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Spatial heterogeneity and plasticity of the mammalian liver are critical for systemic metabolic homeostasis in response to fluctuating nutritional conditions. Here, a spatially resolved transcriptomic landscape of mouse livers across fed, fasted and refed states using spatial transcriptomics is generated. This approach elucidated dynamic temporal‐spatial gene cascades and how liver zonation—both expression levels and patterns—adapts to shifts in nutritional status. Importantly, the pericentral nuclear receptor Nr1i3 (CAR) as a pivotal regulator of triglyceride metabolism is pinpointed. It is showed that the activation of CAR in the pericentral region is transcriptionally governed by Pparα. During fasting, CAR activation enhances lipolysis by upregulating carboxylesterase 2a, playing a crucial role in maintaining triglyceride homeostasis. These findings lay the foundation for future mechanistic studies of liver metabolic heterogeneity and plasticity in response to nutritional status changes, offering insights into the zonated pathology that emerge during liver disease progression linked to nutritional imbalances. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this cross-sectional study is to investigate the levels of NLRP3 in the serum and induced sputum of children with asthma and their potential association with lung function and disease severity. Methods: This cross-sectional study included 83 children with bronchial asthma who sought medical care at our hospital from May 2023 to February 2024. Portable spirometry was used to monitor lung function parameters, including forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow. The expression of C-reactive protein (CRP), interleukin (IL)-6, IL-1β, TNF-α, and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in the serum and induced sputum were measured by enzyme-linked immunosorbent assay. Data analysis was performed using SPSS 25.0 and differences with P < 0.05 were considered statistically significant. Results: Children with asthma exhibited significantly elevated levels of serum NLRP3, CRP, IL-6, IL-1β, and TNF-α compared to healthy controls. In addition, children with moderate–severe asthma had significantly higher levels of serum and induced sputum NLRP3 and IL-1β compared to children with mild asthma. Spearman's correlation analysis revealed a positive correlation between induced sputum NLRP3 and IL-6. Moreover, induced sputum NLRP3 was negatively correlated with lung function parameters. The results of receiver operating characteristic curves showed that induced sputum NLRP3 could be used for diagnosing children with moderate–severe asthma, with an AUC was 0.758, cutoff value of 3.33 ng/mL, sensitivity of 66.1%, and specificity of 70.8%. Furthermore, the logistic regression analysis revealed that serum and induced sputum NLRP3, induced sputum IL-6 and IL-1β were risk factors for children with moderate–severe asthma. Conclusions: In this cross-sectional study, we found a significant increase in NLRP3 levels in induced sputum of children with asthma, which further increased in those with moderate–severe disease. The levels of NLRP3 in induced sputum could serve as potential biomarkers for assessing disease severity. [ABSTRACT FROM AUTHOR]

Background: The Platelet to High-Density Lipoprotein cholesterol Ratio (PHR) is a novel indicator of inflammatory response and metabolic disorders, linked to various chronic diseases. This study aims to investigate the relationship between PHR and hypertension. Methods: Data from the National Health and Nutrition Examination Survey (NHANES), collected across seven consecutive cycles from 2005 to 2018, were analyzed. The dataset included participants' hypertension status as reported by a doctor, their use of antihypertensive medications, and the average of three blood pressure measurements to identify hypertensive adults, along with complete information for PHR calculation. PHR was calculated based on Platelet (PLT) count and High-Density Lipoprotein cholesterol (HDL-C) using the following formula: PHR = [PLT (1000 cells/µL) / HDL-C (mmol/L)]. A multivariable logistic regression model was employed to assess the association between PHR and hypertension, and subgroup analyses were conducted to explore potential influencing factors. Additionally, Restricted Cubic Spline (RCS) curves were applied for threshold effect analysis to describe nonlinear relationships. Results: Higher PHR was associated with an increased prevalence of hypertension. After adjusting for various covariates, including race, education level, Family Poverty Income Ratio (PIR), smoking, alcohol consumption, sleep disturbances, waist circumference, diabetes, coronary heart disease, angina, heart attack, and stroke, the results remained significant (OR = 1.36; 95% CI, 1.32, 1.41, P < 0.001). Participants with the highest PHR levels had a 104% higher risk of hypertension compared to those with the lowest PHR levels (OR = 2.04; 95% CI, 1.89, 2.21, P < 0.001). Conclusion: Elevated PHR levels are strongly associated with an increased risk of hypertension. Specifically, when PHR is below 280, the risk of hypertension increases in proportion to PHR. This suggests that regular monitoring of PHR may help identify patients at risk of hypertension early, allowing for timely interventions to slow disease progression. Larger cohort studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: Depression is closely linked with microglial activation and neuro‐inflammation. Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) plays an important role in M2 activation of microglia. Forkhead box (FOX) O3a has been implicated in the regulation of mood‐relevant behaviour. However, little is known about the inflammatory mechanisms of in the microglia of the brain. Here, we have investigated the role of microglial FOXO3a/PPAR‐γ in the development of depression. Experimental Approach: The effect of FOXO3a on microglia inflammation was analysed in vitro and in lipopolysaccharide (LPS)‐induced depression‐like behaviours in vivo. ChIP‐seq and Dual‐luciferase reporter assays were used to confirm the interaction between FOXO3a and PPAR‐γ. Behavioural changes were measured, while inflammatory cytokines, microglial phenotype and morphological properties were determined by ELISA, qRT‐PCR, western blotting and immunostaining. Key Results: Overexpression of FOXO3a significantly attenuated expression of PPAR‐γ and enhanced the microglial polarization towards the M1 phenotype, while knockdown of FOXO3a had the opposite effect. FOXO3a binds to the promoters of PPAR‐γ and decreases its transcription activity. Importantly, deacetylation and activation of FOXO3a regulate LPS‐induced neuro‐inflammation by inhibiting the expression of PPAR‐γ in microglia cells, supporting the antidepressant potential of histone deacetylase inhibitors. Microglial FOXO3a deficiency in mice alleviated LPS‐induced neuro‐inflammation and depression‐like behaviours but failed to reduce anxiety behaviour, whereas pharmacological inhibition of PPAR‐γ by GW9662 restored LPS‐induced microglial activation and depressive‐like behaviours in microglial FOXO3a‐deficient mice. Conclusion and Implications: FOXO3a/PPAR‐γ axis plays an important role in microglial activation and depression, identifying a new therapeutic avenue for the treatment of major depression. [ABSTRACT FROM AUTHOR]

Background: The incidence of inflammatory bowel disease (IBD) is on the rise in developing countries, and investigating the underlying mechanisms of IBD is essential for the development of targeted therapeutic interventions. Interferon regulatory factor 7 (IRF7) is known to exert pro-inflammatory effects in various autoimmune diseases, yet its precise role in the development of colitis remains unclear. Methods: We analyzed the clinical significance of IRF7 in ulcerative colitis (UC) by searching RNA-Seq databases and collecting tissue samples from clinical UC patients. And, we performed dextran sodium sulfate (DSS)-induced colitis modeling using WT and Irf7−/− mice to explore the mechanism of IRF7 action on colitis. Results: In this study, we found that IRF7 expression is significantly reduced in patients with UC, and also demonstrated that Irf7−/− mice display heightened susceptibility to DSS-induced colitis, accompanied by elevated levels of colonic and serum pro-inflammatory cytokines, suggesting that IRF7 is able to inhibit colitis. This increased susceptibility is linked to compromised intestinal barrier integrity and impaired expression of key molecules, including Muc2, E-cadherin, β-catenin, Occludin, and Interleukin-28A (IL-28A), a member of type III interferon (IFN-III), but independent of the deficiency of classic type I interferon (IFN-I) and type II interferon (IFN-II). The stimulation of intestinal epithelial cells by recombinant IL-28A augments the expression of Muc2, E-cadherin, β-catenin, and Occludin. The recombinant IL-28A protein in mice counteracts the heightened susceptibility of Irf7−/− mice to colitis induced by DSS, while also elevating the expression of Muc2, E-cadherin, β-catenin, and Occludin, thereby promoting the integrity of the intestinal barrier. Conclusion: These findings underscore the pivotal role of IRF7 in preserving intestinal homeostasis and forestalling the onset of colitis. [ABSTRACT FROM AUTHOR]

How different fertilization practices modify soil organic carbon (SOC) sequestration is still unclear. Our study aimed to evaluate the changes in SOC stocks and their physical fractions after 10 years of organic and inorganic fertilization. Five treatments were established under a wheat-maize system in Northern China: control (CK), chemical fertilizer (F), straw plus chemical fertilizer (SF), manure plus chemical fertilizer (MF), and straw and manure plus chemical fertilizer (SMF). The results showed that the SOC sequestration rate at 0–20 cm depth decreased in the following order: SMF (1.36 Mg C/ha/yr) > MF (1.13 Mg C/ha/yr) > SF (0.72 C/ha/yr) > F (0.15 Mg C/ha/yr) > CK (−0.25 Mg C/ha/yr). The values indicated that straw returning and manure application were important measures to achieve the "4 per 1000" target, and the application of manure was a more effective strategy. The high input of chemical fertilizer only maintained the initial SOC level and was not a powerful C-farming practice. A minimum input of 4.93 Mg C/ha/yr was required to keep the initial SOC storage. The SOC associated with small macroaggregate (0.25–2 mm) was the most sensitive indicator for the changes of bulk SOC. In addition, the accumulation of SOC under SMF, MF, and SF treatments mainly occurred in the occluded particulate organic C (oPOC) in small macroaggregates, indicating that the physical protection of macroaggregates played a predominant role in SOC sequestration. The SMF, MF, and SF treatments also displayed higher mineral organic C (mSOC) in soil aggregates than the CK and F treatments. A transformation of oPOC towards the mSOC fraction indicated that exogenous C further shifted into stable C pools under the physical protection of soil aggregates. In conclusion, these findings confirmed the important role of straw returning and manure application in SOC accumulation and stabilization, highlighting that a combination strategy of straw + manure + chemical fertilizer had the best effect. [ABSTRACT FROM AUTHOR]

ABSTRACT A GaCl3‐catalyzed [3 + 2]‐cycloaddition/intramolecular esterification cascade of donor–acceptor cyclopropane‐1,1‐diesters with salicylaldehydes has been reported. A wide range of tetrahydro‐4H‐furo[3,2‐c]chromen‐4‐ones have been efficiently delivered in moderate to good yields. Mechanistic studies suggest that the reaction involves the [3 + 2]‐cycloaddition followed by intramolecular esterification to access 4H‐furo[3,2‐c]chromenones. [ABSTRACT FROM AUTHOR]

Viral infections pose significant threats to human health, leading to a diverse spectrum of infectious diseases. The innate immune system serves as the primary barrier against viruses and bacteria in the early stages of infection. A rapid and forceful antiviral innate immune response is triggered by distinguishing between self-nucleic acids and viral nucleic acids. RNA-binding proteins (RBPs) are a diverse group of proteins which contain specific structural motifs or domains for binding RNA molecules. In the last decade, numerous of studies have outlined that RBPs influence viral replication via diverse mechanisms, directly recognizing viral nucleic acids and modulating the activity of pattern recognition receptors (PRRs). In this review, we summarize the functions of RBPs in regulation of host-virus interplay by controlling the activation of PRRs, such as RIG-I, MDA5, cGAS and TLR3. RBPs are instrumental in facilitating the identification of viral RNA or DNA, as well as viral structural proteins within the cellular cytoplasm and nucleus, functioning as co-receptor elements. On the other hand, RBPs are capable of orchestrating the activation of PRRs and facilitating the transmission of antiviral signals to downstream adaptor proteins by post-translational modifications or aggregation. Gaining a deeper comprehension of the interaction between the host and viruses is crucial for the development of novel therapeutics targeting viral infections. [ABSTRACT FROM AUTHOR]

Inflammations have been linked to tumours, suggesting a potential association between NLRP1 and cancer. Nevertheless, a systematic assessment of NLRP1's role across various cancer types currently absent. A comprehensive bioinformatic analysis was conducted to determine whether NLRP1 exhibits prognostic relevance linked to immune metabolism across various cancers. The study leveraged data from the TCGA and GTEx databases to explore the clinical significance, metabolic features, and immunological characteristics of NLRP1, employing various tools such as R, GEPIA, STRING and TISIDB. NLRP1 exhibited differential expression patterns across various cancers, with elevated expression correlating with a more favourable prognosis in lung adenocarcinoma (LUAD) and pancreatic adenocarcinoma (PAAD). Downregulation of NLRP1 reduced tumour metabolic activity in LUAD. Moreover, the mutational signature of NLRP1 was linked to a favourable prognosis. Interestingly, high NLRP1 expression inversely correlated with tumour stemness while positively correlating with tumour immune infiltration in various cancers including LUAD and PAAD. Through extensive big data analysis, we delved into the role of NLRP1 across various tumour types, constructing a comprehensive role map of its involvement in pan‐cancer scenarios. Our findings highlight the potential of NLRP1 as a promising therapeutic target specifically in LUAD and PAAD. [ABSTRACT FROM AUTHOR]

Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy. [ABSTRACT FROM AUTHOR]

To expand the application prospects of quadrotors in challenging scenes such as those with dense obstacles and narrow corridors, task-driven reconfigurable quadrotors are highly desirable. Aiming to address hazard missions, in this paper, translational reconfigurable quadrotors and rotational reconfigurable quadrotors are proposed with their assumptions and mathematical models. Related motion control laws were designed using model reference adaptive control (MRAC) theory based on Lyapunov stability theory, whose validity was demonstrated by sufficient numerical simulations. The simulation results verify the feasibility of the proposed control laws and reveal the important effect of time delay on the stability of the motion control system. Additionally, the dependence of motion control's stability on the time constant of reference system was discussed. [ABSTRACT FROM AUTHOR]

Leaky Rayleigh wave testing has the advantages of non-contact, high sensitivity, and good beam directivity. However, current leaky Rayleigh wave testing mostly uses monolithic transducers and is seriously affected by acoustic wave attenuation and diffusion, resulting in poor image quality, limited detection range and low imaging efficiency. In this paper, a novel leaky Rayleigh wave testing method using an ultrasonic phased array is developed, and the total focusing method (TFM) is used to achieve high-quality imaging of defects. To improve imaging efficiency, the root-mean-square velocity (RMSV) model is utilised to rapidly acquire an approximate analytical solution for the time of flight of the acoustic wave. To obtain more accurate defect images further, the amplitude of the total focusing imaging signal is calibrated. The experimental results demonstrate that the proposed method achieves a 48% improvement in the imaging accuracy of a 1 mm hole, compared to the traditional Synthetic Aperture Focusing Technique (SAFT) imaging method. The proposed method achieves an 92% reduction in imaging time compared to the conventional TFM. The proposed method provides a new non-contact approach for high-accuracy and high-efficiency defect imaging using leaky Rayleigh wave. [ABSTRACT FROM AUTHOR]

To examine the precise function of influenza A virus target genes (IATGs) in malignancy. Using multi-omics data from the TCGA and TCPA datasets, 33 tumor types were evaluated for IATGs. IATG expression in cancer cells was analyzed using transcriptome analysis. Copy number variation (CNV) was assessed using GISTICS 2.0. Spearman's analysis was used to correlate mRNA expression with methylation levels. GSEA was used for the enrichment analysis. Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50. The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. In 13 solid tumors, IATG mRNA levels were atypically expressed. Except for UCS, UVM, KICH, PCPG, THCA, CHOL, LAMI, and MESO, most cancers contained somatic IATG mutations. The main types of CNVs in IATGs are heterozygous amplifications and deletions. In most tumors, IATG mRNA expression is adversely associated with methylation. RT-PCR demonstrated that EGFR , ANXA5 , CACNA1C , CD209 , UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines, consistent with the TCGA and GTEx data. Genomic changes and clinical characteristics of IATGs were identified, which may offer fresh perspectives linking the influenza A virus to cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of isoliensinine (Iso) on the proliferation, apoptosis and autophagy of colon cancer SW480 cells through PI3K/Akt/mTOR signaling pathway. Methods: Colon cancer SW480 cells were treated with 10, 20 and 40 μmol/L Iso, and the effects of Iso on the cell proliferation capacity, apoptosis and expressions of autophagy related proteins LC3 I, LC3II and p62 were detected by CCK-8, flow cytometry and Western blot, respectively. Then, SW480 cells were treated respectively with 20 μmol/L Iso and 25 μmol/L PI3K activator 740 Y-P, and the cells were divided into the control group, the 740 Y-P group, the Iso group and the Iso+740 Y-P group. The effects of 740 Y-P on the apoptosis and the expressions of LC3 I, LC3 II, p62, PI3K, p-PI3K, mTOR and p-mTOR proteins in each group were detected by flow cytometry and WB. Results: After treatments with 10, 20 and 40 μmol/L Iso, the proliferation capacity of SW480 cells was decreased significantly (all P<0.05); the apoptosis rate was increased significantly (all P<0.05); the expressions of LC3 II/LC3 I were up-regulated significantly (all P<0.05), and the expression of p26 protein was down-regulated significantly (all P<0.05). After treatments with Iso and 740 Y-P, compared with the control group, the apoptosis rate and LC3 II/LC3 I expression of the 740 Y-P group were decreased significantly (both P<0.05), while the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were increased significantly (all P<0.05).The apoptosis rate and LC3 II/LC3 expression in the Iso group were increased (both P<0.05) and the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were decreased (all P<0.05). Compared with the 740 Y-P group, the apoptosis rate and LC3 II/LC3 I expression were increased in the Iso+740 Y-P group (P<0.05), while the expressions of p26, p-PI3K/PI3K and p-mTOR/mTOR were decreased (all P<0.05). Compared with the Iso group, the apoptosis rate and LC3 II/LC3 I expression were decreased (both P<0.05), and the expressions of p26, p-PI3K/PI3K, and p-mTOR/mTOR were increased significantly (all P<0.05) in the Iso+740 Y-P group. Conclusion: Iso inhibits the proliferation and induces the apoptosis and autophagy of SW480 cells by inhibiting PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

The effect of hybridization on vibration response of carbon/glass hybrid composite laminates are studied using the analytical and the numerical models. For this purpose, nine hybrid types of the four-layer hybrid composite laminates are performed in this paper. The first-order shear deformation theory and the higher-order shear deformation theory based on the energy method are utilized. The equations of motion and boundary conditions are derived from Hamilton's principle and Navier solution. Numerical examples are presented to validate the accuracy and reliability of the adopted analytical methods. A good agreement is observed between the current results and FEA ones. The influence of the stacking sequences on the positive/negative hybrid effect is studied. Moreover, the influences of stacking sequences, material properties, and geometries on the vibration response are also studied in detail. The results reveal that the natural frequencies increase with the hybrid ratios due to the increasing stiffness of the hybrid laminates. Moreover, the positive effect of hybrid laminates can only be achieved by arranging the CFRP on the exterior surfaces. [ABSTRACT FROM AUTHOR]

A comprehensive emergency medical service (EMS) system significantly enhances a city's capacity to prevent and mitigate disasters. Using Huangshi as a case study, this research evaluated the service radium coverage rate of the current EMS system by examining its transport capacity, population density, and prevalence rate, finding it to be only 61.49% with an inefficient spatial layout. To address this, we proposed transforming urban brownfields into EMS parks. By selecting the most suitable brownfields based on capacity and service radius, we increased the coverage rate to 90.21%. We introduced a new "consultation-referral" model, where existing EMS facilities serve as pre-diagnosis and triage centers, and the urban brownfield EMS parks function as isolation and centralized treatment centers. GIS network analysis confirmed the feasibility, showing all transit times to be under 30 min. The methodology outlined in this study—comprising "demand assessment, supply optimization, and feasibility verification"—not only strengthens the city's EMS system but also facilitates the renewal of urban brownfields. This approach can serve as a valuable reference for enhancing EMS systems in other cities. [ABSTRACT FROM AUTHOR]

Candida albicans is among the most prevalent invasive fungal pathogens for immunocompromised individuals and novel therapeutic approaches that involve immune response modulation are imperative. Absent in melanoma 2 (AIM2), a pattern recognition receptor for DNA sensing, is well recognized for its involvement in inflammasome formation and its crucial role in safeguarding the host against various pathogenic infections. However, the role of AIM2 in host defense against C. albicans infection remains uncertain. This study reveals that the gene expression of AIM2 is induced in human and mouse innate immune cells or tissues after C. albicans infection. Furthermore, compared to their wild-type (WT) counterparts, Aim2−/− mice surprisingly exhibit resistance to C. albicans infection, along with reduced inflammation in the kidneys post-infection. The resistance of Aim2−/− mice to C. albicans infection is not reliant on inflammasome or type I interferon production. Instead, Aim2−/− mice display lower levels of apoptosis in kidney tissues following infection than WT mice. The deficiency of AIM2 in macrophages, but not in dendritic cells, results in a phenocopy of the resistance observed in Aim2−/− mice against C. albican infection. The treatment of Clodronate Liposome, a reagent that depletes macrophages, also shows the critical role of macrophages in host defense against C. albican infection in Aim2−/− mice. Furthermore, the reduction in apoptosis is observed in Aim2−/− mouse macrophages following infection or treatment of DNA from C. albicans in comparison with controls. Additionally, higher levels of AKT activation are observed in Aim2−/− mice, and treatment with an AKT inhibitor reverses the host resistance to C. albicans infection. The findings collectively demonstrate that AIM2 exerts a negative regulatory effect on AKT activation and enhances macrophage apoptosis, ultimately compromising host defense against C. albicans infection. This suggests that AIM2 and AKT may represent promising therapeutic targets for the management of fungal infections. [ABSTRACT FROM AUTHOR]

AbstractThis study addresses a fundamental scientific issue in digital interface design: the quantification of visual elements to enhance interface efficiency and user satisfaction. We propose an innovative framework combining the Analytic Hierarchy Process with visual design principles to quantitatively define and optimize design elements. The core of our research is a quantitative assessment method for interface design, aiming to advance the scientific understanding and development of digital user experience. We anticipate this approach will reveal the interplay between functionality, aesthetics, and emotion, guiding the creation of more appealing and efficient interfaces. Our findings clarify the scientific issue of integrating aesthetics with functionality in digital interface design, offering a systematic solution. This not only aids designers and researchers in understanding and evaluating the impact of interface design but also lays a solid theoretical and methodological foundation for future studies, encouraging a deeper scientific comprehension of the integration of aesthetics and functionality in interface design and exploring its application in crafting more effective and enjoyable user experiences. [ABSTRACT FROM AUTHOR]