Speed capability is critical for early childhood development, but troubling patterns are emerging in the motor fitness of Chinese preschoolers (3-6 years). This study investigated how compositional 24 Show more
Speed capability is critical for early childhood development, but troubling patterns are emerging in the motor fitness of Chinese preschoolers (3-6 years). This study investigated how compositional 24-h movement behaviours (sleep, sedentary behaviour [SB], light physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) relate to speed capability. Via compositional data analysis and isotemporal substitution modelling, we assessed relationships between 24-h movement behaviours (sleep, SB, LPA and MVPA) and speed capability in 275 preschoolers (mean age 4.98 ± 0.76 years). Participants completed 20-m sprint tests and 7-day accelerometry. Time-reallocation effects were quantified through pairwise behavioural substitutions (5- to 30-min durations), with all models adjusted for age, sex and BMI z scores (z-BMI). Higher relative MVPA time significantly predicted faster sprint times (β = -1.302, p < 0.001), while higher LPA predicted slower times (β = 1.570, p = 0.003). Reallocating 15 min from sleep, SB or LPA to MVPA reduced sprint times by 0.176, 0.201 and 0.385 s, respectively (all p < 0.05). Conversely, reallocating MVPA to other behaviours worsened performance. The effects exhibited asymmetry: displacing time away from MVPA impaired speed capability to a greater extent than equivalent gains in MVPA time improved it. MVPA is the strongest positive predictor of speed capability in preschoolers. Optimizing 24-h movement patterns by reallocating time from LPA or SB to MVPA is associated with enhanced speed performance, supporting targeted interventions for early childhood development. Show less
This study used compositional data techniques that address the interdependence of 24-h movement behaviors (sleep, sedentary behavior [SB], light-intensity physical activity [LPA], moderate-to-vigorous Show more
This study used compositional data techniques that address the interdependence of 24-h movement behaviors (sleep, sedentary behavior [SB], light-intensity physical activity [LPA], moderate-to-vigorous intensity physical activity [MVPA]) to examine: (1) how patients undergoing metabolic bariatric surgery (MBS) allocate time among these behaviors before MBS, and (2) whether overall time-use composition and modeled reallocation patterns relate to early weight loss after MBS. Participants wore an accelerometer 24 h/day for 10 days before MBS to measure time in sleep, SB, LPA, and MVPA. Isotemporal substitution models estimated differences in 6-month post-MBS percentage total weight loss (%TWL) associated with reallocations of these pre-surgery movement behaviors. Forty-five participants provided valid data. Pre-MBS time-use composition was associated with %TWL (23.8 ± 5.1%; F = 2.66, p = 0.047). Reallocating 15-60 SB or LPA minutes/day to MVPA was estimated to relate to 0.9-3.5% greater %TWL. Reallocating 15-30 MVPA minutes/day to SB or LPA was estimated to relate to 1.4-5.0% less %TWL (all comparisons p < 0.05). Other reallocations were non-significant. In conclusion, modeled shifts in time from SB or LPA to MVPA and vice versa were associated with estimated increases or decreases in early post-surgical weight loss, respectively. Experimental research is needed to clarify causal relationships and inform interventions to improve MBS outcomes. Show less
A health-promoting lifestyle involves increasing health awareness and actively adopting healthier habits. For women with osteopenia, becoming more aware of osteoporosis prevention and taking positive Show more
A health-promoting lifestyle involves increasing health awareness and actively adopting healthier habits. For women with osteopenia, becoming more aware of osteoporosis prevention and taking positive preventive actions can effectively improve health outcomes. This study employed latent profile analysis (LPA) to assess the potential categories of healthy lifestyle promotion for women at high risk of primary osteoporosis. It aimed to identify high-risk subgroups, analyze differences and influencing factors among these groups, and offer evidence-based guidance for clinical nursing practice. From December 2024 to July 2025, women were recruited using convenience sampling from endocrine outpatient departments and physical examination centers at two Grade A tertiary hospitals in Guiyang City. Data collection followed the planned time frame, and only eligible samples were included. Latent profile analysis was performed with Mplus 8.3, and univariate and multiple logistic regression analyses were conducted using SPSS 27.0. A total of 340 valid questionnaires were analyzed. Participants were categorized into three latent profiles: the low self-management-ineffective health behaviors group (28.8 %), the moderate self-management-average health behaviors group (45.3 %), and the high self-management-favorable health behaviors group (25.9 %). These findings highlight disparities in the adoption of healthy lifestyles among women at high risk of primary osteoporosis. In clinical practice, nurses help patients with low health management recognize and overcome cognitive biases, use healthcare resources appropriately, and understand the importance of bone health. For patients with moderate health management, the can suggest exercise in addition to calcium supplementation. For those with high self-management, nurses can support their social networks to help maintain healthy behaviors over time. Show less
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in Show more
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in preschool-aged children. 268 preschoolers were included in the cross-sectional study. An accelerometer was used to assess sedentary behavior (SB), light and moderate-to-vigorous physical activity (LPA and MVPA). A parental report was used to collect sleep time. Bioelectrical impedance analysis was employed to assess body composition. Compositional linear regression analysis was employed to explore how daily movement behaviors were associated with body composition. Compositional isotemporal substitution analysis was employed to estimate changes in body composition after reallocating time among behaviors. 24-h movement behaviors composition significantly predicted fat-free mass index (FFMI), soft lean mass index (SLMI), and skeletal muscle mass index (SMMI), but not fat mass index, percent body fat, and bone mineral content index. The compositional isotemporal substitution analyses consistently showed that increasing MVPA at the expenses of SB was positively associated with FFMI (+0.328 kg/m The findings highlight the importance of MVPA in improving preschoolers' body composition. Increasing MVPA at the expenses of SB may be a strategy to improve body composition in preschoolers. Show less
Childhood trauma is a well-established risk factor for poor clinical outcomes in bipolar disorder (BD), yet most studies have relied on cumulative trauma scores, potentially overlooking heterogeneity Show more
Childhood trauma is a well-established risk factor for poor clinical outcomes in bipolar disorder (BD), yet most studies have relied on cumulative trauma scores, potentially overlooking heterogeneity in trauma exposure and its differential impact on psychopathology. This study employed latent profile analysis (LPA) to identify distinct subtypes of childhood trauma based on the Childhood Trauma Questionnaire (CTQ) among 725 individuals with BD in a Chinese clinical sample. Differences across trauma profiles were examined in relation to demographic features, psychiatric symptoms (anxiety, depression, mania), and suicidal ideation (Beck Scale for Suicide Ideation, BSSI). A four-class solution was identified, and the relationship with mental health outcomes was analyzed. Class 4 group, characterized by the most severe emotional abuse and physical neglect, along with the lowest emotional neglect, reported the highest levels of anxiety (HAMA), depression (HAMD), and suicidal ideation (BSSI). In contrast, manic symptoms (YMRS) were present across all groups but did not differ significantly between trauma profiles. Logistic regression indicated that emotional abuse was the strongest predictor of trauma class membership. Distinct trauma profiles in BD are differentially associated with symptom severity and suicide risk. These findings highlight the clinical value of moving beyond cumulative trauma scores to identify trauma-specific subtypes. Early identification of high-risk trauma configurations may inform personalized assessment and intervention strategies for individuals with BD. Show less
To develop a deep-learning model for segmenting and classifying adrenal nodules as either lipid-poor adenoma (LPA) or nodular hyperplasia (NH) on contrast-enhanced computed tomography (CECT) images. T Show more
To develop a deep-learning model for segmenting and classifying adrenal nodules as either lipid-poor adenoma (LPA) or nodular hyperplasia (NH) on contrast-enhanced computed tomography (CECT) images. This retrospective dual-center study included 164 patients (median age 51.0 years; 93 females) with pathologically confirmed LPA or NH. The model was trained on 128 patients from the internal center and validated on 36 external cases. Radiologists annotated adrenal glands and nodules on 1-mm portal-venous phase CT images. We proposed Mamba-USeg, a novel state-space models (SSMs)-based multi-class segmentation method that performs simultaneous segmentation and classification. Performance was evaluated using the mean Dice similarity coefficient (mDSC) for segmentation and sensitivity/specificity for classification, with comparisons made against MultiResUNet and CPFNet. From per-slice segmentation, the model yielded an mDSC of 0.855 for the adrenal gland; for nodule segmentation, it achieved mDSCs of 0.869 (LPA) and 0.863 (NH), significantly outperforming two previous models-MultiResUNet (LPA, p < 0.001; NH, p = 0.014) and CPFNet (LPA, p = 0.003; NH, p = 0.023). Classification performance from per slice demonstrated sensitivity of 95.3% (95% confidence interval [CI] 91.3-96.6%) and specificity of 92.7% (95% CI: 91.9-93.6%) for LPA, and sensitivity of 94.2% (95% CI: 89.7-97.7%) and specificity of 91.5% (95% CI: 90.4-92.4%) for NH. The classification accuracy for patients from external sources was 91.7% (95% CI: 76.8-98.9%). The proposed multi-class segmentation model can accurately segment and differentiate between LPA and NH on CECT images, demonstrating superior performance to existing methods. Question Accurate differentiation between LPA and NH on imaging remains clinically challenging yet critically important for guiding appropriate treatment approaches. Findings Mamba-Useg, a multi-class segmentation model utilizing pixel-level analysis and majority voting strategies, can accurately segment and classify adrenal nodules as LPA or NH. Clinical relevance The proposed multi-class segmentation model can simultaneously segment and classify adrenal nodules, outperforming previous models in accuracy; it significantly aids clinical decision-making and thereby reduces unnecessary surgeries in adrenal hyperplasia patients. Show less
Guangming Li, Yi Jin, Xiaowei Yuan+4 more · 2026 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here Show more
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here, we applied an integrative framework combining network toxicology, Mendelian randomization (MR), multi-omics analyses, molecular docking, molecular dynamics simulations, and in vitro experiments to elucidate the mechanisms underlying DBP-associated HNSC. Lipoprotein lipase (LPL) was identified as the sole overlapping gene between DBP-related targets and HNSC-associated genes. MR analysis supported a potential causal relationship between LPL and HNSC susceptibility. Expression profiling demonstrated tissue- and cell type-specific patterns of LPL and its dysregulation in HNSC, with associations to tumor stage and prognosis. Genomic analyses revealed that LPL alterations were infrequent and mainly driven by copy number loss. LPL expression positively correlated with immune and stromal infiltration. Enrichment analyses implicated immune regulation and PI3K-AKT signaling. Molecular simulations showed stable DBP-LPL binding. Functionally, DBP promoted SCC9 proliferation and reduced LPL expression, and was associated with transcriptional changes in PI3K-AKT-mTOR-related genes, whereas LPL restoration mitigated these effects. These findings reveal a novel DBP-LPL axis in HNSC. Show less
The fat mass and obesity-associated (FTO) gene, though widely studied in human obesity and livestock lipid accumulation, remains poorly understood in bovine adipogenesis. This study investigated its r Show more
The fat mass and obesity-associated (FTO) gene, though widely studied in human obesity and livestock lipid accumulation, remains poorly understood in bovine adipogenesis. This study investigated its role in bovine adipocytes via overexpression, given its high expression in Guanling cattle adipose tissue. Results demonstrated that FTO significantly increased triglyceride content, adiponectin secretion, and lipid droplet accumulation (P < 0.01). It also upregulated key adipogenic markers (PPARγ, C/EBPβ, FABP4, LPL; P < 0.05). Transcriptomic analysis revealed that FTO promotes adipocyte differentiation and lipogenesis through regulating multiple lipid metabolic pathways. These findings reveal that FTO positively regulates bovine adipocyte differentiation by modulating lipid metabolic networks, thereby filling a critical gap in the understanding of FTO-mediated lipid metabolism in ruminants. Show less
Moderate-to-vigorous physical activity (MVPA) is inversely associated with risks of cancer, cardiovascular diseases (CVD), type 2 diabetes (T2D), and their co-occurrence, defined as multimorbidity; ho Show more
Moderate-to-vigorous physical activity (MVPA) is inversely associated with risks of cancer, cardiovascular diseases (CVD), type 2 diabetes (T2D), and their co-occurrence, defined as multimorbidity; however, the underlying biological pathways remain unclear. In 33,806 UK Biobank participants with 2911 measured blood proteins, a proteomic signature of MVPA was derived with linear and LASSO regressions. Multivariable Cox models, adjusted for MVPA, estimated prospective associations with cancer, CVD, T2D, and multimorbidity. We show that after multiple testing corrections, 220 proteins are retained in the MVPA signature. Proteins related to food intake, metabolism, and cell growth (e.g., LEP, MSTN) are inversely associated, while those involved in immune cell migration and musculoskeletal integrity (e.g., integrins, COMP) are positively associated with MVPA. Several proteins positively associated with MVPA are inversely associated with disease risk (e.g., integrins, CLEC4A for cancer; LPL, LEP for T2D), while proteins negatively associated with MVPA are positively associated with disease risk (e.g., CD38, TGFA for CVD). The proteomic signature score is inversely associated with cancer risk (hazard ratio per interquartile range: 0.87; 95% confidence interval: 0.78, 0.96) and T2D (0.66; 0.60, 0.72). For multimorbidity, proteins inversely related to MVPA align with expected risk patterns (e.g., GGT1, HR: 1.32; 95% CI: 1.12, 1.57), but the proteomic signature score is not associated. This study identifies several proteins associated with MVPA that are also associated with cancer, CVD, T2D, and the multimorbidity of these conditions. Further studies investigating the causal nature of these associations are welcome. 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 Show more
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
Backfat thickness, a key selection trait in pig-breeding programmes, has traditionally been measured as a homogeneous layer. However, backfat is anatomically structured into three distinct layers, and Show more
Backfat thickness, a key selection trait in pig-breeding programmes, has traditionally been measured as a homogeneous layer. However, backfat is anatomically structured into three distinct layers, and each layer likely contributes differently to carcass quality. In addition, previous studies have shown that the deposition of the third layer of backfat is phenotypically correlated with intramuscular fat (IMF). Therefore, targeted selection for specific backfat layers, particularly the third layer, represents a potential strategy to increase IMF content while maintaining a high lean meat percentage. However, the genetic architecture of these distinct porcine backfat layers remains poorly understood. The aim of this study was to estimate the genetic parameters and identify key candidate genes underlying the three backfat layers. We collected B-mode ultrasound images from 561 Landrace pigs to measure individual layer thickness, followed by DNA extraction, genotyping, genetic parameter estimation, and a genome-wide association study (GWAS). Our measurements showed that the first layer of backfat (FBF) is the thickest, followed by the second (SBF) and the third (TBF) layers. Genetic parameter estimation yielded heritability estimates of 0.37, 0.42, 0.38, 0.34, 0.32, 0.24, and 0.21 for total backfat (BF), FBF, FBF/BF, SBF, SBF/BF, TBF, and TBF/BF, respectively. Through integrated analysis of GWAS, Bayesian fine-mapping, and gene annotation, we identified 15 non-redundant candidate genes associated with different backfat layers. These included two genes (SOAT1 and ACBD6) shared by BF and SBF, LPL for BF and FBF, and CAND1 for TBF and TBF/BF. Additionally, SERPINA12 and SERPINA6 were associated with BF; PRKAG1 and PRDM16 with FBF; EPRS1 and SLC39A10 with FBF/BF; PTGES and CRAT with SBF; and ACLY, CAVIN1, and PDZRN3 with SBF/BF. Our results indicate that each layer is governed by a distinct set of genes, which advances our understanding of the genetic basis of backfat layers in pigs. Show less
The primary renal complication of diabetes mellitus is diabetic kidney disease (DKD). The precise pathogenic mechanisms of DKD remain poorly elucidated. The aim of this study was to identify potential Show more
The primary renal complication of diabetes mellitus is diabetic kidney disease (DKD). The precise pathogenic mechanisms of DKD remain poorly elucidated. The aim of this study was to identify potential energy metabolism-related genes associated with DKD. The GSE30529 and GSE30528 datasets were retrieved from the Gene Expression Omnibus, and energy metabolism-related genes were obtained from the GeneCards database. Differentially expressed genes (DEGs) between DKD and control groups were analyzed. The biological functions and signaling pathways of these DEGs were evaluated using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The diagnostic performance of hub genes for DKD was assessed using receiver operating characteristic (ROC) curve analysis. Expression levels of five significant energy metabolism-related genes were validated through immunohistochemistry. The Nephroseq V5 tool was used to evaluate gene expression in DKD and to determine correlations between gene expression and renal function in patients with DKD. A total of 17 energy metabolism-related DEGs were identified. Five hub genes-ALB, IGF1, CD36, LPL, and UCP2-were identified. Among these, CD36 and LPL demonstrated relatively high diagnostic accuracy for DKD. The findings suggest that CD36, IGF1, LPL, and UCP2 may serve as potential biomarkers for DKD. The genes CD36, IGF1, LPL, and UCP2 represent potential energy metabolism-related biomarkers with possible applications in the diagnosis and treatment of DKD. Show less
Physical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer's disease and all-cause dementia. However, the specific biological mechanisms through which PA Show more
Physical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer's disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. This study aims to address this gap, with a specific focus on all-cause dementia. We first assessed the conventional observational associations of three self-reported and three device-based PA/SB measures with circulating levels of 2,911 plasma proteins measured in the UK Biobank (n max =39,160) and assessed functional enrichment of identified proteins. We then used bi-directional Mendelian randomization (MR) to further evaluate the evidence for causal relationships of PA/SB with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia. Our findings revealed 41 proteins consistently associated with all PA measures and 1,027 proteins associated with at least one PA measure. Both conventional observational and MR study designs converged on proteins that appear to increase as a result of PA, including integrins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, LPL, and ADGRG2; on proteins that appear to decrease as a result of PA such as LEP, INHBC, CLMP, PTGDS, ADM, OGN, and PI3; and on proteins that are more responsive to high-intensity PA, such as CA14, CA6, CA4, KIT, and ANGPT2. Functional enrichment analyses revealed processes such as cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, GDF15, ITGAV, ITGAM, ITGA11, HPGDS, GFAP, ADM, AHNAK, and DPP4 were among 21 unique proteins found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis, and inflammation. Our results provide insights into how PA affects biological processes and protects against dementia, and provide avenues for future research into the health-promoting effects of PA. Show less
Suhua Wu, Juan Peng, Xiaodong Wang+11 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Obesity has become a global epidemic and a major contributor to the development of Type 2 diabetes (T2D) through the promotion of insulin resistance. Emerging evidence has shown that GPX4 expression i Show more
Obesity has become a global epidemic and a major contributor to the development of Type 2 diabetes (T2D) through the promotion of insulin resistance. Emerging evidence has shown that GPX4 expression is reduced in macrophages under hyperglycemic conditions; however, the involvement of macrophage-specific GPX4 in obesity-associated insulin resistance remains unclear. We generated macrophage-specific Gpx4 knockout (Gpx4 Show less
The international consensus classification or the World Health Organization classifications underrepresented driver alterations enriched in pediatric acute myeloid leukemia (AML). To address this, we Show more
The international consensus classification or the World Health Organization classifications underrepresented driver alterations enriched in pediatric acute myeloid leukemia (AML). To address this, we retrospectively characterized the genomic landscape of 105 pediatric patients with AML of East Asian ancestry using transcriptome and whole-exome sequencing (WES). In addition to the common recurrent fusions such as RUNX1::RUNX1T1 and CBFB::MYH11, we identified rearrangements involving KMT2A, NUP98, GLIS, as well as FLT3 and UBTF tandem duplications. The median somatic mutation rate in AML was 0.97 per megabase, as estimated by WES. Frequently mutated pathways included signaling: 68.6% (72/105), transcription: 37.1% (39/105), epigenetic regulation: 26.7% (28/105), cohesin: 7.6% (8/105), RNA binding: 3.8% (4/105), and protein modification: 5.7% (6/105). When analyzed together, high-risk genetic subtypes including GLISr, UBTF tandem duplications, PICALM::MLLT10, and HOXr were significantly associated with poorer 5 year overall survival (OS) in multivariable analysis (p-value = 0.037). Although FLT3 internal tandem duplications were significantly associated with inferior 5 year OS in univariable analysis, this effect was not significant in multivariable analysis (p-value = 0.382). Patients with RUNX1 mutations had inferior 5 year OS in multivariable analysis (p-value = 0.009). These findings suggest specific genomic alterations that may refine risk stratification and guide future therapeutic protocols in Taiwanese pediatric patients with AML. Show less
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progre Show more
Neuropathic pain (NP), a chronic disorder caused by somatosensory nervous system lesions, severely impairs the quality of life. Microglial metabolic reprogramming and neuroinflammation drive NP progression. Although ChREBP (key metabolic regulator) protects against NP, its specific mechanisms remain unclear. NP rat model was established via spared nerve injury (SNI) surgery, and mechanical allodynia was evaluated using Von Frey tests. ChREBP expression in microglia was detected through immunofluorescence, RT-qPCR, and western blot. Functional studies involved ChREBP knockdown/overexpression to assess effects on microglial polarization, neuroinflammation, neuronal excitability, pain behaviors, and fatty acid metabolism. Mechanisms were explored via dual-luciferase reporter and chromatin immunoprecipitation assays. Mechanical pain thresholds were significantly decreased on the ipsilateral side after SNI. ChREBP was upregulated in SDH microglia after SNI and in LPS-stimulated microglia in vitro. ChREBP knockdown inhibited anti-inflammatory microglial polarization, exacerbated neuroinflammation, and aggravated pain. Conversely, ChREBP overexpression promoted the anti-inflammatory phenotype, suppressed neuroinflammation, and alleviated pain. ChREBP enhanced microglial fatty acid oxidation and energy metabolism. Mechanistically, ChREBP bound to the TFBS1 site on the PGC-1α promoter to activate its transcription. PGC-1α overexpression rescued the impairments caused by ChREBP knockdown, including reduced fatty acid oxidation, suppressed anti-inflammatory polarization, elevated inflammatory factors, and increased neuronal excitability. The protective effects of ChREBP were attenuated by the fatty acid oxidation inhibitor Etomoxir. ChREBP alleviates NP by enhancing microglial fatty acid oxidation and anti-inflammatory phenotype via PGC-1α transcriptional activation, revealing a novel metabolic-immune axis for potential NP therapy. Show less
Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiac disorder characterized by left ventricular hypertrophy and contractile dysfunction. Mutations in sarcomeric genes, particularly cardi Show more
Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiac disorder characterized by left ventricular hypertrophy and contractile dysfunction. Mutations in sarcomeric genes, particularly cardiac myosin-binding protein C (MYBPC3), are a leading cause of HCM. Here, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of patients carrying distinct MYBPC3 mutations (c.2490dupT and c.1800delA). Both lines displayed normal morphology, stable karyotypes, robust expression of pluripotency markers, and trilineage differentiation potential. These patient-specific iPSC lines provide a valuable platform for modeling MYBPC3-associated HCM and enable mechanistic and therapeutic studies of inherited cardiac disease. Show less
Neurodegenerative and psychiatric disorders share overlapping molecular mechanisms, including neuroinflammation, oxidative stress, and neurotransmitter dysregulation. Essential oils from Lavandula ang Show more
Neurodegenerative and psychiatric disorders share overlapping molecular mechanisms, including neuroinflammation, oxidative stress, and neurotransmitter dysregulation. Essential oils from Lavandula angustifolia (TLEO) and Rosa rugosa (PREO) contain neuroactive compounds with therapeutic potential, but their mechanisms remain poorly defined. This study aimed to elucidate the shared and distinct molecular targets and pathways of TLEO and PREO using a multi-scale computational strategy. Compounds identified by GC-MS were evaluated through ADMET profiling, target prediction, and disease-target intersection analysis. Enrichment, network, docking, and dynamics analyses were performed on shared protein-coding targets between essential oils and twelve brain disorders, including seven neurodegenerative conditions (Alzheimer's disease, amyotrophic lateral sclerosis, Friedreich ataxia, Huntington's disease, Lewy body disease, Parkinson's disease, spinal muscular atrophy) and five psychiatric disorders (autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia). A total of 110 compounds yielded 252 common targets, with CHRM2 (GPCR) and NR1H3 (non-GPCR) identified as key hubs. Docking suggested strong binding affinities for caryophyllene oxide at CHRM2 (-7.3 kcal/mol) and α-himachalene at NR1H3 (-8.5 kcal/mol). Molecular dynamics simulations confirmed stable, compact complexes with low RMSD and SASA values. MM/PBSA free energy calculations quantitatively validated these interactions, revealing favorable binding energetics driven predominantly by van der Waals and hydrophobic contributions, consistent with the terpenoid chemical profiles. Functional enrichment highlighted involvement in cholinergic signaling, lipid metabolism, and inflammatory regulation. This study demonstrates that PREO and TLEO can modulate multiple targets relevant to brain disorders through both GPCR and non-GPCR mechanisms. These findings provide a computationally inferred mechanistic framework for the potential neuroprotective synergy of these oils and highlight essential oil-derived compounds as promising leads for further experimental investigation. Show less
This study aimed to systematically elucidate the antihyperlipidemic mechanism of paeoniflorin, and we adopted an integrated multi-omics strategy to screen the key molecular targets and regulatory path Show more
This study aimed to systematically elucidate the antihyperlipidemic mechanism of paeoniflorin, and we adopted an integrated multi-omics strategy to screen the key molecular targets and regulatory pathways involved in its action, followed by experimental validation to verify the potential regulatory effects of paeoniflorin on the screened targets and metabolic processes. Rats with high-fat diet-induced hyperlipidemia received paeoniflorin treatment. Liver histopathology was evaluated using hematoxylin-eosin and Oil Red O staining. Serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bile acids, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen were measured using a biochemical analyzer. Integrated multi-omics analyses were performed to investigate paeoniflorin's lipid-lowering mechanism. Critical pathways and targets identified were validated using Western blotting. Paeoniflorin alleviated pathological liver damage in hyperlipidemic rats and improved blood lipid levels, coagulation function, and liver function markers. Multi-omics analyses verified that paeoniflorin downregulated the expression of TREM-1, TLR4, NF-κB, TNF-α, and IL-1β, thereby alleviating hepatic inflammation. Paeoniflorin also upregulated the expression of low-density lipoprotein receptors (LDLR), liver X receptor alpha (LXRα), and ATP-binding cassette subfamily G member 1 (ABCG1), while downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, contributing to balanced cholesterol metabolism. Paeoniflorin normalized glycerophospholipid and branched-chain amino acid metabolism, which correlated with reduced inflammation and improved cholesterol metabolism. Paeoniflorin ameliorates hyperlipidemia through multitarget mechanisms, potentially by suppressing the TREM-1-TLR4-NF-κB signaling pathway to reduce inflammation and by regulating cholesterol metabolism via the PCSK9-LDLR and LXRα-ABCG1 pathways. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent disease, yet its genetic architecture remains incompletely characterized. We integrated genome-wide association Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent disease, yet its genetic architecture remains incompletely characterized. We integrated genome-wide association study data from multiple cohorts totaling nearly 3 million individuals of European ancestry and applied cross-trait genomic modeling of hepatic fat and seven cardiometabolic traits to construct an MASLD-specific polygenic architecture. We identified 128 risk variants across 100 loci and prioritized 55 effector genes, including established (e.g., Show less
Methotrexate (MTX) is a widely used chemotherapy drug, but its neurotoxicity can lead to cognitive impairments, particularly through effects on hippocampal function. Nevertheless, the underlying molec Show more
Methotrexate (MTX) is a widely used chemotherapy drug, but its neurotoxicity can lead to cognitive impairments, particularly through effects on hippocampal function. Nevertheless, the underlying molecular mechanisms are not fully understood. Deciphering MTX-induced cognitive impairment-linked molecular mechanisms in cells of the hippocampus could uncover novel therapeutic targets. In this study, we established a mouse model of cognitive impairment induced by the chemotherapy drug MTX. We applied single-nucleus RNA sequencing (snRNA-seq) to analyze the transcriptomic alterations in hippocampal cells of mice following MTX treatment, with a focus on neuron-specific gene expression changes. MTX chemotherapy led to a decrease in excitatory neurons but an increase in inhibitory neurons, altering the excitatory-inhibitory balance of neural networks and thus mediate cognitive dysfunction. Furthermore, MTX significantly disrupted the transcriptional regulatory network and potential trajectory of GABAergic neurons. It enhanced the Nrg1-Erbb4 pathway while attenuating the Nrxn3-Lrrtm4 pathway, destabilizing trans-synaptic signaling and causing abnormalities in excitatory and inhibitory synaptic functions. These disruptions may ultimately lead to neural network imbalance and cognitive dysfunction. This study highlights the specific effects of MTX chemotherapy on hippocampal cellular function and provides valuable insights into the molecular mechanisms underlying cognitive deficits and potential therapeutic targets. Show less
This study aims to elucidate the regulatory mechanisms of host genetics on the porcine gut microbiota and their subsequent impact on the feed conversion ratio (FCR). While initial genome-wide associat Show more
This study aims to elucidate the regulatory mechanisms of host genetics on the porcine gut microbiota and their subsequent impact on the feed conversion ratio (FCR). While initial genome-wide association studies (GWAS) did not identify significant SNPs directly associated with FCR, we investigated the gut microbiota as a potential intermediate phenotype influencing feed efficiency. Nonmetric multidimensional scaling (NMDS) based on Bray–Curtis distances demonstrated a distinct separation in microbial community structure between the high-feed conversion ratio (HFCR) and low-feed conversion ratio (LFCR) groups (stress = 0.19), suggesting a link between FCR and gut microbial composition. Furthermore, a significant, albeit weak, negative correlation was observed between the genomic relatedness matrices and microbial Bray‒Curtis dissimilarity ( The online version contains supplementary material available at 10.1186/s42523-026-00527-y. Show less
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, w Show more
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, we identify a regulatory axis wherein the transcription factor ZBED6 activates the expression of the autophagy-initiating kinase PIK3C3 via the repression of IGF2, thereby driving pro-tumorigenic autophagy. Spatial analysis confirms the co-localization of ZBED6 and PIK3C3 in tumor tissues. Using genes associated with this axis, we develop a six-gene prognostic signature that stratifies patients with distinct survival outcomes and differential responses to immunotherapy and targeted therapy. Functional assays show that ZBED6 promotes ccRCC cell proliferation, migration, and invasion. This work elucidates a pathway governing autophagy in ccRCC and provides a framework for prognostic assessment and precision therapy. Show less
The mammalian class III phosphatidylinositol-3-kinase complex (PtdIns3K) forms two biochemically and functionally distinct subcomplexes including the ATG14-containing complex I (PtdIns3K-C1) and the U Show more
The mammalian class III phosphatidylinositol-3-kinase complex (PtdIns3K) forms two biochemically and functionally distinct subcomplexes including the ATG14-containing complex I (PtdIns3K-C1) and the UVRAG-containing complex II (PtdIns3K-C2). Both subcomplexes adopt a V-shaped architecture with a BECN1-ATG14 or UVRAG adaptor arm and a PIK3R4/VPS15-PIK3C3/VPS34 catalytic arm. NRBF2 is a pro-autophagic modulator that specifically associates with PtdIns3K-C1 to enhance its kinase activity and promotes macroautophagy/autophagy. How NRBF2 exerts such a positive effect is not fully understood. Here we report that NRBF2 binds to PIK3R4/VPS15 with moderate affinity through a conserved site on its N-terminal MIT domain. The NRBF2-PIK3R4/VPS15 interaction is incompatible with the UVRAG-containing PtdIns3K-C2 because the C2 domain of UVRAG outcompetes NRBF2 for PIK3R4/VPS15 binding. Our crystal structure of the NRBF2 coiled-coil (CC) domain reveals a symmetric homodimer with multiple hydrophobic pairings at the CC interface, which is in distinct contrast to the asymmetric dimer observed in the yeast ortholog Atg38. Mutations in the CC domain that rendered NRBF2 monomeric led to weakened binding to PIK3R4/VPS15 and only partial rescue of autophagy deficiency in Show less
Retinal ischemia-reperfusion (I/R) injury is a key pathological feature of acute glaucoma that induces oxidative stress, inflammation, and retinal glial activation, ultimately leading to retinal degen Show more
Retinal ischemia-reperfusion (I/R) injury is a key pathological feature of acute glaucoma that induces oxidative stress, inflammation, and retinal glial activation, ultimately leading to retinal degeneration and neuronal dysfunction. This study evaluated the therapeutic potential of 3,4-dihydroxybenzalacetone (DBA) in protecting against I/R-induced retinal damage. DBA was tested in LPS-stimulated BV-2 microglia, in TNFα- or tBHP-treated rMC-1 Müller glial cells, and in a rat model of retinal I/R injury. In vitro assays demonstrated that DBA suppressed oxidative and inflammatory responses in microglia by reducing ROS, NO, IL-6, iNOS, and COX-2 levels. In Müller cells, DBA activated the NRF2/HO-1 pathway under oxidative stress and attenuated TNFα-induced upregulation of MMP-9 and MCP-1. Signaling analysis revealed that DBA inhibited the phosphorylation of p65 and STAT3 in both glial cell types, with additional ERK inhibition observed specifically in Müller cells. In vivo, DBA preserved retinal electrophysiological activity, as evidenced by maintained a- and b-wave responses, and reduced the expression of MMP-9, GFAP, and CD68 in the retina. These findings indicate that DBA confers partial retinal protection by modulating multiple glial-related signaling pathways and suggest its potential as a multi-target therapeutic agent for retinal neurodegenerative diseases. Show less
Prostate cancer (PCa) is the most general cancer in men and is often linked with distant metastasis in its later stages. The caffeic acid (CA) derivative, N-(4-methoxyphenyl)methylcaffeamide (MPMCA), Show more
Prostate cancer (PCa) is the most general cancer in men and is often linked with distant metastasis in its later stages. The caffeic acid (CA) derivative, N-(4-methoxyphenyl)methylcaffeamide (MPMCA), demonstrates superior liver-protective effects compared to CA. Nevertheless, the functions of MPMCA on prostate cancer metastasis remain unclear. Here, we demonstrate that MPMCA blocks migration and invasion in prostate cancer cells without affecting cell viability. By suppressing the production of mesenchymal markers Vimentin, N-cadherin and β-catenin and upregulating the production of the epithelial marker Zonula Occludens-1 (ZO-1), MPMCA also controls Epithelial-Mesenchymal Transition (EMT). The Phosphoinositide 3-kinase (PI3K), Protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) pathway has been documented to regulate MPMCA-inhibited cell motility. Transfection with Snail and Slug cDNA reverses MPMCA's suppression of EMT, migration, and invasion in prostate cancer cells. Importantly, our in vivo data indicates that MPMCA reduces Snail and Slug expression and prostate cancer metastasis. Our evidence suggests that MPMCA is a novel therapeutic candidate for treating metastatic prostate cancer. Show less