Furaneol and sotolone are caramel aroma isomers with distinct sensory qualities, yet how their differential perception emerges from molecular to neural levels remains unclear. This study integrates sensory analysis, molecular dynamics, and EEG to address this gap. Sensory evaluation showed furaneol was more pleasant and had a tenfold lower detection threshold than sotolone. Simulations revealed furaneol binds stably to OR5M3 via TYR-257, while sotolone interacts selectively with OR8D1 via HIS-159/ASN-206. EEG identified that furaneol uniquely enhanced frontal θ power (4-8 Hz), associated with cognitive engagement, whereas both odorants increased α/β power. These results demonstrate that perceptual differences originate from receptor-specific binding and are cortically encoded in distinct oscillatory patterns. This multi-level approach provides a mechanistic framework linking molecular interactions to perception, supporting the rational design of flavors.

Pyruvate carboxylase (PC) replenishes tricarboxylic acid cycle intermediates, driving cancer metabolic reprogramming. To improve the metabolic stability of erianin, a potent PC inhibitor from Dendrobium chrysotoxum Lindl, we designed and synthesized 55 derivatives, culminating in the identification of CIB-Q22, which exhibited potent PC inhibition (IC50 = 1.74 nM) and suppressed HCC cell viability (IC50 = 25.18 nM), comparable to erianin. Notably, CIB-Q22 demonstrated significantly improved in vivo stability, with a half-life (T1/2 = 1.21 h) much longer than erianin (T1/2 ∼ 0.1 h). Mechanistically, CIB-Q22 suppressed HCC proliferation and metastasis by inducing apoptosis and ferroptosis. Moreover, it promoted mitochondrial oxidative stress and inhibited glycolysis, thereby sensitizing cells to glutamine deprivation. In vivo, CIB-Q22 exhibited comparable antitumor efficacy but improved safety compared to sorafenib. With its potent PC inhibition and favorable drug-like properties, CIB-Q22 represented a promising therapeutic candidate for HCC treatment.

Nucleophilic addition to strained rings is an efficient approach for the synthesis of polysubstituted cyclobutanes, which are privileged structural scaffolds in many pharmaceuticals. In this work, we have developed a simple, efficient, transition-metal-free, and scalable route for the synthesis of trisubstituted methylenecyclobutanes via ring opening of bicyclo[1.1.0]butanes with silyl ketene imines, using B(C6F5)3 as the catalyst under mild reaction conditions. In this fashion, 24 new potential bioisosteres containing trisubstituted methylene cyclobutanes were obtained in good to excellent yields (up to 99% yield). Furthermore, example reactions were performed on a gram scale, and a proposed mechanism is discussed.

Linalool, a major bioactive compound of lavender essential oil, has been reported to produce analgesic and anxiolytic effects when delivered through olfactory pathways. However, the molecular and structural mechanisms remain unclear. In this study, we investigated behavioral, transcriptomic, and morphological changes in the piriform cortex (Piri) following linalool odor exposure in a CFA-induced inflammatory pain model. Behavioral assessments showed that daily 10-min linalool exposure for 8 consecutive days produced progressive and sustained analgesic effects, as indicated by increased mechanical withdrawal thresholds and prolonged thermal withdrawal latencies. Linalool exposure also reduced anxiety-like behaviors in the open field test and elevated zero maze without affecting locomotor activity. Transcriptomic analysis of Piri tissues revealed 496 differentially expressed genes between linalool-exposed and control mice. Functional enrichment analysis indicated that these genes were primarily involved in neural signal transduction, neurotransmitter release, synaptic function, and behavioral regulation. Several genes associated with vesicle trafficking and neuronal communication, including Hap1, Baiap3, and Sytl4, were significantly upregulated. Golgi staining revealed increased dendritic branching complexity and spine density in pyramidal neurons of the Piri, particularly a selective increase in stubby spines, indicating enhanced synaptic structural plasticity. Collectively, these findings demonstrate that repeated linalool odor exposure produces sustained analgesic and anxiolytic effects accompanied by transcriptional remodeling and synaptic structural plasticity in the Piri. These results provide molecular and structural evidence supporting a potential role for olfactory cortical plasticity in odor-induced modulation of pain.

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is regarded as a novel molecular imaging approach that integrates DESI source with conventional mass spectrometry to provide spatial information and molecular composition on the sample’s surface. In this review, the principle of DESI-MSI was elucidated, including its desorption process and ionization mechanism. Through the applications in biological tissues and organs, the advantages of DESI-MSI technology were demonstrated in exploring the tissue functional roles and disease mechanisms, including brain, liver, kidney, and lung. Building on these findings, we review DESI-MSI’s unique capability to map both exogenous and endogenous biomolecules, thereby providing insights into spatial distribution of exogenous organisms and endogenous metabolic of transformation pathways and pharmacokinetics. Finally, the recent applications of DESI-MSI in biomedicine, environmental monitoring, and food safety are also reviewed. With the continuous improvement of instruments and analysis methods, DESI-MSI is expected to bring meaningful changes across a growing number of fields, opening up exciting opportunities to support innovative technologies and applied research.

The high-fidelity encapsulation and controlled release of natural aromas remain significant challenges in flavor science due to the compositional complexity of essential oils and heterogeneous host-guest interactions in conventional co-inclusion systems. Using rose aroma as a representative model, this study presents a "divide-and-conquer, precise reconstruction" strategy that integrates multiscale simulation with experimental validation. Seven key aroma-active compounds were screened through GC-MS combined with odor activity value (OAV) analysis. Their host-guest interactions with β-cyclodextrin (β-CD) were subsequently investigated using molecular docking, molecular dynamics simulations, and MM/PBSA free-energy calculations. The results suggest that hydrophobic interactions dominate the complexation process, and the calculated binding free energies (ΔG_bind: -1.67 to -7.34 kcal/mol) show semi-quantitative consistency with experimentally observed encapsulation behavior and release trends. Individual inclusion complexes (ICs) exhibited markedly improved thermal stability, with decomposition onset temperatures increasing by more than 150 °C compared with free compounds. Successful complex formation was confirmed through FTIR, XRD, and 1H NMR characterization. Release kinetics analysis revealed compound-specific release behaviors governed by interaction strength and molecular compatibility with β-CD. Based on these differentiated release profiles, physical blending of individually prepared ICs enabled reconstruction of a headspace aroma composition highly consistent with that of the original rose extract, outperforming conventional co-inclusion under identical conditions. Beyond demonstrating a successful case for rose aroma, this work establishes a simulation-guided design framework integrating key component screening, interaction prediction, precise preparation, and release-controlled reconstruction. The proposed methodology provides a rational strategy that can potentially be extended to other complex natural aroma systems for the development of advanced flavor delivery system.

Understanding the dynamic evolution of volatile organic compounds (VOCs) in crushed garlic is important for controlling sensory quality during processing and storage. Herein, a quasi-real-time analytical platform based on acoustic levitation (AL) coupled with GC-MS and chemometric analysis was developed for monitoring VOCs changes during the color transition of crushed garlic. The gas-liquid interface of acoustically levitated droplets enabled efficient contactless enrichment of VOCs, improving detection sensitivity and minimizing contamination. During a six-day color transition, 94 VOCs were identified, among which 24 flavor-active compounds were classified into nine aroma categories. Chemometric analyses (PCA and OPLS-DA) clearly differentiated four color stages based on VOC profiles and aroma categories. Generalized additive models (GAMs) revealed nonlinear temporal changes in representative VOCs. Integrated analysis of OPLS-DA variable importance on projection results, GAMs indicated that diallyl trisulfide was strongly associated with garlic discoloration and could serve as a potential marker compound for color-related flavor evolution. Finally, sensory evaluation revealed significant differences in aroma attributes across color stages (p < 0.05), with green and cooling notes peaking early and sulfur, burnt, fruity, and dairy notes increasing at later stages, consistent with VOC profiles. This study demonstrates the capability of AL-GC-MS for quasi-real-time VOC monitoring and provides new insights into the relationship between color development and flavor evolution in crushed garlic.

A Br & Oslash;nsted acid-catalyzed peroxidation of 3-hydroxyisoindolinones with hydroperoxides has been established for the first time, which constructs alpha-amino peroxides bearing a tetrasubstituted stereocenter in good to high yields and enantioselectivities. The transformation uses of environmentally benign solvents, and features operational simplicity, and high atom economy. The synthetic utility was demonstrated with the gram-scale reactions and further transformations of the products. Notably, preliminary bioactivity studies reveal that these valuable alpha-amino peroxides show potential anticancer activity.

Real-time monitoring of dopamine (DA) is vital for understanding neurophysiological processes and diagnosing neurological disorders. Flexible and stretchable sensors are particularly attractive for wearable or implantable bioelectronics, as they offer conformal contact with soft, dynamic biological tissues. However, achieving high selectivity in such platforms remains a major challenge, especially in the presence of structurally similar catecholamines such as epinephrine (EP), which often coexist with DA in physiological environments. Here, we report a highly stretchable hydrogel-based DA sensor constructed from acrylamide (AAM), carbon nanotubes (CNTs), and molybdenum disulfide (MoS2). CNTs enhance the electrical conductivity of the hydrogel network, while MoS2 provides selective affinity toward DA, enabling strong molecular discrimination against EP and common electroactive interferents such as ascorbic acid and uric acid. The resulting AAM/CNT/MoS2 hydrogel exhibits excellent mechanical durability, maintaining structural integrity under 50% strain and surviving 15 repeated stretch-release cycles (0-50%) without loss of sensing performance. The sensor achieves a low detection limit of 6.1 nM and maintains reliable DA response even in the presence of high concentrations of EP. This work presents a promising strategy toward soft, selective, and interference-resilient biosensors for dynamic neurochemical sensing.

Pain perception is a multidimensional process encompassing sensory, affective, and cognitive components. In recent years, accumulating evidence suggests that olfactory stimulation can modulate pain perception through neurophysiological and emotional mechanisms. However, systematic understanding of how olfactory processing contributes to analgesia across different experimental and clinical contexts remains limited. This review aims to provide an integrative overview of current evidence regarding the role of olfactory pathways in pain modulation, summarizing findings from human and animal studies that investigated the analgesic potential of volatile compounds. A systematic literature search was conducted across PubMed, Web of Science, OVID, Cochrane Reviews, Embase, CNKI, and WanFang databases. A total of 4360 records were retrieved, screened for relevance, and refined to 147 studies, including 138 human-based and 9 animal-based investigations. Lavender, peppermint, chamomile, bergamot, and citrus-derived oils were most frequently associated with analgesic outcomes. Olfactory stimulation was found to modulate pain via central integrative circuits involving affective, autonomic, and sensory processing, engaging conserved pathways that support descending pain inhibition. Olfactory stimulation by specific flavor and fragrance compounds holds translational potential for non-pharmacological pain management. Nevertheless, methodological standardization and mechanistic validation are necessary to advance this emerging field.

Pain is a complex sensory and affective experience regulated by distributed neural circuits that integrate internal physiological states with external stimuli. Orexinergic neurons, a widely projecting neuronal population within the lateral hypothalamus (LH), play a central role in this process. This review synthesizes current evidence on the involvement of LH orexinergic neurons in nociceptive regulation and highlights their role as a key integrative substrate for non-pharmacological analgesia. Orexin peptides (orexin A and orexin B) modulate both the sensory-discriminative and affective-motivational components of pain via their receptors (OX1R and OX2R) in a context-dependent manner, producing antinociceptive or pro-nociceptive effects depending on peptide subtype, receptor distribution, circuit architecture, and pain modality. In parallel, emerging evidence indicates that orexinergic neurons are critically engaged in diverse non-pharmacological analgesic paradigms, including stress-induced analgesia, olfactory modulation, electroacupuncture, and exercise-induced hypoalgesia. In addition, other neuronal populations within the LH, such as glutamatergic, GABAergic, and neurotensinergic neurons, also contribute to pain regulation in a circuit-specific manner and partially overlap anatomically and functionally with orexinergic neurons. Collectively, these findings position LH orexinergic neurons as a central node linking neural circuit dynamics with the behavioral and physiological modulation of pain. Targeting orexin-related pathways may therefore provide novel avenues for the development of non-pharmacological and integrative pain management strategies.

The molecular architecture of odorants, nuanced by factors such as chirality and carbon chain length, significantly influences sensory perception. Despite this, the role of double bond isomerization in olfactory evaluation remains underexplored. This study delves into how the double-bond rearrangement in damascone impacts flavour perception, combining sensory evaluation and computational simulation. Sensory results showed that alpha- and delta-damascone had more pronounced minty notes, while beta-and delta-damascone exhibited more significant floral ones. Notably, the odour thresholds determined via the S-curve method were 0.0145 mu g/mL, 0.0373 mu g/mL and 0.0011 mu g/mL for alpha-, beta- and delta-isomers, respectively, indicating a significant difference in potency. To further investigate the influence of double bond rearrangement on receptor binding, molecular docking and molecular dynamic simulations were utilised. Molecular docking revealed that delta-damascone had the lowest binding energy, correlating with its high potency, and identified key interactions with residues such as TYR-262 and TYR-251. Molecular dynamics simulations further demonstrated that double bond isomerization affected the binding stability between the three damascones and olfactory receptors, as evidenced by root-mean-square deviation (RMSD) fluctuations, with alpha- and delta-damascone forming more stable complexes. Together, these results provide a mechanistic understanding of how double bond configuration dictates damascone odour perception through distinct receptor binding modes.

Bioelectronic systems integrated with artificial intelligence (AI) are transforming neurochemical diagnostics, enabling intelligent, real-time decoding of brain chemistry. Here, we present an AI-driven biomimetic electrochemical chip with intestine-inspired wrinkled MoS2 electrodes, enabling dynamic in vivo dopamine monitoring and neuromodulation. This wrinkled structural design promotes efficient molecular capture and alleviates laminar flow limitations, achieving a 23-fold enhancement in dopamine sensitivity over planar electrodes, with detection limits as low as 37 nM in 4.1 μL of biofluid. Moreover, coupled with an AI-assisted decision module, the platform translates neurochemical fluctuations into adaptive modulation, enabling real-time closed-loop neuromodulation. In vivo studies in rats demonstrate autonomous regulation of endogenous dopamine transients, directly linking electrode architecture to functional neural outcomes. This work highlights how bioinspired electrode design, integrated with intelligent signal interpretation, establishes a scalable pathway toward next-generation neurodiagnostics and adaptive bioelectronic interfaces.

Sensory peptides are short-chain peptides with flavor characteristics or affecting flavor effects.Beyond their advantages of diverse sources,high bioavailability,and safety,certain peptides exhibit physiological regulatory functions.Firstly,the four stages of research on sensory peptides were summarized.The initial stage was the 1950s to the 1970s,when sensory peptides were isolated from natural food materials and their artificial synthesis was achieved.The rapid development stage was the 1980s to the 1990s,when analytical techniques and taste receptor research were used to systematically explore the structure-activity relationship and sensory evaluation methods.The process and application stage took place in the first decade of the 21st century,when the focus was placed on the optimization of enzymatic hydrolysis processes and the development of compound condiments to promote industrialization.And the multi-functional and precision stage has continued from 2010 to the present,when artificial intelligence and green manufacturing were combined to expand the high-throughput screening of sensory peptides and their nutritional and health functions.Secondly,by integrating multi-source databases and conducting systematic literature mining,a standardized dataset covering 781 sensory peptides was constructed from dimensions including screening strategies and information,inclusion principles of sensory peptides,standardized database category information,taste types,chain lengths,molecular weights,sources,and processing technologies.Their taste-type distribution,sequence characteristics,and source discovery were comprehensively analyzed to map current research landscapes.Furthermore,182 sensory peptides with clear bioactivity reports were screened through high-throughput sequence alignment,and their sensory types,bioactivities,and"sensory-bioactivity"distribution characteristics were summarized.The research paradigms for three high-frequency bioactivities,ACE inhibition,DPP-Ⅳ inhibition,and antioxidant effects,were systematically summarized.This study aimed to provide multi-dimensional database support for the sensory peptide industry and offer a reference for the synergistic study of"flavor-function"dual attributes of sensory peptides.

In this study, we compiled three categories of odorants with spicy aromas: anise class, clove class, and cinnamon class. We aimed to use molecular dynamics simulation techniques to uncover potential regularities in the activation mechanisms of the same odorant across different olfactory receptors, or vice versa, the activation mechanisms of different odorants on the same olfactory receptor. Here, molecular dynamics simulation results reveal that anisaldehyde and estragole preferentially bind to TYR residues, thereby activating the corresponding olfactory receptors. Both eugenol and isoeugenol activate OR5D18 at similar binding sites, but ultimately lead to differential conformational changes in the olfactory receptor. Additionally, the binding conformations of eugenol and methyl eugenol are nearly identical, whereas cinnamaldehyde and cinnamyl alcohol, methyl cinnamaldehyde, exhibit distinct binding conformations with the olfactory receptor. These results underscore how subtle structural changes can impact the binding mechanism of odorants.

The use of sustained-release carriers to encapsulate fragrances effectively mitigates their high volatility and chemical instability. This study aims to investigate the feasibility of employing biomass-derived starch aerogels (SA) as a novel sustained-release carrier for fragrances. First, SA with a porosity of 85.33% and a specific surface area of 229.89 m2/g were prepared using supercritical carbon dioxide (scCO2) drying. Further, linalool, geraniol, linalyl acetate, citral, and limonene were incorporated into the SA by scCO2 impregnation, with adsorption amounts reaching 168.40 to 336.00 mg/g. Moreover, fragrances with higher polarity and lower steric hindrance achieve higher loading efficiency in SA. Temperature-controlled release experiments indicate that SA exhibits prominent sustained release effect on fragrances. Especially for polar fragrances, free fragrances are completely released within 5 min at 60 degrees C, In contrast, after loading into SA, the release duration of polar fragrances is prolonged to 40-60 min. This study provides a theoretical foundation and technical support for the development of high-loading, eco-friendly fragrance delivery systems with sustained-release functionality.

Despite the critical role of aroma interactions in shaping food flavor, their molecular mechanisms remain elusive. Here, binary interactions between furaneol and five co-odorants (guaiacol, acetylpyrazine, eugenol, 2-phenylethanol, valeric acid) with OR5M3 were investigated using an integrated sensory-computational approach. Sensory analysis classified furaneol-eugenol as synergistic, furaneol-valeric acid as masking, and the remaining pairs as additive or indifferent. Docking revealed that the synergistic pair had the most favorable binding energy (-10.11 kcal/mol), while the masking pair had the weakest (-7.95 kcal/mol). MD simulations showed synergy correlated with low RMSD and sustained H-bonds, whereas masking involved large RMSD fluctuations, fewer H-bonds. MM/PBSA quantified these differences: the synergistic complex displayed the strongest binding affinity (-23.64 kcal/mol), the masking complex the weakest (-4.24 kcal/mol) due to a large solvation penalty. This work establishes a predictive strategy based on the OR5M3 receptor model for decoding and designing aroma interactions at the molecular level.