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Organic afterglow materials are garnering increasing attention due to their great potential in practical applications. To date, most organic afterglow materials can achieve only millisecond- or second-scale afterglow lifetimes, while realizing long persistent luminescence (LPL) lasting for hours or even days remains a significant challenge. Since 2017, when Adachi and Kabe first achieved LPL lasting over an hour in a purely organic system, LPL materials have undergone a decade of development, with polymer-based LPL materials exhibiting rapid progress in recent years. The energy level alignment in exciplex polymers and the resulting charge separation characteristics are closely associated with their unique LPL functional properties, primarily stemming from the well-designed donor and acceptor organic structures. This article provides a systematic review of the design strategies for LPL polymers and summarizes their current application advances in optical anti-counterfeiting, night-time illumination, smart textiles, and other related fields. Show less

The role of central histamine in diabetes induced behavioral despair is still an enigma. Therefore, the current research explored the plausible impact of the central histaminergic activity on the expression of diabetes-induced behavioral despair in mice using the tail suspension test (TST) and surose preference test (SPT) along with changes in the levels of BDNF and phosphorylated CREB (pCREB) in the whole brain, hippocampus, PFC, and amygdala. Post-streptozotocin (STZ) (200 mg/kg, i.p.) injection, on the 4 Show less

ObjectiveThis review synthesizes current evidence on the efficacy of acupuncture in managing chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients, focusing on its mechanisms, clinical applications, and future research directions.MethodsThis narrative review synthesizes and critically appraises findings from randomized controlled trials (RCTs), meta-analyses, and preclinical studies, evaluating acupuncture's impact on pain relief, neurological function, and quality of life. Key databases were searched for studies published up to 2024.ResultsNineteen RCTs ( Show less

This paper presents the Assimilation Modified Emotional (AME) algorithm, which is an enhanced version of the traditional label propagation algorithm (LPA) designed to address key challenges in social network analysis and emotional feature extraction. Traditional LPA methods, such as asynchronous label propagation and the Louvain algorithm, do not incorporate emotional representations and are often limited by local structural dependencies. The AME algorithm addresses these limitations by applying spectral algorithms, Markov chains, graph coarsening, and link prediction to simulate and optimize emotional transitions within the network. In addition, the AME algorithm enhances label representation through multi-label encoding, which allows for more accurate simulation of dynamic emotional states. Experimental results show that the AME algorithm achieves better performance than traditional LPA methods in terms of both accuracy and loss values. These findings indicate that the AME algorithm has strong potential for improving AI models used in social network analysis and emotional feature extraction. Show less

Pyroptosis, a pro-inflammatory form of regulated cell death mediated by gasdermin pore formation and typically triggered by inflammasome activation, has been increasingly recognized as an important contributor to liver inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). Despite accumulating evidence linking pyroptosis to MASH pathogenesis, the diagnostic value of pyroptosis-related genes in this disease remains largely undefined. Therefore, the present study aims to identify key pyroptosis-associated molecular signatures with potential utility for the diagnosis of MASH. Transcriptomic datasets and corresponding clinical information for MASH patients and healthy individuals were retrieved from the Gene Expression Omnibus (GEO) database. Differential expression analysis using the Limma package, followed by pathway enrichment analyses, was conducted to identify pyroptosis-related genes associated with MASH. Machine learning approaches were applied to systematically screen for core pyroptosis-associated markers and construct predictive models for MASH diagnosis. The robustness of selected gene signatures was further validated in independent datasets and in vivo animal models and vitro cellular models. Prognostic risk assessment was performed using a nomogram informed by key pyroptosis-related genes. Additionally, molecular subtyping of MASH based on pyroptosis gene expression profiles was explored to delineate disease heterogeneity. Through integrative bioinformatics and machine learning, five principal pyro-related genes-LPL, FABP4, STMN2, AKR1B10 and EEF1A2-were identified in MASH. Validation studies in animal model and cell culture systems confirmed the differential expression patterns of these genes. Among evaluated algorithms, Random Forest achieved the highest AUC (0.957) for diagnostic performance. All the five symbols were subsequently included in logistic regression and nomogram models, both demonstrating strong predictive value for MASH diagnosis. Molecular subtyping uncovered substantial variation in pyroptosis gene signatures, immune microenvironment characteristics, and pathway enrichment across MASH subgroups. This study highlights the relevance of pyroptosis-related gene signatures in MASH, providing a basis for enhanced diagnostic accuracy and paving the way for individualized therapeutic interventions targeting disease subtypes. Show less

High-grade serous ovarian cancer (HGSC) is the most aggressive subtype of ovarian epithelial cancer (OEC), with characters of late-stage diagnosis, high recurrence rate, and poor survival outcomes. Fucosyltransferase 8 (FUT8) is responsible for α1,6-core fucosylation biosynthesis, and aberrant FUT8/α1,6-core fucosylation level is involved in tumor progression. However, the roles and mechanisms of protein FUT8 and α1,6-core fucosylation in HGSC tumorigenesis and progression remain elusive. Here, our study confirms that elevated levels of FUT8/α1,6-core fucose in the tissues and serum of HGSC patients, and the elevation is associated with poor patient prognosis. By applying glycoproteomic assay, we globally screen and identify NCEH1 as the specific scaffold protein of α1,6-core fucosylation. Alpha 1,6-core fucose modification stabilizes NCEH1 by preventing its degradation through proteasomal pathway. Importantly, combined with non-targeted metabolomics analysis, α1,6-core fucosylated NCEH1 facilitates LPA secretion, driving M2-like polarization of tumor-associated macrophages in the tumor microenvironment, thus leading to oncogenesis and peritoneal metastasis of HGSC in vitro and in vivo. These findings broaden the understanding of FUT8/α1,6-core fucosylation/NCEH1 in HGSC progression and metastasis, and offer glycosylated diagnostic indicators and targets for therapeutic strategies in HGSC. Show less

Healthcare professionals are expected and motivated to engage empathetically with patients, their families, yet how different components of empathy, coping traits interact to shape psychological responses remains unclear. This study examined these relationships in medical, nursing students to inform tailored educational interventions METHODS: Participants who completed two surveys 2 years apart (30 medical students and 88 nursing students) were included. Empathy traits were assessed using the Interpersonal Reactivity Index, coping traits using the Brief Coping Orientation to Problems Experienced Inventory, and psychological responses using the Professional Quality of Life Scale. Mixed-effects models for repeated measures analyzed the impact of empathy and coping traits. Latent profile analysis (LPA) classified participants by empathy and coping traits. Personal distress was significantly associated with increased secondary traumatic stress (STS) and burnout, and decreased compassion satisfaction. Empathic concern was associated with increased compassion satisfaction. Active coping and support seeking were associated with increased compassion satisfaction and reduced burnout, whereas indirect coping was associated with increased STS and burnout. LPA identified three distinct profiles of empathy and coping traits, showing significant differences in psychological responses. Differences in empathy and coping traits influence psychological responses in medical and nursing students. Tailored interventions that consider these traits may be more effective. Show less

High-grade astrocytoma with piloid features (HGAP) has recently emerged as an aggressive glioma entity with distinct molecular alterations, yet its clinicogenomic distinction from pilocytic astrocytoma (PA) remains to be fully elucidated. This study aims to clarify the clinical, pathological, and genomic differences between pediatric PA, adult PA, and HGAP, and to provide evidence supporting the recognition of HGAP as a new, aggressive entity. We retrospectively analyzed 100 genetically and histopathologically confirmed PA cases (87 pediatric, 13 adult) and 25 HGAP cases (all > 19 years old) diagnosed at Seoul National University Hospital between 2015 and 2024. Next-generation sequencing using a brain tumor-specific gene panel and immunohistochemistry evaluation. Pediatric PAs (median age 7 years) were predominantly cerebellar (61%) and showed classic biphasic histology (72%) with frequent HGAP represents a clinically aggressive and molecularly distinct high-grade glioma, clearly separable from pediatric and adult PA. Its poor prognosis and unique genetic drivers justify its recognition as a new entity. Accurate molecular profiling is essential for diagnosis and management of these tumors, and the poor survival outcomes observed in HGAP highlight the need for further larger cohort studies to identify optimal therapeutic strategies. Show less

Community-acquired pneumonia (CAP) is still a leading cause of death due to infection globally, yet precise severity assessment remains a significant clinical problem. More than any other group of cytokines, interleukins are central to the regulation of inflammation and shed light on this intricate pathology. In the present review we summarize the biological and clinical characteristics of some of the principal interleukins (ILs) in CAP, classified primarily according to their physiological activity as pro-inflammatory (IL-2, IL-6, IL-8 and IL-12), anti-inflammatory (IL-7, IL-10 and IL-37), dual-action (IL-4 and IL-17), and emerging factors (IL-3, IL-27 and IL-33). Additionally, recent multimodal approaches are discussed such as combining cytokines with organ dysfunction parameters (MR-proADM) or revealing host-response patterns to inform antibiotic and corticosteroid management. We propose that the field needs to transition to immunological endotyping, multi-omics (integrating genetics and lung microbiome), and artificial intelligence (AI) models based on dynamic patient data to achieve precision medicine in CAP management. Show less

Sevoflurane, a widely used volatile anesthetic, has raised concerns regarding its potential developmental toxicity, particularly due to its extensive application in non-obstetric surgeries and fetal intervention procedures during pregnancy. However, its effects on heart development and function remain unclear. Using zebrafish larvae as a model, we investigated the effects of prolonged sevoflurane exposure (0.04-0.08%) from 10 to 72 h post-fertilization (hpf). Under these conditions, treated larvae exhibited dose-dependent developmental abnormalities, including reduced body length, pericardial edema, and impaired heart tube looping. Cardiac function analysis revealed significant decreases in ejection fraction, stroke volume, heart rate, and cardiac output, indicating impaired cardiac contractility and pumping efficiency. These functional impairments were accompanied by structural changes including ventricular wall thinning and chamber dilation, along with upregulation of cardiac stress markers (nppa, nppb) - characteristic features of dilated cardiomyopathy (DCM). Molecular analysis demonstrated downregulation of sarcomeric (tnnt2a, mybpc3) and calcium-handling (atp2a2a, slc8a1a) genes, suggesting disruption of sarcomere integrity and calcium homeostasis. Additionally, sevoflurane exposure elevated inflammatory cytokines (il-6, tnf-α, il-1β) and promoted leukocyte infiltration into cardiac tissue. RNA sequencing analysis implicated dysregulation of Apelin signaling pathway, with reduced prkaa2 (AMPKα2) expression and phosphorylation observed in both zebrafish and H9C2 cardiomyocytes. Critically, pharmacological activation of AMPK using A-769662 effectively mitigated sevoflurane-induced cardiotoxicity, identifying AMPKα2 as a potential therapeutic target. Collectively, these findings delineate the molecular mechanisms underlying sevoflurane-induced developmental cardiotoxicity following prolonged exposure in zebrafish and suggest that targeting AMPKα2 signaling merits investigation as a potential strategy to mitigate anesthetic-related cardiac developmental risks. Show less

This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HFD, n = 30). After 8 weeks of HFD feeding, 24 obese rats were further randomised into three subgroups: HFD (H, n = 8), HFD + moderate-intensity training (HMT, n = 8), and HFD + HIIT (HHT, n = 8). The HMT and HHT groups underwent 8 week training interventions (six sessions/week). The HMT protocol included a 10 min warm-up (treadmill speed: 10 m/min), a 40 min moderate-intensity aerobic phase (60%-70% of maximum speed), and a 10 min recovery (10 m/min). The HHT protocol featured 10 min warm-up and recovery phases (10 m/min), with 40 min of alternating treadmill training: 3 min at 50% maximum speed followed by 3 min at 90% maximum speed. No significant differences in body weight were observed between the HHT and HMT groups. HHT rats displayed significantly lower plasma triglyceride levels than H and HMT rats. Compared with HMT, HHT reduced adipose mass and adipocyte size and increased mitochondrial succinate dehydrogenase and cytochrome c oxidase (COX) activities in adipose tissue. However, HHT rats displayed lower COX activity in visceral white adipose tissue than HMT rats. Training upregulated browning-related genes and uncoupling protein 1 (UCP1) in adipose tissue, with stronger effects in HHT than in HMT. Plasma and adipose tissue IL-27 levels, as well as p38 MAPK-PGC-1α signalling pathway activation, were significantly elevated in both training groups, with greater increases in HHT. HIIT promotes adipose tissue browning by activating the IL-27 signalling pathway and ameliorates obesity-associated metabolic disorders more effectively than MAIT, supporting its potential as a therapeutic strategy for obesity. Show less

Myocardial ischemia/reperfusion (I/R) injury commonly occurs in patients undergoing cardiac or noncardiac surgeries, increasing perioperative mortality risk. Although numerous endogenous mediators released during I/R contribute to myocardial damage, their mechanisms require further elucidation. We investigated whether lysophosphatidic acid (LPA), a bioactive phospholipid, mediates myocardial I/R injury by interacting with cardiac transient receptor potential vanilloid 1 (TRPV1). A TRPV1K710N knock-in mouse model was generated by CRISPR/Cas9, introducing a point mutation at K710, the known LPA-binding site on TRPV1. Langendorff perfused isolated hearts from TRPV1K710N and wild-type (WT) mice underwent global I/R injury with or without exogenous LPA (10 μM). Myocardial infarct size, coronary effluent LDH levels, and mitochondrial ultrastructure/function were assessed. Additionally, H9c2 cardiomyocytes were transfected with a pCMV6-entry plasmid carrying TRPV1-K710N or TRPV1-WT for mitochondrial calcium influx and cell viability assays. The V1-Cal peptide (1μM), targeting the K710 region, was applied ex vivo and in vitro to block LPA-TRPV1 interaction. TRPV1K710N hearts exhibited resistance to global I/R injury versus WT hearts, with reduced infarct size (28.3 ± 2.4% vs 39.9 ±2.3%, respectively, P= 0006), lower LDH levels, and attenuated mitochondrial damage. Exogenous LPA exacerbated I/R injury in WT hearts, increasing infarct size (63.7 ± 1.2% vs vehicle: 38.4 ± 2.4%; P <.0001), LDH release, and mitochondrial damage. TRPV1K710N hearts were resistant to LPA-induced injury, with no significant increase in infarct size after LPA treatment. Exogenous LPA induced pronounced swelling in mitochondria isolated from WT hearts, while mitochondria from TRPV1K710N hearts showed resistance to LPA challenge. In H9c2 cells, LPA significantly decreased viability in rTRPV1-WT cells and elevated mitochondrial calcium influx relative to rTRPV1-K710N cells. V1-Cal peptide attenuated LPA-mediated myocardial injury in WT hearts and reduced mitochondrial calcium overload in H9c2 cells. Blockade of the TRPV1 K710 site by K710N mutation or V1-Cal peptide mitigates LPA-mediated myocardial injury and mitochondrial damage/dysfunction in isolated mouse hearts. Targeting the cardiac LPA-TRPV1 interaction represents a promising therapeutic strategy against perioperative myocardial injury. Show less

Rosette-forming glioneuronal tumors (RGNTs) are rare, World Health Organization grade 1 tumors that typically arise around the fourth ventricle. However, cerebral hemisphere RGNTs have recently been reported, with some exhibiting clinical features resembling low-grade epilepsy-associated tumor (LEAT). We report a case of multifocal RGNT in a patient with drug-refractory epilepsy. A 14-year-old woman was incidentally found to have multifocal brain tumor involving the left temporal lobe and bilateral thalamus, she developed drug-resistant epilepsy ten years later and underwent surgery. Partial tumor resection and anterior temporal lobectomy were performed. Histopathology revealed a glioneuronal tumor with oligodendroglia-like cells, neurocytic rosette, and perivascular pseudorosette, exhibiting an infiltrative growth pattern extending into the white matter. Genetic analysis revealed Fibroblast Growth Factor Receptor 1 mutation. The methylation profile analysis matched the low-grade glioneuronal tumor class but did not yield to any subclass category. Finally, the tumor was diagnosed as RGNT-like low-grade glioneuronal tumor with dysembryoplastic neuroepithelial tumor (DNT) features. Cases presenting with a LEAT-like clinical course and exhibiting histopathological features of RGNT are often difficult to definitively distinguish from DNT based on histological and genetic findings. Epilepsy-associated RGNT may harbor genetic profiles distinct from those of prototypical RGNTs, highlighting the need for further investigation. Show less

Pemigatinib is a selective, potent, orally administered inhibitor of fibroblast growth factor receptor (FGFR)1-3 with antitumor activity in multiple solid tumors. Pemigatinib is used to treat adults with previously treated metastatic or surgically unresectable cholangiocarcinoma with Show less

Lecanemab is a monoclonal antibody targeting amyloid-beta protofibrils, indicated for patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease. This study reports interim findings of an ongoing, multicenter, prospective, observational post-marketing study for all patients treated with lecanemab in routine clinical practice in Japan, focusing on amyloid-related imaging abnormalities (ARIAs) and infusion-related reactions primarily observed during up to 28 weeks after treatment initiation. Patients treated with lecanemab at any medical institutions across Japan are included in the study. Data are collected using an electronic data capture system via standardized case report forms (CRFs). Study items included the incidence of ARIA, ARIA-edema or effusion (-E), ARIA-hemorrhage (-H: cerebral microhemorrhages, superficial siderosis, and macrohemorrhage), and infusion-related reactions, reported as adverse drug reactions. As of July 5, 2025, CRFs from 2675 patients were collected, of whom 2672 had data available for the interim analysis. The median age was 76.0 years, and 62.6 % (1672/2672) of patients were diagnosed with MCI. At Week 28, 7.3 % (195/2672) of patients discontinued treatment, with a mean treatment duration of 189.6 ± 34.4 days. Among 2634 patients confirmed to have undergone MRI scans after treatment initiation, ARIA was observed in 7.1 % (188/2634) of patients, ARIA-E in 3.0 % (78/2634), and ARIA-H in 5.2 % (137/2634). Serious ARIA-H (macrohemorrhage) occurred in two patients (0.1 %). Infusion-related reactions were observed in 17.0 % (455/2672), including 0.7 % (18/2672) serious cases. The proportion of patients who experienced ARIA was highest in patients with apolipoprotein E (APOE) ε4 homozygotes. This interim analysis represents one of the largest real-world lecanemab cohorts reported globally to date. Although absolute rates are not directly comparable with those from clinical trials, the trends in ARIA distributions across APOE genotypes and infusion-related reactions were comparable to those observed in clinical trials. Show less

Lipid abnormalities are emerging as key pathogenic mechanisms in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Astrocytes in the brain provide apolipoprotein E (APOE) proteins and influence neuronal metabolism and health. Using live-cell imaging and objective neurite imaging techniques, we induced cellular lipid load (cholesterol and triglycerides) by inhibiting the lysosomal cholesterol transport protein NPC1 in human neuron-astrocyte cocultures and examined the effects of CRISPR-edited APOE3 and APOE4 human astrocytes on the rescue of dystrophic neurites, where axons and dendrites of nerve cells become disfigured. APOE3, but not APOE4 or APOE knockout, astrocytes prevented cholesterol- and lipid-induced neurite damage in APOE4 neurons. In the media of APOE3 neuron-astrocyte cocultures, high-density lipoprotein-like particles were larger and presumably more lipidated than those in equivalent APOE4 cocultures. This discovery highlights that living APOE3 astrocytes control key biological mechanisms by physiologically enhancing lipid cellular homeostasis and rescuing lipid-induced neurite structural abnormalities relevant to Alzheimer's disease and neurodegenerative diseases. Show less

This study investigated the synergistic effects of combining ferulic acid esterase (FAE)-producing lactobacillus with homofermentative and heterofermentative lactic acid bacteria (LAB) on the fermentation quality, nutrient composition, and aerobic stability of corn stover silage. In this study, five LAB strains were isolated and identified from various silages. Among them, strain AR1 was identified as The results showed that the co-fermentation of homofermentative and heterofermentative strains improved silage fermentation quality. The addition of AR1 to the combination of homofermentative and heterofermentative LAB further enhanced lactic acid and acetic acid production, decreased neutral and acid detergent fiber contents, and improved aerobic stability. Principal component analysis and membership function analysis identified the LPLR group (an equal mixture of AR1, R10, JF2, and R3 at 1 × 10 Show less

Ovarian cancer remains a major cause of mortality in women aged 74 years and under. Dysregulation of the PI3K/AKT/mTOR and NFκB signaling pathways has been associated with poor outcomes and treatment resistance. This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling). Their efficacy was tested in 3D collagen models of ovarian cancer, using SKOV3 and OVCAR8 cell lines, activated by tumor necrosis factor-alpha (TNFα) and lysophosphatidic acid (LPA). Using concentrations derived from 2D assays, viability, collagen gel sizes, secretion of interleukin 6/8 (IL-6/8) and signal pathway proteins were analyzed. All compounds were less effective in 3D models than in 2D cultures, with high cell viability maintained. TNFα and LPA did not significantly alter drug sensitivity, and collagen gel contraction was largely unaffected. While the compounds did not consistently change signaling protein levels, they generally reduced secretion of pro-inflammatory cytokines IL-6 and IL-8. Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models. Show less

Chemotherapy has significantly improved survival in breast cancer and, in the neoadjuvant setting, contributes to tumor downstaging and increased rates of breast-conserving surgery while enabling in vivo assessment of tumor biology and chemosensitivity. Pathological complete response (pCR) is a key endpoint associated with favorable outcomes; however, tumor heterogeneity highlights the need for reliable predictive biomarkers. This study evaluated the mRNA expression of 13 candidate genes in relation to molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) to identify potential predictive and prognostic markers. Pretreatment core biopsies from 92 patients receiving NAC were analyzed by quantitative RT-PCR. Molecular subtypes were determined by immunohistochemistry (ER, PR, HER2, Ki67), and pathological response was classified using the Miller-Payne scale as good (MP 4/5) or poor (MP 1-3). Multivariate logistic regression assessed associations between gene expression, subtype, and pCR. Hormone receptor-positive tumors showed significantly higher expression of Show less

IntroductionPulmonary artery (PA) cannulation is emerging as a method for concurrent cardiac and respiratory failure, but limited data exists on how cannula positioning, particularly cannula tip angle, affects perfusion symmetry. Due to varying pulmonary bifurcation geometry between patients, ensuring even distribution of oxygen-saturated blood becomes critical. This computational fluid dynamics (CFD) study investigated the effects of cannula positioning and angles on oxygen delivery within the PA using 6 different configurations.MethodAn idealized PA geometry based on a CT scan was constructed including the 6 different cannula configurations: two straight (short and long) and four angled (5° and 10° toward either pulmonary branch). Simulations assumed laminar, steady-state flow at 6 L/min total (50% ECMO contribution). Oxygen transport was modeled as a passive scalar with 75% saturation from the heart and 100% from the cannula. Perfusion symmetry was quantified using the absolute difference in mean oxygen saturation (ΔSaO Show less

This study aimed to use latent profile analysis (LPA) to identify heterogeneous configurational patterns of short video addiction and emotion dysregulation among college students, and to systematically examine the predictive effects of cognitive reappraisal, emotional loneliness, and sociodemographic factors on latent profile membership. A cross-sectional survey design was employed. From April to July 2025, full-time undergraduate students were recruited from multiple universities in Shandong Province using a combination of convenience sampling and snowball sampling. Participants completed online questionnaires including the Short Video Addiction Scale, the Emotion Dysregulation Inventory (EDI), the Cognitive Reappraisal Scale, and the Emotional Loneliness Scale. A total of 1,168 valid questionnaires were obtained. LPA identified four optimal profiles: Profile 1 ("low short video addiction-low emotion dysregulation"), Profile 2 ("medium to lower short video addiction-medium to lower emotion dysregulation"), Profile 3 ("medium to upper short video addiction-medium to upper emotion dysregulation"), and Profile 4 ("high short video addiction-high emotion dysregulation"). Multivariable logistic regression analyses indicated that, with Profile 4 as the reference category, cognitive reappraisal significantly increased the likelihood of membership in lower-risk profiles, whereas emotional loneliness significantly decreased the likelihood of membership in lower-risk profiles. Among sociodemographic factors, being female and having an urban background significantly increased the likelihood of membership in Profile 1 (vs. Profile 4); being a non-only child and having no part-time work experience significantly predicted membership in Profile 3. Marked heterogeneity exists among college students in the measured dimensions of short-form video addiction and emotion dysregulation, and the two constructs exhibit highly concordant co-variation. The findings provide empirical support for developing risk-stratified and precision-oriented mental health intervention strategies. Show less

This study investigated the relationships between vacant land and key adverse health behaviors, including smoking, insufficient sleep, and no leisure-time physical activity (No LPA), across census tracts in Chicago, Illinois. Using both global regression and geographically weighted regression (GWR), we evaluated whether neighborhood vacant land ratios (VLRs) were associated with the prevalence of these adverse health behaviors and assessed how these associations varied spatially across the city. We found significant spatial clustering in both vacant land and health behavior indicators, and the spatial clustering patterns of neighborhood vacancy and adverse health behaviors were broadly consistent. In global models, higher VLRs were associated with higher prevalence of adverse health behaviors; after accounting for spatially autocorrelated errors, the associations remained robust for smoking and insufficient sleep but were attenuated for No LPA. GWR results further revealed clear spatial non-stationarity, with stronger positive local associations concentrated in low-income neighborhoods on the south and west sides. When overlaid with Healthy Chicago Zones (HCZs), the strong vacancy-behavior associations aligned primarily with the West, Southwest, Near South, and Far South zones, highlighting these HCZs as priority areas where vacancy was most strongly linked to adverse health behaviors. Our findings support theories of neighborhood disorder and spatial inequality, emphasizing that vacant land is a potentially modifiable environmental determinant of health behaviors and calling for tailored interventions that consider local social and economic contexts to improve community health and advance health equity. Show less

The full impact of APOE4 (apolipoprotein E4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear, particularly during early preclinical stages of disease. Here we show that young APOE4 knockin (E4-KI) mice exhibit hippocampal region-specific network hyperexcitability that predicts later cognitive deficits. This early phenotype arises from cell-type-specific subpopulations of smaller, hyperexcitable neurons and is eliminated by selective removal of neuronal APOE4. With aging, E4-KI mice develop granule cell hyperexcitability, progressive inhibitory dysfunction and excitation-inhibition imbalance in the dentate gyrus. Single-nucleus RNA sequencing with multilevel gene filtering reveals age-dependent and cell-type-specific transcriptional changes and identifies candidate mediators of early neuronal hyperexcitability, including Nell2. Targeted CRISPR interference knockdown of Nell2 rescues abnormal excitability, implicating Nell2 as a contributor to APOE4-driven dysfunction. Together, these findings define molecular and circuit mechanisms linking neuronal APOE4-induced early network impairment to AD pathogenesis with aging. Show less

Elevated lipoprotein(a) predicts high risk of cardiovascular disease among a modest proportion of healthy individuals, an issue that complicates screening guidelines. To examine spline models, clinical thresholds, and percentiles of baseline lipoprotein(a) levels as 30-year determinants of cardiovascular risk. This cohort study was conducted among female health professionals participating in the Women's Health Study, who were followed up prospectively from 1993 to 2023. Women without cardiovascular disease, cancer, and other major chronic illnesses had blood samples taken at baseline. All individuals with lipoprotein(a) measurements and/or of European ancestry with genotype information for the LPA rs3798220 variation were included. Data analyses were performed from January through April 2025. Continuously valued baseline lipoprotein(a), lipoprotein(a) clinical thresholds and percentiles, and LPA rs3798220 genotypes known to predict lipoprotein(a) levels among individuals of European ancestry. The primary outcomes were incident major cardiovascular events, coronary heart disease, ischemic stroke, and cardiovascular death. Age- and multivariable-adjusted cause-specific Cox models were used to calculated hazard ratios for the cardiovascular outcomes. The hypothesis was formulated after collection of the data. A total of 27 748 women with baseline lipoprotein(a) measurements and 23 279 women of European ancestry with rs3798220 genotype information were included (median [IQR] age, 53 [49-60] years), among whom 3707 and 3165 major cardiovascular events, respectively, accrued during a median (IQR) follow-up period of 27.8 (22.8-29.4) years. Among women with lipoprotein(a) measurements, lipoprotein(a) levels above 30 mg/dL or the 75th percentile (31 mg/dL) were associated with increased 30-year risk of major cardiovascular events and coronary heart disease. Levels above 120 mg/dL or the 99th percentile (131 mg/dL) were associated with increased risk of ischemic stroke and cardiovascular death. Multivariable adjusted hazard ratios for levels above 120 mg/dL vs below 10 mg/dL or above the 99th percentile vs below the 50th percentile (11 mg/dL) were 1.54 (95% CI, 1.24-1.92) and 1.74 (95% CI, 1.35-2.25) for major cardiovascular events, 1.80 (95% CI, 1.36-2.37) and 2.06 (95% CI, 1.49-2.84) for coronary heart disease, 1.41 (95% CI, 0.93-2.15) and 1.85 (95% CI, 1.17-2.93) for ischemic stroke, and 1.63 (95% CI, 1.16-2.28) and 1.86 (95% CI, 1.26-2.72) for cardiovascular death, respectively. Among women with genotype information, rs3798220 minor allele carriers had a higher risk of major cardiovascular events. Per the results of this cohort study, very high lipoprotein(a) levels correlated with increased 30-year risk of cardiovascular disease among healthy women. Screening for elevated lipoprotein(a) in the general population may be warranted. Show less

To identify latent profiles of Fear of Progression (FoP) in parents of children with cancer, explore their associated factors, and test the mediating role of Sense of Coherence (SOC) between FoP and psychological distress (PD). A cross-sectional study was conducted with 273 parents of children with cancer in China. We used latent profile analysis (LPA) to identify FoP profiles, multinomial logistic regression to determine associated factors, and mediation analysis to test the role of SOC. Three distinct FoP profiles were identified: medication sensitive with low fear (38%), treatment sensitive with moderate fear (21%), and overall high fear (41%). These profiles were significantly differentiated by disease-related (e.g., treatment history), individual-related, and interpersonal-related (e.g., self-disclosure) factors. Across the sample, higher FoP was associated with greater PD. Importantly, mediation analyses revealed that SOC significantly mediated the relationship between FoP and PD for the moderate and high FoP profiles, but not for the low LoP profile. Parents of children with cancer exhibit heterogeneous FoP profiles. SOC acts as a crucial mediator between FoP and PD, particularly for parents with moderate and high FoP profiles. These findings underscore the importance of screening for specific FoP profiles and suggest that tailored interventions designed to enhance SOC could effectively reduce PD in high-risk parents. Show less

Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of and in interaction with polygenic risk. Using the Multi-Ethnic Study of Atherosclerosis (N = 5687), we assessed the associations of contextual determinants representing the social, chemical, and built environment with incident dementia and late-life cognition using proportional hazards regression and generalized estimating equation models, then evaluated their joint effects stratified by genetic risk via Bayesian kernel machine regression. Neighborhood disadvantage was associated with higher dementia risk and poorer cognitive scores after adjusting for genetic risk and other individual-level covariates. Joint analysis of all contextual determinants indicated that more deleterious mixtures of contextual determinants are associated with lower late-life cognition among apolipoprotein E ɛ4 non-carriers with intermediate polygenic risk. Contextual determinants are associated with dementia and late-life cognition after adjusting for age, sex, education, and genetic risk. Show less

This study aims to elucidate the role of FGFR1 in activating the Wnt/β-catenin signaling pathway and the underlying mechanisms by which it promotes malignant progression in lung squamous cell carcinoma (LUSC). By integrating multi-omics analysis with functional experiments, the clinical heterogeneity of FGFR1 amplification, signaling crosstalk, and their regulatory networks governing tumor phenotypes were revealed. Using TCGA data (n = 490), we analyzed the relationship between FGFR1 copy number variation (CNV) and mRNA expression in LUSC, and validated the correlation with protein expression in a clinical cohort (n = 38). GSEA and single-gene GSEA were performed to identify signaling pathways associated with high FGFR1 expression. The interaction between FGFR1 and the Wnt/β-catenin pathway was investigated by immunohistochemistry, immunofluorescence, stable cell lines, Western blot, qPCR, and functional assays. FGFR1 amplification correlated with increased mRNA and protein expression. The top 25% FGFR1 high-expression group enriched Wnt/β-catenin, PI3K-Akt, and cAMP pathways. Mechanistically, FGFR1 promoted β-catenin nuclear accumulation and enhanced β-catenin signaling through PKA-associated phosphorylation and Akt/GSK3β-related regulation of β-catenin stability, and these effects were attenuated by AKT inhibition. CTNNB1 knockdown significantly inhibited proliferation, migration, invasion, and tumor growth of LUSC cells. Our findings indicate that FGFR1 activates Wnt/β-catenin signaling through coordinated regulation of β-catenin phosphorylation, stability, and subcellular localization, thereby promoting malignant progression in LUSC. These results provide a rationale for targeting the FGFR1-Wnt/β-catenin axis as a potential therapeutic strategy. Show less

Patients hospitalized due to an exacerbation of chronic obstructive pulmonary disease (ECOPD) often exhibit increased sedentary behavior (SB), which may persist after discharge and negatively affect recovery. However, early determinants of SB during this period remain unclear. To identify the factors at hospital discharge that predict SB 30 days later in patients with ECOPD. This observational longitudinal study included patients hospitalized for ECOPD, assessed during the first week after discharge and reassessed 30 days later. Data collected included sociodemographic information (age, sex, name, telephone number, and address), anthropometric measurements (weight, height, and body mass index [BMI]), clinical history (previous hospitalizations, exacerbations, and smoking status), dyspnea (Medical Research Council scale, mMRC), health status (COPD Assessment Test, CAT), co-morbidities (Charlson Comorbidity Index), and exercise capacity (6-minute walk test, 6MWT). Physical activity and sedentary behavior-including SB, light (LPA), moderate (MPA), and vigorous (VPA) physical activity, step count, and sleep-were measured using a triaxial accelerometer worn for seven consecutive days. Accelerometer data were processed with ActiPASS software, and statistical analyses were performed in RStudio. Stepwise regression analysis was used to identify the discharge variables that could predict SB at 30 days. Forty-four patients (61% female; age 66 ± 8 years; FEV Show less

Coronary microvascular dysfunction (CMD) is increasingly recognized as a major driver of myocardial ischemia, with important implications for cardiovascular prognosis and quality of life, particularly in populations with ischemia and non-obstructive coronary arteries (INOCA) and heart failure with preserved ejection fraction (HFpEF). Despite increasing recognition of its importance, the mechanisms underlying CMD remain incompletely defined, and disease-modifying therapies are lacking. Lipoprotein(a) [Lp(a)], a genetically determined and causal cardiovascular risk factor, has been extensively studied in epicardial coronary atherosclerosis; however, its role in the coronary microcirculation has received comparatively limited attention. Lp(a) exhibits unique structural and biological properties, including the antifibrinolytic effects of apolipoprotein(a) and carriage of oxidized phospholipids, which promote endothelial dysfunction, oxidative stress, inflammatory activation, microvascular remodeling, and microthrombotic susceptibility-key processes implicated in CMD pathophysiology. Observational studies link elevated Lp(a) levels to impaired coronary flow reserve and endothelial dysfunction in patients with microvascular angina and related syndromes. Imaging and interventional studies further suggest that reduction of Lp(a)-associated circulating factors can improve myocardial perfusion and perfusion reserve in clinical settings dominated by microvascular disease. This review synthesizes current mechanistic, translational, and clinical evidence linking Lp(a) to CMD, identifies key knowledge gaps, and highlights future research priorities. Show less