Search Results (76,001)

Background/Objectives: Mindfulness-based interventions show promise for treating childhood ADHD, yet the mechanisms through which they produce effects remain unclear. This study provides the first direct comparison of treatment mechanisms between a mindfulness-based family intervention (MYmind) and methylphenidate. Methods: Data were drawn from a preregistered trial combining randomized and preference arms, comparing MYmind (2-month parallel parent–child mindfulness training) with 4-month methylphenidate in children aged 8–18 with ADHD (N = 120 children, 224 parents). Families were assessed at baseline, 2, 4 and 10 months. Multilevel mediation analyses tested whether treatment effects on ADHD symptoms were transmitted through 111 treatment-to-mediator-to-outcome pathways across three mechanism categories: child emotion regulation and coping (all children); adolescent self-regulation and mindfulness (ages 11+); and parent-level mechanisms, including mindful parenting, parental mindfulness, parenting style and self-compassion. Results: Direct treatment effects favored methylphenidate for ADHD symptom reduction at 4 months, with mindfulness catching up by 10 months. MYmind produced significantly greater improvements than methylphenidate in adolescent healthy self-regulation, parental self-compassion, mindful parenting and over-reactive parenting. Treatment did not differentially affect the remaining mechanisms. Across model sets, observed emotion regulation, maladaptive coping, parental self-compassion and mindful parenting each predicted ADHD outcomes. Across 111 pathways tested in 18 models, numerous significant individual pathways were consistent with theoretical predictions, yet no complete mediation chains reached statistical significance. Conclusions: MYmind engages distinct psychological and family-level processes compared to methylphenidate that are separately associated with ADHD symptom improvement. The absence of significant mediation effects likely reflects power limitations. These findings support mindfulness-based family intervention as a viable alternative to medication and highlight the need for larger-scale mechanism research. Full article

Background: Cancer represents a major concern in rheumatology. Epidemiological studies have demonstrated associations between rheumatic conditions and increased cancer risk at specific sites. However, comprehensive Italian epidemiological data on this association remain lacking. Methods: We conducted a nationwide retrospective cohort study using Italian Hospital Discharge Records from patients hospitalized between 1 January and 31 December 2018, with follow-up until 31 December 2023. Adult patients with Immune-mediated inflammatory diseases (IMID), including rheumatoid arthritis (RA) and diffuse diseases of connective tissue (DDCT), were the exposed group. The unexposed group included patients with primary diagnoses of injury and poisoning, with no IMID history. We used multivariable logistic regression models to assess cancer association, adjusting for demographics, geography, time of follow-up and comorbidities. Results: We included 54,896 IMID patients (exposed) and 301,126 unexposed. During the five-year follow-up, the IMID group was significantly associated with cancer (adjusted OR 1.32, 95% CI 1.27–1.38; p < 0.001). The OR_adj decreased over time, from 1.83 (p < 0.001) in year one to 1.20 (p < 0.001) from the fifth year onward. Significant association with lung cancer (OR_adj 1.74; p < 0.001), leukemia and lymphoma (OR_adj 1.98; p < 0.001), bladder (OR_adj 1.48; p < 0.001) and melanoma (OR_adj 1.48; p = 0.009) were observed in the IMID group. DDCT patients showed an overall higher cancer risk (OR_adj 1.53, p < 0.001) than RA patients (OR_adj 1.20, p < 0.001). Conclusions: This first nationwide Italian study confirms an association with cancer in IMID patients, with the highest association in the first year post-diagnosis. The temporal decrease in cancer risk generates the hypothesis that inflammation, rather than medication, may be the primary driver. These findings support enhanced cancer surveillance in IMID patients, particularly during the first year after diagnosis. Full article

Erythroid acute myeloid leukemia (AML) cell line OCI-M2 expresses a particular oncogenic network: IRF6, in concert with ETV2 and HEY1, aberrantly activates NKL homeobox gene NKX2-4, which in turn represses megakaryocytic lineage factor FLI1. Interestingly, in keratinocytes, IRF6 is able to bind glucose which promotes IRF6-dimerization and thus alters its binding site selection. Here, we used OCI-M2 as a model to investigate the role of glucose level and IRF6 in leukemogenesis. Treatment of OCI-M2 with high glucose or 2-deoxy-glucose resulted in the downregulation of IRF6 and NKX2-4, and the upregulation of FLI1, indicating that glucose-mediated dimerization of IRF6 altered its reported autoactivation. The screening of this cell line for genes encoding glycolytic enzymes identified aberrant overexpression of glucose-6-phosphate isomerase (GPI) and phosphofructokinase L (PFKL), which were targeted by genomic amplification and chromothripsis-like alterations, respectively. Furthermore, GPI was activated by NKX2-4 and ETV2, and PFKL by ETV2. Finally, siRNA-mediated downregulation of PFKL resulted in elevated glucose levels, suppressed expression of IRF6 and NKX2-4, and activated FLI1. Thus, we connected an oncogenic regulatory network with deregulated glycolytic enzymes and glucose metabolism, thereby establishing a new in vitro model to develop novel therapeutic avenues in AML subsets. Full article

Background: The progression of idiopathic pulmonary fibrosis (IPF) involves distal airway remodeling and bronchiolization; however, the mechanisms driving these changes, particularly the contributions of epithelial stem cells, are not fully understood. K13⁺ hillock cells, normally quiescent in proximal airways, were examined for their potential contribution to IPF pathogenesis. Methods: Spatial immunofluorescence was used to profile K13 expression along the airway axes in IPF and control lungs. Multiplex staining complemented by ex vivo culture assays was used to test expression stability. Single-cell RNA-sequencing (scRNA-seq) data were re-analyzed to identify cell subclusters and pathway enrichments. Meanwhile, cell–cell communication was inferred by using CellChat. Results: K13 was ectopically upregulated in IPF honeycomb cysts, triggering a proximal-like pseudostratified phenotype. This shift was marked by surges in K13⁺ regionally overlapping expression patterns (K5⁺, ~9%; CC10⁺, ~53%; ACE-TUB⁺, ~44%; MUC5AC⁺, ~23%) and a decline in SOX2 expression (~95% to ~64%), with ~70% of residual SOX2^low cells exhibiting elevated K13. Accompanying the expansion of K13⁺ subclusters (basal: 1.8% to 41.5%; club: 10.7% to 31.5%), it was observed that the profibrotic markers (K17, S100A2, LGALS7, IGFBP6) and ontologies related to RNA processing, stress response, and senescence were also enriched. These subclusters also amplified pro-fibrotic signaling (e.g., TGF-β, SEMA3, and GALECTIN-9) associated with epithelial subtypes and HAS1^high fibroblasts. Conclusions: Here, we demonstrate that K13⁺ cell activation is a pivotal event, driving the dysregulated proximalization of distal airways in IPF through fate reprogramming and epithelial-mesenchymal crosstalk. Thus, elucidating these K13-mediated fate dynamics provides a critical framework for understanding IPF pathogenesis. Full article

Background/Objective: Frailty is a major public health concern among older adults, particularly those living alone who may experience limited social support and increased nutritional vulnerability. With the rapid expansion of digital technologies, electronic device usage has become an important factor influencing daily life and health behaviors in older populations. This study aimed to examine the association between electronic device usage and frailty among older adults living alone and to investigate whether nutrition management mediates this relationship. Methods: This cross-sectional study conducted a secondary analysis using data from the 2023 Korean Elderly Survey. A total of 3423 adults aged ≥ 65 years who were living alone and completed the survey independently were included in the analysis. Descriptive statistics, independent t-tests, one-way analysis of variance, and Pearson correlation analyses were performed using SPSS version 26.0. Mediation analysis was conducted using Model 4 of the PROCESS macro (version 4.1) to examine the mediating role of nutrition management in the relationship between electronic device usage and frailty. Results: Electronic device usage was negatively associated with frailty and positively associated with nutrition management. Frailty was significantly higher among individuals with poorer nutrition management. Mediation analysis indicated that electronic device usage had both a direct effect on frailty and an indirect effect through nutrition management. Nutrition management partially mediated the relationship between electronic device usage and frailty, accounting for approximately 18% of the total effect. Conclusions: Electronic device usage was associated with lower levels of frailty among older adults living alone, and this relationship was partially mediated by nutrition management. These findings suggest that improving digital engagement may support better nutrition management and potentially contribute to frailty prevention among older adults living alone. Future longitudinal studies are needed to clarify the causal relationships among these variables. Full article

Rapid housing expansion exacerbates the urban heat island (UHI) effect, yet the influence of household-level awareness on sustainable housing decisions remains underexplored, particularly in tropical contexts. This study integrates the Theory of Planned Behavior (TPB) into a moderated-mediation model to examine how UHI awareness shapes the relationships among attitude, subjective norms, perceived behavioral control, socioeconomic factors, purchase intention, and willingness to pay (WTP) for heat-mitigating housing. Survey data from 441 homebuyers in Bandung City, Indonesia, were analyzed using partial least squares structural equation modeling (SEM). Results reveal that awareness fundamentally alters decision pathways: without awareness, subjective norms (β = 0.066, p-value = 0.007) and perceived behavioral control (β = 0.050, p-value = 0.005) significantly influence WTP via purchase intention; with high awareness, attitude becomes the sole significant predictor (β = 0.109, p-value = 0.035), while the effects of social pressure (β = −0.015, p-value = 0.130) and perceived control (β = −0.005, p-value = 0.376) diminish. The model explains 50.1% of the variance in purchase intention (R² = 0.501) but only 14.7% of the variance in WTP (R² = 0.147), reflecting the low-price premiums respondents are willing to pay (0–5%). These findings highlight that climate-specific awareness acts as a cognitive filter, guiding pro-environmental housing choices, and underscore the importance of awareness-driven interventions for promoting sustainable urban development in tropical cities. Full article

This study investigates the impact of sustainable destination marketing on enhancing tourists’ intention for responsible visitation in Saudi Arabia by fostering destination trust through two manageable digital levers: the quality of sustainability storytelling and the interactivity of smart tourism. Based on a trust-based S-O-R framework and supplemented by signaling and uncertainty reduction theories, the research posits that high-quality, credible sustainability narratives and responsive, two-way smart touchpoints serve as trust indicators that lead to enhanced responsibility-oriented intentions. An online survey of digitally engaged tourists and potential tourists (N = 420) was used to gather the data. We used SmartPLS, version 4.1.1.7 (SmartPLS GmbH, Monheim am Rhein, Germany), with bootstrapping (5000 resamples) to assess the measurement and structural models. The findings demonstrate that the quality of sustainability storytelling significantly predicts destination trust (β = 0.418, p < 0.001), as does smart tourism interactivity (β = 0.347, p < 0.001). Destination trust positively affects responsible visit intention (β = 0.318, p < 0.001) and partially mediates the impacts of storytelling quality (β = 0.133, p < 0.001) and interactivity (β = 0.110, p < 0.001) on responsible visit intention. The model elucidates 40.9% of the variance in destination trust and 40.6% in responsible visit intention, underscoring trust as a pivotal mechanism by which credible sustainability storytelling and efficient smart interactivity can promote more responsible visitation. Full article

This study investigated the bioactive properties of fractions derived from Rhynchosia nulubilis cultivated with Ganoderma lucidum mycelium (RNGM), focusing on cytotoxic and apoptosis-related responses in cancer cells. Fractions obtained using n-hexane, chloroform, ethyl acetate, and water were evaluated for cytotoxic effects against A549, Hep3B, HeLa, and HeLa229 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phenolic acid composition of each fraction was determined by high-performance liquid chromatography (HPLC). Among the fractions, the ethyl acetate fraction showed the highest total phenolic acid content and exhibited the strongest cytotoxic activity, particularly against HeLa cells. Apoptosis induction was supported by increased caspase-3/7 activity, apoptotic nuclear morphology observed by 4′,6-diamidino-2-phenylindole (DAPI) staining, and accumulation of cells in the sub-G1 phase. In addition, treatment with the ethyl acetate fraction upregulated p53 and Bax mRNA expression and increased the Bax/Bcl-2 ratio. These findings suggest that the ethyl acetate fraction of RNGM induces apoptosis-mediated growth inhibition in cervical cancer cells. Full article

The long-term accumulation of phosphogypsum (PG) stacks has caused combined pollution of total phosphorus (TP), fluoride (F⁻), metals and metalloids (MMs), posing a severe threat to regional ecological security. To clarify the migration characteristics of pollutants in PG stacks, water leaching experiments and environmental risk assessment were conducted in 21 typical PG stacks in Southwest China. The spatial differentiation and vertical migration characteristics of pollutants under various coverage measures (high-density polyethylene (HDPE) film covering, soil covering, a composite of film–soil covering, and open-air storage) at different pH conditions were systematically analyzed. Results indicated that under open-air stockpiling conditions, the surface accumulation of TP and F⁻ was the most significant among all covering measures, corresponding to the highest environmental risk. In contrast, the membrane–soil composite covering exhibited the optimal inhibitory effect on the surface diffusion of TP and F⁻, but was less effective for metal and metalloid enrichment. Under acidic conditions (pH < 6), the vertical migration capacity of TP, F⁻, and MMs (Cu, Cd, Cr, Pb, and Zn) increased, leading to enrichment in the deep layers of the stack. With the increase in pH, the calcium-mediated precipitation–adsorption effect created a “geochemical barrier”, facilitating the solid-phase fixation of pollutants. A significant positive correlation among pollutants indicates synergistic release and fixation behaviors. In addition, a pH-controlled P-F-MM source-to-sink conceptual model was established, outlining the dissolution, precipitation, adsorption, fixation and re-enrichment pathway from fresh stock to leachate. This work provides insights for optimizing cover designs and pollution control strategies. Full article

Green finance is an important policy for facilitating corporate environmental transformation and supporting sustainable economic development under China’s “dual-carbon” strategy. This study investigates how green financial policies influence a firm’s TFP. A DID framework is employed to estimate the policy effect and to further explore its transmission mechanisms and heterogeneous impacts across firms, applying the data of China’s A-share-listed companies from 2013 to 2024. It is found that green financial policies significantly improve a firm’s TFP. Specifically, firms located in pilot regions exhibit an average increase of 0.4509 in TFP. The results remain stable across multiple robustness checks. In addition, the policy improves TFP through three primary channels: alleviating financing constraints, stimulating green technological innovation, and promoting digital transformation. The mediation analysis based on Bootstrap resampling confirms the statistical significance of the identified transmission channels. Among them, digital transformation plays the most prominent role, contributing 20.62% to the overall mediating effect. Furthermore, the policy can enhance the TFP of non-state-owned enterprises and for firms operating in industries with lower pollution intensity. Finally, this study proposes further improving the green financial policy framework and strengthening support for green technological innovation and digital transformation, thereby better leveraging green finance to enhance firms’ TFP. Full article

With the continuous development of the construction industry, work pressure faced by construction workers has been increasing, leading to a growing prominence of job burnout that adversely affects workers’ physical and mental health as well as work efficiency. Constantly exposed to high-pressure environments, construction workers are prone to symptoms such as emotional exhaustion, depersonalization, and diminished personal accomplishment, which in turn impair their work performance and quality of life. However, existing literature has largely overlooked the potential role of leisure activities such as music in alleviating job burnout. Although music is widely recognized as an effective tool for emotional regulation, its application and impact among construction workers remain underexplored. Based on a sample of 1086 construction workers (71.09% male, 48.99% aged 36–45), this study examines four dimensions of music engagement, including Time Commitment (TC), Economic Spending (ES), Emotional Investment (EI), and Personal Participation (PP), and investigates how these dimensions, through the mediating role of leisure crafting (LC), negatively influence job burnout (JB) among this population. This study employed covariance-based structural equation modeling (CB-SEM) with a sample of 1086 construction workers (71.09% male, 48.99% aged 36–45) to examine how four dimensions of music engagement, namely Time Commitment (TC), Economic Spending (ES), Emotional Investment (EI), and Personal Participation (PP), influence job burnout through leisure crafting. The results show that: (1) time commitment, economic spending, emotional investment and personal participation all have a negative influence on job burnout; and (2) leisure crafting mediates the effect of music engagement by construction workers on job burnout. This study emphasizes the necessity of incorporating mental health interventions into high-pressure work environments, providing guidance for companies to develop more flexible and effective employee care and welfare policies. This research therefore holds significant theoretical and practical value, as it promotes sustainable development in the construction industry, improves workers’ well-being and enhances the design of related work environments. Full article

Background/Objectives: Psoriasis and periodontitis share inflammatory pathways. Current evidence suggests a bidirectional non-causal relation. However, the evidence on the effects of periodontal treatment on psoriasis outcomes (severity, inflammatory markers, quality of life) is limited. This study aims to synthetize the available clinical and preclinical evidence of periodontal treatment effects on psoriasis outcomes, in patients with comorbid psoriasis and periodontitis (CRD420261298145). Methods: Several databases (PubMed, WebOfScience, ScienceDirect, ProQuest and GoogleScholar) were searched for relevant articles, without language or time restrictions. We included randomised and non-randomised clinical studies on humans, and controlled animal experiments. Interventions included periodontal treatment (surgical and non-surgical). Outcomes were the Psoriasis Area and Severity Index and dermatology-specific quality of life scores; secondary outcomes included inflammatory biomarkers and periodontal parameters. Studies were screened in duplicate, data extracted independently and risk of bias was assessed using Cochrane RoB 2, ROBINS I, NOS and SYRCLE. Results: A total of five studies were included in this systematic review (four clinical studies and one preclinical studies). Three studies directly assessed post-treatment psoriasis outcomes, with two studies investigating inflammation mediators as secondary outcomes. Two studies directly assessed PASI (Psoriasis Area and Severity Index) modifications, both studies confirming PASI scores decreasing post-periodontal treatment; one study also reported DLQI (Dermatology Life Quality Index). Typical follow-up durations ranged from 8 to 10 weeks for interventional studies, to 5 years for one cohort study. Conclusions: Although momentarily limited by the small number of available studies, the results of this review suggest that periodontal treatment may be associated with improvements in psoriasis outcomes. Further studies on larger samples, with longer follow-up periods would be necessary to confirm and possibly strengthen the existing results. Full article

Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity associated with autografts or allografts. However, conventional delivery systems suffer from burst release, rapid clearance, off-target effects, and supraphysiologic dosing, which can lead to undesirable complications such as ectopic ossification and inflammation, with some reports raising concerns about the long-term tumorigenic risk. Heparin, a naturally highly sulfated glycosaminoglycan structurally related to heparan sulfate, has emerged as a particularly attractive candidate for affinity-based biomaterial systems. It naturally binds over 300 growth factors, including bone morphogenetic proteins. By protecting these proteins from enzymatic degradation, enhancing their bioavailability, and mediating receptor clustering, heparin provides both biochemical stability and biofunctional modulation. This review provides a comprehensive overview of heparin-based delivery strategies in bone tissue engineering. We begin by describing the biological functions of heparin in modulating growth factor activity. We then discuss in detail the different heparin-based biomaterials designed to sustain the release of growth factors for bone tissue engineering, including the heparin–polycation coacervate system; heparin-based supramolecules; and heparin-based hydrogels, nanoparticles, and microspheres for sustained release of bone morphogenic proteins and other growth factors for bone tissue engineering. Finally, we assess the clinical and translational relevance of heparin-based systems, identify key challenges, and outline future perspectives, highlighting the potential of these biomaterials for providing safer and more effective therapies for bone regeneration. Full article

The microbial production of 1,5-pentanediol (1,5-PDO), a versatile platform chemical with extensive industrial applications, remains limited by suboptimal fermentation titers and incomplete understanding of metabolic bottlenecks. To address these challenges, this study employed comparative transcriptomics to systematically identify novel genetic targets capable of enhancing 1,5-PDO biosynthesis in engineered Escherichia coli. Transcriptomic profiling of the 1,5-PDO-producing strain relative to the parental E. coli W3110, conducted at both exponential (24 h) and stationary (96 h) growth phases, revealed 1384 significantly differentially expressed genes, including 851 upregulated and 533 downregulated genes. From these, 20 candidate metabolic genes associated with 1,5-PDO synthesis were selected for functional validation through plasmid-based overexpression or CRISPR interference (CRISPRi)-mediated repression. Reverse engineering confirmed that overexpression of fecA (encoding an iron(III)-citrate transporter) and deletion of gadA (encoding glutamate decarboxylase) significantly enhanced 1,5-PDO production. Subsequent chromosomal integration of fecA at the neutral ilvG locus and deletion of gadA generated the optimized strain S7, which achieved a 1,5-PDO titer of 1.7 g/L in shake flask cultures, representing a 13.3% increase over the parental strain, with a concomitant 50% improvement in glucose yield (0.18 mol/mol). In fed-batch fermentation at the 5 L bioreactor scale, strain S7 attained a titer of 12.45 g/L and a glucose yield of 0.26 mol/mol, marking a 15.6% enhancement in carbon conversion efficiency relative to the parental strain (0.225 mol/mol), while concurrently improving biomass accumulation by 7.6%. These findings demonstrate that transcriptomics-guided reverse engineering constitutes an effective strategy for elucidating nonobvious metabolic determinants and optimizing microbial cell factories for efficient 1,5-PDO production. The identification of fecA and gadA as beneficial targets provides valuable insights into the metabolic rewiring underlying enhanced 1,5-PDO biosynthesis and establishes a foundation for further strain improvement through systems metabolic engineering. Full article

As artificial intelligence (AI) increasingly engages in managing consumer interactions on e-commerce platforms, an important question arises: how do public AI-generated replies to negative reviews compare with human replies in fostering consumer trust? This study investigates consumer trust in reply source (AI review bots vs. human agents) across three reply strategies, namely, default, thinking, and feeling, in a public review context. AI review bots are defined as automated systems that publicly respond to consumer reviews. Using a controlled laboratory experiment, we find that when using the default strategy, human replies elicit greater trust than AI replies, mediated by higher perceived authenticity and persuasiveness. Conversely, when using the thinking strategy, AI replies outperform human replies in building consumer trust, as they are perceived as more authentic and persuasive. In the feeling strategy, there is a convergence between AI and human replies. These findings demonstrate that the effectiveness of AI versus human replies depends on the strategy adopted. Theoretically, this study extends research on human–AI interaction by introducing a three-strategy framework to systematically compare AI and human communicators in public review contexts. Practically, the results guide e-commerce sellers and platforms on when and how to deploy AI review bots to effectively manage consumer trust in response to negative reviews. Full article