Osteosarcoma, the most common primary malignant bone tumor with poor prognosis, underscores the need for a deeper understanding of its molecular mechanisms. Recent studies have highlighted the importa Show more
Osteosarcoma, the most common primary malignant bone tumor with poor prognosis, underscores the need for a deeper understanding of its molecular mechanisms. Recent studies have highlighted the importance of RNA modifications, including 5-methylcytosine (m5C), in cancer progression, yet the m5C modification landscape in osteosarcoma remains unexplored. Here, we performed transcriptome-wide profiling of m5C modifications in osteosarcoma using meRIP-seq and RNA-seq, analyzing four pairs of osteosarcoma and adjacent normal tissues. Furthermore, through conjunction analyses of meRIP-seq and RNA-seq data, we identified 637 genes with significant changes in both the m5C modification and mRNA levels. Among these, GPRC5B emerged as a key prognostic gene, with its high expression and m5C hypermethylation significantly associated with poor survival in osteosarcoma patients. Functional experiments demonstrated that GPRC5B suppresses apoptosis and promotes osteosarcoma cell proliferation and migration. Mechanistically, NSUN2-mediated m5C modification upregulates GPRC5B expression, and the anti-apoptotic effects of NSUN2 are primarily dependent on its ability to modulate GPRC5B m5C modification and expression. Knockdown of GPRC5B partially rescues the anti-apoptotic effects of NSUN2, highlighting the critical role of GPRC5B in osteosarcoma survival. Our study identified an m5C-dependent NSUN2-GPRC5B regulatory axis, providing insights into osteosarcoma progression and revealing its therapeutic potential. Show less
Metabolic syndrome (MetS) is a recognized risk factor for prostate cancer (PCa), yet the precise biological mechanisms driving this association remain poorly understood. Unraveling these molecular pat Show more
Metabolic syndrome (MetS) is a recognized risk factor for prostate cancer (PCa), yet the precise biological mechanisms driving this association remain poorly understood. Unraveling these molecular pathways is essential for developing targeted interventions to improve patient outcomes. In this study, we analyzed NHANES (2005-2014) data to examine associations between MetS and PCa outcomes, finding that MetS was significantly associated with higher PCa risk (OR = 1.52), all-cause mortality (HR = 1.53), and cancer-specific mortality (HR = 2.17). Through integrated multi-omics, weighted gene co-expression network analysis, and machine learning, we identified the orphan receptor GPRC5B as a critical hub gene downregulated in both conditions. Single-cell transcriptomic analysis further confirmed that GPRC5B is predominantly expressed in endothelial cells. Mechanistically, GPRC5B loss was found to hyperactivate p38 MAPK signaling through a specific dual mechanism: increasing phosphorylation of upstream MKK3/6 kinases while concurrently suppressing the negative feedback phosphatase DUSP1. This synergistic dysregulation drove enhanced endothelial proliferation, migration, and tube formation in vitro. In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression. Show less
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a Show more
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were observed in HS tissues, with macrophages in stiff mechanical microenvironments identified as the primary lactate source. Lactate influx through MCT1 upregulated H3K23la, thereby promoting transcriptional activation of profibrotic genes HEY2 and COL11A1. Mechanistically, HEY2 activated YAP1/SMAD2 signaling, while COL11A1 stabilized MCT1 to enhance lactate transport, forming a positive loop that amplified fibrosis. Fibroblast-specific Mct1 deletion or pharmacological inhibition of Mct1 in male mice reduced collagen deposition, accelerated wound healing, and attenuated scar formation. Our findings redefine the macrophage-fibroblast crosstalk in HS and establish the MCT1-H3K23la-HEY2/COL11A1 axis, particularly its self-reinforcing loop, as a novel therapeutic target. Show less
Periodontitis is a prevalent chronic infectious condition affecting the oral cavity. This research was conducted to analyze the role of GATA6 in LPS-stimulated human periodontal ligament cells (hPDLCs Show more
Periodontitis is a prevalent chronic infectious condition affecting the oral cavity. This research was conducted to analyze the role of GATA6 in LPS-stimulated human periodontal ligament cells (hPDLCs). Dysregulated genes associated with periodontitis were acquired from the GEO database (GSE23586). Cell viability was measured utilizing the MTT assay, while apoptosis was analyzed through flow cytometry. The expression levels of mRNA and proteins were examined using qRT-PCR and Western blot techniques, respectively. Levels of IL-1β, IL-6, and TNF-α were measured using specific ELISA kits. The mouse periodontitis model was established to evaluate the effect of GATA transcription factor 6 (GATA6) in vivo.The results demonstrated that GATA6 was downregulated in periodontitis and LPS-stimulated hPDLCs. Overexpression of GATA6 enhanced cell viability, while inhibited apoptosis in hPDLCs. It also reduced the levels of IL-1β, IL-6, and TNF-α in LPS-stimulated hPDLCs. Additionally, after transfection with a GATA6 overexpression vector, the expressions of Caspase 3 and Bax proteins were suppressed, while Bcl2 was upregulated. Furthermore, in LPS-stimulated hPDLCs, the protein levels of Notch1, Hey1, and Hey2 were enhanced after GATA6 overexpression. Silencing of Notch1 neutralized the effects of GATA6 in LPS-stimulated hPDLCs. In addition, GATA6 overexpression alleviated the progression of periodontitis in vivo. In conclusion, GATA6 alleviated the progression of periodontitis by activating the Notch signaling pathway. Show less
Psoralea corylifolia(PF) is widely utilized for the treatment of conditions such as kidney yang deficiency, frequent urination, and cold pain in the waist and knees. However, both basic research and c Show more
Psoralea corylifolia(PF) is widely utilized for the treatment of conditions such as kidney yang deficiency, frequent urination, and cold pain in the waist and knees. However, both basic research and clinical reports indicate that it induce hepatotoxicity. Our preliminary research has confirmed that PF has hepatotoxicity and in vitro research indicated that psoralidin is hepatotoxic. but it remains unclear whether psoralidin is the hepatotoxic component of PF and the mechanism of psoralidin induces hepatotoxicity. This study aimed to investigate the hepatotoxicity induced by psoralidin and its toxic mechanisms. Kunming mice were used to conduct long-term toxicity experiments. Liver function indices, organ coefficients, and histopathological observations were employed to assess the hepatotoxicity of psoralidin. Non-targeted metabolomics and proteomics analyses were conducted to elucidate the potential pathways and targets associated with psoralidin-induced hepatotoxicity. Furthermore, immunofluorescence staining, molecular docking and Western blotting analyses were utilized to validate the mechanisms underlying psoralidin hepatotoxicity. The elevation of ALT and AST, accompanied by hepatic steatosis and lipid droplet aggregation were observed after psoralidin treatement. Psoralidin affected biosynthesis of unsaturated fatty acid, fatty acid metabolism, arachidonic acid metabolism, phospholipid metabolism, and oxidative phosphorylation. Further validation research found that psoralidin induced the expressions of Acot4 and Plin5, which in turn caused up-regulations of TGs and FFA in mice, and increased the HSD17B12 level, thereby promoting the synthesis of long-chain fatty acids and facilitating lipid synthesis. And psoralidin catalyzed the conversion of phosphatidylcholine into LPC by enhancing Pla2g6 and Pla2g12b levels, which promoted the synthesis and accumulation of TGs, ultimately inducing disorders in glycerophospholipid metabolism. Furthermore, psoralidin caused upregulation of ROS and mitochondrial damage, leading to a decrease in FA oxidation. Psoralidin is one of the hepatotoxic components of PF, which induced hepatotoxicity via promoting lipid synthesis and inhibiting lipid oxidative degradation. Show less
Steroid-refractory (SR) disease develops in a substantial fraction of patients with grade II-IV acute graft-versus-host disease (aGvHD) and is associated with poor long-term survival. Improved mechani Show more
Steroid-refractory (SR) disease develops in a substantial fraction of patients with grade II-IV acute graft-versus-host disease (aGvHD) and is associated with poor long-term survival. Improved mechanistic insight is needed to identify reliable predictors of steroid resistance. We retrospectively profiled peripheral blood collected prior to glucocorticoid treatment from allogeneic hematopoietic cell transplantation recipients without aGvHD, with steroid-sensitive aGvHD, and with SR-aGvHD using an integrated multi-omics approach, and validated findings in an independent multicenter cohort. Mass cytometry revealed expansion of activated CD28+ CD8+ effector-memory T (Tem) cells in SR-aGvHD. Absolute counts of these cells at neutrophil engraftment predicted subsequent steroid resistance in the multicenter cohort and performed comparably to established clinical classifiers. This phenotype was associated with a proinflammatory milieu enriched for IL-2, IL-27, and IFN-γ. Single-cell RNA sequencing and functional assays implicated a STAT1-glucocorticoid receptor (GR) regulatory axis in which inflammatory cytokines induce STAT1 phosphorylation and suppress GR expression, consistent with intrinsic glucocorticoid resistance. JAK inhibition rescued cytokine-induced steroid resistance in vitro, while in SR-aGvHD patients, clinical response to ruxolitinib was accompanied by reduced STAT1 activation, restoration of GR expression, and contraction of the expanded CD8+ Tem pool. These findings identify immune dysregulation at SR-aGvHD centered on CD8+ Tem cells with a STAT1-dependent GR deficit and support a mechanistic link to steroid refractoriness. CD28+ CD8+ Tem cell counts may serve as a biomarker of SR-aGvHD and inform development of pre-emptive, pathway-targeted strategies. Show less
Humans and mice display elevated levels of IL-27, an immunosuppressive cytokine shown to increase during neonatal bacterial sepsis and compromise survival. This study explores two hypotheses for regul Show more
Humans and mice display elevated levels of IL-27, an immunosuppressive cytokine shown to increase during neonatal bacterial sepsis and compromise survival. This study explores two hypotheses for regulation of IL-27 expression: 1) decreased DNA methylation in newborns that contributes to increased expression of IL-27 genes; 2) neonatal hormones regulate IL-27 expression through upstream hormone response elements (HREs). Whole genome methyl-seq analysis of neonatal and adult blood-derived macrophages identified differentially methylated regions (DMRs) at steady-state. Quantitative PCR (qPCR) measured expression of IL-27 genes ( The IL-27p28 promoter contained DMRs that were increased in the neonatal cohort. The analysis did not identify DMRs within the EBI3 promoter. Dexamethasone stimulation increased These data suggest glucocorticoid (GC) signaling increases EBI3 expression. This has importance in the context of antenatal GC administration that may increase IL-27 levels. ▪ Elevated expression of IL-27 in early life impairs the host response to invasive bacterial infection in neonates.▪ Understanding the regulatory mechanisms contributing to increased IL-27 during the neonatal period is necessary to reduce susceptibility to infection in this vulnerable population.▪ The methylation status of the IL-27 genes in macrophages from neonatal and adult blood donors does not suggest regulation of differential expression with age.▪ Glucocorticoids are a signal that can induce EBI3 gene expression in a GR-dependent manner.▪ Glucocorticoid therapy for premature infants may increase IL-27 expression and promote enhanced susceptibility to infection. Show less
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HF Show more
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HFD, n = 30). After 8 weeks of HFD feeding, 24 obese rats were further randomised into three subgroups: HFD (H, n = 8), HFD + moderate-intensity training (HMT, n = 8), and HFD + HIIT (HHT, n = 8). The HMT and HHT groups underwent 8 week training interventions (six sessions/week). The HMT protocol included a 10 min warm-up (treadmill speed: 10 m/min), a 40 min moderate-intensity aerobic phase (60%-70% of maximum speed), and a 10 min recovery (10 m/min). The HHT protocol featured 10 min warm-up and recovery phases (10 m/min), with 40 min of alternating treadmill training: 3 min at 50% maximum speed followed by 3 min at 90% maximum speed. No significant differences in body weight were observed between the HHT and HMT groups. HHT rats displayed significantly lower plasma triglyceride levels than H and HMT rats. Compared with HMT, HHT reduced adipose mass and adipocyte size and increased mitochondrial succinate dehydrogenase and cytochrome c oxidase (COX) activities in adipose tissue. However, HHT rats displayed lower COX activity in visceral white adipose tissue than HMT rats. Training upregulated browning-related genes and uncoupling protein 1 (UCP1) in adipose tissue, with stronger effects in HHT than in HMT. Plasma and adipose tissue IL-27 levels, as well as p38 MAPK-PGC-1α signalling pathway activation, were significantly elevated in both training groups, with greater increases in HHT. HIIT promotes adipose tissue browning by activating the IL-27 signalling pathway and ameliorates obesity-associated metabolic disorders more effectively than MAIT, supporting its potential as a therapeutic strategy for obesity. Show less
Probiotics such as The intestinal colonization ability of CIQ249 was assessed using cFDA-SE labeling and flow cytometry. Growth performance and intestinal morphology were evaluated in mice. Antimicrob Show more
Probiotics such as The intestinal colonization ability of CIQ249 was assessed using cFDA-SE labeling and flow cytometry. Growth performance and intestinal morphology were evaluated in mice. Antimicrobial activity of CIQ249 cell-free supernatant was tested against various pathogens, and pathogen damage was visualized by scanning electron microscopy. Protective effects against CIQ249 demonstrated strong intestinal colonization and increased villus height and the villus-to-crypt ratio, contributing to improved growth performance. Its cell-free supernatant selectively inhibited enteropathogens and induced structural damage in CIQ249 enhances mucosal defense against enteropathogenic bacteria through a dual mechanism-strengthening the epithelial barrier and activating a coordinated DC-Tfh-IgA immune axis. These findings provide a multi-level mechanistic basis for its application as a microecological agent against intestinal infections. Show less
Neonatal regulatory T (Treg) cells in secondary lymphoid organs have greater proliferative capacity and more potent suppressive functions than adult Treg cells. However, the phenotypic and functional Show more
Neonatal regulatory T (Treg) cells in secondary lymphoid organs have greater proliferative capacity and more potent suppressive functions than adult Treg cells. However, the phenotypic and functional features of Tregs in neonatal nonlymphoid organs are not well understood. Our prior work demonstrated that thymus-derived Treg cells entering the neonatal mouse liver enhance immune tolerance and periportal liver maturation. Compared to splenic Treg cells, these hepatic Tregs have faster turnover and superior suppression of naïve T-cell proliferation. To further define this population, we conducted single-cell transcriptomic and immunophenotypic analyses of liver- and spleen-derived Tregs from neonatal and adult mice. Our analysis revealed a distinct T-box transcription factor Tbx21 (T-bet) Show less
This study aimed to examine the mechanisms by which Interleukin-27 (IL-27) contributes to the pathogenesis of oral squamous cell carcinoma (OSCC) through focal adhesion-induced stemness protein 1 (FSI Show more
This study aimed to examine the mechanisms by which Interleukin-27 (IL-27) contributes to the pathogenesis of oral squamous cell carcinoma (OSCC) through focal adhesion-induced stemness protein 1 (FSIP1)-mediated activation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway. The effects of IL-27 on cellular proliferation, apoptosis, and migration were examined in human OSCC cell lines [squamous cell carcinoma cell line-27 (CAL-27) and squamous cell carcinoma-4 (SCC-4)] using Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays. Western blot (WB) analysis was performed to determine the expression of epithelial-mesenchymal transition (EMT) markers. High-throughput sequencing was used to identify differentially expressed genes and enriched pathways, while quantitative Polymerase Chain Reaction (qPCR) and WB validated the expression of FSIP1 and PI3K-Akt pathway-related proteins. An oral carcinogenesis mouse model was established using 4-nitroquinoline-1-oxide (4NQO). Following IL-27 treatment, histopathological alterations in tongue tissue were examined with Hematoxylin-Eosin (HE) staining, while IL-27, IL-27 receptor subunit alpha (IL-27RA), FSIP1, and PI3K-Akt pathway proteins were measured through immunohistochemistry and WB. In addition, FSIP1 overexpression vectors and interfering constructs were utilized to examine the regulatory role of FSIP1 in the presence of IL-27. Expression levels of IL-27 and IL-27RA were significantly elevated in OSCC. Treatment with IL-27 enhanced proliferation and migration, suppressed apoptosis, upregulated mesenchymal markers [Neural cadherin (N-cadherin), Vimentin], and downregulated the epithelial marker E-cadherin. Sequencing analysis identified FSIP1 as a key differentially expressed gene enriched in the PI3K-Akt pathway. IL-27 upregulated FSIP1 expression and elevated phosphorylation of PI3K and Akt (p-PI3K/PI3K, p-Akt/Akt). In the murine model, oral carcinogenesis was characterized by epithelial dysplasia, squamous epithelial thickening, and inflammatory cell infiltration. IL-27 treatment intensified these histopathological features and further upregulated protein expression. Overexpression of FSIP1 produced effects comparable to IL-27 treatment by enhancing malignant phenotypes and activating related pathways, while FSIP1 interference mitigated IL-27-induced cellular and molecular changes. IL-27 promotes OSCC progression by upregulating FSIP1, leading to PI3K-Akt pathway activation, enhanced proliferation and migration, and reduced apoptosis. FSIP1 represents a central mediator of the oncogenic activity of IL-27 and may serve as a potential therapeutic target in OSCC. Show less
Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available Show more
Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less
Lung adenocarcinoma (LUAD) exhibits substantial heterogeneity in tumor immune microenvironment (TIME) composition, shaping disease progression and therapeutic response. Here, we integrated transcripto Show more
Lung adenocarcinoma (LUAD) exhibits substantial heterogeneity in tumor immune microenvironment (TIME) composition, shaping disease progression and therapeutic response. Here, we integrated transcriptomic and clinical data from TCGA-LUAD to develop a TIME-associated prognostic model. LASSO Cox regression identified eight key genes-S100P, CPLX2, CD200R1, LINC01857, CLEC7A, CLEC17A, COL6A5, and CX3CR1- that yielded a risk score separating patients into two groups with distinct immune states. High-risk tumors were characterized by diminished CD4 Show less
Psoriasis and atopic dermatitis (AD) are two prevalent inflammatory skin disorders, each characterized by distinct adaptive immune responses. However, recent evidence suggests that these diseases may Show more
Psoriasis and atopic dermatitis (AD) are two prevalent inflammatory skin disorders, each characterized by distinct adaptive immune responses. However, recent evidence suggests that these diseases may share overlapping immune mechanisms, especially concerning keratinocyte function. The specific cytokines that coordinate these inflammatory pathways remain largely undefined. The expression of IL-27 and its receptor was analyzed using data derived from GEO datasets. Imiquimod-induced psoriasis-like and MC903-induced AD-like skin inflammation models were established in wild-type and Il27ra knockout littermates. Skin inflammation was evaluated using clinical scoring, histology, and immunostaining. Flow cytometry was employed to characterize immune cell populations in skin. Expression of relevant cytokines and signaling molecules was assessed using quantitative PCR, bulk RNA sequencing, and Western blotting. We found significantly elevated expression of the IL-27 receptor in the lesional skin of patients with psoriasis or AD. IL-27 receptor-deficient mice exhibited markedly reduced skin inflammation in both psoriasis-like and AD-like murine models. Mechanistic investigations revealed that IL-27 induces tumor necrosis factor-α production via signal transducer and activator of transcription 1 activation in keratinocytes, thereby potentiating inflammatory responses. Our findings identify IL-27 signaling in keratinocytes as a pivotal regulator of skin inflammation in both psoriasis and AD. This highlights IL-27 as a promising therapeutic target for inflammatory skin diseases. Show less
To detect the expression of Interleukin-27 (IL-27) and Interleukin-35 (IL-35) in orbital fat in patients with severe TAO (thyroid-related eye disease) exophthalmos, and to investigate its potential ro Show more
To detect the expression of Interleukin-27 (IL-27) and Interleukin-35 (IL-35) in orbital fat in patients with severe TAO (thyroid-related eye disease) exophthalmos, and to investigate its potential role and significance in the development of TAO. A study group of 30 patients (30 eyes) who underwent orbital decompression with severe TAO exophthalmos in the Department of Ophthalmology, Provincial Hospital affiliated to Shandong First Medical University from January 2022 to December 2023, the expression of IL-27 and IL-35 of the orbital adipose tissue was detected by western-blot, and which in 30 patients (30 eyes) underwent orbital fracture surgery and plastic repair as control group. The contents of IL-27 and IL-35 were higher in severe TAO patients than in normal controls, and the difference was significant ( Show less
Haichao Wang, Hongyi Zhang · 2026 · Immunological investigations · Taylor & Francis · added 2026-04-24
Periodontal disease is a prevalent chronic inflammatory condition of the tooth-supporting tissues characterized by progressive loss of connective attachment and alveolar bone. The IL-12 cytokine famil Show more
Periodontal disease is a prevalent chronic inflammatory condition of the tooth-supporting tissues characterized by progressive loss of connective attachment and alveolar bone. The IL-12 cytokine family-comprising IL-12, IL-23, IL-27, and IL-35-plays key yet divergent roles in shaping periodontal immune responses through heterodimeric subunits and distinct JAK-STAT signaling pathways. These cytokines differentially regulate inflammation, microbial interactions, and bone resorption. This review integrates experimental and clinical evidence assessing IL-12 family members in saliva, gingival crevicular fluid, and periodontal tissues. Studies examining cytokine expression profiles, their correlation with disease activity, microbial dysbiosis, and treatment response were analyzed. Mechanistic data elucidating how IL-12 family signaling modulates inflammatory cascades and osteoclastogenic pathways were also evaluated. IL-12 and IL-23 predominantly amplify pro-inflammatory responses by promoting Th1/Th17 polarization, enhancing neutrophil recruitment, and driving osteoclastogenesis, thereby linking dysbiotic biofilms to tissue destruction. In contrast, IL-27 and IL-35 exhibit context-dependent immunoregulatory properties, inducing IL-10-mediated anti-inflammatory signaling and expanding regulatory T and B cell compartments to support the resolution of inflammation. Across clinical samples, cytokine levels consistently reflect disease severity and demonstrate modulation following periodontal therapy, underscoring their potential as adjunctive biomarkers. Members of the IL-12 cytokine family exert both pathogenic and protective influences in periodontal disease. Therapeutic strategies that suppress IL-12/IL-23-driven inflammation while augmenting IL-27/IL-35-mediated regulation show promise as host-modulatory approaches in periodontal treatment. A deeper understanding of these immunologic dynamics may advance precision-based periodontal therapies. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, ac Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60-70% of all clinically diagnosed cases worldwide. The growing focus on microglia-neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia-neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia-neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia-neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions. Show less
Lipoprotein(a) [Lp(a)] has emerged as a critical determinant of residual cardiovascular risk. However, its impact on plaque morphology remains underinvestigated. This study aimed to elucidate the rela Show more
Lipoprotein(a) [Lp(a)] has emerged as a critical determinant of residual cardiovascular risk. However, its impact on plaque morphology remains underinvestigated. This study aimed to elucidate the relationship between the serum Lp(a) levels, coronary plaque vulnerability, and vascular remodeling characteristics by utilizing intravascular ultrasound (IVUS). We retrospectively enrolled 292 consecutive patients with coronary artery disease who underwent IVUS. Target lesions were classified into vulnerable (n = 83) or stable (n = 209) plaque groups based on the IVUS criteria. Multivariate binary logistic regression was performed to identify independent predictors. The morphological parameters were further compared between the high (＞18.8 mg/dL) and low (≤ 18.8 mg/dL) Lp(a) groups. The vulnerable plaque group exhibited significantly higher median serum Lp(a) levels than the stable group (14.56 vs. 11.04 mg/dL, P = 0.011). After adjusting for age, sex, LDL-C, smoking, diabetes, and hypertension, Lp(a) ＞18.8 mg/dL remained an independent predictor of plaque vulnerability (OR = 1.76; 95% CI: 1.00-3.07; P = 0.049). Notably, the LDL-C levels did not predict vulnerability in this cohort. Furthermore, the high Lp(a) group demonstrated significantly larger vascular dimensions (EEM CSA: 14.67±4.95 vs. 13.22±4.20 mm Elevated serum Lp(a) levels are independent predictors of coronary plaque vulnerability. The underlying mechanism involves Lp(a) promoting compensatory vascular enlargement, accompanied by an increased plaque volume. These findings underscore the necessity of Lp(a) screening to identify any residual risk, particularly in patients with effectively controlled low-density lipoprotein cholesterol (LDL-C). Show less
Aortic aneurysm (AA) is a life-threatening vascular disease with high fatality upon rupture. While physical activity (PA) reduces cardiovascular risk, its role in AA prevention remains uncertain, part Show more
Aortic aneurysm (AA) is a life-threatening vascular disease with high fatality upon rupture. While physical activity (PA) reduces cardiovascular risk, its role in AA prevention remains uncertain, particularly when assessed objectively. We analyzed 93,165 UK Biobank participants (56% women; median age 57 years) with valid 7-day wrist-worn accelerometer data. PA was categorized as light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA). Diagnosed AA was ascertained through linked hospital, death, and primary care records. Cox models estimated hazard ratios (HRs) for AA across quartiles and per-standard deviation (SD) increments, with adjustment for demographic, lifestyle, and cardiometabolic factors. Over a median 7.9-year follow-up, 499 clinically recorded AA cases occurred. Higher accelerometer-measured PA was inversely associated with AA risk. Per-SD increments in total PA, MPA, VPA, and MVPA corresponded to 17%, 22%, 19%, and 23% lower risks, respectively. Compared with the lowest quartile, the highest MVPA quartile had a 44% lower AA risk (HR = 0.56, 95% CI 0.42-0.76). Subtype analyses revealed stronger protective effects for abdominal aortic aneurysm (AAA) than thoracic aortic aneurysm (TAA), while LPA was not significantly associated. These findings demonstrate that higher levels of accelerometer-measured MVPA are robustly associated with a decreased risk of clinically detected AA in a dose-dependent manner. The associations were particularly pronounced for AAA. This study provides objective evidence supporting the potential benefits of MVPA for aortic health. Show less
With the widespread use of smartphones among adolescents, smartphone addiction has become a growing mental health concern. Adolescents' limited self-regulation makes them particularly vulnerable to us Show more
With the widespread use of smartphones among adolescents, smartphone addiction has become a growing mental health concern. Adolescents' limited self-regulation makes them particularly vulnerable to using smartphones to escape real-life stress, heightening addiction risk. However, the heterogeneity of addictive behaviors and the dynamic role of experiential avoidance have been underexplored. This 6-month longitudinal study surveyed 547 Chinese primary and secondary students using the Smartphone Addiction Scale (SAS) and the Acceptance and Action Questionnaire-II (AAQ-II). Latent profile analysis (LPA) and latent transition analysis (LTA) were applied to identify subgroups and examine transitions between these subgroups. Cross-lagged panel network analysis (CLPN) revealed key symptom interactions between experiential avoidance and addiction. The study identified two addiction subgroups: a stable "low-risk group" (84.9 percent) and a "high-risk group," 51.4 percent of whom transitioned to low risk over time. Logistic regression showed that experiential avoidance significantly predicted high-risk membership (odds ratios [OR] = 1.083-1.102) and deterioration within the low-risk group (OR = 1.036). The CLPN identified "online intimacy" (SPA-3) and "hesitation and overcautious" (EA-7) as driver nodes, with "withdrawal symptoms" (SPA-2) serving as a central node. These findings emphasize the crucial role of experiential avoidance in adolescent smartphone addiction and suggest symptom-level targets for early intervention. The results support acceptance and commitment therapy (ACT) as a promising approach for reducing smartphone addiction among youth. Show less
Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, includ Show more
Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the "block-and-lock" strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4 Show less
The purpose of this study was to explore the latent profiles of ambivalence over emotional expression (AEE) in breast cancer patients and its influencing factors. From July 2024 to June 2025, breast c Show more
The purpose of this study was to explore the latent profiles of ambivalence over emotional expression (AEE) in breast cancer patients and its influencing factors. From July 2024 to June 2025, breast cancer patients were recruited using a convenience sampling method from a tertiary hospital in China. A total of 388 participants completed demographic and clinical characteristic questionnaires, the Ambivalence Over Emotional Expression Questionnaire (AEQ), the Perceived Stress Scale-14 (PSS-14), the Social Support Rating Scale (SSRS), and the Irrational Beliefs Scale (IBS). Latent profile analysis (LPA) was used to identify AEE subgroups, followed by univariate analysis, ANOVA, and multinomial logistic regression to examine associated influencing factors. Based on the level of AEE, breast cancer patients were divided into 3 sub groups: "low conflict-active disclosure group " (34.5%), "moderate conflict-inhibition and regret group " (46.5%), and "high conflict-inhibition and regret group " (19.3%). The multivariate logistic regression analysis showed that retirement status, perceived stress, social support and irrational beliefs were factors influencing participants' AEE (P < .05). There was significant variability in AEE among 3 subgroups of breast cancer patients. Retirement status, perceived stress, social support, and irrational beliefs have an impact on AEE in breast cancer patients. It is crucial for healthcare professionals to promptly identify high-risk groups and implement targeted interventions to improve AEE. This study can help healthcare providers identify patients at high risk of AEE, enabling early intervention and targeted psychological nursing interventions. Healthcare providers can assist patients in establishing correct beliefs about their illness and alleviating perceived stress, thereby reducing the negative impact of AEE. Show less
To explore the latent profiles of self-stigma and their relationship with meaning in life among individuals with substance use disorders(SUDs). A total of 1001 participants were recruited from six dru Show more
To explore the latent profiles of self-stigma and their relationship with meaning in life among individuals with substance use disorders(SUDs). A total of 1001 participants were recruited from six drug rehabilitation centers in Sichuan Province between July and August 2025 and completed the self-stigma Scale for Drug Addicts (SSSDA) and the Meaning in Life Questionnaire (MLQ). Latent profile analysis (LPA) was used to identify latent profiles of self-stigma. Multinomial logistic regression was employed to analyze influencing factors, and analysis of variance (ANOVA) was used to compare differences in meaning in life across the different profiles. The self-stigma of individuals with SUDs can be categorized into four latent profiles: the "stigma-resistant profile"(10.0%), "moderate stigma-concealment profile"(46.3%), "internalized stigma profile"(19.5%), and "low internalization-adaptation profile"(24.3%). Among these, the "moderate stigma-concealment profile", "internalized stigma profile", and "low internalization-adaptation profile" represent categories with higher levels of self-stigma. Risk factors associated with these profiles include male sex, low income, a history of being left-behind children, low social support, multiple rehabilitation attempts, as well as mental illness or HIV infection. Statistically significant differences were found among the four profiles in the total score of meaning in life and its sub-dimensions-presence of meaning and search for meaning (p < 0.001). The "stigma-resistant profile" presented the highest level of MIL, whereas the "internalized stigma profile" presented the lowest level. Significant heterogeneity exists in self-stigma among individuals with substance use disorders (SUDs), and the level of self-stigma is significantly negatively correlated with MIL. Show less
Jianlei Liu, Yaling Cui, Hongyu Wang+2 more · 2026 · Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · Blackwell Publishing · added 2026-04-24
With global population aging, the number of older adults in Chinese nursing homes is rising rapidly, and depression is the most prevalent mental health problem in this population. Most previous studie Show more
With global population aging, the number of older adults in Chinese nursing homes is rising rapidly, and depression is the most prevalent mental health problem in this population. Most previous studies assessed depression via total scale scores, ignoring individual heterogeneity of depressive symptoms. This study aimed to identify distinct depressive symptom profiles and their associated factors in this population. Data were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), with 353 valid nursing home older adults included. Depressive symptoms, anxiety and functional status were assessed using the CESD-10, GAD-7 and IADL scales. Latent profile analysis (LPA), univariate tests and multinomial logistic regression were performed, with supplementary effect size and sensitivity analyses to verify result robustness. Three distinct depressive symptom profiles were identified: low level (39%, n = 135), medium level (52%, n = 187) and high level (9%, n = 31). Town residence and anxiety were risk factors for moderate depression, while good self-rated health, regular exercise and social activity participation were protective factors. Good self-rated health protected against severe depression, while occasional television/radio viewing and anxiety were risk factors. Anxiety was the only independent correlate of high-level versus medium-level depression (OR = 1.322, p < 0.001). Supplementary analyses confirmed the robustness of core findings. The CESD-10, as a screening tool, has limited diagnostic efficacy for clinical depression, and the cross-sectional design cannot confirm causal relationships. Depressive symptoms in Chinese nursing home older adults show significant heterogeneity with three distinct latent profiles. Early screening and targeted stratified interventions should be implemented for this population to improve quality of life and promote healthy aging. Show less
Hypertension-linked renal fibrosis leads to the gradual loss of renal function and eventually progresses to end-stage renal failure, which exhibits poor clinical efficacy and is difficult to reverse. Show more
Hypertension-linked renal fibrosis leads to the gradual loss of renal function and eventually progresses to end-stage renal failure, which exhibits poor clinical efficacy and is difficult to reverse. Therefore, clarifying the development mechanism of hypertension-linked renal fibrosis is crucial for its prevention and treatment. In this review, we conducted an in-depth exploration of the pivotal elements, along with their detailed mechanistic linkages in the pathogenesis of hypertension-linked renal fibrosis. It was found that the renin-angiotensin-aldosterone system (RAAS) is overactivated in hypertension. Angiotensin II (Ang II) and aldosterone (Aldo) jointly cause the abnormal accumulation of reactive oxygen species (ROS) by increasing the activity and expression of Nox2 and Nox4, inducing the inhibition and uncoupling of endothelial nitric oxide synthase (eNOS), enhancing expression of selected microRNAs (miRNAs), and reducing glucose-6-phosphate dehydrogenase (G6PD) expression. In turn, elevated ROS trigger renal inflammation by activating the mitogen-activated protein kinase (MAPK)-nuclear factor-kappa B (NF-κB) pathways as well as ferroptosis. Thereafter, renal inflammation can promote the process of renal fibrosis by activating the transforming growth factor β (TGF-β), platelet-derived growth factor (PDGF), and lysophosphatidic acid (LPA). This review not only emphasizes the core role of the mechanistic axis that plays a crucial role in the development of hypertension-driven renal fibrosis-the "RAAS-ROS-inflammation-fibrosis" axis-but also proposes promising therapeutic strategies targeting this axis, including modulating RAAS activity, controlling the increase in ROS, inhibiting inflammation, and blocking fibrotic progression. It aims to provide novel insights and potential therapeutic directions for hypertension-related renal fibrosis in the future. Show less
Psychiatric nurses engage in high levels of emotional labor, which can significantly influence their burnout and job performance. While prior research has linked emotional labor to burnout, the nuance Show more
Psychiatric nurses engage in high levels of emotional labor, which can significantly influence their burnout and job performance. While prior research has linked emotional labor to burnout, the nuanced interplay between different emotional regulation strategies remains underexplored. This study examines the distinct roles of surface acting (modifying outward expressions without changing internal feelings) and deep acting (adjusting internal emotions to align with external expectations) in psychiatric nursing, identifying their differential associations on burnout through network bridge analysis and latent profile analysis. A cross-sectional survey was conducted among 199 psychiatric nurses in a mental hospital in Wenzhou, China. Emotional labor was assessed using the Emotional Labor Scale, and burnout was measured with the Maslach Burnout Inventory-GS. Network bridge analysis was applied to identify key connections between emotional labor strategies and burnout dimensions. LPA was applied to reveal distinct emotional labor patterns. Surface acting emerged as the primary bridge linking emotional labor to burnout, displaying strong associations with emotional exhaustion and depersonalization. LPA identified four emotional labor profiles: These findings highlight the maladaptive effects of surface acting and the protective role of deep acting. Targeted interventions fostering deep acting may enhance psychiatric nurses' well-being and resilience. Future research should explore longitudinal shifts in emotional labor strategies. Show less
Enzyme immobilization is critical for enhancing enzyme stability and reusability. Catalytically active inclusion bodies (CatIBs) have emerged as a promising immobilization strategy due to their straig Show more
Enzyme immobilization is critical for enhancing enzyme stability and reusability. Catalytically active inclusion bodies (CatIBs) have emerged as a promising immobilization strategy due to their straightforward production, ease of separation, and high purity. Unlike traditional cross-linked enzyme aggregates (CLEAs) that require a precipitation step, CatIBs form through carrier-free self-aggregation during expression. To overcome the limitations of conventional methods, a novel technique has been developed in this study, focusing on L-phenylserine aldolase (LPA) as the model enzyme. A hybrid tag (HLHLHL) was fused to the N-terminus of LPA to generate 3HL-LPA, which promotes the formation of active inclusion bodies. Based on structural prediction and surface properties, the active aggregation process of 3HL tags through electrostatic interactions and hydrophobic interactions was analyzed. Innovatively, we combined CatIBs and CLEAs technologies to develop novel CatIBs-CLEAs. For comparison, a control was prepared by fusing a hexahistidine tag (HHHHHH) to LPA's N-terminus (6H-LPA) to enhance soluble expression, followed by conventional CLEAs preparation. Results showed that CatIBs-CLEAs achieved an activity recovery of 69.87% after glutaraldehyde crosslinking, significantly higher than the 48.1% for conventional CLEAs. CatIBs-CLEAs also exhibited superior thermal stability across temperatures, high stability between pH 5-9, and retained over 70% activity after seven batch cycles. The integrated CatIBs-CLEAs technology combines the production advantages of CatIBs with the stability benefits of CLEAs, offering a promising strategy for designing efficient, robust industrial biocatalysts with broad application potential. Show less
Using a person-centered approach, this study examined the heterogeneity of posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) co-occurrence among breast cancer patients and identified Show more
Using a person-centered approach, this study examined the heterogeneity of posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) co-occurrence among breast cancer patients and identified factors associated with distinct latent profiles. A total of 600 breast cancer patients undergoing chemotherapy at a tertiary hospital were recruited. Latent profile analysis (LPA) and multinomial logistic regression were conducted to identify PTSD - PTG profiles and to examine the predictive roles of caregiver burden and demographic variables. LPA identified three distinct profiles: (1) Show less
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-inte Show more
Frailty is associated with increased risks of falls, disability, hospitalization, and mortality. The 24-h movement behaviors (24HMB) framework conceptualizes sleep, sedentary behavior (SB), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) as mutually constrained components of daily time use and may inform frailty prevention and management. This scoping review maps evidence on associations between 24HMB and frailty and identifies methodological gaps to inform future research and nursing practice. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and follows Joanna Briggs Institute (JBI) guidance. We searched PubMed, Embase, CINAHL, and Web of Science. We included observational studies of adults aged ≥18 years. Exposures were objectively measured or validated self-reported sleep, SB, LPA, and MVPA, including step counts, breaks in SB, isotemporal substitution models (ISM), and compositional data analysis (CoDA). Outcomes were frailty or prefrailty assessed using validated instruments. Quality was appraised with JBI tools. Thirty-three studies showed good methodological quality. Longer SB, particularly prolonged, uninterrupted bouts, was associated with higher frailty. Greater MVPA was consistently associated with lower frailty. Light-intensity physical activity was generally beneficial but often attenuated when MVPA or total activity volume was modeled. Sleep fragmentation and poor sleep quality were associated with frailty. Isotemporal substitution models and compositional data analysis indicated that reallocating sedentary time to MVPA would yield the largest theoretical benefit, followed by reallocating to LPA. Higher daily step counts and more frequent or higher-intensity breaks in SB were associated with lower frailty. Evidence supports a 24-h integrated movement-behavior approach centered on MVPA, combined with reducing prolonged SB and improving sleep quality, for the prevention and nursing management of frailty. The study design and analytical protocol were prospectively registered on the Open Science Framework (OSF). The unique identifier is S39Y4, and the publicly accessible URL is https://doi.org/10.17605/OSF.IO/S39Y4. Show less