while the flux of nitrogen metabolism pathway might increase, resulting in increased nitrite content and NH3 release. To further verify the effect of the ncd2 gene on ammonia removal, ncd2 was successfully overexpressed and knocked out in Sphingomonas sp. Z392. ncd2 Overexpression exhibited the most ammonia reduction capability, the ammonia concentration of ncd2 overexpression group decreased by 43.33% than that of without Sphingomonas sp. group, and decreased by 14.17% than that of Sphingomonas sp. Z392 group. In conclusion, Sphingomonas sp. Z392 might reduce the release of NH3 by reducing the flux of purine and arginine metabolisms, while enhancing ammonia assimilation to form nitrite. In this context, ncd2 might be one of the key genes to reduce ammonia.PMID:40376685 | PMC:PMC12078293 | DOI:10.3389/fmicb.2024.1437056

JOR Spine. 2025 May 15;8(2):e70074. doi: 10.1002/jsp2.70074. eCollection 2025 Jun.ABSTRACT[This corrects the article DOI: 10.1002/jsp2.70042.].PMID:40376566 | PMC:PMC12080346 | DOI:10.1002/jsp2.70074

Front Microbiol. 2025 May 1;16:1589415. doi: 10.3389/fmicb.2025.1589415. eCollection 2025.ABSTRACTSoil salinization is a substantial impediment to agricultural production, and investigating sustainable mitigation measures is essential for addressing food security. We conducted a two-year pot experiment to investigate the shaping mechanism of sorghum rhizosphere microbial community in sorghum-peanut intercropping system under salt stress. The experiment comprised four treatments: sole-cropped sorghum under normal soil conditions (NSS), intercropped sorghum under normal soil conditions (NIS), sole-cropped sorghum under salt-stress conditions (SSS), and intercropped sorghum under salt-stress conditions (SIS). The sorghum rhizosphere soil metabolites were examined using GC-MS, and the rhizosphere microbial community was characterized through metabolome sequencing. We identified 123 metabolites across treatments, with significant differences between normal and salt-stress soil conditions. The major metabolite classes included carbohydrates, alcohols, and acids. Key carbohydrates, including fructose and sucrose, were significantly reduced in the SIS than in SSS, NSS, and NIS treatments. Metabolic pathway analyses revealed that these differences were primarily associated with "Fructose and mannose metabolism," "Starch and sucrose metabolism" and "ABC transporter." Metabolome analyses revealed significant differences in microbial community structure across diverse soil conditions and cropping patterns. At phylum level, Proteobacteria, Gemmatimonadetes, and Verrucomicrobia predominated, with their relative abundance experiencing substantial changes under salt stress. SIS facilitated the enrichment of specific genera (Rhodanobacter), which were associated with soil health and stress tolerance. Additionally, the responses of rare microbial taxa to salt stress and intercropping varied, with specific rare microbial taxa (Rhizopus) exhibiting relative abundance under salt stress. Correlation analysis of metabolites and microbial taxa revealed that certain carbohydrates were significantly positively correlated with specific microbial phyla (Cyanobacteria and Nitrospirae) while demonstrating a significant negative correlation with Planctomycetota and Bacteroidota. These correlations indicate that sorghum intercropped with peanuts can promote the enrichment of microbial taxa under salt stress, thereby enhancing soil metabolic functions and stress tolerance by optimizing the rhizosphere microbial community. This study reveals the mechanism through which sorghum-peanut intercropping under salt stress influences the composition of sorghum's rhizosphere microbial community by modulating soil sugar metabolism pathways. This finding provides a new perspective on sustainable agricultural practices in saline soils and emphasizes the pivotal role of plant-metabolite-microbe interactions in abiotic stress mitigation.PMID:40376464 | PMC:PMC12078205 | DOI:10.3389/fmicb.2025.1589415

Front Microbiol. 2025 May 1;16:1592549. doi: 10.3389/fmicb.2025.1592549. eCollection 2025.ABSTRACTPancreatic cancer is one of the most lethal malignant neoplasms. Pancreatic cancer is related to gut microbiota, but the associations between its treatment and microbial abundance as well as genetic variations remain unclear. In this study, we collected fecal samples from 58 pancreatic cancer patients including 43 pancreatic ductal adenocarcinoma (PDAC) and 15 non-PDAC, and 40 healthy controls, and shotgun metagenomic sequencing and untargeted metabolome analysis were conducted. PDAC patients were divided into five groups according to treatment and tumor location, including treatment-naive (UT), chemotherapy (CT), surgery combined with chemotherapy (SCT), Head, and body/tail (Tail) groups. Multivariate association analysis revealed that both CT and SCT were associated with increased abundance of Lactobacillus gasseri and Streptococcus equinus. The microbial single nucleotide polymorphisms (SNPs) densities of Streptococcus salivarius, Streptococcus vestibularis and Streptococcus thermophilus were positively associated with CT, while Lachnospiraceae bacterium 2_1_58FAA was positively associated with Head group. Compared with Tail group, the Head group showed positive associations with opportunistic pathogens, such as Escherichia coli, Shigella sonnei and Shigella flexneri. We assembled 424 medium-quality non-redundant metagenome-assembled genomes (nrMAGs) and 276 high-quality nrMAGs. In CT group, indole-3-acetic acid, capsaicin, sinigrin, chenodeoxycholic acid, and glycerol-3-phosphate were increased, and the accuracy of the model based on fecal metabolites reached 0.77 in distinguishing healthy controls and patients. This study identifies the associations between pancreatic cancer treatment and gut microbiota as well as its metabolites, reveals bacterial SNPs are related to tumor location, and extends our knowledge of gut microbiota and pancreatic cancer.PMID:40376462 | PMC:PMC12078283 | DOI:10.3389/fmicb.2025.1592549

AoB Plants. 2025 Mar 31;17(2):plaf019. doi: 10.1093/aobpla/plaf019. eCollection 2025 Feb.ABSTRACTTo increase the cannabidiol (CBD) content of industrial hemp, male hemp was screened out by spraying cytokinin at the three-leaf stage of seedlings, and more female hemp was cultivated. 6-BA 60 mg·L-1 treated female flowers of industrial hemp were subjected to transcriptomic, proteomic, and metabolomic analyses to investigate the changes and molecular mechanisms of gene expression and metabolites and related pathways of 6-BA in the development of female flowers of industrial hemp. The results showed that 1189 differentially expressed genes (DEGs), 168 differentially expressed proteins (DEPs), and 138 DAMs were screened compared with the control. Functional enrichment analysis revealed that phytohormone signaling, starch and sucrose metabolism, flavonoid biosynthesis, phenylpropane metabolism, and glutathione metabolism were the major pathways enriched, and differential genes, proteins, and metabolites enriched in the above pathways were further followed up and analyzed. It was found that, among them, CCL1, PAL1, and C4H were the key genes and proteins involved in the phenylpropane metabolic pathway, CYP450 and FLS were not only the upstream genes in the flavonoid biosynthesis pathway, but CYP450 were also involved in the synthesis of phytohormones and catabolism. FLS was related to the synthesis of saccharides. It was hypothesized that the carbohydrates might synergistically act with cytokinins to induce female flower differentiation in industrial hemp. The flavonoid biosynthesis pathway and glutathione metabolism pathway are also closely related to feminization. This paper provides a reference for subsequent studies on sex differentiation in hemp or other plants.PMID:40376452 | PMC:PMC12079373 | DOI:10.1093/aobpla/plaf019

IMA Fungus. 2025 May 7;16:e147558. doi: 10.3897/imafungus.16.147558. eCollection 2025.ABSTRACTCordycepsblackwelliae is an entomopathogenic fungus with significant potential for research and development due to its ease of cultivation. However, the lack of omics-based studies has limited our understanding of the molecular mechanisms governing its growth and fruiting body development. This study employed a multi-omics approach, integrating genomic, transcriptomic and metabolomic analyses. Utilising both Illumina and Nanopore sequencing technologies, we assembled a 31.06 Mb nuclear genome comprising 11 scaffolds, with telomere presence at one or both ends in eight scaffolds and annotated 8,138 identified genes (8,136 from genome prediction and two from local BLAST searches). Transcriptomic analysis identified 2,078 differentially expressed genes across three developmental stages: liquid culture mycelia, wheat culture mycelia and fruiting bodies. Amongst these, 745 genes were up-regulated in fruiting bodies, primarily associated with biosynthetic and catabolic pathways. Metabolomic analysis identified 1,161 metabolites, with 1,014 showing significant variations across developmental stages. Integrated transcriptomic and metabolomic analyses uncovered 17 genes positively correlated with 34 metabolites, which are likely crucial regulators of fruiting body development. These findings provide new insights into the molecular networks underlying C.blackwelliae growth and fruiting body formation.PMID:40376252 | PMC:PMC12079115 | DOI:10.3897/imafungus.16.147558

Front Plant Sci. 2025 May 1;16:1567247. doi: 10.3389/fpls.2025.1567247. eCollection 2025.ABSTRACTPURPOSE: Persian walnut (Juglans regia L.) is one of the world's economically significant dry fruits, which stems from the high nutritional value of its kernel and its uses in diverse industries. Walnuts species can employ sexual and apomictic reproductive strategies. Multi-omics analyses of apomictic walnut embryos have not yet been conducted. This study integrates transcriptomic and metabolomic analyses to reveal new insights into the formation of sexual and apomictic walnut embryos, providing a valuable foundation for future research on apomictic embryo development in walnuts.METHOD: To elucidate the mechanisms underlying these reproductive modes, transcriptomic and metabolomic analyses were performed on the embryos of sexual and apomictic walnut species at different developmental stages.RESULTS: Our findings revealed 321 differentially expressed genes (DEGs) and 19 differentially accumulated metabolites (DAMs) in apomictic vs. sexual walnut embryos. The joint transcriptomic and metabolomic analysis revealed that DEGs and DAMs were mainly enriched in metabolic pathways, biosynthesis of secondary metabolites, plant hormone signal transduction, and tryptophan metabolic pathways. The content of DAMs, such as tryptamine, jasmonic acid (JA), and JA-isoleucine, was significantly higher in embryos derived from flowers that had been forced to reproduce apomictically (subjected to polyvinyl alcohol-capped stigma treatment) than embryos derived from flowers that had been subjected to normal artificial pollination. COMT, PME, TAT, CHIB, FG3, CYP82C4, CYP82G1, aceB, SDR, ribBA, AFS1, BHMT2, GN1_2_3, SGR, BAK1, trpB, AOC3, ASN, IAA, TDC, ZEP, JAZ, and ACO were positively correlated with DAMs. 9 genes related to DAMs were verified by real-time quantitative PCR, and their relative expression differences were consistent with the results of the transcriptome analysis. BAK1, trpB, AOC3, ASN, IAA, TDC, ZEP, JAZ, ALDH, and ACO played a role in regulating the formation of apomictic embryos in walnut by regulating DAMs, such as auxin(tryptamine) and JA.CONCLUSION: TRA, JA, and JA-ILE play important roles with metabolites involved in apomixis. BAK1, trpB, AOC3, ASN, IAA, TDC, ZEP, JAZ, ALDH, and ACO may be the key genes involved in apomixis. These candidate genes could be strongly associated with the molecular mechanisms underlying apomixis in walnut were identified, and this will help clarify the formation of apomictic embryos in walnut.PMID:40376170 | PMC:PMC12078271 | DOI:10.3389/fpls.2025.1567247

Front Plant Sci. 2025 May 1;16:1537273. doi: 10.3389/fpls.2025.1537273. eCollection 2025.ABSTRACTEuchresta japonica, a medicinal plant in Chinese herbal medicine, lacks comprehensive metabolite data to explain its health benefits despite its long-standing use. Here, widely targeted metabolome at six different tissues of E. japonica was investigated, identifying 2,140 metabolites, including flavonoids, phenolic acids, amino acids, lipids, and alkaloids. Among them, 305 were annotated as key active ingredients, and 364 were active pharmaceutical ingredients for nine human disease-resistance, with 206 co-annotated. Metabolic profiles varied significantly across tissues, with medicinally active metabolites highly concentrated in lateral roots and inflorescences, indicating great medical potential. Notably, the lateral root, rather than the main root, was the primary source of root-derived bioactive metabolites. Additionally, KEGG analysis demonstrated that secondary metabolic pathways, especially "isoflavonoid biosynthesis" and "flavonoid biosynthesis" pathways, played important roles. Overall, lateral roots and inflorescences exhibit the strongest potential for disease treatment, particularly for chronic and multifactorial diseases. This study significantly advances our understanding of E. japonica's chemical composition and underscores its potential as a valuable resource for novel therapeutic applications, providing a strong foundation for further investigation into its pharmacological properties and drug development prospects.PMID:40376159 | PMC:PMC12078262 | DOI:10.3389/fpls.2025.1537273

Front Endocrinol (Lausanne). 2025 May 1;16:1551172. doi: 10.3389/fendo.2025.1551172. eCollection 2025.ABSTRACTBACKGROUND: Although brain-derived neurotrophic factor (BDNF)has garnered extensive attention as a neuroendocrine marker in schizophrenia (SZ), its clinical utility remains limite due to inconsistent findings.METHODS: To address this gap, serum samples were collected from 24 female patients with SZ and 25 healthy controls. The metabolic profiling was performed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to capture abroad range of metabolites.RESULTS: Our results revealed that BDNF is not a robust discriminatory biomarker. Marked differences in metabolic profiles were identified between patients with SZ and healthy individuals. The GC-MS analysis revealed significant differences in 79 metabolites; while the LC-MS analysis identified 419 significantly differential metabolites. Functional analysis reveals that these differential metabolites predominantly contribute to metabolic and neuro-related processes. Our findings demonstrate that norepinephrine and melatonin, two additional neuroendocrine compounds, are significantly elevated in patients with SZ compared to healthy controls. Notably, their higher areas under the curve (AUC) values compared to BDNF highlight their potential as more reliable biomarkers for SZ.CONCLUSION: This study offers valuable insights into the altered metabolic patterns of female patients with SZ and establishes melatonin and norepinephrine as promising neuroendocrine biomarkers, underscoring their diagnostic value and role in the neuroendocrine regulation of mental disorders.PMID:40375951 | PMC:PMC12078152 | DOI:10.3389/fendo.2025.1551172

Food Funct. 2025 May 16. doi: 10.1039/d4fo05696e. Online ahead of print.ABSTRACTBackground: Multiple myeloma (MM) is a hematologic malignancy closely associated with diets and metabolic disorders, showing an increasing incidence trend. Genome-wide association studies (GWAS) contribute to exploring the causal relationships between diets, metabolites, and MM, thereby revealing biological mechanisms underlying cancer progression. Methods: This study included large-scale GWAS data for two diets, four metabolomics, and MM. The two-sample Mendelian randomization (MR) analysis was conducted to assess causalities between these dietary patterns, metabolites, and MM. The MR analysis primarily employed the inverse variance weighted (IVW) method, supported by multiple sensitivity analysis and reverse MR analysis to validate significant associations. Mediation analysis identified specific metabolites mediating the causal relationships between diets and MM. Results: Univariate MR analysis suggested that coffee consumption (ORIVW = 2.72; 95% CI: 1.21-6.10; PIVW = 0.015, P_fdr = 0.022), decaffeinated coffee consumption (ORIVW = 7.10; 95% CI: 1.33-37.87; PIVW = 0.022, P_fdr = 0.022), ground coffee consumption (ORIVW = 4.04; 95% CI: 1.25-13.02; PIVW = 0.019, P_fdr = 0.022), instant coffee consumption (ORIVW = 6.13; 95% CI: 1.95-19.34; PIVW = 0.002, P_fdr = 0.008), and coffee max liking (ORIVW = 2.94; 95% CI: 1.23-7.03; PIVW = 0.015, P_fdr = 0.035) were associated with increased MM risk. Metabolomic MR analysis identified 19 plasma metabolites, 1 blood and urine biomarker, and 4 plasma lipids with significant association with MM. Mediation analysis indicated that hippurate and cinnamoylglycine mediated 35.55% (P < 0.001) and 21.85% (P = 0.002) of the genetically predicted effect of coffee consumption on MM risk, respectively. Cinnamoylglycine contributed 12.63% (P = 0.042) to the total causal effect of ground coffee consumption on MM. Hippurate (21.43%, P < 0.001), 3-hydroxyhippurate (4.39%, P = 0.031), and cinnamoylglycine (8.79%, P = 0.010) mediated the genetically predicted impact of instant coffee consumption on MM risk. Metabolic pathway analysis suggested that glutathione metabolism significantly contributes to MM pathogenesis (P = 0.002, FDR < 0.05). Conclusions: Our findings support the adverse causal effects of various coffee consumption on MM risk, identifying hippurate, 3-hydroxyhippurate, and cinnamoylglycine as key mediators, driving the relationship potentially through the glutathione metabolism pathway.PMID:40375831 | DOI:10.1039/d4fo05696e

Biomed Chromatogr. 2025 Jul;39(7):e70113. doi: 10.1002/bmc.70113.ABSTRACTInocutis tamaricis is a medicinal fungus with significant pharmacological activity. In this study, ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC/MS) was used to conduct a comprehensive non-targeted metabolomics analysis of the metabolites of wild fruiting body (WF), cultured fruiting body (CF), and liquid cultured mycelium (LCM). Orthogonal partial least square discriminant analysis (OPLS-DA) was used to compare the three culture methods, to describe the regulatory effect of specific culture methods on metabolite distribution and yield of I. tamaricis, and the differential metabolites were enriched and analyzed to identify key metabolic pathways. The results showed significant differences in the types and abundances of active substances produced in different culture methods. There were 35 compounds in common, the WF, CF, and LCM had their unique metabolites, which were 39, 16, and 29 respectively, confirming the significant differences in the metabolites in different cultures, six key metabolic pathways were identified, including unsaturated fatty acid biosynthesis, linoleic acid, and α-linolenic acid metabolism, etc.PMID:40375813 | DOI:10.1002/bmc.70113

Biomed Chromatogr. 2025 Jul;39(7):e70112. doi: 10.1002/bmc.70112.ABSTRACTDiabetes retinopathy (DR) is one of the serious complications of diabetes. Clinical practice has proved that Tang Wang Ming Mu Granule (TWMM) can improve symptoms of DR patients. The mechanism of TWMM in treating DR in mice was studied, combining gut microbiota with metabolomics. A high-fat and high-sugar diet combined with streptozotocin (STZ) injection was used to create a mouse model of DR. The C57BL6/J wild-type mice were divided into five groups, including normal control, DR model, TWMM (2.7 and 10.8 g/kg) treatment, and the positive control treatment groups. Based on urine metabolomics and 16S rDNA sequencing of fecal samples, the effects of TWMM on host metabolism and intestinal microbiota were studied. The results showed that TWMM reverses the disordered intestinal flora to normal. In addition, the pathway prediction of intestinal microorganisms was related to the metabolic pathways. Meanwhile, the metabolomics analysis found that the differential metabolites were mainly concentrated in amino acids and their metabolites, carbohydrates, and their metabolites. The Shigellosis pathway attracted attention, and Shigella shows good indication in the treatment. The research provides a method for metabolic disease study with gut microbiota combined with metabolomics and treatment targets and pathways of DR.PMID:40375786 | DOI:10.1002/bmc.70112

Plant Cell Environ. 2025 May 15. doi: 10.1111/pce.15614. Online ahead of print.ABSTRACTIn grafted combinations, the scion cultivar, representing the aboveground portion, possesses the potential to influence the rhizosphere bacterial community. However, the precise mechanisms by how the scion cultivar contributes to the recruitment and assembly of rhizosphere bacteria remain poorly understood. In this study, we conducted a comprehensive analysis of the root transcriptome and metabolomics coupled with the amplification of the rhizosphere bacterial 16S rRNA gene. We found that scion cultivars with different net photosynthesis rates significantly impacted root metabolites and the expression of root sugar metabolism genes. Moreover, rhizosphere-specific taxa (Rhizobium, Nitrospira and Ensifer) are associated with root sugar metabolites, particularly sucrose. The foliar application of 2% sucrose on leaves enhanced root sugar metabolism and shaped the rhizosphere microbiota, notably promoting the growth and colonization of the bacterial isolation in the rhizosphere of apple plantlets. This study has significant implications for future studies on plant-microbe interactions in grafted combinations.PMID:40375577 | DOI:10.1111/pce.15614

Physiol Plant. 2025 May-Jun;177(3):e70260. doi: 10.1111/ppl.70260.ABSTRACTThe jasmonic acid (JA) pathway is central for plant defence against herbivores, and genes related to this pathway have received increased attention. Here, we evaluated the functions of the allene oxide cyclase (AOC)-encoding gene GmAOC3 and the caleosin-encoding gene GmCLO1, which may affect JA synthesis in soybean, and explored the anti-insect mechanisms of these two genes. The overexpression of GmAOC3 increased soybean resistance to the common cutworm (CCW). The strongest resistance to CCW was observed in the GmAOC3-overexpressing line GmAOC3-OE-1. Whole-genome resequencing and expression analysis revealed that in this line, GmCLO1 silencing was caused by insertion of the GmAOC3 gene into the GmCLO1 sequence. GmCLO1 expression responded to CCW induction. Compared with the controls, the knockdown or knockout of GmCLO1 increased soybean resistance to CCW. Conversely, the overexpression of GmCLO1 decreased CCW resistance. Transcriptomic and metabolomic analyses revealed that the gmclo1-knockout line shared 653 differentially expressed genes (DEGs) and 87 differentially abundant metabolites with the GmAOC3-OE line. Among these common DEGs, anti-insect genes related to JA, such as the 9-lipoxygenase gene Glyma.13G347800, the vegetative storage protein gene Glyma.08G200100, and the trypsin inhibitor gene Glyma.06G219900, showed upregulated expressions in both lines. Additionally, JA and JA-isoleucine contents were notably elevated in the GmAOC3-OE-1 line but decreased in the GmCLO1-overexpressing line. Measurements of yield-related traits revealed that GmAOC3 overexpression and/or GmCLO1 knockout did not affect soybean yield. In conclusion, we identified two new target genes for insect-resistant soybean breeding and contributed to an in-depth understanding of the JA-mediated insect resistance mechanisms in soybeans.PMID:40375436 | DOI:10.1111/ppl.70260

Diabetes Obes Metab. 2025 May 15. doi: 10.1111/dom.16467. Online ahead of print.ABSTRACTAIMS: Higher cruciferous vegetable (e.g., broccoli) intake is associated with lower risk of type 2 diabetes and cardiovascular disease, but limited causal evidence exists. We investigated if cruciferous vegetable intake improved glycaemic control compared to root/squash vegetables in non-diabetic adults with elevated blood pressure.MATERIALS AND METHODS: This randomized, controlled, crossover trial consisted of two 2-week dietary interventions (300 g/day cruciferous [active] and root/squash [control] soups with standardized lunch/dinner meals) separated by a 2-week washout. Participants were blinded to the intervention allocation. Glycaemic measures were a pre-specified secondary outcome. Flash glucose monitoring measured interstitial glucose every 15-min throughout both interventions. Mealtimes and consumption were recorded in food diaries. Differences in continuous glucose, glycaemic variability (coefficient of variation [CV]), and overall, lunch, and dinner postprandial glucose response (PPGR; 2-h mean glucose [PPGR 2-h] and area under the curve [AUC]) were assessed using linear mixed-effects regression.RESULTS: Eighteen participants (female = 89%) completed the study (median [IQR] age: 68 [66-70 years]). Glycaemic variability was lower in the active versus control (mean difference: -2.0%, 95% CI -2.8, -1.1, p < 0.001). Overall PPGR 2-h and AUC were lower in the active versus control (mean difference: -0.14 mmol/L, 95% CI -0.24, -0.04, p = 0.005 and -20.1 mmol/L × min, 95% CI -34.1, -6.1, p = 0.005, respectively), driven by the dinner PPGR (p = 0.004 and p = 0.003, respectively). There was no difference in mean continuous glucose for active versus control (p = 0.411).CONCLUSIONS: Cruciferous vegetable consumption improved postprandial glycaemic control compared with root/squash vegetables. The clinical impact remains uncertain and warrants further investigation, particularly in individuals with impaired glycaemic control.CLINICAL TRIAL REGISTRY: This trial was registered at www.anzctr.org.au (ACTRN12619001294145).PMID:40375391 | DOI:10.1111/dom.16467

Chin Med. 2025 May 15;20(1):64. doi: 10.1186/s13020-025-01123-z.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) with cold pattern is an important type of RA according to the theory of traditional Chinese medicine. Fuzi (also known as the lateral roots of Aconitum carmichaelii Debx.) represents a typical traditional Chinese medicine that has been clinically used for treatment of the RA especially cold-related RA for thousands of years, yet its mechanism remains unknown.PURPOSE: The purpose of the research was to study the therapeutic effects of Fuzi on cold-related RA, and to investigate the mechanism of its action.METHODS: Here, we investigated the pharmacological effects of Fuzi on cold-related RA using micro-CT, histopathological analysis, and inflammatory cytokine test. Then, a gut microbiota composition analysis in combination with fecal microbiota transplantation were used to confirm the role of gut microbiota in the therapeutic effects of Fuzi. Further, targeted bile acid metabolomics was used to screen the possible differential microbial bile acids involved in the mechanism of Fuzi. In vitro bioactivity analysis of differential bile acids was used to assess their anti-inflammation activity. Finally, western blot was used to investigate the signaling pathways of Fuzi in reducing the inflammation of cold-related RA.RESULTS: The results showed that Fuzi alleviates cold-related RA by improving arthritis index, paw swelling, bone damage, and inflammatory cytokines. In addition, the ameliorative effect of Fuzi is dependent on gut microbiota such as the taxa Lachnospiraceae and Ruminococcaceae. Targeted analysis of fecal and serum bile acids showed that TCA and THDCA were the main differential metabolites. In vitro, TCA and THDCA showed anti-inflammation effects on RAW264.7 cells. Western blot showed that Fuzi regulates TGR5-cAMP-PKA signaling and NLRP3 inflammasome to reduce cold-related arthritis.CONCLUSION: Overall, our results demonstrated that Fuzi could regulate gut microbiota and microbial bile acid metabolism, the microbial metabolite THDCA acts on TGR5-cAMP-PKA signaling pathway and NLRP3 inflammasome to reduce cold-related arthritis. Our study suggests that supplementation of Fuzi or THDCA can be of great value for the prevention and clinical treatment of cold-related RA.PMID:40375326 | DOI:10.1186/s13020-025-01123-z

J Headache Pain. 2025 May 15;26(1):116. doi: 10.1186/s10194-025-02054-8.ABSTRACTNeuropathic pain is a chronic condition with limited effective treatments, closely associated with astrocytes and their role in central sensitization. Apolipoprotein E (ApoE), predominantly expressed in astrocytes in central nervous system, exists in three ApoE isoforms (ApoE2, ApoE3, and ApoE4) in humans, with ApoE4 linked to increased susceptibility to neurological diseases. However, the relationship between ApoE4 and neuropathic pain, as well as underlying mechanisms, remains poorly understood. Here, we demonstrated that mice expressing human ApoE4 (ApoE4-TR) displayed increased pain sensitivity following spared nerve injury (SNI) compared to ApoE3-TR mice. This increased sensitivity was also observed in mice with astrocyte-specific expression of ApoE4, achieved through Cre-mediated recombination. Metabolomic profiling revealed reduced spermidine levels in the spinal dorsal horn of ApoE4-TR mice relative to ApoE3-TR mice. Daily gavage administration of spermidine alleviated mechanical pain to a comparable level in ApoE3-TR and ApoE4-TR mice, as assessed by von Frey test. However, lower dose of spermidine effectively alleviated neuropathic pain in ApoE3-TR mice but showed reduced efficacy in ApoE4-TR mice, likely due to limited spermidine retention in ApoE4 astrocytes, as demonstrated in vitro. Transcriptomic analysis identified Nos2 as a critical gene upregulated in ApoE4-TR mice. Mechanistically, spermidine suppressed Nos2 expression by inhibiting the NF-κB pathway in astrocytes, thereby alleviating neuropathic pain. These findings highlight an enhanced pain sensitivity associated with ApoE4 and suggest spermidine as a potential therapeutic strategy, emphasizing a tailored dosage approach for ApoE4 carriers.PMID:40375206 | DOI:10.1186/s10194-025-02054-8

BMC Plant Biol. 2025 May 15;25(1):640. doi: 10.1186/s12870-025-06666-9.ABSTRACTBACKGROUND: The extreme high-altitude conditions of the Tibetan Plateau, characterized by intense solar radiation, low temperatures, and reduced oxygen levels, poses significant challenges to plant survival. Plants inhabiting this region have evolved specialized mechanisms to adapt to high-altitude environments. While most studies have focused on genomic and ecological perspectives, few have explored adaptive mechanisms in a metabolic context. In particular, comparative studies examining similarities and differences in the metabolomes of closely related species are exceedingly rare. As sister species, the nettle species Urtica hyperborea and U. dioica are distributed above 4000 m above sea level, with a sympatric distribution on the Tibetan Plateau, they provide an ideal system to investigate the aforementioned question.RESULTS: In this study, we conducted non-targeted metabolic profiling of the leaves from U. hyperborea and U. dioica collected at three sympatric sites on the Tibetan Plateau. A total of 2906 annotated metabolites were detected. Differential metabolites at Sites 1 (4697 m) and 3 (4465 m) were enriched in pathways for flavonoid, flavone and flavonol, and phenylpropanoid biosynthesis. In contrast, Site 2, located at the highest altitude (5007 m), primarily exhibited enrichment in carbon metabolism pathways. Regarding the altitudinal variation of the same species, common metabolic pathways between the two groups included fructose and mannose metabolism, α-linolenic acid metabolism, and glycerophospholipid metabolism. The metabolic pathways enriched only inU. hyperboreaincluded starch and sucrose metabolism, galactose metabolism, and phenylpropanoid biosynthesis. The metabolically enriched pathways specific toU. dioicaincluded pantothenate and coenzyme A biosynthesis, as well as glutathione metabolism.CONCLUSIONS: We found that the metabolic differences between the two sympatric species are primarily in carbohydrate and phenylpropanoid contents. The differential metabolites of the same species across different altitudes were enriched mainly in carbon metabolism pathways and lipid metabolism pathways. Thus, our study revealed that the high-altitude adaptation mechanisms of sympatric species are not identical. Moreover, adaptation strategies within the same species were generally consistent across altitudes, exhibiting only slight variations. This study provide novel insights into the adaptive metabolic strategies of U. hyperborea and U. dioica, contributing to a deeper understanding of the mechanisms underlying plant adaptation to extreme high-altitude conditions.PMID:40375155 | DOI:10.1186/s12870-025-06666-9

BMC Gastroenterol. 2025 May 15;25(1):375. doi: 10.1186/s12876-025-03929-5.ABSTRACTPURPOSE: High salt diet (HSD) has been considered as a risk factor for the development of metabolic disorders. However, less is known about long-term implications of HSD. Therefore, the aim of this study was to conduct a preliminary investigation into the effects of mice feeding with long-term HSD on gut microbial and metabolic profiles.METHODS: In this study, C57BL/6 J mice were fed with HSD for 22 weeks, after which fat and feces were collected. The composition of fecal microbiota was determined using 16S rRNA gene sequencing. Fecal metabolic profiling of mice was identified through untargeted ultrahigh-performance liquid chromatography-mass spectrometry. In addition, the serum levels of adipocytokines, including fibroblast growth factor 21 (FGF21) and adiponectin (APN), were measured.RESULTS: Long-term HSD disrupted the growth performance of mice. Compared to those fed a normal salt diet, mice on a long-term HSD showed slower weight gain, as well as lower fat accumulation and serum levels of APN, while experiencing elevated blood pressure and levels of serum FGF21 and glucose. The 16S rRNA sequencing revealed changes in community richness and diversity, with long-term HSD affecting the abundance of certain gut microbiota, including Firmicutes, Christensenella, Barnesiella, and Lactococcus. Fecal metabolomic analysis also uncovered alterations in metabolites, such as myriocin, cerulenin, norcholic acid, 7-ketocholesterol, and prostaglandins B2. Further analysis indicated that these gut and microbiota and metabolites are predominantly involved in the lipid metabolism of the organism. Importantly, variations in these gut metabolites and microbiota were significantly correlated with body weight, fat accumulation, and the levels of FGF21 and APN.CONCLUSION: Long-term HSD affects physiological traits, alters gut metabolites profiles, and impacts the composition and function of gut microbiota, thus causes a certain impact on lipid metabolism.PMID:40375136 | DOI:10.1186/s12876-025-03929-5