The cornerstone of treating lower extremity deep venous thrombosis (LEDVT) lies in anticoagulation therapy to prevent thrombus progression and recurrence. However, patient adherence to medication is a Show more
The cornerstone of treating lower extremity deep venous thrombosis (LEDVT) lies in anticoagulation therapy to prevent thrombus progression and recurrence. However, patient adherence to medication is a critical factor influencing treatment efficacy. Traditional research often simplifies adherence into binary categories of "adherent" and "non-adherent," which fails to comprehensively reflect the complex behavioral patterns. Based on latent profile analysis (LPA), medication adherence in LEDVT patients can be categorized into distinct classes, enabling more precise identification of their characteristics. Therefore, exploring these latent classes and their influencing factors holds significant importance for optimizing intervention strategies and improving prognosis. A cross-sectional survey was used to study LEDVT. From March 14, 2024 to September 20, 2024, a random sampling method was used to recruit 469 patients with LEDVT from four grade-A tertiary hospitals in Urumqi, China. Participants completed questionnaires on general demographic information, the Medication Adherence Scale, the Perceived Health Competence Scale, the Herth Hope Index, the Patient Activation Measure, the Beliefs about Medicines Questionnaire-Specific. LPA was conducted to analyze the medication adherence characteristics of patients with LEDVT. Univariate analysis and multivariate logistic regression were used to identify the influencing factors of their latent profiles. Data analysis was performed using Mplus 8.3 and SPSS 25.0 software. LPA was employed to investigate medication adherence in LEDVT patients, revealing three distinct latent classes: the poorest adherence group (44.99%), the moderate adherence group (19.83%), and the good adherence group (35.18%). The logistic regression results demonstrated that, perceived health competence, hope, activation, beliefs about medication necessity, and concerns about medication were influential factors affecting the potential profile of medication adherence (all p < 0.05). LEDVT patients exhibit significant individual differences in medication adherence. Personalized intervention strategies can be designed based on different adherence classes to enhance medication adherence. Additionally, targeted interventions addressing perceived health competence, hope, positive affect, and medication beliefs can effectively improve adherence. 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
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of ph Show more
Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC). DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln. RNA sequencing (RNA-seq) was employed to explore the mechanism of PAGln in DIC. Subsequently, the differentially expressed genes (DEGs) were subjected to comprehensive analysis using diverse public databases, and RT-PCR was used to confirm the expression levels of the candidate genes. Finally, molecular docking techniques were used for validation. PAGln effectively prevented both in vivo and in vitro Dox-induced myocardial injury and cell apoptosis. RNA-seq results showed that 40 genes were up-regulated and 54 down-regulated in the Dox group compared to the Con group, displaying opposite changes in the Dox + PAGln group. Enrichment analysis highlighted several mechanisms by which PAGln alleviated Dox-induced cardiotoxicity, including the lipid metabolic process, calcium-mediated signaling, positive regulation of store-operated calcium channel activity, and hypertrophic cardiomyopathy. In vitro and in vivo experiments confirmed that PAGln treatment could reverse the changes in the expression levels of Klb, Ece2, Nmnat2, Casq1, Pak1, and Apob in Dox. Molecular docking results showed that these genes had good binding activity with PAGln. PAGln shows potential in alleviating Dox-induced cardiotoxicity, with Ece2 identified as key regulatory molecules related to endothelial dysfunction. Show less
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in th Show more
Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in the development and recovery of tracheal injury from septic shock. Nine New Zealand white rabbits were randomized to control (CON), septic shock model (SS), and septic shock norepinephrine treatment (SSNE) groups (each group n = 3). The SS and SSNE groups were injected with lipopolysaccharide to induce septic shock. The SSNE group was administered Ringer lactate with norepinephrine to maintain normal blood pressure. All animals underwent cuffed endotracheal intubation for 2 h. The injured tracheal segment was harvested. RNA sequencing was performed to identify the DEGs, followed by bioinformatics analysis, and pathological staining (both HE and Masson) was performed for pathological evaluation. Bioinformatics analysis included principal component analysis (PCA), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network construction. Key findings were validated by qRT-PCR and immunohistochemistry. We obtained 124 upregulated and 28 downregulated DEGs in SS vs. CON groups, along with 60 upregulated and 178 downregulated DEGs in SSNE vs. SS groups. The pathological score showed that trachea tissue in the SS group had the highest score. The protein-protein interaction (PPI) prediction identified APOB and CD36 as the hub genes. The molecular experiments further confirmed that at mRNA and protein levels, APOB was significantly upregulated, while CD36 was significantly downregulated. Subsequent qRT-PCR and immunohistochemical analyses confirmed that APOB expression was significantly upregulated while CD36 was downregulated in the septic shock group, a trend partially reversed by norepinephrine treatment. Our study results suggest that APOB and CD36 may be involved in the pathogenesis of tracheal injury recovery in septic shock patients treated with NE. Not applicable. Show less
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high m Show more
Acute kidney injury (AKI), a critical clinical syndrome marked by high incidence and mortality, is currently diagnosed mainly by serum creatinine (SCr) and blood urea nitrogen (BUN), which have high miss rates. This study innovatively proposes using urinary hydrogen peroxide (H Show less
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key g Show more
Staphylococcus aureus is a significant pathogen that poses a threat to both human and animal health. Its pathogenicity in humans has been extensively studied, however, the signaling pathways and key genes in Koi Carp responding to S. aureus from human rhinitis remain unclear. In this study, we established an intraperitoneal infection model in koi carp (Cyprinus carpio) using an S. aureus isolate from patients with rhinitis and integrated RNA-seq, qPCR, and ELISA to dissect the host response. Our findings reveal a dual-module immune evasion strategy employed by S. aureus in koi carp. Module I: The pathogen down-regulated the entire complement coagulation cascade (C3, C9, CFH, F7/9/10) and apolipoprotein-mediated opsonins (APOA1, APOB, APOC1/2), thereby crippling innate clearance. Module II: The host mounted a restricted but potent counter-response, characterized by type I IFN signalling (gvin1, MHC-I), NK/T-cell co-stimulation (CD244, SLAMF5), and the selective induction of IL-8 and IL-1β, while IL-6, IL-10, and TNF-α remained unchanged. Functionally, serum superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM) activities surged, confirming an oxidative burst, whereas splenic CD22R protein decreased, indicating B-cell disinhibition. These results establish a molecular basis for understanding the interaction between human-derived S. aureus and the immune system of aquatic organisms. Show less
Postmenopausal metabolic syndrome and its associated liver injury have attracted considerable research interest, yet their underlying mechanisms and treatment strategies remain insufficiently elucidat Show more
Postmenopausal metabolic syndrome and its associated liver injury have attracted considerable research interest, yet their underlying mechanisms and treatment strategies remain insufficiently elucidated. This study aimed to investigate the relationship between aberrant lipid metabolism and hepatic injury in ovariectomized (OVX) females and to evaluate the therapeutic potential of ingenol (Ing), a natural diterpenoid, via the SIRT1-LXRα signaling pathway. Data from 3047 females in NHANES (2017-2020) were analyzed to compare serum triglyceride (TG) and liver injury markers between OVX and non-OVX women. An OVX mouse model was established to examine hepatic lipid metabolism and SIRT1 expression. Molecular docking, dual luciferase assays, and SIRT1 silencing were performed to evaluate Ing-SIRT1 binding and regulation. HepG2 cells were used to assess Ing's effects on lipid levels and expression of LXRα, CYP39A1, CPT1, and ACOX1. In vivo studies in OVX mice confirmed the therapeutic effects of Ing and further investigated its mechanism via the SIRT1-LXRα pathway. NHANES data indicated that OVX women had significantly higher serum TG levels and more severe liver injury. OVX mice exhibited downregulated SIRT1 expression and disrupted lipid homeostasis. Ing showed high binding affinity to SIRT1, outperforming several known agonists. In HepG2 cells, Ing reduced intracellular TG and total cholesterol (TC), while upregulating LXRα, CYP39A1, CPT1, and ACOX1. In OVX mice, Ing treatment notably attenuated weight gain, reduced TG and TC levels, and ameliorated liver histopathological damage. These effects were mediated through the SIRT1-LXRα pathway. Ing effectively mitigates OVX-induced liver injury by activating SIRT1 and modulating downstream LXRα-mediated lipid metabolic pathways. These results support Ing as a promising therapeutic candidate for liver injury in postmenopausal or OVX women. Show less
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, d Show more
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, death. The global incidence of AD is projected to increase significantly, with late-onset AD being predominantly sporadic in nature. Over the past three decades, the Apolipoprotein E (APOE) gene has been recognized as the most important single genetic determinant of sporadic AD risk. The APOE4 allele is a major risk factor for AD and is known to exacerbate the pathological process for AD. Identifying protective variants that may reduce the risk or delay the onset of AD is of great significance for the development of effective treatments. This review comprehensively examines the protective effects of APOE and its related protective mutations. It also explores the impact of these unique protective variants at the cellular level during the pathological progression of AD. Furthermore, the review compiles new insights for AD treatment offered by these protective mutations, exploring the potential applications of APOE and its related protective variants in advanced therapeutic strategies, including gene editing, RNA editing, and stem cell therapy. Show less
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, and the accurate, non-invasive assessment of liver fibrosis remains an important clinical c Show more
The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, and the accurate, non-invasive assessment of liver fibrosis remains an important clinical challenge. This study aimed to identify ferroptosis biomarkers associated with MASLD-related liver fibrosis progression, explore their potential biological links with MRI-derived parameters, and provide new clues for developing non-invasive diagnostic strategies for ferroptosis. A MASLD-related liver fibrosis model was established using 30 Sprague-Dawley (SD) rats. Hub differentially expressed ferroptosis-related genes (DE-FRGs) were identified through the integration of weighted gene co-expression network analysis (WGCNA), differential expression analysis, and LASSO regression. The role of ferroptosis in MASLD was evaluated using transmission electron microscopy (TEM) and measurements of glutathione (GSH) and Fe²⁺ content. T2*, R2*, and proton density fat fraction (PDFF) were obtained through magnetic resonance imaging (MRI) and were analyzed for correlations with hub DE-FRGs and Fe²⁺ levels. A total of eight hub DE-FRGs were identified: Pck2, Idh2, Nr1d1, Fads1, Sat1, Abhd12, Got1, and Srebf1. Enrichment analyses revealed that these hub DE-FRGs were predominantly implicated in carbohydrate response, amino acid biosynthesis, insulin resistance, and the AMPK signaling pathway. TEM and biochemical markers analyses demonstrated an association between MASLD-related liver fibrosis and ferroptosis. MRI‑derived parameters were significantly correlated with Fe²⁺ levels and the expression of hub DE-FRGs. This study preliminarily identified hub DE-FRGs associated with liver fibrosis in MASLD and their signaling pathways, verified indirect indicators related to ferroptosis, and proposed their potential correlation with MRI-derived parameters. Show less
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile an Show more
Fear of progression (FoP) is a prevalent psychological issue among stroke patients. Previous studies failing to distinguish characteristics of patient groups with varying FoP levels. Latent profile analysis (LPA) classifies individuals into distinct subgroups via continuous FoP indicators, boosting classification accuracy by accounting for variable uncertainty. Given FoP's heterogeneity, investigating FoP profiles and their influencing factors in stroke patients is clinically significant for personalized psychological care and improved patient quality of life. A total of 366 stroke patients were selected as study subjects through convenience sampling, and a cross-sectional survey was conducted. FoP was assessed using the Fear of Progression Questionnaire-Short Form (FoP-Q-SF, 2 dimensions, 12 items). Independent variables included demographic characteristics, clinical indicators, the Recurrence Risk Perception Scale for Stroke patients (RRPSS), and the Medical Coping Modes Questionnaire (MCMQ). LPA was performed on the FoP-Q-SF items to identify subgroups. The R3STEP method was used to analyze influencing factors of subgroup membership, and the BCH method was applied to compare differences in distal outcomes across subgroups. Statistical significance was set at The study sample had a mean age of 63.93 ± 10.58 years, with 70.5% males and 65.0% first-ever stroke patients. Two latent profiles were identified: Low-FoP Adaptive Type (C1, 48.6%) and High-FoP Sustained Type (C2, 51.4%). The R3STEP showed that age 18-59 years (OR = 0.476, 95%CI = 0.245-0.924, This study revealed significant heterogeneity in FoP among stroke patients. Age, hypertension comorbidity, excessive recurrence risk perception, MCMQ-confrontation, and MCMQ-avoidance were associated with high FoP. Healthcare providers should prioritize identifying high-risk individuals and develop tailored interventions to reduce FoP and improve rehabilitation outcomes. Show less
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To addre Show more
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To address this, we performed multi-tissue metabolomic profiling (liver, heart, and serum) in apolipoprotein E-deficient (ApoE-/-) mice subjected to CR. Metabolomic analyses of the multiple tissues revealed that glycerophospholipid metabolism pathway was consistently modulated by CR. To explore its relevance in vascular diseases, we performed serum metabolomic profiling in an abdominal aortic aneurysm (AAA) model induced by angiotensin Ⅱ (AngⅡ) infusion in ApoE-/- mice. The level of lysophosphatidylethanolamine (LPE) (16:0/0:0), a metabolite in the glycerophospholipid metabolism pathway, was elevated during AAA progression and significantly reduced by CR intervention, suggesting its potential as a vascular disease risk factor. Notably, glycerophospholipid metabolism and LPE (16:0) were significantly associated with vascular diseases and aging-related indicators in human multi-omics data, including public transcriptomic and lipidomic, and our serum multi-omics profiling of 76 healthy aged individuals. Collectively, our findings establish glycerophospholipid metabolism and LPE (16:0) as systemic signatures of CR with diagnostic potential. They highlight a crucial link between systemic metabolism and vascular remodeling and remodeling-associated vascular diseases, while also functioning as indicators of systemic aging. Show less
Gliomas comprise a heterogeneous group of central nervous system tumors in which gene fusions (GFs) are significant oncogenic drivers and emerging diagnostic and therapeutic biomarkers. In cancer diag Show more
Gliomas comprise a heterogeneous group of central nervous system tumors in which gene fusions (GFs) are significant oncogenic drivers and emerging diagnostic and therapeutic biomarkers. In cancer diagnosis, GF detection largely relies on targeted short-read sequencing fusion panels, such as the Children's Hospital of Philadelphia (CHOP) Fusion Panel (FUSIP). While these panels are effective for detecting recurrent, well-characterized GFs, they are limited to predefined gene sets and cannot identify full-length transcripts. Here, we analyzed 49 high- and low-grade gliomas previously classified as fusion-negative by FUSIP using an untargeted whole-transcriptome RNA sequencing approach with Oxford Nanopore Technologies (ONT) long-read sequencing. This enabled transcriptome-wide fusion discovery of additional known and potentially novel oncogenic GFs beyond panel constraints. Long-read sequencing further allowed direct resolution of full-length fusion transcripts and their associated isoform structures. By integrating GF detection with isoform-level transcript analysis, we identified fusion-associated transcript isoforms with alternative splicing patterns that aligned near reported GF breakpoints, including Show less
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context Show more
ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since human cathelicidin LL-37 binds to ApoB-100 in this pathological context, we investigated whether the circulating LL-37-ApoB-100 complex could serve as a biomarker for CAD. We performed surface plasmon resonance and protein-protein docking to demonstrate the direct LL-37-ApoB-100 interaction. We developed a specific polyclonal antibody against the complex and measured its levels in human atherosclerotic plaques and plasma, as well as in We identified that LL-37 directly interacted with multiple distinct binding sites on ApoB-100. Plasma levels of LL-37-ApoB-100 complex were significantly elevated in human patients with atherosclerosis. Consistently, levels of this complex were positively correlated with atherosclerotic plaque area in Circulating LL-37-ApoB-100 levels are strongly associated with angiographically documented CAD, highlighting LL-37-ApoB-100 as an independent predictor for CAD. Show less
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise ant Show more
COG133, a peptide fragment derived from apolipoprotein E (ApoE) corresponding to residues 133-149, has demonstrated significant anti-inflammatory and neuroprotective activity. However, its precise anti-inflammatory mechanisms and its potential to ameliorate depression-like behaviors remain incompletely understood. This study investigated the effects of COG133 in mouse models of depression induced by lipopolysaccharide (LPS), chronic social defeat stress (CSDS), and corticosterone (CORT), as well as in LPS-stimulated BV-2 microglial cells. We found that COG133 treatment significantly alleviated depression-like phenotypes and suppressed hippocampal neuroinflammation by inhibiting microglial overactivation. Using RNA sequencing (RNA-seq) and biochemical validation, we identified the MKK3/6-p38-ATF2 signaling axis as a central mechanism underlying the anti-inflammatory effects of COG133. Pharmacological modulation of p38 MAPK further confirmed that this pathway is essential for COG133-mediated behavioral and cellular recovery. Together, these findings identify COG133 as a promising peptide candidate for the treatment of depression through modulation of the p38 MAPK-mediated neuroinflammation axis. Show less
Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non- Show more
Hypercholesterolemia and a high-fat diet promote 2 macrophage subtypes involved in atherosclerosis by inducing lipid droplet accumulation in foamy macrophages (FMs) and inflammatory activation in non-foamy macrophages (NFMs). MicroRNAs are key regulators of macrophage function; for instance, The role of Unlike FMs, NFMs are primarily located in the plaque core and show higher Show less
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible Show more
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible mechanism by which TUG1 inhibits neural repair subsequent to ICH through adjusting miR-381-3p/brain-derived neurotrophic factor (BDNF). After the ICH model was created, miR-381-3p agomir and pcDNA-TUG1 were injected. The neural function of rats was estimated using the modified neurological severity score. To quantify the expression of genes and proteins, western blotting, immunohistochemistry, and qRT-PCR were used. To confirm the interaction between TUG1 and miR-381-3p and between miR-381-3p and BDNF mRNA, a luciferase reporter assay was employed. In rats treated with miR-381-3p agomir, a trend of improvement in neurological dysfunction was observed, while the pcDNA-TUG1-treated ones showed deterioration. Furthermore, miR-381-3p agomir increased, while pcDNA-TUG1 reduced the expression level of BDNF in ICH rats. TUG1 and BDNF mRNA were validated to attach directly to miR-381-3p. Overexpressing TUG1 inhibited the level of BDNF by sponging miR-381-3p and antagonized its protective effect on neural repair in ICH rats. Our study suggests that TUG1 can sponge miR-381-3p to downregulate BDNF expression and inhibit neural repair following ICH, demonstrating a potential signaling pathway that is conducive to a better understanding of the pathological mechanisms of ICH. Show less
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEA Show more
Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEAD) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently studied. Given the overlapping metabolic disturbances in both conditions, such as insulin resistance and lipid abnormalities, a potential relationship between Lp(a) and peripheral vascular injury in MASLD is biologically plausible. This study aimed to investigate the cross-sectional association between circulating Lp(a) concentrations and the presence of LEAD in a well-characterized MASLD population. A total of 468 MASLD patients undergoing routine health check-ups were included. Lp(a) levels were stratified into three categories: <10 mg/dL, 10–30 mg/dL, and ≥ 30 mg/dL. LEAD was diagnosed using duplex ultrasonography. Multivariable logistic regression models were used to assess the relationship between Lp(a) levels and the presence of LEAD, with adjustments for demographic variables, metabolic conditions, and lipid-related parameters. Subgroup analyses were conducted to assess potential effect modification. LEAD was diagnosed in 61.5% ( Elevated Lp(a) levels were associated with a higher prevalence of LEAD in patients with MASLD. Although the magnitude of association per unit increase was modest, higher Lp(a) concentrations were associated with greater LEAD prevalence. These findings should be interpreted cautiously and viewed as hypothesis-generating, particularly with respect to subgroup analyses. Prospective studies are needed to clarify causality and clinical relevance. The online version contains supplementary material available at 10.1186/s12872-026-05600-7. Show less
Prednisone is used clinically during pregnancy. This study investigates whether prenatal prednisone exposure (PPE) affects susceptibility to high-fat diet (HFD)-induced metabolic dysfunction-associate Show more
Prednisone is used clinically during pregnancy. This study investigates whether prenatal prednisone exposure (PPE) affects susceptibility to high-fat diet (HFD)-induced metabolic dysfunction-associated fatty liver disease (MAFLD) in adult offspring and explores underlying mechanisms. Pregnant Kunming mice were administered prednisone (0.25 or 1 mg/kg; PPE-L or PPE-H) or vehicle control (5% carboxymethyl cellulose; Ctrl) by daily gavage from gestational days 0-18. Offspring were assessed metabolically, histologically, and via RNA-Seq. Primary hepatocytes were treated with fatty acids with or without the epigenetic inhibitors to evaluate Nr1h3 expression and lipid deposition. Offspring body weight was similar in PPE-L vs Ctrl, but was reduced in PPE-H group followed by delayed growth. After 6-week HFD feeding, PPE-L offspring showed mild metabolic issues, while PPE-H males exhibited significant glucose/lipid disorders and hepatic steatosis compared to controls. RNA-Seq showed upregulation of hepatic lipid pathways in the PPE-H male offspring when challenged by HFD. The liver X receptor alpha (LXRα)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway and the expression of genes involved in de novo fatty acid synthesis were increased in PPE-H offspring under HFD. A485 significantly downregulated the expression of Nr1h3 in primary hepatocytes from male PPE-H offspring and alleviated lipid deposition in these hepatocytes treated with fatty acids. The H3K27ac level in the Nr1h3 promoter in the PPE-H offspring's liver was significantly upregulated. PPE-L impairs offspring glucose/lipid homeostasis, whereas PPE-H increase MAFLD risk of the offspring by epigenetic programming of the hepatic LXRα-SREBP1 pathway, especially in the males. Show less
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the Show more
Decline in pulmonary function (PF) and respiratory muscle strength (RMS) is influenced by environmental and genetic factors and is inconsistently linked to cognitive outcomes. This study explores the associations between PF, RMS, and cognitive function among community-dwelling older adults in China, analyzing interactions with APOE Ɛ4 and the mediating effect of serum total bilirubin. About 1,081 Hubei Memory and Aging Cohort (HMACS) participants underwent PF (PEF, FEV1 and FVC), RMS (MIP and MEP) assessment, cognitive tests, APOE genotyping, and bilirubin measurement. Multivariate logistic regression and general linear regression were used to analyze associations. Among 1,081 participants (mean age 70.52 ± 5.55 years), 26.1% had cognitive impairment. Lower PF and RMS scores were associated with cognitive impairment. Higher comprehensive PF (c-PF) and RMS indices protected against cognitive impairment (eg, c-PF: OR = 0.482-0.609, PF (especially PEF) and RMS (especially MEP) indices are significantly associated with cognitive function and impairment in older adults, independent of APOE Ɛ4 status. These findings provide biomarkers for assessing cognitive health risk and a basis for interventions targeting PF and RMS to preserve cognitive function. Show less
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a Show more
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a natural flavonoid, exhibits anti-inflammatory and neuroprotective properties, yet its potential therapeutic effects on UC and associated anxiety, as well as the underlying mechanisms, remain largely unexplored. A murine model of DSS-induced colitis was established and treated with HYP. Disease activity was assessed through body weight, colon length, and histopathology. Anxiety-like behaviors were evaluated using open field and elevated plus maze tests. Neuroinflammation was examined through immunohistochemistry of BDNF expression and microglial activation. Gut microbiota composition was profiled by metagenomic sequencing, and metabolomic profiling was conducted using the Q300 Kit. Network pharmacology and molecular docking were employed to predict signaling pathways, which were further validated by Western blotting. Additionally, antibiotic depletion experiments were conducted to determine microbiota dependency. HYP administration significantly ameliorated DSS-induced colitis, as evidenced by attenuated weight loss, restored colon length, and improved histopathology. It suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restored intestinal barrier integrity by upregulating Mucin-2 and ZO-1. Furthermore, HYP also alleviated anxiety-like behaviors and mitigated neuroinflammation by increasing BDNF levels and suppressing microglial activation. HYP treatment also restored gut microbial homeostasis, enriching beneficial bacteria such as Our findings demonstrate that HYP effectively alleviates DSS-induced colitis and comorbid anxiety-like behaviors. Its efficacy is dependent on the gut microbiota and is associated with the restoration of microbial homeostasis, enhancement of arginine metabolism, and modulation of the MAPK/PI3K-Akt/NF-κB signaling pathways. HYP represents a promising microbiota-targeting therapeutic candidate for UC and its neuropsychiatric comorbidities. Show less
This study aimed to investigate the current status of career calling among novice nurses, to identify potential subtypes and their population characteristics, and to further explore the factors associ Show more
This study aimed to investigate the current status of career calling among novice nurses, to identify potential subtypes and their population characteristics, and to further explore the factors associated with the different subtypes. A cross-sectional descriptive study was used. From January to February 2024, 845 novice nurses from 11 hospitals in Shanxi Province were selected for an online questionnaire survey using convenience sampling. The demographic questionnaire, transition shock of newly graduated nurses scale, medical staff resilience scale, and career calling scale were used as study instruments. Latent profile analysis (LPA) was used to explore the subtypes of novice nurses' career calling, and multifactorial logistic regression was used to analyze the related factors of novice nurses' career calling. Three subtypes of career calling of novice nurses in this study were identified, namely, lacking-calling group (10.3%), stable-calling group (50.0%), and sufficient-calling group (39.7%). Education, weekly working hours, weekly frequency of night shifts, reasons for choosing nursing, level of transition shock, and level of resilience were significantly associated with the three latent profiles of career calling of novice nurses in this study. Novice nurses' career calling presents 3 latent profiles and is heterogeneous in this study. Nursing administrators could pay attention to the differences in the level of career calling of novice nurses and adopt targeted management strategies based on the type of characteristics of the population in order to improve the level of career calling of novice nurses, help them develop their careers, and stabilize the nursing workforce. Show less
Wenjie Li, Chen Li, Xing Li+1 more · 2026 · The aging male : the official journal of the International Society for the Study of the Aging Male · Taylor & Francis · added 2026-04-24
Prostate cancer (PCa) is a leading cause of male cancer-related death globally. While the gut microbiota is linked to PCa, its genetic association remains unclear. We screened genetic instruments rela Show more
Prostate cancer (PCa) is a leading cause of male cancer-related death globally. While the gut microbiota is linked to PCa, its genetic association remains unclear. We screened genetic instruments related to the gut microbiota and paired them with PCa genome-wide association study data to conduct Mendelian randomization (MR) analysis. Positive MR findings were then subjected to colocalization analysis. Subsequently, we utilized the Gene Expression Omnibus (GEO) dataset to perform differential expression analysis, aiming to identify differentially expressed associated genes (DEAGs). We determined the importance scores of these DEAGs through four machine learning models and constructed a nomogram based on these findings, and then validated it in another group of the GEO dataset. MR analysis found 16 gut bacteria causally linked to PCa (7 risk, 9 protective), with 144 related genes. PLCL1, VSNL1, ROR2, NRXN3, and TEAD1 were identified as feature genes for constructing a nomogram that provides a quantitative prediction of the risk of PCa onset. This study indicates that there are causal links between the gut microbiota and PCa. Feature genes may affect the occurrence of PCa by inhibiting the epithelial-mesenchymal transition, proliferation, migration, and invasion of cells. Show less
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morronisid Show more
Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morroniside (Mor), an iridoid glycoside compound in Cornus officinalis, is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used ApoE4 transgenic mice and ApoE4-transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10-month-old mice were randomly divided into the ApoE3 control group (ApoE3 + Veh), the ApoE4 model group (ApoE4 + Veh), and the ApoE4 + Mor 10, 20, and 40 mg/kg groups as in vivo models. The in vitro BV2-ApoE model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of ApoE4 transgenic mice by reducing Aβ plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1/PU.1 signaling axis, and alleviated the dysfunction of microglia both in vitro and in vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce Aβ accumulation, and improve synaptic damage in ApoE4 mice via the CX3CL1/CX3CR1/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD. Show less
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key Show more
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key genes involved in KC development and in anoikis and endoplasmic reticulum (ER) stress. KC and control datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). These were cross-referenced with anoikis and ER stress-related genes from Genecards. Functional enrichment, immune infiltration analysis, and machine learning techniques (LASSO, Random Forest) were used to identify candidate molecular signatures, which were then validated in an animal model. We identified 46 DEGs associated with anoikis and 41 DEGs related to ER stress. Functional analysis linked them to apoptosis and IL-17 signaling. Five key molecular signatures were identified: CDKN1A, MCL1, PTGS2, PTHLH, and ANGPTL4. The expression of ANGPTL4, CDKN1A, and MCL1 was consistent in the animal model. These genes are associated with inflammatory and oxidative stress responses. Twelve potential therapeutic drugs were predicted. This study identifies five candidate molecular signatures for KC related to anoikis and ER stress, offering insights into KC pathogenesis and potential targeted therapies. Show less
Ying Yang, Xiang Li, Dan-Li Tang+4 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
This study established a hyperlipidemia model by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The rats were randomly assigned to the following groups: model group, atorvastatin calcium gro Show more
This study established a hyperlipidemia model by feeding Sprague-Dawley rats a high-fat diet for 8 weeks. The rats were randomly assigned to the following groups: model group, atorvastatin calcium group(4.8 mg·kg~(-1)), low-, medium-, and high-dose Tanyu Tongzhi Optimization Decoction(TYTZD) groups(3.6, 7.2, and 14.4 g·kg~(-1)), and a normal diet control group. After 4 weeks of continuous administration, hematoxylin-eosin(HE) and oil red O staining were used to observe liver pathological changes and lipid infiltration. Automatic biochemical analyzer were performed to assess blood lipid profiles, coagulation function, and liver function. Transcriptomic and proteomic analyses were employed to identify differentially expressed genes(DEGs) and proteins(DEPs), followed by enrichment analysis. The MCODE algorithm was applied to classify DEGs and DEPs into modules, and network separation index(S₍AB)) was calculated to assess module separation, enabling construction of a gene-protein co-expression network for core target screening. The diagnostic accuracy of core targets was evaluated by area under the receiver operating characteristic(ROC) curve(AUC), and ELISA was used to measure core target expression. Western blot detected the expression of core pathway-related proteins in liver tissue. RESULTS:: demonstrated that TYTZD significantly improved dyslipidemia, coagulation dysfunction, liver injury, hepatic pathology, and lipid infiltration in hyperlipidemic rats. Transcriptomic analysis identified 571 DEGs significantly reversed by TYTZD, mainly enriched in inflammatory signaling pathways such as Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB). Proteomic analysis identified 102 reversed DEPs, mainly involved in cholesterol metabolism pathways. Integrated analysis identified core targets including TLR4, tumor necrosis factor-α(TNF-α), integrin subunit alpha M(ITGAM), Toll-like receptor 2(TLR2), matrix metalloproteinase 9(MMP9), interleukin-1β(IL-1β), apolipoprotein E(APOE), and apolipoprotein C2(APOC2), all with AUC values greater than 0.70. ELISA showed that TYTZD intervention significantly downregulated MMP9, TNF-α, IL-1β, TLR2, ITGAM, and TLR4, and upregulated APOC2 and APOE. Western blot indicated that TYTZD reduced TLR4, p-NF-κB, and IL-1β protein expression in liver tissue. In conclusion, TYTZD may exert anti-hyperlipidemic effects through regulation of core targets such as ITGAM, TLR4, and APOC2, and by modulating the TLR4/NF-κB signaling pathway to intervene in inflammatory responses and cholesterol metabolism, thereby achieving multi-target, multi-pathway therapeutic effects against hyperlipidemia. Show less
The poor efficacy of chemotherapy for glioma is mainly due to the difficulty of drug penetration through the blood-brain barrier (BBB), as well as the difficulty of drug concentration in the tumor tis Show more
The poor efficacy of chemotherapy for glioma is mainly due to the difficulty of drug penetration through the blood-brain barrier (BBB), as well as the difficulty of drug concentration in the tumor tissue to reach the effective therapeutic level. The emerging tumor-targeted delivery technology can facilitate the precise enrichment of drugs in the tumor site. Apolipoprotein E (ApoE(159-167) Show less