Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, neuroinflammation, and neuronal apoptosis. Trofinetide, an analog of insulin-like growth fac Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, neuroinflammation, and neuronal apoptosis. Trofinetide, an analog of insulin-like growth factor 1 (IGF-1), has shown neuroprotective effects in various neurological disorders, but its role in AD remains unclear. Six-month-old APP/PS1 transgenic mice received intraperitoneal trofinetide for 2 months. Cognitive function was assessed using the Morris water maze (MWM) test. Immunohistochemistry (IHC) and immunofluorescence (IF) evaluated β-amyloid (Aβ) pathology, microglial activation, and neuronal loss. In vitro, BV2 microglial cells and HT22 hippocampal neurons were treated with trofinetide against AβO-induced cytotoxicity. Western blot (WB) was used to analyze inflammation and apoptosis-related proteins. Trofinetide significantly improved cognitive deficits, reduced Aβ plaque deposition, and decreased microglial activation and neuronal loss in APP/PS1 mice. In vitro, it rescued AβO-induced cytotoxicity, suppressed inflammatory cytokines (TNF-α, IL-6, IL-1) in BV2 cells, and inhibited apoptosis in HT22 cells. Mechanistically, trofinetide upregulated PPAR-γ, reduced BACE1, suppressed NF-κB phosphorylation, inhibited caspase-3 activation, and restored Bax/Bcl-2 balance, alleviating neuroinflammation and apoptosis. This study provides the first evidence that trofinetide improves cognitive function and mitigates Aβ pathology, neuroinflammation, and apoptosis in APP/PS1 mice and AβO-treated cells, highlighting its therapeutic potential for AD. Show less
Head and neck squamous cell carcinoma (HNSCC) poses a global health challenge. The management of HNSCC is complicated by the difficulty in detecting occult lymph node metastases, leading to dilemmas i Show more
Head and neck squamous cell carcinoma (HNSCC) poses a global health challenge. The management of HNSCC is complicated by the difficulty in detecting occult lymph node metastases, leading to dilemmas in elective neck dissection decisions, which will impair patients' quality of life without improving survival for nodal negative patients. We conducted a comparative analysis of the clinical features, genomic alterations, gene expression and methylation, tumor microenvironment and cellular states between the clinically N0 and pathologically N0 (cN0-pN0) patients and occult lymph node metastatic patients. Patients with occult lymph node metastases typically present with more poorly differentiated primary tumors and higher rates of angiolymphatic and perineural invasion. We identified a distinctive genomic mutation spectrum in the primary tumors of patients with occult metastases, notably in genes such as NSD1, ARHGAP15 and SMARCA4. A whole-genome DNA hypomethylation and altered gene expression profiles are identified in occult lymph node metastatic patients. Analysis of the tumor microenvironment revealed an enrichment of CARNS1 + NK cells and CBX1 + tumor cells in occult metastatic patients. In conclusion, patients with occult lymph node metastases exhibit distinct molecular and clinical features compared with cN0-pN0 patients. Show less
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments in the elderly. Microglia, the resident immune cells of the Show more
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments in the elderly. Microglia, the resident immune cells of the central nervous system, play a crucial role in modulating the pathological processes associated with AD. Jiajian Shuyu Pills (JJSYP) are frequently employed in the treatment of AD, purportedly by enhancing the physiological functions of human tissues and organs to modulate the immune response. Nevertheless, the underlying mechanisms by which JJSYP exert their therapeutic effects in the context of AD remain inadequately elucidated. This study aimed to assess the effects of JJSYP on cognitive enhancement and the alleviation of neuroinflammation in the treatment of AD, as well as to explore the underlying mechanisms using mouse models. The components of JJSYP in serum were analyzed using HPLC-Q/TOF-MS. APP/PS1 transgenic mice served as AD models in this investigation. Cognitive function in the AD mice was assessed through the Mirror Water Maze Test and the Novel Object Recognition Test. The quantification of apoptotic hippocampal cells was conducted using Nissl staining and TUNEL staining. Immunofluorescence (IF) and Western blot (WB) analyses were employed to examine microglial activation and the expression of relevant proteins. Transcriptomic sequencing analysis and network pharmacology were administrated to explore the potential mechanisms of JJSYP in AD treatment. Inflammatory cytokine levels in the brain were measured using RT-PCR. A total of 74 absorbed prototype components from JJSYP were identified. JJSYP effectively improved cognitive function and neuroapoptosis in AD model mice by modulating the activation of microglia. The JJSYP intervention alleviated neuroinflammation by suppressing microglial activation and reducing the accumulation of amyloid β-protein. Through transcriptome sequencing and WB verification, 34 differentially expressed genes (DEGs) were identified, including ACKR3, NR1H3 and Adra1a. Following treatment with a high dose of JJSYP, both ACKR3 and NR1H3 showed a significant decrease compared to the model group. Conversely, ADRA1A expression was reduced in model group compared to the control group, but increased following high dose JJSYP treatment. Research involving RNA sequencing and network pharmacology indicated that JJSYP altered the activation of CXCL12/ACKR3 signaling pathways in the hippocampus. JJSYP exhibits potential anti-Alzheimer's Disease effects and warrants further investigation and development as a prosper treatment for AD. Show less
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases, with a range of manifestations, such as hepatic steatosis. Our previous study showed that Kaili Sour Soup Show more
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases, with a range of manifestations, such as hepatic steatosis. Our previous study showed that Kaili Sour Soup (KSS) significantly attenuated hepatic steatosis in rats. This study explored the main components of KSS and the mechanisms by which it exerts its protective effects against NAFLD. Twenty-four 6-week-old male Sprague-Dowley (SD) rats were randomly assigned to three treatments: feeding a normal standard diet, a high-fat diet, or a high-fat diet plus gavage KSS. The effects of KSS treatment on hepatic lipid accumulation were assessed using biochemical, histological, and molecular experiments. The amounts of KSS ingredients were measured using biochemical assays. Network pharmacology analyses were performed to identify the hub genes of KSS targets and enriched pathways. CCK-8 assay was used to determine the effect of free fatty acids (FFA), lycopene, and estrogen on HepG2 viability. Quantitative Real-Time polymerase chain reaction (qRT-PCR) and Western blot assays were performed to determine the effect of KSS or lycopene on estrogen signaling and expression of lipid metabolism-related molecules. Statistical analyses were performed using GraphPad Prism and SPSS. KSS alleviated fat deposition in rat liver tissue and affected the expression of hepatic lipid synthesis, catabolism, and oxidative molecules. Lycopene was identified as the ingredient with the highest amount in KSS. Network pharmacology analyses showed that the hub genes were enriched in the estrogen signaling pathway. Cellular experiments showed that lycopene increased the expression of Estrogen Receptor α (ERα), Carnitine palmitoyltransferase 1 A ( KSS ameliorated abnormal lipid metabolism in patients with NAFLD. Lycopene was the major component of KSS, and it affected estrogen signaling and the expression of lipid metabolism molecules. In short, both KSS and LYC could change lipid metabolism by lowering lipid accumulation and raising lipolysis. Show less
Growth Factor Receptor-Binding Protein 10 (GRB10) is an adaptor protein implicated in tyrosine kinase signaling, yet its pan-cancer role and clinical impact remain incompletely characterized. This stu Show more
Growth Factor Receptor-Binding Protein 10 (GRB10) is an adaptor protein implicated in tyrosine kinase signaling, yet its pan-cancer role and clinical impact remain incompletely characterized. This study aims to define the pan-cancer landscape of GRB10 dysregulation and its clinical implications for prognosis and immunotherapy response. Multi-omics analysis of 33 TCGA cancers and validation in GEO cohorts assessed GRB10 expression, prognostic impact (Cox regression, Kaplan-Meier), functional enrichment (Gene Set Enrichment Analysis, Gene Set Variation Analysis), immune correlates (Spearman with immune genes, ESTIMATE/CIBERSORT/EPIC/TIMER/xCell infiltration), tumor mutational burden (TMB), and immunotherapy predictive power. In the TCGA pan-cancer cohort, GRB10 was significantly elevated in 11 cancer types (CHOL, COAD, ESCA, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, STAD, THCA) and downregulated in 4 (BLCA, BRCA, CESC, UCEC). Aberrant GRB10 expression was strongly associated with adverse prognosis in LGG, CESC, COAD, and LUAD for OS, DSS, and PFI, a finding validated externally in GEO colon cancer cohorts. Conversely, it served as a protective factor in KIRC. Functionally, GRB10 was implicated in epithelial-mesenchymal transition (EMT), evidenced by positive correlations with EMT pathway scores and key regulators (ZEB1, ZEB2, SNAI1, SNAI2). GRB10 expression robustly correlated with an immunosuppressive tumor microenvironment (TME), evidenced by negative enrichment of immune response pathways (e.g., IFN-α/γ) and complex associations with immune-related genes. Immune infiltration analysis revealed consistent positive correlations with CD4⁺ memory-resting T cells and negative correlations with CD4⁺ effector memory T cells across most cancers. Critically, high GRB10 expression predicted significantly shorter survival and poorer response rates in multiple immunotherapy-treated cohorts (urothelial carcinoma, melanoma, gastric cancer). GRB10 also showed significant associations with TMB in several cancers, and its protein interaction network was enriched in PI3K-Akt, FoxO, and Rap1 signaling pathways. Our pan-cancer analysis establishes GRB10 as a key facilitator of tumor progression, linked to EMT and an immunosuppressive microenvironment, and nominates it as a novel biomarker for adverse prognosis and resistance to immune checkpoint blockade therapy. The online version contains supplementary material available at 10.1007/s12672-025-04333-x. Show less
Cardiovascular disease (CVD) is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet traditional risk predictors remain limited in clin Show more
Cardiovascular disease (CVD) is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet traditional risk predictors remain limited in clinical practice. To develop machine learning (ML) models for classifying prevalent atherosclerotic cardiovascular disease (ASCVD) risk in MASLD patients, and to enhance model interpretability using SHapley Additive exPlanations (SHAP). Methods: This retrospective study included 590 MASLD patients diagnosed at the Affiliated Hospital of Qingdao University between December 2019 and December 2024. Patients were randomly divided into a training set (n=413) and a validation set (n=177), and further stratified based on ASCVD status. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Six ML models were developed and evaluated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and F1 score. SHAP analysis was performed to interpret feature contributions. ASCVD was present in 434 of 590 patients (73.6%). The Gradient Boosting (GB) model achieved the best performance, with AUCs of 0.918 (95% CI: 0.890-0.944) in the training set and 0.817 (95% CI: 0.739-0.883) in the validation set. SHAP analysis identified the top predictors as the Cholesterol-HDL-Glucose (CHG) index, Castelli Risk Index II (CRI-II), lipoprotein(a) [Lp(a)], serum creatinine (Scr), and uric acid (UA). The GB model demonstrated strong high accuracy in identifying existing ASCVD in MASLD patients and may serve as a useful tool for early risk stratification in clinical settings. Show less
A comprehensive understanding of protein corona (PC) composition is critical for engineering nanoparticles (NPs) with optimal safety and therapeutic performance, because the PC governs NP pharmacokine Show more
A comprehensive understanding of protein corona (PC) composition is critical for engineering nanoparticles (NPs) with optimal safety and therapeutic performance, because the PC governs NP pharmacokinetics, biodistribution, and cellular interactions. Yet systematic analyses are hampered by the absence of standardized, richly annotated data sets. Here, we introduce the Protein Corona Database (PC-DB), which compiles data from 83 studies (2000-2024) and integrates 817 NP formulations with quantitative profiles of 2497 adsorbed proteins. The PC-DB exposes pronounced heterogeneity in NP materials (metal 28.8%, silica 22.8%, lipid-based 14.8%), surface modifications, sizes (1-1400 nm), and ζ-potentials (-70 to +70 mV). Subsequent meta-analysis shows that silica, polystyrene, and lipid-based NPs smaller than 100 nm with moderately negative to neutral ζ-potentials preferentially bind the lipoproteins APOE and APOB-100, which are linked to receptor-mediated uptake and enhanced delivery efficiency. In contrast, metal and metal-oxide NPs carrying highly negative surface charge enrich complement component C3, indicating a greater likelihood of immune recognition and clearance. Interpretable machine learning models (LightGBM and XGBoost; ROC-AUC > 0.85) confirm NP size, ζ-potential, and incubation time as the most influential predictors of protein adsorption. These results delineate how physicochemical parameters dictate PC composition and illustrate the power of predictive modeling to guide rational NP design. Show less
Brachydactyly type E (BDE) is characterized by variable shortening of metacarpals or metatarsals, often involving phalanges. It may occur as an isolated anomaly or as part of congenital syndromes. Wit Show more
Brachydactyly type E (BDE) is characterized by variable shortening of metacarpals or metatarsals, often involving phalanges. It may occur as an isolated anomaly or as part of congenital syndromes. With advancements in molecular diagnostic technologies, how genetic testing enhances the precise diagnosis of BDE remains unclear. Our aims were to establish an algorithm for molecular genetic diagnostics in Chinese children with BDE and to explore the phenotype-genotype correlations of Chinese patients with BDE. We reviewed left-hand wrist X-rays from children visiting Children's Hospital of Soochow University (Jun 2021-Dec 2023). From 60,650 films, 135 BDE cases were identified, and their comprehensive phenotypes were collected. Whole-exome sequencing (WES) with copy number variation (CNV) analysis was performed on 60 patients and their parents. Sanger sequencing was used to validate single nucleotide variants (SNV) and indels. Causative variants were found in 19 patients. SNVs and indels affecting 10 genes were identified in 15 patients, and CNVs in four. Through comprehensive evaluation of genotype-phenotype correlations, we propose a diagnostic algorithm for precise molecular diagnosis in Chinese children with BDE. Show less
Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause Show more
Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause of their life expectancy being 15-20 years shorter than that of the general population. Identifying comorbidity patterns and uncovering differences in immune and metabolic function are crucial steps toward improving prevention and management strategies. A retrospective cross-sectional study was conducted using electronic medical records of inpatients discharged between 2015 and 2024 from a municipal psychiatric hospital in China. The study included patients diagnosed with Schizophrenia, Schizotypal, and Delusional Disorders (SSDs) (ICD-10: F20-F29). Comorbidity patterns were identified through latent class analysis (LCA) based on the 20 most common comorbid conditions among SSD patients. To investigate differences in peripheral blood metabolic and immune function, linear regression or generalized linear models were applied to 44 laboratory test indicators collected during the acute episode. The Benjamini-Hochberg method was used for p-value correction, and the false discovery rate (FDR) was calculated, with statistical significance set at FDR < 0.05. Among 3,697 inpatients with SSDs, four distinct comorbidity clusters were identified: SSDs only (Class 1), High-Risk Metabolic Multisystem Disorders (Class 2, n = 39), Low-Risk Metabolic Multisystem Disorders (Class 3, n = 573), and Sleep Disorders (Class 4, n = 205). Compared to Class 1, Class 2 exhibited significantly elevated levels of apolipoprotein A (ApoA; β = 90.62), apolipoprotein B (ApoB; β = 0.181), mean platelet volume (MPV; β = 0.994), red cell distribution width-coefficient of variation (RDW-CV; β = 1.182), antistreptolysin O (ASO; β = 276.80), and absolute lymphocyte count (ALC; β = 0.306), along with reduced apolipoprotein AI (ApoAI; β = -0.173) and hematocrit (HCT; β = -35.13). Class 3 showed moderate increases in low-density lipoprotein cholesterol (LDL-C; β = 0.113), MPV (β = 0.267), white blood cell count (WBC; β = 0.476), and absolute neutrophil count (ANC; β = 0.272), with decreased HCT (β = -9.81). Class 4 was characterized by elevated aggregate index of systemic inflammation (AISI; β = 81.07), neutrophil-to-lymphocyte ratio (NLR; β = 0.465), and systemic inflammation response index (SIRI; β = 0.346), indicating a heightened inflammatory state. The comorbidity patterns of patients with SCZ can be distinctly classified. During the acute episode, those with comorbid metabolic disorders exhibit a higher risk of cardiovascular diseases and immune system abnormalities, while patients with comorbid sleep disorders present a pronounced systemic inflammatory state and immune dysfunction. This study provides a basis for the chronic disease management and anti-inflammatory treatment, while also offering objective biomarker insights for transdiagnostic research. Show less
Hyperlipidemia is a common metabolic disorder and a risk factor for cardiovascular disease. The traditional medicine herb, Hippophae rhamnoides L., known as sea buckthorn, has anti-obesity and lipid-l Show more
Hyperlipidemia is a common metabolic disorder and a risk factor for cardiovascular disease. The traditional medicine herb, Hippophae rhamnoides L., known as sea buckthorn, has anti-obesity and lipid-lowering effects, while Silybum marianum (L.) Gaertn, known as milk thistle, has hepatoprotective properties and exhibits antioxidant effects. To evaluate the effect of sea buckthorn and milk thistle solid beverage (H-S solid beverage) in alleviating hyperlipidemia in rats and explore the underlying mechanisms by analyzing plasma and liver metabolomics, lipidomics, and liver transcriptomics. A hyperlipidemic rat model was established after 2 weeks of high-fat diet (HFD) feeding in Sprague Dawley rats. The administered doses of H-S solid beverage were 0.30 g/kg/d, 0.15 g/kg/d and 0.075 g/kg/d. Serum biochemical parameter detection, histopathological section analysis, untargeted plasma and liver metabolomics, lipidomics, and liver transcriptomics were performed to determine the therapeutic effects of H-S solid beverage and predict the related pathways in rats with hyperlipidemia. Changes in genes and proteins related to lipid metabolism were detected using real-time quantitative polymerase chain reaction and western blotting. Eighty-nine components were identified in H-S solid beverage using ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry, with flavonoids being the major constituents. The H-S solid beverage significantly reduced body weight, liver index, body fat percentage, lipid accumulation, and liver injury in HFD-fed rats. Fatty acids (FA), bile acid, phosphatidyl ethanolamine, phosphatidylcholine, triglyceride, cholesterol ester, diglyceride and phosphatidylinositol levels were significantly altered in the liver and plasma. Moreover, the transcriptomic analysis suggested that H-S solid beverage significantly altered the hepatic gene expression of cholesterol synthesis (Pdk4, Hmgcs1, and Dhcr24), lipogenesis (Scd, Angptl4, and Angptl8), and FA β-oxidation (Cpt1α, Pparδ, Acsl, Pgc-1α, and Pla2g2d). The solid beverage of sea buckthorn and milk thistle was firstly demonstrated to ameliorate HFD-induced hyperlipidemia. The lipid-lowering and hepatoprotective effects of H-S solid beverage significantly regulated cholesterol synthesis and de novo lipogenesis, as well as FA β-oxidation. In summary, this study highlights the potential of H-S solid beverages for the treatment of hyperlipidemia. Show less
This study aimed to examine reticulon 4 (RTN4), neurite outgrowth inhibitor protein expression that changes in high-altitude traumatic brain injury (HA-TBI) and affects on blood-brain barrier's (BBB) Show more
This study aimed to examine reticulon 4 (RTN4), neurite outgrowth inhibitor protein expression that changes in high-altitude traumatic brain injury (HA-TBI) and affects on blood-brain barrier's (BBB) function. C57BL/6J 6-8-week-old male mice were used for TBI model induction and randomized into the normal altitude group and the 5000-m high-altitude (HA) group, each group was divided into control (C) and 8h/12h/24h/48h-TBI according to different times post-TBI. Brain water content (BWC) and modified Neurological Severity Score were measured, RTN4 and autophagy-related indexes (Beclin1, LC3B, and SQSTM1/p62) were detected by western blot, immunofluorescence technique, and PCR in peri-injury cortical tissues. The expression of NgR1, Lingo-1, TROY, P75, PirB, S1PR2, and RhoA receptors' downstream of RTN4 was detected by PCR. HA-TBI caused increased neurological deficits including motor, sensory, balance and reflex deficits, increased BWC, earlier peak RTN4 expression and a longer duration of high expression in peri-injury cortical tissues, and enhanced levels of Beclin1, LC3B, and SQSTM1/p62 to varying degrees. Concurrently, the transcription of S1PR2 and PirB, the main signaling molecules downstream of RTN4, was significantly increased. In HA-TBI's early stages, the increased RTN4 may regulate enhanced autophagic initiation and impaired autolysosome degradation in vascular endothelial cells via S1PR2 receptor activation, thereby reducing BBB function. This suggests that autophagy could be a new target using RTN4 intervention as a clinical HA-TBI mechanism. Show less
Dietary interventions with food-derived natural products have emerged as a promising strategy to alleviate obesity. This study aims to investigate the anti-obesity effect of
Lung adenocarcinoma (LUAD), the predominant histological subtype of non-small cell lung cancer, demonstrates critical regulatory involvement of RNA-binding proteins (RBPs) and circular RNAs (circRNAs) Show more
Lung adenocarcinoma (LUAD), the predominant histological subtype of non-small cell lung cancer, demonstrates critical regulatory involvement of RNA-binding proteins (RBPs) and circular RNAs (circRNAs) in tumorigenic processes. Emerging evidence highlights the circRNA-autophagy regulatory axis as a crucial modulator of cancer progression. This study systematically investigates the functional interplay within the RBP-circRNA-autophagy network in LUAD pathogenesis. Employing RNA pull down, mass spectrometry and RNA immunoprecipitation facilitated the exploration of the circRAPGEF5 binding protein. M6A methylation RNA immunoprecipitation-PCR was utilized for m6A analysis. Immunofluorescence (IF) and fluorescence in situ hybridization (FISH) assays were conducted to ascertain the subcellular localization of target genes. Employing mRFP-GFP-LC3 fluorescent lentivirus labelling facilitated the monitoring of autophagy flow levels. Xenografts in mice were instrumental in affirming the role of circRAPGEF5. Through comprehensive molecular profiling, we identified elevated circRAPGEF5 expression in LUAD cells, which significantly suppressed autophagic flux while promoting malignant phenotypes including enhanced proliferation, migration, and invasion. Mechanistic investigations revealed that circRAPGEF5 directly interacts with the KH3-4 functional domain of Insulin-like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2), an m6A reader protein. This interaction facilitated IGF2BP2-mediated stabilization of NUP160 mRNA, a nuclear pore complex component. Genetic ablation of NUP160 through RNA interference effectively restored autophagic activity, thereby attenuating the aggressive biological behaviors of LUAD cells. In vivo validation using xenograft models demonstrated that the circRAPGEF5/IGF2BP2/NUP160 signaling axis promotes tumor growth and metastatic dissemination through autophagy suppression. Our findings reveal a novel epigenetic regulatory mechanism wherein m6A-modified circRAPGEF5 orchestrates autophagy inhibition via IGF2BP2-dependent stabilization of NUP160 transcripts, ultimately driving LUAD progression and metastasis. These results establish the circRAPGEF5/IGF2BP2/NUP160 axis as a potential therapeutic target for LUAD intervention. Show less
Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential Show more
Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD model mice and negatively correlated with amyloid-beta (Aβ) load in patients with AD. Enhancing GLP-1 signaling through GLP-1RAs increased CaMKK2-AMPK signaling, which subsequently reduced BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ generation. GLP-1RAs also increased AMPK activity in microglia, inhibiting neuroinflammation and promoting Aβ phagocytosis. Consequently, GLP-1RAs inhibited plaque formation and improved memory deficits in AD model mice. Our findings indicate that AMPK activation mediates the effects of GLP-1RAs on AD, highlighting the therapeutic potential of GLP-1RAs for the treatment of AD. Show less
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contr Show more
Despite the well-established association between the apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio and ischemic stroke, its specific relationship with the underlying vascular pathologies contributing to stroke remains poorly understood. This study aims to investigate the association between the apoB/apoA1 ratio and intracranial or extracranial atherosclerosis. We enrolled 408 patients with acute ischemic stroke who had never been treated with statins or fibrates. Based on the images from computed tomography angiography (CTA), the patients were categorized into four groups: intracranial atherosclerosis stenosis (ICAS, n = 136), extracranial carotid atherosclerosis stenosis (ECAS, n = 45), combined intracranial and extracranial atherosclerosis stenosis (COAS, n = 73), and non-cerebral atherosclerosis stenosis (NCAS, n = 154). Demographic characteristics, clinical factors, and serum lipid levels were collected and then compared across groups. The apoB/apoA1 ratio was significantly higher in patients with ICAS, ECAS and COAS compared to those in the NCAS group. Multivariable logistic regression analysis demonstrated that the ApoB/ApoA1 ratio was independently associated with ICAS, but not with ECAS. ROC curve analysis showed that the ApoB/ApoA1 ratio had a good diagnostic ability for ICAS, with an area under the curve (AUC) of 0.764, an optimal cut-off value of 0.8122, a sensitivity of 81.3%, and a specificity of 59.8%. An higher apoB/apoA1 ratio is associated with ICAS in ischemic stroke patients. Show less
In school settings, nomophobia-a newly identified form of problematic mobile phone use characterized by anxiety and discomfort experienced when an individual is unable to use or access their smartphon Show more
In school settings, nomophobia-a newly identified form of problematic mobile phone use characterized by anxiety and discomfort experienced when an individual is unable to use or access their smartphone-poses significant challenges to students' learning and daily life. Prior research on nomophobia has predominantly adopted a variable-centered perspective. However, if nomophobia is heterogeneous across subgroups, acknowledging this heterogeneity may inform the advancement of more tailored and productive therapeutic methods. Latent profile analysis (LPA) was conducted separately among high school students (N = 446) and college students (N = 667) to identify potential subgroup heterogeneity in nomophobia. To examine cross-group similarities in nomophobia profiles, a multi-group LPA was employed. Based on multiple model fit criteria, a three-profile solution-high nomophobia, moderate nomophobia, and low nomophobia-was identified for both groups. However, the multi-group LPA provided only partial support for the similarity of nomophobia profiles across educational stages, specifically in terms of configural and dispersion similarity. While similar nomophobia profiles emerged across groups, the partial equivalence suggests that intervention strategies for nomophobia may not be universally applicable across different educational levels. Additional studies should investigate the mechanisms underlying students' nomophobia profiles and to inform differentiated interventions for educators, institutions, and policymakers. Show less
Ting Yi, Shimeng Dai, Jingrui Tao+4 more · 2025 · Journal of professional nursing : official journal of the American Association of Colleges of Nursing · Elsevier · added 2026-04-24
Undergraduate nursing students face significant academic and practical challenges, with their responses reflecting their academic resilience. However, most studies have overlooked the differences in t Show more
Undergraduate nursing students face significant academic and practical challenges, with their responses reflecting their academic resilience. However, most studies have overlooked the differences in their levels of academic resilience and the factors contributing to these differences. To identify the latent profiles of undergraduate nursing students' academic resilience and to analyze their influencing factors. A cross-sectional study was carried out among 1795 undergraduate nursing students from November 2022 to October 2023 by employing the general information questionnaire, the academic resilience questionnaire for college students, and the brief 2-way social support scale. Latent profile analysis (LPA) was used to analyze the latent profiles of academic resilience, and multiple logistic regression was utilized to explore the factors associated with the identified profiles. Four potential profiles were identified: low academic resilience group, moderate academic resilience group, high academic resilience but low focus and dissociation group, and high academic resilience group. Residence, attitude towards the nursing profession, self-directed study duration, academic performance rank, received and provided instrumental support were found to be associated with the different profiles. These findings highlight the heterogeneity in academic resilience and support tailored educational interventions based on students' specific academic resilience profiles. Show less
To investigate the role of apelin in regulating proliferation, migration and angiogenesis of bladder cancer cells and the possible regulatory mechanism. GEO database was used to screen the differentia Show more
To investigate the role of apelin in regulating proliferation, migration and angiogenesis of bladder cancer cells and the possible regulatory mechanism. GEO database was used to screen the differentially expressed genes in bladder cancer tissues and cells. Bladder cancer and paired adjacent tissues were collected from 60 patients for analysis of apelin expressions in relation to clinicopathological parameters. In cultured bladder cancer J82 cells and human umbilical vein endothelial cells (HUVECs), the effects of transfection with an apelin-overexpressing plasmid or specific siRNAs targeting apelin, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) on proliferation and migration of J82 cells and tube formation in HUVECs were examined using plate cloning assay, Transwell assay, and angiogenesis assay; the changes in FGF2 expression and FGFR1 phosphorylation were detected using Western blotting. The expression level of apelin was significantly higher in bladder cancer tissues than adjacent tissues, and bladder cancer cell lines (T24 and J82) also expressed higher mRNA and protein levels of apelin than SV-HUC-1 cells. Apelin expression level in bladder cancer tissues was correlated with tumor invasion, distant metastasis and advanced TNM stages. Apelin knockdown significantly suppressed proliferation and migration of J82 cells and decreased the total angiogenic length of HUVECs. In contrast, apelin overexpression significantly promoted proliferation and migration and enhanced FGFR1 phosphorylation in J82 cells, and increased the total angiogenesis length in HUVECs, but this effects were effectively mitigated by transfection of the cells with FGF2 siRNA or FGFR1 siRNA. High expression of apelin promotes J82 cell proliferation and migration and HUVEC angiogenesis by promoting activation of the FGF2/FGFR1 pathway. Show less
Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addr Show more
Time-restricted feeding (TRF) is a dietary intervention that has been shown to have numerous health benefits. However, it is important to further investigate the potential effectiveness of TRF in addressing sarcopenic obesity (SO), which is characterized by a combination of age-related obesity and sarcopenia. In this study, 14-month-old C57BL/6J male mice were fed either regular chow diet or high-fat diet (HFD), and had either ad libitum or restricted access to food for 8 hours daily (Intervention for 7 months). For the human trial (ChiCTR2100052876), obese individuals (n=21) with a Body Mass Index ≥28 were recruited and instructed to adopt an 8-hour eating window and a 16-hour fasting period. Here, we found that the TRF intervention significantly reduced global fat mass (P < .001) and volume (P < .05), and increase lean mass compared to mice fed with HFD. Furthermore, TRF improved overall metabolic mobility (8h TRF+HFD vs. AL+HFD). This intervention also enhanced liver FGF21 protein levels (P < .01) and the expression of FGFR1 and FGF21 target genes in adipose and muscle tissues, thus improving mitochondrial quality control in these tissues. Notably, TRF interventions led to a significant decrease in serum FGF21 levels (P < .05). In the human trial, TRF intervention resulted in a significant reduction in weight (P < .001) and body fat levels (P < .001) among obese individuals, as well as a decrease in serum GLU (P < .001), insulin (P < .001), and TC levels (P < .05). Overall, the findings indicate that TRF intervention improves SO by regulating liver FGF21 expression, thereby enhancing FGF21 sensitivity in adipose and muscle tissues. Show less
Early life air pollution exposure may play a role in development of respiratory infections, but underlying mechanisms are still not understood. We utilized data from two independent prospective birth Show more
Early life air pollution exposure may play a role in development of respiratory infections, but underlying mechanisms are still not understood. We utilized data from two independent prospective birth cohorts to investigate the influence of prenatal and postnatal ambient air pollution exposure of PM Show less
In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, interleukin (IL)-27 stimulates interferon γ (IFNγ) production by CD4 and CD8 T cells and is essential for disease development. Here, Show more
In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, interleukin (IL)-27 stimulates interferon γ (IFNγ) production by CD4 and CD8 T cells and is essential for disease development. Here, we tested the role of IL-27 in cellular communication. Single-cell RNA sequencing and T cell adoptive transfer showed that IL-27 intrinsically controlled the differentiation of islet-infiltrating CD4 T cells by driving them toward an IL-21 Show less
Abnormal glymphatic system may play a critical role in amyloid-β (Aβ) accumulation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients. This study aims to use diffusion tensor ima Show more
Abnormal glymphatic system may play a critical role in amyloid-β (Aβ) accumulation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients. This study aims to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) and perivascular space volume fraction (PVSVF) to investigate the aberrant glymphatic functions and the association between Aβ deposition and clinical symptoms in AD spectrum. The ALPS index was significantly lower in AD patients compared to MCI and normal controls (NC) groups. Additionally, the AD group showed a significantly higher PVSVF in hippocampus (HP) compared to NC group. No notable variations were observed in the ALPS index or PVSVF across various regions when comparing the MCI group to the NC group. Apolloprotein E (APOE) ε4 + group showed significantly higher PVSVF-HP and PVSVF in basal ganglia compared to APOE ε4 − group. All participants’ HP volume, lower cognitive scores, and higher Our findings demonstrate that glymphatic dysfunction is associated with cognitive decline, underscoring the critical roles of Aβ pathology and the APOE genotype in mediating this relationship. Further exploration of glymphatic function holds significantly promise for advancing research on AD pathogenesis. The online version contains supplementary material available at 10.1186/s13550-025-01339-y. Show less
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregn Show more
To establish the reference interval for the serum lipid index in pregnant women and to explore the relationship between lipid metabolism levels and pregnancy outcomes. Data were derived from 446 pregnancy women and 317 healthy non-pregnant women. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and hypersensitive C-reactive protein (hs-CRP) were measured in both groups. The mean and standard deviation of each index were calculated to establish the reference range of normal serum lipid levels in pregnant women in mid-to-late pregnancy. The associations between serum lipid levels and perinatal outcomes were assessed statistically. There were no significant differences in age, pregnancy, or parity between the adverse outcome and normal delivery groups, but the caesarean section rate was significantly higher in the adverse outcome group. The levels of hs-CRP, TG, TC, HDL-C, LDL-C, and ApoA1 were significantly higher in the adverse outcome group. Elevated hs-CRP, TG, and HDL-C levels were risk factors for adverse pregnancy outcomes. According to the receiver operating characteristic curve, the optimal threshold of the combined diagnosis of these three indicators to predict adverse pregnancy outcomes was 0.534, and the area under the curve was 0.822. The establishment of lipid reference intervals in the second and third trimesters of pregnancy can effectively evaluate lipid metabolism in pregnant women, and the measurement of lipid metabolism in pregnant women is helpful in predicting adverse pregnancy outcomes. Show less
Xueli Chen, Li Dai · 2025 · Biochemical genetics · Springer · added 2026-04-24
Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltra Show more
Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltransferase. The purpose of this study was to explore the specific mechanism of WTAP in asthma progression, and clarify the intricate interplay between m6A modifications, WTAP, AXIN1, and their collective impact on airway smooth muscle cells (ASMCs) proliferation in asthma. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were used to establish an asthma model in vitro. The cell phenotype was tested using CCK-8, transwell, and wound healing assays. The expression of the Wnt signalling pathway was detected by western blotting. In addition, the relationship between WTAP/YTDHF2 and AXIN1 was assessed by a double luciferase reporter assay. Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1. We found that WTAP was significantly increased in PDGF-BB-treated ASMCs. Knockdown of WTAP inhibited the excessive cell viability and migration of ASMCs induced by PDGF-BB. Furthermore, WTAP knockdown increased AXIN1 levels and inhibited the Wnt signalling pathway. Furthermore, WTAP knockdown decreased the m6A levels and enhanced the mRNA stability of AXIN1. WTAP overexpression showed the opposite effect. In addition, YTHDF2 was demonstrated to be the reader that recognizes the WTAP-mediated m6A modification of AXIN1. YTHDF2 knockdown enhanced the mRNA stability of AXIN1 and reversed the effect of WTAP overexpression on PDGF-BB-treated ASMCs. WTAP knockdown inhibited the excessive cell viability and migration of ASMCs by enhancing the m6A levels of AXIN1, which was further recognized by YTHDF2. The upregulation of AXIN1 mediated by the WTAP/YTHDF2 axis further inhibited the Wnt signalling pathway. Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms. Show less
Xian Chen, Sichen Xia, Xue Han+4 more · 2025 · Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · Springer · added 2026-04-24
Cervical cancer incidence in China has risen to 13.83/100,000, particularly affecting younger women. Following recent family policy changes, reproductive concerns among cervical cancer patients have i Show more
Cervical cancer incidence in China has risen to 13.83/100,000, particularly affecting younger women. Following recent family policy changes, reproductive concerns among cervical cancer patients have intensified. While fertility-sparing treatments show good survival rates, many patients still experience significant anxiety about future fertility. This study aims to examine distinct reproductive concern profiles and their influencing factors in cervical cancer patients of childbearing age. We studied 247 patients from a Nanjing tertiary hospital between October 2023 and October 2024. Participants completed surveys including a demographic questionnaire, Reproductive Concerns After Cancer Scale, Patient Health Questionnaire-9, Benefit Finding Scale, and Fear of Cancer Recurrence Scale. Latent profile analysis (LPA) was conducted to identify reproductive concerns. Latent profile analysis revealed three distinct reproductive concern profiles: (1) a low-concern group with reproductive expectations (27.94%), (2) a moderate-concern group with self and child health preoccupations (49.39%), and (3) a high-concern group with impaired reproductive adaptation (22.67%). Significant influencing factors included age, number of children, residential location, depressive symptoms, and fear of cancer recurrence. These cross-sectional findings emphasize the need for careful consideration of individualized, multiple-disciplinary care for young women with cervical cancer. Benefit finding was associated with lower reproductive concerns. Show less
Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings. Previous genome-wide association studies (GWASs) have identified many loci associated with Show more
Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings. Previous genome-wide association studies (GWASs) have identified many loci associated with neuroblastoma susceptibility; however, their application in risk prediction for Chinese children has not been systematically explored. This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models. We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children, consisting of 402 neuroblastoma patients and 473 healthy controls. Genotyping these polymorphisms was conducted via the TaqMan method. Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk. We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve (AUC) analysis. We also established a polygenic risk scoring (PRS) model for risk prediction by adopting the PLINK method. Fourteen loci, including ten protective polymorphisms from Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models, particularly the PRS, in improving risk prediction. These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children. Show less
The limited response rate to immune checkpoint inhibitors (ICIs) remains a significant challenge in the treatment of lung adenocarcinoma (LUAD). In our study, we identified a lactate-based chemical ba Show more
The limited response rate to immune checkpoint inhibitors (ICIs) remains a significant challenge in the treatment of lung adenocarcinoma (LUAD). In our study, we identified a lactate-based chemical barrier surrounding FAP Show less
Notch2 activation promotes kidney cyst growth. Silencing Notch2 ameliorated cyst growth in mice with autosomal dominant polycystic kidney disease. Notch signaling, a conserved mechanism of cell-to-cel Show more
Notch2 activation promotes kidney cyst growth. Silencing Notch2 ameliorated cyst growth in mice with autosomal dominant polycystic kidney disease. Notch signaling, a conserved mechanism of cell-to-cell communication, plays a crucial role in regulating cellular processes, such as proliferation and differentiation, in a context-dependent manner. However, the specific contribution of Notch signaling to the progression of polycystic kidney disease (PKD) remains unclear. We investigated the changes in Notch signaling activity (Notch1–4) in the kidneys of patients with autosomal dominant PKD (ADPKD) and two ADPKD mouse models (early and late onset). Multiple genetic and pharmacologic approaches were used to explore Notch2 signaling during kidney cyst formation in PKD. Notch2 expression was significantly increased in the kidney tissues of patients with ADPKD and ADPKD mice. Targeted expression of Notch2 intracellular domain in renal epithelial cells resulted in cyst formation and kidney failure in neonatal and adult mice. Mechanistically, Notch2/Hey2 signaling promoted renal epithelial cell proliferation by driving the expression of the E26 transformation–specific homologous factor (Ehf). Depletion of Ehf delayed Notch2 intracellular domain overexpression–induced cyst formation and kidney failure in mice. A gain-of-function mutation in exon 34 of Notch2 signaling promoted kidney cyst growth, partially by upregulating Ehf expression. Show less