Obesity arises from an imbalance between adipogenesis and adipocyte thermogenesis. Interleukin-27 (IL-27), a heterodimer cytokine, is known to promote thermogenesis in brown adipose tissue. However, i Show more
Obesity arises from an imbalance between adipogenesis and adipocyte thermogenesis. Interleukin-27 (IL-27), a heterodimer cytokine, is known to promote thermogenesis in brown adipose tissue. However, its role in adipogenesis remains unclear. This study aims to investigate the effects of IL-27 on adipogenesis both in vitro and in vivo, and to elucidate the underlying mechanisms. In vitro, an adipogenic differentiation model of adipose-derived mesenchymal stem cells (ADSCs) demonstrate that IL-27 is non-cytotoxic to ADSCs and inhibits ADSCs adipogenic differentiation. In vivo, using a high-fat diet (HFD)-induced obese mouse model and a targeted adipose tissue-specific IL-27 overexpression adeno-associated viral (AAV) vector, we confirm that IL-27 suppresses adipogenesis, prevents weight gain, and improves glucose and lipid metabolic homeostasis in obese mice. Additionally, the inhibition of adipogenesis by IL-27 is mediated through HDAC6 activation of the TGFβ/Smad3 signaling pathway. Our study suggests that IL-27 is a potential therapeutic target for obesity and metabolic disorders. Show less
Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous Show more
Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous research has demonstrated that inflammatory activity from autoimmune diseases is involved in neurological diseases. However, some studies question the association between inflammatory activities and neurodevelopmental disorders. Herein, we attempt to clarify this relationship using Mendelian randomization (MR) analysis. We used systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes mellitus (T1D) to represent autoimmune diseases. First, we conducted MR analysis to examine associated SNPs between autoimmune and neurodevelopmental disorders. Second, we performed bidirectional MR analysis to identify 429 types of signalling peptides and proteins or relevant receptors with causality reported diseases. Finally, we compared the genes with the gene loci identified in the available TWAS-hub site. The MR results of autoimmune diseases on neurodevelopmental disorders did not present any significant association in all models. However, we identified 20-45 factors in ADHD, ASD, and schizophrenia, including semaphorin 3, IL-27 receptor subunit alpha, and fibroblast growth factor 16, which were considered clinically significant pro-inflammatory mediators. GO and KEGG enrichment analyses revealed unequal integrities among the three neurodevelopmental diseases, and we failed to identify a shared pathway linking autoimmune diseases and neurodevelopmental disorders. TWAS analysis indicated that CHRNA5 potentially mediates inflammatory activities in schizophrenia. According to our data, we failed to identify an association between autoimmune diseases and neurodevelopmental disorders. However, we demonstrated that some pro-inflammatory factors are involved in neurodevelopmental disorders. Show less
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the m Show more
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the mechanisms of disease resistance in these breeds could lay the groundwork for genetic improvements in pig immunity, potentially augmenting overall pig productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Min and Large White pigs for transcriptome sequencing. The mRNA and lncRNA in both pig breeds were analyzed, and intra-group and inter-group comparisons were also conducted. The results indicated that a greater number of immune-related pathways such as the JAK-STAT and PI3K-AKT signaling were enriched in Min pigs. Furthermore, genes involved in inflammation and antiviral responses, including IL16, IL27, USP18, and DHX58, were upregulated in post-vaccination Min pigs compared to post-vaccination Large White pigs. This heightened immune responsiveness could contribute to the observed differences in disease resistance between Min pigs and Large White pigs. Show less
Zijun Zhu, Rongxing Wei, Hailong Li+5 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since Show more
Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions. Subsequently, we revealed tissue and cell-specific heritability enrichment, particularly in whole blood, small intestine terminal ileum, spleen, lung, and colon transverse. Leveraging multi-omics datasets, we adopted a two-pronged approach comprising summary data-based Mendelian randomization (SMR) and transcriptome-wide association study (TWAS) to pinpoint likely causal genes and variants. Further, RNA-seq analysis facilitated the evaluation of differential expression and co-expression in intestinal tissues. Through a multi-stage prioritization strategy, compelling evidence for putative targets was nominated; notably highlighting several potential susceptibility genes such as IL27 and SBNO2. Finally, we utilized Mendelian randomization (MR) analysis with diverse datasets to verify the convergence of these two endophenotype-driven genes. Our investigation yields valuable insights to inform genetic mechanisms in IBD and reveal potential causal gene targets. Show less
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit ant Show more
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1β, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB. Show less
Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critica Show more
Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critical homeostasis regulator, but its function in liver immune homeostasis is unknown. We aimed to clarify the role of hepatocyte FoxO1 in liver immune homeostasis and inflammation. Human liver FoxO1 expression and its association with inflammation were analyzed in patients with various inflammation-related liver diseases. Hepatocyte-specific Foxo1 knockout (FoxO1 △hepa ) mice were established. Hepatocyte-specific gene interference was employed in alcoholic hepatitis and hepatic schistosomiasis murine models. Transcriptomic, single-cell RNA sequencing, and CUT&Tag analyses were performed to elucidate the underlying mechanisms. Hepatocyte FoxO1 levels in human inflammatory livers declined prevalently and were inversely correlated with inflammation and fibrosis. Around 15-18 weeks after birth, FoxO1 △hepa mice exhibited mild spontaneous hepatic inflammation with natural killer T (NKT) cell and neutrophil accumulation. NKT cell depletion in FoxO1 △hepa mice with alcoholic hepatitis or hepatic schistosomiasis (HS) significantly reduced neutrophil accumulation and protected against liver inflammation and damage. Mechanistically, FoxO1 promoted retinoic acid synthesis to induce hepatocyte CD1d expression, which is necessary for regulating NKT cell apoptosis. Innovatively, decreased JMJD1C expression in hepatocytes caused histone H3 lysine 9 (H3K9) dimethylation at the Foxo1 promoter, repressing its transcription and disrupting local immune homeostasis. Our findings uncover a hitherto unrecognized mechanism for hepatocyte-based control of liver inflammation, in which hepatocyte FoxO1 maintained by JMJD1C restrains local NKT cells and neutrophils via CD1d induction, providing promising targets for inflammatory liver diseases. Show less
Estrogen receptor-positive (ER+) breast cancer is the most common molecular subtype of breast cancer and is strongly influenced by hormonal and environmental factors. Endocrine-disrupting chemicals (E Show more
Estrogen receptor-positive (ER+) breast cancer is the most common molecular subtype of breast cancer and is strongly influenced by hormonal and environmental factors. Endocrine-disrupting chemicals (EDCs), which interfere with hormone signaling, have been suggested to contribute to ER+ breast cancer risk, but causal mechanisms remain unclear. We integrated chemical-gene interaction data from the TEDX and CTD databases with large-scale genomic datasets to investigate the relationship between EDC-regulated gene expression and ER+ breast cancer. A total of 5797 EDC-related genes were identified and filtered using cis-expression quantitative trait loci (cis-eQTL) data from eQTLGen. Mendelian randomization (MR) and colocalization analyses were performed using ER+ breast cancer GWAS summary statistics to assess causal associations and shared genetic signals. Interacting EDCs were mapped to colocalized genes. Among 4207 genes with available cis-eQTLs, 50 showed statistically significant associations (FDR < 0.05) with ER+ breast cancer. Of these, 24 genes, including CIRBP, JMJD1C, and TET2, demonstrated strong evidence of colocalization. Key EDCs, such as bisphenol A and phthalates, were identified to interact with multiple high-risk genes, suggesting potential environmental drivers of ER+ breast cancer. This study provides genetic evidence supporting the causal role of EDC-regulated gene expression in ER+ breast cancer. The integration of MR, colocalization, and chemical-gene networks offers a novel framework for identifying environmentally relevant risk factors and contributes to understanding the gene-environment mechanisms underlying hormone-dependent cancers. Show less
Neuropathic pain (NP) is a chronic debilitating disease caused by nerve damage or various diseases, significantly impairs patients' quality of life. Super-enhancers (SEs) are important cis-regulatory Show more
Neuropathic pain (NP) is a chronic debilitating disease caused by nerve damage or various diseases, significantly impairs patients' quality of life. Super-enhancers (SEs) are important cis-regulatory elements, but how they affect NP remains elusive. Therefore, we aim to explore the molecular mechanism by which SEs are involved in NP progression and identify potential drug candidate targets. We first established a NP model in rats, and subsequently performed H3K27ac ChIP-Seq and RNA-Seq on their spinal cord tissues to analyze the active enhancers. By integrated analysis of ChIP-seq data and RNA-seq data, we clarified a series of SE-associated genes involved in NP progression. qPCR and double immunofluorescence staining results suggested that Show less
JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with differen Show more
JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias. Show less
Although studies have suggested a potential link between the nervous system and prostate cancer, the underlying regulatory mechanisms remain unclear. Therefore, it is crucial to identify the genes inv Show more
Although studies have suggested a potential link between the nervous system and prostate cancer, the underlying regulatory mechanisms remain unclear. Therefore, it is crucial to identify the genes involved in regulating prostate cancer within the nervous system. We utilized eQTL data from eight neural cell types as exposure factors and GWAS data for prostate cancer as outcome events. Mendelian randomization (MR) analyses were performed to identify causative genes associated with prostate, bladder, and renal cancers in Astrocytes, Endothelial cells, Excitatory neurons, Inhibitory neurons, Microglia, Oligodendrocytes, OPCs/COPs, and Pericytes. Bladder and renal cancers were used as controls. Sensitivity analyses (heterogeneity, pleiotropy, and leave-one-out tests) were conducted to ensure reliability. In astrocytes, seven positive genes were identified as being causally related to prostate cancer: KANSL1, AC005670.2, ARL17B, LRRC37A2, LRRC37A, MAPT, and LINC02210. In. Endothelial cells, Inhibitory neuron and Microglia, three genes (LRRC37A2, ARL17B, and KANSL1) were identified as risk genes that are associated with prostate cancer. Four protective genes were identified in excitatory neurons, including LRRC37A2, ARL17B, KANSL1 and LINC02210. In oligodendrocytes, eight genes were identified, with LRRC37A2, ARL17B, and KANSL1 acting as protective factors, while OR2L13, OR2L3, OR2L5, OR2L2, and OR2M4 were identified as risk factors. Additionally, sensitivity analyses showed no heterogeneity or horizontal pleiotropy in the MR results, confirming their reliability and stability. In addition, no positive genes were found in bladder cancer and renal cancer. Our study highlights the role of the nervous system, particularly astrocytes, in regulating prostate cancer. We identified three genes, with LRRC37A2, ARL17B, and KANSL1 emerging as key protective factors. These findings provide potential targets for prostate cancer diagnosis and treatment. The online version contains supplementary material available at 10.1007/s12672-025-03711-9. Show less
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes tha Show more
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isolated from both cerebellum and frontal cortex of AD/ADRD patients and normal controls. Using peak-to-gene linkage analysis, we identified 431,834 significant linkages between gene expression and cell subtype-specific chromatin accessibility regions enriched for candidate cis-regulatory elements (cCREs). These cCREs were associated with AD/ADRD-specific transcriptomic changes and disease-related gene regulatory networks, especially for RAR Related Orphan Receptor A (RORA) and E74 Like ETS Transcription Factor 1 (ELF1) in cerebellar Purkinje cells and granule cells, respectively. Trajectory analysis of granule cell populations further identified disease-relevant transcription factors, such as RORA, and their regulatory targets. Finally, we pinpointed two likely causal genes, Seizure Related 6 Homolog Like 2 (SEZ6L2) in Purkinje cells and KAT8 Regulatory NSL Complex Subunit 1 (KANSL1) in granule cells, through integrative analysis of cCREs derived from snATAC-seq, genome-wide AD/ADRD loci, and three-dimensional (3D) genome data. Via CRISPRi experiments, we found that perturbation of rs4788201 and rs62056801 significantly inhibited the expression of their target genes, SEZ6L2 and KANSL1, in human iPSC-derived neurons. This cell subtype-specific regulatory landscape in the human cerebellum identified here offers novel genomic and epigenomic insights into the neuropathology and pathobiology of AD/ADRD and other neurological disorders if broadly applied. Show less
Hui Wang, Timothy S Chang, Beth A Dombroski+64 more · 2025 · Movement disorders : official journal of the Movement Disorder Society · Wiley · added 2026-04-24
The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear pa Show more
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) is a neuronal system-specific transmembrane protein that is highly expressed in the brains o Show more
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) is a neuronal system-specific transmembrane protein that is highly expressed in the brains of patients with Alzheimer's disease (AD), and our previous findings showed that LINGO-1 antagonism can improve cognitive function and protect hippocampal GABAergic interneurons in AD model mice. However, the specific mechanism underlying these effects is not clear. In this study, an adeno-associated virus (AAV) was used to directly interfere with hippocampal LINGO-1 in vivo, and LINGO-1 antagonists, cannabinoid type 1 receptor (CB1R) agonists, and CB1R antagonists were used to treat mouse hippocampal neurons (HT22 neurons) in vitro. We found that overexpressing hippocampal LINGO-1 in normal young mice impaired spatial learning and memory and reduced hippocampal CB1R protein levels, whereas silencing hippocampal LINGO-1 in AD model mice had the opposite effect. Additionally, antagonizing LINGO-1 increased CB1R/tyrosine kinase receptor B (TrkB) signalling and rescued CB1R- rich cholecystokinin-GABAergic (CCK-GABAergic) interneurons in HT22 neurons transduced with an APP/PS1-expressing virus. Competitive inhibition of LINGO-1 and CB1R was observed, and antagonizing LINGO-1 reversed the changes in HT22 neurons caused by the inhibition of CB1R, such as the decreases in the protein levels of doublecortin (DCX), TrkB, and phosphorylated TrkB (p-TrkB). These findings provide an important scientific basis for further exploration of the mechanism by which LINGO-1 regulates cognitive function and hippocampal GABAergic interneurons in AD model mice. Show less
Bladder cancer (BC) is one of the most common urological malignancies, ranking as the eleventh most common cause of cancer-related deaths worldwide. The lack of specific and sensitive prognostic bioma Show more
Bladder cancer (BC) is one of the most common urological malignancies, ranking as the eleventh most common cause of cancer-related deaths worldwide. The lack of specific and sensitive prognostic biomarkers presents a significant challenge in the early diagnosis and treatment of BC. We used the Gene Expression Omnibus (GEO) dataset GSE13507 and the Cancer Genome Atlas (TCGA) database to screen differentially expressed genes related to BC. By using Weighted Gene Co-expression Network Analysis (WGCNA), two modules associated with BC were investigated in GSE13507 and TCGA. Hub genes were identified through Protein-Protein Interaction (PPI) network analysis and their functions were validated through multiple approaches, including Gene Expression Profiling Interactive Analysis (GEPIA), Western Blotting (WB) assay, Human Protein Atlas (HPA), Oncomine analysis, and quantitative Real-Time PCR (qRTPCR) analysis. Additionally, miRNAs associated with hub gene expression were identified using various databases to predict the progression and prognosis of BC. WCGNA and differential gene expression analysis identified 171 common genes as target genes. Ten genes (MYH11, ACTA2, TPM2, ACTG2, CALD1, MYL9, TPM1, MYLK, SORBS1, and LMOD1) were identified using the PPI tool and the CytoHubba plugin of Cytoscape. The CALD1 and MYLK genes showed a significant prognostic value for overall survival and diseasefree survival in patients with BC. According to the HPA and Oncomine databases, CALD1 and MYLK expression levels were significantly lower in BC tissues than in normal tissues. Additionally, qRT-PCR analysis, WB assay, and immunohistochemical analysis confirmed CALD1 and MYLK as tumor suppressor genes in BC. Furthermore, miR-155 showed a significant positive correlation with MYLK. This study established MYLK as a direct target gene of miR-155, functioning as an actionable survival-related gene correlated with BC development. Show less
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentia Show more
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, gene function enrichment analysis, and comparative toxicology database analysis. Finally, the gene expression heat map was drawn, and miRNA information regulating core DEGs was retrieved. A total of 1151 DEGs were found, most of them focusing on systematic development, cell development, cell differentiation, regulation of multicellular biological processes, anatomical morphogenesis, MAPK signaling pathway, proteoglycans in cancer, fluid shear stress, and atherosclerosis. The core genes (MYL9, TAGLN, SMTN, CNN1, MYH11, MYLK, MYOCD, ACTC1, LMOD1, and TPM2) obtained in end are all lowly expressed in prostate cancer samples and are associated with hypertension, tumor metastasis, prostate tumors, and tumor aggressiveness. LMOD1 and SMTN are lowly expressed in prostate cancer and may be used as markers in prostate cancer nursing. Show less
Psychological empowerment is a critical factor for employee work well-being, particularly within high-stress professions such as policing. However, experiences of empowerment among individuals are not Show more
Psychological empowerment is a critical factor for employee work well-being, particularly within high-stress professions such as policing. However, experiences of empowerment among individuals are not uniform. This study aims to identify distinct profiles of psychological empowerment among police officers and to examine their associations with perceived coworker support and work well-being. A person-centered approach was adopted. Data were collected from 505 Chinese police officers. Latent Profile Analysis (LPA) was employed to identify subgroups based on their psychological empowerment patterns. The analysis revealed two distinct profiles: a "Globally Disempowered" profile and a "Globally Empowered" profile. Perceived emotional support from coworkers was a significant predictor of profile membership, where higher levels of support increased the likelihood of belonging to the empowered group. Furthermore, officers in the high empowerment profile reported significantly greater work well-being compared to those in the low empowerment profile. The findings underscore the heterogeneity in psychological empowerment experiences within the policing context. They emphasize the pivotal role of fostering emotional peer support as a means to enhance officers' psychological empowerment and, consequently, their work well-being. Practical implications for organizational interventions are discussed. Show less
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and phys Show more
With the aging population in China, research on preventing frailty is crucial. This study aims to investigate the independent and combined associations of the Dietary inflammatory index (DII) and physical activity (PA) with frailty among Chinese older adults. A total of 285 participants aged ≥60 years with 87 males and 186 females were recruited from Hunan Province. Daily moderate physical activity (MPA), vigorous physical activity (VPA) and light physical activity (LPA) were objectively measured using a triaxial accelerometer. A Food Frequency Questionnaire 25 (FFQ25) was used to assess the participants' dietary patterns, and DII was calculated. Six combined exposure groups were formed based on PA and DII: pro-inflammatory diet and insufficient PA group, neutral diet and insufficient PA group, anti-inflammatory diet and insufficient PA group, pro-inflammatory diet and sufficient PA group, neutral diet and sufficient PA group, and anti-inflammatory diet and sufficient PA group. Frailty was assessed using the Frailty Phenotype (FP), logistic regression analyzed the associations between dietary patterns, PA, and frailty. A total of 285 older adults participants were initially recruited, but 12 were excluded due to missing data. Consequently, 273 participants were included in the final analysis. Compared to individuals with insufficient PA, those with sufficient PA were associated with significantly lower odds of frailty (OR = 0.468, 95%CI = 0.242-0.907). Participants following an anti-inflammatory diet had significantly lower odds of frailty compared with those following a pro-inflammatory diet (OR = 0.467, 95%CI = 0.221-0.988). In the combined groups, frailty prevalence was significantly lower the group with anti-inflammatory diet and sufficient PA group (OR = 0.204, 95%CI = 0.072-0.583), compared with pro-inflammatory diet and insufficient PA group. The sensitivity analysis showed that the associations between anti-inflammatory diet and sufficient PA with frailty remained statistically significant, with the direction of the associations unchanged. These findings suggest that the results are robust. Our study indicates that adhering to an anti-inflammatory diet and maintaining sufficient PA may be associated with a lower likelihood of frailty. Achieving an adequate amount of PA and following a healthy dietary pattern may serve as potential preventive measures against frailty. Show less
This study aimed to explore the potential categories of resourcefulness in patients with type 2 diabetes mellitus (T2DM) and their relationship with self-management. A total of 513 hospitalized T2DM p Show more
This study aimed to explore the potential categories of resourcefulness in patients with type 2 diabetes mellitus (T2DM) and their relationship with self-management. A total of 513 hospitalized T2DM patients in Xi'an were surveyed using a general information questionnaire, the Resourcefulness Scale, and the Diabetes Self-management Activities Scale for Type 2 Diabetes. Latent profile analysis (LPA) was conducted to identify resourcefulness subgroups, and their relationship with self-management was examined. Patients with type 2 diabetes could be classified into three potential categories based on their resourcefulness status: a low resourcefulness level group (17.54%), a moderate resourcefulness level-social alienation group (66.66%), and a high resourcefulness level group (15.78%). Educational level, monthly per capita family income, and the presence or absence of complications were identified as factors influencing the potential categories of resourcefulness. Significant differences were observed in the total self-management scores among patients belonging to different potential categories of resourcefulness ( Type 2 diabetes patients can be classified into three potential categories of resourcefulness, with those in the high resourcefulness level group demonstrating higher self-management ability. Improving the level of resourcefulness can contribute to enhancing patients' self-management capabilities. Show less
Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising intervention for Autism Spectrum Disorder (ASD), but objective markers for rTMS tolerance remain lacking. This case-control study exp Show more
Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising intervention for Autism Spectrum Disorder (ASD), but objective markers for rTMS tolerance remain lacking. This case-control study explored gaze behavior variability toward emotional faces in ASD children undergoing rTMS, focusing on identifying subgroups associated with rTMS intolerance. Eye-tracking data (Tobii technology, preferential-looking paradigm) were collected from 104 ASD children (48 intolerant, 56 tolerant) receiving DLPFC-targeted rTMS (left high-frequency, right low-frequency). Latent Profile Analysis (LPA) identified fixation subgroups across eight conditions. Demographic (sex, age), clinical (CARS scores) differences, and profile-tolerance associations were analyzed. LPA revealed three gaze profiles: moderate non-preferential fixation (80.76%), low diverse fixation (9.62%), and increased fixation with mild variability (9.62%). Sex and CARS scores differed across profiles (age did not). Intolerance rates were 38.1%, 60.0%, and 100%, with profiles predicting rTMS intolerance (OR = 0.210, 95% CI: 0.079-0.557). ASD children exhibit heterogeneous emotional face gaze patterns. Findings highlight the need for personalized rTMS interventions, especially for those with higher CARS scores and increased emotional face fixation-at elevated intolerance risk. Show less
Lysophosphatidic acid (LPA) has anti-inflammatory and protective effects in sepsis, yet clinical evidence on its correlation with sepsis progression and outcomes is limited. This study aimed to evalua Show more
Lysophosphatidic acid (LPA) has anti-inflammatory and protective effects in sepsis, yet clinical evidence on its correlation with sepsis progression and outcomes is limited. This study aimed to evaluate the association of plasma LPA levels with sepsis development, severity, and mortality. A total of 42 sepsis patients and 29 controls with common infections were included. Among the sepsis patients, 15 succumbed during hospitalization. Plasma LPA levels were measured, and clinical data were retrospectively analyzed. Plasma LPA was significantly lower in sepsis patients compared to controls, and further reduced in non-survivors. Notably, correlation analyses suggested that LPA levels were negatively correlated with neutrophil count, procalcitonin, interleukin-6, and Sequential Organ Failure Assessment (SOFA) score. Multivariate regression analysis identified LPA as an independent risk factor for sepsis onset and in-hospital mortality. Receiver operating characteristic (ROC) curve analysis revealed that LPA had a high diagnostic accuracy for sepsis (area under the ROC curve [AUC] = 0.92, 95% CI = 0.86-0.99, P < 0.001) and was a strong predictor of in-hospital mortality (AUC = 0.86, 95% CI = 0.76-0.97, P < 0.001). Reduced plasma LPA levels in sepsis patients are inversely correlated with infection/inflammation markers and SOFA scores. Together, these results suggest that LPA may serve as a potential diagnostic and prognostic biomarker for sepsis, supporting its potential as a complementary tool to enhance early risk stratification and guide bedside clinical decision-making. Show less
This study investigates the heterogeneity in kindergarten teachers' perceptions of organizational climate and its impact on job burnout. Guided by the AGIL model from social systems theory and the Job Show more
This study investigates the heterogeneity in kindergarten teachers' perceptions of organizational climate and its impact on job burnout. Guided by the AGIL model from social systems theory and the Job Demands-Resources (JD-R) model, it addresses the need to move beyond variable-centered approaches to understand how distinct climate profiles are associated with teacher well-being. A person-centered latent profile analysis (LPA) was employed. A sample of 1,008 kindergarten teachers from China completed measures assessing organizational climate and burnout. The analysis aimed to identify distinct climate profiles and examine their relationships with demographic variables (kindergarten type, assessment level, teaching experience) and the three dimensions of burnout (emotional exhaustion, depersonalization, reduced personal accomplishment). The LPA revealed five distinct organizational climate profiles: Controlled, Moderate, Indifferent, Positive, and Authoritative. Profile membership was significantly predicted by kindergarten assessment level and teachers' years of experience, but not by kindergarten type. Crucially, the profiles differed significantly across all burnout dimensions. Teachers in Positive climates reported the lowest burnout levels, whereas those in Controlled and Indifferent climates experienced the highest. The findings underscore the structural diversity of organizational climates in early childhood settings and their profound psychological consequences. This study validates the application of social systems theory and the JD-R model in this context, revealing how different configurations of job demands and resources shape teacher well-being. The results provide a theoretical lens for understanding educational organizations and offer practical implications for developing tailored, climate-specific intervention strategies to mitigate burnout and support sustainable professional development. Show less
The present study aimed to clarify heterogeneity in music performance anxiety (MPA) by identifying latent profiles, examining sociodemographic and psychological predictors of profile membership, and t Show more
The present study aimed to clarify heterogeneity in music performance anxiety (MPA) by identifying latent profiles, examining sociodemographic and psychological predictors of profile membership, and testing mediation pathways. A total of 819 Chinese musicians participated in an online survey that assessed MPA, performance worry (PW), and perceived memory reliability (PMR), along with demographic variables. Latent profile analysis (LPA) revealed a three-profile solution that distinguished low, moderate, and high MPA groups. Multinomial logistic regression indicated that older age, higher education levels, lower household income, and unstable employment were significantly associated with membership in the moderate and high MPA profiles. In addition, PW emerged as a significant psychological predictor of elevated MPA, whereas PMR showed a protective effect and was negatively associated with MPA. Mediation models further demonstrated that PW played an important role in transmitting the effect of PMR on MPA, suggesting that cognitive factors related to memory reliability shape worry processes, which, in turn, intensify performance anxiety. These findings advance understanding of MPA by demonstrating that Chinese musicians can be meaningfully categorized into distinct risk groups, each shaped by sociodemographic vulnerabilities and cognitive-emotional pathways. From a practical perspective, the results highlight the importance of targeted prevention and intervention strategies that address both memory-related cognitions and performance worry in order to reduce MPA in vulnerable populations. Show less
Older adults' physical and sensory function and self-perceived health state are associated with their daily health behavior, such as moderate-to-vigorous physical activity (MVPA), light physical activ Show more
Older adults' physical and sensory function and self-perceived health state are associated with their daily health behavior, such as moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SEB), and sleep duration (SD), though most studies examine these independently, overlooking 24-hour interactions. This study aims to investigate the relationships between physical and sensory function (vision, hearing, activity limitations), self-perceived health and the pattern of 24-hour activity behaviors via compositional data analysis. A secondary data analysis was conducted on data from the Survey of Health, Ageing and Retirement in Europe. Compositional data analysis was employed to account for the inherently interdependent nature of these behaviors. Linear regression models were implemented, designating activity behaviors as the dependent variable and sensory/physical function as the independent variable. The results indicated that vision and hearing showed weaker and nonsignificant associations with activity behaviors. Activity limitations significantly influence health behavior patterns, with no limitations associated with more time in MVPA and less time in SEB and SD. Self-perceived health is significantly positively associated with more MVPA, while inversely associated with SEB and SD. This study revealed that older adults with limitations in their daily activities showed the most sedentary daily activity pattern. Future research should develop targeted interventions to improve activity behaviors in this population. Show less
Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for fami Show more
Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for family functioning, socioeconomic status, and public health policies. Therefore, this study aims to explore different potential profiles of sleep quality in perimenopausal women in the community and analyze the influencing factors of different profiles. A cross-sectional study was conducted from July 2024 to December 2024, and a total of 281 perimenopausal women in the community were recruited from 4 communities in Bengbu by convenience sampling. The participants completed the pittsburgh sleep quality index (PSQI), and self-rating anxiety scale (SAS), self-rating depression scale (SDS) and simplified coping style questionnaire (SCSQ). Latent profile analysis(LPA) was employed to identify latent profiles of sleep quality of perimenopausal women in the community. The predictors of sleep quality in different latent profiles were assessed via multinomial logistic regression analysis. One-way ANOVA, chi-square test or Fisher exact test, and the Kruskal-Walis test were used to compare the PSQI scores of perimenopausal women in the community under different latent profile characteristics. The mean age of 281 perimenopausal women was 50.09 ± 5.08 years, and the prevalence of sleep disorders was 31.3%. The sleep quality of perimenopausal women in community could be divided into three different latent profiles: good sleep quality group (68.7%), falling sleep and maintenance difficulty group (24.2%), and poor sleep quality with sleep disorder group (7.1%). Taking the good sleep quality group as the reference group, drinking history (OR = 2.061), chronic disease history (OR = 2.154), spouse's health status (OR = 1.871) and anxiety (OR = 4.390) were the risk factors to predict the difficulty in falling asleep and maintaining sleep in community perimenopausal women (P < 0.05). Spouse's health status (OR = 2.139) and anxiety (OR = 19.029) were the risk factors for poor sleep quality and sleep disorders in community perimenopausal women (P < 0.05). There are three qualitatively different potential profile categories of sleep quality in perimenopausal women in the community, and drinking history, chronic disease, poor spouse health and anxiety have predictive effects on their profile categories. In the future, community nursing staff can take targeted interventions according to different categories of sleep quality in perimenopausal women to improve sleep quality and level of health promotion. Show less
The relationship between ambient air pollution and chronic liver disease (CLD), and whether physical activity (PA) modifies this association, remains unclear. We analyzed 17,708 middle-aged and older Show more
The relationship between ambient air pollution and chronic liver disease (CLD), and whether physical activity (PA) modifies this association, remains unclear. We analyzed 17,708 middle-aged and older adults from the 2013 China Health and Retirement Longitudinal Study (CHARLS). Individual-level exposures to CO, O In fully adjusted models, higher pollutant levels were associated with increased CLD risk: CO (OR 1.13, 95% CI 1.04-1.19, p = 0.025), O Ambient CO, O Show less
Amyloid transthyretin (ATTR) amyloidosis is a rare, life-threatening disease frequently manifesting with cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN) or both (ATTR-mixed). We retrospectively ana Show more
Amyloid transthyretin (ATTR) amyloidosis is a rare, life-threatening disease frequently manifesting with cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN) or both (ATTR-mixed). We retrospectively analysed US electronic health records and claims data to provide up-to-date estimates of ATTR amyloidosis epidemiology (overall and by phenotype). Data were extracted from the Clarivate Real-World Data repository (2016-2023). Given the lack of established coding for ATTR amyloidosis, we used different combinations of diagnostic codes to obtain narrow and broad estimates of incident and prevalent cases in the USA in 2022. Temporal trends (2019-2022) were also assessed. Using narrow definitions, the 2022 estimated incidence of ATTR amyloidosis overall, ATTR-CM, ATTR-PN and ATTR-mixed was 16.6, 12.7, 3.5 and 1.9 cases per million people, respectively; the corresponding prevalence estimates were 59.8, 41.1, 15.1 and 9.8 cases per million people. Estimates were consistently lower with the narrow (vs broad) definitions. Over time, the incidence and prevalence of ATTR amyloidosis overall increased, driven by ATTR-CM cases. No major changes were reported for the other phenotypes. This study provides comprehensive and up-to-date epidemiological data for ATTR amyloidosis in the USA. Our findings corroborate the need for appropriate differential diagnostic coding and standardised criteria. Show less
Calcific aortic stenosis (CAS) is frequently accompanied by systemic comorbidities, but their causal relationships and shared genetic architecture remain poorly defined. We aimed to map the multisyste Show more
Calcific aortic stenosis (CAS) is frequently accompanied by systemic comorbidities, but their causal relationships and shared genetic architecture remain poorly defined. We aimed to map the multisystem comorbidity network of CAS and clarify underlying genetic mechanisms. In 467 484 participants from the UK Biobank, observational and polygenic phenome-wide association studies evaluated associations between CAS and 1571 phenotypes, integrating disease-trajectory analyses to visualise temporal patterns. Associations replicated across observational and polygenic analyses were tested using two-sample Mendelian randomisation (MR) based on 22 CAS-related variants from FinnGen. Polygenic risk score (PRS) analyses excluding specific genes assessed their contributions, particularly LPA and plasma lipoprotein(a) (Lp(a)) levels. CAS was associated with higher risks of 42 cardiovascular and non-cardiovascular conditions, most prominently metabolic, endocrine, haematological and respiratory disorders. Temporal analyses showed that circulatory and metabolic diseases typically precede other comorbidities in CAS trajectories. MR findings were consistent with causal effects of CAS on multiple cardiovascular diseases, iron-deficiency anaemia, mental disorders and pleural effusion. When LPA variants were removed from the CAS PRS or plasma Lp(a) concentration was adjusted for, most associations lost significance, indicating a shared LPA/Lp(a)-mediated genetic pathway. CAS is embedded within a broad multisystem comorbidity network, driven largely by genetic variation at LPA and elevated Lp(a). These findings highlight pleiotropic mechanisms linking valvular calcification with systemic disease and support LPA-targeted therapies as a promising avenue for reducing the multisystem burden of CAS. Show less
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain t Show more
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain tumor patients in Shanghai, China, using Latent Profile Analysis (LPA) to guide personalized diagnosis, treatment, and supportive care. A longitudinal study was conducted among 161 patients with primary brain tumors in Shanghai. Participants completed the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) at three intervals: the day of admission (T1), three days after surgery (T2), and two weeks after surgery (T3). Latent Profile Analysis (LPA) was used to identify subgroups with unique symptom patterns. Six distinct subgroups were identified (entropy = 0.964), ranging from low-burden to persistently severe patterns. Subgroup membership was partially associated with age, tumor grade, and diagnosis. These subgroups were: transient postoperative burden group, stable symptom with cognitive emergence group, distress-predominant, low burden group, elderly-high grade, persistently severe group, nausea-dominant recovery group, and distress-plus-nausea, younger urban group. Our findings reveal substantial heterogeneity in perioperative symptom experiences among brain tumor patients. Identifying subgroups with high and persistent symptom burden may help clinicians target interventions such as enhanced education, proactive monitoring, rehabilitation, psychological support, and antiemetic management. This subgroup-based approach may improve quality of life, reduce morbidity, and guide precision supportive care in neuro-oncology. Show less