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Head and neck cancer (HNC) is a biologically heterogeneous malignancy with limited actionable therapeutic targets. The fibroblast growth factor receptor (FGFR) family comprises receptor tyrosine kinases implicated in tumor progression; however, their specific roles in HNC remain incompletely defined. Genomic alterations, transcriptomic profiles, and clinical relevance of Among FGFR4 functions as an oncogenic driver in HNC, promoting tumor progression through the ERK–RUNX3–MMP2 axis and mediating chemoresistance via FGFR4–ERK signaling. The ERK-dependent induction of FGF19 and FGFR4 establishes a positive feedback circuit that sustains oncogenic activation. Targeting the FGF19/FGFR4 axis, particularly when combined with MEK/ERK inhibitors, represents a promising strategy to overcome resistance in HNC. The online version contains supplementary material available at 10.1186/s12967-026-07999-1. 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

While family resilience is a recognized determinant of adaptation following stroke, the distinct, empirically derived profiles of family resilience among Chinese stroke survivor-caregiver dyads have not been clearly delineated. Identifying these profiles and their determinants is crucial for developing targeted interventions. To identify latent profiles of family resilience and examine the socio-demographic and clinical factors associated with profile membership among stroke patient-caregiver dyads in China. In this cross-sectional study, a convenience sample of 773 stroke survivor-caregiver dyads was recruited from three hospitals in Zhejiang Province, China. Latent profile analysis (LPA) was conducted on the 20-item Family Resilience Questionnaire (FRQ). Multinomial logistic regression was used to determine factors associated with profile membership. LPA supported a four-profile solution: Profile 1 "Low-Functioning Families" (22%), Profile 2 "Moderately Resilient - Low Cohesive Families" (24%), Profile 3 "Highly Resilient - Well-Functioning Families" (31%), and Profile 4 "High-Functioning - Optimistically Resilient Families" (24%). Multinomial logistic regression revealed that lower caregiver competence (higher FCTI scores) was strongly associated with profile membership (standardized aORs ranged from 2.58 to 43.19), whereas higher perceived social support (PSSS) was a significant protective factor (standardized aORs ranged from 0.03 to 0.19). Caregiver relationship and payment source were also significantly associated with profile membership. Family resilience among Chinese stroke families manifests in four distinct profiles, which are differentiated predominantly by caregiver competence and perceived social support. Our findings advocate for a precision family support paradigm, shifting from one-size-fits-all approaches to interventions tailored to distinct resilience profiles. Given the strong association, intervention programs should prioritize enhancing core caregiver competencies as a primary leverage point for building family resilience. 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

Probiotics such as The intestinal colonization ability of CIQ249 was assessed using cFDA-SE labeling and flow cytometry. Growth performance and intestinal morphology were evaluated in mice. Antimicrobial activity of CIQ249 cell-free supernatant was tested against various pathogens, and pathogen damage was visualized by scanning electron microscopy. Protective effects against CIQ249 demonstrated strong intestinal colonization and increased villus height and the villus-to-crypt ratio, contributing to improved growth performance. Its cell-free supernatant selectively inhibited enteropathogens and induced structural damage in CIQ249 enhances mucosal defense against enteropathogenic bacteria through a dual mechanism-strengthening the epithelial barrier and activating a coordinated DC-Tfh-IgA immune axis. These findings provide a multi-level mechanistic basis for its application as a microecological agent against intestinal infections. 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

Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a temporally controlled hydrogel microneedle system that integrates ginseng-derived exosomes (G-Exos) with biomimetic polydopamine nanoparticles (PDA@PEGs) to concurrently target the pathogenic triad of vitiligo, including oxidative stress, inflammation, and melanocyte deficiency. This system employs methacrylated hyaluronic acid (HAMA) hydrogel microneedles for rapid PDA@PEG release while utilizing glyceryl monostearate micelles to achieve matrix metalloproteinase-9 (MMP-9)-responsive G-Exo release at inflammatory foci, enabling intelligent spatiotemporal control. Functionally, G-Exos help restore redox homeostasis and suppress inflammation through bioactive constituents, thereby protecting melanocytes and enhancing keratinocyte proliferation. Moreover, PDA@PEG promotes repigmentation through the dual mechanisms of exogenous melanin deposition and endogenous melanogenesis stimulation. In murine models, this strategy achieves significant repigmentation within 3 weeks by activating follicular stem cells, upregulating melanogenic markers (Tyr/Mc1r), increasing antioxidant defense (ApoE), and suppressing inflammatory signaling (IL-17). This natural-biomimetic hybrid design leverages biocompatible materials to co-target multiple pathological axes, offering a novel self-adaptive approach for microenvironmental rehabilitation in vitiligo. 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

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

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

Endothelial lipase (EL) is a key regulator of high-density lipoprotein (HDL) metabolism. Many aspects of EL function remain incompletely understood due to challenges in purifying active EL. This study identifies apolipoprotein J (ApoJ) as a novel chaperone for EL, crucial for its solubility and activity. Using an optimized purification protocol that yields active EL, we discovered that ApoJ consistently co-purifies with EL, maintaining its activity. We further show that knocking down ApoJ decreases the activity of EL. We demonstrate that ApoJ interacts with EL via its hydrophobic lid and tryptophan loop regions, and that mutating these regions abolishes the effect of ApoJ on the solubility and activity of EL. We show that ApoJ, EL, and ApoA1 (the defining lipoprotein of HDL particles) colocalize in HDL particles in mouse plasma. However, we find that ApoJ is not a direct carrier for EL to HDL particles. Instead, our data suggest that ApoJ primarily serves to enhance EL activity through its role as a chaperone, even when incorporated into lipid substrates. Our findings suggest a model in which ApoJ protects EL in plasma and enhances its hydrolysis of lipoprotein substrates. We propose that ApoJ is an accessory protein for EL, analogous to GPIHBP1 for LPL and co-lipase for PL. Further study of the interaction between EL and ApoJ will promote a better understanding of HDL metabolism. Show less

To examine associations between the 24-h composition of movement behaviors (sedentary behavior [SB], light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], and sleep) and physical and mental health in older adults using compositional data analysis. Data came from 4,150 adults aged ≥ 60 in the 2015 China Health and Nutrition Survey. Multiple‑balance isometric log‑ratio regression and compositional isotemporal substitution models were used to assess relative associations and the effect of time reallocation. The 24‑hour geometric mean composition was 43.1% sleep, 30.6% SB, 21.8% LPA, and 4.5% MVPA. LPA was positively associated with physical (β = 0.062, Replacing sedentary time or sleep with LPA, even in small amounts, is associated with better physical and mental health in older adults, supporting integrated 24‑hour activity guidelines that emphasize light‑intensity movement. Show less

Left ventricular non-compaction (LVNC) can be observed as a phenotypic trait in patients with dilated cardiomyopathy. Familial cases have been increasingly recognized, with sarcomeric gene mutations-particularly in We report a 7-year-old girl with a clinical diagnosis of dilated cardiomyopathy with LVNC since infancy. Genetic analysis revealed two heterozygous missense variants in sarcomeric genes associated with inherited cardiomyopathies: This report highlights the clinical relevance of identifying digenic sarcomeric variants in paediatric cardiomyopathy, particularly when associated with a positive maternal history of PPCM. Familial evaluation and recognition of genotypic overlap may aid in risk stratification and management. 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

Prior to a cardiovascular outcomes trial (CVOT), novel cholesterol-lowering therapies undergo phase 2/3 studies for their lipid and atherosclerotic effects and safety (non-CVOTs). Since the occurrence of major adverse cardiovascular events (MACE) is part of the safety assessment, nominal reductions or increases may be observed prior to definitive testing of the effect in a CVOT. To investigate if the observed MACE treatment effect in non-CVOT lipid-lowering registration studies holds value in predicting the outcome in a CVOT trial, typically reported later than the initial lipid-lowering studies. We reviewed recent development programs for cholesterol-lowering drugs that had completed non-CVOT and CVOT studies. MACE data were compared for phase 2/3 non-CVOT versus pivotal CVOT results. Our primary outcome was a qualitative comparison for directionally concordant consistency in MACE risk ratio treatment effects (harm, neutrality, or benefit). Correlation analysis was also performed. Seven drugs were reviewed in 3 cholesterol-lowering classes: CETP inhibitors, bempedoic acid, and PCSK9 inhibitors. Concordance in non-CVOT vs CVOT results was seen in 6 of 7 drugs. One drug (dalcetrapib) had a trend for benefit observed, albeit with very small numbers, in early development, but showed a neutral CVOT. There was a moderate correlation between the risk reductions or increases from the non-CVOTs and CVOTs: Within the limitations of the drugs studied and the variability in MACE definitions, there is value in the results of non-CVOTs to predict the CVOT outcome. Show less

This study aims to identify the 24-h movement behavior patterns of preschool children using Latent Profile Analysis based on Compositional Data Analysis (CoDA), and to examine their associations with physical fitness. The study employs a cross-sectional design. A total of 329 healthy children aged 4-6 years were selected. Accelerometers (ActiGraph wGT3-BT, Pensacola, FL, USA) were used to measure light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB), while sleep was assessed through parent and teacher questionnaires. The assessment of physical fitness was conducted in accordance with the "Chinese National Physical Fitness Test Standards" (Preschooler Section). To address the multicollinearity problems among components of physical activity (PA), CoDA was first applied, subsequently, Latent Profile Analysis was utilized to categorize 24-h movement behavior patterns, while a Generalized Ordered Logit Model (GOLM) was applied to investigate their associations with physical fitness. Three distinct behavioral patterns emerged from the analysis: the "brown bear group" (moderate PA and SB, high SP, N = 176, 53.5%), the "cheetah group" (high PA/MVPA, low SB, moderate SP, N = 102, 31%), and the "koala group" (low PA, high SB, lower SP, N = 51, 15.5%). After adjusting for potential confounding factors, it was found that compared with the "koala group", the "brown bear group" and the "cheetah group" exhibited higher levels of physical fitness, with the probability of improving their physical fitness rating being 3.69 times and 6.36 times that of the "koala group," respectively. This study highlights the significant impact of active and healthy activity patterns on the physical fitness of preschool children, providing a foundation for formulating personalized preventive and interventional approaches in early childhood. Show less

Serum lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease. However, whether hypertension modifies the association between Lp(a) and adverse outcomes in acute decompensated heart failure (ADHF) remains unclear. We investigated how hypertension status influences the relationship between Lp(a) and all-cause mortality in ADHF. We conducted a single-center retrospective observational study including 2610 patients hospitalized with ADHF. We normalized the distribution of Lp(a) by a logarithmic transformation and assessed the risk of all-cause mortality with Lp(a), using Cox regression with adjustment for potential confounders. Among 2610 patients (39.0% women; mean age, 68.8 years), 1606 (61.5%) had hypertension. Over 4.1 years (median), 1287 deaths occurred. In all patients, log-transformed Lp(a) was significantly associated with mortality (adjusted HR 1.21; 95% CI, 1.05-1.39; Increased admission Lp(a) levels were associated with a higher risk of all-cause mortality in ADHF patients with hypertension. Further studies are needed to explore the mechanistic links among Lp(a), hypertension and ADHF. Show less

Assessment of muscle coordination during cycling can provide insight into motor control strategies and movement efficiency. This study evaluated muscle synergy patterns as indicators of neuromuscular coordination in the lower limbs across three power levels of cycling (LPL = Lowest Power Level, MPL = Middle Power Level, HPL = Highest Power Level). Twenty recreational cyclists performed a graded cycling test on a stationary bicycle ergometer. Electromyography (EMG) was recorded bilaterally from seven lower-limb muscles and muscle synergies were extracted using non-negative matrix factorization. The Synergy Index (SI) and Synergy Coordination Index (SCI) were calculated to assess muscle coordination patterns. Four muscle synergies were identified consistently across power levels, with changes in synergy composition and activation timing correlated with increasing muscular demands. At the dominant hip, SI remained consistent across power levels (0.50 ± 0.11 at LPL, 0.56 ± 0.15 at MPL, 0.54 ± 0.15 at HPL). At the dominant knee, SI decreased with increasing power (0.47 ± 0.07 at LPL to 0.34 ± 0.05 at HPL; p < 0.01, η These findings provide insight into how the central nervous system modulates its response to increasing mechanical demands. Combining synergy indices offers a promising approach to assess motor control, inform rehabilitation, and optimize performance in cycling tasks. Show less

Lipoprotein(a) [Lp(a)] is a well-established independent risk factor for cardiovascular disease. However, the long-term effects of Lp(a) on coronary plaque phenotype remain unclear. To explore the potential association between Lp(a) levels and coronary plaque volume, composition, and progression using coronary computed tomography angiography (CCTA). Patients with available data for Lp(a) and underwent baseline CCTA examinations between January 2009 to December 2015 and subsequently underwent a follow-up coronary CTA were retrospectively enrolled. Quantitative CCTA analyses measured plaque length, total plaque volume and composition volume. Patients were categorized into an elevated Lp(a) group (≥30 mg/dL) and a normal Lp(a) group (<30 mg/dL). The association between Lp(a) and baseline plaque characteristic and progression were investigated in linear mixed-effects models adjusted for clinical factors. Subgroup analyses were also conducted. Among 453 patients (mean age 64.7 years, 77.7% male) with a median follow-up of 6.15 years. elevated Lp(a) was linked to higher baseline plaque burden (all Elevated Lp (a) level was associated with high coronary artery plaque burden at baseline and rapid progression of LAP at follow-up. Lp(a) may serve as a significant residual risk factor in seemingly "low-risk" populations. Show less

Lipoprotein (a) [Lp(a)] is viewed as a cholesterol-rich, LDL-like particle, yet potential heterogeneity in its lipid composition is not well understood. We developed and validated a novel immune-isolation assay to directly quantify triglycerides (TGs) associated with Lp(a) [Lp(a)-TGs]. Lp(a) was selectively isolated from plasma using magnetic beads conjugated with monoclonal antibody LPA4 targeting apolipoprotein(a), followed by enzymatic quantification of TGs. Assay specificity was ensured using washing buffers to prevent nonspecific lipoprotein interactions. Spike-in experiments with purified VLDL/intermediate density lipoprotein lacking Lp(a) demonstrated no measurable interference. Lp(a)-cholesterol [Lp(a)-C] was measured using an established immune-isolation method. The ratio of Lp(a)-TG to Lp(a)-C was calculated to distinguish TG-enriched Lp(a) particles from the typical cholesterol-rich, LDL-like phenotype. Lp(a)-TG, Lp(a)-C, Lp(a) molar concentration, and estimated compositional ratios were quantified in 36 normotriglyceridemic individuals and 114 individuals with moderate hypertriglyceridemia (150-500 mg/dl). In normotriglyceridemic individuals, mean (SD) TGs were 98.4 (31.9) mg/dl, Lp(a)-TG 1.42 (2.83) mg/dl, Lp(a)-C 4.03 (4.01) mg/dl, and the Lp(a)-TG/Lp(a)-C ratio was 0.59 (1.27). Lp(a)-TG and Lp(a)-C accounted for mean (SD) 1.22% (0.10) of total plasma TGs and 2.62% (2.01) of total plasma cholesterol. In individuals with hypertriglyceridemia, mean (SD) TGs were 284 (85) mg/dl, Lp(a)-TG 53.7 (25.3) mg/dl, Lp(a)-C 14.4 (6.9) mg/dl, and the Lp(a)-TG/Lp(a)-C ratio was 3.99 (1.20). Lp(a)-TG and Lp(a)-C accounted for mean (SD) 19.9% (6.53) of total plasma TGs and 9.68% (4.41) of total plasma cholesterol. This immune-isolation assay is the first validated, high-throughput method for direct quantification of Lp(a)-TG. This study demonstrates that Lp(a) lipid composition is variable and enriched in triglycerides and cholesterol in hypertriglyceridemic states. It provides a platform for future mechanistic, epidemiologic, and pharmacologic studies of Lp(a)-triglyceride interactions. This immune-isolation assay is the first validated, high-throughput method for direct quantitation of Lp(a)-TG. Show less

This study examined heterogeneous patterns of trauma-related adaptation among Chinese adolescents during the post-COVID-19 recovery phase, focusing on the co-occurrence of posttraumatic distress (PTD) and posttraumatic growth (PTG). We also investigated how modifiable psychosocial protective and vulnerability factors were associated with membership in different adaptation profiles. A large-scale cross-sectional survey was administered to 5, 044 students (aged 9-17 years; 46.6% male) from 15 primary and secondary schools in Wuhan, China. Validated instruments assessed posttraumatic stress symptoms (PCL-C), posttraumatic growth (PTGI), depressive symptoms (CES-D), and anxiety (SAS). Protective and vulnerability factors included resilience (CD-RISC), perceived social support (SSRS), physical activity (PARS-3), school belonging (PSSM), adaptive coping (SCSQ), and trait anxiety (TAI). Latent profile analysis (LPA) was used to identify adaptation profiles, and multinomial logistic regression examined how modifiable psychosocial factors were associated with profile membership. LPA revealed four empirically derived profiles: a High Distress/High Growth-Moderate PTSD profile (76.9%), a Low Distress-High Growth profile (4.8%), a Low Growth-Moderate Distress profile (3.9%), and a High Distress/High Growth-High PTSD profile (14.4%). The vast majority of adolescents showed some degree of both PTD and PTG, consistent with dual-process perspectives. In multinomial models, higher resilience, social support, school belonging, adaptive coping, and physical activity were associated with greater likelihood of belonging to the Low Distress-High Growth profile rather than more distressed profiles, whereas higher trait anxiety was associated with increased odds of membership in profiles characterized by greater distress. In this large school-based sample of Chinese adolescents, distress and growth frequently co-occurred and clustered into distinct adaptation profiles that differed systematically in psychosocial resources. Resilience, social connectedness, school belonging, and physical activity emerged as promising targets for trauma-informed, school-based support, whereas trait anxiety appeared to mark heightened vulnerability. Given the cross-sectional and single-region design, these findings should be interpreted as exploratory, and longitudinal and cross-cultural studies are needed to clarify temporal and contextual influences on adolescent trauma adaptation. Show less

Cancer patients face a markedly elevated risk of thromboembolism (TE), including both venous thromboembolism (VTE) and arterial thromboembolism (ATE), which contribute substantially to morbidity and mortality in this population. This study examined sex disparities in associations between sleep, sedentary behavior (SB), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and TE risk, in cancer patients using data from the UK Biobank. A longitudinal cohort analysis of 6,765 cancer patients (2,774 men and 3,991 women) from the accelerometry subsample was conducted using Cox proportional hazards and isotemporal substitution models stratified by sex. The incidence of VTE was 3.0% in men versus 2.2% in women, while ATE incidence was 5.0% versus 2.2%, respectively. Compared with high LPA, medium and low durations were associated with 2.75- and 2.88-fold higher VTE risk only in men. Reallocating 1 h per day from sleep or SB to LPA reduced VTE risk by 24% and 19% in men. Low MVPA was associated with 3.35- and 1.59-fold higher ATE risk in women and men, respectively. Reallocating 1 h per day from sleep, SB, or LPA to MVPA reduced ATE risk by 71%, 70%, and 66%, respectively, only in women. LPA was associated with a lower risk of VTE only in male cancer patients, whereas MVPA was linked to a lower risk of ATE in female patients, indicating sex-specific associations between movement behaviors and TE risk. Show less

Clear cell renal cell carcinoma (ccRCC) is characterized by high recurrence and metastatic potential, leading to poor clinical outcomes. There is a critical need to identify reliable prognostic biomarkers and therapeutic targets to improve patient stratification and personalized treatment. This study integrated single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data to identify prognostic genes and therapeutic targets. Prognostic modeling and validation were performed using The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. In addition, functional analyses were conducted to explore the biological roles of candidate genes. Seven prognostic genes (CYFIP2, MPPED2, HHLA2, ADAM8, ATP1A1, ARC, and MXD3) were identified and used to construct a risk model that stratified patients into high- and low-risk groups. The high-risk group exhibited significantly poorer survival, a finding validated in both TCGA and ICGC datasets. A nomogram incorporating risk score and age improved survival prediction accuracy, with Area Under the Curve (AUC) values of 0.79, 0.75, and 0.78 at 1, 3, and 5 years, respectively. ATP1A1 was highly expressed in endothelial cells and was significantly associated with M1 macrophages; thus, it was selected as a potential therapeutic target. Functional analyses revealed its role in angiogenesis inhibition and M1 macrophage polarization. The risk model and nomogram demonstrate strong prognostic value and may aid in clinical risk stratification for ccRCC. ATP1A1 emerges as a potential therapeutic target, with functional implications in angiogenesis and immune modulation. These findings highlight the clinical relevance of the identified gene signatures and support the development of personalized treatment strategies for ccRCC patients. Show less

Coronary artery anomalies are rare both in coronary angiogram and computed tomography angiography. Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. The phenotype of HCM associated with anomalous coronary origin is not commonly seen especially in children. We describe a case series of two children with HCM combined right coronary artery (RCA) originated from left coronary sinus. Case 1 was a 9-month-old female with HCM coexisted with anomalous origin of RCA has different clinical presentation, and it maybe due to different gene mutation. Show less

Major depressive disorder (MDD) in adolescents is a critical public health concern, yet objective diagnostic biomarkers remain lacking. We conducted an integrative lipidomics study across human cohorts and a chronic unpredictable mild stress (CUMS) rat model. Targeted UPLC-MS/MS profiling was applied to a training cohort (95 MDD, 40 controls), and untargeted UPLC-HRMS profiling to an independent cohort (56 MDD, 37 controls). Candidate biomarkers were identified using univariate tests, partial least squares discriminant analysis, and three feature-selection methods (Boruta, LASSO, RFE), with predictive performance evaluated by cross-validation and external replication. Translational relevance was examined in CUMS rats through behavioral assays and lipidomic profiling of serum and brain tissues. Pathway enrichment and regression models explored metabolic context and clinical associations. In the training cohort, we found that 244 lipids were significantly altered, highlighting altered glycerophospholipid, glycerolipid, and sphingolipid metabolism. A 29-lipid panel achieved 90.4% cross-validation accuracy, while a reduced 7-lipid subset reached 94.8%. In the validation cohort, an 8-lipid panel achieved 71.2% accuracy, and a minimal 2-lipid set-LPA(18:2) and SPH(d16:1)-reached 72.1%. Cross-species analysis confirmed consistent downregulation of SPH(d16:1) in serum of both humans and rats, and of LPC(0:0/16:0) specifically in the rat prefrontal cortex. Regression analyses linked sex, age, and anxiety severity to lipid alterations. This cross-platform, cross-species study identifies reproducible lipid signatures of adolescent MDD, highlights SPH(d16:1) and LPC(0:0/16:0) as translational biomarkers, and implicates glycerophospholipid metabolism in MDD pathophysiology, providing a foundation for biomarker-guided diagnostics and therapeutics. Show less

Diabetic nephropathy (DN) is a major complication of type 1 diabetes (T1D). Current diagnostic parameters, such as albuminuria and estimated glomerular filtration rate (eGFR), often detect the disease at advanced stages, promoting the identification of additional inflammatory markers. This study investigated the potential roles of pro-inflammatory interleukin-26 (IL-26), anti-inflammatory interleukin-35 (IL-35), and Signal Transducer and Activator of Transcription 1 (stat1) gene expression as potential biomarkers of DN in T1D. To evaluate serum levels of IL-26 and IL-35 and the gene expression of stat1 in T1D patients with and without renal dysfunction to assess their involvement in DN. This case-control study included 80 T1D patients (subgrouped to nephropathy status) and 60 healthy controls. Serum cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and stat1 expression in the blood was assessed using quantitative real-time PCR (qPCR). Statistical analyses included ANOVA, correlation tests, and receiver operating characteristic (ROC) curve analysis. IL-26 levels were not significantly elevated in hemodialysis T1D patients. IL-35 levels were significantly higher in T1D patients with nephropathy and in those on hemodialysis. A significant positive correlation was observed between IL-26 and IL-35 levels (r = 0.561, p = 0.0002). stat1 gene expression was significantly elevated in all T1D subgroups compared to controls, with the highest level observed in the hemodialysis group. ROC analysis indicated that stat1 had a discriminative ability for T1D, whereas IL-35 showed an acceptable diagnostic value for end-stage renal disease. This study showed that stat1 expression and IL-35 levels were linked with renal impairment in the T1D context, with stat1 expression elevated across T1D subgroups, and IL-35 expression was more accentuated in advanced renal dysfunction. Despite its limited discriminative value, IL-26 correlates with IL-35, suggesting simultaneous regulation within the inflammatory microenvironment. Show less