Acute inflammation, when unresolved, can lead to complications that impair tissue repair and therapeutic outcomes. In this study, we employed a model of lipopolysaccharide (LPS)-induced acute subcutaneous abdominal inflammation in mice to investigate the modulatory effects of elastic compression. LPS administration elicited a robust inflammatory response, characterized by increased leukocyte infiltration, edema, and upregulation of pro-inflammatory mediators. Elastic compression significantly attenuated this response, reducing leukocyte counts in subcutaneous lavage, histological inflammatory infiltrates, and the expression of key pro-inflammatory genes and proteins, including NF-κB, IL-1β, and TNF-α, at both 24 and 72 hours post-induction. Mechanistically, these effects may result from the compressive force altering microvascular dynamics and modulating macrophage polarization and mechanotransduction pathways, including TLR4 and integrin signaling. Additionally, compression preserved redox homeostasis, as indicated by stable oxidative stress markers and antioxidant responses. To our knowledge, this is the first study to demonstrate that elastic compression modulates inflammation at molecular, cellular, and tissue levels in an acute inflammation model. These findings support the therapeutic potential of elastic compression as a non-pharmacological strategy for managing acute inflammation, with possible applications in postoperative care, traumatic edema, and other soft tissue inflammatory conditions. Further translational and clinical studies are warranted to validate these outcomes and guide evidence-based application protocols. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Laboratory and patient-oriented research on photoreceptors and vision in ageing and early and intermediate age-related macular degeneration (AMD) were conducted in parallel starting in the 1990s by Christine Curcio and Cynthia Owsley, respectively. They joined forces in two longitudinal observation studies, the Alabama Study on Age-related Macular Degeneration (ALSTAR) in 2009 and in ALSTAR2 in 2019, together involving >1100 participants. These studies established rod-mediated dark adaptation (RMDA) measured close to the fovea as the first functional biomarker for incident early AMD and the progression of AMD. These studies used standardised grading of colour fundus photography and prioritised large samples for statistical power. RMDA is a global measure of dysregulated transport between the circulation and photoreceptors, involving at least seven different steps in a retinoid re-supply route especially needed by rods, and a surrogate for the delivery of other essentials across this route. The choice of functional and imaging outcome measures was informed by a model of AMD pathophysiology based on drusen biology, as discovered in the laboratory using high-quality human donor eyes. Specifically, high-risk drusen in the central retina were thought to result from large lipoproteins constitutively made by the retinal pigment epithelium and impaired in transit to circulation by ageing changes in Bruch's membrane and choriocapillaris. Imaging studies in ALSTAR/2 thus included optical coherence tomography (OCT) angiography assessments of choriocapillaris flow signal and OCT assessments of outer bands involved in intercellular transfer (interdigitation zone). Of seven vision tests utilised in ALSTAR2, only RMDA achieved a Minimum Clinically Important Difference at 3 years follow-up. This research highlights the importance of developing functionally valid structural endpoints for use in early and intermediate AMD intervention trials. Research to date supports the idea that functional changes emerge earlier than structural changes in early and intermediate AMD. Clinicaltrials.gov # NCT04112667 (registration date October 7, 2019).
Although pelvic landmarks have traditionally been used to estimate the femoral head center (FC), their reliability may be limited in patients with developmental dysplasia of the hip (DDH). In contrast, femoral-based reference methods have been insufficiently investigated. This study aimed to evaluate the feasibility and clinical utility of estimating the FC location in DDH using a three-dimensional model derived from trochanteric landmarks. We retrospectively analyzed 128 femurs from 84 female patients with DDH (mean age, 36.9 years) who underwent curved periacetabular osteotomy (CPO) from April 1, 2010, to September 30, 2020, and had no symptoms involving the spine or knee. The FC was estimated using multiple regression models based on the three-dimensional coordinates (x, y, and z) of the greater and lesser trochanter tips. Differences between the estimated and actual FC positions were assessed along all three axes. Correlation coefficients between the estimated and actual FC ranged from 0.725 to 0.875 across the three directions. The mean absolute error was 2-3 mm, with greater errors observed in the anteroposterior direction than in the craniocaudal direction. An estimation error within 3 mm may be considered relatively small in the context of clinically acceptable ranges reported in previous studies for restoring femoral offset and leg length during total hip arthroplasty (THA), supporting the practical applicability of this method in preoperative planning. The accuracy of the present approach was comparable to that reported in healthy populations and exceeded that of previous pelvic landmark-based regression techniques. This trochanter-based three-dimensional method enables clinically acceptable estimation of the FC in patients with DDH and may serve as a useful adjunct for planning of the femoral component when the native FC is difficult to identify.
Night vision goggles (NVGs) enhance vision under scotopic conditions by amplifying near-infrared light and converting it to a wavelength that can be seen by the human visual system. Although significantly more expensive than monocular systems, binocular NVGs provide the user with independent inputs to each eye, and therefore facilitate stereopsis, the ability to discriminate differences in depth from binocular cues. Past work examining stereopsis through NVGs has been mixed, with early-generation systems showing no evidence for stereopsis while more-modern systems show some evidence for (and others against) stereopsis, albeit at levels below that observed under natural photopic viewing conditions. These studies have examined stereopsis through NVGs under ideal conditions that isolate binocular contributions to depth perception. In the present study, stereopsis through NVGs was examined under more realistic conditions and for more operationally relevant tasks. The results show that stereopsis through NVGs persists even under degraded viewing conditions and provides a binocular advantage for real-world tasks where the perception of depth plays an important role. These results show that limitations in stereoacuity through NVGs are not driven by visual acuity limits, as has been previously argued, and more generally a dissociation between visual acuity and stereoacuity.
Leishmaniasis remains a major public health challenge in many tropical and subtropical regions despite long-standing emphasis on controlling adult sandflies. This commentary highlights an important ecological gap that has received limited attention: the immature stages of sandflies. Unlike mosquitoes, sandflies develop in cryptic terrestrial microhabitats that are rarely detected through routine surveillance. Consequently, most vector control programmes concentrate on suppressing adult populations, while the biological processes that generate new adult vectors remain poorly understood. Recent ecological studies indicate that breeding activity may be spatially structured and biologically detectable. Surveillance approaches that consider oviposition behaviour and breeding ecology may therefore help make vector population dynamics more measurable and support more sustainable, biology-based control strategies.
Activities of daily living (ADL) are associated with declines in physical fitness and subjective health. However, it remains unclear as to whether ADL impairments are related to specific components of physical fitness and health variables. Therefore, we examined differences between community-dwelling older persons with versus without ADL impairments with regard to various physical fitness components, physical complaints as well as subjective and objective health outcomes. Cross-sectional study among 254 participants aged ≥ 55 years [51% female; 84 with ADL impairments; mean (SD) age 62.1 (6.6) years] enrolled in the population-based "Gesundheit zum Mitmachen" study in Southwestern Germany. ADL, physical complaints and subjective health status were assessed using a self-report questionnaire, physical fitness (cardiorespiratory fitness, strength, gross motor coordination, flexibility, and functional mobility) was assessed using a fitness test battery, and objective health status was derived from health exam performed by a physician. We ran analyses of covariance, adjusted for age, sex, body mass index and education. Participants with ADL impairments had statistically significantly worse subjective (p < 0.001) and objective (p < 0.001) health and reported more physical complaints (p < 0.001) compared to those without ADL impairments. Regarding physical fitness, ADL-impaired participants performed worse in 10 out of 12 variables. The findings provide additional evidence that ADL impairments are related to decreased objective and subjective health and physical fitness in older community-dwelling adults. Future studies employing more comprehensive, preferably objective, ADL assessments and considering cognitive impairments, which may also impact ADL performance, are warranted.
Introduction: A vast body of cognitive research in psychosis has focused on auditory hallucinations, though more recent studies are turning towards other sensory modalities. This study aimed to compare the cognitive profile of persons experiencing uni- or multisensory versus multimodal hallucinations. Methods: Participants with primary diagnosis of a psychotic disorder were subdivided into those experiencing uni- or multisensory (UMS; n = 31) versus multimodal (MM; n = 28) hallucinations relative to non-clinical controls (NC; n = 32). Cognitive assessment comprised the MATRICS Consensus Cognitive Battery, supplemented by a Colour Word Interference Test. Analyses of variance (ANOVAs) and correlation analyses were performed. Results: The UMS and MM groups performed significantly worse than the NC group on some cognitive domains (i.e. speed of processing, attention/vigilance, working memory, verbal learning), but not others (i.e. reasoning and problem-solving, social cognition). For visual learning, the MM group performed significantly worse than the NC group only, whereas for inhibition, the UMS group performed significantly worse than the NC group only. Conclusion: A novel cognitive profile associated with multimodal hallucinations was documented. Dissociation between performance of the two clinical groups on visual learning and inhibition suggests these cognitive domains may be of relevance to hallucinations, pending further investigations.
PIWI-interacting RNAs (piRNAs) are an important class of non-coding RNA molecules in epigenetic regulation. It plays a crucial role in maintaining genomic stability and inhibiting transposable elements, and have been proven to participate in various diseases by regulating gene expression and influencing signaling pathways. Traditional biological experimental methods have limitations such as low throughput, long cycles, and high costs, making them difficult to meet the requirements of large-scale systematic screening. In this study, we develop a predictive framework named PiDA-DVLSA. We integrate autoencoder, dual graph transformer, and multi-head self-attention mechanisms, and construct an end-to-end multimodal deep learning system. We use autoencoder to perform nonlinear dimensionality reduction and denoising on piRNA sequence features and disease phenotype semantic features, and extract potential representations with strong discriminative ability. Then, we use graph transformers to model the high-order topological relationships between nodes in isomorphic similar graphs, and input heterogeneous graph transformers to learn complex cross-entity interaction patterns in heterogeneous networks. Finally, we achieve adaptive fusion of multi-source information through multi-head self-attention mechanisms. PiDA-DVLSA performs excellently on the benchmark dataset, with AUC and AUPR reach 0.9437 and 0.9195, respectively, significantly outperform eight mainstream algorithms. In independent case validations for breast cancer, clioblastoma, and Alzheimer disease, our model successfully predicts multiple biologically significant potential associations, further confirming its practicality and effectiveness in real scientific research scenarios and providing a solid computational basis for future precision diagnostic and therapeutic applications. PiDA-DVLSA is freely available at https://github.com/zhaoqi106/PiDA-DVLSA .
Shaken Baby Syndrome and Abusive Head Trauma are significant traumatic brain injuries observed in infants and represent a critical public health issue. Although there is a vast literature on this subject, conducting a descriptive bibliometric analysis is essential to map the topic's quantitative development over time and to reveal its current geographical and conceptual distribution objectively. This study systematically analyzes 3,571 articles published between 1977 and 2025 in the Web of Science Core Collection database, examining the distribution of publications by year and country, leading journals, citation rates, and keyword networks. Our findings indicate a linear increase in the volume of SBS/AHT research publications since the 2000s. The analysis highlights two significant strengths and shifts in the literature. First, the emergence of countries from diverse regions-such as Romania, the United Arab Emirates, Malaysia, and Russia-in the literature network, alongside traditional research hubs, objectively confirms the subject's expanding global scope. Second, the fact that the highest citation rates and publication density are not limited to clinical medicine journals (e.g., Pediatrics) but are simultaneously concentrated in pioneering journals with social and legal content (e.g., Child Abuse & Neglect) highlights the field's multidimensional and interdisciplinary nature. In conclusion, this study provides an objective resource for all stakeholders-including physicians, forensic scientists, and legal professionals-by visualizing the current geographic diversity of scientific output, key terms, and journal dynamics.
Fair distribution of limited health funding is a universal challenge for health systems. Decisions about funding new technologies provide a helpful lens on this complex issue. This study examined how two of the world's most mature centralised review processes for health technology funding, namely the Australian Pharmaceutical Benefits and Medical Services Advisory Committees (PBAC and MSAC) have approached fairness over time. Using the Accountability for Reasonableness (A4R) framework, which defines fair priority-setting through four conditions (Relevance, Publicity, Revision, and Enforcement), we conducted (i) a detailed document review of policy changes (2014-2022) and (ii) semi-structured interviews with decision-makers at PBAC and MSAC in 2014 (n = 12) and 2021/22 (n = 11). In both the document review and the interviews, we found increased alignment with A4R principles over time, including enhanced Relevance through increased consumer representation, increased Publicity of decision rationales, and greater Enforcement through broader committee deliberation. However, Revision was not a pressing concern of committee members at either time point despite notable policy changes that improved Revision. Persistent barriers to Publicity were identified, particularly the redaction of decision rationales in public summary documents due to sponsor confidentiality requirements and challenges of explaining nuanced deliberations rather than formulaic criteria. Our findings illustrate how A4R principles are applied in practice and highlight the challenge of balancing procedural fairness with substantive ethical considerations, such as equity and cost effectiveness, that underlie the criterion of Relevance.
One-to-one face matching is widely used for identity verification yet becomes difficult with unfamiliar faces or when parts of the face are covered. We investigated whether observers could accurately verify identity from different nonoverlapping facial fragments. Each stimulus of our novel face-matching task had the appearance of a single face image as revealed through four circular 'spotlights,' one from each quadrant of the face. Observers judged whether the designated target spotlight (from Image A) depicted the same identity as the three reference spotlights sampled from a different image (all from Image B). Across three experiments, we examined observers' matching performance for familiar and unfamiliar faces under Baseline (Experiment 1), Scrambled (Experiment 2), and Inverted (Experiment 3) spotlight arrangements. Accuracy reliably exceeded chance across all but one condition: familiar inverted faces. A familiar-face advantage emerged under baseline conditions, disappeared when the spatial layout was scrambled, and reversed under inversion-while unfamiliar-face accuracy remained robust to these manipulations. These findings demonstrate that observers can exploit latent identity information without direct feature correspondence to achieve above-chance accuracy in identification and reveal an unexpected dissociation between familiar-face and unfamiliar-face matching when spatial orientation is disrupted in these highly challenging conditions.
Bacillus thuringiensis (Bt) is widely employed as a biological control agent against pests in tea plantations, yet its impacts on soil health and microbial ecology remain insufficiently understood. This study investigated the effects of two Bt application regimes, namely moderate-frequency conventional Bt application (Bt1, 3 sprays over 21 days) and high-frequency intensive Bt application (Bt2, 6 sprays over 42 days), on soil physicochemical properties, enzyme activities, and microbial community structure and function in tea soils. The moderate-frequency conventional Bt1 significantly improved soil nutrient status by increasing organic matter, available nitrogen, and potassium, and boosted acid protease, sucrase, and cellulase activities, while Bt2 achieved the maximum urease and polyphenol oxidase activities but failed to promote soil available nutrients and organic matter as effectively as Bt1. Although neither Bt treatment induced notable shifts in overall microbial alpha-diversity indices, community composition differed distinctly between the two treatments. Bt1 enriched beneficial taxa related to nitrogen fixation and organic matter degradation including Pseudomonas, Bradyrhizobium, and Sphingomonas, and sharply suppressed pathogenic fungi such as Aspergillus and Curvularia, whereas Bt2 caused an 18.29% reduction in Sphingomonas abundance with limited enrichment of beneficial bacteria. Functional predictions indicated that Bt1 amplified microbial carbon degradation and nitrogen cycling, enriched saprotrophic and symbiotic fungi and reduced plant pathogens by 85.78%, while both Bt treatments elevated saprotrophic fungi yet Bt2 only reduced pathogens by 11.84%. Co-occurrence network analyses revealed enhanced microbial interactions and community stability under Bt1, while excessive high-frequency Bt2 reduced network connectivity and stability compared with CK and Bt1. These results suggest that moderate-frequency conventional Bt application can positively modulate soil microbial communities and ecosystem functions, providing valuable insights for sustainable pest management and soil health maintenance in tea agroecosystems.
Glucagon receptor (GCGR) signaling is essential for glucose and lipid homeostasis, making it a potential therapeutic target for metabolic disorders. Zebrafish possess two GCGR co-orthologs, GCGRa and GCGRb, however, their distinct function remain unclear. In this study we employed CRISPR/Cas9 gene editing to generate GCGRa⁻/⁻, GCGRb⁻/⁻, and double-knockout (GCGR⁻/⁻) zebrafish to dissect isoform-specific functions. RNA-Seq analysis was performed to characterize transcriptomic alterations, while an overfeeding protocol was used to assess metabolic tolerance, and ligand-response assays in cell lines evaluated isoform activation dynamics. Transcriptomic analysis revealed that both isoforms regulate overlapping but distinct metabolic pathways. Functional enrichment analysis linked GCGRa to lipid and energy metabolism, cholesterol biosynthesis and glucose homeostasis, through key signaling cascades such as glucagon, PPARγ and PI3K-AKT. In contrast, GCGRb loss altered fatty acid β-oxidation, GPCR signaling, and oxidative phosphorylation networks, implicating roles in metabolism and cellular stress. The GCGR⁻/⁻ primarily impacted core metabolic networks including lipid, gluconeogenesis and energy metabolism, indicating complementary and overlapping functions of both receptors in maintaining hepatic metabolic homeostasis. Ligand-response assays revealed that GCGRb, but not GCGRa, is activated by both glucagon (GCGa) and glucagon like-peptide-1 (GLP1a), supporting the post-duplication receptor diversification theory. Notably, all knockouts exhibited impaired growth under high-nutrient conditions, confirming GCGR's role in diet-responsive development. This study provides the first systematic functional comparison of zebrafish GCGR isoforms, establishing zebrafish as a valuable model for investigating glucagon-based metabolic regulation and therapeutic interventions.
Knee osteoarthritis (KOA) is a common degenerative bone disease, and transcutaneous electrical nerve stimulation (TENS) is an alternative and complementary therapy (ACM). This study revealed the role of TENS in regulating the intestinal microbiota in KOA rats. This study concentrated on the intestinal microbiota of KOA rats which were treated with TENS for 1, 2, and 3 weeks. Three intensities of TENS were used to treat KOA rats, and the expressions of IL6/8, PI3K-AKT were measured. The intestinal microbiota was analyzed by 16 S rDNA sequencing. Compared with the Model Control group, TENS could improve symptoms of KOA rats and inhibit the expressions of IL6/8 by down-regulating the PI3K-AKT expression. After 3 weeks of treatment with TENS, compared with the Model Control group, the abundances of Bacteroidetes, Bacteroidetes, and Thermodesulfobacteria increased in the TENS groups; the abundances of Ficmicutes, Campylobacter, and Verruca decreased in the TENS groups. TENS could improve the histomorphology of knee and inhibit inflammation in KOA rats. After treatment with TENS, the intestinal microbiota gradually changed from 1,2,3 weeks and the abundance of them was different with three intensities of TENS. Further study will elucidate the underlying mechanisms of TENS in altering gut microbiota and the potential therapeutic applications of these intestinal microbiota for KOA.
In the context of mating, individuals of the same sex often act as rivals in the pursuit, attraction, and retention of desirable partners. This study explored the relationships between intrasexual competition and various aspects of human mating psychology across three countries: Canada, Hungary, and Indonesia. A total of 661 adults (including women, men, non-binary, and gender-unspecified individuals) completed an online questionnaire assessing sensation seeking, aggression, beauty-enhancing behavior, openness to cosmetic surgery, sexual motivation, and sociosexuality. Hypotheses were tested via Bayesian multilevel modeling. Measurement invariance testing and alignment procedures were conducted to address potential cross-cultural non-invariance. Results indicated that the superiority enjoyment component of intrasexual competition showed consistent positive associations with the examined psychological variables. Associations involving inferiority frustration were generally weaker and less consistent. The findings for openness to cosmetic surgery, sociosexuality, and aggression replicate prior research, whereas the links with sensation seeking, beauty-enhancing behavior, and sexual motivation extend the literature. Cross-national comparisons revealed no significant country differences in superiority enjoyment, whereas Canadian participants scored significantly lower than Hungarian and Indonesian participants in inferiority frustration, with no significant difference between the latter two groups. Overall, the findings suggest that intrasexual competition-particularly its superiority enjoyment component-shows consistent associations with mating-relevant psychological traits across cultural contexts, even when mean levels differ between societies.
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Cancer stem cells (CSCs) serve as critical drivers of cancer relapse, metastasis and drug resistance, and are closely associated with poor prognosis. Increasing evidence has highlighted the regulatory effects of CSCs on immune cells such as macrophages in the tumor microenvironment (TME). Therefore, it is imperative to thoroughly study the specific mechanisms by which cancer stemness traits modulate macrophages. Transcriptomic and clinical data of STAD were retrieved from The Cancer Genome Atlas (TCGA). A prognostic Lasso-Cox model was constructed based on CSC-related genes using the R package 'glmnet'. Pathway enrichment analysis was performed using the 'clusterProfiler' package. Composition estimation of infiltrating immune cells in STAD tissues was conducted by CIBERSORTx. Western blotting and flow cytometry were used to detect the expression of CSC-related and macrophage polarization-related markers. Through analysis of the TCGA-STAD dataset, 35 CSC-related genes were upregulated in tumor tissues and associated with shorter survival, whereas 4 CSC-related genes were downregulated and correlated with longer survival. These 39 genes were used to construct the prognostic model, from which an optimal 17-gene CSC-related signature was derived and used to stratify patients into high-risk and low-risk groups. The high-risk group was related to poorer prognosis than the low-risk group in both training and testing cohorts. Within this model, CXCR4 exhibited the highest regression coefficient and was significantly associated with poor prognosis in STAD patients. Furthermore, CXCR4 inhibition significantly attenuated CSC-like properties in STAD cells and reduced expression of the CSC markers CD44 and CD24. Immune infiltration analysis revealed that the proportion of M2 macrophages was significantly increased, while M1 macrophages were decreased in the high-risk group. Moreover, CXCR4 expression was positively correlated with hypoxia-inducible factors and glycolysis regulators, and CXCR4 facilitated M2 macrophage polarization and migration by regulating lactate secretion. We established and validated a CSC-related prognostic model that was closely associated with macrophage polarization and clinical outcomes in STAD. CXCR4 was identified as the key gene in this model, which unregulated lactate secretion to drive M2 macrophage polarization and maintain CSC properties in STAD, and may serve as a putative regulatory factor in STAD progression. The CXCR4 inhibitor AMD3100 exerted significant anti-tumor effects in vitro, suggesting that CXCR4 may serve as a promising prognostic biomarker and a candidate target for STAD.
The popularity of domestic cats (Felis catus) as companion animals is undisputed. However, the human-feline proximity poses potential health risks due to zoonotic disease transmission as well as physical injuries from bites and scratches. It is alarming to note that epidemiological data supports the prevalence and colonisation of Staphylococcus spp., including methicillin resistant Staphylococcus aureus (MRSA) in the oral cavity of cats. Considering the problem of antibiotic resistance globally, this review collates recent findings on the role of cats as reservoirs of antibiotic resistant pathogenic Staphylococcus spp. and examines the clinical implications of staphylococcal infections in cats. It provides an in-depth study into the link between pathogenesis and antibiotic resistance. In the context of "one health" the pathogenesis mechanisms enabling persistence and virulence such as colonisation, invasion, toxin and enzyme production, and immune evasion are also discussed. A mechanistic overview of promotion of antibiotic resistance in bacteria is provided, focusing on genetic adaptations such as target modification, efflux pumps, and gene acquisition. Patterns of antimicrobial resistance (AMR) among cat-derived isolates are critically assessed, outlining emerging trends and their implications for therapeutic strategies. Zoonotic concerns, vis-a-vis the impact of resistant Staphylococcus spp. on human health are addressed. The threats posed by rising antibiotic resistance, such as compromised treatment outcomes and the heightened risk of transmission across species are reviewed and strategies for mitigation, including preventive methods, ongoing surveillance, and the adoption of alternative non-antibiotic measures such as probiotics, bacteriophage therapy, and antimicrobial peptides, are suggested herein.
Atopic dermatitis (AD) is a heterogeneous disease often preceding food allergy (FA). However, it remains unclear how different developmental trajectories of AD/eczema influence the risk of FA. This study aimed to characterize longitudinal AD/eczema phenotypes from infancy to early adolescence and evaluate their specific associations with FA risk. We analyzed data from the Longitudinal Survey of Newborns in the 21st Century in Japan, including 23,767 participants followed from age 0.5 to 12 years. Distinct AD/eczema phenotypes were identified using group-based trajectory modeling derived from healthcare visit histories. Multivariable logistic regression examined the association between AD/eczema phenotypes and cumulative FA healthcare visit history, adjusting for sociodemographic factors and asthma comorbidity. Five AD/eczema phenotypes were identified: "Early-onset transient" (6.4%), "Early-onset persistent" (23.2%), "Toddler-onset persistent" (17.3%), "Late-onset" (2.1%), and "No/minimal symptoms" (51.0%). Compared with the "No/minimal symptoms" group, all AD/eczema phenotypes were associated with increased FA risk. The "Early-onset transient" (adjusted odds ratio [aOR], 2.33; 95% CI, 1.98-2.74) and "Early-onset persistent" (aOR, 2.33; 95% CI, 2.10-2.59) groups showed the strongest associations. The "Late-onset" phenotype was also associated with increased risk (aOR, 1.42; 95% CI, 1.04-1.93), with elevated risk observed in early childhood preceding the peak of overt skin symptoms. Distinct developmental trajectories of AD/eczema are differentially associated with FA risk. While early-onset phenotypes confer the highest risk, the elevated risk in "Late-onset" trajectories before peak symptoms suggests shared underlying susceptibility or subclinical pathology. Monitoring FA development is important across all clinical trajectories of AD/eczema. • Atopic dermatitis (AD) is a primary precursor for the atopic march, but how different longitudinal trajectories influence food allergy (FA) risk remains unclear. • Early-onset persistent AD is considered to pose the highest risk for FA. • Early-onset transient AD/eczema carries a high FA risk comparable to persistent cases, indicating that timing of onset is more critical than disease duration for FA development. • Late-onset AD/eczema trajectories show elevated FA risk in early childhood preceding peak skin symptoms, suggesting shared underlying susceptibility or subclinical pathology.
The AHL (acyl-homoserine lactone)-mediated quorum-sensing (QS) regulatory mechanism is ubiquitously distributed in gram-negative pathogens. In Dickeya oryzae, N-(3-oxo-hexanoyl)-L-homoserine lactone (OHHL), synthesised by ExpIEcz, regulates bacterial swimming motility and virulence. However, the role of its putative cognate receptor ExpREcz has not yet been characterised. In this study, we showed that deletion of expREcz alone did not cause significant changes in various phenotypes associated with D. oryzae physiology and pathogenesis. However, in the absence of a functional OHHL synthase ExpIEcz, ExpREcz was a potent repressor modulating the production of cellulases, polygalacturonases and zeamines, biofilm formation and pathogenicity of D. oryzae EC1, and it was a positive regulator modulating bacterial swimming motility. Further analysis showed that the regulatory activity of ExpREcz was abolished by OHHL, and that the QS signal might relieve the regulation of ExpREcz by interacting with two conserved AHL-binding residues of ExpREcz. Moreover, we found that ExpREcz repressed its own expression through a region in the 5' noncoding region of expREcz that lacks a canonical lux box. These findings suggest that the mechanism may enable D. oryzae to relieve ExpREcz suppression and initiate infection at high cell density when the QS signal reaches a threshold level.