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The biosynthetic capacity of a cell governs the production and exchange of amino acids. Given the distinct metabolic origins and intracellular requirements for amino acids, it is essential to establish quantitative amounts of internal amino acid pools and how these change across growth phases. Using Saccharomyces cerevisiae, here we establish an absolute, quantitative blueprint of the intracellular and extracellular amino acid economy, defining the fluxes of production, secretion, and consumption across 24 hours of cell growth. While the intracellular pool is dominated by a group of amino acids, their relative proportions continuously change over time. The extracellular pool is notably distinct in terms of composition and amounts. Only select amino acids are public goods secreted in significant amounts, and a subset of these (Ala, Val, Gln, Trp, and Phe) are subsequently re-consumed. Five amino acids, Asp, Lys, His, Arg, and Met, remain "privatized" even in nutrient abundance. We demonstrate that the strictly privatized amino acid Asp continuously sustains diverse carbon metabolism, while the public Ala is utilized following carbon depletion. Furthermore, nitrogen limitation triggers a significant shift toward storage, privatizing otherwise abundant nitrogen-rich compounds like Gln, Asn, and Pro. We thereby rationally establish pairs of stable synthetic communities of paired public good auxotrophs that show effective growth. Our results identify frameworks for feasible amino acid trade and provide a basis for engineering stable, synthetic communities of amino acid auxotrophs.IMPORTANCEAmino acids are central to a metabolic economy and are extensively exchanged between cells; yet, the scale of this economy remains unknown even in model microbes. This study establishes a quantitative blueprint of the amino acid economy in Saccharomyces cerevisiae by mapping production, secretion, and consumption fluxes. The findings reveal a distinction between public goods-such as alanine, which is secreted and re-consumed-and privatized resources, such as aspartate, which cells retain to sustain carbon metabolism. These pools shift across growth phases and move toward privatization during nitrogen limitation. By defining these frameworks, this study enables the rational design of stable, synthetic communities of auxotrophs.

The northward expansion of mosquito-borne viruses such as West Nile virus (WNV) and Usutu virus (USUV) in Europe, driven partly by climate-related changes affecting vectors and hosts, poses an increasing threat to human and animal health. Reliable diagnostic tools are therefore essential for early detection and effective surveillance. This study aimed to develop and evaluate sensitive molecular assays for WNV and USUV, apply them to screen wild birds and human patients in Finland, assess bird exposure through serology, and evaluate national preparedness for emerging arboviral threats. Real-time PCR assays for WNV and USUV nucleic acids were developed, optimized and evaluated for the detection of WNV and USUV nucleic acids using bird and human samples. Bird samples were also tested for anti-WNV antibodies using an in-house immunofluorescence assay (IFA). The real-time PCR assays showed high sensitivity, with limits of detection of 13.0 copies per reaction for WNV and 14.6 copies per reaction for USUV. A total of 163 deceased birds and 337 human serum samples collected during the summer months from patients with suspected acute infections were screened. No WNV or USUV nucleic acids were detected, and bird samples tested negative for WNV antibodies. However, given the active migratory bird flyways from Africa and Southern/Central Europe, and recent detections in neighbouring countries, the introduction of WNV into Finland appears likely. Continued surveillance and the availability of efficient diagnostic tools remain critical for preparedness and early response.

The genus Streptococcus contains some of the most important commensals and pathogens of the human microbiome. To obtain the fatty acids required for cell membranes, Streptococcus either produce fatty acids de novo through the fatty acid biosynthesis (fab) pathway or uptake host fatty acids through the fatty acid kinase (fak) pathway. Although both the fab and fak pathways represent potential therapeutic targets to prevent or treat infection, progress is limited because of an incomplete understanding of taxon-to-taxon variability in streptococcal lipid metabolism. Here, we examined the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. In all three species, deletion of fabM abolished MUFA production and caused severe growth defects, decreased stress tolerance, increased antibiotic susceptibility, and defects in cell viability, morphology, and division. In S. mutans, loss of fabM also markedly reduced competence signaling and production of the mutacin IV bacteriocin. Deletion of fabM increased susceptibility to killing by human neutrophils in S. mutans and S. pneumoniae, but not S. pyogenes. Together, these findings illustrate that MUFA synthesis is broadly important for streptococcal physiology and cell membrane homeostasis, while its contribution to pathogenesis is strongly species- and context-dependent, providing leads to guide the development of novel therapeutic and/or preventative strategies.IMPORTANCEStreptococcus spp. exert profound effects on human health, with several species causing significant morbidity and mortality. Although streptococcal fatty acid biosynthesis and utilization are attractive metabolic targets for development of therapeutics, this opportunity is vexed by an incomplete understanding of taxon-to-taxon variability in lipid metabolism. In this study, the role of de novo monounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits was examined in Streptococcus mutans, Streptococcus pyogenes, and Streptococcus pneumoniae, three major pathogens that cause disease at distinct body sites. MUFA synthesis was important for stress and antibiotic tolerance across all three species, while its impact on virulence was species- and context-dependent. Overall, these discoveries provide leads to guide the development of novel therapeutic and/or preventative strategies.

In this work, we established a decarboxylative cascade process to achieve functionalized pyrazolones. This approach directly employs carboxylic acids as alkylating reagents. An inexpensive iron photocatalyst enables this process when irradiated by visible light. The reaction demonstrated a broad substrate scope, proving compatible with various carboxylic acids and N-acrylohydrazones. Furthermore, biological activity evaluation revealed that compound 3ak acted as a potent inhibitor of NO production, while compound 3al exhibited potent antiproliferative activity against the PANC-1 cell line, with an IC50 value of 14.3 μM.

This study prepared yogurt by adding pre-treated egg liquid to milk to modify the texture and nutritional composition, and systematically analyzed the effects of fermentation and egg liquid addition on yogurt metabolites. Results showed that the addition of pre-treated egg liquid significantly improved the nutritional value of both milk and yogurt, enhanced the sense of thickness in taste, and resulted in a more compact microstructure. A total of 935 metabolites were identified through metabolomics analysis. Compared with ordinary yogurt, the abundance of "amino acids and its metabolites", "organic acid and its derivatives", "glycerophospholipids", and "fatty acyls" in egg-milk yogurt was significantly increased. Differentially abundant metabolites were mainly enriched in pathways such as "glycerophospholipid metabolism" and "ABC transporters". Specifically, the addition of egg liquid increased small peptides (e.g., γ-Glu-Phe), glycerophospholipids (e.g., LPC(0:0/22:6), LPC(0:0/20:4)), and long-chain polyunsaturated fatty acids (e.g., FFA (22:4), FFA (22:5)), which maintained a significant advantage after fermentation. These findings provide a theoretical basis and new insights for the processing of egg-dairy composite products and the development of functional yogurts.

Recent studies have indicated the relationships between the human reproductive system, gut microbiota and immune crosstalk. These interactions can influence pregnancy outcomes, which occasionally result in adverse consequences for the mother and fetus. However, key questions remain unresolved, such as identifying the microbiota capable of modulating immune cells during pregnancy. The present review aimed to investigate the relationship between microbiota and T cell types and to clarify the mechanism through which these interactions occur. In pregnancy‑related disease models, it is still unclear whether T helper cell (Th17)/regulatory T cells (Treg cells) are generated in situ or migrate into inflamed tissues. The present review explored the association of gastrointestinal dysbiosis with the female reproductive system and the role of the maternal‑fetal interface. In particular, the effect of gut microbiota‑derived short‑chain fatty acids, bile acids, indoles and their derivatives on immune signaling networks is discussed. Furthermore, the effects of these networks on infectious, metabolic and female pregnancy periods are summarized. Finally, the translational potential of modulating gut microbiota through probiotics and dietary interventions to restore immune homeostasis and improve pregnancy outcomes in Recurrent pregnancy loss (RPL) is also evaluated. The present review aimed to assist patients in developing a more profound comprehension of the underlying causes of unexplained RPL and broaden the spectrum of potential therapeutic strategies for infertility.

Rapid access to molecules with tailored function is essential to advancing the discovery of new medicines, materials, and agrochemicals. Chemical reaction discovery enables it by expanding access to underexplored chemical space and providing more strategies for constructing molecular targets. Among new technologies, photochemical transformations have been revived as a valuable platform for uncovering new reactivity, especially when combined with accelerated reaction discovery platforms. Herein, we report a strategy for accelerated photochemical reaction discovery based on the dynamic speciation of copper complexes, enabled by their metal-ligand bond lability. This approach simplifies reaction screening by employing an earth-abundant copper(II) salt and commercially available ligands to reversibly generate multiple catalytic species in situ, thereby obviating the need for well-defined complexes or photocatalysts. The workflow engaged ubiquitous functional groups in multiple transformations. Specifically, amines and carboxylic acids were employed in deaminative and decarboxylative alkyl azidation of alkenes, enabling the modification of amino acids, peptides, and complex molecules. These products can be further derivatized in one pot through click reactions or by a modular heteroannulation strategy.

Tuberculous meningitis (TBM), caused by Mycobacterium tuberculosis, is the most severe form of extrapulmonary tuberculosis and isassociated with high morbidity and mortality, particularly when diagnosis is delayed. Improved understanding of the metabolic alterations associated withTBM may support the development of novel diagnostic biomarkers and provide insights into disease pathophysiology. In this study, we applied anuntargeted two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) metabolomics approach to formalin-fixed, paraffin-embedded (FFPE) postmortem human brain tissue from 41 TBM cases and 36 tissue sections from 6 non-TBM control cases. Metabolomics data wereprocessed, normalized, and analyzed using multivariate and univariate statistical approaches, including principal component analysis (PCA) and partialleast squares-discriminant analysis (PLS-DA), with variable importance in projection (VIP) scores. These results were further correlated with patient clinical data. Distinct metabolic profiles were observed between TBM and control tissues. Several metabolites were significantly reduced in TBM samples, particularly within the alkane and alkene classes, with additional decreases observed in metabolites associated with alcohols, fatty acids, lipids, carbohydrates, and amino acids. These metabolic alterations suggest substantial perturbations, primarily in the host lysine degradation pathway (linked to the kynurenine pathway), in TBM-affected brain tissue. Collectively, these findings provide insight into the metabolic landscape of terminalTBM and suggest potential metabolic pathways that may contribute to disease pathophysiology. Further investigation of these metabolic signatures in accessible patient tissue and biofluids may support the development of biomarkers and inform future therapeutic strategies for TBM.

Heart failure accounts for more than 43% of annual deaths worldwide, and isdriven by widespread pathological remodeling, in which myocardial fibrosis plays an important role. Currently, accurate clinical diagnosis of myocardialfibrosis (MF) remains difficult, with even greater challenges in differentiating among lesser-understood etiologies, such as cardiac sarcoidosis (CS) andcardiac amyloidosis (CA). To investigate the capability of high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR)spectroscopy to differentiate amongst patients with MF of different origins (CS, CA) using blood sera. HRMAS NMR spectroscopy of 10 ìL ofblood sera from three patient groups, with matched controls, was conducted:1)MF due to common causes including hypertension and coronary arterydisease (n = 13),2)transthyretin CA (n = 18), and3)CS (n = 12). NMR spectra were analyzed as regions of interest (ROIs). ROIAL-NMR was used toidentify metabolites present in the determined ROIs. Statistical analysis, such as hierarchical clustering, Wilcoxon/Kruskal-Wallis tests (paired andunpaired), and unsupervised multivariate principal component analyses (PCA), were performed to distinguish diseased individuals from their matchedcontrols. Analysis of NMR spectra identified 61 ROIs highlighting metabolite alterations such as changes in fatty acids, branched chain aminoacids, and markers of energy and inflammatory states, that may contribute to disease-specific metabolic signatures. HRMAS NMRmetabolomics results may enhance our understanding of the patho-mechanisms underlying myocardial fibrosis across etiologies and serve as a clinicallypractical tool to improve diagnostic precision and identify new therapeutic targets.

Cardiovascular disease remains the leading cause of global morbidity and mortality and arises from complex interactions among metabolic dysregulation, inflammation, thrombosis, and vascular dysfunction. In recent years, the gut microbiota has emerged as an important regulator of cardiovascular pathophysiology, largely through the production of bioactive metabolites that act on distant organs. This review summarizes the major classes of gut microbiota-derived metabolites involved in cardiovascular disease, with particular emphasis on trimethylamine N-oxide, short-chain fatty acids, phenylacetylglutamine, bile acids, and tryptophan-derived metabolites. We discuss how these metabolites influence endothelial dysfunction, immune activation, lipid handling, platelet reactivity, cardiac remodeling, gut barrier integrity, and blood pressure regulation through interconnected signaling pathways. We further examine their disease-specific relevance in atherosclerosis, heart failure, hypertension, and coronary artery disease/acute coronary syndrome. In addition, we evaluate current translational strategies targeting microbial metabolism, including dietary modulation, probiotics and prebiotics, fecal microbiota transplantation, and selective inhibition of microbial enzymes. Rather than viewing individual metabolites as uniformly harmful or protective, we propose that cardiovascular risk is better understood as the net consequence of interacting microbial metabolic pathways within specific host contexts. This metabolite-centered framework may help refine biomarker development, risk stratification, and pathway-guided interventions in cardiovascular medicine.

Animal protein sources may differentially influence glucose homeostasis, yet the underlying mechanisms remain unclear. We investigated how casein, pork, beef, mutton, chicken, duck, and goose proteins differentially affected glucose homeostasis in mice and their associations with gut microbiota and bile acids. Mice fed duck protein exhibited more favorable glucose tolerance and insulin sensitivity than those fed pork protein. These differences were accompanied by coordinated alterations in gut microbiota and bile acid profiles, including enrichment of Clostridium, increased abundance of the baiE gene, and elevated secondary bile acids. Compared with pork protein, duck protein intake increased ileal fibroblast growth factor 15 expression and portal active glucagon-like peptide-1 concentrations, upregulated adipose thermogenic and lipid oxidation genes, while downregulating hepatic gluconeogenic genes. Correlation analysis revealed associations between these genes and glucose metabolic parameters. Collectively, alterations in the microbiota-bile acid axis may contribute to the favorable glucose homeostasis observed in duck protein-fed mice.

A method for the fluorination of phosphonic acids is described that does not require anhydrous conditions. Mechanistically, we show that pentafluoropyridine (PFP) functions as an activator and fluoride source, quantitatively forming phosphonofluoridic acids (phosphonofluoridates). Mechanistic pathways were postulated using 31P and 19F NMR spectroscopy and mass spectrometry data. Furthermore, we show that either altering reaction conditions or the provision of a fluoride scavenger results in the formation of corresponding phosphonic acid anhydrides.

Endosomal sorting complex required for transport (ESCRT-III) is a membrane remodeling complex involved in a large number of cellular processes. It appears to perform an essential function in eukaryotes, since to date no eukaryotic organism completely devoid of ESCRT-III has been found. Yet, yeast cells with a deletion of all eight known ESCRT-III genes are viable. We therefore searched for new, previously undiscovered ESCRT-III like proteins in yeast. HHPred uncovered several proteins with similarity to Snf7. The similarity was mostly restricted to the α1-α2 hairpin region of Snf7. A conserved pattern of amino acids was detected in this region. One of the proteins with an ESCRT-III like sequence pattern, which strikingly resembled Snf7 in its secondary structure, was studied more closely. We named the protein encoded by ORF YPL199c Etl1 (ESCRT-three-like 1). Etl1 is palmitoylated and localizes to the plasma membrane. In contrast to other palmitoylated proteins, Etl1 does not appear to be associated with lipid rafts, since it could be easily extracted from the membrane by Triton X-100 treatment. When ETL1 was deleted in the octuple ESCRT-III deletion background, the yeast cells were still viable. So far, despite a number of experiments, a bona fide ESCRT-III function could not be demonstrated for Etl1.

The resin of masson pine (Pinus massoniana L.) exhibits considerable economic value and primarily consists of diterpenoid resin acids. However, the upstream regulation of the key diterpene biosynthetic gene, PmLAS, remains largely unclear. In the present study, through yeast one-hybrid screening, three PmMYB transcription factors were identified: PmMYB30, PmMYB68, and PmMYB74. Subsequent verification through dual-luciferase assays substantiated that these transcription factors interact with the PmLAS promoter, thereby facilitating its transcriptional activation. Subcellular localization analysis indicated that all three PmMYBs are localized in the nucleus, and transcriptional activation assays in yeast further revealed that their C-terminal regions are responsible for the transcriptional activation activity. Meanwhile, the transcript levels of three PmMYBs exhibited a significant positive correlation with resin yield in the xylem of 12-year-old masson pine trees. Moreover, the heterologous overexpression of these genes in tobacco resulted in a growth-inhibiting phenotype, a marked increase in leaf glandular trichome numbers, and an elevated proportion of diterpenoids compared to wild-type tobacco. To further elucidate the molecular regulation of the PmLAS gene by the transcription factor PmMYB30, yeast two-hybrid library screening was performed to screen its interacting proteins. A RING-type E3 ubiquitin ligase was identified from the screening results and designated PmRDUF1. Subsequent luciferase complementation imaging assays provided further evidence supporting the interaction between PmRDUF1 and PmMYB30. Furthermore, dual-luciferase reporter assays demonstrated that this interaction suppresses the ability of PmMYB30 to activate the expression of PmLAS, forming a PmRDUF1-PmMYB30-PmLAS regulatory module. Collectively, our findings suggest that a complex transcriptional network governs diterpenoid biosynthesis in masson pine, offering new perspectives on the regulation of terpenoid metabolism.

Metabolic disorders have grown more common, with obesity representing a significant chronic illness that leads to various severe health complications. The Obesity Atlas 2022 predicts one billion obese people by 2030. Contributors to obesity encompass heightened oxidative stress, hyperlipidemia, hunger enhancement, fat accumulation, insulin resistance, and diminished caloric expenditure. Numerous synthetic interventions for obesity are accessible today ; nonetheless, they frequently entail detrimental side effects. This research aimed to investigate the formulation of a prospective anti-obesity drug derived from plant origins. The anti-obesity effectiveness of a polyherbal formulation, derived from the ethanolic extract of both Hugonia mystax and Blumea lacera in a 1:1 ratio, was assessed in female mice with progesterone-induced obesity. The preliminary phytochemical screening of the formulation specifies the presence of phenolic acids, flavonoids, and tannins. In accordance to OECD recommendations, 200 mg/kg and 400 mg/kg were designated after performing acute oral toxicity assessment as a low dose and high dose. During the study, body weight, BMI, abdomen circumference, glucose levels, lipid profile, SGOT, SGPT, atherogenic index, lipid peroxidation (LPO), and glutathione (GSH) levels were evaluated in all groups. The treatment markedly corrected the abnormal levels of these parameters and dramatically restored GSH levels. Metabolic disorders, especially obesity, are increasing globally. Synthetic therapies have negative consequences; therefore, exploration of plant substitutes is encouraged A polyherbal extract of Hugonia mystax and Blumea lacera has shown significant anti-obesity properties in mice. It restored biochemical parameters, likely due to phytochemicals such as polyphenols. Histological examination validated its therapeutic efficacy. The formulation's efficacy in addressing obesity is likely attributable to the presence of polyphenols, saponins, and terpenoids. Histopathological examination of hepatic and adipose tissues further corroborated the anti-obesity efficacy of the polyherbal formulation. Future research will focus on isolating and identifying the active chemicals in both plants to better understand their composition.