This study aimed to investigate the association between objectively and subjectively measured 24-hour movement behaviors and physical fitness, and explore how the reallocation of time between 24-hour Show more
This study aimed to investigate the association between objectively and subjectively measured 24-hour movement behaviors and physical fitness, and explore how the reallocation of time between 24-hour movement behaviors is associated with changes in physical fitness in adolescents. A total of 690 adolescents aged 14-17 years (55% girls) were included in this cross-sectional study conducted in Foshan, China. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, and sleep were assessed using accelerometers in combination with a questionnaire. Physical fitness was tested through body mass index, forced vital capacity, 50-m sprint, standing long jump, sit-and-reach, gender-specific 800/1000-m run, and pull-ups/sit-ups. MVPA was significantly associated with better performance in the 50-m sprint ( Show less
Remote ischemic preconditioning (rIPC) has been reported to protect against kidney ischemia-reperfusion injury (IRI) through the delivery of extracellular vesicles (EVs). Among these, apoptosis-induce Show more
Remote ischemic preconditioning (rIPC) has been reported to protect against kidney ischemia-reperfusion injury (IRI) through the delivery of extracellular vesicles (EVs). Among these, apoptosis-induced compensatory proliferation signaling-related vesicles (ACPSVs) can transmit proliferation signals to surrounding cells. However, the underlying mechanisms remain unclear. This study aimed to investigate the role of ACPSVs in renal IRI following rIPC and to elucidate the associated mechanisms. We demonstrated that rIPC plasma or ACPSVs alleviated renal damage and inflammation, with the protective effects abolished upon the removal of ACPSVs from the plasma. EVs isolated via differential centrifugation exhibited defining characteristics of ACPSVs. Co-culture experiments revealed that ACPSVs reduced apoptosis and enhanced the viability of HK-2 cells under hypoxia/reoxygenation (H/R) conditions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted the critical role of macrophage migration inhibitory factor (MIF) protein in ACPSVs. Using CRISPR/Cas9 technology, we generated MIF-knockout HeLa cells to induce the production of MIF-deficient ACPSVs. The protective effects of ACPSVs were significantly attenuated when MIF was knocked out. Transcriptome sequencing and chromatin immunoprecipitation (ChIP) assays revealed that MIF suppresses dual-specificity phosphatase 6 (DUSP6) expression by promoting H3K9 trimethylation (H3K9me3) in the DUSP6 promoter region, thereby activating the JNK signaling pathway. In rescue experiments, treatment with the DUSP6 inhibitor BCI effectively restored the protective function of MIF-deficient ACPSVs. This study underscores the protective role of ACPSVs derived from rIPC-treated rats and serum-starved cells against renal IRI through the MIF/DUSP6/JNK signaling axis, offering a potential clinical therapeutic strategy for acute kidney injury induced by IRI. [Image: see text] The online version contains supplementary material available at 10.1186/s12951-025-03505-9. Show less
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which Show more
Hypertrophic cardiomyopathy (HCM) is a common inherited heart condition. Traditional genetic testing is typically conducted on the proband only, with family members undergoing Sanger sequencing, which may overlook other pathogenic variants. This study explores the gene sequencing strategy in a three-generation family based on genetic carrier status and examines the relationship between phenotypic characteristics and genotype. High-throughput second-generation sequencing was performed on the proband to analyze HCM-related pathogenic genes. Subsequently, the identified pathogenic variants were validated by Sanger sequencing in the proband and family members. Clinical, electrocardiographic, and echocardiographic assessments were conducted for family members. Second-generation sequencing of the proband (III7) revealed a pathogenic variant MYBPC3-P453Lfs. Initially, no HCM-related pathogenic variants were detected in another patient (III11), prompting additional sequencing of III11, which identified the MYH7-G823E pathogenic variant. Both patients had severe left ventricular outflow tract obstruction. Sanger sequencing showed that five family members carried both mutations. Among them, three died suddenly before age 40, one required an implantable cardioverter defibrillator for arrhythmias, and one developed HCM before adulthood. Cardiac magnetic resonance imaging (MRI) of patients carrying both mutations showed myocardial fibrosis of 32.75%, significantly higher than the 6.98% observed in patients carrying only one mutation. In families with varying HCM phenotypes, second-generation sequencing should be considered for all members. In this family, carrying one variant led to outflow tract obstruction, while carrying both variants resulted in severe disease, including sudden death and early onset. Cardiac MRI is crucial for assessing the severity of the disease within the family. Show less
Ankylosing spondylitis (AS) is a chronic and progressive inflammatory arthritis involving disorders of both the immune and skeletal systems. Multiple osteochondromas (MO) is a rare skeletal disorder w Show more
Ankylosing spondylitis (AS) is a chronic and progressive inflammatory arthritis involving disorders of both the immune and skeletal systems. Multiple osteochondromas (MO) is a rare skeletal disorder with a variety of clinical manifestations characterized by multiple benign exostoses. Here, we investigate a Chinese family with HLA-B27-negative AS complicated with MO. Whole-exome sequencing (WES) and Sanger sequencing were used to screen and identify the pathogenic gene. In vitro functional analysis was performed, and a pathogenesis-associated interleukin (IL)-17 receptor C (IL17RC) mutation was analyzed to investigate its effect on phenotypes. WES was used to identify a known missense mutation, NM₀₀₀₁₂₇.3:c.1019 G > A(p.Arg340His), in the pathogenic gene EXT1 that is causal for MO. Moreover, a missense mutation, NM₁₅₃₄₆₁.3:c.1067 C > T(p.Thr356Met), in the IL17RC gene was identified as potentially responsible for AS or spondyloarthritis symptoms in this family. In vitro over-expression of mutant IL17RC decreased its expression and increased the expression of IL17RA, consistent with the expression of these two genes in patients. Mechanistically, mutant IL17RC enhanced the activation of the NF-κB pathway. This study increases our understanding of the pathogenesis and progression of these diseases. Our findings broaden the risk factors in non-HLA-B genes associated with the NF-κB pathway in AS. Show less
Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism. Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficien Show more
Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism. Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R The results revealed that IL-27 exacerbated systemic inflammation and liver damage in AHI mice by promoting M1 macrophage polarization, thereby increasing pro-inflammatory phenotype macrophages (M1). This further exacerbated the inflammatory response and pyroptosis in vivo and in vitro. Additionally, IL-27 down-regulated p-AMPK and SIRT1 protein expression while overexpressing macrophage inflammatory mediators including IL-1β/6 and TNFα. Furthermore, IL-27 promoted increased RAGE and caspase-11 protein expression, aggravating macrophage pyroptosis. Employing CC to block the AMPK pathway further aggravated M1 macrophage polarization and pyroptosis in vitro and in vivo, ultimately worsening liver injury. Here, IL-27 aggravates AHI by promoting macrophage M1 polarization to induce caspase-11-mediated pyroptosis in vitro and in vivo, which may be linked to the AMPK/SIRT1 signaling pathway. Show less
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in l Show more
Peritoneal metastasis (PM) in gastric cancer (GC) remains a formidable clinical challenge. Although exosomes are critical mediators of tumor-microenvironment communication, their mechanistic role in linking mesothelial-mesenchymal transition (MMT) to peritoneal dissemination remains poorly understood. This study elucidates a GC-derived exosomal microRNA (miRNA)-driven pathway that orchestrates peritoneal metastasis. Integrated exosomal miRNA sequencing and The Cancer Genome Atlas (TCGA) analysis identified miR-196a-5p as highly enriched in GC-derived exosomes. Functional assays, including in vitro co-culture experiments, and in vivo PM models, demonstrated that GC-derived exosomal miR-196a-5p directly induces MMT in peritoneal mesothelial cells (HMrSV5) and contributed to the formation of metastatic tumors. Mechanistically, miR-196a-5p binds the 3'-untranslated region (UTR) of F-box protein 45 (FBXO45), an E3 ubiquitin ligase, suppressing its expression and thereby stabilizing snail family transcriptional repressor 1 (Snai1)-a key transcription factor in epithelial-mesenchymal transition (EMT). RNA immunoprecipitation sequencing (RIP seq), dual-luciferase reporter assays, co-immunoprecipitation (CO-IP), and rescue experiments validated the miR-196a-5p/FBXO45/Snai1 axis. Notably, miR-196a-5p disrupts FBXO45-mediated Snai1 ubiquitination and degradation, promoting MMT-driven peritoneal niche remodeling and metastatic progression. These findings reveal a novel exosome-mediated mechanism underlying GC dissemination and highlight miR-196a-5p and FBXO45 as promising therapeutic targets for PM. Show less
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive v Show more
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, Show less
Pulmonary embolism is a potentially fatal cardiovascular condition that demands prompt and accurate diagnostic imaging. Traditional single-energy computed tomography pulmonary angiography (CTPA), whil Show more
Pulmonary embolism is a potentially fatal cardiovascular condition that demands prompt and accurate diagnostic imaging. Traditional single-energy computed tomography pulmonary angiography (CTPA), while widely used, is associated with high radiation doses and substantial volumes of contrast agents, which may increase the risks of radiation-induced tissue damage and contrast-induced nephropathy (CIN), respectively. Dual-energy CTPA (DE-CTPA) presents a promising alternative, though challenges, including elevated image noise at low kilo-electron volt (keV) levels (e.g., 40 keV), persist. The primary aim of this study is to evaluate and compare the image quality of 40 keV virtual monoenergetic images (VMI) reconstructed using deep learning image reconstruction (DLIR) and Adaptive Statistical Iterative Reconstruction-V (ASIR-V) algorithms within the context of low-dose DE-CTPA protocols. This prospective study enrolled patients who underwent DE-CTPA between January and April 2025. Using a Revolution CT scanner, 40 keV VMI were reconstructed with four distinct algorithms: ASIR-V 50%, ASIR-V 70%, Deep learning image reconstruction with medium setting (DLIR-M), and deep learning image reconstruction with high setting (DLIR-H). Iodixanol (350 mgI/mL) was administered at a dose of 0.4 mL/kg. The image quality was assessed through both objective measures [image noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR)] and subjective evaluation via a Likert scale. Statistical analysis was conducted using SPSS 27.0, employing analysis of variance (ANOVA) for normally distributed data and the Kruskal-Wallis test for non-normally distributed data. A total of 75 patients with clinical suspicion of pulmonary embolism were included in the study. The mean effective dose (ED) was 3.76±1.02 mSv, with a mean CT volume dose index (CTDIvol) of 6.13±1.69 mGy and a mean dose-length product (DLP) of 221.12±59.85 mGy·cm. The mean contrast agent volume was 26.0±5.0 mL. Statistical analysis of image quality revealed significant differences between the four groups in terms of image noise, CNR, and SNR, measured at the levels of the main pulmonary artery, left pulmonary artery, and right pulmonary artery (P<0.001). Post-hoc analysis demonstrated that the DLIR-H algorithm provided the highest image quality, significantly reducing noise while enhancing CNR and SNR relative to both ASIR-V and DLIR-M (P<0.001). Compared with ASIR-V 50%, DLIR-H reduced image noise by 45% at the PA [24.25±16.18 The DLIR-H algorithm significantly enhances the image quality of 40 keV VMI images under low-dose DE-CTPA scanning protocols. It outperforms DLIR-M, ASIR-V 50%, and ASIR-V 70%, making it a promising tool for improving image quality in CTPA, particularly in clinical settings where minimizing radiation dose and contrast agent volume is essential. Show less
Yifei Dou, Ying Li, Meng Zhang · 2025 · Wei sheng yan jiu = Journal of hygiene research · added 2026-04-24
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 p Show more
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 police officers were selected using cluster random sampling in the Inner Mongolia Autonomous Region between September and December 2021. Participants completed a basic information questionnaire and the Pittsburgh sleep quality index(PSQI). Latent profile analysis(LPA) was employed to examine heterogeneity in sleep quality, and multinomial Logistic regression was used to identify associated factors of the latent profiles. The mean age of participants was(43.08±8.98) years. The sample comprised 920 males(79.2%) and 242 females(20.8%), 987(84.9%) were married and 175(15.1%) were single, 644(55.4%) had a high school education or below, and 518(44.6%) had college education or above. By department, 607(52.2%) worked in grassroots police stations, 200(17.2%) were criminal police, and 355(30.6%) served in other units. Significant heterogeneity in sleep quality was identified, revealing four distinct latent classes: good sleep group(n=821, 70.6%), moderate sleep group(n=46, 4.0%), sleep-disordered group(n=249, 21.4%), and medication-assisted sleep group(n=46, 4.0%). Using the good sleepers as the reference group, multinomial Logistic regression indicated that older age was a significant risk factor for belonging to the medication-assisted sleep group(OR=1.348, 95%CI 1.078-1.822). Higher education level was a protective factor against membership in the moderate sleep group(OR=4.101, 95%CI 1.304-12.893). Serving as a grassroots police station officer or criminal police officer was a significant risk factor for membership in both the moderate sleep group(OR = 3.329, 95%CI 1.338-8.284; OR=4.188, 95%CI 1.415-12.396) and sleep-disordered group(OR=1.701, 95%CI 1.196-2.420; OR=1.587, 95%CI 1.073-2.533). Sleep quality among police officers demonstrates significant heterogeneity. Age, police department assignment, and educational level are key associated factors of distinct latent classes of sleep quality. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2025.05.015
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutriti Show more
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutritional strategies. This study examined the potential of stevia chlorogenic acid (SCGA), a bioactive byproduct of stevia processing, to alleviate intestinal injury, gut microbiota dysbiosis, and lipid metabolism disorders induced by oxidized fish oil in turbot. Four diets with equal nitrogen and lipid contents were formulated: a control diet (PC) containing 5 % fresh fish oil, an oxidized fish oil diet (OFO) comprising 5 % oxidized fish oil, and two additional OFO diets supplemented with 200 mg/kg (OFO200) or 400 mg/kg (OFO400) of SCGA. Each dietary treatment was randomly assigned to three replicates, each containing 40 fish weighing approximately 16.99 ± 0.01 g, and administered over a 10-week period. Fish fed the OFO diet exhibited significantly compromised growth performance, as indicated by decreased WGR and SGR, along with reduced serum immune indices (IgM, C3, and C4) and lipid parameters (TC, HDL, LDL), and elevated serum D-LA levels (P < 0.05). Moreover, dietary OFO markedly suppressed antioxidant enzyme activities (serum SOD; intestinal SOD, GSH-Px, and CAT) and elevated MDA concentrations (P < 0.05). Additionally, OFO reduced intestinal expression of tight junction-associated genes (Claudin-4, Claudin-7, Occludin) while increasing expression levels of MLCK, Keap1, inflammatory mediators (IL-6, IL-1β, TNF-α2, NF-κB, IFN-γ), and Caspase7 (P < 0.05). Notably, the TLR signaling pathway-related genes were upregulated, accompanied by pronounced shifts in gut microbiota composition (P < 0.05). In hepatic tissue, lipogenesis-associated genes (FAS, ACC) were significantly increased, while key genes involved in lipid transport and β-oxidation (CD36, LPL, ACOX1, PPARγ) exhibited reduced expression (P < 0.05). Dietary supplementation with 200 and 400 mg/kg SCGA effectively mitigated these detrimental impacts. SCGA restored growth performance, serum immune parameters, and antioxidant enzyme activities to levels comparable to the PC group. It also normalized gene expression related to intestinal barrier function, inflammation, apoptosis, and hepatic lipid metabolism. Furthermore, SCGA supplementation modulated gut microbiota structure by increasing beneficial genera and decreasing potential pathogens. In conclusion, SCGA effectively improves growth performance, alleviates OFO-induced intestinal injury and microbial dysbiosis, and regulates lipid metabolism in turbot. These findings provide theoretical insights and technical support for the application of SCGA in aquaculture. Show less
Wei Zhang, Na Li · 2025 · Frontiers in psychiatry · Frontiers · added 2026-04-24
Individuals with bipolar disorder (BD) exhibit a significantly increased risk of cardiovascular disease, yet the specific mechanisms linking heart failure (HF) and BD remain poorly understood. This st Show more
Individuals with bipolar disorder (BD) exhibit a significantly increased risk of cardiovascular disease, yet the specific mechanisms linking heart failure (HF) and BD remain poorly understood. This study aimed to identify common potential diagnostic biomarkers associated with both conditions. Differentially expressed genes (DEGs) were analyzed separately in HF (GSE57338) and BD (GSE5389) datasets. Key module genes for each condition were identified through co-expression network analysis and intersected with DEGs to pinpoint candidate genes. Subsequently, a protein-protein interaction (PPI) network, receiver operating characteristic (ROC) analysis, and expression validation were employed to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) and drug predictions were also conducted. Clinical validation of biomarker expression was performed via quantitative polymerase chain reaction (qPCR). A total of 44 candidate genes were identified as being associated with both HF and BD. Six potential diagnostic biomarkers ( This study preliminarily explored the common molecular mechanisms between HF and BD, and identified 6 potential biomarkers for early detection, providing a solid theoretical basis for future research on HF and BD. Show less
Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency. Methionine (Met) is an essential amino acid required for feather follicle development; yet t Show more
Poor feather growth not only affects the appearance of the organism but also decreases the feed efficiency. Methionine (Met) is an essential amino acid required for feather follicle development; yet the exact mechanism involved remains insufficiently understood. A total of 180 1-day-old broilers were selected and randomly divided into 3 treatments: control group (0.45% Met), Met-deficiency group (0.25% Met), and Met-rescue group (0.45% Met in the pre-trial period and 0.25% Met in the post-trial period). The experimental period lasted for 56 d, with a pre-trial period of 1-28 d and a post-trial period of 29-56 d. In addition, Met-deficiency and Met-rescue models were constructed in feather follicle epidermal stem cell by controlling the supply of Met in the culture medium. Dietary Met-deficiency significantly (P < 0.05) reduced the ADG, ADFI and F/G, and inhibited feather follicle development. Met supplementation significantly (P < 0.05) improved growth performance and the feather growth in broilers. Met-rescue may promote feather growth in broilers by activating the Wnt/β-catenin signaling pathway (GSK-3β, CK1, Axin1, β-catenin, Active β-catenin, TCF4, and Cyclin D1). Compared with Met-deficiency group, Met-rescue significantly (P < 0.05) increased the activity of feather follicle epidermal stem cell and mitochondrial membrane potential, activated Wnt/β-catenin signaling pathway, and decreased the content of reactive oxygen species (P < 0.05). CO-IP confirmed that mitochondrial protein PGAM5 interacted with Axin1, the scaffold protein of the disruption complex of the Wnt/β-catenin signaling pathway, and directly mediated Met regulation of Wnt/β-catenin signaling pathway and feather follicle development. PGAM5 binding to Axin1 mediates the regulation of Wnt/β-catenin signaling pathway, and promotes feather follicle development and feather growth of broiler chickens through Met supplementation. These results provide theoretical support for the improvement of economic value and production efficiency of broiler chickens. Show less
Depression is a pervasive mental illness that has a significant impact on public health globally. This study aimed to identify risk factors for depression and elucidate their causal relationships. Usi Show more
Depression is a pervasive mental illness that has a significant impact on public health globally. This study aimed to identify risk factors for depression and elucidate their causal relationships. Using data from the National Health and Nutrition Examination Survey (NHANES) and Genome-Wide Association Studies (GWAS). Serum ApoB was log-transformed and further divided into 4 groups. Multifactorial logistic regression analysis was used to assess the relationship between serum ApoB and depression. Subgroup analyses and interaction tests were used to observe the stability of the association between them. Smooth curve fitting was used to investigate nonlinear correlations. The causal effect of serum ApoB on depression was assessed using Mendelian randomization (MR) analysis. A total of 6531 participated in the study. After adjusting for all covariates, serum ApoB levels were positively associated with depression after adjustment for all covariates (OR = 1.40, 95 % CI = 1.06-1.84; P = 0.0176). Unfortunately, there was no significant causal relationship between serum ApoB and depression (OR = 0.9985,95 % CI = 0.9962-1.0008; P = 0.1923). Sensitivity analysis verified the reliability of the results. Serum ApoB was positively associated with an increased risk of depression, but MR analysis did not show a genetic causal relationship between ApoB and depression. Based on the results of the current study, no indication maintaining high levels of ApoB contributes to the management of depression. The main limitation of this study is the inconsistency of the cross-sectional study and the MR population. Show less
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis an Show more
The embryos of lotus (Nelumbo nucifera Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis and mechanisms of this medicine are still unclear. Isoliensinine (IL) is a major alkaloid derived from lotus embryos. Our previous research has demonstrated that IL can exert strong anti-inflammatory and neuroprotective effects in vitro. To reveal the underlying therapeutic effect and mechanism of IL on Alzheimer's disease (AD)-like mice induced by AlCl The AD-like mice were modeled by intragastric injection (i.g.) of AlCl IL (1, 3, and 10 mg/kg) treatment effectively ameliorated cognitive impairment in AD-like model mice. IL inhibited the decrease of brain index and body weight in AD-like mice and alleviated neuronal damage in the cortex and hippocampus (DG, CA1, and CA3). IL decreased the levels of Ca IL has a significant therapeutic effect on pathological alterations and cognitive impairment in AlCl Show less
As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA i Show more
As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA in tumor diagnosis have gradually attracted the attention of researchers. However, methylation detection, which is more advantageous than mutation detection in tumor diagnosis, has not been widely practiced in EV DNA, and its value in PCa diagnosis also remains underexplored. This study aims to establish and optimize an EV DNA methylation detection system and evaluate its diagnostic and classification potential for PCa. We characterized EV DNA biological properties, optimized pretreatment strategies, validated its correlation with genomic DNA methylation, and explored urine EV DNA methylation targets in 86 benign prostatic hyperplasia (BPH) and 109 PCa patients across three cohorts (screening: 30 BPH/33 PCa; training: 27 BPH/30 PCa; validation: 29 BPH/46 PCa). Heterogeneous biological characteristics were observed among DNA from different subtypes of EV, but methylation profiles remained consistent across subtypes and post-DNase I treatment. EV DNA accurately reflected the methylation state of source cell genomic DNA. By combining our screening results with data from the TCGA database and previously reported, we developed a panel consisting of 667 PCa-specific methylation targets for detection. Among these, six methylation sites (MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25) demonstrated high diagnostic value for PCa, enabling construction of PCa and aggressive PCa differential diagnosis model with AUCs up to 0.74 and 0.91 respectively. The diagnostic value of these six markers was further confirmed using methylight PCR in the validation cohort which also displayed promising performance as a tool for diagnosing PCa. This study highlights the potential of urine EV DNA methylation as a novel diagnostic marker for PCa and lays a foundation for future EV DNA research. Show less
Individual differences in immune responses to African swine fever virus (ASFV), whether induced by vaccination or natural infection, may be linked to genetic variation in the genes involved in antigen Show more
Individual differences in immune responses to African swine fever virus (ASFV), whether induced by vaccination or natural infection, may be linked to genetic variation in the genes involved in antigen presentation. A total of nine pigs from the 112-population were selected for RNA-seq analysis. To pinpoint key transcription factors (TFs) regulating gene expression in the lymph nodes, weighted Kendall's Tau rank correlation analysis was performed to link the TF binding potential with the extent of differential expression of target genes. CD8 These mutations may disrupt TFs binding to the ELK4 promoter, potentially reducing ELK4 expression and impairing antigen processing and presentation. Show less
Meng Xiong, Renjie Luo, Zhijiao Zhang+4 more · 2025 · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · Springer · added 2026-04-24
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulate Show more
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced ARDS. A cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R In vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R Oltipraz may alleviate ARDS-related lung injury by up-regulating Nrf2 expression and concurrently inhibiting macrophage ferroptosis. Show less
Lung adenocarcinoma (LUAD) is one of the leading causes of death worldwide, and thus, more biomarker and therapeutic targets need to be explored. Herein, we aimed to explore new biomarkers of LUAD by Show more
Lung adenocarcinoma (LUAD) is one of the leading causes of death worldwide, and thus, more biomarker and therapeutic targets need to be explored. Herein, we aimed to explore new biomarkers of LUAD by integrating bioinformatics analysis with cell experiments. We firstly identified 266 druggable genes that were significantly differentially expressed between LUAD tissues and adjacent normal lung tissues. Among these genes, SMR analysis with Show less
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from Show more
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from colorectal cancer (CRLM) remain poorly understood. Here we show that patients with CRLM whose liver metastases (LM) exhibited tumor fibrosis (Fibrosis+ LM) had significantly worse progression-free survival (P = 0.025) and overall survival (P = 0.008). Single-cell RNA sequencing revealed that the tumor microenvironment of the Fibrosis+ LM was characterized by T cells with an exhausted phenotype, macrophages displaying a profibrotic and suppressive phenotype and fibrosis-promoting fibroblasts. Further investigation highlighted the pivotal role of VCAN_eCAF in remodeling the tumor fibrosis in the tumor microenvironment of Fibrosis+ LM, emphasizing potential targetable interactions such as FGF23 or FGF3-FGFR1. Validation through multiplex immunohistochemistry/immunofluorescence and spatial transcriptomics supported these findings. Here we present a comprehensive single-cell atlas of tumor fibrosis in LM, revealing the intricate multicellular environment and molecular features associated with it. These insights deepen our understanding of tumor fibrosis mechanisms and inform improved clinical diagnosis and treatment strategies. Show less
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to u Show more
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD. Show less
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offe Show more
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offer promising alternatives to conventional grafts, most techniques fail to replicate the multi-scale fibrous architecture of native bone extracellular matrix, limiting their biofunctionality. To address this, we developed a hybrid manufacturing strategy integrating low-temperature thermally induced phase separation with extrusion-based 3D printing of polylactic acid (PLA) scaffolds. By optimizing solvent ratios (THF: DMF = 3:1) and freezing temperatures (-196 °C-4 °C), we produced scaffolds with tunable micro-nano fibrous surfaces and macroporous structures. Key findings revealed that scaffolds processed at -196 °C (PLA-196) exhibited the highest porosity (pore size: 6.01 ± 2.06 μm), superior hydrophilicity, and enhanced compressive modulus. These scaffolds significantly promoted BMSC adhesion, proliferation, and osteogenic differentiation via activation of Show less
Previous studies have shown that astrocytes can transfer healthy mitochondria to dopaminergic (DA) neurons, which may serve as an intrinsic neuroprotective mechanism in Parkinson's disease (PD). LRRK2 Show more
Previous studies have shown that astrocytes can transfer healthy mitochondria to dopaminergic (DA) neurons, which may serve as an intrinsic neuroprotective mechanism in Parkinson's disease (PD). LRRK2 G2019S is the most common pathogenic mutation associated with PD. In this study, we explored whether mitochondrial transfer is influenced by genetic and environmental factors and whether dysfunction in this process is one of the mechanisms of the pathogenic LRRK2 G2019S mutation. DA neurons and astrocytes were differentiated from induced pluripotent stem cells generated from the peripheral blood of a healthy individual and a PD patient carrying the LRRK2 G2019S mutation. A coculture system of astrocytes and DA neurons was established to explore the pathogenic mechanisms of LRRK2 G2019S. Exposure to the environmental toxin rotenone impaired mitochondrial transfer from astrocytes to DA neurons. Compared with the co-culture system from the healthy participant, the co-culture system harboring the LRRK2 G2019S mutation experienced more pronounced damage. Specifically, STX17 was colocalized with the mitochondrial outer membrane marker TOM20, and its knockdown caused damage to mitochondrial transfer. Drp1 interacted with STX17. LRRK2 G2019S-mutant astrocytes exhibited markedly increased phosphorylation of Drp1 at Ser616 upon rotenone exposure. Moreover, the degree of colocalization of STX17 with TOM20 decreased. The Drp1 phosphorylation inhibitor DUSP6 restored the colocalization of STX17 and TOM20, as well as the mitochondrial transfer efficiency and neuronal survival. The impairment of mitochondrial transfer is a potential pathogenic mechanism associated with LRRK2 G2019S mutation. The molecular mechanisms of mitochondrial transfer were observed to occur through a Drp1-STX17-dependent pathway. Notably, inhibitors for Drp1 Ser616 phosphorylation may offer neuroprotection through mitigating mitochondrial transfer impairments. This study provides novel insights into the pathogenesis of PD and the development of new therapeutic targets. Show less
The entorhinal cortex (ERC) is implicated in early progression of Alzheimer's disease (AD). Here we investigated the impact of established biological risk factors for AD, including
Abnormalities in lipid metabolism play an important role in diabetic macular edema (DME), and the aim of this study was to investigate the correlation between ApoB/A1 levels and best corrected visual Show more
Abnormalities in lipid metabolism play an important role in diabetic macular edema (DME), and the aim of this study was to investigate the correlation between ApoB/A1 levels and best corrected visual acuity (BCVA) and macular microstructural changes in DME patients after anti-VEGF treatment. Through a retrospective cohort analysis of 61 patients (61 eyes) with non-proliferative diabetic retinopathy combined with macular edema treated with 3 + PRN anti-VEGF regimen and followed up for three months, grouped by median ApoB/A1, the differences between the efficacy indexes of the two groups were compared. The results showed that the macular edema regression rate was significantly higher in the high ApoB/A1 ratio group than in the low ratio group at one month after treatment(P < 0.05), and at three months after treatment, the high ApoB/A1 ratio group was better than the low ratio group in BCVA improvement (58.1% vs. 26.7%), inner retinal layer restoration (38.7% vs. 10.0%), and hyperreflective foci (HF) reduction (41.9% vs. 6.7%). aspects were better than those in the low ratio group (P < 0.05). The results of ordered logistic regression analysis showed that the ApoB/A1 ratio was significantly correlated with the change in macular edema at one month after treatment and the change in the number of HF at three months after treatment. Conclusions showed that the ApoB/A1 ratio was significantly correlated with short-term improvement of BCVA and macular microstructure after anti-VEGF treatment in DME patients, and it is expected to be used as an objective biomarker for assessing the efficacy of anti-VEGF treatment in DME patients. Show less
The objective was to assess the clinical efficacy of long non-coding RNA (lncRNA) alpha-2-macroglobulin-antisense 1 (A2M-AS1) in acute myocardial infarction (AMI). One hundred patients with AMI and ei Show more
The objective was to assess the clinical efficacy of long non-coding RNA (lncRNA) alpha-2-macroglobulin-antisense 1 (A2M-AS1) in acute myocardial infarction (AMI). One hundred patients with AMI and eighty patients with chest pain were recruited in the case-control study. A2M-AS1 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was utilized for evaluating the diagnostic value. Pearson's correlation analysis was used to analyze the correlation between A2M-AS1 and conventional AMI biomarkers. AMI-associated risk indicators were identified using logistic regression analysis. A significant reduction of serum A2M-AS1 was measured in AMI patients relative to chest pain patients. A2M-AS1 had an area under the curve (AUC) of 0.927 to distinguish AMI patients from those with chest pain. Pearson's correlation analysis showed that A2M-AS1 was adversely correlated with white blood cell (WBC) (r=-0.6682, P < 0.001), low density lipoprotein cholesterol (LDL-C) (r=-0.5795, P < 0.001), creatine kinase MB (CK-MB) (r=-0.6022, P < 0.001) and cTnl (r=-0.5473; P < 0.001), while positively correlated with high density lipoprotein cholesterol (HDL-C) (r = 0.6445, P < 0.001). Relative to non-Major Adverse Cardiovascular Events (non-MACE) group, serum A2M-AS1 was obviously declined in the MACE group of AMI patients with high capacity to distinguish the MACE group from the non-MACE patients (AUC = 0.802). Additionally, A2M-AS1 (P = 0.013; OR = 0.268; 95%CI = 0.095-0.760) was a risk indicator for predicting MACE with AMI patients, as well as age (P = 0.014; OR = 3.478; 95%CI = 1.285-9.414). A reduction in A2M-AS1 expression was observed in AMI patients, suggesting its potential as an underlying indicator for AMI diagnosis. Show less
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their Show more
To optimize livestock production of integrated farms, dietary crude fat levels are often increased, making efficient fat utilization crucial. Bile acids are known to improve fat utilization, but their impact on growth performance and breast muscle development in Zhijiang ducks remains unclear. In this study, a total of 360 twenty-day-old Zhijiang ducks with similar body weights were divided into three groups: the control group (CN) received a basal diet; the high-fat group (FA) received the basal diet plus 1.25 % rapeseed oil; and the high-fat plus bile acids compound (BA) group (FB) received the FA diet supplemented with 250 mg/kg BA for 30 days. Results indicated that the addition of rapeseed oil and BA significantly increased (P < 0.05) average daily gain (ADG) and reduced (P < 0.05) feed conversion ratio (FCR). Slaughter data showed that BA significantly enhanced (P < 0.05) breast muscle weight and percentage while decreasing (P < 0.05) abdominal fat weight. Additionally, BA increased (P < 0.05) the cross-sectional area of breast muscle fibers, total bile acid content, and levels of insulin-like growth factors 1/2 (IGF1/2). Transcriptomic analysis further revealed that BA significantly upregulated (P < 0.05) the levels of PPARα, CPT1α, NR1H4, and CETP in breast muscle. 16S rRNA analysis showed a significant increase (P < 0.05) in the relative abundances of genera Enorma, [Eubacterium nodatum group], Rikenellaceae RC9 gut group, and SP3-e08. Additionally, the Spearman correlation suggested a positive correlation between the genera Olsenella, SP3-e08, Enorma, Rikenellaceae_RC9_gut_group, and [Eubacterium_nodatum_group] with PPARα, CETP, NR1H4, and CPT1α. In contrast, the genera Christensenellaceae_R₇_group and Sutterella exhibited negative correlations with PPARα. These findings provide new insights into the role of BA in promoting growth performance and skeletal muscle development in Zhijiang ducks fed a high-fat diet, with this effect potentially linked to changes in the gut microbiota. Show less