Search Results (1,162)

Yield losses due to water-deficit (WD) conditions, especially during the reproductive stages of plant development, pose a significant threat to global canola (Brassica napus L.) production. Therefore, it is critical to investigate traits contributing to improved productivity under increased WD conditions. Here we present phenotypic, physiological and transcriptomic changes in response to WD across contrasting canola accessions exhibiting variation in drought resistance-related traits. WD significantly reduced shoot biomass, plant height, harvest index, leaf water content, photosynthetic CO₂ assimilation rate, intrinsic water-use efficiency and carbon isotope discrimination. WD caused 49 to 100% of the seed yield reduction: the minimum seed yield reduction (49.66%) was observed in a doubled-haploid (DH) line, 06-5101.137, while the maximum yield reduction (94.1 to 100%) occurred in the late-flowering DH lines (06.5101.088, 06-5101.306). Seed yield showed a positive correlation (r = 0.35 to 0.97) with shoot biomass, plant height, harvest index, leaf water content, photosynthetic CO₂ assimilation rate, intrinsic water use efficiency and carbon isotope discrimination. However, it showed negative correlations with days to flower, specific leaf weight, root length and root biomass (r = −0.08 to −0.80) across water treatments. The leaf transcriptome analysis of the two parental lines of DH population that exhibit variation for effective water use under well-watered and water-deficient conditions revealed different categories of differentially expressed genes (DEGs): WD-responsive DEGs in BC1329 parental line (1116) and BC9102 (1205) with 754 and 853 DEGs unique to BC1329 and BC9102, respectively, WD-responsive DEGs (906), genotype-dependent DEGs (8465) and genotype × treatment interaction DEGs (353). DEG annotations revealed that the WD-treatment-affected genes were involved in stress responses and growth and development. We further located 235 DEGs within the QTL regions underlying agronomic and physiological performance. Our study provides a conceptual framework for the morphological, physiological and molecular determinants involved in water-use efficiency. Seedlings’ traits with high heritability values, such as shoot biomass, leaf weight, leaf water content and Δ¹³C, serve as proxies for trait-based selection for improved seed yield under both water-limited and non-water-limited conditions. Full article

Introduction: The clinical translation of biomaterial-based strategies for ear reconstruction remains limited by several challenges, including scaffold design, selection of an optimal cell source, and stability of the new cartilage tissue. Most recent studies still rely on animal-derived cells and fail to demonstrate the long-term maintenance of the chondrogenic phenotype. Methods: In this study, we developed an off-the-shelf poly(lactide-b-ethylene glycol) (PLA-PEG) scaffold combined with clinical-grade alginate (Alg) and cellularized with human nasal chondrocytes for auricular cartilage engineering. Cellularized constructs were evaluated using histological and immunofluorescence analyses to assess extracellular matrix production and quality. In parallel, constructs retrieved after 12 weeks of in vivo implantation were mechanically characterized using a UniVert CellScale testing system to determine variations in compressive strength. Finally, the chondrogenic maturation of the new tissue was evaluated through bulk RNA transcriptomic profiling. Results: Histological, immunofluorescence, and transcriptomic analyses demonstrated robust cartilage matrix deposition with improved compressive properties and high expression of chondrogenic markers, such as ACAN, PRG4, and COL2A1. Furthermore, positive staining for the human-specific Ku80 antibody confirmed the presence of cells of human origin in the newly formed tissue after implantation. Conclusions: Overall, this study provides evidence that the combination of a PLA-PEG + Alg scaffold with human nasal septal chondrocytes represents a promising strategy for future reconstructive applications in auricular tissue engineering. Full article

Stem diameter is an important agronomic trait determining plant architecture, lodging resistance and yield formation, yet its cytological and molecular mechanisms in the major cucurbit crop Luffa remain largely unclear. Herein, two Luffa inbred lines, S1174 (Luffa acutangula, thin stem) and P93075 (Luffa cylindrica, thick stem), were analyzed. Dynamic phenotyping uncovered a sigmoidal growth pattern with three key developmental stages: initiation (0 d), rapid growth (6 d), and maturation (20 d), during which P93075 consistently exhibited a significantly larger stem diameter than S1174 from 6 d onward. Anatomical analysis showed that P93075 displayed greater parenchyma cell size and vascular bundle area than S1174, suggesting that stem diameter variation is closely associated with parenchyma cell expansion and vascular bundle enlargement. Transcriptome profiling further identified 2611 differentially expressed genes (DEGs), mainly enriched in cell wall organization, phenylpropanoid biosynthesis, and hormone signaling pathways. Through temporal expression patterns of shared DEGs across developmental phases and co-expression network analysis, LacEXT3, encoding a cell wall extensin protein, was prioritized as a promising candidate gene associated with stem radial growth. Consistent with its markedly higher expression in P93075, heterologous overexpression of LacEXT3 in Arabidopsis resulted in increased stem diameter accompanied by reduced plant height. Overall, this study provides new insights into the developmental, cytological, and transcriptomic landscape underlying stem diameter variation in Luffa and offers a valuable resource for future investigation of the molecular mechanisms of stem thickening. Full article

Chronic infection with Helicobacter pylori (H. pylori) is a major environmental risk factor for gastric carcinogenesis. Malignancy is largely driven by variations within the virulence factor CagA, with East Asian lineages exhibiting higher oncogenic potential than Western ones. However, how these variants modulate cellular crosstalk remains poorly understood. We integrated molecular dynamics (MD) simulations with single-cell transcriptomics across progressive disease stages, including chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Local niche remodeling was evaluated via cell–cell communication profiling among epithelial, stromal, and immune circuits, while simulations of MARK2 kinase bound to distinct CagA lineages determined binding affinities. Single-cell analysis revealed that H. pylori toxicity progressively dampens epithelial–stromal crosstalk, marked by severe epithelial polarity aberrations that disrupt neuroendocrine-like secretory and synaptic pathways during malignant transformation. Mechanistically, MD simulations and MM/GBSA calculations demonstrated that East Asian CagA lineages exhibit higher binding affinity toward host MARK2 than Western lineages. Specific East Asian amino acid substitutions dramatically tighten the protein interface, driving stronger signaling perturbations. This study bridges atomistic structural virulence with microenvironmental shifting, establishing geographic CagA toxicity divergence as a critical determinant for pathogen-driven gastric cancer risk. Full article

Background/Objectives: Chronic pruritus of unknown origin (CPUO) is mechanistically poorly resolved, and its relationship to atopic dermatitis (AD) is unclear. We asked how much apparent separation survives removal of leakage. Methods: Public bulk skin data (GSE237920; four healthy, four AD, four CPUO) were analyzed by differential expression and an XOmiVAE-inspired latent model, with public single-cell and atlas resources for context. Every label-dependent step was then re-executed inside each cross-validation fold, with label permutation and 1000 bootstraps. A frozen composite niche score was applied unchanged to prurigo nodularis (GSE210854) and AD (GSE174582) cohorts. Results: Fully nested, the latent classifier separated CPUO from healthy skin (AUC 1.000; permutation p = 0.020) but not from AD (0.741; p = 0.140); randomized labels also reached 1.00. The composite score reached 0.919 against healthy skin but did not exceed its null (p = 0.086). Six genes recurred in ≥80% of bootstraps, five within the signature. Cell-type-restricted blood analysis recovered CPUO-associated monocyte CCL3 upregulation. In both validation cohorts, the frozen score was reduced, not elevated, in lesional skin. Conclusions: CPUO skin differs from healthy skin and occupies the low-inflammatory, epidermal-stress-dominated pole opposite lesional inflammatory skin, but cannot be robustly separated from AD at twelve samples. Full article

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with lymph node metastasis (LNM) being a key predictor of recurrence and poor prognosis. Preoperative detection of LNM remains challenging due to the limitations of imaging modalities, leading to inadequate surgical resection in 20–30% of patients. While immune checkpoint molecules have been implicated in PTC progression, the heterogeneity of CD8⁺ T cell exhaustion subsets and their specific association with LNM remain poorly defined. In this study, we aimed to perform an exploratory characterization of the distinct immune landscape of PTC prone to LNM, with a focus on terminal immune exhaustion, in order to generate hypotheses for improved risk stratification and therapeutic strategies. Methods: Fresh PTC tissues from 40 patients (22 LNM-positive and 18 LNM-negative) were analyzed via flow cytometry (FCM) to quantify immune cell subsets, inflammatory cytokines, and chemokines. Immunohistochemistry (IHC) validated CD45⁺ immune cell infiltration. Transcriptomic and clinical data from 448 PTC patients in The Cancer Genome Atlas (TCGA-PTC) cohort were used for bioinformatic analysis consistent with the observed phenotype, including Gene Set Variation Analysis (GSVA) of terminal exhaustion gene signatures. Results: LNM-positive PTC exhibited a unique inflammatory milieu with significantly elevated IL-6, IL-1ra, CCL5, and IL-9 levels (all p < 0.05) in tumor interstitial fluid. FCM analysis revealed that LNM-positive PTC had increased infiltration of total CD45⁺ immune cells, CD3⁺ T cells, and CD3⁺CD8⁺ T cells (all p < 0.05). Critically, terminally exhausted PD-1^hiTIM-3⁺ CD8⁺ T cells were significantly enriched in LNM-positive PTC (p = 0.022) and positively correlated with extrathyroidal extension (p = 0.044). Additionally, LNM risk was associated with increased CD4⁺ regulatory T (Treg) cell frequency (p = 0.023) and elevated CTLA-4 expression on CD4⁺ T cells (p = 0.047). In TCGA-PTC validation, the terminal exhaustion gene signature was predominantly enriched in LNM-positive (p < 0.0001) and advanced-stage PTC (p < 0.001) and strongly correlated with BRAF mutation (predominantly V600E) (p < 0.0001)—the most common oncogenic driver in aggressive PTC. Conclusions: Our findings suggest a terminal immune exhaustion phenotype (characterized by PD-1^hiTIM-3⁺ CD8⁺ T cells and Treg enrichment) as a potential key feature associated with LNM-prone PTC. This phenotype shows consistency across clinical samples and TCGA datasets, linking BRAF mutation (predominantly V600E) to immune suppression and metastatic potential. These insights provide a novel exploratory immune-based biomarker for LNM risk stratification and support the potential of combining anti-PD-1/TIM-3 therapy with BRAF inhibitors for high-risk PTC, which should be confirmed in future studies. Full article

The Min pig, a Chinese indigenous breed, is valued for its excellent meat quality and stress tolerance. Nevertheless, its growth rate falls considerably short of commercial pig breeds, a pattern typical of most unselected indigenous populations, and marked individual variation further undermines its economic viability. To explore the genetic basis of this variation, we evaluated a series of nonlinear fixed-effects and mixed-effects models based on the Gompertz, Logistic, and von Bertalanffy functions using body weight records from 92 Min pigs. Model selection was based on AIC, BIC, and leave-one-out cross-validation. The best-fitting model was a Logistic nonlinear mixed-effects model with individual-level random effects on all three growth parameters (Asymptotic weight, timing parameter, and be parameter), which clearly outperformed models with simpler random-effect structures and fixed-effects models. From this model, we identified three characteristic growth transition points: the early transition point (Growth Rate Index, GRI) at 94.83 days (22.32 kg), the single inflection point (Maximum Growth Rate, MGR) at 166.06 days (52.80 kg), and the late transition point (Late Growth Rate Index, LGRI) at 237.29 days (83.29 kg), with a maximum absolute growth rate of 488.2 g/day. These points partitioned growth into initial acceleration, rapid growth, deceleration, and Asymptotic growth phases. Using individual fitted growth curves, we selected five fast-growing and five slow-growing pigs that reached approximately 90 kg during the plateau phase, defined as a predicted body weight of at least 95% of the individual Asymptotic weight. The fast-growing group reached 90 kg at 240.5 ± 20.42 days, whereas the slow-growing group reached the same weight at 286.67 ± 19.20 days. At the 90 kg slaughter weight, we collected longissimus dorsi muscle samples from these pigs during the plateau phase and performed RNA-seq. Transcriptome analysis revealed 864 differentially expressed genes between the two groups, with 540 upregulated and 324 downregulated in the fast-growing group. Pathway enrichment implicated the PI3K-Akt and TGF-β signaling pathways in muscle development, and differential expression of IGFN1, DCN, COL3A1, MYOC, COL1A2, COL1A1, and IGF2 may explain the growth variation between the groups. In summary, the Logistic mixed-effects model with individual-level random effects on all growth parameters effectively captures the growth pattern of Min pigs, and the PI3K-Akt and TGF-β pathways likely mediate growth differences in this breed. Full article

Background & Aims: Signaling within the tumor microenvironment (TME) emerges from dynamic crosstalk among cancer cells, host tissues, and the microbiome. Orthotopic and ectopic xenograft models are widely used in preclinical liver cancer research, yet it remains unclear to what extent tumor location shapes systemic host responses and gut–liver communication. We therefore investigated how anatomical context influences host transcriptomes and spatially resolved intestinal microbial ecosystems in hepatoblastoma (HB). Methods: We integrated bacterial/archaeal ecology with host and xenograft transcriptomes in orthotopic versus ectopic hepatoblastoma xenografts in male athymic CAnN.Cg-Foxn1nu/Crl mice. Single-sample GSEA, sparsity-aware networks, and DIABLO multi-block integration mapped pathway-level coordination across intestinal segments, stool, secondary lymphoid organs, livers, and tumors. Results: Tumor localization was associated with compartment-specific differences in host signaling, with the mesenteric lymph node and liver showing prominent shifts in TNFA/NF-κB, hypoxia, unfolded protein response, xenobiotic metabolism, mTORC1, KRAS, epithelial–mesenchymal transition, and MYC/E2F cell-cycle axes. Archaea exhibited pronounced, niche-specific signatures that showed positive correlations with proliferative and inflammatory Hallmarks and negative correlations with interferon pathways. Multi-omics integration (r ≥ 0.85) indicated coordinated variation linking specific microbial families to host and tumor programs and positioned the xenograft block as a hub connecting EMT, mTORC1, and angiogenesis to defined archaeal and bacterial taxa. Conclusions: Tumor topography remodels TME signaling through compartment-dependent host–microbiome–tumor crosstalk, with archaeal domains emerging as salient correlates of proliferative and stress-response networks. These findings provide a systems framework and testable hypotheses for therapeutic modulation of TME signaling via interkingdom interactions. Full article

Background: Hyperlipidemic acute pancreatitis (HAP) is a severe disease driven by systemic lipid overload. While free fatty acids (FFAs) are known to mediate pancreatic lipotoxicity, the intracellular enzymatic mechanisms generating these toxic lipid mediators remain unclear. We aimed to identify the core metabolic drivers linking systemic hyperlipidemia to local pancreatic injury and evaluate targeted prophylactic strategies for HAP. Methods: We integrated public transcriptomic datasets of severe AP and obesity/hyperlipidemia. Three machine learning algorithms were employed to identify comorbidity-associated signature genes. The underlying mechanisms were explored via gene set variation analysis, immune infiltration profiling, and single-cell in silico knockout. In vivo validation was performed using a P-407/caerulein-induced HAP mouse model treated with WWL113, followed by comprehensive histological, biochemical, and lipidomic analyses. Results: A robust three-gene signature (FASN, CES1, IL10) was identified with excellent diagnostic accuracy. Notably, within this signature, the triglyceride hydrolase CES1 was aberrantly upregulated, serving as the primary driver of a maladaptive lipolytic shift. CES1 overexpression was strongly correlated with neutrophil infiltration. Single-cell virtual knockout suggested a potential association between Ces1d and markers of endothelial barrier disruption and neutrophil chemotaxis. In vivo, WWL113 significantly attenuated HAP-induced pancreatic necrosis and systemic inflammation. Crucially, lipidomics confirmed that WWL113 sequestered exogenous lipids in inert triglyceride states, drastically reducing toxic FFAs. Conclusions: This study highlights CES1 as a critical intracellular mediator of lipotoxicity in HAP. Pharmacological inhibition of CES1 effectively halts maladaptive lipolysis, providing proof-of-mechanism for a metabolism-directed prophylactic strategy for HAP. Full article

Plant GH5 family genes function in both cell wall biosynthesis and stress responses. However, comprehensive studies on GH5 genes in the soybean remain limited. Here, we identified 28 GmGH5 genes from the soybean genome. Phylogenetic analysis assigned these genes to three subfamilies (I–III), with no representatives in subfamily IV. The GmGH5 family harbors 15 conserved motifs, which are largely similar within subfamilies but differ across subfamilies. Additionally, exon–intron structures (2–7 introns) exhibit clade-specific patterns, with members within the same clade sharing similar intron numbers and lengths, whereas distinct clades show some variation. The promoter regions of GmGH5 genes contained various cis-acting regulatory elements associated with stress responses and developmental processes. Transcriptome-based expression profiling revealed distinct tissue-specific expression patterns of GmGH5 genes. RT-qPCR further confirmed their differential expression under salt, alkaline, cold, and drought stresses, especially a significant increase in GmGH5-22 expression under salt stress (approximately 22-fold at 6 h, **** p < 0.0001). Furthermore, GmGH5-22 was highly expressed in roots, and transient expression in tobacco leaves showed its peripheral localization, which aligns with its predicted extracellular localization, suggesting that GmGH5-22 is highly likely localized to the cell wall. Overexpression of GmGH5-22 in soybean hairy roots significantly improved tolerance to salt stress. These findings establish a foundation for functional characterization of GmGH5 genes and provide viable targets for molecular breeding to enhance salt tolerance in soybeans. Full article

Hispanics of Mexican American descent in South Texas show a very high prevalence of MASLD, with some studies reporting rates as high as 50% in adults. However, assessment of genetic risk factors underlying this prevalence is complicated by a high co-occurrence of other metabolic disorders and variable endogenous and exogenous environmental risk factors. To map the transcriptomic architecture of MASLD hepatic steatosis risk, we conducted an epidemiological-scale investigation using human induced pluripotent stem cell (iPSC)-derived hepatocyte cultures from 193 participants in our longitudinal South Texas Family Study (STFS). iPSC-based models offer greater power to map genetic risk factors by experimentally controlling for confounding organismal and environmental factors. We combined transcriptome-wide gene expression analysis with high-content cellular measurements of neutral lipids to define a core hepatic steatosis MASLD phenotype at baseline (vehicle-treated) and following a lipid challenge. The additive genetic heritability of hepatic steatosis measures was 0.44 (p-value = 0.03) at baseline and 0.42 (p-value = 0.03) at post-lipid challenge. Multivariable linear regression comparing each gene’s expression against hepatic steatosis measures identified 1070 genes at baseline and 1229 genes post-lipid challenge, whose expression showed a transcriptome-wide statistically significant association (standardized |β| ≥ 0.24; Bonferroni-corrected p-value ≤ 0.001) with baseline and post-lipid challenge hepatic steatosis measures, respectively. Functional annotation and pathway enrichment analyses of these genes implicated a broad range of hepatocellular functions, mapping an overall transcriptomic architecture of MASLD-associated steatosis risk in Mexican Americans. The genes whose expression was positively correlated with hepatic steatosis measures suggest a direct role of variation in fatty acid (FA) and cholesterol uptake, de novo lipogenesis (DNL), and carbohydrate shunts in hepatic steatosis risk, as well as a cellular stress-associated and high-turnover metabolic state marked by elevated FA-oxidation and ketogenesis. In contrast, the genes whose expression was inversely correlated with hepatic steatosis measures suggest a significant role of the cellular cytoskeleton, hepatocyte epithelial integrity, and endosomal and autophagic clearance machinery in steatosis risk. Full article

Rind color is an important quality trait in zucchini (Cucurbita pepo). As a core transcription factor in plant pigment biosynthesis, APRR2 plays a conserved yet mechanistically diverse regulatory role in the formation of rind color in various vegetables. However, the APRR2 transcription factor regulates rind color but has not been systematically identified in C. pepo. In this study, 50 APRR2 genes were defined by the presence of the conserved REC domain verified. These genes were identified and found to be unevenly distributed across the 20 chromosomes, primarily expanded through tandem duplication events. Phylogenetic and structural analysis classified these genes into three distinct subgroups, all featuring the conserved REC domain essential for pigment regulation but exhibiting variations in motifs and intron–exon structures. Promoter analysis revealed abundant light-responsive, hormone-responsive and stress-responsive elements that may contribute to environmental adaptation and photomorphogenesis. Crucially, transcriptome analysis during rind development (0 and 10 days after pollination) in green (GR) and white (WR) rind lines demonstrated profound functional divergence. Expression clusters indicated temporal shifts in metabolism and enriched “circadian rhythm-plant” and “photosynthesis” pathways in WR at 0 DAP. Specific APRR2 genes were tightly correlated with rind color. qPCR validation of the 24 selected APRR2 genes classified them into four trend groups based on the direction of expression change at 10 DAP. In total, 14 genes were upregulated in both GR and WR, 6 were downregulated in both lines, 1 was upregulated in GR but downregulated in WR, and 3 were downregulated in GR but upregulated in WR. Furthermore, protein–protein interaction prediction and yeast two-hybrid (Y2H) assays detected a physical interaction in yeast between a core APRR2 protein and a bHLH62 transcription factor, suggesting a potential interaction that may be involved in rind color regulation, pending in planta validation. The study first identified the members of the APRR2 gene family in C. pepo and conducted a bioinformatics analysis on them. The study establishes the molecular basis of APRR2 function and offers valuable resources for breeding improved C. pepo varieties. Full article

The kernel oil content of macadamia can reach up to 80%, yet the molecular basis underlying cultivar-dependent variation in lipid accumulation remains insufficiently understood. In this study, four macadamia cultivars with contrasting oil traits (O.C, QA1, QA2, and QA3) were investigated using integrated transcriptomic, metabolomic, and nutritional analyses to explore the metabolic pathways associated with kernel oil accumulation. Phenotypic evaluation revealed significant differences in fruit characteristics and nutritional composition among cultivars, with O.C exhibiting the highest crude fat content and QA1 showing the highest crude protein content. Transcriptomic analysis identified numerous differentially expressed genes (DEGs), which were mainly enriched in glycerolipid metabolism, α-linolenic acid metabolism, and amino acid biosynthesis pathways. Metabolomic profiling detected 778 metabolites, among which lipid-related compounds represented a major proportion. Integrated analysis revealed three major metabolic pathways associated with oil accumulation, including amino acid biosynthesis, glycerolipid metabolism, and linoleic acid metabolism. In the amino acid biosynthesis pathway, differential accumulation of amino acids and expression changes of genes including ASNS, GLUL, and MAT were observed among cultivars. In glycerolipid metabolism, differential expression of TAG biosynthesis-related genes (DGAT and PDAT) and variation in phospholipid-related metabolites, including LysoPC and LysoPE, were detected among cultivars. In linoleic acid metabolism, differential expression of fatty acid desaturation and elongation genes (SAD, FAD2, FAD3, and FAE1/KCS) was accompanied by cultivar-dependent differences in the abundance of several fatty acid-related metabolites. Overall, this study provides a comprehensive characterization of transcriptomic and metabolic variation associated with crude fat content and fatty acid-related metabolites in macadamia kernels and identifies candidate genes for further functional validation and molecular breeding studies. Full article

Erythritol is a widely used low-calorie sugar substitute, but its relationship with cerebrovascular risk remains uncertain. We investigated the association between genetically predicted erythritol levels and ischemic stroke and explored stroke-related molecular features using an integrative bioinformatics framework. Two-sample and multivariable Mendelian randomization were performed across cardiovascular–kidney–metabolic outcomes, followed by target prediction, enrichment and protein–protein interaction analyses, transcriptomic profiling, machine-learning feature selection, SHAP interpretation, immune-cell analysis, gene set variation analysis, and exploratory molecular docking. Genetically predicted erythritol showed the strongest association with stroke among the tested sweetener-related traits (OR = 1.246, 95% CI: 1.101–1.410, p < 0.001) and remained significant after adjustment for selected hemodynamic, glycometabolic, and lipid-related traits. Downstream analyses highlighted inflammatory, oxidative-stress, hypoxic, and vascular-injury pathways and prioritized MMP9, TLR4, and HIF1A as a reproducible stroke-related three-gene signature. These downstream bioinformatic findings are exploratory and do not establish erythritol-specific molecular regulation. Overall, the results support an association between genetically predicted erythritol levels and ischemic stroke and identify candidate pathways and genes for further investigation; the MR exposure should not be interpreted as direct evidence that dietary erythritol intake causes stroke. Full article

Perilla (Perilla frutescens) is an important oil-bearing crop rich in α-linolenic acid (ALA), and seed oil quality varies greatly among different germplasms. However, the molecular and metabolic mechanisms underlying genotypic differences in ALA accumulation remain unclear. In this study, four Perilla varieties with distinct seed phenotypic traits were used to investigate the variations in seed quality, metabolome, and transcriptome. Significant genotypic differences were observed in seed color, thousand-grain weight, and oil content. QO8 showed the highest seed oil content, while QS5 and QO10 exhibited relatively lower oil accumulation levels. Metabolome analysis revealed that lipid metabolism was the dominant metabolic category in Perilla seeds. Multiple differentially accumulated metabolites (DAMs), including ALA, stearic acid, traumatic acid, and 10-OPDA, displayed genotype-specific accumulation patterns. KEGG enrichment demonstrated that α-linolenic acid metabolism and unsaturated fatty acid biosynthesis were the most significantly divergent pathways among different Perilla germplasms. Transcriptome analysis identified numerous differentially expressed genes (DEGs) involved in fatty acid and ALA biosynthesis, such as FAD2, LOX, AOS, AOC, OPR, KAT, ECH, and ACOX. Integrated transcriptome and metabolome analysis further confirmed that the differential expression of structural genes altered the metabolic flux of the ALA and downstream jasmonic acid pathway, resulting in varied accumulation of core lipid intermediates. In addition, WRKY and MYB transcription factors were identified as key upstream regulators that positively or negatively modulated ALA metabolic homeostasis. This study systematically clarified the phenotypic, metabolic, and transcriptional differences in seeds of different Perilla varieties and revealed the core regulatory network of ALA biosynthesis. These findings provide valuable candidate genes and a theoretical foundation for elucidating the molecular mechanism of high ALA accumulation and quality improvement in Perilla seeds. Full article