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With improved survival rates in breast cancer, managing long-term morbidity of breast cancer patients is becoming increasingly relevant. Chronic pain after breast cancer surgery affects 20% to 60% of patients, of which 30% to 68% are neuropathic in nature. However, there is an existing gap in the literature concerning the exact prevalence of neuropathic pain, specifically regarding surgical axillary procedures in breast cancer patients. This systematic review and meta-analysis aimed to investigate the prevalence of neuropathic pain after axillary procedures, including axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). The electronic bibliographic databases Embase, Medline, and Web of Science were searched from inception until February 2025. Inclusion and exclusion criteria were defined to include studies reporting on neuropathic pain prevalence following axillary procedures in breast cancer patients. Meta-analyses were performed to quantify pooled prevalences. Overall, 15 studies met the inclusion criteria, of which 14 were included in the meta-analyses, encompassing 2725 patients. A pooled neuropathic pain prevalence after axillary procedures of 22.6% (95% confidence interval [CI], 15.5-30.6) was estimated in the meta-analysis. The meta-analyses on ALND (10 studies, 1253 patients) and SLNB (5 studies, 860 patients) revealed an estimated pooled prevalence of 26.9% (95% CI, 17.1-37.9) and 18.8% (95% CI, 10.5-28.5), respectively. Neuropathic pain affects approximately 1 in 5 breast cancer patients following axillary surgery, with higher rates after ALND than SLNB.

The introduction of radiolabeled nanoparticles in the realm of brachytherapy has led to a promising therapeutic strategy for cancer management called 'nanobrachytherapy'. In the quest of developing a potent radiolabeled inorganic biomaterial for use in nanobrachytherapy, we report the synthesis and evaluation of 169Yb [T1/2 = 32.02 d]-labeled glucuronic acid (GA) functionalised hydroxyapatite (HA) nanoparticles (GAHAnp) and established its potency in pre-clinical settings. GAHAnp having average hydrodynamic diameter of 45 ± 3 nm was synthesized and characterized using various analytical methods. Ytterbium-169 was produced with adequate radionuclidic purity by direct neutron activation of isotopically enriched Yb-target in research reactor. Radiolabeling protocol of GAHAnp with 169Yb to obtain [169Yb]Yb-GAHAnp in high yield and purity was optimized. Adsorption of [169Yb]Yb3+ on GAHAnp followed Langmuir-Freundlich isotherm and pseudo-second order kinetics. The mechanism of incorporation of [169Yb]Yb+3 on GAHAnp was investigated using density functional theory (DFT) and experimentally verified by radiotracer investigations and XAFS studies, which suggested replacement of Ca2+ with Yb3+ in GAHAnp matrix. The [169Yb]Yb-GAHAnp formulation demonstrated excellent in vitro radiochemical stability in physiological media and cell toxicity in Raji cells. SPECT/CT imaging and ex vivo biodistribution carried out after intra-tumoral administration of [169Yb]Yb-GAHAnp in tumor bearing mice showed near-complete retention of the formulation in the tumor mass upto 2 weeks. Tumor growth could be significantly arrested after administration of 30 MBq dose of the formulation compared to the control. These findings demonstrate the potential utility of synthesized [169Yb]Yb-GAHAnp formulation in the treatment of solid tumors through nanobrachytherapy.

Stroke remains a leading cause of mortality and neurological disability, highlighting the need for new therapeutic strategies. Recent studies have indicated that PARP7 is a novel target for stroke treatment. Herein, we report a series of small-molecule PARP7 inhibitors. Among these compounds, B-6 exhibited potent inhibitory activity on PARP7 (IC50 = 22.8 nM) and efficient blood-brain barrier (BBB) penetration (B/P = 63.7%). In vivo,B-6 demonstrated efficacy across multiple stroke models, significantly reducing cerebral infarct volume in the rat tMCAO model, and in both the rat tMCAO and mouse dMCAO models, suppressing acute inflammatory cytokine production and promoting sustained neurological and sensorimotor recovery over 21 days. Notably, B-6 retained neuroprotective efficacy when treatment was delayed for up to 12 h after ischemic onset. Cellular studies demonstrated that B-6-mediated PARP7 inhibition was accompanied by reduced neuroinflammation and astrocyte activation, attenuated autophagy-related alterations, and preserved synaptic marker expression. In summary, we have identified a brain-penetrable PARP7 inhibitor, B-6, and utilized it as a tool to further demonstrate that PARP7 could be a potential therapeutic target for stroke.

Impaired fatty acid oxidation (FAO) and neutrophil extracellular trap (NET) formation (NETosis) contribute to myocardial ischemia-reperfusion injury (MIRI). Whether cardiomyocyte metabolic dysfunction contributes to neutrophil activation remains unclear. We performed two-sample Mendelian randomization (MR) of 1400 plasma metabolites with ischemic heart disease (IHD) as the outcome, followed by summary-data-based MR (SMR) to prioritize candidate genes for the selected metabolite. Five mouse MIRI microarray datasets and a published cardiac single-cell RNA-sequencing dataset were analyzed to identify the relevant cell type and predict intercellular signaling. Direct binding of miR-221-3p to the Cpt2 3' untranslated region (3'UTR) was tested by dual-luciferase reporter assay. The proposed pathway was then examined in vivo using miR-221-3p antagomir, AAV9-shCpt2, and DNase I. Untargeted myocardial metabolomics was performed in Sham, MIRI, and MIRI + anti-miR-221-3p mice. MR identified 18 metabolites associated with IHD after false-discovery-rate (FDR) correction. Nervonoylcarnitine (C24:1) was the only risk-direction acylcarnitine (OR = 1.065, q = 0.030), whereas octadecanedioylcarnitine (C18-DC) showed the strongest protective association (OR = 0.924, q = 2.13 × 10-6). SMR using C24:1 as the exposure prioritized CPT2 as a candidate gene (b_SMR = -0.52). Across five MIRI microarray datasets, Cpt2 was shared by downregulated FAO and upregulated NET-related gene sets (area under the curve [AUC] = 0.869) and was negatively correlated with Ncf4 (r = -0.83) and Cyba (r = -0.80). Single-cell analysis localized Cpt2 downregulation to cardiomyocytes at day 1 after reperfusion. The cardiomyocyte FAO score was inversely correlated with the neutrophil NETosis score across animals (ρ = -0.49, P = 0.036), and CellChat predicted increased damage-associated molecular pattern (DAMP) and chemokine signaling from Cpt2-low cardiomyocytes to myeloid cells. Mmu-miR-221-3p was the only upregulated MIRI miRNA predicted by both miRWalk and TargetScan to target Cpt2, and the interaction was confirmed by reporter assay. In vivo, miR-221-3p antagomir pre-treatment restored CPT2, reduced reactive oxygen species (ROS) and NET-associated markers, lowered apparent infarct burden (percentage of total left ventricular area, %LV), and improved acute cardiac function. Concurrent AAV9-shCpt2 largely reversed these effects. Annotated C24:1 increased 68.9-fold in MIRI myocardium and decreased 11.4-fold after antagomir treatment (P = 9.2 × 10-4). MR and SMR prioritized C24:1 and CPT2, and subsequent transcriptomic, single-cell, in vivo, and metabolomic analyses supported the involvement of miR-221-3p-mediated CPT2 suppression in cardiomyocyte FAO impairment and NET-associated inflammation during acute MIRI. In this pre-treatment model, miR-221-3p inhibition restored CPT2, reduced cardiac injury and NET-associated changes, and lowered myocardial C24:1.

The high recurrence rate of herpes simplex keratitis (HSK) is primarily attributed to the reactivation of herpes simplex virus type 1 (HSV-1) within the trigeminal ganglion (TG), a latent viral reservoir cannot be eradicated by current antiviral or anti-inflammatory therapies. This study aims to elucidate the novel immune mechanisms regulating viral reactivation within the TG and to develop a targeted therapeutic strategy based on this mechanism. We found that macrophages are the key effector cells inhibiting viral reactivation in recurrent HSK models, exerting their core antiviral function through the release of macrophage extracellular traps (METs) rather than neutrophil extracellular traps (NETs). Mechanistically, MET formation is highly dependent on the activity of peptidylarginine deiminase 2 (PAD2). Importantly, METs function not merely as physical capture structures but act as signaling vehicles by releasing osteopontin (OPN) as a key messenger. OPN activates the expression of the interferon-stimulated gene ISG15 in adjacent neurons, thereby establishing a previously unrecognized "PAD2-METs-OPN-Neuron ISG15" immune-neuron synergistic antiviral axis. To translate this mechanism into a therapeutic strategy, we engineered a lipid nanoparticle encapsulating a PAD2-overexpressing plasmid, which was further camouflaged with macrophage membranes to construct the biomimetic delivery system pPAD2@MNPs. Unlike conventional gene delivery platforms, this system leverages the "homing effect" via VLA-4/LFA-1 on the membrane surface binding to VCAM-1/ICAM-1 at inflammatory sites, this system achieves precise targeting of TG lesions. In vivo experiments confirmed that local administration of pPAD2@MNPs significantly upregulates PAD2 expression within the TG, effectively reducing viral load and improving corneal pathology scores. Furthermore, biosafety evaluations revealed no significant systemic toxicity or major organ damage induced by this nano-system. In summary, this study reveals a novel mechanism of immune-neuron crosstalk in regulating HSV-1 latency within the TG and provides a safe and effective targeted nanomedicine strategy for the radical treatment of recurrent HSK.

Myocardial ischemia-reperfusion (I/R) injury is a major cause of ischemic cardiomyopathy and chronic heart failure, underscoring the need for new cardioprotective strategies. ATP synthase inhibitory factor 1 (IF1) maintains mitochondrial function and limits oxidative damage during I/R injury. Our previous work showed that IF1 protects the heart through AMPK activation; however, IF1 protein levels decline sharply during I/R despite stable mRNA expression, suggesting post-translational regulation. This study aimed to elucidate the molecular mechanism underlying IF1 instability and to characterize a newly identified phosphorylation site at serine 27 (S27). Mass spectrometric analysis of HEK293 cells overexpressing human IF1 identified a novel phosphorylation site at serine 27 (S27), and subsequent experiments validated that phosphorylation at this specific site was markedly induced during the I/R process. The functional role of IF1 was further investigated in an IF1-KO mouse model of myocardial I/R, comparing the effects of wild-type IF1 (WT) and a non-phosphorylatable IF1 mutant (S27A). Mass spectrometric analysis revealed S27 as a novel phosphorylation site of IF1 that is markedly induced during I/R injury. This phosphorylation promoted the interaction between IF1 and the E3 ubiquitin ligase NEDD4, enhancing IF1 ubiquitination and proteasomal degradation. In vivo, restoration of IF1-either WT or S27A-attenuated acute and chronic myocardial injury, preserved mitochondrial integrity, and improved cardiac function. Notably, the S27A mutant, resistant to phosphorylation-dependent degradation, provided superior cardioprotection compared with WT IF1. Glycogen Synthase Kinase-3 beta (GSK3β) mediated phosphorylation of IF1 at the newly identified S27 site destabilizes IF1 via the ubiquitin-proteasome pathway, contributing to myocardial I/R injury. Blocking this modification stabilizes IF1 and enhances cardioprotection. These findings reveal a previously unrecognized mechanism of IF1 regulation and identify S27 phosphorylation as a promising therapeutic target against reperfusion-induced cardiac damage.

Salivary cytokines can provide information about oral health and systemic diseases. We aimed to assess the salivary concentration of inflammatory cytokines in outpatients with Crohn's disease (CD) and whether the levels are modified by the presence of periodontal diseases. This cross-sectional study selected 72 individuals, 35 CD patients and 37 controls. Comprehensive medical and periodontal examinations were performed. Unstimulated saliva was collected and concentrations of interleukin (IL)-1&#x3b2;, IL-4, IL-6, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, IL-23, IL-27, interferon (IFN)-y, and tumoral necrosis factor (TNF)-&#x3b1; were analyzed by a bead-based multiplex assay. Salivary concentrations of TNF-&#x3b1;, IL-10 and IL-12p70 were significantly higher in CD patients compared to controls (p&#xa0;<&#xa0;0.05). Patients taking anti-TNF agents (n&#xa0;=&#xa0;16) and those taking conventional medication for IBD (n&#xa0;=&#xa0;14) had significantly higher levels of IL-12p70 and IL-23 than patients taking no medications (p&#xa0;<&#xa0;0.05). Linear regression analysis showed that CD was positively associated with the salivary concentrations of TNF-&#x3b1; and IL-10, while the percentage of pathological periodontal pockets associated positively with IL-1&#x3b2; and IL-10. CD patients showed higher salivary concentrations of TNF-&#x3b1; and IL-10, regardless of the periodontal condition.

A healthy diet rich in fibre-containing foods such as oats supports cardiometabolic health. Bioprocessing methods, including fermentation and enzymatic treatment, may further enhance the health benefits of oat-based foods by altering their physicochemical properties. The aims of this study were to investigate the effects of consuming fermented and non-fermented oat-based products enriched with fibre and protein on cardiometabolic outcomes gastrointestinal symptoms, and to consider how assessed physicochemical and nutritional differences between the products might relate to any observed effects. In a 12-week randomised crossover trial, 56 adults with mild metabolic deterioration consumed fermented (gurt) and non-fermented (porridge) oat-based products enriched with fibre and protein as part of their habitual diet for three weeks each. The study products were specifically developed and prepared for this study using identical ingredients. Primary cardiometabolic factors and gastrointestinal symptoms (GSRS) were measured at four time points, while secondary outcomes were assessed at baseline and after both product periods. Physicochemical and nutritional characterization of the study products included cereal &#x3b2;-glucan (BG) and protein molecular weight distribution, starch and sugar analysis, microscopy, acidity, and viscosity. During the gurt consumption, non-high-density lipoprotein (non-HDL) and low-density lipoprotein (LDL) cholesterol concentrations decreased (-0.15 &#xb1; 0.51 mmol/L, p = 0.028; and -0.12 &#xb1; 0.46 mmol/L, p = 0.047, respectively), with a minimal impact on blood pressure and GSRS scores. Additionally, ferritin was lower after the gurt compared with baseline (-4.00 [-16.50, 6.25] &#x3bc;g/L, p = 0.015). Similarly, ferritin levels were lower after the porridge period (-7.50 [-20.50, 4.25] &#x3bc;g/L), accompanied with a modest decrease in blood pressure and HbA1c. These effects, however, did not substantially differ between the product periods. Insulin showed a significant sequence effect (psequence&#x2217;time <0.05) and was analysed in sequence groups. Insulin levels significantly decreased during the gurt consumption in the group that started with the porridge (-2.22 &#xb1; 6.16 mU/L, p = 0.015). Fermentation and enzymatic treatment induced significant changes in BG MW, starch, and composition in the gurt, which may alongside with increased fibre intake during the intervention explain the observed results. Consuming a fermented, oat-based gurt as part of habitual diet may improve cholesterol metabolism, likely due to increased oat fibre intake rather than fermentation as such. Moreover, greater intake of oat-based products, regardless of processing, can reduce ferritin concentrations and marginally improve other cardiometabolic factors. The study was registered in ClinicalTrials.gov as NCT06393114.

Messenger RNA (mRNA) therapeutics formulated in lipid nanoparticles (LNPs) have transformed vaccinology and enabled a versatile platform for protein-based therapy across a wide range of diseases. Despite their clinical success, LNP-encapsulated mRNA (LNP-mRNA) systems are still largely designed through empirical screening due to an incomplete understanding of their in vivo behavior. This review systematically examines how in vivo imaging modalities have been used in the recent literature to interrogate LNP biodistribution, cellular uptake, and functional mRNA expression. Across the studies reviewed, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers have demonstrated that LNP biodistribution, including organ tropism and size-dependent transport, is governed by formulation parameters and route of administration. Liver and spleen accumulation dominate current systemic delivery profiles. Particles in the 20-100&#x202f;nm range generally favor efficient extravasation, cellular uptake, and lymphatic transport, while larger ones are gradually associated with reduced cellular internalization and increased reliance on cell-mediated transport to reach draining lymph nodes. Quantitative fluorescence and reporter-gene studies identified endosomal escape as the principal intracellular bottleneck, with less than 2% of internalized RNA typically reaching the cytosol. MRI results, although currently limited, have provided coherent evidence while offering a non-invasive approach for longitudinal monitoring of intracellular RNA trafficking. Imaging has also revealed a recurrent disconnect between LNP exposure and protein expression, demonstrating that LNP organ accumulation alone is an inadequate measure of productive delivery. Bioluminescent imaging approaches have enabled tracking of protein expression kinetics, showing that peak expression often occurs within hours post-administration, but varies significantly with ionizable lipid nature. Collectively, the recent literature indicates that in vivo imaging can help connect biodistribution and functional delivery with LNP designs. This review highlights that integrating quantitative in vivo imaging into the LNP-mRNA development pipeline enables mechanistic identification of delivery barriers and supports rational optimization of formulations.

The human brain exhibits a complex and hierarchical organization that supports efficient information integration across local and global scales. Accurately characterizing such topological organization from neuroimaging data remains challenging. Conventional graph neural networks (GNNs) effectively capture local dependencies through neighborhood aggregation but often overlook higher-order topological structures that reflect the brain's small-world organization. Although Transformer architectures enable global dependency modeling, their high computational cost limits scalability for large connected brain networks. To address these challenges, we propose a Topology-Constrained Graph Transformer Network (TC-GTN) that explicitly integrates brain network topology into graph learning. TC-GTN combines two complementary modules: a cycle-constrained graph convolution, which captures localized edge aggregation and models modular brain organization, and an MST-guided Transformer, which constrains global attention along minimum spanning tree (MST) pathways to efficiently model long-range dependencies while reducing redundant communication. Moreover, we introduce cycle-based edge positional encodings (CEPE) that provide a topological coordinate system for distinguishing edges with similar local structures but different cycle-level contexts. We evaluate TC-GTN on both structural and functional brain networks, extracted from diffusion-weighted imaging (DWI) and functional MRI (fMRI) respectively, using large-scale datasets, including UK Biobank (38557 participants; 18100 females/20457 males; age 40-70 years) and ABCD (7684 participants; 3782 females/3902 males; age 9-10 years). Experiments on sex classification and brain-age estimation demonstrate that TC-GTN consistently outperforms state-of-the-art graph network approaches, achieving superior accuracy, interpretability, and generalizability. Clinical significance analysis further demonstrates that the model accurately characterizes neuroanatomical divergence across pathological states. Using the brain age gap (BAG) as a biomarker, systemic accelerated aging is identified in multiple sclerosis and dementia, alongside heterogeneous structural alterations in stroke and Parkinson's disease. Our code is available at https://github.com/bieqa/TC-GTN.

The effects of long-term parental microplastic exposure on offspring immunity remain unclear. This study investigated how different parental exposure patterns affect immune status in F1 offspring. Parental rats were divided into four groups: paternal, maternal, dual-parental, and control. Treated groups received polystyrene microplastics (5&#xa0;mg/L) in drinking water for 90&#xa0;days. F1 offspring were raised under standard conditions until 8&#xa0;weeks of age, after which fecal samples, thymus, spleen, and serum were collected for immune evaluation. Maternal microplastic exposure significantly disrupted gut microbiota &#x3b1;-diversity, dysbiosis index, and composition in F1 offspring (all P&#xa0;<&#xa0;0.05). These changes were accompanied by decreased RBCs and PLT counts, elevated serum TNF-&#x3b1;, reduced thymic CD3+ and CD4+ T cells, and downregulated IL-10 mRNA and NF-kB protein expression. Histological examination revealed blurred corticomedullary boundaries, sparse cellularity, and lymphocyte vacuolization in the thymus, along with thinning of the periarteriolar lymphatic sheaths in the spleen, further indicating immune imbalance. Paternal and dual-parental exposure also induced gut microbiota dysbiosis and reduced thymic CD4+ T cells. Paternal exposure upregulated Th17-related ROR&#x3b3;t and TNF-&#x3b1; mRNA in the thymus, whereas dual-parental exposure decreased thymic Nrf2 protein, splenic CD4+/CD8+ ratios, and white pulp area. Thymic pathology was observed in both groups. In conclusion, our findings suggest that prolonged parental exposure to microplastics may disrupt immune homeostasis in F1 offspring by altering gut microbiota composition and modulating oxidative stress or inflammatory responses. Moreover, the extent of these effects varies with the different parental exposure patterns.

Intra-abdominal infections caused by Candida spp. (IAC) represent a major clinical challenge requiring a multidisciplinary approach due to difficulties in diagnosis, severity of disease, and the limited availability of therapeutic options. In the field of antifungal therapy, the armamentarium has recently been expanded with rezafungin, a novel echinocandin. The favourable pharmacokinetic and pharmacodynamic profile of rezafungin may support a potential role for this agent in the treatment of IAC. We performed a retrospective review of all consecutive patients treated with rezafungin as first- or second-line therapy for IAC during 2025 at IRCCS Humanitas Research Hospital, Rozzano, Italy. In addition, a narrative review of the English-language literature on the role of rezafungin in the management of IAC was conducted. A total of eight patients with IAC were included (75% male; median age [Q1-Q3]: 65 years (61-76)). Six patients were diagnosed with concomitant Candida bloodstream infection. Rezafungin was administered as first-line therapy in 37.5% (3/8) of cases. Microbiological eradication was achieved within 5 days in 50% (4/8), within 14 days in 87.5% (7/8) of patients, including those with incomplete source control. Two patients died within 30 days. No recurrence at 30 days were reported. No adverse events occurred. Based on our experience, rezafungin may be considered for the treatment of IAC both as first-line and salvage therapy. Further studies and clinical trials are needed to confirm and support these findings.

Heterogeneous graph neural networks capture rich heterogeneous semantics through meta-path modeling, but such semantic propagation may also amplify the prediction instability under structural perturbations. Existing robustness methods are often built upon specific assumptions about perturbation patterns, such as identifying and removing unreliable edges, which limits their generalization when structural perturbations deviate from these assumptions. To address this limitation, we propose a proactive structural stabilization framework for robust learning on heterogeneous graphs, termed Proactive STructural stAbilization for roBust LEarning (PSTABLE). During vulnerability assessment, PSTABLE identifies vulnerable nodes by jointly evaluating structural influence, predictive instability, and semantic participation from complementary perspectives. Based on this analysis, PSTABLE introduces learnable auxiliary nodes along key meta-paths to locally strengthen structural support around vulnerable regions. With model parameters fixed, PSTABLE optimizes auxiliary node representations using the prediction confidence of vulnerable nodes as feedback, thereby enhancing local semantic support while preserving semantic integrity. Extensive experiments under both poisoning and evasion attack settings demonstrate that PSTABLE consistently improves robustness under diverse structural perturbations while maintaining competitive performance on clean graphs.

Microplastics are emerging pollutants in aquatic systems that cause environmental and health threats and the detection methods are significantly important to guide the proper removal and degradation. However, rapid, sensitive and field-adaptable methods for microplastics analysis remain challenging. In this study, an electrocoagulation-assisted portable surface-enhanced Raman scattering (SERS) workflow was developed for the enrichment and detection of microplastics in aquatic matrices. Electrocoagulation was employed as a pre-concentration to recover microplastics from complex matrices, and the detection conditions, including pH, current density, and processing time were optimised for sensitive detection. Under the optimised calibration conditions, we can detect as low as 0.16-0.62&#x202f;&#x3bc;g/mL, depending on the type of microplastics and nanoparticle substrates. The spiked lake and river water samples were used to evaluate the recovery. Because microplastics can act as carriers for co-existing organic contaminants, caffeine was selected as a representative co-contaminant to assess microplastic-contaminant interactions, showing that oxidative ageing increased caffeine adsorption onto microplastic surfaces. Experimental results demonstrate the integration of electrocoagulation enrichment and portable SERS detection for near-site microplastic analysis, while also highlighting the influence of co-contaminant interactions on microplastic-associated signal interpretation.

Second-order understanding of mental states develops during middle childhood. However, due to the limited number of longitudinal studies on this topic, the timing of developmental changes and the stability of individual performance remain insufficiently explored. The current study examined the development of recursive theory of mind abilities, namely second-order ignorance and false-belief understanding, between the ages of 5 and 7. Using the Ice Cream Task and the Birthday Puppy Task, we longitudinally tested 166 Polish children at three time points (mean ages: MT1&#xa0;=&#xa0;5.64&#xa0;years, SDT1&#xa0;=&#xa0;0.23; MT2&#xa0;=&#xa0;6.69, SDT2&#xa0;=&#xa0;0.11; and MT3&#xa0;=&#xa0;7.63, SDT3&#xa0;=&#xa0;0.13). Although we observed overall growth in second-order mental state understanding, understanding of ignorance emerged two years earlier, showing smaller gains between ages 5 and 7 compared to false-belief understanding. Moreover, most children demonstrated consistent developmental trajectories in individual performance. These findings provide a comprehensive developmental overview of second-order mental state attribution, suggesting that, alongside gradual improvement, the observed rank-order stability in rToM may reflect partially stable individual differences over time.

To investigate somatic mutations in the whole genes of tissue samples from patients with oral leukoplakia (OLK), as the most typical precursor of oral cancer; and identify the specific genes as a mutational panel for predicting OLK malignant transformation. A total of 123 consecutive OLK patients with long-term follow-up (median, 73&#xa0;months) were prospectively enrolled, and divided into training set (n&#xa0;=&#xa0;92) and independent test set (n&#xa0;=&#xa0;31) based on chronological order of enrollment. Genomic DNA was isolated from the fresh-frozen biopsy tissues and somatic mutations in all genes were measured by whole-exome sequencing. We constructed a 3-gene (TP53, CASP8, and CYP2B6) mutational panel for risk stratification (any mutation vs. no mutation) of OLK malignant transformation. Kaplan-Meier analysis showed that the prognostic power of the 3-gene panel (log-rank P&#xa0;<&#xa0;0.0001) for risk stratification in malignant progression was better than that of pathological grade in the training and test set, respectively. Multivariate Cox regression analysis revealed that this panel was an independent variable significantly associated with progression in the training (hazard ratio [HR]&#xa0;=&#xa0;8.05; P&#xa0;<&#xa0;0.001) and test set (HR&#xa0;=&#xa0;11.26; P&#xa0;=&#xa0;0.0421), respectively. The area under the curve (AUC) with 95&#xa0;% confidence interval was 0.770 (0.648-0.892) and 0.877 (0.705-1.000) in the training and test set, respectively, for predicting malignant transformation in OLK patients. We established a 3-gene (TP53, CASP8, and CYP2B6) mutational panel as risk stratification model could effectively predict OLK malignant transformation, outperforming pathological grading-based assessment. Such genetic markers may provide a foundation for developing personalized management strategies.

Face processing is essential for social cognition, yet little is known about how race and gender biases in face processing develop as children encounter increasingly diverse social environments. This study investigated how preschool-aged children's prior familiarity with race and gender groups influences neural responses during face processing. Children aged 3-6 years viewed a stream of face stimuli using a fast period visual stimulation (FPVS) technique to record steady state visual evoked potentials (ssVEPs). In this task, images of different faces from one race/gender group were presented at 6 Hz (base category), with every fifth face presentation from a different race or gender, eliciting an oddball response at 1.2 Hz. Familiarity with different race and gender groups was determined by parental report. Robust frequency-tagged neural responses were observed across conditions, indicating reliable face processing responses. Faces from familiar race groups elicited larger general visual responses (6 Hz), whereas oddball responses (1.2 Hz) were enhanced for faces from unfamiliar race groups. These results suggest that children's prior familiarity with race groups biases visuocortical responses to faces and sensitivity to changes within the visual stream. No significant effects of face gender were observed. Topographic analyses revealed increasing right occipitotemporal activity with age, suggesting emerging lateralization of face processing networks. These findings demonstrate that experience with race groups, but not gender, modulates neural responses to faces in early childhood, and highlights the importance of real-world social exposure as a contributor to face-processing biases.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.