Search Results (11,885)

Background/Objectives: Germ cell tumors (GCTs) are thought to arise from primordial germ cells that fail to appropriately differentiate and instead retain pluripotency programs. PRDM14 is a key regulator of pluripotency and primordial germ cell specification and is aberrantly expressed in multiple GCT subtypes. However, the role of PRDM14 in GCT malignancy remains unclear. In this study, we investigated whether PRDM14 functions in GCTs through CBFA2T2, a transcriptional corepressor previously identified as a PRDM14-interacting partner in pluripotent stem cells and developmental models. Methods: To determine the presence and level of PRDM14 and CBFA2T2 in GCT, a panel of GCT lines were assessed for RNA and protein expression and interaction. Then, to better understand the biological effects of PRDM14 and CBFA2T2 within GCTs, PRDM14 and CBFA2T2 knockdowns were employed. Results: We show that PRDM14 and CBFA2T2 are expressed across GCT cell lines, colocalize predominantly in the nucleus, and cooperate as a complex in GCT cell lines. Knockdown of either PRDM14 or CBFA2T2 resulted in reduced expression of key pluripotency genes and a significant impairment of cell proliferation, indicating a shared role in maintaining an undifferentiated, proliferative state. Transcriptomic analysis following PRDM14 or CBFA2T2 depletion revealed extensive overlap in differentially expressed genes and convergent alterations in developmental and metabolic signaling pathways. Conclusions: Together, these findings suggest that PRDM14 and CBFA2T2 form a functional complex that sustains pluripotency and proliferation in GCT cells. This supports a model in which persistence of germline regulatory mechanisms contributes to GCT malignancy, highlighting this interaction as a novel component of GCT biology. Full article

Introduction: Chronic kidney disease (CKD) involves a progressive loss of renal function and is characterized by chronic oxidative stress and kidney fibrosis. Tetrahydrocurcumin (THCu), a metabolite of curcumin, may possess antioxidant benefits in CKD. This study evaluated the transcriptomic changes and therapeutic potential of THCu against kidney damage and fibrosis in the 5/6 nephrectomy rat CKD model. Methods: Adult female Sprague–Dawley rats were randomized into CKD groups and three THCu doses were tested (100, 300 and 500 mg/kg). A liposomal formulation of THCu was given twice daily via oral gavage for 4 weeks. Serum creatinine and proteinuria were measured, and kidney fibrosis was assessed on histology. Kidney lysates were processed for total RNA sequencing to analyze differential gene expression in the experimental groups. The data were screened for outliers prior to ANOVA and correlation analyses. Results: In the untreated CKD group, serum creatinine and proteinuria were increased compared to control animals. Transcriptomic profiling revealed that untreated CKD animals exhibited marked upregulation across three key gene categories: immune cell activation, kidney injury and fibrosis, and inflammation and oxidative stress. THCu treatment mitigated these pathways by which there was downregulation of markers of immune cell activation as well as the kidney injury marker Kim1, while the fibrosis markers Col1a1 and Col3a1 were decreased to expression levels similar to non-CKD control animals. Furthermore, the highest dose of THCu at 500 mg/kg triggered a cellular detoxification and metabolic clearance response, with highly significant upregulation of Abcb11 and Gls2. Antioxidant benefit was evidenced by upregulation of Gpx1 in the high-dose THCu group compared to the untreated CKD group. Pathway enrichment analysis demonstrated that the high-dose THCu group restored key metabolic and signaling pathways disrupted in renal fibrosis, including small and organic solute metabolism, fatty acid oxidation, lipid biosynthesis, and peptide hormone response. Furthermore, the treatment upregulated essential anion and organic solute transport functions. Proteinuria was reduced with THCu therapy; however, serum creatinine and urine creatinine clearance were not significantly modified in comparison to untreated CKD rats. Conclusions: Oral THCu therapy demonstrated promising transcriptional changes in antioxidant and anti-fibrotic pathways in a rat CKD model. Confirmatory protein-level studies are needed to clarify benefits on kidney function. Full article

Cartilage engineering is a new therapeutic approach in regenerative medicine. This study explored the chondrogenic potential of human dental pulp stem/stromal cells (hDPSCs) and adipose-derived stem/stromal cells (hAD-MSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold in relation to the phenotype of primary chondrocytes on PLCL. The effects of PLCL scaffold on the biological features of hDPSC, hAD-MSC, and their chondrogenic differentiation and chondrocytes biology were evaluated via flow cytometry, immunochemistry, biochemistry, and RT‒PCR. The results demonstrated that PLCL supported hDPSC, hAD-MSC, and chondrocyte viability and cellular attachment. The chondrogenic potential of hDPSCs and hAD-MSCs on PLCL scaffold was evidenced by the mRNA expression of the cartilage-specific genes. Collagen type II (Col II) and aggrecan (Acan) gene expression and their proteins significantly increased in chondrogenically differentiated hDPSCs and hAD-MSCs on PLCL compared with undifferentiated stem/stromal cells on PLCL. The phenotype of differentiated hDPSCs and hAD-MSCs was comparable to primary chondrocytes grown on PLCL. The results of this study showed that PLCL scaffold promoted chondrogenic differentiation of hAD-MSCs and hDPSCs toward chondrocytes with phenotypic similarities to native chondrocytes. The PLCL scaffold composition has a positive effect on hDPSC, hAD-MSC, and chondrocyte behavior, chondrogenic gene expression, and matrix protein synthesis. Full article

Psoriasis is a chronic inflammatory autoimmune skin disease for which no standardised and reliable molecular biomarkers of disease course or activity are currently available. Here, we aimed to identify serum biomarkers of psoriasis. Serum samples from 40 patients with psoriasis and 40 healthy volunteers were analysed using ELISA and Proximity Extension Assay proteomics. ELISA revealed significantly increased serum levels of AGO2 and APOA1 in psoriatic patients versus controls, with a strong association between APOA1 and psoriasis (OR = 20.72, 95% CI of 4.57–93.87, p = 0.000137). Targeted serum proteomics additionally identified 35 differentially expressed proteins, including well-known psoriasis drivers (e.g., top upregulated IL17A and SERPINB4). The most downregulated was adrenomedullin (ADM, FC = −10.12). For 14 altered proteins, no previous direct associations with psoriasis were reported. Among them, DEFB103A_DEFB103B and DSG3 showed the best discrimination between psoriasis and control samples, while SERPINB4 correlated with psoriasis severity. APOA1, DEFB103A_DEFB103B, and DSG3 emerge as novel candidate circulating psoriasis biomarkers, and SERPINB4 as a biomarker of psoriasis severity. The functional role of DSG3 and other newly identified proteins (ACRV1, HAO1, ADH4, GPD1, GFER, PTGES2, DSG3, AFAP1L1, GALNT3, RASGRP2, MAP2K6, LXN, NBEAL2, and VPS54) in psoriasis requires further studies. Full article

The voltage-dependent anion channel (VDAC) is the primary conduit for ion and metabolite transport across the mitochondrial outer membrane. Positioned at the interface between the cytosol and the mitochondrial compartment, VDAC is uniquely accessible to proteins on both sides of the membrane, making it an interaction hub whose biophysical properties and signaling functions are shaped by protein complexation in addition to its intrinsic pore specialization. Mammals express three isoforms—VDAC1, VDAC2, and VDAC3—sharing a conserved β-barrel scaffold with about 70% identity. However, minor differences in the sequence lead to drastic changes in VDAC isoform affinity with other proteins. Here, we review the molecular mechanisms and physiological consequences of VDAC complexation with a set of well-characterized partners: hexokinase, dimeric tubulin, α-synuclein, mitochondria-associated membrane proteins, B-cell lymphoma 2 (BCL-2) family proteins, and the Translocase of the Outer Membrane (TOM) protein import complex. For each complex, we evaluate the available structural, biophysical, and genetic evidence for isoform specificity, highlight where mechanistic understanding is most advanced, and identify open questions. A consistent principle emerges across all complexes: functionally nonredundant isoform contributions are primarily governed by differential partner affinity and complexation, rather than by differences in pore architecture alone. This framework has direct implications for mitochondria-associated pathologies, including cancer, cardiovascular disease, and neurodegeneration, as well as for the rational design of VDAC-targeting therapeutics. Full article

Aspartame is a widely used artificial sweetener, but its possible relationship with rheumatoid arthritis (RA) remains insufficiently understood. This study aimed to explore, rather than prove, potential molecular links between aspartame-related targets and RA-associated gene networks. Three public RA transcriptomic datasets (GSE55235, GSE55457, and GSE77298) from the Gene Expression Omnibus (GEO) database were integrated as discovery/training data. Because these datasets included different tissue origins, batch correction was used to reduce dataset-level technical variation, whereas tissue-origin-related biological variation was not assumed to be fully removable. After differential expression analysis, RA-associated differentially expressed genes (DEGs) were identified. The single-cell dataset GSE200815 was used for cell annotation and cellular expression visualization; because its comparator group consists of psoriatic arthritis (PsA) samples rather than healthy controls, single-cell results were interpreted as RA-vs-PsA observations and were not treated as disease-versus-healthy-control evidence. Potential targets of aspartame were retrieved from ChEMBL, SwissTargetPrediction, and the Similarity Ensemble Approach (SEA), and were intersected with RA-related DEGs to construct an aspartame-gene-RA regulatory network. Diagnostic models were developed using 113 machine-learning algorithm combinations to determine an optimal multigene model and its core genes. HLA-DRB1 was selected for exploratory scTenifoldKnk-based virtual knockout mainly because it was included in the optimal model and has a well-established role in RA immunogenetics; the single-cell analysis was used only to describe cellular distribution in the RA/PsA dataset. Molecular docking was then used to evaluate the possible interaction between aspartame and HLA-DRB1. Forty-four intersected genes linked the predicted aspartame targets with RA DEGs. The random forest plus partial least-squares generalized linear model (RF + plsRglm) identified 16 core genes. Network-level interpretation indicated that these genes were distributed across immune/antigen-processing, inflammatory-signaling, protease/extracellular-matrix-remodeling, adhesion, metabolic, and proliferation-related modules; therefore, HLA-DRB1 was treated as a prioritized immune-module candidate rather than as the sole driver of the network. Following virtual knockout of HLA-DRB1, affected genes were enriched in extracellular matrix organization, extracellular structure organization, extracellular matrix, collagen trimer, extracellular matrix structural constituent, and collagen binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included integrin signaling, focal adhesion, proteoglycans in cancer, cytoskeleton in muscle, and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling. Molecular docking showed a minimum binding energy of −6.7 kcal/mol, which was more negative than the preset stability criterion of −5.0 kcal/mol, and the docking pose suggested contacts around ARG-146. This integrative analysis suggests a hypothesis-generating association between aspartame-related predicted targets and RA-relevant molecular networks involving HLA-DRB1 and other core genes. The findings do not establish causality and require experimental, epidemiological, biophysical, and tissue-stratified validation before any causal or clinical inference can be made. Full article

Leishmaniasis, a neglected tropical disease endemic to 98 countries, affects more than 300 million people worldwide. The disease is transmitted through the bite of infected female phlebotomine sand flies harboring Leishmania parasites. Although infection initiates at the cutaneous inoculation site, Leishmania species exhibit distinct tissue tropisms, resulting in three primary clinical manifestations: cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). The initial stage of infection involves the engulfment of metacyclic promastigotes (MPs) by host phagocytes, a process mediated by early interactions between the MP flagellum and the host cell surface. This study investigates how species-specific MP-flagellar proteomic profiles dictate unique interactions with host cell populations, thereby driving divergent pathogenic outcomes. To address this, we conducted a comparative quantitative proteomic analysis of flagella from Leishmania species representing each clinical form. Our analysis revealed distinct flagellar proteomic signatures that differentiate the VL-causing species, L. infantum, from others. Notably, we identified five virulence factor families that were differentially expressed: amastins, cysteine peptidases, heat shock proteins, promastigote surface antigens, and leishmanolysins. These findings link flagellar surface composition to species-specific pathogenicity, providing molecular insights into early infection dynamics and identifying potential antigenic targets for developing species-specific vaccines and therapeutics. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which senescence-associated secretory phenotype (SASP)-related transcriptional programs may contribute to synovial inflammation and fibroblast activation. This study aimed to integrate bulk transcriptomic cohorts with the gene-expression component of a single-nucleus multimodal dataset to identify reproducible SASP-related candidate biomarkers and prioritize fibroblast-associated signals in RA. Methods: SASP-score correlation analysis, differential expression analysis, cross-cohort evaluation, logistic regression, gene set enrichment analysis, single-nucleus transcriptomic characterization, predicted regulatory network analysis, and RT-qPCR assessment were performed. GSE89408 was used as the discovery bulk transcriptomic cohort, GSE77298 as the external evaluation cohort, and GSE243917 as the single-nucleus gene-expression dataset. Results: Fibroblasts showed relatively high SASP-related transcriptional scores within the RA single-nucleus dataset. The cross-cohort evaluation retained RCAN1, IRF1, CFB, and TIMP1 as reproducibly elevated candidates. Among all 15 non-empty panels derived from these four genes, the RCAN1/IRF1/CFB panel achieved the highest five-fold cross-validated AUC in GSE89408 and tied for the highest external AUC in GSE77298. Adding TIMP1 did not improve the external AUC or the 95% confidence interval. Among the retained genes, CFB showed the strongest fibroblast-associated expression pattern and SASP-score correlation. The RT-qPCR analysis provided preliminary mRNA-level support for the increased expression of RCAN1, IRF1, and CFB in the RA-related cell samples. Conclusions: RCAN1, IRF1, and CFB form a reproducible SASP-related candidate panel in RA, with CFB prioritized as a fibroblast-associated marker. Further protein-level, functional, and controlled single-cell validation studies are required. Full article

Objectives: Autologous bone grafting remains the gold standard for maxillofacial reconstruction but is limited by tissue scarcity and donor-site morbidity. Consequently, substitutes like bioactive glass (BG), beta-tricalcium phosphate (β-TCP), and deproteinized bovine bone (DBB) are widely used. However, comprehensive mechanistic comparisons among them remain scarce. Materials and Methods: We systematically evaluated these substitutes under standardized in vitro conditions to compare their physicochemical transformations, degradation profiles, biological performances, and underlying osteogenic molecular pathways. Results: In simulated body fluid, BG underwent rapid hydroxyapatite mineralization, whereas the highly porous DBB and dense β-TCP remained structurally inert. Degradation assays revealed BG exhibited the fastest mass loss and ion release, β-TCP showed intermediate degradation, and DBB maintained high in vitro structural stability. Biologically, all materials showed favorable cytocompatibility and comparable angiogenic potential. However, BG demonstrated significant antibacterial activity (E. coli, S. aureus) and a strong potential to enhance osteogenic differentiation, significantly upregulating the protein-level expression of RUNX2 and OCN, alongside the transcriptional upregulation of Bmp2, Runx2, and Ocn. Transcriptomic profiling and pharmacological validation suggest that the enhanced osteogenic performance of BG might be associated with specific regulatory pathways, supporting the hypothesis that the suppression of NF-κB-mediated inflammation and the activation of the ECM-Integrin-FAK mechanotransduction axis play potential roles. Conclusions: BG offers high bioactivity and notable potential to enhance osteogenic differentiation in vitro but degrades rapidly. DBB ensures structural durability without intrinsic osteoinductivity, and β-TCP provides a balanced, intermediate profile. These in vitro mechanistic insights provide a theoretical foundation for future in vivo evaluations and designing next-generation bone scaffolds. Full article

Organophosphate pesticides (OPPs) are widely used in agriculture and are associated with metabolic dysregulation and cognitive impairment. Emerging evidence links OPP exposure to insulin resistance and diabetes mellitus, a condition known to negatively impact brain function. Prior investigations in our laboratory identified significant dysregulation of arachidonic acid (AA) metabolites associated with the endocannabinoid system in both diabetic patients and those with chronic OPP exposure, with a marked reduction in serum AA levels in the OPP-exposed cohort. This study investigates the impact of OPP exposure and pre-diabetes on the hippocampal proteome and whether AA supplementation can mitigate the resulting neuronal proteomic alterations. Using a controlled rat model, high-resolution LC-MS/MS-based proteomics identified differentially expressed proteins across experimental groups. Both OPP exposure and pre-diabetes were associated with increased cognitive impairment and were associated with overlapping disruptions in pathways related to insulin resistance, mitochondrial function, synaptic plasticity, and neuronal development. AA supplementation mitigated cognitive decline and stabilized synaptic and metabolic proteins; however, residual pathway dysregulation highlights the complexity of these stressors. Our results reveal novel molecular intersections between environmental and metabolic drivers of cognitive impairment, establishing a rationale for further research into inexpensive, protective dietary interventions. Full article

Chronic Kidney Disease of Unknown Etiology (CKDu) is an ongoing global health concern, particularly affecting agricultural communities in equatorial regions. Unlike traditional chronic kidney disease (CKD), CKDu occurs without common risk factors such as diabetes, hypertension, or kidney stones. Its etiology remains poorly understood, with environmental exposures, occupational hazards, and genetic susceptibility proposed as contributing factors. Omic technologies including genomics, transcriptomics, proteomics, metabolomics, and exposomics offer promising avenues to elucidate CKDu pathogenesis by enabling comprehensive molecular profiling and identification of biomarkers. Recent genomic studies have explored single nucleotide polymorphisms (SNPs) linked to kidney injury susceptibility, while transcriptomic analyses have identified differential expression of genes involved in oxidative stress and tubular injury pathways. Proteomic investigations have revealed candidate urinary biomarkers such as heat shock proteins and inflammatory mediators, and metabolomic profiling has highlighted alterations in amino acid and energy metabolism in affected individuals. Exposomic approaches are beginning to characterize cumulative chemical exposures, including pesticides and heavy metals, in endemic regions. This narrative review synthesizes current evidence on the application of omics approaches in CKDu research, highlights knowledge gaps, and proposes future directions for integrating multi-omics studies with machine learning and artificial intelligence approaches. Advancing omics-based investigations may provide critical insights into disease mechanisms, improve diagnostic precision, and inform targeted interventions for vulnerable populations. Full article

Background: Spinal cord injury (SCI) triggers secondary injury processes involving neuroinflammation and systemic immune remodeling. The endocannabinoid system (ECS) has been implicated in neuroimmune regulation, but its transcriptional relationship with immune remodeling and its translational relevance in human SCI blood remain incompletely defined. Methods: A cross-species discovery–validation–translation framework was applied using a rat spinal cord discovery cohort (GSE45006), an independent mouse validation cohort (GSE171441), and a human peripheral white blood cell cohort (GSE151371). Analyses included differential expression profiling, ECS-focused assessment, cross-species comparison, immune-cell signature scoring, ECS–immune correlation analysis, receiver operating characteristic (ROC) analysis, LASSO-based biomarker prioritization, network analysis, disease enrichment, drug–gene interaction querying, and transcription factor/microRNA regulatory annotation. Results: ECS-related transcriptional remodeling was identified across rodent and human datasets in a compartment-dependent manner. In human SCI blood, CNR2, PTGS2, and DAGLB were significantly altered and showed biomarker-prioritization potential. Human SCI blood also showed innate immune enrichment, adaptive immune depletion, and significant ECS–immune correlations. The integrated 28-gene SCI–ECS immune panel formed a functionally coherent protein–protein interaction (PPI) network enriched in immune-response pathways. Disease enrichment supported an immune/inflammatory pathological context, whereas DGIdb identified hypothesis-generating drug–gene relationships involving ECS-related targets. ChEA 2022 revealed nominal transcription factor annotations that did not survive multiple-testing correction, and miRNet identified database-derived miRNA regulators of panel genes. In a secondary sensitivity analysis, the combined ECS signature also retained discriminatory performance against non-CNS trauma controls, suggesting that the observed transcriptional pattern was not fully attributable to generalized trauma-related responses. Conclusions: This study proposes an ECS-associated immune remodeling signature in SCI with translational biomarker-prioritization and pharmacologic target-annotation context in human peripheral blood. These findings are exploratory and require prospective and functional validation. Full article

Tropical maize often exhibits photoperiod sensitivity, which limits its adaptation to temperate regions. Understanding its proteomic dynamics under long-day conditions is therefore crucial for germplasm improvement. This study employed a Tandem Mass Tag (TMT)-based proteomic approach to investigate stage-specific protein expression patterns in the tropical maize inbred line QR273 under long-day conditions (16 h light/8 h dark). Seeds were cultivated in climate chambers, and leaves were collected at the four-leaf (P4) and nine-leaf (P9) stages. A total of 2881 differentially expressed proteins (DEPs) were quantified between the P4 and P9 stages, among which only 7 were upregulated and 2874 were downregulated at the P9 stage. Gene Ontology (GO) enrichment analysis revealed that these DEPs were significantly enriched in processes related to proteolysis, membrane components, and ATP binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the enrichment of DEPs in amino acid biosynthesis, secondary metabolite biosynthesis, and aminoacyl-tRNA biosynthesis pathways. Protein–protein interaction (PPI) network analysis identified 60S ribosomal protein L12, adenosine 5′-phosphosulfate reductase, and RuvB helicase as core hub proteins. Based on functional annotation of representative DEPs, the DEPs were classified into four categories: 9 proteins related to storage material protection, 14 proteins related to protein modification, 12 proteins related to photosynthesis, and 25 proteins with other biological functions. Comparative analysis demonstrated a decrease in storage material protection, protein modification, and photosynthetic capacity at the P9 stage relative to the P4 stage. These findings provide insights into the proteomic dynamics underlying tropical maize development under long-day conditions and offer a theoretical basis for genetic improvement of tropical maize germplasm. Notably, inferences regarding nutrient reallocation based on DEP downregulation are derived solely from proteomic data and require further experimental validation. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury and remains a widely used model of xenobiotic-induced hepatotoxicity. Oxidative stress, mitochondrial dysfunction, and ferroptosis are key events in APAP-mediated liver damage. In this study, we investigated whether L-menthol pretreatment protects against APAP-induced acute liver injury and explored the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were pretreated with L-menthol (100 mg/kg/day) for 7 days before APAP challenge (300 mg/kg). L-menthol markedly attenuated hepatic necrosis, inflammatory infiltration, and hepatocyte injury, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, suppressed IL-1β, IL-6, and TNF-α production, restored hepatic glutathione and superoxide dismutase levels, and decreased malondialdehyde accumulation. Transcriptomic analysis revealed significant enrichment of differentially expressed genes in reactive oxygen species- and ferroptosis-related pathways. In APAP-challenged HepG2 cells, L-menthol improved cell viability, preserved mitochondrial ultrastructure, reduced ferrous iron accumulation, was associated with upregulation of Keap1/Nrf2/HO-1/NQO1 pathway-related proteins, and restored GPX4 expression. Collectively, these findings indicate that L-menthol pretreatment attenuates APAP-induced hepatotoxicity, possibly through enhancement of antioxidant defenses and attenuation of ferroptosis-associated changes, supporting its potential as a preventive hepatoprotective small molecule against xenobiotic-induced liver injury. Full article

Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and developmental regulation, JH signaling pathways have also been implicated in carbohydrate and lipid metabolism. In the present study, we investigated the effects of two JH analogs, pyriproxyfen and hydroprene, on the migratory locust, Locusta migratoria, with particular emphasis on lipid metabolic regulation and the function of midgut-enriched fatty acid-binding protein gene (Mg-FABP). Bioassays were performed to evaluate insecticidal activity, and transcriptomic analyses were conducted to identify differentially expressed genes associated with endocrine signaling and lipid metabolism. Functional characterization of Mg-FABP was further performed using RNA interference (RNAi) and Oil Red O staining assays. In addition, the tertiary structure of LmMg-FABP was predicted using AlphaFold 3, and molecular docking analyses were carried out to investigate its interactions with fatty acid ligands. Both pyriproxyfen and hydroprene caused approximately 70% mortality in locust nymphs and induced significant transcriptional changes in pathways related to hormone signaling and lipid metabolism. Transcriptomic analysis revealed pronounced downregulation of Mg-FABP following JH analog exposure. RNAi-mediated silencing of Mg-FABP significantly reduced lipid droplet accumulation in the fat body, indicating that Mg-FABP plays an essential role in lipid transport and metabolic homeostasis in L. migratoria. Structural analyses further demonstrated that LmMg-FABP possesses a conserved tertiary structure highly similar to FABP homologs from other insect species. Molecular docking identified key amino acid residues involved in fatty acid binding and suggested that hydrophobic interactions are critical for ligand stabilization within the binding cavity. Collectively, our findings demonstrate that pyriproxyfen and hydroprene disrupt insect development not only through endocrine imbalance but also through perturbation of Mg-FABP-associated lipid metabolic pathways. This study provides new mechanistic insight into the coordinated interaction between hormonal signaling and lipid metabolism during JH analog exposure and identifies FABP-mediated lipid transport as a potential molecular target for the development of more selective insect growth regulators. Full article