Search Results (20,951)

Chronic neuroinflammation driven by microglial activation is a pathological hallmark of neurodegenerative diseases, and the NF-$\kappa$B/iNOS signaling axis plays a central role in propagating this damage. NF-$\kappa$B-mediated iNOS transcription generates excessive nitric oxide, causing oxidative neuronal injury. The medicinal mushroom Hericium erinaceus produces cyathane diterpenoid erinacines and isoindolinone erinacerins, both reported to attenuate neuroinflammation; however, the molecular basis of their interactions with iNOS and NF-$\kappa$B remains poorly characterized. We screened 21 erinacerins and 18 erinacines against both targets using validated molecular docking, then subjected top-ranked candidates and negative controls to 100 ns molecular dynamics simulations, MM-PBSA binding free energy calculations (±SEM), per-residue energy decomposition, backbone RMSD, and ligand–protein minimum distance analyses, with quercetin as reference. The analysis revealed scaffold-dependent target selectivity: erinacerins exhibited preferential stability with iNOS (erinacerin L: RMSD 0.185 nm), whereas erinacines formed more stable complexes with NF-$\kappa$B (erinacines G and J: RMSD < 0.36 nm). Minimum-distance monitoring confirmed that the elevated ligand RMSD in iNOS predominantly reflected surface relocation rather than dissociation. Erinacine S emerged as the most promising dual-target candidate ($\Delta G_{bind}$: −24.31 ± 0.16 and −14.24 ± 0.11 kcal/mol for iNOS and NF-$\kappa$B, respectively), over twofold stronger than quercetin for iNOS. Negative controls revealed that docking-based ranking was target-dependent in its discriminative capacity, underscoring the need for MD-based refinement. These results identify erinacine S as a priority candidate for experimental validation. Full article

Thoracic aortopathies, including aneurysm and dissection, are complex vascular disorders characterized by structural alterations of the aortic wall that disrupt normal haemodynamics. Altered shear stress, turbulent flow, and endothelial dysfunction promote thrombus formation and modulate systemic hemostasis via platelet activation and the von Willebrand factor–ADAMTS13 axis. The Total Thrombus-Formation Analysis System (T-TAS) is a microfluidic, flow-dependent assay that quantitatively evaluates thrombus formation under physiological shear conditions. Although studied in various cardiovascular contexts, its application in aortopathies remains largely unexplored, and no prospective studies have validated its clinical utility. Integrating T-TAS with computational haemodynamic approaches, such as two-way fluid–structure interaction simulations, enables assessment of the interplay between blood flow, vessel wall mechanics, pulse wave propagation, and local shear patterns. Patient-specific modelling, including individualized flow profiles, pressure distributions, and wall properties, may enhance mechanistic insights. Genetic variants in Fibrillin-1 gene (FBN1), Transforming Growth Factor Beta Receptor 1/2 (TGFBR1/2), Actin Alpha 2 (ACTA 2), and Myosin Heavy Chain 11 (MYH11) further contribute to structural vascular heterogeneity and diverse systemic haemostatic phenotypes, highlighting the need for personalized assessment. T-TAS should currently be considered an exploratory research tool rather than a validated diagnostic or prognostic method. This narrative review proposes a hypothesis-generating framework integrating structural, haemodynamic, molecular, and functional perspectives. Combining flow-based thrombosis assays with advanced modelling may inform future translational studies, improve mechanistic understanding of thrombus formation, and support personalized risk stratification and management in patients with thoracic aortopathies. Full article

This study presents a thorough investigation of chemical outcomes during the reaction of cisplatin and 2-thiohydantoin ligands in the presence of DMSO. Aided by NMR spectroscopy and quantum chemical calculations, the influence of DMSO substitution on the reaction factors is specified, and key intermediates and products in the reaction mechanism are identified and characterized. Coordination modes, reaction orders, and important thermodynamic parameters, such as Gibbs free energies, stabilization energies, and reaction rate constants, are determined. Molecular docking was utilized to propose the binding modes of the final products to DNA and predict their anticancer properties. The results of this study represent a unique kinetic and mechanistic outlook into the influence of DMSO on platinum(II) coordination, as ligand substitution with DMSO was previously found to alter the coordination environment in a biologically relevant manner. Full article

Isoflurane is a widely used volatile anesthetic with context-dependent effects on neuronal survival, particularly in neurodegenerative conditions. Increasing evidence suggests that brief, sublethal stress exposure can induce adaptive cellular responses through hormesis-based preconditioning mechanisms. In this study, we investigated whether isoflurane preconditioning enhances neuronal tolerance to amyloid-β (Aβ)-induced toxicity and explored the underlying redox-dependent molecular pathways. Using HT-22 murine hippocampal neuronal cells, we demonstrate that short-term exposure to low-dose isoflurane induces a delayed neuroprotective phenotype characterized by improved cell viability, reduced apoptotic signaling, and maintained mitochondrial membrane potential following Aβ challenge. Mechanistically, isoflurane preconditioning elicited a mild and transient increase in intracellular reactive oxygen species (ROS), which is critical for the activation of the PI3K/Akt signaling pathway. Pharmacological scavenging of reactive oxygen species abolished Akt phosphorylation and reduced the protective effects of preconditioning, supporting a hormetic signaling model rather than direct antioxidant action. Following Akt activation, isoflurane preconditioning promoted the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), decreased Keap1 protein levels, and facilitated nuclear translocation and transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, the expression of Nrf2-regulated antioxidant genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 1 and 2 (SOD1/2), and catalase, was significantly upregulated. Collectively, these findings indicate that isoflurane preconditioning confers neuroprotection through hormesis-like mild oxidative signaling and coordinated activation of endogenous antioxidant defenses rather than via direct antioxidant scavenging. Full article

Boule is the ancestral member of the Deleted in Azoospermia (DAZ) family and is pivotal for gametogenesis and male fertility in most animals. However, there is a dearth of information on molluscan boule. Here, we identified a counterpart (Pcbol) from the genome of Pomacea canaliculata, which has emerged as a cosmopolitan alien species and notorious pest that causes devastating damage to aquatic biodiversity, freshwater ecosystems and crop production in invaded ranges. This study aimed to investigate the biological roles of Pcbol in male reproduction and to decipher the molecular mechanisms underpinning its modulation via dsRNA-delivered RNA interference (RNAi). The bioinformatic analysis showed that the Pcbol genomic sequence is 12,934 nt in length, harboring an open reading frame of 294 nt that encodes 97 aa residues, with an RRM domain evolutionarily conserved among molluscan orthologues. Spatiotemporal expression profiling indicated the predominant abundance of Pcbol in adult males and testis tissues. dsPcbol, injected at a dose of 4 μg/per snail for 5 days, yielded optimal silencing at both transcript and translation levels of Pcbol, as revealed by qRT-PCR and Western blotting. Immunofluorescence echoed a pronounced reduction in Pcbol signal intensity following RNAi. In addition to the arrested reproductive gland phenotype, the number of sperm cells substantially dwindled upon dsPcbol treatment relative to the dsGFP control. In biochemical and fecundity assays, Pcbol depletion triggered a significant decrease in Te/SP/Arg content and suppressed the number of deposited eggs and hatchability. Furthermore, spermatogenic genes like CDC25/TSSK1/SPATA17/DDX4/Dmrt2/Sox2/Kelch10/SPO11 displayed considerable downregulation post Pcbol silencing, with molecular docking predicting a strong affinity between CDC25 and Pcbol. These molecular modules may interact with Pcbol to mediate knockdown effects on spermatogenesis dysfunction. Collectively, our findings not only confirmed that boule was indispensable for spermatogenesis and male fertility in a mollusk, but also highlighted the Pcbol-based male sterile technique (MST), which can be incorporated into precision pest management (PPM) strategies for sustainable control of P. canaliculata. Full article

Wildlife trafficking poses a severe threat to global biodiversity and ecosystem stability, necessitating robust forensic tools for tracing the origins of illegally traded taxa. In this study, we developed a method of single-nucleotide polymorphism (SNP)-based molecular markers to enable precise geographical traceability of four animal species native to China: the Tibetan macaque (Macaca thibetana), brown eared pheasant (Crossoptilon mantchuricum), blue eared pheasant (Crossoptilon auritum), and Chinese pangolin (Manis pentadactyla). We studied these four species because their DNA is characterized by distinct population genetic structure, they are subjected to illegal trafficking, and given their diverse evolutionary histories, this allowed us to assess the general applicability of our forensic genetic framework in reducing wildlife crime. Based on whole-genome resequencing data from 26 Tibetan macaques, 51 eared pheasants and 42 Chinese pangolins, we performed population genetic analyses to elucidate their genetic structure and identify population-specific loci. The results indicated that all samples from these four species showed clear genetic differentiation and distinct clustering, allowing us to design primers to facilitate PCR-based traceability. We also assessed the utility of mitochondrial DNA (mtDNA) for tracing Tibetan macaques and both species of eared pheasants. We found that traceability accuracy using mtDNA was lower than when using SNPs. Our research offers a SNP-based traceability framework that accurately determines the geographical origin of wildlife samples to the genetic population level, and this provides a powerful tool for combating illegal trade and aiding conservation efforts. Full article

Background: Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a fatal inflammatory disorder driven by M1 macrophages and the associated inflammatory cascade. Targeted drug delivery to these cells is a promising therapeutic strategy. Methods: L-arginine was conjugated to chitosan of different molecular weights. The resulting curcumin nanocrystals (Arg-CS-Cur) were characterized for conjugation efficiency, zeta potential, stability, and drug release profile. Cellular uptake mechanisms and mitochondrial targeting were investigated in lipopolysaccharide (LPS)-induced M1 macrophages using specific endocytic inhibitors and confocal microscopy. Results: Low-molecular-weight chitosan (MW 50 kDa) showed the highest L-Arg conjugation efficiency (22.31%). The optimized Arg-CS-Cur nanocrystals exhibited high zeta potential (± 47.5 mV), excellent stability, and a superior drug release. They were internalized by M1 macrophages more efficiently than unmodified CS-Cur or free curcumin (p < 0.05). Uptake occurred via clathrin-mediated endocytosis (p < 0.001) and was mediated by CAT-2, which was highly expressed in M1 macrophages (p < 0.001). Arg-CS-Cur specifically targeted the mitochondria, reducing ROS and NLRP3 expression, thus inhibiting the NLRP3 inflammasome pathway (p < 0.001). Conclusions: This L-arginine-modified chitosan-based nanodelivery system synergistically exploits CAT-2 and clathrin pathways to deliver curcumin to M1 macrophage mitochondria, inhibiting the NLRP3 inflammasome. This dual-targeted strategy offers a promising approach for treating ALI/ARDS. Full article

Background: Cancer patients are highly susceptible to microbial infections due to immune suppression, necessitating therapeutic strategies that integrate anticancer efficacy with effective antimicrobial intervention. Chalcone-derived nitrogen-fused heterocycles represent a promising platform for developing multi-target agents with relevance to antimicrobial drug delivery, particularly for localized infections. Methods: A series of chalcone-based pyrazoline-thiadiazole nitrogen-fused azole hybrids was synthesized via thiosemicarbohydrazide-functionalized intermediates and fully characterized. Antiproliferative activity was evaluated against MCF-7, HepG-2, HeLa, and HCT-116 cell lines, alongside selectivity toward WI-38 normal fibroblasts. Antibacterial, antibiofilm, and in vivo efficacy were assessed against methicillin-resistant Staphylococcus aureus (MRSA USA300) and Acinetobacter baumannii AB5057. Mechanistic investigations included cell-cycle analysis, apoptosis assays, ERK2, RIPK3, p53, BAX/Bcl-2 quantification, DNA gyrase inhibition, molecular docking, molecular dynamics simulations, and density functional theory calculations. Results: Compound 13 exhibited potent cytotoxicity, particularly against MCF-7 (IC₅₀ = 3.87 ± 0.2 µM), outperforming doxorubicin (IC₅₀ = 4.17 ± 0.2 µM), with high selectivity indices (SI = 10.7 for MCF-7). Mechanistically, compound 13 induced G₂/M arrest (40.16% vs. 14.15% control), increased apoptosis to 32.89%, up-regulated ERK2 (3.17-fold), RIPK3 (11.97-fold), and p53 (3.54-fold), and markedly increased the BAX/Bcl-2 ratio (~42-fold). Compounds 7 and 13 displayed bactericidal activity against MRSA and A. baumannii (MIC/MBC = 10 mg/mL), potent antibiofilm effects, and significant in vivo efficacy in an MRSA skin infection model. Compound 13 reduced bacterial load by ~5 log units, outperforming vancomycin. DNA gyrase inhibition (IC₅₀ = 17.10 ± 0.17 µM) and computational studies supported target engagement. Conclusions: Pyrazoline-thiadiazole-based nitrogen-fused azole hybrids, particularly compound 13, demonstrated quantifiable anticancer and antimicrobial efficacy with strong in vivo validation, supporting their potential as multi-target candidates relevant to antimicrobial drug delivery in infection-prone cancer patients. Full article

Background/Objectives: Among cotton species, Gossypium barbadense produces the strongest fibers. Examining cytoskeletal dynamics in single epidermal cells of G. barbadense ovules offers a direct approach to investigating fiber quality. Microtubules are major cytoskeletal components whose organization and dynamics are precisely regulated by microtubule-associated proteins (MAPs). However, information on the TPX2 family remains limited, and characterizing its features in G. barbadense is critical to clarifying the role of TPX2 family members in fiber strength formation. Methods: Using the Arabidopsis thaliana TPX2 sequence as a reference, 40, 49, 26, and 26 TPX2 family members were identified in the genomes of G. barbadense, Gossypium hirsutum, Gossypium arboreum, and Gossypium raimondii, respectively. We further analyzed the expression pattern of GbTPX2-35 and validated its function via virus-induced gene silencing (VIGS). Results: In G. barbadense, GbTPX2-35 (Gbar_D11G59825.1) was significantly upregulated in fiber samples of the parental lines at 25 days post-anthesis, and this expression pattern was further validated in G. barbadense lines with extreme fiber strength phenotypes. Next, VIGS-mediated silencing of GbTPX2-35 downregulated the transcript levels of cellulose synthase and microtubule-related protein genes, a finding further validated by mature fiber strength phenotypic data. Conclusions: This study preliminarily validated a pathway in which GbTPX2-35 regulates fiber strength by coordinating cellulose biosynthesis with microtubule cytoskeleton dynamics, providing valuable candidate genes and theoretical support for molecular breeding of high-strength cotton fibers. Full article

Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics—including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies—have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70–80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology. Full article

HIV latency, driven by a complex interplay of host factors, remains a key barrier to viral clearance. Current latency-reversing agents (LRAs) demonstrate limited efficacy and specificity, and none have been approved for clinical use. Although natural products have shown promise as LRAs, the therapeutic potential of fungal metabolites remains underexplored. Candida albicans, a prevalent human commensal and opportunistic pathogen, produces diverse secondary metabolites that can influence host pathways, affecting latency dynamics. This study aimed to investigate the latency-modulating potential of secondary metabolites of C. albicans using an integrative network pharmacology and computational pipeline. C. albicans secondary metabolites were retrieved from the literature, screened for drug-likeness, and mapped to human targets and biological pathways annotated in HIV latency. Key metabolites, hub genes, and pathways were systematically characterized through network and computational analyses. Six drug-like candidates, identified from 185 absorption, distribution, metabolism, excretion, and toxicity (ADMET)-screened metabolites, collectively mapped to 369 human genes with a 6.5% overlap in HIV latency (176 shared and 20 hub genes). These overlapping genes were significantly enriched for signal transduction, membrane localization, and adaptive responses to chemical stimuli. Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed oncogenic diseases (non-small cell lung, pancreatic, and prostate cancers) and latency-associated cascades, including PD-L1/PD-1, HIF-1, Ras, PI3K-Akt, calcium, and cAMP signaling. Six hub targets (MAPK1, PIK3CA, MAPK3, EGFR, MTOR, and AKT1) were consistently annotated within the top 30 KEGG pathways and displayed strong binding affinities for MET 15 and MET 119. Molecular dynamics (MD) simulations confirmed favorable binding free energies (BFEs) and stable conformational dynamics for the top-ranked metabolite MET 15. C. albicans secondary metabolites preferentially target oncogenic signaling networks central to HIV latency maintenance, notably PI3K/AKT/MTOR and MAPK/ERK, which regulate cell survival, metabolic homeostasis, and viral transcriptional repression. MET 15 is a top-ranked candidate metabolite for HIV latency-reversing therapeutics and warrants experimental validation in established latency models. Full article

Background: Diabetic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, and impaired angiogenesis. Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential, and their therapeutic effects and optimization strategies for diabetic wounds warrant further exploration. Objective: This study aimed to improve the therapeutic efficacy of BMSCs in diabetic wound healing via chrysin pretreatment, as well as to evaluate the healing capacity and molecular mechanisms of the derived chrysin-pretreated BMSC-conditioned medium (Chrysin-CM). Methods: BMSCs were pretreated with 1 μM chrysin for 48 h to generate Chrysin-CM. The therapeutic effects were evaluated in vitro by analyzing the proliferation, migration, and matrix synthesis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs) under high-glucose (HG) conditions. In vivo, a diabetic mouse model with full-thickness excisional wounds was established and treated topically with Chrysin-CM. Transcriptomic sequencing and immune infiltration analysis of wound tissues were performed on day 14 in order to investigate the underlying mechanisms. Results: Chrysin pretreatment significantly enhanced the functional activity of BMSCs, accompanied by increased proliferative capacity and accelerated cell cycle progression. In vitro, Chrysin-CM demonstrated superior efficacy, robustly protecting HUVECs and HSFs from HG-induced dysfunction. In vivo, Chrysin-CM significantly accelerated wound closure, re-epithelialization, and neovascularization compared to the control. Mechanistically, RNA sequencing (RNA-seq) revealed that Chrysin-CM induced multi-level remodeling, characterized by reduced inflammatory gene expression and immune cell infiltration, along with the upregulation of regenerative genes and alternative splicing events. Conclusions: Chrysin successfully improved the therapeutic efficacy of the BMSC secretome in wound healing. Chrysin-CM effectively accelerated diabetic wound healing by actively resolving chronic inflammation and promoting angiogenesis and structural remodeling, thus providing a potential strategy for stem cell-based cell-free treatment for chronic diabetic wounds. Full article

Tuber encompasses ectomycorrhizal fungi (EMF) of significant ecological and economic importance. This study reports the first controlled synthesis of ectomycorrhizae between the near-threatened species T. umbilicatum and Quercus glauca, confirmed through molecular analysis and detailed morphological characterization. Colonization dynamics, assessed over eight months, revealed substantial physiological benefits for the host. At six months post-inoculation, seedling height and above-ground biomass increased by 20.8% and 27.1%, respectively; these increments persisted to eight months, with above-ground biomass remaining 16.9% higher and below-ground biomass elevated by 25.4%. Concomitantly, the photosynthetic performance was markedly improved: a net photosynthetic rate (A) rose by 136.8% and stomatal conductance (g_s) by 36.5% at six months. Available phosphorus (AP) in the mycorrhizosphere was concurrently enhanced, exhibiting a 10.9% increment at eight months. These results underscore the agronomic and conservation utility of T. umbilicatum inoculation for Q. glauca and provide a critically experimental foundation for the ex situ preservation and sustainable truffle cultivation of this threatened fungal taxon. Full article

Natural product research has experienced substantial growth over the past two decades, driven by a renewed appreciation for the structural complexity and biological relevance of compounds derived from nature. Technological advances in separation science, spectroscopic characterization, and high-sensitivity bioassays have collectively restored natural products to a position of prominence in modern drug discovery efforts. Nature remains the most prolific source of bioactive molecular diversity, drawing from microorganisms, plants, and marine life to offer a vast reservoir of structurally novel scaffolds whose pharmacological potential remains largely unexplored. Effective extraction and isolation remain foundational to natural product research, as the quality and purity of isolated compounds directly govern the reliability of downstream biological evaluation. Recent years have witnessed remarkable innovation in this space, spanning green and designer solvent systems, pressurized and ultrasound-assisted extraction platforms, supercritical fluid techniques, and integrated purification workflows that dramatically reduce processing time while improving compound recovery and analytical throughput. Particularly noteworthy is the growing application of artificial intelligence and machine learning tools for solvent selection, extraction optimization, and metabolite dereplication, which in combination with advanced phase-separation strategies and informatic platforms have substantially expanded the scope of detectable and characterizable metabolites within complex biological matrices. This review summarizes recent progress in extraction and isolation methodologies supporting natural product research, with particular emphasis on combinatorial extraction strategies, next-generation solvent systems, and AI-driven applications that have collectively improved operational efficiency, selectivity, and analytical output over the past five years. Full article

Background: Alzheimer’s disease (AD) remains an incurable disorder with severe clinical consequences. The type 3 diabetes hypothesis posits that AD may constitute a neuroendocrine disorder driven by disrupted insulin and insulin-like growth factor signaling. Amyloid pathogenesis in AD is characterized by the accumulation of beta-amyloid (Aβ) monomers, their subsequent oligomerization, and amyloid deposition. One of the causes of Aβ accumulation is disruption of amyloid precursor protein (APP) processing due to imbalance in ADAM10 and BACE1 expression. In recent years, increasing attention has been devoted to investigating the role of environmental factors in AD pathogenesis. The receptor for advanced glycation end products (RAGE) serves as a key molecular link between environmental exposure and neuroinflammatory pathology. Formaldehyde (FA) is one of the most widespread environmental pollutants. Its involvement in amyloid plaque formation has been previously reported; however, the molecular mechanisms underlying this process remain insufficiently understood. Moreover, most available data are based on prolonged FA exposure, whereas industrial FA emissions are often short-term. The objective of this study was to determine whether brief intranasal administration of FA, modeling episodic industrial pollution, induces RAGE-mediated neuroinflammation and amyloid deposition in CD1 mice. Methods: Mice received intranasal FA at environmentally relevant 0.02 mg/day or 0.2 mg/day doses for seven days; an additional group was co-treated with insulin. Cognitive function was assessed using passive avoidance (PA) and radial arm maze (RAM) tests, and synaptic plasticity was evaluated by electrophysiology. Hippocampal tissue was analyzed for RAGE expression, ADAM10/BACE1 gene balance, Aβ42 monomer levels, and amyloid deposits using optimized Thioflavin-S (Th-S) staining. Results: We observed cognitive decline in mice receiving intranasal FA administration. Elevated blood glucose levels were also observed following intranasal FA exposure. Sustained impairment of glucose metabolism led to overexpression of the RAGE in the hippocampus. There was also an imbalance of ADAM10 and BACE1 expression in the hippocampus. This was caused by overexpression of RAGE, as the enhanced interaction of the ligand and RAGE is a key factor disrupting this balance. Finally, Th-S staining confirmed amyloid deposition in mice subjected to intranasal FA exposure. Conclusions: This study provides new insights into the RAGE-mediated mechanisms by which FA contributes to the pathogenesis of AD. Full article