Search Results (235)

Background/Objectives: Leptin is a pleiotropic adipokine linking energy metabolism with innate and adaptive immunity. Its relationship with clinical severity across distinct airway disease phenotypes remains insufficiently characterized. This study examined serum leptin concentrations in adults with allergic rhinitis, non-allergic asthma, and allergic asthma associated with allergic rhinitis. Methods: This single-center retrospective observational study analyzed fully anonymized clinical and laboratory data from 88 adults: patients with allergic rhinitis (n = 31), non-allergic asthma (n = 15), or allergic asthma with allergic rhinitis (n = 22) and healthy controls (n = 20). Serum leptin was measured using a quantitative sandwich enzyme-linked immunosorbent assay. Disease severity was classified using the Allergic Rhinitis and its Impact on Asthma and Global Initiative for Asthma frameworks applicable during the study period. Statistical analyses were performed using IBM SPSS Statistics, version 26.0 (IBM Corp., Armonk, NY, USA), and available original statistical outputs were summarized using retained t statistics and two-sided p values. Results: Stage-specific mean serum leptin concentrations were heterogeneous and non-monotonic. Statistically significant relationships between leptin concentration and disease stage were reported for allergic rhinitis (t = 2.844; p = 0.008), non-allergic asthma (t = 4.240; p = 0.001), and allergic asthma with allergic rhinitis (t = 2.700; p = 0.013). In the allergic rhinitis subgroup, 64.5% of participants had normal weight, 32.3% were overweight, and 3.2% had grade II obesity; weight category was not significantly related to rhinitis stage. Conclusions: The retained analyses indicate statistically significant relationships between serum leptin concentration and clinical disease stage across the investigated airway phenotypes. However, the stage-specific descriptive means were heterogeneous and non-monotonic and therefore do not support a uniform progressive increase in leptin with increasing disease severity. Because complete model outputs and covariate-adjusted estimates were unavailable, these findings should be regarded as exploratory and require prospective validation with appropriate adjustment for adiposity and other relevant metabolic confounders. Full article

Polyploidy is widely used in plant breeding to increase phenotypic variation and potentially improve stress-related traits; however, its effects in common bean remain poorly characterized. Here, colchicine-induced polyploidy was evaluated in Phaseolus vulgaris cv. Zorzal to determine whether tetraploid lines exhibit coordinated changes in stomatal anatomy, physiology, pigment composition, oxidative balance, and ploidy inheritance. Polyploidy was induced using different colchicine exposure regimes and confirmed by flow cytometry. Stomatal traits, gas-exchange parameters, photosynthetic pigments, oxidative stress markers, antioxidant capacity, and multivariate phenotypic relationships were subsequently analyzed in confirmed tetraploid lines. Colchicine treatments successfully generated tetraploid and mixoploid plants, although induction efficiency was highly variable among replicates. Tetraploid lines showed heterogeneous physiological responses, including increases in the photosynthetic rate and stomatal conductance in some genotypes, but no consistent reduction in stomatal pore area index. Pigment composition and antioxidant-related traits also varied among lines, without a uniform response pattern. Multivariate analyses revealed coordinated but highly divergent phenotypic profiles among tetraploid genotypes. Importantly, the induced tetraploids were not stably transmitted to the C1 generation, with a predominance of diploid progeny among the evaluated offspring. Overall, colchicine-induced polyploidization generated substantial physiological variability among independently derived tetraploid plants of P. vulgaris cv. ‘Zorzal’; however, the predominance of diploid individuals among the evaluated C1 progeny indicates limited transmission of the induced tetraploid state to the subsequent generation. Full article

Understanding the biochemical networks governing seed longevity is essential for germplasm conservation. Integrating germination potential with biochemical profiling elucidates metabolic transitions during decadal cold storage. As phenotypic evidence of ageing, extended cold storage induces a uniform decline in germination energy, reaching a terminal “floor effect” characterised by the complete exhaustion of repair-and-defence strategies, whilst residual germination capacity averages 21%. Metabolic profiling reveals that prolonged storage causes systemic decoupling of the protein–sugar axis, leading to the loss of protein-dependent vigour. The structural collapse of the proteomic architecture—manifested by the decoupling of embryo albumin-led coordination and endosperm α-zein dynamics—induces a transition to a low-vigour state, paralleled by carbohydrate shifts consistent with glassy matrix destabilisation, implicitly linking the displacement of sucrose-dominated stability to the molecular crowding of reducing sugars. Re-anchoring germination potential from primary metabolic drivers to soluble-free phenolics prompts a compensatory antioxidant reorganisation; under conditions of phenolic matrix degradation and carotenoid exhaustion, the observed stability of total antioxidant capacity likely reflects scavenging sustained by phenolic degradation products rather than native, intact protective mechanisms. Ultimately, seed ageing manifests as a genotype-specific systemic reconfiguration of biochemical coordination, where the physiological state of the cytoplasmic matrix and the maintenance of redox homeostasis determine residual viability, thereby defining the critical benchmarks for germplasm longevity. Full article

To address the core breeding demand for greater seedling vigor in bread wheat (Triticum aestivum L.) varieties adapted to the uniform sowing system in China’s Huang-Huai Wheat Region, we aimed to dissect the genetic architecture and identify core candidate genes for shoot length (SL) and root length (RL) at the germination stage. A natural population consisting of 204 wheat accessions was genotyped using the 660K SNP array, and a genome-wide association study (GWAS) integrated with transcriptomic, metabolomic, and proteomic analyses of extreme phenotypic accessions was performed. Both SL and RL were typical quantitative traits with an extremely significant positive correlation. A total of 111 and 176 significant SNPs were associated with SL and RL, respectively, including 56 shared loci. Glutathione metabolism was identified as the conserved core pathway for both tissues, while photosynthesis–antenna proteins and phenylpropanoid biosynthesis were identified as tissue-specific pathways in shoots and roots, respectively. Finally, we identified 7 core candidate genes for SL and 13 for RL, including three pleiotropic genes regulating both traits. This study provides valuable genetic resources and key targets for the molecular breeding of wheat varieties specialized for uniform sowing. Full article

Background: Cyclophosphamide (CTX)-induced immunosuppression involves systemic toxicity, splenic atrophy, and broad transcriptomic disruption. Icariin (ICA) has immunomodulatory activity, but the systems-level features associated with splenic recovery remain incompletely defined. Methods and Results: Male mice were assigned to control, CTX, and CTX plus ICA (20, 40, or 80 mg/kg) groups. Phenotypic measurements were integrated with splenic RNA sequencing, differential expression analysis, targeted gene-set analysis, and weighted gene co-expression network analysis (WGCNA). ICA produced dose-associated improvement in spleen index and body weight trajectory, with the most consistent phenotypic response at 80 mg/kg. Overall transcriptomic separation was supported by permutational multivariate analysis of variance (PERMANOVA) (F = 17.18, R² = 0.873, p < 0.001). WGCNA identified a recovery-associated turquoise module; Myb was assigned to this module, whereas Gata1 belonged to a distinct royalblue module. Complement and chemokine gene sets provided the strongest targeted enrichment evidence, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed dose-associated changes in selected innate immune transcripts. Marker-based lineage signatures indicated non-uniform recovery, including persistent depression of the B-cell signature. Conclusion: ICA-associated phenotypic recovery coincided with partial, non-uniform remodeling of splenic transcriptional programs. The Myb- and Gata1-associated findings are hypothesis-generating co-expression signals and do not establish transcription-factor binding or causality. Full article

Large yellow croaker (Larimichthys crocea) is an economically important mariculture species in China, but marked individual variation in body weight reduces production uniformity. To explore molecular features underlying this phenotypic divergence, liver tissues from high-weight and low-weight fish from the Naozhou population were subjected to integrated transcriptomic and untargeted metabolomic analyses. A total of 3390 DEGs were identified in the high-weight group (HWG) compared with the low-weight group (LWG), including 1576 upregulated and 1814 downregulated genes. Functional annotation indicated that the DEGs were predominantly associated with pathways governing cell-cycle progression, DNA synthesis and replication, lipid turnover, and amino acid-related metabolic processes. Untargeted metabolomic profiling identified 2263 annotated metabolites, of which 241 were differentially accumulated between the two groups. Pathway enrichment indicated that these altered metabolites were primarily associated with lipid-related processes, amino acid turnover, and cellular energy metabolism. Integrated analysis further revealed significant correlations between DEGs and differential metabolites and highlighted several co-enriched pathways, including linoleic acid metabolism, biosynthesis of amino acids, carbon metabolism, and fatty acid biosynthesis. These findings provide preliminary evidence that body-weight differences in large yellow croaker may reflect coordinated changes at both the transcriptomic and metabolomic levels, with lipid metabolism, amino acid metabolism, and energy-related pathways being particularly involved. As an exploratory study, these results should be regarded as candidate molecular associations that require further validation in larger populations before being applied to breeding or nutritional regulation. Full article

Melon (Cucumis melo L.) germplasm resources are vital for seed-industry innovation and cultivar breeding. To systematically characterize their phenotypic variation, classification relationships, and breeding potential, 403 melon accessions were evaluated using nine quantitative characteristics specified in the guidelines for tests of distinctness, uniformity, and stability. These characteristics included fruit longitudinal diameter, fruit transverse diameter, fruit peduncle length, internode length, flesh thickness, petiole length, rind thickness, soluble solids content, and seed cavity diameter. The evaluated population exhibited extensive phenotypic variation, with coefficients of variation ranging from 14.0% to 57.4%. Rind thickness showed the greatest variation, while fruit transverse diameter, flesh thickness, fruit peduncle length, and fruit longitudinal diameter also displayed considerable differentiation. The Shannon–Weaver diversity index ranged from 1.74 to 1.96, indicating substantial diversity in fruit morphology, vegetative growth, internal fruit structure, and quality-related characteristics. Spearman rank correlation analysis revealed close developmental relationships among fruit-related characteristics, with rind thickness showing the strongest positive correlation with flesh thickness. Principal component analysis extracted three components with eigenvalues greater than one, which together explained 65.22% of the total phenotypic variation and primarily represented fruit morphological structure, vegetative growth, and fruit quality. Hierarchical cluster analysis classified the 403 accessions into four quantitative phenotypic groups, with highly significant differences among the groups for all nine characteristics. Furthermore, a weighted comprehensive selection index identified several accessions with superior combined agronomic performance, among which accession 20225110454A ranked first. These findings provide a quantitative phenotypic basis for melon germplasm conservation, core collection development, parental selection, and breeding-oriented resource utilization. Full article

During the COVID-19 pandemic, healthcare systems experienced significant disruption, increasing the risk of multidrug-resistant (MDR) pathogen transmission. Acinetobacter baumannii, a critical-priority MDR pathogen, is known for its ability to persist in hospital environments and rapidly acquire resistance. To investigate the genomic characteristics, antimicrobial resistance determinants, and phylogenetic relationships of outbreak-associated Acinetobacter baumannii isolates, whole-genome sequencing (WGS) and comparative genomic analyses on 24 clinical and environmental strains collected during the COVID-19 period were performed. Twenty-four A. baumannii isolates collected between August 2020 and February 2021 from clinical and environmental samples were analyzed by WGS. All isolates displayed an MDR phenotype, with uniform resistance to carbapenems and aminoglycosides, and preserved colistin susceptibility. One environmental strain showed extreme drug resistance. WGS confirmed medium-quality genome assemblies and the clonal spread of a single A. baumannii lineage. Most resistance genes, including OXA-23, ADC-type β-lactamases, and ade efflux pumps, were chromosomally encoded and shared across all isolates. Plasmid-mediated resistance genes were variably distributed. This outbreak of MDR A. baumannii was driven by the clonal dissemination of a genomically stable lineage. Combined genomic and epidemiological analyses underscore the importance of integrated surveillance and environmental decontamination to prevent the spread of MDR pathogens. Full article

Background: Severe Mycoplasma pneumoniae pneumonia (SMPP) presents with heterogeneous clinical complications and imaging manifestations, including pleural effusion (PE), bronchiolitis obliterans (BO), and distinct imaging/bronchoscopic phenotypes. The precise systemic immune subpopulation dynamics underlying these distinct phenotypes remain poorly defined. Methods: We conducted flow cytometric profiling of peripheral blood mononuclear cells (PBMCs) from pediatric patients to compare mild MPP (MMPP-N) and severe MPP subtypes. SMPP patients were stratified into subgroups including those with BO (SMPP&BO, n = 3), PE (SMPP&PE), and three imaging/bronchoscopic phenotypes: Group A (SMPP-GA, mucous plugs), Group B (SMPP-GB, mucosal necrosis), and Group C (SMPP-GC, diffuse bronchiolitis). Composite immune indices and multi-marker discriminant analysis were constructed for secondary analysis. Results: Comprehensive high-dimensional profiling suggested that a fundamental innate-adaptive immune rebalancing may represent a key pathophysiological axis in severe disease. Patients with PE exhibited massive CD16⁻ monocyte expansion (Delta = 40.0%) coupled with CD8⁺ Teff collapse (Delta = −9.2%). Preliminary data also suggest BO may be marked by CD56⁻CD11C⁺ monocyte depletion (Delta = −23.1%, n = 3), warranting further validation. Imaging subgroup profiling revealed that SMPP-GC featured major B-cell maturation alterations (HLADR⁺CD45RA^high expansion and CD38⁺CD25^low depletion). Composite indices including the Adaptive Exhaustion Score suggested discriminatory power (AUC = 0.90 for PE vs. uncomplicated SMPP). The Innate-Adaptive Ratio increased progressively with severity (Spearman rho = +0.40, p = 0.0002). Conclusions: SMPP is not immunologically uniform. Innate-adaptive rebalancing underlies complication-specific phenotypes: inflammatory monocyte mobilization with adaptive exhaustion is strongly associated with PE, whereas B-cell maturation alterations characterize diffuse bronchiolitis. These findings identify potential biomarker candidates for patient stratification, though small-cohort observations require extensive validation in larger prospective studies. Full article

This study investigated how defatted silkworm pupae meal (DSPM) modulates flesh quality in pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). A total of 360 size-uniform fish were randomly assigned to four dietary treatments for 8 weeks: D0, the fishmeal (FM) based control diet; and D1, D2, and D3, in which DSPM substituted 25%, 50%, and 100% of dietary FM, respectively, with three replicates per treatment and 30 fish per replicate. Compared with D0, D1 and D2 improved final body weight, weight gain rate, specific growth rate, and feed conversion ratio, whereas D3 reduced survival and feed utilization. For flesh quality, D2 showed the most favorable phenotype, characterized by higher crude protein, collagen, flavor-associated amino acids, pH, texture attributes, and muscle fiber density, together with lower ether extract, cooking loss, freezing loss, and shear force. DSPM substitution also increased unsaturated and polyunsaturated fatty acid proportions and improved lipid health indices. Moderate substitution, especially D2, enhanced oxidative stability by increasing SOD and CAT activities and reducing MDA accumulation. Non-targeted metabolomics combined with qPCR analysis of selected flesh quality-related genes suggested that these improvements were associated with osmotic regulation, collagen remodeling, purine metabolism, membrane lipid homeostasis, nutrient sensing, myogenesis, and antioxidant defense. Complete FM substitution impaired muscle structure, water retention, and redox balance. Thus, 50% FM substitution with DSPM effectively optimized grouper flesh quality in this study. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and dysfunction of the exocrine glands, with manifestations extending beyond glandular sicca symptoms to multiple extraglandular systems. Although the pathogenesis of SjD remains incompletely understood, growing evidence indicates that a complex cytokine network involving both innate and adaptive immune pathways plays a central role in disease development. This narrative review summarizes recent updates on cytokine signaling in SjD across three clinically relevant domains. In glandular inflammation, activation of salivary gland epithelial cells through Toll-like receptor pathways triggers type I interferon (IFN) signaling via plasmacytoid dendritic cells, while IFN-γ, Th17-related cytokines (IL-6, IL-17, IL-22), BAFF/APRIL, and chemokines (CXCL10, CXCL12, CXCL13) collectively sustain local inflammation and ectopic lymphoid organization. The BAFF/APRIL axis, a systemic type I IFN signature, and IL-21–follicular helper T cell–B cell interactions primarily drive systemic immune activation, which together underlie autoantibody production, hypergammaglobulinemia, and a lymphoma-prone phenotype. In contrast, constitutional symptoms such as fatigue, pain, and dryness frequently dissociate from classical inflammatory activity and are better explained by neuroimmune–metabolic mechanisms, including the IFN-γ–IDO–kynurenine pathway and symptom-associated proteomic signatures. Collectively, these findings underscore the heterogeneous nature of SjD, in which glandular inflammation, systemic immune activation, and constitutional symptoms are driven by distinct yet partially overlapping cytokine pathways. Recognizing this heterogeneity has direct implications for cytokine-targeted therapy, suggesting that future trials should stratify patients by disease phenotype (IFN-high, B cell-dominant, and symptom-dominant) rather than treating SjD as a uniform population. Full article

Blackberry micropropagation enables the rapid production of pathogen-free and genetically uniform plant material, although the evaluation of in vitro shoot development still relies on destructive and time-consuming measurements. This study investigated a low-cost smartphone-based 3D imaging approach for the non-destructive characterization of in vitro blackberry shoots (cultivar ‘Thornfree’) grown under different sucrose concentrations in the media (0, 7.5, 15, and 30 g ${\mathrm{L}}^{-1}$). Explants were cultured for 30 days under controlled environmental conditions in ventilated vessels containing 15 explants. Three-dimensional reconstructions generated using the viDoC RTK rover system coupled with an Apple iPhone 15 Pro Max were used to extract geometric traits, including shoot height, projected area, and shoot volume estimated through three complementary approaches, together with voxel-derived structural descriptors of shoot spatial organization and compactness. The proposed approach enabled the quantitative assessment of shoot architectural responses to sucrose availability, revealing differences in volumetric development and internal structural organization among treatments that would not be detectable by conventional measurements. The results highlight the potential of smartphone-based 3D phenotyping as a rapid, low-cost, and non-destructive tool for monitoring structural traits in micropropagated plant material and for supporting the optimization of in vitro culture conditions. Full article

Obesity is a complex, chronic, relapsing disease that affects nearly all physiological functions and homeostatic mechanisms, extending far beyond mere excess adiposity. Traditional clinical practice often relies on uniform interventions that fail to account for diverse patient phenotypes. This review synthesizes current evidence on personalized obesity management, dietary interventions, and advanced pharmacotherapies aligned with the new 2025 Lancet Commission framework. A comprehensive narrative review was conducted across major biomedical databases to evaluate the efficacy, safety, and mechanisms of metabolic interventions, focusing on phenotype-specific dietary matching, bioactive compounds, and modern multi-receptor glucagon-like peptide-1 (GLP-1)-based therapies across preclinical and clinical intervention tiers in adult and pediatric populations. While specific nutraceutical extracts display promising secondary metabolic benefits, their overall weight-loss efficacy remains modest due to variable clinical data and limited sample sizes. Conversely, high-potency anti-obesity medications demonstrate unprecedented weight-reduction efficacy, with semaglutide 2.4 mg and tirzepatide yielding mean body weight losses of ~14.9% and ~20.9%, respectively. Furthermore, landmark outcome data from the SELECT trial confirms that semaglutide 2.4 mg achieves a significant 20% relative risk reduction in major adverse cardiovascular events (MACE), independent of baseline glycemic status or heart failure. However, clinical extension data reveal rapid weight rebound upon drug cessation, highlighting that obesity requires continuous, long-term therapeutic strategies. Effective obesity care demands an operational shift from traditional, one-size-fits-all treatments to personalized, multi-tiered strategies. Combining phenotype-specific lifestyle modifications with potent, long-term multi-hormonal pharmacotherapies or metabolic surgery optimizes long-term therapeutic durability, systemic metabolic health, and sustained cardioprotection. Full article

Myxofibrosarcoma (MFS) is a common yet understudied type of soft tissue sarcoma. It is characterized by diverse cellular morphology, unusual growth patterns, and a propensity for local tumor recurrences. A 76-year-old patient underwent multiple surgical removals of MFS recurrences of the thoracic cavity and surrounding tissues with the subsequent development of metastases. Single-cell RNA sequencing was used to analyze the earlier (R7) and later (R8) MFS recurrences, with R8 removed less than a year before the detection of metastases in the lungs. The earlier MFS recurrence displays tumor clusters with multiple immunomodulatory markers (DKK1, APP, CD24, GRN) and genes involved in lipid metabolism and cell stress (DDIT3, ABCA1, ABCA10, ATF4, NEU1), combined with an anti-inflammatory TME. The later MFS recurrence shifts to a functionally less diverse phenotype, enriched in fibroblast-typical markers (POSTN, NES, COL1A1/A2), and a pro-inflammatory TME. The proliferative (MKI67, TOP2A, BUB1B) and mRNA splicing and processing (SNRNP70, SRSF2/5/11, RSRP1, LUC7L/7L3, SRRM1/2) tumor clusters are observed in both MFS recurrences, and their signatures match the previous data on primary MFS tumor populations. ScRNA-seq analysis of two subsequent MFS recurrences from one patient show a change from functionally diverse to more uniform ECM remodeling enriched tumor populations, an accompanying shift to the pro-inflammatory TME, and the presence of two common tumor clusters enriched in proliferative and mRNA-processing gene signatures. Full article

Natural killer (NK) cells are key mediators of antitumor immunity; however, NK cell dysfunction in epithelial ovarian cancer should be considered not as a uniform defect, but rather as compartment-specific states that differ across the blood, ascites, primary tumor, and metastatic sites according to their local cellular interactions, soluble factors, and metabolic constraints. Peripheral blood provides an accessible systemic reference and may support immune monitoring. However, it does not fully reflect NK cell states in local or distant disease compartments. In ascites, cytokine-responsive and partially recoverable NK cell populations coexist with soluble, biochemical, and metabolic suppressive signals. In primary tumors, NK cells often acquire tissue-adapted suppressive phenotypes, characterized by altered activating receptors, increased inhibitory checkpoints, and reduced cytotoxic effector function. In metastatic lesions, NK cells appear to share suppressive phenotypes with primary tumors, although these phenotypes may be reinforced within metastatic niches through coordinated inhibitory receptor–ligand interactions. The above compartment-specific states imply that NK cell-targeted therapy for ovarian cancer should not rely on a unilateral strategy. Instead, therapeutic design may need to be multifaceted but coordinated, combining cytokine-based activation, adoptive NK cell transfer, checkpoint blockade, local delivery, and antigen-directed chimeric antigen receptor NK cell approaches according to the dominant biology of each compartment. Paired multi-compartment profiling and longitudinal functional assessment will be essential for biomarker development and compartment-guided treatment design. Full article