Global warming profoundly alters the stability of soil organic matter (SOM) in permafrost zones, yet the underlying mechanisms governing SOM stability in permafrost landscapes at different stages of degradation remain unclear. This study utilised soil samples from the 0–50 cm layer collected from both continuous and isolated patches permafrost zones in the Daxing’an Mountains for laboratory incubation experiments at constant temperatures of 5 and 15 °C. The results for SOC, Fe and Al oxide content, δ 13C and MBC indicate that SOM in isolated patchy permafrost possesses greater bioavailability and higher decomposability under warming, and carbon mineralization in shallow soils is more temperature-sensitive (Q10 = 4.24). After 89 days of incubation, the mineralisation rate in mineral-rich deep soil was only half that of organic-rich surface soil. Furthermore, as the ratio of Fe/Al oxides to organic carbon increased, the sensitivity of SOM decomposition to temperature decreased significantly. Overall, the stability of organic matter in permafrost is jointly regulated by the intrinsic molecular properties of the organic matter and the protective effect of minerals; furthermore, this protective effect can significantly delay the process by which peatlands in permafrost regions transition from carbon sinks to carbon sources.
Olopatadine (OLO) is a second-generation antihistamine approved for the treatment of allergic conjunctivitis as ophthalmic and nasal solutions. Due to its intrinsic absorption in the near-UV region (approximately 300 nm), OLO may be susceptible to photodegradation and understanding this behavior is essential for ensuring the quality and safety of OLO-containing pharmaceutical formulations. The forced photodegradation of OLO was investigated under UV/Vis irradiation (300–800 nm) over a wide pH range. Photodegradation kinetics was evaluated using a selective LC-UV method. OLO degradation followed first-order kinetics, with rate constants ranging from 3.45 × 10−5 to 6.91 × 10−5 s−1, corresponding to degradation levels in the range 45.54–81.95%. Photodegradation products were characterized using UHPLC-HRMS/MS, leading to the identification of twelve, including seven previously unreported compounds. Seven degradants were isolated by preparative LC-UV and their structures were confirmed by NMR spectroscopy, including three newly reported compounds. The potential toxicity of all identified photodegradants was evaluated using the in silico tools OSIRIS Property Explorer and Toxtree. Five products were predicted to exhibit reproductive toxicity and irritation potential, whereas one compound showed a potential tumorigenic risk. Overall, this study provides comprehensive insight into the photostability of OLO and the formation of its photodegradation products.
Chemical examination of Penicillium steckii HJT-A-10, an endophytic fungus derived from Rhodiola tibetica, led to the isolation of ten metabolites. Structural elucidation by spectroscopic methods revealed that two of these were previously unreported compounds (1 and 2), though the absolute stereochemistry of 2 remained provisional; the other eight isolates (3–10) were identified as known compounds. All ten metabolites were tested for their capacity to inhibit nitric oxide (NO) production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Compounds 1–4 and 7–10 exhibited marked inhibitory effects. Among the two new compounds, 2 displayed stronger activity, with an IC50 value of 19.01 µM. To explore the potential mechanisms of action, network pharmacology and molecular docking analyses were subsequently conducted to predict the relevant targets and signaling pathways.
Starch, a natural source of energy in the form of glucose chains, is widely utilized in various industrial and scientific fields. In its native state, starch is thermally unstable and undergoes gelatinization. Physicochemical modifications of starch aim to increase its thermal and structural stability while simultaneously enhancing its reactivity by introducing new functional groups. The primary objective of this study was to develop thermally stable and economically viable starch-based drug carriers capable of the controlled release of a negatively charged component sourced from aronia extract. Potato starch underwent a series of chemical modifications, specifically quaternary amine etherification, citric acid esterification, and/or hydrothermal modification. The characterization involved determining several parameters: the degree of amino substitution groups; starch particle size using a laser particle size analyzer; viscosity and pH; gelation temperature and heat capacity measured by scanning calorimetry (DSC); mass degradation analyzed via thermogravimetric analysis (TG); crystallinity determined by X-ray diffraction (XRD); potential intermolecular interactions studied by Fourier-Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR); and the rate of chlorogenic acid release from aronia extract tablets quantified by spectrophotometry. The highest cationization results were achieved using citrate starches, reaching up to 86%. The combined application of citric acid esterification and cationization, coupled with an annealing process, resulted in increased viscosity, amorphousness, and enzyme resistance of the starch. Citric acid esterification significantly improved the thermal stability of the starch. Furthermore, FTIR studies revealed the formation of electrostatic interactions between the functional groups of the starch and the components of aronia extract. The amount of chlorogenic acid released showed significant variation (70–100%) depending on the type of starch modification. Collectively, these studies confirmed that both hydrothermal and chemical modifications influence the thermal and structural stability of the starch. Utilizing all combination modification strategies ensured the production of highly promising carriers for active substances.
An efficient, catalyst-free, and room-temperature protocol has been developed for the ring-opening reactions of ring cyclic ethers with indoles in Hexafluoroisopropanol (HFIP). Under these mild conditions, a diverse range of indoles smoothly reacted with oxirane within 6 h, affording the corresponding C3-alkylated indoles in good-to-excellent yields. Notably, this method also shows promising reactivity toward four-membered oxetanes. Furthermore, stereospecific investigations employing enantiopure (R)-styrene oxide afforded the corresponding products with high enantiomeric excess, suggesting an SN2 pathway with inversion of configuration. The unique hydrogen-bonding ability and acidity of HFIP are crucial for driving this facile transformation. This protocol offers a green, atom-economical, and sustainable approach for constructing structurally diverse indole derivatives, showcasing high practical utility for organic synthesis.
Artesunate (ART) is an FDA-approved antimalarial drug and is currently being repurposed for various solid tumor treatments. However, there are no safety or pharmacokinetic (PK) studies in mice exploring its potential application in murine brain tumor models. This study aims to delineate the tolerability and PK of ART in healthy NOD scid gamma (NSG) mice to inform future efficacy studies. The maximum tolerated dose (MTD) of ART following intraperitoneal (IP) administration was determined by a single-dose escalation method. PK and brain penetration of ART and its active metabolite, dihydroartemisinin (DHA), were analyzed using an optimized LC-MS/MS bioanalytical method, following single oral and IP doses (100 mg/kg). A 350 mg/kg IP dose was well tolerated with no evidence of systemic and organ-specific toxicities. Bioanalytical assay results were linear (R2 > 0.99) over a range of 5–1000 ng/mL. An optimized extraction method employing low sample volume improved analyte recovery from brain homogenate by 2-fold. PK studies showed rapid absorption with short elimination half-lives (t1/2: 8–22 min) and higher systemic and brain exposure for ART and DHA following IP administration over oral dosing. We conclude that ART is well-tolerated at high doses (350 mg/kg, IP) in NSG mice, although repeated doses may be necessary for therapeutic efficacy in brain tumors given its rapid elimination kinetics.
Owing to their high nutritional value, functional proteins, and low environmental impact, legume proteins have emerged as sustainable alternatives to animal proteins. However, their broader utilization is constrained by antinutritional factors (ANFs), which can adversely affect protein digestibility, mineral bioavailability, and techno-functional features. Fermentation has appeared as a promising approach to overcoming these limitations. Through microbial and enzymatic activities, fermentation can reduce ANFs, modify protein structures, and promote proteolysis, generating peptides and free amino acids that may improve digestibility, bioavailability, and functional properties. This review critically explores the effects of fermentation on legume proteins, concentrating on ANF reduction, protein degradation and structural modification, proteolysis, and their consequences for nutritional and techno-functional properties. Particular attention is given to protein hydrolysis and peptide generation, as well as the limitations and potential trade-offs of fermentation, including extreme proteolysis, loss of desirable functional properties, unwanted sensory changes, variability among strains and substrates, and prolonged processing. The review also discusses the incorporation of fermented legume proteins into relevant food systems, with emphasis on their functional performance and application potential. Finally, current knowledge gaps and future research priorities are highlighted to support the development of controlled fermentation strategies for nutritionally improved, functionally tailored, and industrially feasible legume protein ingredients.
Carvone is a naturally occurring monoterpene and the principal volatile constituent of spearmint (Mentha spicata) and caraway (Carum carvi), plants long used as carminative, digestive, antimicrobial, and flavoring agents. The compound exists as two enantiomers—S-(+)-carvone (predominantly associated with caraway) and R-(−)-carvone (predominantly associated with spearmint)—widely used in food, fragrance, and herbal preparations. Although carvone is a naturally occurring compound, the material used in experimental studies may be synthetically produced, isolated from plant essential oils, or used as a racemic or stereochemically enriched preparation. This review synthesizes evidence from 108 literature sources, complemented by PubChem (1535 records, accessed on 14 July 2026) and ChEMBL (136 records, accessed on 14 July 2026) bioassay data, to compile carvone’s molecular targets and biological activities and align the pharmacological evidence with traditional uses. We identified 45 molecular targets and 99 documented biological activities across 38 classes, spanning evidence tiers from comprehensively characterized (Tier A/B) to screening-level observations (Tier C/D), each assigned a four-tier evidence grade (A/B/C/D). Tier A targets comprise the aryl hydrocarbon receptor (AhR) and the GABA-A receptor. Negative results are reported to prevent publication bias, including NCI-60 inactivity across 55 cancer cell lines and a comprehensive counterscreen of steroid/nuclear receptors, human protein kinases, phosphatases, and HSP90—all inactive. The aryl hydrocarbon receptor emerges as the most robustly characterized target by the evidence-tiering criteria: both enantiomers act as noncompetitive allosteric antagonists, validated in vivo in mouse skin. This designation reflects the breadth and quality of evidence for AhR antagonism specifically, not a claim that AhR mediates all of carvone’s traditional or pharmacological effects. By mapping mechanistic evidence onto carvone’s traditional carminative, antimicrobial, and topical applications, this work provides a plausible mechanistic basis for several of the empirical uses documented in the ethnopharmacological literature.
The synthesis and multi-step spectroscopic characterization of diastereomeric 3-spiro-1,2,4-trioxolanes obtained by Griesbaum co-ozonolysis of sitostanone O-methyl oxime with two types of fluorinated ketones are reported. The reaction furnished four possible diastereomers that differ in the α/β orientation of the peroxide bridge relative to the steroid A-ring and in the syn/anti orientation of the trifluoromethyl group at C5′. A chemometric PLS2 approach, linking experimental and DFT-calculated 13C chemical shifts, was used for the objective stereochemical assignment of each diastereomer in the inseparable mixtures. Single-crystal X-ray analysis of the isolated 3R,5′R and 3R,5′S stereoisomeric pair (α-anti and α-syn ozonides) provided unambiguous absolute configurations that validated the stereochemical assignments obtained by the combined NMR/DFT/PLS2 approach. This integrated synthetic, crystallographic, spectroscopic, and chemometric methodology provides reliable configurational assignment in complex spiro-peroxide mixtures and expands the analytical toolkit for such systems.
This study evaluates caffeine-assisted aqueous extraction systems for the enhanced extraction of Σ16 US EPA priority polycyclic aromatic hydrocarbons (PAHs) from waste creosote-infused wood. Aqueous solutions of eight water-soluble organic acids were investigated with and without caffeine to assess its effect on PAH extraction. Caffeine improved extraction across all systems, but the extent of this improvement varied depending on the initial performance of each extraction agent without caffeine. Deionized water exhibited a negligible extraction yield (0.0027%), whereas caffeine addition increased the yield to 1.6886%, corresponding to a 625-fold improvement. Despite substantial differences among agents without caffeine, most caffeine-containing systems achieved similar extraction yields (4.2–5.3%), indicating that caffeine-induced hydrotropic solubilization became the dominant factor governing PAH extraction. Based on the maximum extraction performance achieved in the presence of caffeine, the investigated systems can be ranked as follows: acetic acid-caffeine > citric acid-caffeine > p-TsOH-caffeine ≈ tartaric acid-caffeine ≈ lactic acid-caffeine ≈ formic acid-caffeine > ascorbic acid-caffeine. These findings identify caffeine-assisted aqueous extraction as a promising approach for enhancing PAH extraction from creosote-treated waste wood while reducing reliance on conventional organic solvents in the primary extraction step.
Biogenic synthesis based on microorganisms and plants utilizes biomolecules and metabolites that act as reducing and stabilizing agents. Furthermore, these biomolecules confer enhanced properties, increasing their effectiveness as antibacterial agents, even against multidrug-resistant bacteria. However, there is currently a lack of knowledge regarding the characteristics of the biomolecules involved and their mechanisms during synthesis, which limits their wider application. This research study focused on the synthesis of AgNPs using extracellularly secreted biomolecules from the filamentous fungus R. stolonifer. The results indicated that the concentration of the biomolecules depends on the response of the fungus to specific operational conditions. Furthermore, a relationship was found between the concentrations of total proteins and polyphenols, an optimal protein-to-polyphenol ratio, and the formation of AgNPs. Characterization of the fungus extracts revealed a complex mixture of over 100 metabolites, primarily phenolic compounds, proteins, and methoxylated compounds, thereby identifying a synergistic mechanism that enables the reduction and stabilization of AgNPs. Disinfection tests confirmed the antibacterial efficacy of all biosynthesized AgNPs, achieving 100% elimination of Escherichia coli and Staphylococcus aureus. The study outcomes highlight the important role of fungal biomolecules for creating a sustainable and efficient method for synthesizing antimicrobial nanoparticles with high efficacy for disinfectant applications.
Rice husk, an abundant agro-industrial by-product rich in SiO2, represents a promising precursor for the sustainable synthesis of zeolites. In this study, rice husk ash was used to synthesize faujasite-type X and faujasite-type Y, and their performance for Hg2+ removal from aqueous solutions was comparatively evaluated. X-ray diffraction confirmed the successful formation of the faujasite structures, while physicochemical characterization revealed differences in pore structure and surface chemistry. FAU-type X exhibited higher Hg2+ removal than FAU-type Y, consistent with the combined influence of its lower Si/Al ratio, higher framework charge density and ion-exchange capacity, as well as its larger pore volume and average pore diameter. Based on its higher Hg2+ removal, FAU-type X was selected for a comprehensive evaluation of its adsorption performance and applicability under environmentally relevant conditions. The pseudo-second-order model best described adsorption kinetics for both zeolites, whereas thermodynamic analyses indicated that the adsorption process was spontaneous and endothermic. Optimal adsorption conditions for FAU-type X were achieved at pH 6.8, using an adsorbent dosage of 0.75 g L−1, a contact time of 24 h, and an initial Hg2+ concentration of 1 mg L−1. Equilibrium data were best fitted by the Sips isotherm model, indicating adsorption on a heterogeneous surface with a maximum adsorption capacity of 83.14 mg g−1. FAU-type X retained appreciable adsorption performance after four regeneration cycles, although Hg2+ removal efficiency decreased in Caquetá River water because of competition from coexisting metal ions. To assess the environmental implications of the treated water beyond Hg2+ removal efficiency, ecotoxicological assays demonstrated the sensitivity of Daphnia magna to residual Hg2+ concentrations, whereas reductions in Escherichia coliforms were mainly attributed to the adsorption process. In addition, Lactuca sativa seedlings exhibited approximately 50% inhibition of elongation after treatment. Overall, these findings demonstrate the potential of rice husk-derived faujasite-type X as a sustainable adsorbent for Hg2+ removal, while highlighting the need for complementary treatment strategies to ensure the environmentally safe discharge of water and its agricultural reuse.
Rapeseed oil is an important edible oil with a favorable fatty acid composition and contains endogenous phospholipids (PLs) and lipid-soluble minor components that are relevant to refining, oxidative stability, and product quality. In this study, water degumming (WDG), citric acid degumming (ADG), and ethanol degumming (EDG) were systematically evaluated for their effects on oil quality, phospholipid recovery, and bioactive lipid concentrations. A modified Folch extraction was included solely as a laboratory solvent-extraction benchmark for the compositional characterization of phospholipid-rich fractions. WDG and ADG showed the highest phosphorus removal efficiency, reducing phosphorus to undetectable levels, whereas EDG also achieved substantial dephosphorization. ADG produced the highest PL yield (83.22%), while WDG gave the highest oil recovery (98.42%) and PL purity (95.49%). Although the bulk FA composition of the oil remained largely unchanged after treatment, the recovered PL fractions showed clear differences in FA distribution and PL subclass composition. EDG yielded the highest phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) contents, indicating selective enrichment of choline-containing PLs. The concentrations of carotenoids, tocopherols, and phytosterols were also process-dependent. Untargeted metabolomic and lipidomic analyses further showed that EDG induced distinct compositional remodeling relative to crude rapeseed oil. Overall, WDG was preferable for oil retention, ADG for maximum PL recovery, and EDG provided a distinct balance between oil recovery, PL recovery, and enrichment of PC- and LPC-containing fractions.
Nanomaterials are increasingly expected to do more than transport a payload, yet added complexity is useful only when it resolves a rate-limiting diagnostic, transport, release, or monitoring problem. This review develops a function-first framework for precision diagnostics and drug delivery in which formation and processing are linked to nanoscale structure, material properties, demonstrated function, route-specific evidence, and translational value. The scope includes AI-assisted plasmonic and terahertz biosensing; biopolymer nanoparticles and hydrogel depots; barrier-directed nose-to-brain and systemic delivery; graphene and carbon nanotube interfaces; lipid nanoparticles for nucleic acid packaging and endosomal escape; nanoporous, magnetic, and plasmonic carriers; and closed-loop theranostic systems. A platform is treated as genuinely multifunctional only when at least two deliberately engineered functions are experimentally supported and either act on distinct rate-limiting steps or close a sensing–intervention–monitoring loop. This review therefore distinguishes total loading from bioavailable payload, cellular uptake from productive delivery, imaging labels from intact carrier fate, and nominal stimulus responsiveness from controlled release in response to a physiologically realistic trigger. Recent independent studies are used to broaden comparisons across material classes and to separate proof-of-concept performance from translational evidence. Artificial intelligence is considered in three distinct roles—sensor interpretation, formulation/material optimization, and prediction of in vivo behavior—with external validation and, where a model is intended to guide decisions, prospective testing treated as essential. The resulting framework emphasizes biological identity, route-specific safety, carrier-versus-payload tracking, critical quality attributes, manufacturing reproducibility, and a minimum-evidence roadmap from concept to product.
Coumarins are heterocyclic compounds with diverse biological activities and potential applications as alternative acaricidal agents. In this study, nine coumarin derivatives were synthesized through a solvent-free Pechmann reaction using Preyssler heteropolyacid as a reusable catalyst under green chemistry conditions. The synthesized compounds were evaluated against adult females of Rhipicephalus (Boophilus) microplus using the adult immersion test. Survival analysis was performed using the Cox proportional hazard model, while molecular docking studies were carried out on triosephosphate isomerase (TIM). In addition, post hoc analysis of the structures predicted to be most active by the QSAR model suggested an association between higher predicted activity, the presence of hydroxyl groups, and the polarity of C7 side chains, although the topological descriptor identified by the model does not admit a direct physicochemical interpretation. The results showed that hydroxylated coumarins, particularly those substituted at C5 and C7, exhibited the highest acaricidal activity, with IC50 values between 7.24 and 8.78 mg/mL. Docking analysis suggested plausible interactions with residues located at the TIM interface cavity, mainly Lys-112, Asn-65, and Glu-77. The QSAR model indicated that hydroxyl substitution and side-chain polarity contributed positively to activity. This study integrates Preyssler heteropolyacid-catalyzed green synthesis of coumarins with Cox proportional hazard survival modeling, TIM molecular docking, and QSAR analysis within a single acaricidal evaluation against R. (B.) microplus, providing a multi-pronged framework for prioritizing structural modifications in future coumarin-based acaricide development.
Heterocycle-containing calixarenes have attracted increasing attention over the past three decades owing to the unique combination of the preorganized macrocyclic framework of calixarenes with the structural and functional diversity of heterocyclic building blocks. The incorporation of heterocycles significantly expands the coordination, supramolecular, electronic, catalytic, and biological properties of these macrocycles, enabling the rational design of multifunctional molecular systems for a wide range of applications. This review provides a comprehensive overview of the synthesis, structural diversity, and applications of heterocycle-containing (thia)calixarenes reported over the last 30 years. Synthetic methodologies are critically analyzed and classified into convergent and divergent approaches, with emphasis on their advantages, limitations, and synthetic scope. Particular attention is devoted to the effects of linker type, heterocycle structure, substitution pattern, and macrocyclic conformation on the physicochemical properties and functional behavior of the resulting compounds. By integrating synthetic strategies with a systematic analysis of structure–property relationships, this review highlights how molecular design governs the performance of heterocycle-containing calixarenes across coordination, supramolecular, sensing, catalytic, and biomedical applications. Finally, current challenges and emerging research directions are discussed, providing perspectives for the rational development of advanced calixarene-based functional systems.
Hydrogen is employed as a therapeutic gas in the treatment of stroke, tissue repair, and cancer, owing to its excellent biocompatibility, antioxidant properties, anti-inflammatory effects, and regulation of cellular metabolism. Moreover, nanometallic materials generate hydrogen through pH-responsive, light-responsive, ultrasound-responsive, and electrical stimulation and play a pivotal role in cancer therapy by activating anti-tumor immune responses, reversing immunosuppressive microenvironments, inducing immunogenic cell death, and sensitising radiotherapy and chemotherapy. Consequently, hydrogen therapy based on nanometallic materials has emerged as a novel research focus in cancer treatment. This review systematically elucidates the unique anti-cancer immunobiological effects of hydrogen therapy based on novel nanometallic materials. It meticulously analyses the reversal effects of different metals (Ca, Mg, Fe, Cu, Yb, etc.) in overcoming obstacles within the cancer immune cycle (including antigen presentation, T-cell activation, and resistance mechanisms). It highlights the structure–activity relationships between ‘metal type-specific activity-immune effects’ in the latest hydrogen therapies, elucidates the primary signaling pathways involved in hydrogen-mediated immune regulation, and systematically summarises breakthrough advances in how hydrogen therapy modulates immune responses against tumors. Building upon current cancer treatment trends, this review will synthesise key factors from clinical translation and immunological research perspectives to propose future directions for the field, addressing prevailing challenges.
This study investigates the performance of a diesel engine exhaust gas-driven Rankine Cycle-supported vapor compression refrigeration system using quantum chemical approaches beyond conventional thermodynamic analyses. The study focuses on R448A and its components, namely R32, R125, R134a, R1234yf, and R1234ze(E), evaluated at both the system level and the molecular level. At the system level, the Rankine–VCR system was analyzed using a Fortran-based macroscopic thermodynamic model, in which the thermophysical properties of the working fluids were obtained from the NIST Chemistry WebBook. At the molecular level, Density Functional Theory (DFT) calculations were performed to determine molecular structure parameters, including entropy, heat capacity, chemical hardness, and thermal enthalpy correction. The main objective is to investigate the possible relationships between these molecular descriptors and system-level performance indicators, while considering that mass flow rate is primarily governed by cycle thermodynamic properties. The results show that molecular stability and structural order are strongly associated with system performance. Among the R448A components, R32, with the highest chemical hardness (8.19 eV) and lowest molecular entropy (58.9 cal/mol K), exhibits the most favorable exergetic behavior and achieves the highest plant exergy efficiency of 44.92%. In contrast, R1234ze(E), chemically softer (η = 4.42 Ev) and higher in entropy, exhibits the lowest performance. Additionally, R32’s lower thermal enthalpy correction is associated with higher latent heat of vaporization under the selected operating conditions, reducing the required mass flow by approximately 60–70% compared to the other components. This study demonstrates that, in refrigerant selection, not only the global warming potential (GWP) but also quantum parameters such as chemical hardness, molecular entropy, heat capacity, and thermal enthalpy correction can serve as important complementary performance indicators when interpreted together with macroscopic thermodynamic and exergetic results.
Black highland barley, rich in phenolic compounds and β-glucans, is increasingly used in craft beer brewing, but the dynamic metabolic changes across its processing chain remain unclear. This study integrated GC×GC-TOF MS based flavoromics with UHPLC-QTRAP-MS based widely targeted metabolomics to track volatile and non-volatile metabolites from raw grain (K1) through germinated malt (K2) and roasted malt (K3) to finished beer (K4). A total of 256 volatile compounds and 615 non-volatile metabolites were identified. Alcohols and hydrocarbons dominated K1. Germination (K2) enriched aldehydes and reduced esters by 66%. Roasting (K3) generated Maillard reaction products, including 2,3,5-trimethylpyrazine (198.4-fold increase) and furfural (20.2-fold increase). Fermentation (K4) shifted the profile to ester dominance (40.95%), with isoamyl alcohol (ROAV = 71.59) and 2-undecanone (ROAV = 65.37) as the principal aroma contributors. Notably, 94.1% of phenolic and flavonoid compounds (168 of 184) exhibited higher abundance in finished beer than in raw grain. Their levels declined after roasting and then accumulated during fermentation. Cross-omics correlation indicated a strong association between furfural and its pentose phosphate precursor (ρ = 1.00, p < 0.001). These findings demonstrate that fermentation acts as the decisive metabolic turning point that simultaneously shapes the flavor profile and nutritional quality of black highland barley beer. The finished beer contained 250.45 mg GAE/L total phenolics and 97.91 mg RE/L total flavonoids, with ABTS and DPPH radical scavenging rates of 87.41% and 92.68%, respectively.
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic disorder characterized by persistent intestinal inflammation. Although corticosteroids such as prednisolone effectively control disease symptoms, prolonged treatment is associated with severe side effects, including immune suppression and metabolic disturbances. To enable site-specific drug delivery, four phospholipid–linker–prednisolone conjugates were designed and synthesized as prodrugs targeting the overexpression of phospholipase A2 (PLA2) in inflamed intestinal tissues. The conjugates were prepared using a reversed synthetic strategy, in which the phospholipid–linker scaffold was assembled before drug coupling. The effect of spacer length on molecular conformation and predicted structural determinants of enzymatic activation was investigated through in silico analysis. Molecular docking simulations performed using the AutoDock Vina v1.2.7 framework, followed by structural and distance analysis in UCSF Chimera and 50 ns molecular dynamics simulations in GROMACS, suggested that linker length may influence ligand orientation, conformational orientation, ligand stability, and the spatial positioning of the ester bond relative to the catalytic histidine residue within the PLA2 active site. Among the two conjugates examined in detail by molecular dynamics, C6 maintained comparatively lower ligand mobility and a shorter average distance to the catalytic residue His47 than C12. These computational findings provide structural insights that may guide the future design and optimization of phospholipid-based corticosteroid prodrugs for targeted IBD therapy.
