Search Results (6,401)

Background/Objectives: Atrasentan is a selective endothelin A receptor antagonist (SERA) developed as a potential therapy for chronic renal diseases, including diabetic nephropathy and immunoglobulin A nephropathy. Despite this potential, understanding its metabolic bioactivation is essential for assessing the risks of drug-induced liver injury (DILI). However, the metabolic profile of atrasentan remains poorly characterized, and the mechanisms underlying its potential hepatotoxicity remain underexplored. Therefore, this study aims to investigate the metabolic pathways of atrasentan in human liver microsomes (HLMs) in the presence of nicotinamide adenine dinucleotide phosphate (NADP⁺), uridine diphosphate glucuronic acid (UDPGA), or glutathione (GSH). Methods: A liquid chromatography–high resolution mass spectrometry (LC-HRMS) coupled with a feature-based molecular networking approach was used to characterize metabolites. Characterization of the major metabolites was achieved through cytochrome P450 (P450) phenotyping with human recombinant P450 isoforms. Results: A total of eighteen metabolites were characterized through phase I and II metabolic reactions, including demethylenation, N-dealkylation, O-demethylation, hydroxylation, dehydrogenation, and glucuronidation. Atrasentan acyl glucuronide (M8) was confirmed as the predominant metabolite, and we also putatively annotated a catechol intermediate (M5) and its corresponding GSH conjugate (M15). Characterizing the GSH conjugate (M15) indicates that catechol intermediate (M5) can be further oxidized to a reactive ortho-quinone intermediate, which is subsequently trapped by GSH, suggesting the potential for a bioactivation mechanism. Reaction phenotyping demonstrated that the formation of M5 is catalyzed almost exclusively by the CYP3A subfamily. However, its direct translation to in vivo oxidative stress or covalent protein binding requires further studies. Conclusions: These findings demonstrate that feature-based molecular networking is a valuable strategy for metabolite characterization, underscoring the urgent need for further in vivo metabolism studies to definitively assess hepatotoxic risks associated with these reactive metabolites. Full article

Background: Glioblastoma (GBM) is among the malignant tumors with the lowest five-year survival rate. Current treatments offer limited efficacy and first-line options are scarce, highlighting the urgent need for novel drugs. Cariprazine can cross the blood–brain barrier and has been reported to inhibit certain tumors; however, its effect on GBM remains unknown. This study aims to elucidate its anti-GBM effects and mechanisms. Methods: Cell proliferation and apoptosis were assessed by wound healing, Transwell, colony formation assays, flow cytometry and JC−10 staining. Co-immunoprecipitation (Co-IP) examined the effect of cariprazine on D2/D3–ARRB2 interaction. Direct binding of cariprazine to ARRB2 was determined by molecular docking and CETSA. Western blotting and immunofluorescence detected changes in proliferation and apoptosis-related proteins. In vivo anti-GBM activity was evaluated in subcutaneous mouse models. Results: Cariprazine inhibited GBM cell proliferation and migration, promoted apoptosis, and showed low astrocyte toxicity. In mice, it suppressed GBM allograft growth without overt systemic toxicity. These effects were mediated through D2/D3 receptors, as cariprazine disrupted the D2/D3–ARRB2 interaction and thereby inhibited ERK signaling. It also upregulated ARRB2, further inhibiting the growth of GBM. Molecular docking and CETSA confirmed the direct binding of cariprazine to ARRB2 at LEU-245 and PHE-246. Conclusions: This study is the first to repurpose cariprazine for GBM, elucidating a unique ARRB2-centered dual mechanism, thus offering a new therapeutic strategy. Full article

The scaffold protein RACK1 (Receptor for Activated C Kinase 1) integrates signaling and translation, acting as a core component of the 40S ribosomal subunit. It binds activated Protein Kinase C (PKC) isoforms and membrane receptors. We used an auxin-inducible degron (AID2) system in human HAP1 cells to selectively deplete the free (cytoplasmic) pool of RACK1. The engineered RACK1–mAID–mClover3 fusion was rapidly degraded in the cytoplasm upon addition of 5-phenyl-indole-3-acetic acid (5-Ph-IAA), while the ribosome-bound pool remained detectable in ribosomal fractions, indicating that ribosome association makes RACK1 relatively less accessible to AID2-mediated proteolysis. Upon activation of PKCβII with phorbol-12-myristate-13-acetate (PMA), imaging at defined time points revealed closely matched kinetics of PKCβII membrane recruitment and membrane-proximal enrichment of ribosome-bound RACK1, peaking at ~10 min. Our data support a model in which activated PKCβII engages ribosome-bound RACK1 at membrane-proximal sites, consistent with a diffusion–capture mechanism in which PKCβII first accumulates at the membrane and then captures ribosome-bound RACK1, thereby recruiting the translational machinery to sites of signal input for membrane-proximal translation. These findings provide new insights into the spatial organization of translation. Full article

Background: Although prolonged inflammatory symptoms are an infrequent and problematic adverse effect of vaccination that can occur in some people, the transient activation of acute phase reactants (APRs) is expected with adjuvanted vaccines and helps to potentiate immune responses. Methods: This experiment examined the association between vaccine reactogenicity and immunogenicity in monkeys immunized with an adjuvanted recombinant protein including a receptor binding domain–human IgG1-Fc fusion protein (RBD-Fc) sequenced from the ancestral Wuhan strain of SARS-CoV-2. The acute inflammatory reaction to immunization was assessed by determining the decline in serum iron levels at 24 h and the increase in the neutrophil-to-lymphocyte ratio (NLR) as the adherent neutrophil pool trafficked into circulation. Results: Robust primary and secondary antibody responses were elicited. Larger decreases in serum iron and higher NLRs were associated with a stronger inhibition of RBD binding with angiotensin-converting enzyme (ACE2) when five early viral variants of SARS-CoV-2 were tested, including Wuhan, Alpha, Beta, Gamma and Delta. Inhibition of ACE2-RBD binding was less evident when the Omicron variant was tested. Individual variation in the APR was also predictive of the persistence of cell-mediated immunity based on the number of interferon-expressing mononuclear cells activated by viral antigen in ELISpot assays. Conclusions: Rapid antibody responses to primary immunization and large secondary responses to booster immunizations were elicited by this adjuvanted recombinant RBD-Fc vaccine, and our analysis affirmed the view that a transient APR can enhance antibody binding with antigen proteins. Full article

Background/Objectives: Vitamin D is a nutrient-related secosteroid system with endocrine, paracrine, immunological, and neurodevelopmental actions relevant to nutritional psychiatry. Psychiatric research has often treated vitamin D either as a cross-sectional correlate of depression or as a non-specific supplement expected to act across heterogeneous diagnostic categories. This narrative review aimed to develop a more discriminating framework in which vitamin D is considered a lifespan neuroimmune and immunometabolic signal whose psychiatric relevance depends on developmental timing, biological context, and phenotype. Methods: Evidence was integrated from developmental epidemiology, neonatal dried-blood-spot studies, randomized trials, meta-analyses, Mendelian randomization studies, clinical guidelines, and mechanistic neuroscience. The review focuses on prenatal and neonatal 25-hydroxyvitamin D, vitamin D-binding protein, free and bioavailable vitamin D, vitamin D receptor signaling, immune and microglial pathways, neurotransmitter systems, neurotrophic signaling, mitochondrial function, oxidative stress, hypothalamic–pituitary–adrenal-axis regulation, and the gut–microbiota–immune–brain axis. Results: The available evidence does not support vitamin D as a universal treatment for psychiatric disorders. Instead, vitamin D deficiency and altered vitamin D biology appear most relevant in biologically and clinically defined risk states, including neurodevelopmental vulnerability, inflammatory depression, psychosis liability, severe mental illness with nutritional deprivation, metabolic comorbidity, and cognitive frailty. Mechanistic data support plausible links with cytokine biology, the tryptophan–kynurenine pathway, dopaminergic and serotonergic systems, stress regulation, and neuroimmune homeostasis. Conclusions: Vitamin D should be conceptualized in psychiatry as a context-dependent neuroimmune and immunometabolic signal rather than a generic psychotropic intervention. Future studies should prioritize biomarker-enriched, developmentally timed, nutrition-centered models of precision prevention and adjunctive care. Full article

CXCL8, a pro-inflammatory chemokine, which can be induced by TNF-α or IL-1, is responsible for the recruitment and activation of neutrophils. Chemokines interact with glycosaminoglycans on endothelial cells and are thus protected from degradation and sequestration, holding them in an optimal position for recruiting immune cells. Inhibiting the interaction of chemokines with their glycosaminoglycan co-receptors represents an attractive approach for the treatment of chemokine-mediated diseases. Two polyketide-pyrone compounds, PA501 and PA502 were synthesized, which bind to CXCL8 with affinities higher than the natural glycosaminoglycan ligand heparan sulfate, and in a similar range as heparin. Significant structural changes were induced in the chemokine by interacting with the two compounds, as expressed in fluorescence and far-UV CD experiments. In filter binding assays, both compounds were found to displace heparan sulfate efficiently from CXCL8, with PA501 displaying the highest competition efficacy. Using a C-terminally truncated form of the chemokine, CXCL81-58, which lacks the main glycosaminoglycan-binding α-helical domain, the two compounds are suggested to use—to a varying degree—different binding sites on the protein, which have also been proposed for the natural heparan sulfate ligand. In a transmigration assay, PA501 and PA502 exhibited dose-dependent modulation of CXCL8-induced neutrophil mobilization and migration. The compounds PA501 and PA502 may thus be regarded as early novel lead compounds in the quest for anti-inflammatory, chemokine-targeting drugs. Full article

Acute kidney injury (AKI) caused by ischemia–reperfusion injury (IRI) involves rapid activation of innate immune responses, in which myeloid-derived immune cells critically shape injury severity. Y-box binding protein 1 (YB-1) regulates pro-inflammatory gene expression intracellularly and can be secreted to function extracellularly, yet how these two compartments jointly influence early IRI pathology remains poorly understood. To dissect the roles of intracellular myeloid versus extracellular YB-1, we subjected myeloid-specific Ybx1 knockout, Ybx1^fl/fl × LysM^cre, mice and wild-type (WT) littermates to unilateral renal IRI following administration of either a neutralizing anti-YB-1 antibody or control IgG. Kidney injury, inflammation, immune cell recruitment, neutrophil extracellular trap (NET) formation, antibody localization, and Fcγ receptor expression were assessed by qRT-PCR, histology, immunostaining, Western blotting, and flow cytometry. Myeloid-specific knockout of Ybx1 markedly reduced renal inflammation, neutrophil infiltration, NET formation, and tubular injury. This protective phenotype was lost when extracellular YB-1 was simultaneously reduced: anti-YB-1 treatment in knockout mice restored pro-inflammatory cytokine expression, increased tubular damage markers such as NGAL and KIM-1, exacerbated neutrophil recruitment and NET formation, and led to luminar accumulation of YB-1/anti-YB-1 immune complexes in tubular cells. Mechanistically, Ybx1-deficient myeloid cells exhibited significantly reduced CD16 expression, pointing to impaired Fcγ receptor-mediated phagocytosis as the cause of defective immune complex clearance. In contrast, wild-type mice efficiently cleared extracellular YB-1 complexes and showed no injury aggravation upon antibody treatment. Our findings identify myeloid YB-1 as a central regulator of early inflammatory injury in renal IRI and reveal that its protective depletion becomes pathogenic when extracellular YB-1 is simultaneously neutralized, likely due to unmasked defects in immune complex clearance. Full article

Monoclonal antibodies (mAbs) have been the subject of extensive study in recent years due to their recognition as highly promising therapeutic molecules offering high specificity and a low risk of side effects. Monitoring the structure of these molecules is crucial for developing new therapeutics, characterizing interactions with antigens or receptors, and explaining potential changes in activity between antibody production batches. However, commonly used biophysical approaches provide only low-spatial-resolution information, and conventional structural biology techniques such as crystallography and cryo-electron microscopy (cryo-EM) are difficult to apply to these highly dynamic proteins. Solution nuclear magnetic resonance (NMR) spectroscopy is the method of choice for structural studies of flexible proteins at atomic resolution; however, it has traditionally been limited to low-molecular-weight biological systems. In this review, we present recent advances in NMR spectroscopy and advanced isotopic labeling methods that have enabled the atomic-resolution study of both the crystallizable (Fc) and antigen-binding (Fab) fragments of antibodies. We show how NMR is becoming a powerful tool for investigating full-length mAbs at an atomic level, opening up new possibilities for the characterization and in-depth quality control of therapeutic antibodies in solution. Full article

Background: Esophageal squamous cell carcinoma (ESCA) represents one of the most common aggressive malignancies worldwide. Insulin-like growth factor binding protein 1 (IGFBP1), a typical member of the IGF superfamily, is closely linked to adverse prognosis in numerous cancers. Up to now, little is known about its functional relevance to cell migration and tumor progression in ESCA. This work focuses on clarifying the relationship between IGFBP1 expression and the progression and migratory characteristics of ESCA. Methods: mRNA expression profiles from ESCA patients were obtained from the TCGA and GEO databases. Differential expression analysis was performed using R software(version 4.2.2), followed by an intersection of DEGs between datasets. The STRING database was applied to establish PPI networks. Cytoscape software(Version 3.7.2) was then used for visual presentation and hub gene identification. IGFBP1 expression was validated in ESCA tissues versus adjacent normal tissues. Prognostic correlation was assessed using GEPIA, while diagnostic and predictive values were evaluated through ROC analysis and Cox regression. Genetic alterations of IGFBP1 were analyzed via cBioPortal. Immune cell infiltration patterns were investigated using TIMER. Functional enrichment analyses (GO, KEGG) were performed on IGFBP1-associated DEGs. In the in vitro experiments, esophageal cancer cell lines (such as Eca109 and TE-1) and normal human esophageal epithelial cell lines (such as HEEC) were selected. The transcriptional level of IGFBP1 was examined using RT-qPCR, while Western blot analysis was conducted to validate its protein expression changes. Changes in the proliferative capacity of cancer cells after IGFBP1 silencing were detected by the CCK-8 assay, and cell migration capacity was determined via wound scratch assays to clarify the related biological effects. Results: Overall, 2870 DEGs were screened from the GEO database, 153 DEGs were screened from the TCGA database, and 34 genes were found to be common to both databases; 10 core genes were screened from the PPI network. IGFBP1 was abnormally expressed in esophageal cancer. Cox regression confirmed that IGFBP1 is an independent risk factor, and prognostic analysis indicated that IGFBP1 is closely associated with poor prognosis. Gene mutation analysis showed that amplification mutations are the most common type of IGFBP1 gene mutation, and genetic alterations in IGFBP1 in ESCA patients are significantly associated with overall survival (OS) (p = 0.0002568). GO analysis indicated that IGFBP1-related differentially expressed genes were enriched in organic anion transport, epidermal development, apical cell components, and metal ion transmembrane transporter activity. Pathway enrichment based on the KEGG database illustrated the main enrichment of target genes in neuroactive ligand–receptor interactions, calcium signaling and cAMP signaling pathways. Additionally, remarkable differences in immune cell infiltration were observed between IGFBP1 high-expression and low-expression subgroups through tumor immune profiling. IGFBP1 expression differed significantly between esophageal cancer cells and normal esophageal epithelial cells, as detected by RT-qPCR (p < 0.05). Moreover, knockdown of IGFBP1 markedly inhibited the proliferation (p < 0.05) and migration abilities (p < 0.05) of TE-1 and Eca109 cells. Conversely, IGFBP1 overexpression facilitated these cellular processes. Conclusions: As a key oncogenic driver for ESCA, IGFBP1 may participate in the oncogenesis of ESCA, possibly influencing clinical outcomes via IGF signaling and the tumor microenvironment. Its dual functions in tumor and immune systems suggest it might be a candidate for ESCA immunotherapy research. Full article

Background: Positron emission tomography (PET) is a molecular imaging technique that exploits the β⁺ decay of selected radionuclides to enable non-invasive in vivo investigation of biochemical and physiological processes, including early and subclinical disease alterations. Radiotracers are designed to bind specific molecular targets with high affinity and selectivity. Among the targets to which PET devotes increasing attention are G protein-coupled receptors (GPCRs)—the largest class of transmembrane receptors—which orchestrate a wide spectrum of biological outcomes and are widely implicated in human disease. Objectives: This review analyzes patents published between 2020 and 2025 focusing on GPCR-targeted PET radiotracers, highlighting design strategies, radionuclide selection, and translational perspectives across oncology, central nervous system (CNS) disorders, and inflammatory diseases. Results: Patent activity shows that most GPCR-targeted PET tracers are derived from validated ligands adapted for imaging while preserving affinity and selectivity. Oncology patents mainly favor peptide-based or modular metal–chelator platforms enabling radionuclide flexibility and theranostic extension, whereas CNS tracers rely on drug-like small molecules optimized under strict ADME and blood–brain barrier constraints. Increasing emphasis on non-orthosteric, function-sensitive, and dual-targeting approaches reflects a shift toward interrogating GPCR signaling states, while inflammatory indications remain comparatively underrepresented despite clear biological foundations. Conclusions: Current patent trends consolidate GPCR-targeted PET tracers as well-established diagnostic tools while progressively expanding their clinical utility, both as platforms supporting translational research—informing mechanistic insight and drug development—and as components of emerging theranostic strategies across multiple disease areas. Full article

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1), driven by high mutation and recombination rates, poses significant challenges for diagnostics, therapy, and vaccine development. While variable regions enable immune escape, hyperconserved regions are critical for viral function and represent promising targets for novel therapeutic interventions. This study aimed to develop and validate a bioinformatic algorithm for quantitative assessment of sequence conservation and automated identification of functionally significant conserved regions across all major HIV-1 proteins. A total of 1119 full-length HIV-1 genome sequences representing major subtypes (A1, A2, A6, B, C, D, F1, F2, G, H, J, K) were analyzed. Normalized Shannon entropy (S-index) was calculated for each alignment column. Statistical thresholds for conserved regions were established using 95% confidence intervals derived from bootstrap resampling. Two complementary algorithms, clustering and local maxima detection, were applied to identify conserved regions, which were subsequently mapped to known functional domains based on literature data. Protein conservation varied markedly, with S_m values ranging from 0.784 (Vpu) to 0.920 (Pol). Gag, Pol, and Vpr demonstrated the highest overall conservation, while Env, Rev, Tat, and Vpu exhibited pronounced variability interspersed with conserved domains. In total, 25 conserved regions in Gag, 49 in Pol, 28 in Env, and 6–4 regions in accessory proteins (Vif, Vpr, Rev, Tat, Nef, Vpu) were identified. These regions corresponded to critical functional elements including enzyme catalytic centers, zinc fingers, receptor-binding sites, protein interaction interfaces, and membrane-anchoring domains. The developed computational framework enables statistically grounded identification of evolutionarily constrained regions across analyzed HIV-1 subtypes. The identified conserved regions represent candidate sites for further investigation and may inform downstream studies focused on antiviral target prioritization, immunogen design, and diagnostic assay development. However, their translational applicability requires additional analytical, structural, and experimental validation. Full article

Allergic rhinitis (AR) is one of the most prevalent allergic disorders worldwide. Current pharmacological treatments are often limited by suboptimal efficacy and notable adverse effects. Herbal medicines, with their multi-component and multi-target therapeutic characteristics, have attracted increasing attention. Artemisia ordosica Krasch. (AOK), a traditional Chinese/Mongolian medicine has demonstrated immunomodulatory, antioxidant, and anti-inflammatory activities. The anti-AR potential of AOK extract fractions was evaluated using in vitro mast cell degranulation inhibition assays, network pharmacology analysis, molecular docking, and molecular dynamics simulations to elucidate underlying pharmacological mechanisms. The P815 mast cell model induced by compound 48/80 was employed to assess the inhibitory activity and cytotoxicity of different extract fractions. Among the tested fractions, the ethyl acetate fraction exhibited the most potent inhibitory effect on mast cell degranulation without significant cytotoxicity. Network pharmacology analysis identified 254 potential AR-related targets of AOK, with Signal Transducer and Activator of Transcription 3(STAT3), Src protein(SRC), Tumor protein 53(TP53), AKT Serine/Threonine Kinase 1(AKT1), Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Estrogen Receptor 1(ESR1), and Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) identified as key hub proteins. Gene Ontology and KEGG pathway enrichment analyses indicated that AOK primarily modulated inflammatory and oxidative stress-related processes through the lipid and atherosclerosis, hypoxia-inducible factor-1, and AGE-RAGE signaling pathways. Molecular docking and dynamics simulations demonstrated strong binding affinities and stable interactions between major active constituents, particularly hydroxygenkwanin, and key targets such as SRC. The ethyl acetate fraction of AOK extract exhibited significant mast cell degranulation inhibitory activity, likely mediated via a synergistic multi-component, multi-target mechanism involving regulation of inflammatory and immune-related signaling pathways. These findings provide a pharmacological basis for the potential application of AOK in AR treatment. Full article

Breast cancer is one of the leading causes of cancer incidence and mortality in many countries worldwide although there is considerable geographic variation. Diet is thought to impact risk of developing breast cancer but identifying specific dietary factors involved in the etiology of this disease has proven difficult. The two primary factors that initially led to an interest in soy are the historically low breast cancer incidence and mortality rates in Japan and the uniquely high concentration of isoflavones in soybeans and foods derived from this legume. Isoflavones bind to both estrogen receptors although preferentially to estrogen receptor-β. Prospective cohort studies indicate that isoflavone intake is associated with a reduced risk of developing breast cancer, but randomized controlled trials in which the impact of soy and isoflavones on markers of breast cancer risk has been evaluated are not supportive of this protective association. It may be that for isoflavones to reduce risk, intake needs to occur during childhood and/or adolescence. The notion that consuming soy early in life reduces risk of adult breast cancer, herein referred to as the “early soy intake hypothesis” (ESIH), was proposed >30 years ago. The results of rodent studies and retrospective observational studies that examined incidence and/or markers of breast cancer risk support the ESIH. However, a lack of randomized controlled trials precludes a clear recommendation for soy consumption during childhood and/or adolescence specifically for breast cancer prevention. Although soy foods provide high-quality protein and a variety of nutrients and can be part of a healthy diet for young and adolescent girls, more research is needed to advance the ESIH. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by the accumulation of the toxic protein amyloid-β, formation of tau-containing neurofibrillary tangles, neuroinflammation, and synaptic dysfunction, highlighting the need for new therapeutic strategies capable of modulating multiple pathological pathways simultaneously. In this study, a structure-based in silico approach was applied to evaluate the multi-target potential of two previously reported pyrrole-based compounds (pyrrole 1 and pyrrole 2) with known monoamine oxidase-B (MAO-B) inhibitory activity and low neurotoxicity. Molecular docking studies were performed against a panel of key AD-related targets, including GSK-3β, APP, MAO-B, BACE1, AChE, BChE, COX-2, GABA-B receptor, NMDA receptor, and E3 ubiquitin ligase CHIP, using Glide XP docking. The results revealed that compound pyrrole 1 may have favorable predicted binding affinities across several targets, with relatively strong docking scores for GSK-3β and COX-2. The binding mode analysis indicated that pyrrole 1 adopts poses consistent with interaction patterns commonly observed for ATP-competitive GSK-3β inhibitors and COX-2 ligands. In silico ADMET profiling using the software SwissADME and ProTox 3.0 indicated distinct pharmacokinetic and safety profiles for the two compounds, with pyrrole 2 showing superior drug-likeness and predicted blood–brain barrier penetration, while pyrrole 1 displayed a more favorable overall toxicity profile. Collectively, these findings identify pyrrole 1 as a theoretically promising multi-target candidate for AD requiring experimental validation, while providing a strong structural basis for further optimizations and subsequent experimental confirmation. Full article

The perception of the odor of fatty acids provides individuals with information about the nutritional content of foods. This perception varies depending on biological and genetic factors. Previous studies have shown that odorant binding proteins (OBPs) present in olfactory mucus play an important role in capturing and transporting odorants, typically lipophilic molecules, through the mucus to the olfactory receptors (ORs). The main objective of this research was to study the role of the rs2590498 (A/G) polymorphism of the human OBPIIa gene on the threshold and intensity of odor perception of palmitic (PA), oleic (OA) and linoleic (LA) acids. Volunteers were genotyped for OBP polymorphisms and classified as normosmic or hyposmic based on their threshold for n-butanol. The results show that normosmic or AA genotype participants perceived the odors of PA, OA, and LA at lower concentrations and with greater intensity than hyposmic or AG/GG genotype participants. Furthermore, the perception intensity reported by participants showed the following decreasing order: LA > OA > PA. These findings indicate that the intensity and threshold of perception depend on the lipophilicity of the molecule. These results indicate that genetic and biological factors, as well as the chemical properties of the molecules, play a key role in the olfactory perception of fatty acids. Full article