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by Moster Zhangazha, Alex Somto Arinze Alochukwu, Elizabeth Jonck, Ronald John Maartens, Eunice Mphako-Banda, Simon Mukwembi and Farai Nyabadza

Math. Comput. Appl. 2026, 31(1), 9; https://doi.org/10.3390/mca31010009 (registering DOI) - 9 Jan 2026

Abstract

The accurate determination of bond lengths is fundamental to understanding molecular geometry and the physicochemical behavior of chemical compounds. However, obtaining these measurements is often challenging, as both experimental techniques and advanced quantum-chemical methods are complex, computationally demanding, and costly to apply across diverse molecular systems. In this work, we present a novel graph-theoretical model for predicting bond lengths in flavonoid molecules based on molecular descriptors derived from atomic and topological parameters. By integrating atomic electronegativity with graph-based descriptors, such as the weighted second-order neighborhood, the proposed model predicts the bond lengths of luteolin with a coefficient of determination of

R^{2} = 0.990

. This approach offers a computationally efficient and highly accurate alternative to conventional experimental and theoretical methods, providing a practical framework for bond length estimation when experimental data are unavailable. Full article

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19 pages, 4719 KB

Open AccessArticle

The Track-Long Scale Response Modes of Sea Surface Temperature Identified by the Western North Pacific Typhoons

by Rui Liu, Liang Sun, Haihua Liu, Mengyuan Xu, Gaopeng Lu, Xiuting Wang and Youfang Yan

Oceans 2026, 7(1), 7; https://doi.org/10.3390/oceans7010007 (registering DOI) - 8 Jan 2026

Abstract

Although previous studies composited response of sea surface temperature (SST) to typhoon sea surface wind (SSW) forcing around typhoon center, how SST responded spatiotemporally along the typhoon track over the ocean remains unclear. Through Empirical Orthogonal Function (EOF) analysis, several isolated typhoons in the Western North Pacific (WNP) from 2021 to 2024 were investigated. Two SSW forcing modes and two SST response modes were identified. The first SSW mode spatially reflects the overall distribution of SSW along the track, centering at its maturation position. And the first SST mode exhibits a high spatial correlation (

| R | > 0.85

) with this SSW mode. The second SSW mode displays a distinct track-long scale dipole pattern along the path of the typhoon, representing its intensity variation during the “development–maturation–decay” lifecycle. Similarly, the second SST response mode shows a significant but lower correlation with this second SSW mode. Both corresponding SST response modes typically lag behind their respective wind-forcing by approximately 2 to 4 days, indicating that these SST response modes are direct reactions to SSW forcing. These cases implies that two track-long scale SSW modes are generally present during the lifecycle of typhoons and that their corresponding SST responses are dominated accordingly. Full article

(This article belongs to the Special Issue Recent Progress in Ocean Fronts)

24 pages, 999 KB

Open AccessArticle

From Linear to Circular: Barriers to Sustainable Transition in the Saudi Banking Sector

by Aroop Mukherjee and Luisa Pinto

Sustainability 2026, 18(2), 673; https://doi.org/10.3390/su18020673 (registering DOI) - 8 Jan 2026

Abstract

This study investigates the barriers in adopting the Circular Economy (CE) in Saudi Banking under Vision 2030 and using the Resource-Based View and stakeholder theory. This study examined how customer engagement, process innovation, and dynamic capabilities limit the implementation of CE. A quantitative, cross-sectional survey collected 418 responses from bank employees in Riyadh and was collected from January to March 2024. A 29-item Likert scale was analyzed with SmartPLS 4; measurement quality was strong, and confirmatory factor analysis confirmed construct validity. Results highlight the main barriers as customer resistance regulatory constraints and lack of adequate employee training. The construct is highly interconnected (r = 0.758), showing that improvements in customer engagement and process innovation strengthen dynamic capabilities. The study provides practical guidance for banks and policymakers on designing circular finance products, targeted training, and supportive regulations to accelerate the CE transition and achieve measurable sustainability outcomes in financial sectors, aligning with SDG 3, good health and well-being, and SDG 7, affordable and clean energy. Full article

(This article belongs to the Special Issue Business Circular Economy and Sustainability)

23 pages, 3876 KB

Open AccessArticle

Optimizing Drainage Design to Reduce Nitrogen Losses in Rice Field Under Extreme Rainfall: Coupling Log-Pearson Type III and DRAINMOD-N II

by Anis Ur Rehman Khalil, Fazli Hameed, Junzeng Xu, Muhammad Mannan Afzal, Khalil Ahmad, Shah Fahad Rahim, Raheel Osman, Peng Chen and Zhenyang Liu

Water 2026, 18(2), 175; https://doi.org/10.3390/w18020175 (registering DOI) - 8 Jan 2026

Abstract

The intensification of extreme rainfall events under changing climate regimes has heightened concerns over nutrient losses from paddy agriculture, particularly nitrogen (N), a primary contributor to non-point source pollution. Despite advances in drainage management, limited studies have integrated probabilistic rainfall modeling with N transport simulation to evaluate mitigation strategies in rice-based systems. This study addresses this critical gap by coupling the Log-Pearson Type III (LP-III) distribution with the DRAINMOD-N II model to simulate N dynamics under varying rainfall exceedance probabilities and drainage design configurations in the Kunshan region of eastern China. The DRAINMOD-N II showed good performance, with R² values of 0.70 and 0.69, AAD of 0.05 and 0.39 mg L⁻¹, and RMSE of 0.14 and 0.91 mg L⁻¹ for NO₃⁻-N and NH₄⁺-N during calibration, and R² values of 0.88 and 0.72, AAD of 0.06 and 0.21 mg L⁻¹, and RMSE of 0.10 and 0.34 mg L⁻¹ during validation. Using around 50 years of historical precipitation data, we developed intensity–duration–frequency (IDF) curves via LP-III to derive return-period rainfall scenarios (2%, 5%, 10%, and 20%). These scenarios were then input into a validated DRAINMOD-N II model to assess nitrate-nitrogen (NO₃⁻-N) and ammonium-nitrogen (NH₄⁺-N) losses across multiple drain spacing (1000–2000 cm) and depth (80–120 cm) treatments. Results demonstrated that NO₃⁻-N and NH₄⁺-N losses increase with rainfall intensity, with up to 57.9% and 45.1% greater leaching, respectively, under 2% exceedance events compared to 20%. However, wider drain spacing substantially mitigated N losses, reducing NO₃⁻-N and NH₄⁺-N loads by up to 18% and 12%, respectively, across extreme rainfall scenarios. The integrated framework developed in this study highlights the efficacy of drainage design optimization in reducing nutrient losses while maintaining hydrological resilience under extreme weather conditions. Full article

(This article belongs to the Section Water, Agriculture and Aquaculture)

22 pages, 1587 KB

Open AccessArticle

Characterization of Novel Sigma Receptor Ligands Derived from Multicomponent Reactions as Efficacious Treatments for Neuropathic Pain

by Ryosuke Shinouchi, Bengisu Turgutalp, Rohini S. Ople, Shainnel O. Eans, Ashai K. Williams, Haylee R. Hammond, Andras Varadi, Rebecca Notis Dardashti, Susruta Majumdar and Jay P. McLaughlin

Pharmaceuticals 2026, 19(1), 117; https://doi.org/10.3390/ph19010117 (registering DOI) - 8 Jan 2026

Abstract

Background/Objectives: Neuropathic pain remains a significant clinical challenge, with current treatments often providing inadequate relief and adverse effects. Sigma receptors (SRs) modulate nociception and have emerged as potential therapeutic targets for neuropathic pain. Although putative sigma-1 receptor (S1R) ligands have demonstrated analgesic efficacy in preclinical models, their in vivo efficacy and safety profiles require further clarification. Methods: Analogs of well-known selective S1R ligand UVM147 were synthesized using 3-component Ugi reactions and examined in vitro for receptor affinity in radioligand competition binding assays and in vivo with mouse models of neuropathic and inflammatory pain and adverse effects. Results: Three novel heterocyclic compounds (RO-4-3, RO-5-3, and RO-7-3) displayed in vitro nanomolar affinity with varying selectivity for both SR subtypes (S1R and S2R). When screened in vivo at a dose of 30 mg/kg s.c. in mice first subjected to chronic constriction injury (CCI), RO-5-3 and RO-7-3 possessed anti-allodynic potential, while UVM147 was inactive. Upon full characterization, RO-5-3 significantly attenuated mechanical allodynia in a dose-dependent manner, while RO-7-3 was ineffective at higher doses. Both compounds dose-dependently attenuated nociceptive behaviors in the mouse formalin assay. RO-5-3 induced mild respiratory depression without impairing locomotor activity, whereas RO-7-3 caused transient respiratory depression and locomotor impairment. Additionally, RO-5-3, but not RO-7-3, induced conditioned place aversion consistent with potential S2R involvement. Conclusions: RO-5-3 exerts antinociceptive and anti-allodynic effects with minimal adverse behavioral effects, supporting the role of SRs in pain modulation. These results add to growing evidence supporting the development of SR ligands as efficacious therapeutics for neuropathic pain with fewer clinical liabilities. Full article

(This article belongs to the Special Issue Current Advances in Therapeutic Potential of Sigma Receptor Ligands)

31 pages, 1781 KB

Open AccessArticle

Spatiotemporal Dynamics of Forest Biomass in the Hainan Tropical Rainforest Based on Multimodal Remote Sensing and Machine Learning

by Zhikuan Liu, Qingping Ling, Wenlu Zhao, Zhongke Feng, Huiqing Pei, Pietro Grimaldi and Zixuan Qiu

Forests 2026, 17(1), 85; https://doi.org/10.3390/f17010085 (registering DOI) - 8 Jan 2026

Abstract

Tropical rainforests play a vital role in maintaining global ecological balance, carbon cycling, and biodiversity conservation, making research on their biomass dynamics scientifically significant. This study integrates multi-source remote sensing data, including canopy height derived from GEDI and ICESat-2 satellite-borne lidar, Landsat imagery, and environmental variables, to estimate forest biomass dynamics in Hainan’s tropical rainforests at a 30 m spatial resolution, involving a correlation analysis of factors influencing spatiotemporal changes in Hainan Tropical Rainforest biomass. The research aims to investigate the spatiotemporal variations in forest biomass and identify key environmental drivers influencing biomass accumulation. Four machine learning algorithms—Backpropagation Neural Network (BP), Convolutional Neural Network (CNN), Random Forest (RF), and Gradient Boosting Decision Tree (GBDT)—were applied to estimate biomass across five forest types from 2003 to 2023. Results indicate the Random Forest model achieved the highest accuracy (R² = 0.82). Forest biomass and carbon stocks in Hainan Tropical Rainforest National Park increased significantly, with total carbon stocks rising from 29.03 million tons of carbon to 42.47 million tons of carbon—a 46.36% increase over 20 years. These findings demonstrate that integrating multimodal remote sensing data with advanced machine learning provides an effective approach for accurately assessing biomass dynamics, supporting forest management and carbon sink evaluations in tropical rainforest ecosystems. Full article

(This article belongs to the Special Issue Smart Forest Inventory, Management and Planning: Intelligent Technologies and Their Applications)

13 pages, 306 KB

Open AccessArticle

A Reflected–Forward–Backward Splitting Method for Monotone Inclusions Involving Lipschitz Operators in Banach Spaces

by Changchi Huang, Jigen Peng, Liqian Qin and Yuchao Tang

Mathematics 2026, 14(2), 245; https://doi.org/10.3390/math14020245 (registering DOI) - 8 Jan 2026

Abstract

The reflected–forward–backward splitting (RFBS) method is well-established for solving monotone inclusion problems involving Lipschitz continuous operators in Hilbert spaces, where it converges weakly under mild assumptions. Extending this method to Banach spaces presents significant challenges, primarily due to the nonlinearity of the duality mapping. In this paper, we propose and analyze an RFBS algorithm in the setting of real Banach spaces that are 2-uniformly convex and uniformly smooth. To the best of our knowledge, this work presents the first strong (R-linear) convergence result for the RFBS method in such Banach spaces, achieved under a newly adapted notion of strong monotonicity. Our results thus establish a foundational theoretical guarantee for RFBS in Banach spaces under strengthened monotonicity conditions, while highlighting the open problem of proving weak convergence for the general monotone case. Full article

(This article belongs to the Special Issue Nonlinear Functional Analysis: Theory, Methods, and Applications)

19 pages, 3760 KB

Open AccessArticle

Remote Sensing of Nematode Stress in Coffee: UAV-Based Multispectral and Thermal Imaging Approaches

by Daniele de Brum, Gabriel Araújo e Silva Ferraz, Luana Mendes dos Santos, Felipe Augusto Fernandes, Marco Antonio Zanella, Patrícia Ferreira Ponciano Ferraz, Willian César Terra, Vicente Paulo Campos, Thieres George Freire da Silva, Ênio Farias de França e Silva and Alexsandro Oliveira da Silva

AgriEngineering 2026, 8(1), 22; https://doi.org/10.3390/agriengineering8010022 (registering DOI) - 8 Jan 2026

Abstract

Early and non-destructive detection of plant-parasitic nematodes is critical for implementing site-specific management in coffee production systems. This study evaluated the potential of unmanned aerial vehicle (UAV) multispectral and thermal imaging, combined with textural analysis, to detect Meloidogyne exigua infestation in Coffea arabica (Topázio variety). Field surveys were conducted in two contrasting seasons (dry and rainy), and nematode incidence was identified and quantified by counting root galls. Vegetation indices (NDVI, GNDVI, NGRDI, NDRE, OSAVI), individual spectral bands, canopy temperature, and Haralick texture features were extracted from UAV-derived imagery and correlated with gall counts. Under the conditions of this experiment, strong correlations were observed between gall number and the red spectral band in both seasons (R > 0.60), while GNDVI (dry season) and NGRDI (rainy season) showed strong negative correlations with gall density. Thermal imaging revealed moderate positive correlations with infestation levels during the dry season, indicating potential for early stress detection when foliar symptoms were absent. Texture metrics from the red and green bands further improved detection capacity, particularly with a 3 × 3 pixel window at 135°. These results demonstrate that UAV-based multispectral and thermal imaging, enhanced by texture analysis, can provide reliable early indicators of nematode infestation in coffee. Full article

45 pages, 5665 KB

Open AccessArticle

Adaptive Traversability Policy Optimization for an Unmanned Articulated Road Roller on Slippery, Geometrically Irregular Terrains

by Wei Qiang, Quanzhi Xu and Hui Xie

Machines 2026, 14(1), 79; https://doi.org/10.3390/machines14010079 (registering DOI) - 8 Jan 2026

Abstract

To address the autonomous traversability challenge of an Unmanned Articulated Road Roller (UARR) operating on harsh terrains where low-adhesion slipperiness and geometric irregularities are coupled, and traction capacity is severely limited, this paper proposes a Terrain-Adaptive Maximum-Entropy Policy Optimization (TAMPO). A unified multi-physics simulation platform is constructed, integrating a high-fidelity vehicle dynamics model with a parameterized terrain environment. Considering the prevalence of geometric irregularities in construction sites, a parameterized mud-pit model is established—generalized from a representative case—as a canonical physical model and simulation carrier for this class of traversability problems. Based on this model, a family of training and test scenarios is generated to span a broad range of terrain shapes and adhesion conditions. On this foundation, the TAMPO algorithm is introduced to enhance vehicle traversability on complex terrains. The method comprises the following: (i) a Terrain Interaction-Critical Reward (TICR), which combines dense rewards representing task progress with sparse rewards that encourage terrain exploration, guiding the agent to both climb efficiently and actively seek high-adhesion favorable terrain; and (ii) a context-aware adaptive entropy-regularization mechanism that fuses, in real time, three feedback signals—terrain physical difficulty, task-execution efficacy, and model epistemic uncertainty—to dynamically regulate policy entropy and realize an intelligent, state-dependent exploration–exploitation trade-off in unstructured environments. The performance and generalization ability of TAMPO are evaluated on training, interpolation, and extrapolation sets, using PPO, SAC, and DDPG as baselines. On 90 highly challenging extrapolation scenarios, TAMPO achieves an average success rate (S.R.) of 60.00% and an Average Escape Time (A.E.T.) of 17.56 s, corresponding to improvements of up to 22.22% in S.R. and reductions of up to 5.73 s in A.E.T. over the baseline algorithms, demonstrating superior decision-making performance and robust generalization on coupled slippery and irregular terrains. Full article

(This article belongs to the Special Issue Modeling, Estimation, Control, and Decision for Intelligent Vehicles)

25 pages, 6358 KB

Open AccessArticle

A Novel Chaotic Encryption Algorithm Based on Fuzzy Rule-Based Sugeno Inference: Theory and Application

by Aydin Muhurcu and Gulcin Muhurcu

Mathematics 2026, 14(2), 243; https://doi.org/10.3390/math14020243 - 8 Jan 2026

Abstract

This study proposes a robust chaotic encryption framework based on a Fuzzy Rule-Based Sugeno Inference (FRBSI) system, integrated with high-level security analyses. The algorithm employs a dynamic mixture of Lorenz chaotic state variables, which are numerically modeled using the Euler-Forward method to ensure computational accuracy. Unlike conventional methods, the carrier signal’s characteristics are not static; instead, its amplitude and dynamic behavior are continuously adapted through the FRBSI mechanism, driven by the instantaneous thresholds of the information signal. The security of the proposed system was rigorously evaluated through Histogram analysis, Number of Pixels Change Rate (NPCR), and Unified Average Changing Intensity (UACI) metrics, which confirmed the algorithm’s high sensitivity to plaintext variations and resistance against differential attacks. Furthermore, Key Sensitivity tests demonstrated that even a single-bit discrepancy in the receiver-side Sugeno rule base leads to a total failure in signal reconstruction, providing a formidable defense against brute-force attempts. The system’s performance was validated in the MATLAB/Simulink of R2021a version environment, where frequency and time-domain analyses were performed via oscilloscope and Fourier transforms. The results indicate that the proposed multi-layered fuzzy-chaotic structure significantly outperforms traditional encryption techniques in terms of unpredictability, structural security, and robustness. Full article

(This article belongs to the Topic A Real-World Application of Chaos Theory)

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25 pages, 855 KB

Open AccessArticle

Understanding the Role of Reading and Oral Language Skills Growth in Overcoming Reading Comprehension Difficulties

by Apostolos Kargiotidis and George Manolitsis

Behav. Sci. 2026, 16(1), 90; https://doi.org/10.3390/bs16010090 - 8 Jan 2026

Abstract

The present longitudinal retrospective study examined in a sample of 123 Greek-speaking children whether the raw score growth in a broad range of oral language and reading skills from Grade 1 to Grade 3 differs among children with persistent reading comprehension difficulties (pRCD; N = 49) identified in Grade 3, those exhibiting a resolving tendency of RCD (rRCD; N = 16), and typically developing (TD; N = 58) children. Children were classified into the respective groups, based on their performance on standardized reading comprehension measures in Grades 1, 2, and 3. They were, also, assessed on phonological awareness, rapid automatized naming (RAN), morphological awareness, vocabulary, word reading accuracy, word reading fluency, and text-reading fluency across the three Grades. Mixed ANOVAs showed that children with pRCD displayed slower growth in morphological awareness, word reading fluency, and text-reading fluency than the other two groups. Children with rRCD did not differ from TD children on these measures, but they exhibited a higher growth on RAN. Both groups of children with RCD outperformed TD children on the growth of phonological awareness and word reading accuracy, whereas no group differences revealed in vocabulary. Our results suggest that more rapid gains in morphological awareness, RAN, word reading fluency, and text-reading fluency over time might be associated with a resolving tendency of reading comprehension difficulties, providing valuable insights for intervention policy. Full article

(This article belongs to the Special Issue Learning Disabilities in Reading and Writing: Current Issues in Assessment and Intervention)

39 pages, 13492 KB

Open AccessArticle

High-Spatiotemporal-Resolution Population Distribution Estimation Based on the Strong and Weak Perception of Population Activity Patterns

by Rui Li, Guangyu Liu, Hongyan Li and Jing Xia

ISPRS Int. J. Geo-Inf. 2026, 15(1), 34; https://doi.org/10.3390/ijgi15010034 - 8 Jan 2026

Abstract

Population activity drives urban development, and high-spatiotemporal-resolution population distribution provides critical insights for refined urban management and social services. However, mixed population activity patterns and spatial heterogeneity make simultaneous high-temporal- and -spatial-resolution estimation difficult. Therefore, we propose the High-Spatiotemporal-Resolution Population Distribution Estimation Based on the Strong and Weak Perception of Population Activity Patterns (SWPP-HSTPE) method to estimate hourly population distribution at the building scale. During the weak-perception period, we construct a Modified Dual-Environment Feature Fusion model using building features within small-scale grids to estimate stable nighttime populations. During the strong-perception period, we incorporate activity characteristics of weakly perceived activity populations (minors and older people). Then, the Self-Organizing Map algorithm and spatial environment function purity are used to decompose mixed patterns of strongly perceived activity populations (young and middle-aged) and to extract fundamental patterns, combined with building types, for population calculation. Results demonstrated that the SWPP-HSTPE method achieved high-spatiotemporal-resolution population distribution estimation. During the weak-perception period, the estimated population correlated strongly with actual household counts (r = 0.72) and outperformed WorldPop and GHS-POP by 0.157 and 0.133, respectively. During the strong-perception period, the SWPP-HSTPE model achieves a correlation with hourly population estimates that is approximately 4% higher than that of the baseline model, while reducing estimation errors by nearly 2%. By jointly accounting for temporal dynamics and population activity patterns, this study provides valuable data support and methodological insights for fine-grained urban management. Full article

26 pages, 2530 KB

Open AccessArticle

Deep-Sea Sediment Creep Mechanism and Prediction: Modified Singh–Mitchell Model Under Temperature–Stress–Time Coupling

by Yan Feng, Qiunan Chen, Lihai Wu, Guangping Liu, Jinhu Tang, Zengliang Wang, Xiaodi Xu, Bingchu Chen and Shunkai Liu

J. Mar. Sci. Eng. 2026, 14(2), 133; https://doi.org/10.3390/jmse14020133 - 8 Jan 2026

Abstract

With the advancement in deep-sea resource development, the creep behavior of deep-sea remolded sediments under coupled temperature, confining pressure (σ₃), and stress effects has become a critical issue threatening engineering stability. The traditional Singh–Mitchell model, limited by its neglect of temperature effects and prediction of infinite strain, struggles to meet deep-sea environmental requirements. Based on low-temperature, high-pressure triaxial tests (with temperatures ranging from 4 to 40 °C and confining pressures ranging from 100 to 300 kPa), this study proposes a modified model incorporating temperature–stress–time coupling. The model introduces a hyperbolic creep strain rate decay function to achieve strain convergence, establishes a saturated strain–stress exponential relationship, and quantifies the effect of temperature on characteristic time via coupling through the Arrhenius equation. The modified model demonstrates R² values > 0.96 for full-condition creep curves. The results show several key findings: a 10 °C increase in temperature leads to a 30–50% growth in the steady-state creep rate; a 100 kPa increase in confining pressure enhances long-term strength by 20–30%. 20 °C serves as a critical temperature point. At this point, strain amplification reaches 2.1 times that of low-temperature ranges. These experimental findings provide crucial theoretical foundations and technical support for incorporating soil creep effects in deep-sea engineering design. Full article

(This article belongs to the Section Ocean Engineering)

14 pages, 325 KB

Open AccessArticle

Exploring Associations Between STEAM-Based Interventions and Executive and Cognitive Skills in Children with ADHD

by María del Mar Bueno-Galán, Carlos Barbosa-Torres, María José Godoy-Merino, Alperen Yandi, Alejandro Arévalo-Martínez, María Pilar Cantillo-Cordero, María Elena García-Baamonde Sánchez and Juan Manuel Moreno-Manso

Healthcare 2026, 14(2), 169; https://doi.org/10.3390/healthcare14020169 - 8 Jan 2026

Abstract

Background: This study examines whether participation in STEAM-based educational activities is associated with improvements in executive functions (EFs) and cognitive skills in children with Attention Deficit Hyperactivity Disorder (ADHD). Methods: A total of 60 children diagnosed with ADHD (mean age = 8 years) participated, with 30 following a traditional educational approach and 30 engaged in STEAM-based activities. Executive functions and cognitive abilities were assessed using standardized instruments (BRIEF, WISC-V, CARAS-R), and data were analyzed with IBM SPSS Statistics 25. Results: Children in the STEAM group outperformed the control group across several domains, showing statistically significant gains in inhibition, planning and organization, verbal comprehension, visuospatial skills, processing speed, total IQ, efficiency, and the Impulsivity Control Index (ICI). Conclusions: These findings suggest that STEAM-based educational experiences may support neurodevelopmental growth and enhance cognitive and executive functioning in children with ADHD, although causal inferences cannot be drawn due to the cross-sectional design. Full article

19 pages, 6097 KB

Open AccessArticle

Circuitous Ways of EWS::FLI1 Using Circular RNA ZNF609 to Evade Translational Repression by miR-145 in Ewing’s Sarcoma

by Aakash Koppula, Ahmed Abdelgawad, Brigette Romero, Victoria Beringer, Vijay Parashar and Mona Batish

Biomedicines 2026, 14(1), 129; https://doi.org/10.3390/biomedicines14010129 - 8 Jan 2026

Abstract

Background: Ewing’s sarcoma (EwS) is a pediatric bone and soft tissue cancer driven by the oncogenic fusion protein EWS::FLI1. Currently, EwS lacks targeted therapies, necessitating the identification of novel regulatory mechanisms. While the role of microRNAs and long non-coding RNAs has been explored in EwS, the presence and functional significance of circular RNAs (circRNAs) in EwS is not reported. This is the first study to report the presence and role of oncogenic circRNA, circZNF609 in EwS tumor progression. Methods: Expression of circZNF609 was validated in 5 different EwS cell lines using qPCR. Cellular localization of circZNF609 was identified using circFISH. Functional assays for proliferation, migration and apoptosis were performed in wild type and circZNF609 knocked down (KD) cell lines to confirm its oncogenic role. The impact of circZNF609 on EWS::FLI1 protein levels was confirmed using western blots, immunofluorescence, and polysome fractionation. Mechanistic insights were gained utilizing bioinformatic, dual-luciferase reporter assays, rescue experiments, and microscopy to identify and validate the circRNA-miRNA-mRNA regulatory axis. Results: We report the first identification of circZNF609 in EwS, demonstrating that its expression is EWS::FLI1-dependent. Functional analysis reveals that circZNF609 promotes cell proliferation and metastasis while inhibiting apoptosis. Mechanistically, circZNF609 acts as a molecular sponge for miR-145-5p. By sequestering this miRNA, circZNF609 prevents the translational repression of EWS::FLI1, thereby sustaining oncogenic signaling. Conclusions: These findings identify circZNF609 as a novel post-transcriptional regulator of EWS::FLI1 and establish its critical role in EwS pathogenesis. Our results suggest that targeting the circZNF609/miR-145-5p/EWS::FLI1 axis may offer a promising therapeutic strategy for EwS. Full article

(This article belongs to the Collection MicroRNAs, tRNA Fragments, Long Non-coding and Circular RNAs: Pivotal Regulators of Gene Expression and Their Roles in Human Physiology and Disease)

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