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The genetic and clinical factors influencing the rate of brain structure change in cognitive decline remain poorly understood. This study aimed to identify genetic variants and risk factors contributing to these changes and explore potential causal relationships. We analyzed data from 2036 individuals across three longitudinal cohorts to assess change rates in 17 brain regions associated with cognitive decline. Genome-wide association studies (GWASs) were followed by phenome-wide association studies (PheWASs), Mendelian randomization (MR), and independent replication. We identified loci associated with brain structure change, including known Alzheimer's disease genes (apolipoprotein E, APOC1) and novel signals (BEAN1, SDHC). PheWAS and MR analyses in large biobanks suggested potential causal links between brain atrophy and anemia-related traits as well as type 2 diabetes. Our findings highlight genetic contributors and clinical traits associated with brain structure change in cognitive decline. Larger studies with broader cognitive assessments are needed to validate these findings. Show less

Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less

Lung adenocarcinoma (LUAD) is a prevalent and aggressive subtype of lung cancer, with a 5-year survival rate below 20% due to late-stage diagnosis and drug resistance. Endoplasmic reticulum stress (ERS) and butyrate metabolism (BM) play critical roles in tumor progression, but their co-regulatory features in LUAD remain unclear. This study integrated single-cell transcriptome analysis and Mendelian randomization (MR) to identify prognostic genes associated with ERS and BM in LUAD. Public datasets were analyzed using weighted gene co-expression network analysis, differential expression analysis, and MR. A risk model and nomogram were constructed, and immune microenvironment, gene set enrichment, and single-cell analyses were performed to validate findings. Moreover, the expression of prognostic genes was validated in different Non-small cell lung cancer (NSCLC) cell lines through reverse transcription quantitative polymerase chain reaction (RT-qPCR). Seven prognostic genes ( This study identifies seven ERS- and BM-related prognostic genes and highlights macrophages as pivotal in LUAD progression, the expression differences of candidate genes were verified by RT-qPCR assay. These findings provide novel insights into LUAD diagnosis, prognosis, and potential therapeutic targets, offering a foundation for precision medicine strategies. Further validation in clinical cohorts and functional studies is warranted to translate these discoveries into clinical applications. Show less

This study aimed to assess the prevalence of genetic variants responsible for extreme levels of high-density lipoprotein cholesterol (HDL-C) and evaluate the adequacy of current thresholds for genetic testing of HDL-related dyslipidemia. Using data from the Tromsø Study, a population-based cohort in Northern Norway, we identified 210 individuals with HDL-C levels ≤ 0.5 mmol/L or ≥ 3.0 mmol/L. Six HDL-related genes (ABCA1, APOA1, CETP, LCAT, PLTP, SCARB1) were sequenced in these participants. We classified variants according to ACMG guidelines, incorporating functional assays and UK Biobank data for additional phenotype-genotype associations. We identified 38 variants of interest across six HDL-related genes, of which 10 were considered potentially causative, found in 14 individuals. Genetic causes were detected in 33.3% of individuals with low HDL-C and 5.05% of those with high HDL-C. Sex-specific analyses showed that using HDL-C thresholds aligned with population distributions improved detection of individuals with pathogenic variants, particularly among women with high HDL-C and men with low HDL-C. These findings suggest that current uniform thresholds may overlook clinically relevant cases and that incorporating sex-specific HDL-C distributions could enhance the identification of individuals with suspected genetic HDL disorders. Genetic testing for HDL-related dyslipidemia is underutilized, with many individuals not meeting the current extreme HDL-C threshold criteria. Revised sex-specific thresholds for genetic testing will improve the identification of pathogenic variants and provide more accurate diagnoses of HDL-related disorders. Continued research is essential to refine our understanding of HDL genetics and its clinical implications. Show less

Lymphoplasmacytic lymphoma / Waldenström macroglobulinemia (LPL/WM) is a rare and indolent low-grade B-cell lymphoproliferative neoplasm that often presents with vague symptoms or asymptomatically. While it most commonly involves the bone marrow, LPL/WM can sometimes involve the lymph nodes and spleen, and rarely the central nervous system, skin, and pleural cavities. We report a rare case of lymphoplasmacytic lymphoma/ Waldenström macroglobulinaemia presenting with predominant myometrial and cervical involvement. A 57-year-old G2P2 postmenopausal female with a history of HPV + HSIL presented following a single episode of abnormal uterine bleeding with associated urinary urgency and pelvic pressure. Transvaginal ultrasound examination was unremarkable and endometrial biopsy via hysteroscopy was unsuccessful due to stenotic cervical os. The patient subsequently underwent a total robotic hysterectomy with bilateral salpingo-oophorectomy. Examination of histologic sections showed atypical perivascular lymphoid aggregates consistent with involvement by a low-grade B-cell lymphoma with predominant myometrial and cervical involvement. Differential diagnosis at the time included marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL). Additional testing identified an IgM kappa paraproteinemia with MYD88 p.L265P mutation. Bone marrow biopsy and aspirate confirmed the diagnosis of lymphoplasmacytic lymphoma / Waldenström macroglobulinaemia (LPL/WM). To our knowledge, there have been only two cases previously described in the literature of LPL/WM involvement in the female genital tract; both of which had prominent involvement of the ovaries. Although exceedingly rare, LPL/WM involvement of the female genital tract should be considered on the differential diagnosis if atypical lymphoid cells or dense lymphoid aggregates are observed. Show less

Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in inflammatory pathways beyond lipid metabolism. The effects of PCSK9 inhibition on monocyte subset distribution in high-risk coronary artery disease patients remain unclear. To assess the effects of lipoprotein fractions and PCSK9 inhibitor (PCSK9i) therapy on monocyte subset distribution in patients with stable coronary artery disease and highly elevated Lp(a) levels. We followed 100 statin-treated patients in the stable phase after myocardial infarction with highly elevated Lp(a), randomized to PCSK9i or placebo for six months. Biochemical, genetic, and cellular analyses were performed at baseline and follow-up. At baseline, IM levels correlated with total cholesterol (ρ = -0.202, In high-risk patients, PCSK9 inhibition modulates monocyte-lipoprotein interactions without affecting the monocyte subset distribution. PCSK9 may promote vascular inflammation through CCL2 regulation, which appears more closely related to Lp(a) composition than its circulating concentration. NCT04613167; https://www.clinicaltrials.gov/study/NCT04613167, date of registration: 6th of October 2020. Show less

Current treatments for idiopathic pulmonary fibrosis (IPF) slow but do not stop/reverse disease progression. The lysophosphatidic acid (LPA) axis is identified as a therapeutic target for IPF. This study aims to assess BI 1819479, an LPA pathway inhibitor, in patients with IPF (ClinicalTrials.gov Identifier: NCT06335303). In this placebo-controlled, phase II trial, patients will be randomised (2:1:1:1) to receive one of three oral doses of BI 1819479 or placebo, stratified by nintedanib/pirfenidone use. Patients aged ≥40 years with IPF, forced vital capacity (FVC) ≥45% of predicted normal and haemoglobin-corrected diffusing capacity for carbon monoxide ≥25% of predicted normal at screening will be included. Patients with relevant airway obstruction (pre-bronchodilator forced expiratory volume in 1 s/FVC <0.7), acute IPF exacerbation ≤12 weeks prior to screening, treatment with immunosuppressive medications (other than oral corticosteroids) or prednisone >15 mg·day This trial evaluates the efficacy, safety and dose range of BI 1819479 in patients with IPF, offering a potential additional treatment option, and will establish appropriate dosing for phase III trials. 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

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

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

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

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

Macrophages differentiated with macrophage colony-stimulating factor (M-CSF) (M-Mac) are widely used as an experimental model. Interleukin 27 (IL-27)-polarized M-Mac (27M-Mac) suppresses HIV replication; however, the effects of IL-27 polarization on granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages (GM-Mac) remain less investigation. Here, we compare multiple functional properties and gene expression profiles of 27M-Mac and IL-27-polarized GM-Mac (27GM-Mac). M-Mac and GM-Mac were generated from monocytes of healthy donors and subsequently treated with IL-27 for three days. HIV replication in 27M-Mac, GM-Mac, and 27GM-Mac was suppressed to nearly 10% of that in M-Mac; however, single-cell RNA sequencing showed that M-Mac clustered with GM-Mac, and 27M-Mac clustered with 27GM-Mac. Expression of CD38 and secretion of CXCL9 and C1q were significantly increased in 27M-Mac and 27GM-Mac compared with M-Mac and GM-Mac. Although CD16 and CD64 expression increased in 27M-Mac and 27GM-Mac relative to their respective controls, phagocytic activity in 27M-Mac and 27GM-Mac was 30% of that in M-Mac. Autophagy was promoted 3.7-fold more strongly in 27M-Mac than in M-Mac, reaching levels comparable to those in GM-Mac and 27GM-Mac. Collectively, these findings indicate that IL-27 polarizes M-Mac and GM-Mac toward transcriptionally and functionally similar subtypes, providing insight into the role of IL-27 in macrophage polarization and plasticity. 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

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle that contains a unique apolipoprotein(a) [apo(a)] component covalently bound to apolipoprotein B-100. Elevated levels of Lp(a) have been identified as a well-established and genetically determined risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, and calcific aortic valve stenosis. In contrast to other lipids, Lp(a) concentrations are minimally influenced by lifestyle or traditional lipid-lowering therapies, emphasizing the necessity for novel treatment approaches. This narrative review summarizes current and emerging therapeutic strategies for reducing Lp(a) levels. Such strategies include traditional agents such as niacin and PCSK9 inhibitors, as well as innovative therapies such as antisense oligonucleotides, RNA interference-based molecules, and small-molecule inhibitors. The mechanisms of action of these agents, in addition to clinical trial data and their capacity to modify cardiovascular outcomes, are explored in further detail. Furthermore, the current status of clinical guidelines and the evolving role of Lp(a)-targeted therapies in cardiovascular risk stratification are reviewed. A particular emphasis is placed on therapies that are in the advanced stages of clinical development. These include late-phase outcome trials and orally administered agents, which have the potential to significantly impact future clinical practice. The integration of mechanistic data with ongoing and completed clinical studies has been undertaken in order to provide a comprehensive framework for understanding the therapeutic potential of Lp(a) in the context of cardiovascular prevention. Show less

Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3β, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-κB, TNF-α, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary. Show less

The etiology of Alzheimer's disease (AD) has been extensively studied for a long time, primarily associated with multifaceted mechanisms involving aggregation of amyloid beta, tau hyperphosphorylation, neuroinflammation, and immune regulation. Current therapeutics for AD are significantly targets to attenuate the cognitive decline by modulating neurotransmitters and diminishing aggregation of amyloid beta. However, these therapeutics fail to address the neuroimmune dysregulation that critically facilitates disease progressions. In this study, we have delineated the phytochemical potential to modulate the amyloid beta-triggered immune regulation through in silico approaches. Seventy three phytochemicals were selected from established anti-Alzheimer's plants through literature mining and sequentially administrated to pharmacodynamic and pharmacokinetic investigations. The draggable study has established 14 phytochemicals, and the compounds were further curated based on their molecular interactions with the hub-targets, enriched in the amyloid beta-driven immune regulation. AD-associated proteins were retrieved from different data sets such as GeneCards, DisGeNet, GEO, and Opentargets, and the intersecting targets were curated for downstream analysis. Functional annotation and network pharmacology analysis mapped APOE4, BACE1, TREM2, IL-1β, and TNF-α as key regulatory targets. The molecular interaction analysis revealed that genkwanin and kaempferol exhibited strong binding affinity and stable interactions with the hub-targets as a potent candidates to attenuate the immune regulation in AD. Further molecular mechanics/Poisson-Boltzmannsson-Boltzmann surface area and DFT analysis have revealed their thermodynamic stability and electronic reactivity, highlighting their potential efficacy in mitigating AD progression. Show less

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, represents a paradigmatic condition for precision cardiovascular medicine. Once regarded as a monogenic autosomal dominant disorder driven by rare sarcomeric variants, HCM is now recognized as a genetically complex disease characterized by incomplete penetrance, variable expressivity, and heterogeneous clinical trajectories. This review summarizes current evidence on the evolving genetic architecture of HCM, emphasizing the predominant role of definitively validated sarcomeric genes, particularly 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

Diabetic peripheral neuropathy (DPN), a severe complication of diabetes, is a key risk factor for diabetic foot (DF) that contributes highly to amputation and mortality. The pathogenesis of DPN remains unclear and complex, with no effective treatments currently available. Monoamine oxidase (MAO), a flavin adenine dinucleotide (FAD)-dependent enzyme, catalyzes the oxidative deamination of critical biogenic amines. The MAO family comprises two subtypes, MAOA and MAOB, which play distinct roles in pathophysiology. In this study, we identified that MAOB but not MAOA is pathologically upregulated in the sciatic nerve (SN) tissues of DPN patients and in the SN/dorsal root ganglion (DRG) tissues of DPN model mice. Notably, the selective MAOB inhibitor Khellin (Khe) effectively alleviated DPN-like pathology in mice. To explore the mechanistic role of MAOB in DPN, we performed proteomic profiling of DRG tissues from DPN mice and validated the findings using a MAOB-specific knockdown DPN mice model treated with adeno-associated virus (AAV) 8-MAOB-RNAi. Our results demonstrate that Khe targets MAOB to mitigate DPN pathology through HIF-1α/BACE1/Aβ/NLRP3/tau pathway, mediated by Schwann cell/DRG neuron crosstalk. All findings suggest that selective MAOB inhibition represents a promising therapeutic strategy for DPN, with Khe as a potential candidate for clinical translation against this disease. Show less

This study examined the heterogeneous nature of dual-career stress and its asymmetric associations with on adolescent athletes, aiming to: (1) identify distinct stress profiles based on academic, training, and role-conflict stressors; (2) assess whether stress associations vary across levels of athletic burnout and academic performance; and (3) test whether stress profiles moderate these relationships. A two-wave longitudinal study included 843 adolescent male football players in China. Latent Profile Analysis (LPA) categorized participants using three stressor subscales at Time 1. Quantile Regression (QR) at Time 2 (6 months later) analyzed the association between total stress and athletic burnout and academic performance across five quantiles (τ = 0.10-0.90), with stress profile as moderator, controlling for social support, time management, and demographics. LPA revealed four profiles: Balanced Moderates (37.2%), Academically Overwhelmed (28.1%), Sport-Centric Strained (22.0%), and Dual-Track Distressed (12.7%). QR showed the positive association between stress and burnout increased across quantiles (β = 0.41 at τ = 0.10 to 0.78 at τ = 0.90), with the strongest association observed among already burnt-out athletes most. For academic performance, the negative association between stress and performance was strongest at lower quantiles (β = -0.71 at τ = 0.10) and weaker at higher quantiles (β = -0.29 at τ = 0.90). Stress profiles significantly moderate these relationships: the Dual-Track Distressed profile showed the strongest association with on burnout (β = 0.89), while Academically Overwhelmed and Dual-Track Distressed profiles showed the strongest negative association with on academic performance (β = -0.79 and -0.92, respectively). Dual-career stress experiences and impacts are highly heterogeneous. Adolescents cluster into meaningful stress profiles, and stress is most strongly associated with negative outcomes among those already at extremes of burnout or poor academic performance. Findings underscore the need for personalized interventions tailored to athletes' specific stress profiles and outcome levels, supporting holistic development in dual-career contexts. Show less

Dysembryoplastic neuroepithelial tumours (DNETs) are rare with only a few hundred cases reported in literature. The long-term natural history of paediatric DNETs is still poorly understood. We present a rare case of DNET with recurrent tumour bleeds over 26 years of follow-up and provide a brief literature review of similar events. The patient is a 30-year-old Chinese male who presented with right-sided seizures since 3 years old. Initial neuroimaging was suspicious of left fronto-parietal glioma and was conservatively managed due to its location near the motor strip and concerns of potential surgical complications. Over the follow-up period, the patient suffered three bleeds. Following the third bleed, tumour resection was performed under intraoperative motor mapping, with near total resection. Intraoperatively, the tumour involved the post-central gyrus, with histological findings suggestive of low-grade glioma with FGFR1 alteration, in keeping with DNET. The latest neuroimaging showed no new haemorrhages or infarcts. Features of small residual tumour around the tumour cavity were noted. The patient is currently well with marked reduction of seizure episodes. Our report provides new insight into the long-term natural history of DNET and adds value to limited existing literature of similar cases. 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

Psychiatric nurses engage in high levels of emotional labor, which can significantly influence their burnout and job performance. While prior research has linked emotional labor to burnout, the nuanced interplay between different emotional regulation strategies remains underexplored. This study examines the distinct roles of surface acting (modifying outward expressions without changing internal feelings) and deep acting (adjusting internal emotions to align with external expectations) in psychiatric nursing, identifying their differential associations on burnout through network bridge analysis and latent profile analysis. A cross-sectional survey was conducted among 199 psychiatric nurses in a mental hospital in Wenzhou, China. Emotional labor was assessed using the Emotional Labor Scale, and burnout was measured with the Maslach Burnout Inventory-GS. Network bridge analysis was applied to identify key connections between emotional labor strategies and burnout dimensions. LPA was applied to reveal distinct emotional labor patterns. Surface acting emerged as the primary bridge linking emotional labor to burnout, displaying strong associations with emotional exhaustion and depersonalization. LPA identified four emotional labor profiles: These findings highlight the maladaptive effects of surface acting and the protective role of deep acting. Targeted interventions fostering deep acting may enhance psychiatric nurses' well-being and resilience. Future research should explore longitudinal shifts in emotional labor strategies. Show less

Glioma presents significant therapeutic challenges due to its marked heterogeneity and resistance to conventional treatments. Apolipoprotein E (APOE), a glycoprotein involved in lipid metabolism, has been reported to be dysregulated in glioma; however, its functional role in glioma progression remains poorly understood. APOE expression in glioma was analyzed using publicly available transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Functional studies were performed in U251MG and U87MG glioma cells with APOE overexpression or knockout. Cell proliferation, migration, and invasion were evaluated using CCK-8, Edu, Transwell, and wound-healing assay. Mechanistic analyses included RNA sequencing, immunofluorescence, nucleocytoplasmic fractionation, Western blotting and immunoprecipitation. A nude mouse xenograft model was used to assess tumor growth in vivo. APOE expression was elevated in glioma datasets. Functional assays demonstrated that APOE promotes glioma cell proliferation, migration, and invasion. Notably, APOE was detected in the nucleus, where it exhibited transcriptional regulatory activity. Mechanistically, APOE overexpression significantly activated the PI3K/AKT signaling pathway, and this effect was effectively reversed by the PI3K inhibitor LY294002. Consistently, APOE overexpression enhanced tumor growth in vivo. These findings indicate that APOE promotes glioma progression through nuclear activity and activation of the PI3K/AKT signaling pathway, highlighting APOE-related signaling as a potential therapeutic target in glioma. 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

Neonicotinoid pesticides, including acetamiprid (ACE), are widely used in agriculture and pose increasing concerns due to their persistence in the environment and potential human exposure mainly through diet. Available evidence suggests that ACE may disrupt adipocyte function and promote metabolic dysfunctions such as obesity; however, there is limited research on how ACE negatively affects adipose tissue (AT) in men and women. This study utilizes an Twenty-four subjects with severe obesity (11 men and 13 women) undergoing bariatric surgery were recruited from St. Andrea University Hospital (Rome, Italy). Visceral adipose tissue biopsies were collected and either treated with ACE or left untreated for further gene and protein expression analysis by RT-qPCR and Western blot, respectively. In addition, adipocytokines secretion, reactive oxygen species production, and free fatty acid release were measured in adipose tissue culture media using commercial or in house assays. Our findings demonstrate that ACE induces distinct sex-dependent alterations in lipid metabolism, Adipokines regulation, and inflammatory pathways. Specifically, it significantly lowers PPARγ gene expression but raises protein levels, particularly in men. Free fatty acid release increases and Hormone Sensitive Lipase (HSL) drops in both sexes, while Lipoprotein Lipase (LPL) decreases only in women. ACE also promotes inflammation mainly in women, increasing TNF-α, NF-κB, and reactive oxygen species. These results show that the neonicotinoid ACE worsens AT dysfunction via inflammatory and metabolic pathways in a sex-specific way, likely leading to different risks of obesity-related complications. Overall, these findings provide a mechanistic basis for understanding the toxicological risk of neonicotinoids, highlighting the importance of sex-specific assessment in evaluating metabolic risks of environmental pesticide exposure. Show less