Search Results (289)

Artisanal cheese quality relies on a complex microbiota. The generalized use of commercial starter cultures has been associated with reduced microbial diversity, fueling interest in using indigenous lactic acid bacteria (LAB) as adjunct cultures. This study aimed to evaluate Ligilactobacillus salivarius SP36 as a starter or adjunct culture in ripened cheeses. Culture-based and culture-independent analyses were performed, together with the assessment of some physico-chemical parameters (pH, water activity, and color), including the profile of volatile compounds. All cheeses were microbiologically safe according to current EU legislation. The pH of the cheese made only with the SP36 strain was higher than those of the cheeses manufactured with a commercial starter (with or without strain SP36). L. salivarius SP36 modulated the aroma profile by increasing ethyl esters, alcohols, ketones, organic acids and sulphur compounds. LAB dominated all cheeses, with the highest microbial diversity in the cheese produced without the commercial starter. Lactiplantibacillus plantarum and Lacticaseibacillus paracasei isolates were obtained from all cheeses. Overall, L. salivarius SP36 seems a promising adjunct for mature cheeses, while autochthonous L. plantarum and L. paracasei isolates represent promising candidates for starter or adjunct cultures. Full article

Mitochondria comprise ~1/3rd of the volume of an adult ventricular cardiomyocyte. The gene Immt encodes the Mic60/Mitofilin protein that is hypothesized to organize the mitochondrial contact site and cristae organization system (MICOS) complex that generates mitochondrial cristae junctions between the inner and outer membranes. To investigate the function of the Immt gene in the mouse heart, we generated and characterized mice in which this gene was specifically deleted in the mouse heart using a loxP-targeted allele (Immt^fl/fl) and either the constitutive heart-specific Myh6-Cre transgene or the conditional Myh6-MerCreMer transgene, each of which showed lethality in several weeks. Hearts from these mice showed progressive hypertrophic cardiomyopathy and failure with lost contractility and lung edema. At the ultrastructural level, hearts from these mice showed extreme abnormalities in mitochondrial architecture characterized by lost cristae junctions, stacking of the inner mitochondrial membranes, mitophagy and areas with complete absence of mitochondria. Analysis of mitochondria showed loss of the MICOS complex of proteins as well as loss of mitochondrial membrane potential (Δψ) and increased expression of mitophagy proteins and mitochondrial biogenesis transcription factors. Hearts from these mice also showed widespread cardiomyocyte necrosis and induction of the universal mitochondrial stress response at the mRNA level, as well as major alterations in cardiac metabolites, suggesting greater use of glucose, ketones and amino acids. We conclude that the Immt gene is required for cardiac mitochondrial structure and function, although the ensuing mitochondrial stress response provides molecular clues as to how the heart can compensate metabolically and maintain viability for weeks after mitochondria are absent or unfunctional. Full article

Multiple sclerosis (MS) is characterized by progressive mitochondrial dysfunction affecting complexes I, III, and IV of the electron transport chain, contributing to axonal energy failure and neurodegeneration. This review examines the potential of combining β-hydroxybutyrate (βHB), epigallocatechin-3-gallate (EGCG), and ellagic acid (EA) as a multi-target therapeutic strategy to restore mitochondrial function in patients with MS. Experimental and clinical studies demonstrate that each compound exerts complementary mechanisms. Ketone bodies provide an alternative energy substrate and restore complex I activity via sirtuin-dependent pathways. EGCG acts predominantly at the peripheral level by reducing systemic inflammation and oxidative stress. EA-derived urolithins effectively cross the blood–brain barrier to directly enhance mitochondrial biogenesis and respiratory chain function in the central nervous system. Clinical trials have reported improvements in fatigue, cognition, mood, and muscle function following supplementation with these compounds. The convergence of their actions on energy restoration, reactive oxygen species reduction, and epigenetic modulation of protective pathways suggests their synergistic potential. Optimized delivery strategies, including exogenous ketone salts, liposomal EGCG, and microencapsulated EA, may overcome bioavailability limitations and interindividual variability in the gut microbiota metabolism. Full article

Emerging mosquito-borne flaviviruses, such as Dengue virus (DENV) and Zika virus (ZIKV), pose major global public health threats due to their geographic expansion, climate change, and the absence of effective antiviral therapies. Antiviral development against these pathogens has primarily focused on two complementary strategies. On the one hand, the blocking of viral replication by directly inhibiting essential viral enzymes, and on the other, enhancing the host’s innate immune defenses via targeted activation of intracellular antiviral pathways. Among the viral proteins required for replication, the NS2B–NS3 protease complex is one of the most conserved and druggable targets, prompting extensive efforts to design both covalent and non-covalent inhibitors. Covalent inhibitors, such as boronic acids, aldehydes, trifluoromethyl ketones, phenoxymethylphenyl derivatives, and α-ketoamides, form irreversible or slowly reversible bonds with the catalytic serine residue (Ser 135), producing long-lasting and high-affinity suppression of protease activity. In parallel, several classes of non-covalent, particularly allosteric, inhibitors have emerged as promising alternatives with improved specificity and reduced off-target reactivity. A complementary antiviral strategy involves the use of agonists of key innate immune sensors such as TLRs, RIG-I, and the cGAS–STING axis, which mediate the release of interferons (IFNs). This review brings together current knowledge on these two mechanistically distinct yet convergent approaches, highlighting how both can ultimately restrict flavivirus replication. Future opportunities involving modified peptide scaffolds, advanced delivery systems, and drug-repurposing strategies are finally discussed for the development of next-generation therapeutics against DENV and ZIKV. Full article

Background/Objectives: Beta-hydroxybutyrate (BHB) exists as two enantiomers with potentially distinct biological activities. While D-BHB is the physiological form produced during ketogenesis, L-BHB is present in equal amounts in racemic supplements, yet its biological effects remain poorly understood. Additionally, the ketone precursor 1,3-butanediol (BD) is used in some formulations despite limited safety data. Methods: We investigated acute (single gavage, 2-h time course) and short-term (daily gavage for 8 days) hepatic effects of D-BHB, L-BHB, and 1,3-butanediol compared to a vehicle control in male C57BL/6 mice. Acute studies assessed hepatic ATP dynamics and lipid peroxidation (MDA) at multiple timepoints. Eight-day protocols evaluated mitochondrial function (oxygen consumption, Complex II activity, SDH activity), lipid accumulation (triglycerides), and inflammatory markers (IL-1β, TNF-α, CRP). Results: Acute ATP responses differed markedly among treatments. Compared to the baseline and the control, L- and D-BHB elicited significant increases in ATP, while BD caused sustained ATP depletion. Over this same time, oxidative stress markers remained stable in the control and both BHB groups but increased dramatically with BD. After 8 days, the mitochondrial effects of BD were more apparent with a significant reduction in complex II-supported respiration and activity. Both forms of BHB maintained control levels of inflammation and BD showed significant effects on all inflammatory markers. Hepatic triglycerides increased only with BD treatment. Conclusions: This study reveals striking hepatic effects of various ketone supplements. In contrast to the positive or inert effects of BHB enantiomers, 1,3-butanediol induces significant hepatic stress. These findings have implications for ketone supplement formulation and highlight the therapeutic potential of D- and L-BHB. Full article

The transition from energy sufficiency to deficiency triggers complex metabolic and immune adaptations that have traditionally been viewed through a reductionist pathological lens. During early lactation, coordinated mobilization of adipose tissue, muscle protein, and bone minerals supports milk synthesis, with ketogenesis specifically arising from hepatic oxidation of non–esterified fatty acids. This review introduces the Keto–Inflammatory Network (KIN), a novel framework positioning ketonemia as an evolutionarily conserved adaptive response rather than inherent metabolic dysfunction. The KIN integrates β–hydroxybutyrate (BHB) signaling with immune modulation, epigenetic regulation, circadian rhythms, and microbiota interactions. Through mechanisms including NLRP3 inflammasome inhibition, HDAC–mediated epigenetic modifications, and HCAR2 receptor activation, ketone bodies orchestrate anti–inflammatory responses while maintaining metabolic flexibility. Building upon important precedent work recognizing beneficial roles of ketones in ruminant metabolism, this review synthesizes recent advances in immunometabolism and systems biology into an integrated framework. The KIN encompasses calcium–ketone integration through the Calci–Keto–Inflammatory Code (CKIC), temporal regulation via the Ketoinflammatory Clock, and trans–kingdom signaling through microbiota interactions. In dairy cattle, this perspective reframes periparturient ketonemia as existing on a continuum from adaptive to pathological, with biological meaning determined by integrated metabolic–inflammatory patterns rather than absolute ketone concentrations. The CKIC paradigm, while requiring prospective validation, suggests novel therapeutic approaches leveraging ketone signaling for inflammatory diseases, autoimmune conditions, and metabolic disorders while challenging traditional threshold–based ketosis management strategies. This systems–level understanding opens new avenues for precision interventions that work with, rather than against, evolved adaptive mechanisms refined through millions of years of mammalian evolution. By distinguishing ketonemia (measurable ketone elevation) from pathological ketosis (dysregulated ketone accumulation), and by integrating evidence from both ruminant and monogastric models, this review provides a comprehensive framework for next–generation metabolic medicine. Full article

Near-critical and supercritical carbon dioxide (SC-CO₂) is extensively utilized in high-pressure separation, extraction, polymer processing, and carbon capture and utilization (CCU) technologies owing to its tunable density, low viscosity, high diffusivity, and environmentally benign nature. Reliable phase equilibrium data are indispensable for process design and optimization, especially in the near-critical region characterized by pronounced non-idealities, high compressibility, and density fluctuations. This review synthesizes experimental phase behaviour studies for binary mixtures of CO₂ with diverse components, including hydrocarbons, alcohols, ethers, esters, ketones, water, monomers/polymers, ionic liquids (ILs), and deep eutectic solvents (DESs), compiling extensive vapour–liquid equilibrium (VLE), liquid–liquid equilibrium (LLE), and critical data across industrially relevant pressure (up to 40 MPa) and temperature (up to 400 K) ranges. It critically evaluates analytical (sampling and non-sampling) and synthetic methodologies, addressing challenges in CO₂-rich phase handling, depressurization artefacts, and near-critical phenomena, while assessing data consistency against established reliability criteria. Key trends emerge, such as enhanced solubility with increasing pressure and CO₂ density, chain-length dependencies in hydrocarbons and alcohols, and Lewis acid–base interactions driving solvation in polar systems. The review highlights gaps in multicomponent data and proposes integrating high-quality experiments with advanced thermodynamic modelling to enhance predictive accuracy. Future directions emphasize high-precision in situ techniques, expanded datasets for complex mixtures, and novel CO₂-philic solvents to advance sustainable SC-CO₂ applications. Full article

In Chinese cuisine, seasoning oil enhances the aroma and appearance of dishes. This study examined how processing affects flavor release in multi-ingredient oils. Volatile organic compounds (VOCs), relative odor activity value (ROAV), and variable importance projection (VIP) were used to assess flavor changes. Optimal frying was 160 °C for 15 min with 11% green Sichuan peppercorn, 3% ghost pepper, 6% green onion, 0.1% bay leaf, 0.2% deseeded tsaoko, 0.5% star anise, 0.3% fennel seeds, 1.5% dried Erjingtiao chili, 5% ginger, and 2.5% red Sichuan peppercorn. Gas chromatography–ion mobility spectrometry (GC-IMS) and gas chromatography–mass spectrometry (GC-MS) analyzed heating at 150 °C, 160 °C, and 170 °C. Temperature strongly influenced VOC formation; 160 °C produced the most diverse VOCs, including aldehydes, ketones, terpenes, esters, and alcohols. Multivariate analysis identified 73 key compounds (VIP > 1) between 150 and 160 °C, but only 39 between 160 and 170 °C, indicating that high heat reduces complexity. Compounds such as 2-methylpyrazine and (E)-2-heptenal contributed caramel, nutty, buttery notes, with 2-methoxy-3-(1-methylethyl)-pyrazine as the core aroma. Frying at 160 °C balanced sweet, floral, and roasted aromas, offering guidance for precise seasoning oil flavor control. Full article

This study aimed to explore the evolution of quality and flavor characteristics of braised pork during the cooking process and clarify the underlying formation mechanisms. Texture analysis revealed that shear force and hardness initially increased during blanching but decreased substantially with an extended stewing time. Low-field NMR indicated a progressive shift in water distribution from immobilized to free states, correlating with cooking loss and tenderness development. GC-MS and E-nose analyses showed significant increases in volatile compound diversity and concentrations, with aldehydes and ketones identified as dominant contributors to the evolving aroma profile. Throughout the processing, an enhancement in protein oxidation and nucleotide degradation was observed. Notably, significant increases were detected in the umami amino acids aspartic acid and glutamic acid, as well as in the umami nucleotide inosine monophosphate (IMP). These changes collectively contributed to the development of the characteristic taste profile. These findings indicate that the superior eating quality evolution and flavor development of braised pork during cooking are governed by the coordinated changes in texture, water distribution, lipid oxidation, and taste-active compounds. The interplay between these factors occurs at different stages of processing, leading to the complex, non-linear enhancement of flavor and texture. Full article

For those who did not follow the invention and development of enantioselective catalysis, this review introduces pertinent historical aspects of the field and presents the scientific concepts of asymmetric bio- and organocatalysis. They are powerful technologies applied in organic laboratories and industry. They realize chiral amplification by converting inexpensive achiral substrates and reagents into enantiomerically enriched products using readily recoverable solvents, if any are used. Racemic substrates can also be deracemized catalytically. More sustainable fabrications are now available that require neither toxic metallic species nor costly reaction conditions in terms of energy, atmosphere control, product purification, and safety. Nature has been the source of the first asymmetric catalysts (microorganisms, enzymes, alkaloids, amino acids, peptides, terpenoids, sugars, and their derivatives). They act as temporary chiral auxiliaries and lower the activation free energy of the reaction by altering the reaction mechanism. Reductions, oxidations, carbon-carbon and carbon-heteroatom bond-forming reactions are part of the process panoply. Asymmetric catalyzed multicomponent and domino reactions are becoming common. Typical modes of activation are proton transfers, hydrogen bonded complex formation, charged or uncharged acid/base pairing (e.g., σ-hole catalysts), formation of equilibria between achiral aldehydes and ketones with their chiral iminium salt or/and enamine intermediates, umpolung of aldehydes and ketones by reaction with N-heterocyclic carbenes (NHCs), phase transfer catalysis (PTC), etc. Often, the best enantioselectivities are observed with polyfunctional catalysts derived from natural compounds, but not always. They may combine to form chiral structures containing nitrogen, phosphorus, sulfur, selenium, and iodine functional moieties. Today, man-made enantiomerically enriched catalysts, if not enantiomerically pure, are available in both enantiomeric forms. Being robust, they are recovered and reused readily. Full article

This study aimed to analyze the volatile organic compounds (VOCs) for different rice aroma types using sensory evaluation, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS), and gas chromatography-ion mobility spectrometry (GC-IMS) techniques, and to explore the material basis for the flavor differences. Based on the sensory evaluation results, rice aroma was categorized into three types, distinguished by their unique aroma compounds. Type A was characterized by a prominent sweet, popcorn aroma, type B by a more prominent cereal and starchy flavor, and type C by a more complex aroma. Untargeted metabolomics analysis using HS-SPME-GC-MS identified and characterized 74 volatile compounds. A comparison of A versus B versus C revealed 8 key aroma compounds, primarily alkanes, aldehydes, ketones, alcohols, and heterocyclic compounds. (E)-2-Octenal, 6-Undecanone, 2-Acetyl-1h-pyrrole, and P-menthan-1-ol in type A gave it a better sweet aroma, Dodecane, 2,6,10-trimethyl-, 1-Octen-3-one, and 2-Methyldecane in type B gave it a better starchy and cereal flavor. 2-Acetyl-1h-pyrrole, Heptacosane, and 1-Propanol in type C contributed to a complex aroma. GC-IMS analysis showed that the fingerprints of rice with different aroma types were significantly different. The VOCs of aroma type A contained (+)-limonene, 2-methylpyrazine, 2-pentanone, ethyl butanoate, n-pentanal, styrene, 1-butanol, 3-methyl-, acetate, 1-hexanal, 1-pentanol, and 2-heptanone, which gave it a better sweet aroma. The VOCs of aroma type C contained 1-octen-3-ol, 2,6-dimethyl pyrazine, 2-acetylpyridine, and ethyl hexanoate, which gave it a better complex aroma. Full article

Fused deposition modeling of polyether ether ketone offers distinct advantages for fabricating complex and lightweight structures. Although three principal build orientations theoretically exist for practical 3D engineering components, research on their effects remains limited, especially regarding the influence of the interaction between build orientation and printing path on mechanical performance. This study investigated the tensile and shear properties, as well as the failure mechanisms, of FDM-fabricated PEEK under the coupled effects of build orientation and printing path through mechanical testing, fracture morphology analysis, and statistical methods. The results indicate that the printing path exerts a dominant influence on anisotropic behavior, while the interaction between printing path and build orientation jointly governs the shear failure modes. Under identical printing paths, the elongation at break varied by up to twofold across different build orientations, reaching a maximum of 96%, whereas samples printed with W or T paths exhibited elongations at break below 5%. Although shear and tensile moduli remained largely consistent across build orientations, other mechanical properties demonstrated significant differences. Variations in cross-sectional dimensions induced by build orientation markedly affected tensile performance: the coupled effect of build orientation and printing path was found to render the path repetition frequency a critical factor in determining temperature uniformity within the printed region and the quality of interlayer interfaces, thereby constituting the core mechanism underlying anisotropic behavior. Furthermore, larger cross-sections re-duced tensile modulus but enhanced yield strength and elongation at break, highlight-ing the regulatory role of cross-sectional geometry on mechanical response. Based on these findings, a synergistic optimization strategy integrating printing path, build orientation, and tensile–shear performance is proposed to achieve tailored mechanical properties in FDM-fabricated PEEK components. This approach enables controlled enhancement of structural performance to meet diverse application requirements. Full article

Background: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to its often-late diagnosis and complex molecular heterogeneity. Understanding the metabolic alterations in OC can provide insights into its pathophysiology and potential therapeutic targets. This study aimed to explore serum metabolomic profiles and their correlation with clinical and pathological features in OC patients. Materials and Methods: Thirty serum samples were collected from patients diagnosed with ovarian tumors (OTs) (n = 24 malignant, n = 6 benign) and undergoing treatment at Careggi University Hospital. Additionally, 47 samples were obtained from age-matched healthy female donors. Serum samples underwent processing and analysis using an H-NMR (Nuclear Magnetic Resonance) platform to identify a panel of metabolites. Correlation analysis between the metabolomic data and clinical parameters was performed using R software (v.4.4.0). Results: Differential metabolomic profiling showed a significant upregulation of metabolites associated with the purine salvage pathway (i.e., hypoxanthine and inosine) and the ketone bodies axis (i.e., acetone, 3-hydroxybutyrate, and acetate) in samples from ovarian tumor (OT) patients compared to healthy donors. Within malignant OC samples, metabolomic profiles significantly correlated with BRCA1/2 mutation status (BRCA1/2-mutated vs. wild-type) and homologous recombination deficiency (HRD) status. Conclusions: The analysis revealed significant variation in specific metabolites such as betaine, creatinine, carnitine, glycerol, and mannose; notably, a downregulation of these metabolites was observed in HRD-positive patients. The study identifies significant metabolomic alterations in OC, implicating pathways such as purine salvage and ketone bodies. Intriguingly, consistent variation in specific metabolites across BRCA/HRD phenotypes underscores their potential as OC biomarkers. Further research is needed to validate these findings and explore their prognostic and therapeutic implications. Full article

Fermented tea beverage (FTB) has garnered significant attention owing to its unique combination of tea and wine flavors and its potential health benefits. This study investigates FTB co-fermented using different inoculum sizes of L. plantarum HYY-S10 and P. pastoris, evaluating physicochemical properties during the fermentation process. The final FTB products were comprehensively evaluated for their antioxidant activity, organic acid content, sensory characteristics, volatile flavor compounds, and microbial diversity. Compared with natural fermentation, the 1:1 mixed fermentation of these two microorganisms enhanced the antioxidant capacity and organic acid content of FTB. Furthermore, sensory evaluation revealed higher overall acceptability. Analysis of volatile compounds demonstrated an increase in the production of alcohols, esters, and ketones, leading to enhanced malty, fruity, and creamy aromas in FTB. Among these compounds, 3-methyl-1-butanol, phenylethyl alcohol, 1,2-propanediol, and 3-hydroxy-2-butanone play pivotal roles in shaping the flavor profile. High-throughput sequencing analysis identified Lactobacillus and Weizmannia as dominant bacteria, while Pichia or Issatchenkia was found to be dominant fungi. This study provides a theoretical foundation for the production of FTB through mixed fermentation with L. plantarum HYY-S10 and P. pastoris while contributing to the practical application of FTB production through mixed fermentation techniques. Collectively, our findings demonstrate that the 1:1 co-fermentation of L. plantarum HYY-S10 and P. pastoris is a promising strategy for developing novel fermented tea beverages with enhanced functional properties and complex, desirable flavors, offering valuable insights for the industrial production of specialty FTBs. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder requiring safer and more effective therapeutic alternatives. This study investigates a novel fucoxanthin derivative isolated from the marine brown alga Chnoospora minima using a comprehensive in silico approach. Molecular docking revealed that the derivative exhibited higher binding affinities toward α-amylase (–9.4 kcal/mol) and α-glucosidase (–8.0 kcal/mol) compared to the reference drug acarbose (–8.5 and –7.4 kcal/mol, respectively). Pharmacokinetic analysis predicted good intestinal absorption and P-gp inhibition (0.894) and moderate plasma clearance (7.864 mL/min/kg), while toxicity predictions classified it in toxicity class 3, with no respiratory or ocular toxicity. Drug-likeness evaluation showed only one Lipinski and one Veber rule violation, common for natural products. Molecular dynamics simulations conducted for 100 ns using NAMD 3.0 confirmed stable protein–ligand complexes with average RMSD values of ~1.3 Å and ~1.8 Å for α-amylase and α-glucosidase, respectively, and consistent hydrogen bonding profiles. Structural analysis identified a substitution of the allene bond with an unsaturated ketone at the C8′ position as a key contributor to enhanced enzyme interaction. The findings suggest that this fucoxanthin derivative is a promising natural candidate for T2DM therapy and warrants further investigation through lab experiments (in vitro and in vivo). Full article