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To explore molecular targets for regulating glucose metabolism in carnivorous fish, the glucose tolerance test (GTT) was carried out on the Paralichthys olivaceus. The concentration of glucose and insulin in serum were measured at 0, 1, 3, 5, 7, 9, 12, 24, and 48h after intraperitoneal (IP) injecting. The concentration of insulin was the lowest after 3h of glucose injection, and that of glucose reached the highest after 5h. Therefore, 0h (IP0) was chosen as control group, 3h (IP3) and 5h (IP5) were selected as experimental groups, which the liver samples in three time points were used to high-throughput sequencing. Although, there were no significant KEGG and GO functional enrichment, the differential genes including MAPK binding protein 1 (MAPKBP1), glycosyltransferase (FNG), suppressor of cytokine signaling 3 (SOCS3), CCAAT/enhancer-binding protein alpha (CEBP-α) were closely related to glucose metabolism, among which SOCS3 was worthy of further explore. The full-length cDNA sequence of SOCS3 gene was cloned and the open reading frame (ORF) of SOCS3 encoded 225 amino acids including conserved domains SH2 and SOCS3-box. The results of tissue differential expression showed that SOCS3 was highly expressed in liver and intestine. The SOCS3 was knocked down by specific siRNA in the primary hepatocyte of P. olivaceus. Results showed that the gene expression of insulin receptor substrate 1 (IRS1), protease B1 (AKT1), glucose transporter 2 (GLUT2), pyruvate kinase (PK) and glucokinase (GK) increased significantly after knocking down SOCS3. Meanwhile, the phosphatidylinositol-3-hydroxykinase (PI3K) and glucose-6-phosphatase (G6Pase) decreased significantly. The results of this study indicated that siSOSC3 enhanced the sensitivity of the insulin signaling pathway to promote glucose transport, thereby affecting gluconeogenesis and glycolysis to maintain glucose homeostasis.
A metasurface (MTS) antenna with wideband radiation and low radar cross section (RCS) performance is proposed. The design is based on a two-step RCS reduction (RCSR) strategy applied to a reference antenna – a conventional 4 × 4 square patch array MTS antenna that exhibits stable broadside radiation within 5–6.5 GHz. In the first step, the patch array of the reference antenna is reconfigured into a quasi-chessboard MTS using the principle of reflection cancellation, enabling wideband RCSR under both x- and y-polarized incidences. In the second step, guided by the antenna scattering theory based on characteristic modes, six slots are etched on the ground plane to further enhance RCSR under x-polarized incidence. Characteristic mode analysis is employed throughout the design process to simultaneously analyze radiation and scattering behaviors. Compared with the reference antenna, the proposed MTS antenna maintains similar radiation performance while achieving monostatic RCSR bandwidths of 3.7–11.3 and 4.7–11.3 GHz for x- and y-polarized incident waves, respectively. It also demonstrates significantly broader RCSR bandwidths compared to a metallic plate of the same size.
We investigate flow instability produced by viscosity and density discontinuities at the interface separating two Newtonian fluids in generalised Couette–Poiseuille (GCP) flow. The base flow, driven by counter-moving plates and an inclined pressure gradient at angle $0^\circ \leqslant \phi \leqslant 90^\circ$, exhibits a twisted, two-component velocity profile across the layers, characterised by the Couette–Poiseuille magnitude parameter $0^\circ \leqslant \theta \leqslant 90^\circ$. Plane Couette–Poiseuille (PCP) flow at $ \phi = 0^\circ$ is considered as a special case. Flow/geometry parameters are $(\phi ,\theta )$, a Reynolds number $Re$ and the viscosity, depth and density ratios $(m,n,r)$, respectively. A mapping from the GCP to PCP extended Orr–Sommerfeld equations is found that simplifies the numerical study of interfacial-mode instabilities, including determination of shear-mode critical parameters. For interfacial modes, unstable regions in $(m,n,r)$ space are delineated by three distinct surfaces found via long-wave analysis, with the exception of strict Couette flow where the $(m,n)$ surface asymptotically vanishes with $\theta \rightarrow 0^\circ$. In interfacial stable regions but with unstable shear modes, one-layer PCP stability can be identified with a cut-off $\theta$ that conforms to canonical PCP stability. Competition between the interfacial-mode reversal phenomenon and the shear-mode cut-off behaviour is discussed. Extending to the full GCP configuration with the mapping algorithms applied, we systematically chart how pressure-gradient inclination and perturbation wavefront angle shift the balance between interfacial and shear instabilities in a specific case.
We demonstrate a high-efficiency, high-power Er:CaF2 single-crystal fiber (SCF) continuous-wave (CW) laser pumped by a 976 nm laser diode. By carefully analyzing the thermal lensing effect and optimizing mode matching, we achieved a maximum CW output power of 10.02 W, corresponding to a slope efficiency as high as 32.2% for pump power below 25 W. To the best of our knowledge, this represents the highest output power ever reported for 2.8 μm SCF lasers, approximately an order of magnitude higher than previous results. In addition, a wavelength redshift beyond 2.8 μm was observed at high power, extending beyond the strong absorption region of water vapor. These results indicate that Er-doped CaF2 SCFs are promising candidates for high-power mid-infrared lasers.
Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.
Methods
A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.
Results
Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.
Conclusions
Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.
Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.
Methods
A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.
Results
Significant reductions in nodal efficiency and degree centrality (Dnodal) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, Dnodal in MCPG_R, and WCST scores. Moreover, Dnodal in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.
Conclusions
This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.
Previous studies have reported co-morbidities of autoimmune thyroid disorders (AITD), including Hashimoto’s disease and Graves’ disease and celiac disease (CeD), as well as the possible beneficial effects of a gluten-free diet (GFD) on AITD. Nonetheless, it remains uncertain whether there is a genetic causal relationship between AITD and CeD, while the beneficial effects of a GFD are controversial. This study aims to explore the causal relationship between CeD and AITD, particularly with Hashimoto’s disease, and to determine whether a GFD is beneficial for AITD. We performed a two-sample Mendelian randomisation analysis on data from the largest meta-analysis summary statistics of AITD, CeD and GFD. Genetic instrumental variables were established by pinpointing SNP that relate to corresponding factors. In assessing sensitivity and heterogeneity, we conducted examinations of MR Egger, weighted median, simple mode, weighted mode and MR Egger intercept tests. Hashimoto’s disease was found to play a pathogenic role in increasing the risk of CeD (ORIVW = 1·544 (95 % CI 1·153, 2·068), P = 0·00355), and our Mendelian randomisation study does not support genetic liability related to CeD with Graves’ disease and GFD with AITD. This study supports the positive correlation between Hashimoto’s disease risk and CeD risk, while GFD has no protective effect on AITD and may exert its effect through other mechanisms. These findings provide valuable insights into potential targets for disease intervention and treatment at the genetic level.
Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function.
Objective
Despite increasing evidence, a comprehensive understanding of the exact role of irisin remains elusive, necessitating further research to unravel the complex mechanisms through which irisin influences cognitive function and to explore therapeutic approaches targeting irisin.
Method
A literature review was performed by searching PubMed for articles published between 2012 and 2024, using the keywords ‘fibronectin type III domain-containing 5 (FNDC5)’, ‘irisin’, ‘cognitive impairment’, ‘Alzheimer’s disease’, ‘Age-related cognitive dysfunction’ and ‘Diabetes-associated cognitive dysfunction’, combined with Boolean operators (AND/OR).
Results
This review highlighted the potential impact of irisin on cognitive function in the context of ageing, diabetes and Alzheimer’s disease. The anti-cognitive impairment effects of irisin are associated with the regulation of energy metabolism, insulin resistance, inflammation, oxidative stress, amyloid-beta deposition, synaptogenesis and plasticity. The signalling pathways through which irisin improves cognitive impairment are complex and highly regulated processes, involving multiple signalling pathways such as the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, nuclear factor-κB (NF-κB) signalling pathway, ERK-STAT3 signalling pathway, cAMP/PKA/CREB signalling pathway and Nrf2/HO-1 signalling pathway.
Conclusion
This review delves into the positive effects of irisin on cognitive impairment, examines the signalling pathways related to fibronectin type III domain-containing 5 (FNDC5)/irisin and provides future perspectives for research on the anti-cognitive impairment effects of irisin.
The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.
Antibiotic stewardship programs (ASPs) are crucial to prevent the emergence of antibiotic resistance and to improve outcomes for patients. A validated instrument rooted in a theoretically derived implementation science framework will increase our understanding of ASP implementation and enable comparisons across implementation sites.
Design:
Methods:
Antibiotic stewards (infectious disease pharmacists and physicians) were recruited from Veterans Affairs (VA) hospitals to complete a survey on stewardship implementation. We used the Consolidated Framework for Implementation Research (CFIR) to guide development of an ASP implementation survey assessing 22 potential determinants of implementation across five domains of CFIR. We conducted confirmatory factor analyses (CFA) to assess construct validity of 8 construct measures and evaluated internal consistency.
Results:
A total of 150 stewards completed the survey from 110 VA hospitals. CFA for most CFIR constructs exhibited good fit. Internal consistency for CFIR construct subscales (Cronbach’s alpha) ranged from 0.54–0.96, indicating modest to strong internal consistency. Determinants that were rated highly present at the sites (across site means ≥ 4.0 or above) included Self-Efficacy, Engaging, Evidence Strength and Quality and Relative Advantage, indicating stewards found ASP evidence compelling and felt their personal involvement was effective in engendering positive results for the ASP.
Conclusions:
Psychometric properties indicate validity of the first CFIR-based survey of determinants for ASP implementation outcomes. Clinical, quality improvement, and research teams can use this survey to identify contextual determinants of ASP implementation and use this information to guide selection of strategies and compare results across multiple sites.
The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a highly destructive polyvorous pest with a wide host range and the ability to feed continuously with seasonal changes. This destructive pest significantly damages crops and can also utilize non-agricultural plants, such as weeds, as alternative hosts. However, the adaptation mechanisms of S. frugiperda when switching between crop and non-crop hosts remain poorly understood, posing challenges for effective monitoring and integrated pest management strategies. Therefore, this study aims to elucidate the adaptability of S. frugiperda to different host plants. Results showed that corn (Zea mays L.) was more suitable for the growth and development of S. frugiperda than wheat (Triticum aestivum L.) and goosegrass (Eleusine indica). Transcriptome analysis identified 699 genes differentially expressed when fed on corn, wheat, and goosegrass. The analysis indicated that the detoxification metabolic pathway may be related to host adaptability. We identified only one SfGSTs2 gene within the GST family and investigated its functional role across different developmental stages and tissues by analysing its spatial and temporal expression patterns. The SfGSTs2 gene expression in the midgut of larvae significantly decreased following RNA interference. Further, the dsRNA-fed larvae exhibited a decreased detoxification ability, higher mortality, and reduced larval weight. The findings highlight the crucial role of SfGSTs2 in host plant adaptation. Evaluating the feeding preferences of S. frugiperda is significant for controlling important agricultural pests.
While most research on time preference has focused on gains, understanding time preference for losses is also crucial in practice. Some studies have shown that people prefer to bear a loss earlier rather than later, suggesting negative delay discounting. Nonetheless, most previous research either disallowed an exhibition of negative discounting or analyzed data suggesting opposite directions of discounting together. Furthermore, such research tended to draw conclusions based on aggregate data, although individual behavioral patterns could differ starkly from aggregate ones. To improve knowledge on individual time preference for losses, we conducted 3 experiments examining how systematically changing attribute values affected such preference. Using a choice method with delayed losses, Experiment 1 revealed 3 behavioral effects (i.e., the magnitude, common difference, and delay duration effects) at the aggregate level. For each effect, opposite changes in discount rate were found in data suggesting positive versus negative discounting. Similar results emerged in Experiment 2 using a matching task with delayed losses. Experiment 3 adopted a special form of the matching paradigm, where the amount of an immediate loss should be filled (i.e., an evaluation method). Distinct influences of loss amount were again found under opposite directions of delay discounting. Additionally, a reverse magnitude effect was found more often in Experiment 3 than the other experiments under positive discounting, illustrating the distinctiveness of the evaluation method. Finally, individual analyses revealed more diverse behavioral patterns than aggregate analyses in each study. This underscored the importance of understanding time preference for losses based on individual data.
Previous studies have suggested that nature contact is a protective factor for problem behavior in children. However, there remains a significant gap in research exploring the reciprocal relationship between nature contact and children’s problem behavior, as well as the underlying mechanisms driving this relationship. This study employed a longitudinal three-wave design involving 516 children in China (268 girls, Mage = 10.88 ± 0.66 years old at Time 3). Cross-lagged analyses indicated that nature contact and problem behavior negatively predicted each other over time, and prosocial behavior bidirectionally mediated the relationship between nature contact and problem behavior. These results provided evidence for the relationships among nature interaction, social development, and behavioral development in children. These findings suggested that promoting prosocial behavior could reduce problem behavior and enhance nature engagement, potentially serving as a strategy to foster comprehensive development in children.
We aimed to validate in-body bioelectrical impedance analysis (BIA) measures with dual-energy X-ray absorptiometry (DXA) as reference and describe the body composition (BC) profiling of Tibetan adults.
Design:
This cross-sectional study included 855 participants (391 men and 464 women). Correlation and Bland–Altman analyses were performed for method agreement of in-body BIA and DXA. BC were described by obesity and metabolic status.
Setting:
In-body BIA and DXA have not been employed to characterise the BC of the Tibetan population living in the Qinghai–Tibet Plateau.
Participants:
A total of 855 Tibetan adults, including 391 men and 464 women, were enrolled in the study.
Results:
Concordance correlation coefficient for total fat mass (FM) and total lean mass (LM) between in-body BIA and DXA were 0·91 and 0·89. The bias of in-body BIA for percentages of total FM and total LM was 0·91 % (2·46 %) and –1·74 % (–2·80 %) compared with DXA, respectively. Absolute limits of agreement were wider for total FM in obese men and women and for total LM in overweight men than their counterparts. Gradience in the distribution of total and regional FM content was observed across different BMI categories and its combinations with waist circumference and metabolic status.
Conclusions:
In-body BIA and DXA provided overall good agreement at the group level in Tibetan adults, but the agreement was inferior in participants being overweight or obese.
Contrafreeloading (CFL) refers to animals’ tendency to prefer obtaining food through effort rather than accessing food that is freely available. Researchers have proposed various hypotheses to explain this intriguing phenomenon, but few studies have provided a comprehensive analysis of the factors influencing this behaviour. In this study, we observed the choice of alternative food containers in budgerigars (Melopsittacus undulatus) to investigate their CFL tendencies and the effects of pre-training, food deprivation, and effort required on the CFL tasks. The results showed that budgerigars did not exhibit significant difference in their first choices or the time interacting with less challenging versus more challenging food containers. Moreover, when evaluating each budgerigar’s CFL level, only half of them were identified as strong contrafreeloaders. Thus, we suggest that budgerigars exhibit an intermediate CFL level that lies somewhere between a strong tendency and the absence of such behaviour. Furthermore, we also found that food-deprived budgerigars tended to select less challenging food containers, and pre-trained budgerigars were more likely to choose highly challenging food containers than moderately challenging food containers, which means that the requirement of only a reasonable effort (access to food from moderately challenging food containers in this study) and the experience of pre-training act to enhance their CFL levels, whereas the requirement of greater effort and the experience of food deprivation act to decrease their CFL levels. Studying animal CFL can help understand why animals choose to expend effort to obtain food rather than accessing it for free, and it also has implications for setting feeding environments to enhance the animal welfare of captive and domesticated animals.
Language control in the bilingual brain has remained in the limelight of research over the past decades. However, the mechanisms underlying bilingual language control may be more intricate than typically assumed due to the hierarchical nature of language. This study aimed to investigate the dynamics of bilingual language control at the phonetic level. Participants, who were speakers of Chinese, English and German, named the letters of the alphabet in English (L2) or German (L3) following an alternating language-switching paradigm. Two sets of letters were selected, differing in the phonological similarity of their pronunciation across the two languages, thereby allowing the exploration of cross-language phonological influences. Each participant completed two sessions of letter-naming tasks. In one session, seven phonologically similar letters were randomly repeated either in single-language blocks or in alternate-language blocks. In the other session, seven phonologically dissimilar letters were similarly manipulated. The results indicated local inhibition, reflected by switch costs and global inhibition, reflected by mixing costs. Reversed language dominance, another indicator of global inhibition, was not observed. However, there was a tendency for larger global inhibition to be applied to the more dominant language. Moreover, there was significantly faster naming for phonologically similar letters compared to dissimilar ones, suggesting a facilitation effect for both English and German, irrespective of whether letter naming occurred in single- or alternate-language blocks. These findings provided evidence for the role of inhibitory and facilitative mechanisms at the phonetic level, suggesting language-specific control in the bilingual brain and underscoring the complexity and dynamics of managing language control across multiple levels of processing.
Previous studies have linked social behaviors to COVID-19 risk in the general population. The impact of these behaviors among healthcare personnel, who face higher workplace exposure risks and possess greater prevention awareness, remains less explored.
Design:
We conducted a Prospective cohort study from December 2021 to May 2022, using monthly surveys. Exposures included (1) a composite of nine common social activities in the past month and (2) similarity of social behavior compared to pre-pandemic. Outcomes included self-reported SARS-CoV-2 infection (primary)and testing for SARS-CoV-2 (secondary). Mixed-effect logistic regression assessed the association between social behavior and outcomes, adjusting for baseline and time-dependent covariates. To account for missed surveys, we employed inverse probability-of-censoring weighting with a propensity score approach.
Setting:
An academic healthcare system.
Participants:
Healthcare personnel.
Results:
Of 1,302 healthcare personnel who completed ≥2 surveys, 244 reported ≥1 positive test during the study, resulting in a cumulative incidence of 19%. More social activities in the past month and social behavior similar to pre-pandemic levels were associated with increased likelihood of SARS-CoV-2 infection (recent social activity composite: OR = 1.11, 95% CI 1.02–1.21; pre-pandemic social similarity: OR = 1.14, 95% CI 1.07–1.21). Neither was significantly associated with testing for SARS-CoV-2.
Conclusions:
Healthcare personnel social behavior outside work was associated with a higher risk for COVID-19. To protect the hospital workforce, risk mitigation strategies for healthcare personnel should focus on both the community and workplace.
The incidence of obesity-related glomerulopathy (ORG) is rising worldwide with very limited treatment methods. Paralleled with the gut–kidney axis theory, the beneficial effects of butyrate, one of the short-chain fatty acids (SCFA) produced by gut microbiota, on metabolism and certain kidney diseases have gained growing attention. However, the effects of butyrate on ORG and its underlying mechanism are largely unexplored. In this study, a mice model of ORG was established with a high-fat diet feeding for 16 weeks, and sodium butyrate treatment was initiated at the 8th week. Podocyte injury, oxidative stress and mitochondria function were evaluated in mice kidney and validated in vitro in palmitic acid-treated-mouse podocyte cell lines. Further, the molecular mechanisms of butyrate on podocytes were explored. Compared with controls, sodium butyrate treatment alleviated kidney injuries and renal oxidative stress in high-fat diet-fed mice. In mouse podocyte cell lines, butyrate ameliorated palmitic acid-induced podocyte damage and helped maintain the structure and function of the mitochondria. Moreover, the effects of butyrate on podocytes were mediated via the GPR43-Sirt3 signal pathway, as evidenced by the diminished effects of butyrate with the intervention of GPR43 or Sirt3 inhibitors. In summary, we conclude that butyrate has therapeutic potential for the treatment of ORG. It attenuates high-fat diet-induced ORG and podocyte injuries through the activation of the GPR43-Sirt3 signalling pathway.
This study explores the integration of generative artificial intelligence (GenAI) in informal digital learning of English (IDLE) practices, focusing on its potential to enhance language learning outcomes and addressing the technological challenges language teachers face in utilising AI-based tools to facilitate second language acquisition. Based on the research context of IDLE and holistic learning ecology and drawing on the theoretical frameworks of technological pedagogical and content knowledge and social cognitive theory, we performed a mixed-methods investigation with an empirical experiment to assess the effectiveness of GenAI followed by semi-structured interviews. The results suggest that the GenAI-mediated IDLE practices effectively improve college students’ oral proficiency in English from both technological and humanistic perspectives. However, results also indicate that the GenAI conversational partner alone is not adequate to provoke continuous extramural GenAI-mediated IDLE practices. We discuss the theoretical and pragmatic significance of GenAI-mediated IDLE in educational equity and reformation.