Search Results (421)

Prenatal maternal stress (PNMS) predicts risk for autism spectrum disorders (ASD), although the mechanisms are unknown. Because ASD and autistic-like traits have been associated with both prenatal stress and DNA methylation differences, it is important to examine whether epigenetic mechanisms mediate the pathway from PNMS to later autistic-like outcomes. This study aimed to determine the extent to which DNA methylation mediates the association between PNMS from a natural disaster and autistic-like traits in offspring assessed during adolescence. Five months following the 1998 ice storm in Quebec, we recruited women who had been pregnant during the crisis and assessed their PNMS: objective hardship, subjective distress, and cognitive appraisal. At age 13, their children provided blood samples for DNA. At ages 15, 16 and 19, the youth self-reported their own autistic-like traits using the Broad Autism Phenotype Questionnaire. This longitudinal design allowed us to track the developmental pathway from prenatal exposure, through adolescent DNA methylation, to later behavioral outcomes. Analyses included youth with data on PNMS, DNA methylation, and the BAPQ (n = 27 at age 15; 22 at age 16; and 13 at age 19). Results showed that mothers’ disaster-related objective hardship and their negative cognitive appraisal of the disaster were associated with DNA methylation at age 13, which then were associated with the severity of their children’s Aloof Personality and Pragmatic Language Deficits, but not Rigid Personality, at ages 15, 16 and 19. Mediation was significant particularly through genes within the PI3K/AKT/mTOR pathway, which has been implicated in various neurodevelopmental disorders, including ASD. Interestingly, while greater PNMS predicted more severe ASD traits, the epigenetics effects were for less severe traits. Although other interpretations are possible, these results could suggest that DNA methylation, assessed in early adolescence, may protect against ASD traits at later ages, particularly when there is a mismatch between the prenatal environment (disaster) and the postnatal environment (absence of disaster). The interpretation of these findings benefits from the longitudinal design and is discussed in the context of fetal programming and the predictive adaptive response. Full article

Background: Engineered nanoparticles (NPs)—titanium dioxide, silver, zinc oxide and silica—are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut–skin axis. Current regulatory frameworks typically omit chronic- or microbiome-focused safety assessments, leaving potential gaps. Objectives: This study aimed to evaluate the long-term effects of cosmetic-relevant NPs (titanium dioxide, silver, zinc oxide, silica) on skin and gut microbiota, epithelial-barrier integrity and immune signalling—including telocyte- and exosome-mediated pathways—and to identify regulatory shortcomings, particularly the absence of microbiome endpoints, validated chronic models and consideration of vulnerable populations. Methods: Following PRISMA 2020, PubMed, Scopus and Web of Science were searched for English-language in vivo animal or human studies (December 2014–April 2025) meeting chronic-exposure criteria (≥90 days in rodents or >10% of lifespan in other species; for humans, prolonged, repetitive application over months to years consistent with cosmetic use). Although not registered in PROSPERO, the review adhered to a pre-specified protocol. Two independent reviewers screened studies; risk of bias was assessed using a modified SYRCLE tool (animal) or adapted NIH guidance (zebrafish). Owing to heterogeneity, findings were synthesised narratively. Results: Of 600 records, 450 unique articles were screened, 50 full texts were assessed and 12 studies were included. Oral exposure predominated and was associated with dysbiosis, barrier impairment, immune modulation and metabolic effects. Dermal models showed outcomes from minimal change to pronounced immune activation, contingent on host susceptibility. Comparative human–animal findings are summarised; telocyte and exosome pathways were largely unexplored. Regulatory reviews (EU SCCS, US FDA and selected Asian frameworks) revealed no requirements for chronic microbiome endpoints. Limitations: Evidence is limited by the small number of eligible studies, heterogeneity in NP characteristics and exposure routes, predominance of animal models and a scarcity of longitudinal human data. Conclusions: Cosmetic nanoparticles may disrupt the microbiome, compromise barrier integrity and trigger immune dysregulation—risks amplified in vulnerable users. Existing regulations lack requirements for chronic exposure, microbiome endpoints and testing in vulnerable groups, and neglect mechanistic pathways involving telocytes and exosomes. Long-term, real-world exposure studies integrating gut–skin microbiome and immune outcomes, and harmonised global nanomaterial-safety standards, are needed to ensure safer cosmetic innovation. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) encompasses interconnected cardiovascular, renal, and metabolic disorders, including obesity, hypertension, and type 2 diabetes. Oxidative stress is increasingly recognized as a central driver of this multi-organ dysfunction. Among maternal influences, exposure to a high-fat diet (HFD) during pregnancy and lactation consistently predisposes offspring to CKMS-related phenotypes in animal models. While oxidative stress is implicated as a key mediator, its precise role in developmental programming remains unclear, and comparing the differences in its role between overt CKMS and CKM programming is critical. Critical gaps include whether oxidative stress acts uniformly or in an organ- and time-specific manner, which signals initiate long-term redox alterations, and whether these effects are reversible. Furthermore, its interactions with other programming pathways—such as renin–angiotensin system activation, epigenetic dysregulation, gut microbiota imbalance, and altered nutrient sensing—remain insufficiently explored. This review uniquely highlights maternal HFD-induced oxidative stress as a mechanistic axis of CKMS programming and delineates unresolved questions that limit translation. By integrating evidence across organ systems and proposing priorities for multi-organ profiling, refined models, and longitudinal human studies, we outline a forward-looking agenda for the field. Ultimately, clarifying how maternal HFD and oxidative stress shape offspring CKMS risk is essential to inform targeted antioxidant strategies to reduce the intergenerational transmission of CKMS risk. Full article

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = −0.043, 95% CI: −0.059 to −0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = −0.010, 95% CI: −0.014 to −0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of −0.044, a direct effect of −0.027, and an indirect effect of −0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results. Full article

Against the backdrop of tightened credit conditions, external financing constraints have increasingly become an important factor affecting enterprises’ high-quality development. This study focuses on the impact of financing constraints on the high-quality development of Chinese listed firms and constructs an analytical framework involving investment efficiency as a mediator and contextual factors such as managerial effectiveness and internal control quality as moderators. Using a longitudinal dataset of China’s A-share listed companies from 2007 to 2021, multivariate regression and mediation effect tests are conducted. The observational findings reveal a statistically meaningful U-shaped association between financial constraints and the high-quality development of enterprises. Further analysis confirms that investment efficiency partially mediates the relationship between financing constraints and high-quality development, while managerial effectiveness and internal control quality play significant moderating roles in this relationship. Additionally, the study reveals heterogeneous impacts of financing constraints on high-quality development across different regions. These findings provide insights into how enterprises can mitigate the adverse effects of financing constraints and promote high-quality development. Full article

Objectives: The purpose of this study was to examine the prospective, longitudinal relations among childhood poverty and rural adolescents’ internalizing and externalizing problem behaviors, and the mediational roles of adolescent attachment to parents and peers. Methods: Participants were from a longitudinal study of rural poverty. Two home visits were conducted, roughly four years apart (Time 1: N = 226; Mage = 13.36, 52.7% male; Time 2: N = 215; Mage = 17.47 years, 51.2% male). Each family’s income-to-needs ratio was assessed at each visit. At Time 2, participants completed questionnaires reporting their attachments to parents and peers, and their externalizing and internalizing symptoms. Results: Parent attachment was found to mediate the relationship between Time 1 family income-to-needs ratio and Time 2 internalizing problems. The mediational effects of peer attachment predicting Time 2 internalizing or externalizing symptoms were not significant. Conclusions: The long-term impact of childhood poverty on adolescents’ parent attachment and their well-being is discussed. Full article

Background: The early development of children’s eating behaviors is a complex process shaped by dynamic interactions within the family system. While extensive research has focused on parental feeding practices as a primary predictor of children’s eating behaviors, the role of intergenerational coparenting dynamics (especially with involved grandparents) is less studied. This study aimed to examines how primary caregivers’ feeding behaviors mediate the relationship between parent–grandparent coparenting dynamics and children’s eating behaviors. Methods: We conducted a longitudinal study among 343 stem families with preschool children. The cross-lagged analysis was applied to examine: the mechanism of parent–grandparent coparenting relationships on preschool children’s eating behaviors and the bidirectional relationship between feeding behaviors and eating behaviors. Results: Our results revealed that coparenting agreement significantly and negatively predicted satiety responsiveness through the mediating role of parental encouragement of healthy eating (β = −0.012, 95% CI [−0.022, −0.001]). Similarly, coparenting support had a significant negatively indirect effect on satiety responsiveness, also partially mediated by parental encouragement of healthy eating (β = −0.012, 95% CI [−0.023, −0.002]). The association between coparenting undermining and satiety responsiveness was mediated by parental encouragement healthy eating (β = −0.612, 95% CI [−0.796, −0.429]). Mutual predictive relationships were observed between preschool children’s satiety responsiveness and parental encouragement of healthy eating (p < 0.05). Conclusions: The study results highlighted the critical role of parent–grandparent coparenting relationships as indirect predictors of preschoolers’ eating behavior through mediator of parental feeding behaviors. Importantly, healthcare providers may be able to offer anticipatory guidance or relevant healthy eating resources to parents and grandparents, who should be recognized as important stakeholders in promoting healthy eating among children. Full article

In light of a Volatile, Uncertain, Complex and Ambiguous (VUCA) world, the need for employee adaptability is a critical capacity to navigate challenges and facilitate employees thriving in organizations. One important capacity, systems intelligence, captures employees’ ability to think, adapt and act effectively in interactions with systems. In a three-wave longitudinal study, we examine the relationship between systems intelligence (SI), job crafting (JC), and job performance (JP) over time. We employ the job demands-resources model to demonstrate that SI increases JP, hypothesizing that job resources, as manifested in JC, act as mediator between personal resources (SI) and JP. Data were collected from employees in Pakistan working across the banking, telecommunications, information technology, and engineering sectors. In the first wave, 303 participants completed the survey using validated self-report measures, followed by 212 in the second wave, and 99 in the third wave, each two months apart. Our findings show that systems intelligence at Time 1 was positively related to job performance at Time 3 but not Time 2. We found no significant association of SI at Time 1 with JC at Time 2 or Time 3. JC at Time 2 did not mediate the effects of SI at Time 1 on JP at Time 3. However, JC (T1 & T2) had a significant positive effect on JP (T2 & T3). Overall, our findings suggest that the pathways from systems intelligence and job crafting to job performance are independent. This dual pathway to performance has important theoretical implications as well as practical implications for organizations. Organizations can improve team and individual productivity by fostering systems intelligence and promoting job crafting behaviours. This research directs the attention of leaders and HR functions to the value of tailored interventions in developing these abilities and achieving long-term success and adaptive performance in the workforce. Full article

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically, microRNAs are small non-coding RNAs, routinely detected through quantitative real-time PCR, which act as translational suppressors by regulating protein-coding genes. Considering their high stability in all body fluids and viability in circulation, research is currently focusing on this type of RNAs for the so called “liquid biopsy”, a non-invasive tool for disease diagnosis and longitudinal monitoring. However, several issues remain to be solved including the lack of standardized protocols for exosome isolation and miRNA detection. Starting with this premise, our review aims to provide a wide description of the known microRNA panels employed in the prominent hematological malignancies, which will hopefully redefine the approach to these very challenging diseases in the near future. Full article

Background/Objectives: Emerging evidence suggests a role of immune–inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer a unique opportunity to investigate these associations free from confounding pharmacological effects. Methods: This study included 38 patients with drug-naive first episode psychosis and 22 age- and sex-matched healthy controls. Serum concentrations of IL-1β, IL-2, IL-6, and IL-10 were measured using ELISA. Clinical symptoms were assessed using the PANSS scale. Statistical analyses included Mann–Whitney U tests, Spearman’s correlations, and ROC curve analysis. Results: Significantly elevated serum levels of IL-1β, IL-2, and IL-10 were observed in the FEDN group compared to the controls (p < 0.01), while IL-6 levels did not differ significantly. IL-2 exhibited the highest discriminatory power in differentiating the patients from the controls (AUC = 0.917; 95% CI: 0.759–1000.0; p < 0.001). IL-1β levels positively correlated with negative and general psychopathology symptoms, including hostility and grandiosity. IL-10 was associated with volitional disturbance and overall PANSS severity. Conclusions: Our findings underscore the relevance of immune dysregulation in the early stages of psychosis and highlight the potential of specific cytokines, particularly IL-2 and IL-1β, as peripheral biomarkers. Their diagnostic utility and correlation with symptom dimensions suggest a promising role in the development of precision psychiatry approaches, including early detection strategies and individualised therapeutic targeting. Longitudinal studies are needed to validate these findings and to assess their prognostic significance. Full article

This paper provides a new and significant conceptual framework to enhance understanding of how digital capability and corporate social responsibility (CSR) complement each other in achieving the trade-off of ambidextrous innovation. Building on resource orchestration theory, we propose that opportunity recognition can serve as a mediating bridge to convey the positive impact of digital capability on ambidextrous innovation. Furthermore, these effects are likely to be especially pronounced among enterprises with a higher level of CSR implementation according to the reciprocity principle of social capital theory. We conducted a questionnaire-based survey among executives from 225 non-listed companies and a longitudinal panel study of 1897 listed companies from 2009 to 2022. The results support our hypotheses, showing that CSR implementation strengthens the active indirect effect of digital capability on ambidextrous innovation through accurate opportunity recognition. This paper enriches the research on the positive consequences of digital capabilities, introduces opportunity recognition into resource orchestration theory from the perspective of intangible assets, verifies the mediating role of opportunity recognition between digital capabilities and ambidextrous innovation, and sheds light on how an organization’s CSR strategy and digital capabilities are complementary. CSR can catalyze the positive impact of an enterprise’s digital capability on opportunity recognition and ambidextrous innovation. We advise enterprises on sustainable development, emphasizing the importance of fulfilling their CSR strategies while enhancing their digital capabilities. Full article

This study focuses on the mechanisms of behavior and cognition, providing a comprehensive analysis of the innovative path of multimodal learning theory in the teaching practice of the “Web Front-end Development” course. This study integrates different sensory modes, such as vision, hearing, and haptic feedback, with the core objective of exploring the specific impact of this multi-sensory integration form on students’ cognitive engagement status, classroom interaction styles, and long-term learning behavior. We employed a mixed-methods approach in this study. On the one hand, we conducted a quasi-experiment involving 120 undergraduate students. On the other hand, research methods such as behavioral coding, in-depth interviews, and longitudinal tracking were also employed. Results show that multimodal teaching significantly reduces cognitive load (a 34.9% reduction measured by NASA-TLX), increases the frequency of collaborative interactions (2.3 times per class), and extends voluntary practice time (8.5 h per week). Mechanistically, these effects are mediated by enhanced embodied cognition (strengthening motor-sensory memory), optimized cognitive load distribution (reducing extraneous mental effort), and the fulfillment of intrinsic motivational needs (autonomy, competence, relatedness) as framed by self-determination theory. This study fills in the gap between educational technology and behavioral science. We have developed a comprehensive framework that provides practical guidance for designing technology-enhanced learning environments. With such a framework, learners can not only master technical skills more smoothly but also maintain their enthusiasm for learning for a long time and continue to participate. Full article

Amid escalating regulatory and stakeholder pressures, corporate environmental practices emerge as strategic competitive advantages. Yet, research lacks depth on the interactions among PLU (power, legitimacy, and urgency) attributes and resource-constrained decision pathways. Integrating stakeholder theory and the attention-based view (ABV), a pressure–attention–action model is developed in this study to explain the voluntary adoption of ultra-regulatory proactive environmental practices (PEPs). An analysis of 503 Taiwanese firms using partial least squares structural equation modeling (PLS-SEM) reveals that (1) stakeholder legitimacy (β = 0.146, p < 0.01) and urgency (β = 0.215, p < 0.001) significantly increase perceived stakeholder pressure, whereas power exhibits no significant effect (β = 0.067, p > 0.05); (2) firm size positively moderates the pressure–resource linkage (β = 0.239, p < 0.001); and (3) urgency triggers partial mediation (57.4% VAF) through pressure and resources to drive proactive environmental practices. Firm size moderates pressure–resource linkages, with urgency prompting resource reallocation for environmental proactivity across scales. A dynamic PLU assessment tool and scale-sensitive strategies are proposed, challenging power-centric paradigms and aiding SMEs through collaborative networks. Limitations of the study include cross-sectional data and a regional focus, necessitating longitudinal and cross-industry validation. Full article

The literature has consistently shown the link between parental depressive symptoms and adolescent depressive symptoms. Emotion regulation processes may explain this association, with self-compassion acting as a potential mediating mechanism. This study aimed to explore these developmental trajectories using a longitudinal design. The sample comprised dyads of parents and adolescents (N = 311), assessed across two assessment waves (T1 and T2) over 12 months. The adolescents’ mean age was 13.63 years (SD = 1.30; 173 males). Mediation analyses using structural equation modelling supported the role of self-compassion in mediating the relationship between parental and adolescent depressive symptoms over time (53% of outcome variance explained). The results suggest that fostering self-compassion early in adolescence may help prevent the later adverse effects of depressive symptoms. Full article

Background: Physical inactivity is a major contributor to increased mortality among aging populations, especially in middle-aged and older adults. Methods: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020). Participants self-reported their physical activity frequency, categorized as low (≤1 day/week), medium (2–4 days/week), or high (≥5 days/week). All-cause mortality was tracked through verified records. Cox proportional hazards models were used to estimate hazard ratios (HRs), with adjustments for demographics, lifestyle factors, and baseline health conditions. Results: A total of 2092 participants (mean age = 63.7 ± 10.4 years) were included in the final analytic sample. Higher physical activity frequency was significantly associated with lower mortality in unadjusted models. Participants engaging in activity ≥5 days/week had a 67% reduced mortality risk compared to the low-frequency group (HR = 0.33, p < 0.001). However, after adjusting for health-related covariates, the protective effect was attenuated and no longer statistically significant. In the fully adjusted model, advanced age, current smoking, and ADL limitations emerged as the strongest independent risk factors for mortality, while being married and residing in a rural area were significantly protective effects. Conclusions: The association between frequent physical activity and reduced mortality risk among Chinese older adults is profoundly mediated by baseline health status and functional capacity. These findings highlight the importance of integrated, multifactorial public health interventions that address chronic disease management and functional rehabilitation alongside physical activity promotion. Full article