👤 Wei Yang

Focal articular cartilage defects often progress to osteoarthritis, imposing a substantial global health burden. Current neglect of cartilage developmental regulation and cartilage microenvironment compromises therapeutic efficacy. We developed an innovation CE-SKP/CPH/P2G3 scaffold which effectively repairs focal cartilage defects and emulates native cartilage ontogeny: the superficial CE-SKP hydrogel layer recruits SMSCs and promotes chondrogenesis; the middle CPH hydrogel layer induces chondrocyte hypertrophic calcification, forming cartilage calcified layer; and the basal P2G3 nanofiber membrane isolates subchondral cells, enforcing a top-down developmental sequence and preserving a localized hypoxic niche. Show less

Chemotherapy-induced myelosuppression (MYE) remains a major dose-limiting toxicity that severely compromises treatment efficacy and patient outcomes, while effective therapeutic agents are still lacking. This study aimed to evaluate the therapeutic effects of 20(S)-protopanaxadiol-human serum albumin nanoparticles (20(S)-PPD-HSA NPs) on cyclophosphamide-induced MYE and to elucidate the underlying mechanisms. 20(S)-PPD-HSA NPs were characterized by electron microscopy, particle size, zeta potential, drug loading, and encapsulation efficiency. A cyclophosphamide-induced MYE mouse model was established. Hematopoietic recovery was evaluated via blood counts, ELISA for granulocyte colony-stimulating factor (G-CSF), and flow cytometry for Lin The 20(S)-PPD-HSA NPs exhibited a uniform nanostructure and excellent drug delivery performance. In vivo, the 20(S)-PPD-HSA NPs significantly alleviated cyclophosphamide-induced hematopoietic dysfunction, restored the structure of bone marrow and spleen tissues, and markedly increased the number of LSK cells, with their therapeutic effect being independent of elevated G-CSF levels. Further studies demonstrated that the 20(S)-PPD-HSA NPs activated the FGFR1/ERK signaling pathway, an effect that was partially blocked by FGFR1 or ERK inhibitors. In vitro, 20(S)-PPD-HSA NPs promoted the proliferation of OP9 cells and murine splenic stromal cells, inhibited apoptosis, DNA damage, and cellular senescence, and upregulated SCF and SDF-1 expression via activation of the FGFR1/ERK pathway. Co-culture experiments further confirmed that the NPs improved the hematopoietic microenvironment and enhanced the stromal cells' hematopoietic support function. 20(S)-PPD-HSA NPs effectively enhanced medullary and extramedullary hematopoietic functions in cyclophosphamide-induced MYE mice by activating the FGFR1/ERK pathway, independent of increased G-CSF levels. These findings highlight 20(S)-PPD-HSA NPs as a promising therapeutic strategy for chemotherapy-induced myelosuppression. Show less

Fibroblast growth factor receptor 2 (FGFR2) has gained recognition as a compelling therapeutic target in oncology. We present LHQ766, a novel orally bioavailable FGFR2 inhibitor demonstrating exceptional potency and selectivity, through optimization of our previously reported FGFR2 inhibitor 7. The structures and purity of all target compounds were confirmed by Show less

A plethora of factors contribute to cognitive impairment in Alzheimer's disease (AD), including neuroinflammation, synaptic dysfunction and gene alteration. In search of transcription factors controlling dysregulated genes in AD, we identified that the histone demethylase PHF2 (KDM7C) was a top-ranking candidate. Significant upregulation of PHF2 was found in AD human postmortem tissues, iPSC-derived neurons from AD patients, and a familial AD mouse model (5xFAD). ChIP-seq analysis and quantitative PCR profiling with bidirectional manipulation of Phf2 revealed that Phf2 regulated many genes critically involved in inflammatory pathways and neurodegeneration, including Stat3, Nfkbia, Nfkb2, Tnfrsf1a, Fgfr1, IL6st, Notch2, and Csf1. Knockdown of Phf2 in 5xFAD mice reduced the expression of inflammatory genes, leading to the substantial reduction of microglia/astrocyte activation and the restoration of glutamatergic synaptic function. Behavioral studies showed that Phf2 knockdown in 5xFAD mice significantly improved performance in the Barnes maze test, indicating a mitigation of spatial memory deficits. Our findings have revealed the epigenetic enzyme PHF2 as a regulator of neuroinflammatory processes in AD, linking its activity to both gene expression and cognitive outcomes. It suggests that targeting PHF2 could be a novel therapeutic approach for AD and other brain disorders involving neuroinflammation. Show less

Molecular genetic testing was performed on a fetus with ectrodactyly of the right foot to clarify the pathogenic cause and provide evidence for prenatal counseling. Trio whole-exome sequencing (trio-WES) was performed on the fetus and his parents to identify the underlying genetic cause. Candidate variants were validated by Sanger sequencing, and their molecular effects were analyzed through minigene assays. Trio-WES identified a novel heterozygous variant (c.1977+1G>C) in FGFR1, which is consistent with FGFR1-related Hartsfield syndrome (HS; OMIM#615465). Sanger sequencing confirmed that this variant was de novo. The minigene assay revealed that all variants (c.1977+1G>C, c.1977+1G>A, and c.1977+1G>T) at the splice site generated two aberrant splicing events: (1) complete retention of intron 14, leading to a frameshift and premature termination codon; and (2) skipping of exon 14, causing an in-frame deletion of 41 amino acids. These events collectively impaired the function of the FGFR1 protein's tyrosine kinase domain. To our knowledge, prenatal reports of FGFR1-related HS remain extremely limited, and this is the first molecularly confirmed prenatal diagnosis of HS in China. The findings not only expand the mutational spectrum of HS but also provide genetic counseling and reproductive guidance for this family. Show less

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

This study aimed to identify breast cancer-specific circulating tumor DNA (ctDNA) methylation markers that correspond to tissue DNA methylation. Using The Cancer Genome Atlas (TCGA) database, we selected breast cancer-specific DNA methylation markers. The methylation and expression patterns of candidate genes were analyzed in breast cancer cell lines and tissue samples. We also assessed the methylation status in ctDNA obtained from breast cancer patients and examined associations with the clinicopathological features. Among candidate genes with breast cancer-specific methylation patterns, USP44, ZNF454, and GPRC5B were selected. The methylation status and expression of selected genes varied by molecular subtype of cancer in the cell line. In tissue samples, expression of all three genes was generally lower in breast cancer than in controls. ctDNA methylation patterns showed no significant change before and after treatment for each candidate gene. Correlations between gene expression and DNA methylation status or clinicopathological characteristics in cancer tissues differed among genes. Further studies are needed for clinical application of liquid biopsy using methylation analysis for ctDNA according to individual characteristics for breast cancer. Show less

Macrophages differentiated with macrophage colony-stimulating factor (M-CSF) (M-Mac) are widely used as an experimental model. Interleukin 27 (IL-27)-polarized M-Mac (27M-Mac) suppresses HIV replication; however, the effects of IL-27 polarization on granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages (GM-Mac) remain less investigation. Here, we compare multiple functional properties and gene expression profiles of 27M-Mac and IL-27-polarized GM-Mac (27GM-Mac). M-Mac and GM-Mac were generated from monocytes of healthy donors and subsequently treated with IL-27 for three days. HIV replication in 27M-Mac, GM-Mac, and 27GM-Mac was suppressed to nearly 10% of that in M-Mac; however, single-cell RNA sequencing showed that M-Mac clustered with GM-Mac, and 27M-Mac clustered with 27GM-Mac. Expression of CD38 and secretion of CXCL9 and C1q were significantly increased in 27M-Mac and 27GM-Mac compared with M-Mac and GM-Mac. Although CD16 and CD64 expression increased in 27M-Mac and 27GM-Mac relative to their respective controls, phagocytic activity in 27M-Mac and 27GM-Mac was 30% of that in M-Mac. Autophagy was promoted 3.7-fold more strongly in 27M-Mac than in M-Mac, reaching levels comparable to those in GM-Mac and 27GM-Mac. Collectively, these findings indicate that IL-27 polarizes M-Mac and GM-Mac toward transcriptionally and functionally similar subtypes, providing insight into the role of IL-27 in macrophage polarization and plasticity. 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 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

Skeletal muscle atrophy is a common complication of heart failure, with myocardial infarction (MI) being the primary cause. Yet, the mechanisms linking post-MI cardiac insufficiency to muscle atrophy have remained unclear. The molecular basis for the beneficial effects of exercise on exercise intolerance in MI patients also remains absent. Serum IL-27 levels were measured in 48 MI patients and correlated with cardiac injury markers. Along with this, a rat model of post-MI cardiac insufficiency was used to assess skeletal muscle mass, cross-sectional area (CSA) of muscle fibers, and the expression of atrophy-related (MAFbx, MuRF-1) and differentiation-related markers (MyoD, Myogenin). The impact of exercise on muscle atrophy, cardiac inflammation, and IL-27 expression was then evaluated, with a focus on macrophage polarization. Serum IL-27 level was significantly elevated in MI patients and that it was positively correlated with myocardial injury and cardiac insufficiency. In post-MI rats, skeletal muscle mass and CSA of muscle fibers were reduced. Meanwhile, the expression level of myogenic markers was downregulated, while that atrophy markers was upregulated. IL-27 treatment promoted catabolism in L6 myotubes, and of note, HIF-1α overexpression in macrophages enhanced IL-27 secretion, and increased MAFbx and MuRF-1 expression. IL-27 level was also elevated in the heart, serum, and gastrocnemius muscle of MI rats. Exercise counteracted these effects by promoting M2-like macrophage polarization and suppressing HIF-1α, thereby reducing IL-27 expression. Furthermore, exercise ameliorated IL-27-induced muscle atrophy via the WSX-1/gp130/pSTAT3 signaling axis. IL-27 contributes to muscle atrophy in post-MI cardiac insufficiency. Exercise attenuates IL-27-driven muscle wasting by modulating inflammation and promoting M2-like macrophage polarization. These findings provide insights into the mechanisms of MI-induced muscle atrophy and highlight the therapeutic potential of exercise in cardiac rehabilitation. [Image: see text] The online version contains supplementary material available at 10.1186/s12967-025-07527-7. 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 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

The aim of this study was to investigate the impact of interleukin-27 (IL- 27) gene polymorphism and additional interactions with environmental factors on non-small cell lung cancer (NSCLC) risk based on a Chinese population. SNPStats online software ( http://bioinfo.iconcologia.net/SNPstats ) was used for Hardy-Weinberg equilibrium (HWE) testing. Stratified analysis was performed by logistic regression model to examine the impact of IL- 27 gene SNPs and environmental factors, and additional gene-environment interaction on NSCLC risk. Logistic regression analysis showed a significant association between rs153109, rs181206 and increased NSCLC risk. However, no significant relationship was found between NSCLC risk and rs17855750 or rs40837 genotype with minor allele. Logistic regression also indicated a significant association between smoking status or alcohol consumption and NSCLC risk in this study. We performed crossover analysis to investigate the interaction between two SNPs (rs153109 and rs181206) and two environmental factors (smoking status and alcohol consumption) using logistic regression. We found that ever or current smokers with rs153109- AG or GG genotype have the highest NSCLC risk, compared with never smokers with the AA genotype after covariate adjustment, OR (95%CI) = 3.02 (1.97-5.12), p = 0.012. However, no significant interaction effect was found between rs153109 and alcohol consumption, rs181206 and smoking, rs181206 and alcohol consumption. Our results support an important association of the IL- 27 gene rs153109, rs181206, smoking and alcohol consumption with increased NSCLC risk. We also found a significant impact of an interaction between rs153109 minor allele and ever or current smoking on NSCLC risk. Show less

Persistent chronic hepatitis B virus (HBV) infection leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The immunosuppressive tissue microenvironment in the liver restricts the immune response, potentially facilitating persistent HBV infection. This study examined the expression of immunity-related factors in the liver in response to HBV. We performed gene expression profiling on mice subjected to HBV DNA hydrodynamic transfection to identify transcriptomic changes. The expression of IL-27 was validated through Western blotting, ELISA, and immunohistochemical staining. Liver macrophages in mice were depleted using clodronate-liposomes to evaluate their role in IL-27 production. IL-27 knockout mice were generated to examine the effects of IL-27 deficiency on CD8 T cell dysfunction and HBV persistence. Transcriptomic analysis demonstrated that IL-27 is significantly induced in the liver in response to HBV DNA. The elevated levels of IL-27 are strongly correlated with HBV persistence and are linked to CD8 T cell dysfunction, characterized by increased expression of PD-1 and Tim-3, along with reduced IFN-γ production in liver-infiltrating T cells. Furthermore, depleting macrophage-lineage cells using clodronate-liposomes significantly reduces IL-27 production in the liver and promotes viral clearance. Additionally, mice with IL-27 deficiency exhibit enhanced HBV clearance and restored CD8 T cell function. Collectively, IL-27 is significantly induced by HBV in the liver, and its production is strongly associated with HBV persistence and CD8 T cell dysfunction. This highlights the immunosuppressive role of IL-27 in the liver microenvironment and suggests that IL-27 could serve as a potential therapeutic target for HBV infection. Show less

Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to cancer progression remain poorly understood. Here, we identified a lung cancer-specific chimeric RNA KANSL1-ARL17A (chKANSARL) and its circular variant fusion circular RNA KANSL1-ARL17 A (F-circKA), both derived from the fusion gene KANSARL. Functional assays revealed that overexpression of either chKANSARL or F-circKA significantly enhanced lung cancer cell proliferation, migration, and invasion, while their knockdown suppressed these malignant phenotypes. In vivo experiments demonstrated that chKANSARL overexpression accelerated tumor growth in immunodeficient mice. Notably, coexpression experiments uncovered a synergistic regulatory interaction between F-circKA and chKANSARL, amplifying oncogenic effects. Mechanistically, miRNA sequencing and dual-luciferase assays revealed that F-circKA acts as a molecular sponge for miR-6860, thereby derepressing chKANSARL expression. Rescue experiments further validated this regulatory axis, wherein miR-6860 inhibition reversed the tumor-suppressive effects of F-circKA knockdown. Collectively, our study identifies and characterizes a novel F-circKA/miR-6860/chKANSARL regulatory axis, revealing how dual transcriptional outputs from the KANSARL fusion gene can synergistically drive lung cancer progression. These findings highlight a previously unrecognized layer of cooperative regulation between linear and circular fusion RNAs in oncogenesis and provide a new framework for understanding fusion gene-mediated tumorigenesis. 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, 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

This study aimed to identify CSF and plasma proteins that mediate the association between age and mild cognitive impairment (MCI) and Alzheimer's disease using mediation analysis. By focusing on proteins significantly associated in both CSF and plasma, we sought to identify biomarkers accessible for clinical applications. Proteomic measurements were obtained from CSF and plasma from a cohort of cognitively normal and MCI patients at the Johns Hopkins Alzheimer's Disease Research Center using Olink Proximity Extension Assay technology. Mediation effects were estimated using single- and multiple-mediator models and validated in three independent datasets: Duke (CSF), ADNI (CSF), and UK Biobank (plasma). Over 3000 proteins in 86 patients were analyzed. Three candidates, leiomodin-1 (LMOD1), glial fibrillary acidic protein (GFAP), and elastin (ELN), met the criteria for mediation in both CSF and plasma. Multiple mediator models demonstrated a significant combined mediation effect on MCI in CSF (OR: 1.122, 95 % CI: 1.026-1.439) and plasma (OR: 1.142, 95 % CI: 1.058-1.410). Across validation cohorts, GFAP consistently showed significant mediation effects (Duke CSF: OR: 1.114, 95 % CI: 1.069-1.206; ADNI: OR: 1.004, 95 % CI: 1.000-1.009; UK Biobank: OR: 1.030, 95 % CI: 1.026-1.034). In contrast, ELN and LMOD1 demonstrated mediation effects in the discovery dataset but were not consistently reproduced in external cohorts. Our findings highlight GFAP as a robust mediator of age-related risk of cognitive impairment across CSF and plasma, supporting its utility as a practical biomarker. ELN and LMOD1 may represent exploratory candidates reflecting extracellular matrix and vascular processes requiring further validation. Show less

To explore the associations between accelerometer-measured physical activity patterns and cardiovascular diseases (CVD), CVD-cause mortality, and all-cause mortality in people with osteoarthritis (OA). OA participants from the UK biobank with ≥36 h of accelerometer data, collected over one-week, were analyzed. Moderate to vigorous physical activity (MVPA) patterns were classified as: 'weekend warriors' (≥150 min/week, >50% on 1-2 days), active regular (>150 min/week), or inactive (<150 min/week). Mean min per week of light physical activity (LPA) were categorized into quartiles based on the distribution in the analytical sample. Among 10 210 study participants (mean age 58.1 ± 7.1 years; 64.5% female) followed for a median of 6.9 years, there were 1,538 incident cases of CVD, and 358 deaths, including 90 from CVD. Compared with inactive MVPA, both weekend warrior (adjusted hazard ratio, aHR (95% CIs); 0.73 (0.64-0.82)) and active regular MVPA (0.75 (0.65-0.87)) significantly lowered the risks of incident CVD. Notably, only the weekend warrior group showed significant reductions in CVD-cause mortality (0.55, 0.33-0.92), and all-cause mortality (0.75 (0.59-0.96)). Higher levels of LPA may link to lower CVD, CVD-cause mortality, and all-cause mortality risks in a dose-response manner. Subgroup analysis indicated that more prominent associations were found in individuals with a body mass index >30 or those aged over 60. Engaging in a weekend warrior pattern may confer unique survival benefits for OA patients, especially among older adults and those with obesity. LPA may have dose-dependent protective effects for CVD and mortality risk in OA patients. Show less

Falls have long been a significant safety concern worldwide, not only compromising the physical and psychological health of older adults and limiting their social engagement but also imposing substantial economic and caregiving burdens. Evidence on fall risk perception among Chinese community-dwelling older adults remains limited, especially for those transitioning to community living after hospital discharge. This research examined the subtypes of fall risk perception of Chinese community-dwelling older adults in the post-discharge transition and to explore subgroup characteristics and associated factors. A cross-sectional survey was conducted between January 2024 to March 2025 in Hangzhou, Zhejiang Province. A self-designed questionnaire was used to collect demographic and health-related information, The Fall Risk Perception Scale for Community-dwelling Older Adults was used to assess the fall risk perception, the objective fall risk was assessed by Morse Fall Scale. Latent profile analysis (LPA) was performed to extract latent classes of fall risk perception, and multinomial regression analyses were used to identify differences between these categories. A total of 468 older adults were included, with 56.0% were male. Three fall risk perception subtypes were identified by LPA: Low Perception-Social Context Desensitized Type (29.2%), Moderate Perception - Balanced Type (43.4%), and High Perception - Bio-behaviorally Salient Type (27.4%). Individuals who were aged with 70-79 (OR = 0.46, 95% CI: 0.27-0.77), with college education or above (OR = 0.31, 95% CI: 0.13-0.76), those who underwent surgery during hospitalization (OR = 0.26, 95% CI: 0.15-0.43), reported difficulty falling asleep (OR = 0.40, 95% CI: 0.20-0.82), and those with a history of falls (OR = 0.44, 95% CI: 0.24-0.81) were significantly more likely to be in the High Perception - Bio-behaviorally Salient Type. Compared to objective fall risk level, a third of participants (31.4%) correctly estimated their fall risk, 23.1% overestimated it and 45.5% underestimated it. Most older adults possess a Moderate Perception - Balanced Type toward fall risk. Key determinants of heightened risk perception included advanced age, higher education, fall history, and recent surgical experience. Tailored, profile-specific risk communication strategies are essential to improve perceptual accuracy during the hospital-to-home transition may support post-discharge fall prevention. Show less

This study employs latent profile analysis (LPA) to identify potential categories of nurse burnout and to analyze differences in characteristics and influencing factors across burnout categories. From June to August 2025, a mixed sampling approach combining convenience and snowball sampling was used to recruit nurses from hospitals of varying levels in Southwest China. Three tools were used for data collection: A self-designed routine information questionnaire, Maslach Burnout Inventory-General Survey (MBI-GS) and Practice Environment Scale of the Nursing Work Index (PES-NWI), LPA identifies potential categories of nurses' professional burnout and uses multivariate logistic regression analysis to explore the factors associated with these categories. This study comprised a total of 809 participants. LPA identified four distinct latent classes of nursing burnout: Class 1, low-burnout-high-efficacy (11.5%); Class 2, mild-burnout-unfulfilled (33.9%); Class 3, moderate-burnout-exhausted (44.6%); and Class 4, severe-burnout-dysfunctional (10.0%). Multivariate logistic regression analysis showed that age, years of work experience, hospital level, nurses' participation in hospital management, nursing quality standards, staffing and resource adequacy, and medical care cooperation are significant predictors of burnout among nurses ( Nurse burnout in southwest China is mainly moderate to severe and exhibits distinctive characteristics. It is recommended to implement personalized interventions tailored to the specific characteristics of nurses' professional burnout to alleviate the situation. Particular attention should be given to nurses with fewer than five years of experience by providing enhanced job support and psychological assistance to help them navigate critical periods of professional burnout. These measures aim to safeguard nurses' physical and mental health, improving the overall quality of nursing, and promoting the healthy development of global medical care. Show less

Based on self-determination theory (SDT), this study aimed to identify latent profiles of health motivation characteristics among young and middle-aged individuals with prediabetes and to examine their associations with self-management behaviours and metabolic risk indicators. This cross-sectional study recruited individuals with prediabetes from January 2024 to January 2025 using a convenience sampling method, enrolling 309 participants. Health behaviour motivation, basic psychological needs, prediabetes-related disease knowledge and self-management were assessed using validated questionnaires. Latent profile analysis (LPA) was conducted to identify distinct subgroups. Multinomial logistic regression was used to examine demographic, lifestyle and clinical factors associated with profile membership. Three types of health motivation characteristics were identified: high psychological need satisfaction-autonomous motivation profile (24.0%), moderate psychological need satisfaction-externally controlled motivation dominant profile (15.0%) and low psychological need satisfaction-low motivation profile (61.0%). After adjustment, BMI, comorbidity history and occupation were significantly associated with profile membership, whereas distance to primary healthcare facilities showed a non-robust pattern. Significant heterogeneity exists in health motivation characteristics among young and middle-aged individuals with prediabetes, with the low psychological need satisfaction-low motivation profile representing the largest proportion. Incorporating motivation-oriented stratification into diabetes prevention strategies may provide a useful framework for delivering tailored interventions and supporting more sustainable self-management. Show less

It remains unclear if Yes-associated protein (YAP) is involved in the protection of melatonin against myocardial ischemia/reperfusion (I/R) injury by regulating mitochondrial fission. In this experiment, an in vivo myocardial I/R injury model was used. Animals were randomly assigned to receive the different interventions: Sham, I/R, 10 mg melatonin, 20 mg melatonin, lysophosphatidic acid (LPA, a YAP agonist), LPA + melatonin, verteporfin (a YAP antagonist) and verteporfin + melatonin. Myocardial infarct size and serum cardiac enzyme levels were measured. Histopathological features, mitochondrial morphology, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, apoptosis, and dynamic-related protein 1 (DRP1) and YAP expressions of the I/R myocardium were also evaluated. We observed that melatonin postconditioning significantly reduced myocardial infarct size, ameliorated histological changes, and decreased oxidative stress and apoptosis in the I/R myocardium. These protective effects were associated with enhanced YAP nuclear translocation, increased p-DRP1 Ser637 expression and decreased p-DRP1 Ser616 expression. Activation of YAP with LPA demonstrated a protective effect against myocardial I/R injury, while inhibition of YAP with verteporfin exacerbated myocardial I/R injury and significantly attenuated the protective effect of melatonin postconditioning against myocardial I/R injury. These findings suggest that melatonin postconditioning confers cardioprotection by activating YAP to preserve mitochondrial ultrastructure and attenuate excessive DRP1-mediated fission. These structural changes may contribute to the observed reduction in myocardial injury. While these findings identify YAP activation as a potential therapeutic target, the limited dose range tested precludes determination of an optimal cardioprotective dose. Further studies defining the full dose-response relationship are still necessary to inform potential clinical translation. Show less

The engagement and burnout profiles of preschool teachers are closely linked to young children's developmental outcomes. This study investigated engagement and burnout profiles among 529 Chinese preschool teachers in relation to their emotional states, varying experiences, and professional backgrounds. The sample predominantly consisted of early-career educators, with 47.8% aged between 21 and 30 years and 33.1% having 0-5 years of work experience. Using a quantitative cross-sectional design and latent profile analysis (LPA), this study identified four distinct profiles: slightly exhausted (48.58%), moderately burned out (18.53%), engaged (25.90%), and highly burned out (6.99%). Positive emotional states, such as enjoyment, were associated with higher work engagement, while anxiety was associated with a higher probability of belonging to burnout profiles. In contrast, perceived career success and negative emotions like anger did not significantly predict work engagement and burnout profiles. Teachers with extensive teaching experience and pre-service early childhood education (ECE) training were more likely to maintain high work engagement. This study highlights the critical role of emotional states and professional ECE training in promoting preschool teachers' work engagement and sustainable practice, particularly among early-career teachers. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Structurally composed of a low-density lipoprotein (LDL)-like particle covalently linked to apolipoprotein(a) [apo(a)], Lp(a) exhibits unique atherogenic, thrombogenic, and inflammatory properties, largely due to its role as a carrier of oxidized phospholipids (OxPL). Plasma Lp(a) concentrations are predominantly determined by the number of kringle IV type 2 (KIV-2) repeats in the LPA gene, with minimal influence from lifestyle or environmental factors. Despite substantial evidence linking elevated Lp(a) to cardiovascular risk, clinical testing remains underutilized, especially in East Asian countries. In Taiwan, although population-level Lp(a) concentrations are comparatively low, a significant subset exceeds risk thresholds, with local studies confirming its prognostic value in coronary artery disease and ischemic stroke. Barriers, including limited physician awareness, implementation barriers, and therapeutic nihilism, contribute to its under-recognition. This review highlights the molecular features of Lp(a), its pathogenesis of cardiovascular disorders, epidemiology, and current barriers and future advances in diagnostic testing, with a particular focus on implications for cardiovascular risk management in Taiwan. Show less

Family members of patients with digestive tract cancer represent a high-risk population for cancer development due to shared genetic and lifestyle factors, yet their own disease self-monitoring behaviors remain largely uncharacterized. Understanding the typologies and determinants of these behaviors is essential for precision prevention. A cross-sectional study was conducted among 414 family members of hospitalized patients with esophageal, gastric, or colorectal cancer in Sichuan Province, China (March-October 2023). Self-reported data were collected using validated questionnaires assessing socio-demographics, cancer risk perception, and digestive tract cancer self-monitoring behaviors. Latent profile analysis (LPA) was applied to identify subgroups of monitoring behaviors, and multinomial logistic regression was used to determine influencing factors. LPA revealed three distinct behavioral profiles: poor behavior group (47.10%), average behavior group (38.16%), and good behavior group (14.74%). The mean total self-monitoring score was 2.76 ± 0.69. Multivariate analysis showed that low educational level, family per capita monthly income ≤ 2000 CNY, and not living with patient were significant risk factors for poor monitoring behaviors. Conversely, having existing chronic disease and higher cancer risk perception were strongly associated with better monitoring performance. Nearly half of family members of digestive tract cancer patients exhibit insufficient self-monitoring of early symptoms. Education level, family per capita monthly income, cohabitation, comorbidity, and cancer risk perception are key determinants of behavioral heterogeneity. Tailored, risk-profile-based interventions that enhance risk awareness and promote regular screening are urgently needed to strengthen family-centered cancer prevention. Show less

Previous studies have indicated that Kinesiophobia is associated with adherence to exercise rehabilitation. Given the multifaceted impact of Kinesiophobia and the complex diversity of individual characteristics, existing research struggles to identify the distinct features of Kinesiophobia. Latent Profile Analysis (LPA) identifies individuals’ latent traits based on their response patterns to observable measures, grouping individuals with similar symptom profiles into different categories, thereby better distinguishing differences among individuals. However, there is currently a lack of research on the kinesiophobia in the out-of-hospital early rehabilitation phase after Percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Therefore, the aim of this study is to investigate kinesiophobia in the out-of-hospital early rehabilitation phase after Percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD), classify it based on latent profile analysis, and explore the related factors of Kinesiophobia in CHD patients across different categories. This study selected coronary heart disease patients who were in the early outpatient rehabilitation stage after receiving PCI treatment at a tertiary hospital as the survey subjects. Latent Profile Analysis (LPA) was employed to fit potential classes of kinesiophobia among these patients. Chi-square tests, Kruskal-Wallis tests, and multinomial logistic regression were utilized to explore the factors influencing different kinesiophobia profiles in these patients. A total of 293 survey subjects were included, the age of the 293 patients was 62.31 ± 11.49 years, Males represent 77% of the total population. The results of potential profile analysis revealed that kinesiophobia in the out-of-hospital early rehabilitation phase of CHD in PCI-treated patients could be divided into three potential categories: the low kinesiophobia-exercise avoidance group (52.1%), the medium kinesiophobia-danger perception group (41.6%), and the high kinesiophobia-dysfunction group (6.3%). The logistic regression analysis results revealed that age, mode of residence, chronic comorbidities, polypharmacy, and debilitation were influential factors for different categories of kinesiophobia in the out-of-hospital early rehabilitation phase of CHD patients undergoing PCI. There is obvious group heterogeneity in kinesiophobia in the out-of-hospital early rehabilitation phaseof CHD patients undergoing PCI, and healthcare professionals should carry out individualized intervention Strategies to reduce the degree of kinesiophobia in patients on the basis of the characteristics and influencing factors of different categories. Show less

Diabetic foot (DF) is a serious diabetes complication that increases ulceration, amputation and mortality risks. Effective foot self-care can prevent up to 85% of ulcer events. This study aimed to assess foot self-care behaviors among middle-aged and older DF patients, evaluate the impact of social support, and explore the mediating effects of frailty and fear of progression (FoP). We also identified patient subtypes using latent profile analysis. A cross-sectional study was conducted in a tertiary hospital from November 2024 to March 2025. A total of 361 patients with DF aged ≥45 years completed validated questionnaires, including the Social Support Rating Scale (SSRS), FRAIL Scale, FoP-Q-SF, and DFSQ-UMA. Structural equation modeling (SEM) assessed mediation effects, and latent profile analysis (LPA) identified subgroups based on frailty and FoP. A total of 383 questionnaires were distributed, with 361 valid responses collected, resulting in an effective response rate of 94.3%. The average score for foot self-care behavior was 58.52 ± 13.46, while levels of social support, frailty, and FoP were all at moderate levels. SEM indicated that Social support significantly predicted better foot self-care behavior (β = 0.225, P < 0.01). Frailty and FoP partially mediated this relationship (mediation effect: 6.68%). LPA identified three types of physical and mental profiles: Low FoP - Low Frailty Group (75.1%), Moderate FoP - Moderate Frailty Group (15.2%), and High FoP - High Frailty Group (9.7%). Importantly, patients in the High FoP-High Frailty Group demonstrated the lowest foot self-care behavior (mean = 43.70, P < 0.001), indicating the highest potential risk for ulcer occurrence and poor tissue outcomes. Social support enhances foot self-care in DF patients through reduced Frailty and FoP. Tailored interventions targeting high-risk subgroups may improve tissue outcomes and prevent ulcers. Show less

Lipoprotein(a) [Lp(a)] represents one of cardiovascular medicine's most profound implementation gaps: a genetically determined risk factor affecting 1.5 billion people worldwide, yet historically underutilized in clinical practice despite overwhelming evidence of its importance. This review examines the transformation of Lp(a) from an untreatable genetic burden to a promising therapeutic target through four interconnected perspectives. First, we document the implementation gap, where, despite affecting 20% of the global population, screening remains below 1%. The evolution from selective screening (2018 American College of Cardiology/American Heart Association (ACC/AHA)) to universal measurement (2024 National Lipid Association (NLA) Class I recommendation) reflects growing recognition, yet persistent barriers, including reimbursement challenges, provider knowledge gaps, and laboratory standardization issues, perpetuate underutilization. Second, we synthesize evidence establishing Lp(a)'s dual nature as both a biomarker and a causal factor. Observational studies demonstrate markedly increased cardiovascular risk with elevated Lp(a), while Mendelian randomization confirms causal relationships with coronary heart disease, large-artery stroke, peripheral artery disease, and aortic stenosis, with differential effects on stroke subtypes and non-atherosclerotic outcomes. Third, we examine the transformation from genetic determinism to pharmacological tractability. Despite 70-90% heritability, novel RNA-targeted therapies achieve unprecedented 80-95% reductions, with phase 3 cardiovascular outcome trials (completing 2026-2029) poised to determine whether dramatic Lp(a) lowering translates to clinical benefit. Finally, we provide a practical management algorithm bridging current evidence-based risk stratification with emerging therapies, stratifying patients by Lp(a) levels with corresponding interventions. The Lp(a) story exemplifies how genetic insights and technological innovation can transform immutable disease aspects into treatable conditions, offering a paradigm for precision cardiovascular medicine while highlighting the urgent need to close the gap between scientific knowledge and clinical implementation. Show less

Autotaxin (ATX), the enzyme responsible for generating lysophosphatidic acid (LPA), is a validated target for fibrosis and cancer immunotherapy. Current ATX inhibitors face challenges related to insufficient efficacy or safety concerns, reflecting trade-offs between zinc engagement and selectivity. Here, we report a rigid triazolyl-azabicyclo[3.1.0]hexanyl-oxadiazolyl-pyrimidine scaffold developed through structure-based design, designed to potentially enhance ATX selectivity by promoting defined binding geometry. Systematic studies identified 14e as the most potent inhibitor (IC Show less

This study aimed to assess the childbirth readiness of women in their third trimester of pregnancy and to identify distinct readiness profiles using latent profile analysis (LPA). Additionally, it explored the factors influencing childbirth readiness in order to guide targeted interventions for improved maternal and neonatal outcomes. A cross-sectional study was conducted among women in their third trimester of pregnancy between May and November 2024. Eligible participants completed a general information questionnaire, the Childbirth Readiness Scale (CRS), the Childbirth Attitude Questionnaire (CAQ), and the Perceived Social Support Scale (PSSS). LPA identified three groups with distinct childbirth readiness levels: "Low Readiness - Childbirth Knowledge Deficit" (37.9%), "Moderate Readiness - Good Lifestyle Habits" (47.9%), and "High Readiness - Rich Health Knowledge" (14.2%). In addition, gestational age, previous childbirth history, adverse pregnancy outcomes, childbirth attitudes, and social support had different influences on women in different latent profiles of childbirth readiness. There was significant heterogeneity in childbirth readiness among women in their third trimester. Women with lower readiness-especially in childbirth knowledge-would greatly benefit from targeted educational programs, whereas those with moderate readiness levels would find enhanced emotional and psychological support most advantageous. These findings support the implementation of profile-based, personalized prenatal care strategies to improve childbirth preparedness and optimize maternal and neonatal outcomes. Show less