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Exosomes are small vesicles released by various cell types—compounds of a lipid bilayer and surface proteins that facilitate their recognition, direction, and uptake by the target cell. Inside, exosomes contain proteins, lipids, and nucleic acids, the composition of which varies depending on the cell of origin. Exosomes can be internalized by the target cell by endocytosis, fusion, or ligand–receptor interaction. The main functions of these extracellular vesicles (EVs) are intercellular communication, gene regulation, and the activation of cell regeneration and repair processes. Due to these characteristics, exosomes emerge as a promising option for the treatment of various diseases. Therefore, this review addresses the biology of exosomes and provides examples of studies with the molecular mechanisms by which these vesicles are taken up by target cells; examples of factors that influence the secretion and molecular composition of exosomes, which can be modified through exosome engineering, to enhance their effects. Furthermore, it addresses a diverse range of examples of the potential therapeutic applications of exosomes, including those loaded with different types of molecules, to use them as vehicles for drug delivery, with the objective of achieving safer, more precise, and effective treatments. Finally, it includes some clinical studies conducted with exosomes. Full article

Background/Objectives: Cholesterol sulfate (CS) is a multifunctional signaling molecule implicated in diverse physiological and pathological processes. Its clinical translation as a biomarker is hindered by the lack of established reference intervals, unclear disease-specific alterations, and undefined relationships with routine laboratory parameters. This study aimed to establish a serum CS reference range for Chinese populations, evaluate its associations with various diseases and clinical laboratory parameters, and define its clinical diagnostic utility. Methods: A total of 642 subjects were enrolled, comprising 372 healthy controls and 270 patients with one of six diseases: Alzheimer’s disease, osteoporosis, obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), or Crohn’s disease. Serum CS concentrations were quantified using LC-MS/MS. Reference intervals were established using non-parametric methods. Univariate analyses included Spearman’s rank correlation, Mann–Whitney U test, and receiver operating characteristic (ROC) curve analysis; multivariate analysis employed a gamma-family generalized linear model (GLM) with a log-link function, incorporating age, sex, clinical laboratory parameters, and disease status as covariates. The age-by-sex interaction was examined to assess synergistic effects. Incremental diagnostic value of CS was evaluated using the DeLong test and likelihood ratio test. Results: The serum CS reference interval for healthy individuals was 0.55–2.24 mg/L (males: 0.60–2.25 mg/L; females: 0.54–2.20 mg/L), with a significant sex difference. The age-by-sex interaction effect was significant (two-way ANOVA interaction p = 0.005; GLM interaction β = 0.102, p = 0.002). Stratified analysis revealed a significant positive correlation between age and CS in males, but no such association in females. In univariate analysis, CS correlated significantly with total cholesterol (TC), non-HDL-C, hemoglobin A1c (HbA1c), and other biomarkers; CS levels were elevated in Alzheimer’s disease and reduced in Crohn’s disease. In the multivariate GLM, only TC and male sex emerged as independent significant determinants of CS, whereas HbA1c and NAFLD showed borderline effects; no disease group retained independent significance. After adjustment for TC and sex, the residual area under the curves (AUCs) of CS for all diseases were close to 0.50, and DeLong’s test indicated no incremental diagnostic value beyond the baseline model (all p > 0.70). Conclusions: This study is the first to establish a serum CS reference range for the Chinese population. Serum CS levels are independently regulated by TC and sex, with a significant age-by-sex interaction. The associations between CS and disease status were largely mediated by confounding from lipid profiles and age. CS is not suitable as an independent disease biomarker but may serve as a supplementary indicator for assessing lipid metabolism—particularly in male populations, where it may indirectly reflect age-related changes in cholesterol metabolism. Full article

The rumen is a complex microbial ecosystem in which anaerobic fermentation determines the availability of energy and protein to ruminant hosts and influences feed efficiency, animal productivity, and environmental emissions. This review integrates current knowledge of host–rumen microbiome interactions with particular emphasis on microbial fermentation, nutrient utilization, feed efficiency, methane (CH₄) production, and sustainable ruminant production. We examine how dietary factors, including forage-to-concentrate ratio, carbohydrate fermentability, protein degradability, and lipid supplementation, alter microbial community structure, hydrogen metabolism, volatile fatty acid production, microbial protein synthesis, and nitrogen utilization. The review further evaluates microbiome-targeted strategies, including 3-nitrooxypropanol, red seaweeds (Asparagopsis spp.), nitrate, direct-fed microbials, and plant-derived bioactive compounds, with emphasis on their effects on fermentation pathways and methanogenesis; these strategies differ substantially in evidence base and mechanistic specificity, with 3-nitrooxypropanol supported by the most consistent mechanistic and in vivo evidence and several plant-derived compounds and direct-fed microbials showing more variable responses. Evidence from microbiome-wide and genome-wide association studies indicates that host genetics contributes to variation in rumen microbial composition and function, with potential consequences for feed efficiency and CH₄ emissions. Host-side determinants of the rumen environment, such as feed intake, digesta passage rate, saliva production, and epithelial and immune function, further shape microbial responses. However, responses to microbiome-targeted interventions remain variable because of microbial functional redundancy, dietary context, adaptation, and host-specific effects. We therefore discuss the major constraints limiting the consistent translation of microbiome research into practical feeding strategies and propose an integrated framework combining functional microbiome indicators, precision nutrition, host–microbiome-informed selection, and real-time monitoring. Understanding and manipulating rumen microbial fermentation through coordinated nutritional and host-based approaches may provide a pathway toward improving ruminant productivity while reducing the environmental footprint of livestock production. Among the strategies reviewed, 3-nitrooxypropanol currently has the strongest and most reproducible evidence base, whereas plant-derived bioactives and several direct-fed microbials remain promising but inconsistent, and validated on-farm microbiome biomarkers remain a major gap. Full article

Shrimp shell–derived chitosan and protein hydrolysate–epigallocatechin gallate conjugates (SEC) were used to fabricate hybrid particles (C-SEC) at mass ratios of 1:1, 1:5, and 1:10 using an alkali precipitation method. SEC incorporation significantly enhanced the antioxidant capacity of chitosan particles (p < 0.05). Among the formulations, C-SEC prepared at a ratio of 1:5 (C–SEC–1:5) exhibited the highest antioxidant activities, including DPPH (14.55 mM TE/g) or ABTS (9.80 mM TE/g), or hydroxyl (70.29%) radical scavenging activities, ferric reducing antioxidant power (10.59 mM TE/g), and metal chelating activity (6.37 mM EE/g). The particle size was markedly reduced from 738 nm for chitosan particles (CP) to 112 nm following incorporation of SEC, indicating the formation of finely dispersed hybrid particles. ¹H NMR analysis confirmed successful molecular integration of SEC into the chitosan matrix through non-covalent interactions. Thermal analyses revealed altered degradation and transition behavior of the hybrid particles. TGA showed that the principal degradation stages shifted to higher temperatures, whereas DSC showed an increase in transition enthalpy from 370.74 to 2449.60 J/g. SEM and TEM images revealed that the C–SEC–1:5 formed porous, interconnected particle networks with rough surfaces. The selected hybrid particles also showed superior inhibition of Cu²⁺–induced lecithin liposome oxidation and β-carotene bleaching compared with CP, demonstrating concentration-dependent protection against lipid oxidation. Overall, these findings indicate the potential of C–SEC–1:5 as an antioxidant-based functional ingredient and bioactive delivery vehicle in food and nutraceutical formulations. Full article

Mycoplasma synoviae (M. synoviae) is an avian pathogen responsible for respiratory disease and synovitis. The VlhA (variable lipoprotein hemagglutinin) family of surface adhesins plays a critical role in host cell attachment, yet the specific residues and structural determinants governing this interaction remain incompletely understood. In this study, we selected the C-terminal lipid-associated membrane hemagglutinin (LAM HA) domain within the VlhA family as the bait protein, based on its conserved C-terminal region. Yeast two-hybrid screening identified 18 LAM HA-interacting host proteins, and molecular docking pinpointed five residues (S83, R85, Y88, N124, K192) as the most frequent interaction hotspots. To assess their collective functional relevance, we constructed a combined deletion mutant lacking these five candidate residues. At the optimal pH of 6.0–6.5, wild-type LAM HA showed the highest titer (1:2), significantly exceeding that at pH 7.0–7.5 (no activity) and pH 5.0–5.5 (1:1) (p < 0.05), whereas the deletion mutant displayed a reduced titer (from 2 to 1; p = 0.05). Secondary structure analysis at the same pH revealed decreased α-helix content (from 7.90% to 7.57%), along with increased β-sheet (from 38.92% to 38.83%) and random coil (from 10.83% to 10.44%). Molecular dynamics simulations revealed that the deletion mutant exhibited elevated RMSF (from 2.83 ± 1.88 Å to 4.18 ± 2.65 Å) and Rg (from 40.48 ± 1.31 Å to 54.16 ± 4.47 Å) at pH 6.0–6.5, while RMSD showed a slight decrease (11.17 ± 1.33 Å vs. 12.14 ± 0.21 Å), collectively indicating compromised structural stability of the mutant. Collectively, these findings suggest that the LAM HA domain contributes to hemagglutination activity through pH-sensitive conformational stability and specific residue clusters—a property that may be relevant to M. synoviae colonization in the acidic microenvironments of the respiratory tract and synovial fluid during infection. Full article

Neuroblastoma is among the most aggressive pediatric cancers, and resistance to standard therapies highlights the need for alternative strategies targeting lipid metabolism and apoptosis-associated pathways. This study aimed to investigate the cytotoxic and apoptotic effects of fingolimod, ceranib-2, and carmofur, administered individually and in combination, in SH-SY5Y neuroblastoma cells, with particular emphasis on ceramide metabolism. Cytotoxicity was evaluated using the MTT assay, and morphological alterations were assessed by confocal microscopy. Colony-forming ability was examined using a soft agar assay, apoptosis-associated responses were evaluated by Annexin-V staining and caspase 3/7 activation analysis, and intracellular ceramide levels were determined using an ELISA-based method. The results showed that all three compounds reduced cell viability in a concentration-dependent manner and decreased clonogenic survival. The triple combination produced the most pronounced changes in apoptosis-associated parameters and showed marked inhibition of colony formation, although fingolimod alone exhibited the lowest IC₅₀ value and therefore remained the most potent treatment on an IC₅₀ basis. Confocal microscopy revealed prominent apoptosis-associated morphological alterations, including chromatin condensation, nuclear fragmentation, and cytoskeletal disruption, particularly in the triple-combination group. Annexin-V and caspase 3/7 analyses showed increased apoptotic cell populations, with the highest levels observed following triple-combination treatment. Intracellular ceramide levels were also significantly elevated, particularly in cells treated with ceranib-2 and the triple combination. Collectively, these findings indicate that simultaneous modulation of ceramide- and S1P-associated pathways influences apoptosis-associated responses, clonogenic growth, and intracellular ceramide levels in SH-SY5Y cells. However, because the study was conducted in a single neuroblastoma cell line and did not include comprehensive dose-by-time or formal combination-interaction analyses, the findings should be regarded as preliminary in vitro observations. Further validation in genetically distinct neuroblastoma models, together with systematic dose–response and time–response studies, will be required to determine the reproducibility, biological significance, and broader therapeutic relevance of this approach. Full article

Chronic kidney disease (CKD) confers a high burden of atherosclerotic cardiovascular disease (ASCVD) and a characteristic, evolving dyslipidaemia that is incompletely addressed by conventional care. Statin-based therapy remains first-line in most non-dialysis CKD populations, yet many patients fail to reach lipid goals or remain at substantial residual risk. This structured narrative review evaluates injectable lipid-lowering agents across the CKD spectrum, focusing on the pharmacology and clinical utility of therapies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). The monoclonal antibodies evolocumab and alirocumab are subcutaneous biologics that bind circulating PCSK9, prevent PCSK9-mediated degradation of the low-density lipoprotein (LDL) receptor, and enhance hepatic LDL-cholesterol (LDL-C) clearance. Their catabolic elimination and negligible cytochrome-P450 interaction burden are advantageous in polypharmacy-heavy CKD care. Inclisiran is a hepatocyte-directed, GalNAc-conjugated small interfering RNA that silences PCSK9 messenger RNA, enabling durable LDL-C lowering with twice-yearly maintenance dosing after initiation. Across major programmes, injectable PCSK9 inhibition produces a ~50–60% LDL-C reduction, with consistent efficacy and safety across renal function strata, although outcome data in advanced CKD and dialysis remain limited. Importantly, cardiovascular outcome benefit is established for the monoclonal antibodies evolocumab and alirocumab, whereas inclisiran currently has robust LDL-C-lowering evidence but no completed cardiovascular outcome trial; these agents should not be regarded as having equivalent outcome evidence. Historical dialysis statin trials showed attenuated or neutral cardiovascular benefit, underscoring the biological and trial-design complexity of late-stage kidney disease and the need for dedicated injectable-era trials. We propose a stage-specific framework for integrating injectable therapies into CKD pathways—covering patient selection, sequencing, monitoring and implementation—and outline priorities for CKD-enriched outcome trials, kidney-relevant endpoints, and the integration of emerging lipoprotein(a)-targeted injectables into cardio-renal risk reduction. Full article

In broiler farming, high-fat (HF) diets are frequently incorporated, often leading to hepatic steatosis, oxidative stress, and gut damage. 1-Deoxynojirimycin (DNJ) has emerged as a promising feed additive in animal husbandry due to its significant role in enhancing animal health. This study assessed the protective effects of DNJ-enriched mulberry extract (DNJ) on liver and gut health in broilers subjected to an HF diet, with particular emphasis on the liver-gut interaction. A total of 360 one-day-old Arbor Acres broilers were initially raised on a basal diet for 20 days, after which they were assigned to one of three dietary treatments from days 21 to 42: a control diet (CON), an HF diet, and an HF diet supplemented with 80 mg/kg DNJ (HF + DNJ). By day 42, broilers on the HF diet exhibited increased body weight, feed intake, and body weight gain, alongside reduced feed conversion efficiency. In contrast, DNJ supplementation reduced body weight without affecting feed intake in the HF diet group. It lowered liver T-CHO and LDL-C levels, increased SOD and CAT activities, and decreased MDA. Histological analyses showed that DNJ preserved intestinal mucosal structure and epithelial tight junctions. DNJ supplementation enriched microbes like Actinobacteriota and Baceroidota and reversed the HF-induced Firmicutes-to-Bacteroidota ratio. Furthermore, Bifidobacterium pullorum and Bacteroidota were positively correlated with antioxidant markers. In conclusion, dietary DNJ-enriched mulberry extract serves as an effective functional feed substance that mitigates HF-induced metabolic syndromes in broilers by balancing lipid metabolism, enhancing antioxidant defenses, safeguarding intestinal barrier integrity, and restoring healthy microbial community structures along the liver-gut axis. Full article

Soft fruits are highly perishable due to their delicate surface barriers, rapid cell-wall disassembly, turgor loss, oxidative imbalance, and tightly coordinated ripening and senescence processes that collectively accelerate water loss, softening, and decay after harvest. This review examines how melatonin (MLT) interacts with these deterioration processes in blueberries, raspberries, strawberries, grapes, and sweet cherries. Current evidence identifies redox regulation as the most consistent mechanism of MLT action, including modulation of reactive oxygen species, enhancement of antioxidant enzymes and the ascorbate–glutathione cycle, and maintenance of phenolic and other non-enzymatic antioxidants. These responses are linked with lower lipid peroxidation, reduced membrane leakage, delayed cell-wall degradation, and improved firmness, water retention, and decay resistance. More limited and species-specific evidence suggests that MLT may influence cuticular wax metabolism, endogenous MLT biosynthesis, H₂S signaling, GABA and polyamine metabolism, phenylpropanoid pathways, and host-defense responses. However, direct evidence for effects on cuticular permeability, cellular compartmentation, and hormonal signaling remains limited. Overall, MLT should be regarded as a context-dependent regulator of redox homeostasis, tissue integrity, ripening, and defense rather than as a universal anti-senescence treatment, because its effects vary with species, cultivar, concentration, maturity stage, and storage conditions and still require validation under commercial conditions. Full article

Black soldier fly larvae (BSFL; Hermetia illucens) oil and flaxseed oil provide contrasting fatty acid profiles and may serve as alternative lipid feed materials in ruminant nutrition. This study assessed low-α-linolenic/high-linoleic flaxseed oil, BSFL oil, and their blends using an in vitro rumen fermentation screening with pooled bovine rumen inoculum and a randomized prepartum feeding trial in 32 twin- or triplet-bearing Olkuska ewes. In vitro, the single oils and a 1:1 blend were evaluated at two inclusion levels; total VFA concentration was unchanged, whereas propionate proportion, the acetate-to-propionate ratio, methane, ammonia, and incubation-fluid fatty acid profiles showed treatment-dependent responses. In vivo, an unsupplemented control was compared with flaxseed oil, BSFL oil, and a 2:1 blend supplied at 30 g/day for 21 days before expected parturition. Colostrum fat concentration differed among treatments (p = 0.036); the 2:1 blend group had a higher value than the control group (11.29% vs. 8.26%; Dunnett-adjusted p < 0.05), while major fatty acid classes did not differ. Supplementation was also associated with differences in selected minor colostrum fatty acids and several serum metabolic variables. Colostrum yield was not measured; therefore, this finding reflects fat concentration rather than total colostrum fat output. Serum total antioxidant status (TAS) was unaffected, while a treatment-by-time interaction was observed for γ-glutamyl transferase. The tested plant- and insect-derived oils therefore modified ruminal lipid transformations and selected maternal and colostrum traits without a detectable change in TAS. Full article

Leucopaxillus giganteus, a wild saprotrophic fungus with high edible and medicinal value, has not yet achieved large-scale artificial cultivation. To elucidate the abiotic and biotic factors governing its growth, we analyzed physicochemical properties and bacterial communities of mycosphere and bulk soils from Shanxi Province, China. We observed geographic variation in the diversity, composition, and functional profiles of dominant mycosphere soil bacterial communities. Soil organic carbon, available potassium, altitude, longitude, and latitude were the key factors affecting mycosphere soil bacterial community structure. Distance–decay analysis revealed that the beta diversity of mycosphere soil bacterial communities declined with increasing geographical distance. Bacterial diversity in the L. giganteus mycosphere was significantly lower than that in bulk soil. Genera such as Micromonospora, Streptosporangium, Paraburkholderia, Pedobacter, Caballeronia, Paenibacillus, and Flavobacterium could act as saprotrophic helper bacteria in the mycosphere of L. giganteus. LEfSe analysis revealed 72 genera that exhibited significant abundance differences among samples from six geographic regions, including Bradyrhizobium, Sphingomicrobium, and Phyllobacterium. Functional annotation detected enriched pathways for transport and catabolism, signal transduction, and carbohydrate and lipid metabolism in mycosphere soil bacterial communities. These results advance our understanding of the ecological interactions of L. giganteus and support its artificial cultivation and sustainable resource use. Full article

Phytochemicals modulate lipid metabolism, but it remains unclear whether phytochemical-rich cactus fruits have a similar effect. Accordingly, the effects of Etcho (Pachycereus pecten-aboriginum) fruit juice on lipid accumulation and on the expression of CD36 and ADIPOR1 were investigated, and the potential interactions between its major betalains and the CD36 and ADIPOR1 receptors were predicted. Phytochemical content was determined by spectrophotometry. Human adipocytes were stimulated with a 2:1 (molar) oleic/palmitic acid mixture and then treated with Etcho fruit juice/its hydroethanolic extract/betanin. Lipid accumulation was measured by Oil Red O staining, and CD36 and ADIPOR1 expression were quantified by qPCR. Molecular docking was performed to assess the binding affinities and molecular interactions of betanin, indicaxanthin, and phyllocactin with CD36 and ADIPOR1. All treatments reduced long-chain fatty acid–induced lipid accumulation (p < 0.05). The juice decreased CD36 mRNA and increased ADIPOR1 mRNA levels (p < 0.05), and molecular docking revealed that its betalains bind strongly to the CD36 extracellular domain and the ADIPOR1 orthosteric pocket triad. Etcho fruit juice is a source of phenolics and betalains. It reduces lipid accumulation in human adipocytes and modulates the expression of CD36 and ADIPOR1. The juice’s major betalains may target CD36 and ADIPOR1. Full article

Obesity has become a major global public health concern, with prevalence rates rising dramatically over the past several decades and affecting more than one billion people worldwide. The increasing burden of obesity has been largely driven by sedentary lifestyles and the consumption of energy-dense, nutrient-poor diets, although its etiology is multifactorial, involving complex interactions among genetic, metabolic, endocrine, and environmental factors. Beyond excess adiposity, obesity is closely associated with numerous chronic diseases, including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), hypertension, cancer, and chronic inflammatory disorders. Emerging evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of obesity and its related metabolic complications. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are generated during normal cellular metabolism, serve important physiological functions in cell signaling and redox regulation. However, excessive production of these reactive species or impairment of endogenous antioxidant defense systems disrupts redox homeostasis, leading to oxidative damage to lipids, proteins, and nucleic acids. Such alterations contribute to cellular dysfunction, chronic inflammation, and disease progression. In this context, dietary antioxidants have attracted considerable attention due to their ability to neutralize free radicals, inhibit lipid peroxidation, and restore redox balance. Natural antioxidants derived from fruits, vegetables, and other plant-based foods may act individually or synergistically to enhance cellular defense mechanisms against oxidative stress. Furthermore, growing evidence suggests that antioxidant-rich dietary patterns may offer protective effects against obesity-associated metabolic disturbances and chronic diseases. However, clinical benefits of isolated antioxidant supplementation remain inconsistent and appear to depend on dose, bioavailability, baseline redox status, disease stage, and the preservation of physiological redox signaling. Understanding the molecular mechanisms underlying antioxidant-mediated regulation of redox homeostasis may facilitate the development of nutritional strategies for obesity prevention and management, while contributing to the reduction in oxidative stress and obesity-related disease burden and the promotion of long-term health. Full article

Understanding how vegetable-oil composition evolves during food preparation is essential for evaluating food quality and nutritional value. Palov is Uzbekistan’s most widely consumed and culturally significant dish, serving as an everyday meal and a central element of hospitality and communal traditions. We hypothesised that food–oil interactions during Palov preparation direct molecular changes that cannot be reproduced by controlled heating alone. Two independent batches of Palov were prepared with sunflower or cottonseed oil under household cooking conditions. Oils were sampled at six stages and compared with heating controls conducted under closely matched temperature–time profiles without food ingredients. Samples were analysed using Fourier-transform infrared spectroscopy, benchtop and high-field ¹H nuclear magnetic resonance spectroscopy. Cooking caused substantially greater fatty-acid changes than heating alone. In cottonseed oil, polyunsaturated fatty acids decreased from approximately 44 to 32 mol%, monounsaturated fatty acids increased from approximately 19 to 26 mol%, saturated fatty acids increased from approximately 36.5 to 41.5 mol%, and trans-fatty acids increased from approximately 0 to 2%. Heating alone produced greater accumulation of conjugated dienes and hydroperoxides, whereas cooking produced more dynamic changes in sterol-, aldehyde- and glyceride-related signals. These findings demonstrate that food–oil interactions redirect fatty-acid composition, hydrolysis and oxidation-product evolution rather than merely altering the extent of thermal damage. Realistic culinary models therefore provide a more representative description of edible-oil transformation than heating-only experiments. Full article

Persistent aldehydic off-notes in fish products are influenced not only by lipid oxidation but also by protein-associated retention of odor-active aldehydes. A remaining question is how gingerol side-chain length and aldehyde structure jointly alter this apparent retention. Mackerel myofibrillar protein (MP) was therefore combined with (E)-2-decenal (T2D), (E,E)-2,4-decadienal (DDE), or trans-4,5-epoxy-(E)-2-decenal (E2D), with or without 6-, 8-, or 10-gingerol. Headspace solid-phase microextraction–gas chromatography–mass spectrometry, interaction disruptors, spectroscopy, molecular docking, and 100 ns molecular dynamics simulations were integrated. All three gingerols decreased the apparent aldehyde-binding ratio of MP. At 125 µmol/g protein, 10-gingerol reduced T2D, DDE, and E2D binding from approximately 81%, 72%, and 85% to 68%, 65%, and 68%, respectively. Spectroscopic responses were consistent with changes in the optical and conformational environment; fluorescence was interpreted as apparent quenching without numerical inner-filter correction, and CD band changes provided evidence of a treatment-related conformational response without assigning exact secondary-structure fractions. Docking ranked 8-gingerol most favorably, whereas the selected binary MYH7-10-gingerol trajectory showed greater pocket residence and a more favorable MM/GBSA estimate than the corresponding MYH7-DDE trajectory. The combined evidence supports a three-layer working model involving matrix partitioning, protein-level site accessibility, and pocket-level competition. These findings provide a mechanistic basis for sensory validation rather than direct proof of deodorization. Full article