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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.

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.

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.

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.

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.

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.

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.

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.

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.

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 growing environmental concerns and stricter global fuel regulations on sulfur content have accelerated the search for efficient desulfurization technologies. Oxidative Desulfurization (ODS) has emerged as a promising complement or alternative to conventional Hydrodesulfurization (HDS), offering advantages such as mild operating conditions, reduced energy consumption, and superior performance in removing refractory sulfur compounds. Among various oxidants, hydrogen peroxide (H2O2) has attracted significant interest due to its environmental compatibility, cost-effectiveness, and the benign nature of its by-products-water and oxygen. This review emphasizes mechanistic insights into H2O2-based ODS, focusing on the activation of H2O2 and subsequent oxidation of sulfur species. Catalytic systems such as organic acids, polyoxometalates (POMs), ionic liquids (ILs), deep eutectic solvents (DESs), transition metal oxides, and metal-organic frameworks (MOFs) have been widely explored for enhancing H2O2 activation. The generation of reactive oxygen species (ROS), especially hydroxyl radicals (•OH), plays a pivotal role in oxidizing organic sulfur compounds into polar sulfoxides and sulfones, enabling their easy separation. Recent progress in catalyst design has yielded highly efficient and reusable systems under mild conditions, underscoring the potential of H2O2-assisted ODS as a sustainable pathway for producing ultra-low sulfur fuels.

Nucleic acid synthesis is a dual-use technology that can benefit fields such as biology, medicine, and information storage. However, synthetic nucleic acids could also potentially be used negligently and ultimately cause harm, or be used with malicious intent to cause harm. Thus, this technology needs to be appropriately safeguarded. Sequence screening is one component of a biosecurity protocol for preventing such harm and consists of identifying Sequences of Concern (SOCs). There exist many fit-for-purpose tools that have been developed for nucleic acid synthesis sequence screening. However, questions remain regarding their performance with respect to the consistency of screening. To aid in determining if screening tools are harmonized in regard to baseline sequence screening (which represents a minimum acceptable level of performance), the National Institute of Standards and Technology (NIST) constructed a test dataset based on current screening recommendations. NIST then sent blinded datasets to sequence screening tool developers for testing. Overall, there was a general agreement between the tools and NIST labels given to the sequences, and all tools had a baseline performance of >95% sensitivity and >97% accuracy. Disagreement on specific sequences largely arose from single tools and could be traced to differences in defining a SOC and/or methodological differences in screening algorithms.

Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. The gut microbiota profoundly influences this cancer by modulating immune responses and therapeutic efficacy. Recently, live biotherapeutic products (LBPs), comprising live resident microorganisms in the gut, have emerged as promising agents to reprogram host immunity and enhance treatment efficacy in preclinical CRC models. However, translation of these findings to clinical practice remains limited due to heterogeneous study designs, poorly defined mechanisms in human hosts, unresolved manufacturing and safety concerns, and lack of personalized treatment strategies. This review briefly introduces LBPs as a new class of medicines, categorize them as single strains, composite strains, and engineered strains, and details their multifaceted mechanisms against CRC, including direct immunomodulation to enhance anti-tumor activity, production of protective metabolites like short-chain fatty acids (SCFAs), and restoring gut microbiota. Additionally, the synergistic potential of LBPs with conventional chemo- and immunotherapies and current LBPs in clinical trials for CRC are summarized, highlighting their translational progress. We further address the manufacturing, regulatory, and safety barriers constraining clinical adoption and propose strategies for integrating preclinical and clinical evidence to meet patient needs. By consolidating current knowledge of LBPs as an emerging oncology drug class, this review offers a practical framework for advancing LBPs from preclinical promise to clinical practice, supporting the development of personalized medicine.