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18 pages, 697 KB

Open AccessArticle

Dietary Patterns, Eating Disorder Risk, Emotional Distress, and Amino Acid Intake in Adults Seeking Weight Loss

by Alessia Placanica, Carmelo Pujia, Rossella Bruno, Rosy Conforto, Giovanni Luigi Tripepi, Elisa Mazza, Yvelise Ferro, Alberto Castagna, Samantha Maurotti, Arturo Pujia and Tiziana Montalcini

Nutrients 2026, 18(15), 2497; https://doi.org/10.3390/nu18152497 (registering DOI) - 2 Aug 2026

Abstract

Background: Diet quality and amino acid intake influence both physical health and psychological well-being, potentially affecting eating disorder risk. This study aimed to investigate the relationship between dietary patterns, amino acid intake, and eating disorder risk. Methods: This cross-sectional study included [...] Read more.

Background: Diet quality and amino acid intake influence both physical health and psychological well-being, potentially affecting eating disorder risk. This study aimed to investigate the relationship between dietary patterns, amino acid intake, and eating disorder risk. Methods: This cross-sectional study included 130 adults with overweight or obesity. All participants were assessed for eating disorder risk and body image distortion. Dietary intake was assessed using a validated food frequency questionnaire. Principal Component Analysis was performed to identify major dietary patterns, and logistic regression was used to estimate the odds of eating disorder risk in relation to dietary pattern adherence and specific amino acid intake. Results: Six major dietary patterns were identified; among these, the mixed Mediterranean-like and Comfort Food patterns showed significant associations with eating disorder risk. Greater adherence to the mixed Mediterranean-like pattern was associated with lower odds of eating disorder risk (OR = 0.60; 95% CI: 0.39–0.93; p = 0.023). Conversely, adherence to the Comfort Food pattern, characterized by sweets, milk, and dairy products, showed a trend toward higher odds of eating disorder risk (OR = 1.49; 95% CI: 0.99–2.23; p = 0.05) and body image distortion (OR = 1.70; 95% CI: 1.03–2.79; p = 0.03). Regarding amino acid intake, higher consumption of glutamic acid and glycine was associated with a lower eating disorder risk, whereas higher leucine intake was associated with higher eating disorder risk. Conclusions: Dietary patterns are associated with eating disorder risk and body image distortion. A mixed Mediterranean-like dietary pattern may have protective effects, whereas greater adherence to a Comfort Food pattern and higher intake of specific amino acids may increase the risk of eating disorders. However, further clinical studies are needed to confirm our findings. Full article

(This article belongs to the Special Issue Research on Eating Disorders, Physical Activity and Body Image)

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18 pages, 5806 KB

Open AccessArticle

Role of CaCO₃ in Retarding UV- and Thermally Induced Degradation of PVC Compounds

by Soraya Nait Larbi, Abdallah Hedir, Mustapha Moudoud, David Clark, Ali Durmus, Omar Lamrous and Abderrahmane Haddad

Materials 2026, 19(15), 3270; https://doi.org/10.3390/ma19153270 (registering DOI) - 2 Aug 2026

Abstract

This study provides an in-depth investigation of the influence of calcium carbonate (CaCO₃) filler on the mechanical performance and aging resistance of polyvinyl chloride (PVC)-based composites. PVC/CaCO₃ composites containing 2.5, 5, and 7.5 wt% of CaCO₃ were subjected to [...] Read more.

This study provides an in-depth investigation of the influence of calcium carbonate (CaCO₃) filler on the mechanical performance and aging resistance of polyvinyl chloride (PVC)-based composites. PVC/CaCO₃ composites containing 2.5, 5, and 7.5 wt% of CaCO₃ were subjected to accelerated aging under combined ultraviolet (UV) irradiation and thermal stress for up to 1248 h. The key mechanical properties of specimens —tensile strength and elongation at break—were measured before and after aging. Changes in surface morphology, coloration, hydrophobicity, and chemical composition were characterized using scanning electron microscopy (SEM-EDS), X-ray spectroscopy, atomic force microscopy (AFM), contact angle measurements, and carbonyl index calculation to quantify relationships between the structural and physical properties of the specimens and aging conditions. The results reveal a significant correlation between filler content and the mechanical behavior of aged specimens, highlighting the potential of CaCO₃ reinforcement not only to improve the retention of mechanical properties but also to increase the service life of PVC-based insulation compounds. Full article

(This article belongs to the Section Polymeric Materials)

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19 pages, 298 KB

Open AccessArticle

Discovering a New Genetic Family Relative in Mid to Later Life: Reconstructions of Identity and Self

by Barbara Ann Mitchell, Asli Evrim Ozer and Boah Kim

Genealogy 2026, 10(3), 99; https://doi.org/10.3390/genealogy10030099 (registering DOI) - 2 Aug 2026

Abstract

There has been a significant rise in the number of individuals searching for genetic relatives using home-based DNA kits alongside online historical records, archival sources, and family stories. Initial studies suggest that these experiences can have profound psycho-social and emotional impacts on self [...] Read more.

There has been a significant rise in the number of individuals searching for genetic relatives using home-based DNA kits alongside online historical records, archival sources, and family stories. Initial studies suggest that these experiences can have profound psycho-social and emotional impacts on self and identity. However, research to date has not examined the experiences of older adults who uncover previously unknown relatives and how these discoveries influence their identities in later life. To address this gap, this study draws on life course and identity theories. We conduct three ordinary least squares (OLS) regression analyses to examine how age, the context of discovery, and the subsequent relationship with the newly discovered family member (or proxy) affect three conceptual identity domains: familial belonging, cultural identity, and sense of self/uniqueness. Data are drawn from an international online survey of 293 amateur genealogists aged 55 years and older who located a previously unknown close genetic relative within the past five years using DNA testing. We also synthesize and integrate emergent themes from 50 in-depth qualitative follow-up interviews. Findings show that reported identity changes are associated with stronger relationship quality, more frequent contact, emotionally driven motivations (compared to curiosity), and more complex searches, net of covariates. Qualitative data elucidate the expansive, fluid, and sometimes ambiguous nature of identity reconstruction following unexpected family discoveries today. Full article

37 pages, 7233 KB

Open AccessArticle

Chaotic Random Cloud Drift Optimization with Kent Initialization and Opposition-Based Learning for Engineering Design Problems

by Chaochuan Jia, Xinyu Gao, Jiahui Liu, Yuhui Wang, Maosheng Fu, Zhongrong Shi and Yu Liu

Algorithms 2026, 19(8), 641; https://doi.org/10.3390/a19080641 (registering DOI) - 2 Aug 2026

Abstract

To overcome challenges associated with Cloud Drift Optimization (CDO), primarily involving early stagnation and the imbalance between global exploration and local exploitation in tackling high-dimensional, complex optimization tasks, an improved variant named Chaotic Random Cloud Drift Optimization (CRCDO) is proposed in this study. [...] Read more.

To overcome challenges associated with Cloud Drift Optimization (CDO), primarily involving early stagnation and the imbalance between global exploration and local exploitation in tackling high-dimensional, complex optimization tasks, an improved variant named Chaotic Random Cloud Drift Optimization (CRCDO) is proposed in this study. First, a Kent chaotic initialization mapping is adopted to generate diverse initial solutions. Second, the parameter sensitivity is adjusted to appropriately strengthen the local exploitation capability of the algorithm. Third, a centroid opposition-based learning strategy is introduced to generate mutated clouds, which enables the algorithm to escape local optima. Owing to the cooperative effect of these three strategies, CRCDO achieves faster convergence and higher computational accuracy while maintaining dynamic stability. To evaluate its performance, CRCDO is compared with eleven well-established optimization algorithms on the CEC2017 suites. The experimental results demonstrate that CRCDO exhibits superior optimization performance on a wide range of complex problems. Furthermore, the proposed algorithm has been successfully applied to three representative engineering design problems, including robot gripper design, welded beam design, and compression spring design, as well as a regression task for predicting praeruptorin A and praeruptorin B in Peucedanum praeruptorum. The results show that CRCDO achieves faster convergence, higher solution accuracy, and greater stability on the benchmark problems, while its engineering and prediction applications demonstrate robustness and practical applicability across different problem classes. Full article

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27 pages, 8257 KB

Open AccessArticle

Matrix Architecture and Integrin Branch Balance Distinguish Immune-Regulatory States in Clear Cell Renal Cell Carcinoma

by Caner Karaca, Mehmet Emin Arayici, Hüseyin Salih Semiz, Hulya Ellidokuz and Yasemin Basbinar

Curr. Issues Mol. Biol. 2026, 48(8), 789; https://doi.org/10.3390/cimb48080789 (registering DOI) - 2 Aug 2026

Abstract

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is frequently vascular and immune-infiltrated, yet durable responses to immune checkpoint blockade remain limited. This suggests that immune resistance may reflect tumor microenvironmental organization and mechanotransduction state rather than immune infiltration alone. We aimed to determine [...] Read more.

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is frequently vascular and immune-infiltrated, yet durable responses to immune checkpoint blockade remain limited. This suggests that immune resistance may reflect tumor microenvironmental organization and mechanotransduction state rather than immune infiltration alone. We aimed to determine whether matrix reorganization and branch-specific integrin mechanosensing define immune-regulatory states in ccRCC, with particular attention to adenosine-associated immune resistance. Methods: We performed an integrative computational analysis of TCGA-KIRC bulk RNA-sequencing, clinical, survival, immune feature, and reverse-phase protein array data. Matrix- and mechanobiology-related programs were quantified using ssGSEA, compact z-score-based signatures, and principal component-based sensitivity analyses. Immune-regulatory programs, CAF and ECM scores, FAK/SRC activation features, and MINER-inferred transcriptional regulons were integrated using stage association, correlation, partial correlation, variance partitioning, survival, and transcriptional state analyses. Results: Matrix-centered transcriptional programs were the dominant stage-associated mechanobiology signal in ccRCC, including ECM deposition, collagen organization, matrix remodeling, fluid shear stress, and YAP/TAZ activity. A compact ECM-associated core (ECM_Stiffness_Core; a ten-gene signature whose highest-loading members include FN1, COL1A1, COL6A1, and LOX) captured a matrix reorganization program, indicating remodeling of ECM composition and architecture rather than uniform increases in tumor stiffness, pressure, or bulk mechanical load. Matrix remodeling was associated with CAF abundance, TGFβ signaling, CD276/B7-H3, CSF1-related myeloid biology, ENTPD1/CD39, and PRDM1, whereas associations with cytotoxic immune cells were weaker. Integrin mechanosensing separated into opposing branches: ITGA5/ILK/SRC-associated features aligned with higher-risk biology and adenosine-linked immune regulation, whereas PTK2/FAK–RHOA–ROCK components showed lower-risk directions. RPPA analyses supported SRC–FAK imbalance as an adverse signaling pattern. MINER analyses further separated matrix-associated immune-suppressive regulons from canonical integrin/focal adhesion states. Conclusions: Matrix reorganization and integrin branch imbalance appear to shift ccRCC toward distinct immune-regulatory states. We propose a conceptual model that matrix architecture may act as a directional suppressive amplifier, whereas the relative balance between ITGA5/ILK/SRC-associated signaling and canonical PTK2/FAK–RHOA–ROCK mechanosensing functions as an integrin branch rheostat. This framework identifies matrix remodeling, CD276/B7-H3, CSF1-related myeloid biology, adenosine signaling, and SRC–FAK imbalance as candidate biological axes for future investigation, including their potential relevance to combination strategies beyond PD-1/PD-L1 blockade. Future experimental, spatial, and treatment response studies may further clarify the mechanistic basis of these associations and evaluate their potential therapeutic relevance. Full article

(This article belongs to the Special Issue Bioinformatics in Human Disease Network Analysis)

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18 pages, 2075 KB

Open AccessArticle

LAKF-Based 3D Multi-Object Tracking: Hybrid KalmanNet for Nonlinear Motion Estimation

by Yucheng Long, Jian Song, Yunfeng Xu, Peng He, Lina Bu and Qiang Fu

Electronics 2026, 15(15), 3422; https://doi.org/10.3390/electronics15153422 (registering DOI) - 2 Aug 2026

Abstract

Reliable 3D multi-object tracking (MOT) is essential for autonomous driving. The model-based Kalman filter (KF) is the standard motion estimator in 3D MOT, but its linear-dynamics assumption and constant noise covariances limit its adaptability to nonlinear motion and time-varying noise. The learning-aided Kalman [...] Read more.

Reliable 3D multi-object tracking (MOT) is essential for autonomous driving. The model-based Kalman filter (KF) is the standard motion estimator in 3D MOT, but its linear-dynamics assumption and constant noise covariances limit its adaptability to nonlinear motion and time-varying noise. The learning-aided Kalman filter (LAKF) addresses these issues by learning the Kalman gain (KG) through recurrent neural networks. We adopt CNPE-KalmanNet, a variant that integrates complex-number position encoding to capture semantic correlations among heterogeneous state components. However, the analytical KG is derived under the assumption that the process and measurement noise covariance matrices are positive definite, whereas the learned KG from CNPE-KalmanNet lacks structural constraints. The unconstrained learned KG tends to produce a dense matrix, leading to cross-dimensional coupling, particularly across different scales. This paper proposes a hybrid KG that fuses the model-based analytical KG with the data-driven learned KG. Compared to the AB3DMOT baseline on KITTI and the P3DMOT baseline on nuScenes, our approach improves average recall by 13% and 22%, and IoU by 6% and 7% in state estimation, and AMOTA by 0.7% and 0.5% for overall tracking accuracy. The hybrid design retains the numerical stability of analytical filtering while incorporating the strong nonlinear fitting capacity from deep learning. Full article

(This article belongs to the Special Issue Advances in Electrical and Autonomous Vehicles: Trends, Challenges and Prospects)

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16 pages, 1366 KB

Open AccessReview

Vaccine-Associated Anterior Uveitis

by Seyyedehfatemeh Ghalibafan, Mona Oraei, Mohammadali Ashraf, Ali R. Djalilian, Pooja Bhat and Hajirah N. Saeed

Vaccines 2026, 14(8), 672; https://doi.org/10.3390/vaccines14080672 (registering DOI) - 2 Aug 2026

Abstract

Vaccine-associated anterior uveitis (VAAU) is an uncommon ocular inflammatory phenotype reported after several vaccine platforms. It describes anterior segment inflammation occurring after vaccination when infectious, autoimmune, idiopathic, medication-related, and other possible causes have been reasonably excluded. The current literature indicates that post-vaccination uveitis [...] Read more.

Vaccine-associated anterior uveitis (VAAU) is an uncommon ocular inflammatory phenotype reported after several vaccine platforms. It describes anterior segment inflammation occurring after vaccination when infectious, autoimmune, idiopathic, medication-related, and other possible causes have been reasonably excluded. The current literature indicates that post-vaccination uveitis is rare relative to the scale of immunization, although anterior uveitis is frequently reported among post-vaccination ocular inflammatory events. Evidence remains limited by reliance on case reports, case series, retrospective cohorts, and passive surveillance data, which restricts precise incidence estimation and causal interpretation. Accordingly, the available evidence primarily supports a temporal association rather than a confirmed causal relationship. Proposed mechanisms include innate immune activation, molecular mimicry, adjuvant- or formulation-related immune stimulation, bystander activation, delayed-type hypersensitivity, and host susceptibility related to prior uveitis, autoimmune disease, immune dysregulation, or genetic predisposition. Clinically, VAAU may present with redness, pain, photophobia, blurred vision, anterior chamber cells and flare, keratic precipitates, posterior synechiae, elevated intraocular pressure, vitritis, or cystoid macular edema. Most cases described in the literature are mild to moderate and improve with topical corticosteroids and cycloplegic therapy, whereas recurrent, severe, or treatment-intensive courses have been reported mainly in predisposed individuals. Future work should emphasize active surveillance, standardized phenotype-specific reporting, harmonized case definitions, and mechanistic studies to better define risk, recurrence patterns, and causality. Careful interpretation of suspected cases can support accurate diagnosis, patient counseling, and vaccine-safety monitoring without undermining clinically indicated immunization. Full article

(This article belongs to the Special Issue Safety and Immunogenicity of Vaccination)

21 pages, 1401 KB

Open AccessArticle

Conversion Surgery for Advanced Gastric Cancer According to First-Line Treatment Strategy: A Single-Center Experience with a Focused Review of the Literature

by Jun Kinoshita, Kenta Doden, Kengo Hayashi, Ryota Matsui, Hiroto Saito, Megumi Watanabe, Toshikatsu Tsuji, Daisuke Yamamoto and Noriyuki Inaki

Cancers 2026, 18(15), 2483; https://doi.org/10.3390/cancers18152483 (registering DOI) - 2 Aug 2026

Abstract

Background/Objectives: First-line therapy for advanced gastric cancer (AGC) has evolved from cytotoxic chemotherapy to HER2-targeted and immune checkpoint inhibitor (ICI)-based regimens, yet conversion surgery (CS) outcomes across these strategies remain poorly characterized. We describe CS outcomes and prognostic factors by first-line strategy at [...] Read more.

Background/Objectives: First-line therapy for advanced gastric cancer (AGC) has evolved from cytotoxic chemotherapy to HER2-targeted and immune checkpoint inhibitor (ICI)-based regimens, yet conversion surgery (CS) outcomes across these strategies remain poorly characterized. We describe CS outcomes and prognostic factors by first-line strategy at a single center. Methods: We retrospectively reviewed 187 patients with AGC who began first-line therapy from 2011, grouped as cytotoxic (CTX, n = 127), HER2-targeted (trastuzumab, n = 21), or ICI (n = 39). CS was defined as resection after response, including an extended oligometastatic definition (n = 74). Overall survival (OS) was measured from chemotherapy initiation, and prognostic factors were assessed by Cox regression. Results: Median OS was 14.8, 18.9, and 20.9 months for CTX, trastuzumab, and ICI, respectively (p = 0.048). CS rates were comparable (41%, 33%, and 38%; p = 0.794). Pathological response was more pronounced after trastuzumab/ICI (grade 3 and ypStage 0/1; both p < 0.001). Among CS cases, R0 resection (hazard ratio [HR] 0.31) and trastuzumab/ICI therapy (HR 0.37) were independent favorable factors, whereas high inflammatory–nutritional indices (NLR, CAR) were independent poor prognostic factors. OS was comparable between oligometastatic and conventional CS (p = 0.324). Conclusions: In this hypothesis-generating study, response depth tracked tumor biology, whereas survival was determined by R0 resection, targeted/ICI therapy, and host inflammatory–nutritional status—two largely dissociable axes informing biology- and host-based selection of CS candidates for prospective testing. Full article

(This article belongs to the Special Issue Current Status and Prospects of Multimodal Treatment for Upper Gastrointestinal Cancer)

16 pages, 653 KB

Open AccessArticle

Dimension-Wise Probing of Music Foundation Models for Chinese and Western Music: Timbre, Technique, Key, and Mode

by Xueying Bai, Nanmu Hui, Yanping Li and Xiaowei Han

Electronics 2026, 15(15), 3421; https://doi.org/10.3390/electronics15153421 (registering DOI) - 2 Aug 2026

Abstract

Music foundation models are increasingly used as feature extractors in music information retrieval; yet, their treatment of Chinese tonal organization has received little controlled evaluation. We probe frozen MERT, MuQ, CultureMERT, and an 88-dimensional librosa baseline on instrument timbre, guzheng playing technique, Western [...] Read more.

Music foundation models are increasingly used as feature extractors in music information retrieval; yet, their treatment of Chinese tonal organization has received little controlled evaluation. We probe frozen MERT, MuQ, CultureMERT, and an 88-dimensional librosa baseline on instrument timbre, guzheng playing technique, Western key, and Chinese pentatonic mode. Probes are evaluated with task-specific splits that guard against leakage and with chance-normalized accuracy. Timbre is near ceiling (0.994–0.998), whereas source-aware guzheng-technique accuracy ranges from 0.382 to 0.787. In the unmatched external comparison, GiantSteps key scores 0.441–0.604 and CNPM mode pattern scores 0.294–0.355; this difference is descriptive because the corpora differ in genre, production, provenance, and label distribution. Same-audio CNPM controls identify an important boundary: the TongGong system reaches 0.649–0.734, and absolute tonic reaches 0.433–0.480, whereas their matched five-way mode-pattern labels reach 0.256–0.350 and 0.243–0.366, respectively. Chroma ablations show that pitch-class energy is central to the external key task but does not by itself account for CNPM mode-pattern performance. These results map which musical dimensions are readily decodable from the evaluated frozen representations while avoiding a cultural-capability interpretation of the unmatched cross-corpus comparison. Full article

(This article belongs to the Special Issue Recent Advances in Audio, Speech and Music Processing and Analysis, 2nd Edition)

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26 pages, 752 KB

Open AccessReview

Internal and External Psychological Control and Psychological Reserve: Psychological Change Mechanisms in Psychotherapy

by Gerald Young

Psychiatry Int. 2026, 7(4), 169; https://doi.org/10.3390/psychiatryint7040169 (registering DOI) - 2 Aug 2026

Abstract

This article proposes a general integrative model focusing on psychological control and psychological reserve. The former refers to internal psychological control and external psychological control. Internal psychological control refers to the management of physiological processes associated with arousal and panics. Here, the concept [...] Read more.

This article proposes a general integrative model focusing on psychological control and psychological reserve. The former refers to internal psychological control and external psychological control. Internal psychological control refers to the management of physiological processes associated with arousal and panics. Here, the concept of internal psychological control is differentiated into two components: cognitive control/executive function and self-control/emotional regulation. External psychological control refers to the sense the person has of being able to manage, have agency in, and otherwise not be overwhelmed by the external context in which one is adapting functionally. Here, the concept of external psychological control is differentiated into two major sub-components: managing reactivity to external events, such as to daily stressors or extreme events, e.g., natural disasters, and proactively taking steps to have agency in and using predictive processing to adjust to context by mitigating the probability of experiencing overwhelming events. Psychological reserve refers to the fluid state reservoir of mental, cognitive, emotional, motivational, and stress management/coping space that is available for use in confronting ongoing and new stressors, challenges, or difficulties. Here, this article differentiates psychological reserve into phases of depletion and recovery. This article examines prior work on psychological control and reserve, demonstrating how they can be understood or modified based on the present sub-component differentiation of the concepts involved. The revised model is applied to understanding psychotherapeutic change mechanisms, a biopsychosocial model of the mechanisms, an integrated functional adaptational model, posttraumatic stress disorder, a unified model for psychotherapy and psychology generally, and clinical recommendations. Full article

(This article belongs to the Section Clinical Psychiatry and Psychotherapy)

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27 pages, 2090 KB

Open AccessArticle

Natural Risk Shocks and Rural Household Livelihood Resilience: Does Digital Transformation Make a Difference?

by Bin Yang, Tianshu Quan, Jia Li and Hui Zhang

Agriculture 2026, 16(15), 1665; https://doi.org/10.3390/agriculture16151665 (registering DOI) - 2 Aug 2026

Abstract

The natural disasters caused by climate change are increasingly threatening the livelihood sustainability of rural households. How to enhance the adaptability of farmers has become a major issue that urgently needs to be addressed in rural development. An increasing amount of research suggests [...] Read more.

The natural disasters caused by climate change are increasingly threatening the livelihood sustainability of rural households. How to enhance the adaptability of farmers has become a major issue that urgently needs to be addressed in rural development. An increasing amount of research suggests that the digital transformation in rural areas may provide solutions to this problem. This study selected large sample data from the China Family Panel Studies (CFPS) from 2014 to 2020 to empirically test the role of digital economy in mitigating the adverse impact of natural disasters on livelihood resilience of rural households in China. The empirical results indicate that although natural disasters have a significant negative impact on the livelihood resilience of rural households, the embedding of digital technology can alleviate this negative impact to some extent by expanding non-agricultural employment opportunities for rural households, enhancing households’ access to credit, and improving agricultural production strategies. During this process, the buffering capacity, self-organization ability, and learning ability of rural families have been significantly improved. Moreover, the mitigating effect of the digital economy exhibits heterogeneity. It is more pronounced in the central and western regions than in the eastern regions, and also more evident among high-income families relative to low-income families. The key to improving the benefits of digital technology may lie in tailored policy interventions and digital skills training for farmers. Finally, this study provides empirical evidence from rural China on the role of the digital economy in strengthening farmers’ adaptive capacity against disaster risks. While these findings are context-specific, they may still provide valuable insights for other agriculture-dependent developing countries facing persistent climate risks. Full article

(This article belongs to the Section Agricultural Economics, Policies and Rural Management)

36 pages, 1783 KB

Open AccessArticle

NLU Difficulty-Aware Routing for Conversational Expert Systems, Avoiding Post-Hoc Cascading Through Pre-Inference Decision Making

by Subhin Yang, Donghwan Kim and Sungju Lee

Electronics 2026, 15(15), 3420; https://doi.org/10.3390/electronics15153420 (registering DOI) - 2 Aug 2026

Abstract

Hybrid approaches for conversational NLU commonly rely on cascading strategies, where model selection is performed after inference based on output confidence or uncertainty. Although effective, such post-hoc decision processes introduce redundant computation and accumulated latency due to sequential model execution. In this paper, [...] Read more.

Hybrid approaches for conversational NLU commonly rely on cascading strategies, where model selection is performed after inference based on output confidence or uncertainty. Although effective, such post-hoc decision processes introduce redundant computation and accumulated latency due to sequential model execution. In this paper, we propose a pre-inference routing framework that selects an appropriate model before executing any candidate NLU model and without relying on candidate-model confidence or uncertainty. Instead of relying on output-dependent signals, we model NLU difficulty as a multi-dimensional representation of the joint intent recognition and slot extraction task, thereby distinguishing the proposed approach from prior post-hoc routing methods that rely primarily on confidence or uncertainty. To further reflect real-world dialogue characteristics, we incorporate temporal conversational factors, including contextual dependency and topic transitions. Based on these features, a lightweight routing mechanism efficiently assigns each utterance to an appropriate model from a pool of domain-specialized and general-purpose models. Experimental results on single-domain turns show that the proposed method maintains competitive Semantic Accuracy while reducing high-capacity model invocation, cost, and latency, thereby improving inference efficiency. These results demonstrate that input-observable difficulty features can provide a practical basis for pre-inference model selection without relying on post-hoc cascading. Full article

(This article belongs to the Special Issue Machine/Deep Learning Applications and Intelligent Systems, 2nd Edition)

23 pages, 2685 KB

Open AccessArticle

The Halo Effect of Health Image on Consumer Decision-Making: Evidence from Sterilized Milk Products

by Surianto Surianto, Usep Suhud and Somnuk Aujirapongpan

Adm. Sci. 2026, 16(8), 370; https://doi.org/10.3390/admsci16080370 (registering DOI) - 2 Aug 2026

Abstract

Health-related product positioning has become an important strategy for influencing consumer evaluations and consumption behaviour. Previous studies have shown that favourable health-related perceptions positively affect consumer responses, yet the cognitive mechanism linking these perceptions to consumption decisions remains insufficiently understood. This study examines [...] Read more.

Health-related product positioning has become an important strategy for influencing consumer evaluations and consumption behaviour. Previous studies have shown that favourable health-related perceptions positively affect consumer responses, yet the cognitive mechanism linking these perceptions to consumption decisions remains insufficiently understood. This study examines the mediating role of perceived product quality in the relationship between perceived health image and consumption decision toward Bear Brand sterilized milk in Indonesia. A survey of 200 consumers was analyzed using Partial Least Squares Structural Equation Modelling (PLS-SEM). The findings indicate that perceived health image influences consumption decisions both directly and indirectly through perceived product quality. More importantly, consumers ultimately rely on quality evaluations rather than favourable health-related impressions alone when making consumption decisions. This study contributes to consumer behaviour literature by demonstrating how the Health Halo Effect, Cue Utilization Theory, and Signalling Theory jointly explain the sequential cognitive process underlying health-related consumption decisions. In practice, the findings suggest that firms should complement health-oriented brand positioning with consistently superior product quality to strengthen consumer confidence and improve the effectiveness of health-related marketing communications. Full article

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25 pages, 5554 KB

Open AccessArticle

Black-Box and Interpretable Artificial Intelligence Models for Hydrogen Uptake Across Various Metal–Organic Frameworks

by Regan Solomon Ward Taylor, Shahin Alipour Bonab and Mohammad Yazdani-Asrami

Algorithms 2026, 19(8), 640; https://doi.org/10.3390/a19080640 (registering DOI) - 2 Aug 2026

Abstract

Hydrogen (H₂) is expected to play a critical role in modern industry, particularly in ammonia synthesis, petroleum refining, and low-carbon transportation. The safe storage of H₂ remains a major challenge due to its low volumetric density under ambient conditions. Metal–Organic [...] Read more.

Hydrogen (H₂) is expected to play a critical role in modern industry, particularly in ammonia synthesis, petroleum refining, and low-carbon transportation. The safe storage of H₂ remains a major challenge due to its low volumetric density under ambient conditions. Metal–Organic Frameworks (MOFs), highly porous crystalline materials, have emerged as promising H₂ storage candidates owing to their high surface areas and tuneable pore structures. Molecular simulations such as grand canonical Monte Carlo or density functional theory are costly and limited in exploring large material spaces, motivating efficient predictive tools to accelerate discovery. Here, Machine Learning (ML) techniques are compared to an explainable artificial intelligence (XAI) approach using symbolic regression (SR), trained on 10,123 experimentally measured H₂ adsorption datapoints from real-world MOFs. The best performing model achieved a goodness of fit of 0.9986 with lower computational demand, but reduced interpretability, addressed using XAI analysis and clustering. SR achieves a lower goodness of fit of 0.914 but produces a physically meaningful equation highlighting structural features driving high gravimetric efficiencies. These results demonstrate strong ML capability for predicting how MOF properties and environmental conditions affect H₂ uptake. This offers engineers and researchers a practical means of screening potential MOFs for H₂ storage applications, with the XAI analyses providing additional confidence in the predictions. They allow researchers to understand the physical reasoning behind each output, assess the reliability of individual predictions, and make fully informed decisions, enabling predictive models to be acted upon with confidence in real-world contexts. Full article

(This article belongs to the Topic Sustainable Energy Systems)

24 pages, 1370 KB

Open AccessArticle

Screening of Candidate SNPs Potentially Associated with Multi-Parity Litter Size and Litter Weight in Hu Sheep

by Qinghua Zhao, Yuan Gou, Shanhe Wang, Huiguo Yang, Kanati Shalike, Zehu Yuan and Wei Sun

Animals 2026, 16(15), 2365; https://doi.org/10.3390/ani16152365 (registering DOI) - 2 Aug 2026

Abstract

Multi-parity records improve ewe evaluation but require long-term follow-up. This study compared litter size, litter weight, and lambing type across four parities in 256 Hu sheep and 90 Tan sheep and evaluated six candidate SNPs in Hu sheep. The SNPs were confirmed by [...] Read more.

Multi-parity records improve ewe evaluation but require long-term follow-up. This study compared litter size, litter weight, and lambing type across four parities in 256 Hu sheep and 90 Tan sheep and evaluated six candidate SNPs in Hu sheep. The SNPs were confirmed by PCR and Sanger sequencing and genotyped using PARMS; repeated records were analyzed with mixed-effects models. The Hu sheep population showed higher litter weight and multiple-birth proportions than the Tan sheep population, together with a higher mean litter size. Analysis of 822 records from 256 Hu ewes showed that both traits increased from the first to the third parity and then remained stable; the same pattern occurred in 156 ewes with complete records. After BH-FDR correction, BMPR1B rs418841713 and TSHR rs406686139 were significantly associated with both traits. Association directions were unchanged when analyses were restricted to complete records, low-frequency genotypes were recoded, or lambing year was included. In an independent population, combined-genotype differences were nonsignificant, although GGCG had the numerically highest total litter size. An exploratory model indicated that first-parity litter size and both genotypes provided information on subsequent litter weight, but predictive performance was limited. These findings support further validation of BMPR1B and TSHR in Hu sheep. Full article

(This article belongs to the Section Animal Genetics and Genomics)

30 pages, 21036 KB

Open AccessArticle

HAp/PLGA/Chitosan Scaffolds Fabricated by Freeze-Drying and 3D Printing for Bone Regeneration: In Vitro Evaluation and Finite Element Analysis

by Jhon M. Pérez-Bohórquez, María C. Acero-Garzón, Sandra J. Gutiérrez-Prieto, Henry A. Méndez-Pinzón, Sandra J. Perdomo-Lara, Hernán Rodríguez-Hernández, María B. Solís-Valencia and Luis G. Sequeda-Castañeda

Biomimetics 2026, 11(8), 537; https://doi.org/10.3390/biomimetics11080537 (registering DOI) - 2 Aug 2026

Abstract

Tooth loss and bone resorption of the alveolar cavity caused by dental caries and periodontal disease remain major clinical challenges that compromise oral function. Tissue engineering approaches based on biocompatible scaffolds have emerged as promising strategies for bone regeneration; however, the influence of [...] Read more.

Tooth loss and bone resorption of the alveolar cavity caused by dental caries and periodontal disease remain major clinical challenges that compromise oral function. Tissue engineering approaches based on biocompatible scaffolds have emerged as promising strategies for bone regeneration; however, the influence of fabrication methods on scaffold performance remains unclear. This study developed hydroxyapatite/poly (lactic-coglycolic acid)/chitosan scaffolds (HAp/PLGA/CS) using freeze-drying and 3D-printing techniques and evaluated their physicochemical, biological, and biomechanical properties. The morphology, porosity, elemental composition, and mechanical properties of the scaffold were characterized, while the biocompatibility and osteogenic potential were evaluated using human dental pulp stem cells (hDPSCs). Finite element analysis (FEA) using COMSOL Multiphysics^® Version 6.2. was performed to evaluate scaffold behavior under simulated dental implant loading conditions. The 3D-printed scaffolds exhibited significantly higher cell viability than the freeze-dried scaffolds, reaching approximately 85% in the 50% filling group compared with 50% in the freeze-dried group. Microstructural analysis revealed interconnected hierarchical porosity, including macro-, micro-, and submicrometer scale pores. Although the 50% infill scaffold showed the highest cell viability, the 70% infill scaffold demonstrated the most favorable osteogenic profile, with enhanced expression of RUNX2 and OSX. Both types exhibited degradation profiles compatible with early bone regeneration. FEA simulations indicated that further mechanical optimization is required to improve load transfer and reduce deformation at the implant–scaffold interface. Overall, HAp/PLGA/CS scaffolds showed potential as experimental bioactive platforms for bone tissue engineering, with 3D-printed scaffolds providing greater architectural control and favorable early osteogenic responses. However, the translational relevance of these findings remains preliminary and requires validation through long-term degradation studies, in vivo bone regeneration and osseointegration models, cyclic mechanical testing, and implant fixation experiments. Full article

(This article belongs to the Special Issue Next-Generation Bone Regeneration and Dental Implant Therapies: Biomaterials, Digital Innovation, and AI Integration)

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15 pages, 528 KB

Open AccessArticle

Digital Learning Tools in Language Education: An Explanatory Model of Their Effects on Language Skills and Quality of Life

by Abdulaziz M. Alshammari, Faisal F. Alshammari and Ali Essa A. Alshammari

Educ. Sci. 2026, 16(8), 1220; https://doi.org/10.3390/educsci16081220 (registering DOI) - 2 Aug 2026

Abstract

This study examines the extent to which Arabic language teachers employ digital learning tools and proposes an explanatory model of their effects on language skills development and students’ quality of life. An explanatory approach was adopted, and data were collected through a questionnaire [...] Read more.

This study examines the extent to which Arabic language teachers employ digital learning tools and proposes an explanatory model of their effects on language skills development and students’ quality of life. An explanatory approach was adopted, and data were collected through a questionnaire administered to a sample of 266 Arabic language teachers. Overall, the use of digital learning tools was high across all dimensions. Lesson preparation recorded the highest level, followed by quality of life, lesson implementation, and lesson evaluation. The results indicate that digital learning tools have a positive effect on both language skills development and quality of life. Among the examined dimensions, lesson implementation showed the strongest effect, whereas lesson preparation did not yield a statistically significant effect. Language skills also showed a direct positive effect on quality of life. In addition, the findings indicate an indirect effect of digital learning tools on quality of life through language skills, supporting the mediating role of language skills in explaining the relationships among the study variables. Full article

(This article belongs to the Section Curriculum and Instruction)

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20 pages, 20627 KB

Open AccessArticle

Microstructure, Mechanical Properties, and Corrosion Resistance of ZrO₂ Nanoparticle-Modified Micro-Arc Oxidation Composite Coatings

by Xiaoben Qi, Jingkai Zhang, Moussa Athmani, Yuxian Lu, Yongchen Shi, Qilin Tang and Hailong Shang

Coatings 2026, 16(8), 920; https://doi.org/10.3390/coatings16080920 (registering DOI) - 2 Aug 2026

Abstract

In this study, to further improve the performance of micro-arc oxidation (MAO) coatings, ZrO₂ nanoparticles at different concentrations were added to the electrolyte. The effects of ZrO₂ concentration on the microstructure, mechanical properties and corrosion resistance of the MAO composite coatings [...] Read more.

In this study, to further improve the performance of micro-arc oxidation (MAO) coatings, ZrO₂ nanoparticles at different concentrations were added to the electrolyte. The effects of ZrO₂ concentration on the microstructure, mechanical properties and corrosion resistance of the MAO composite coatings were systematically investigated. The coatings mainly consisted of α-Al₂O₃ and γ-Al₂O₃. The detection of ZrO₂ confirmed the incorporation of the added particles. As the concentration increased from 0 to 6 g/L, the porosity decreased from 1.352% to 0.864%, whereas further addition increased the porosity. At 6 g/L, the mean microhardness reached 623 ± 50 HV_0.05. Moreover, this coating showed the lowest friction coefficient of 0.135. In addition, its corrosion potential was −0.148 V, while its corrosion current density was 2.578 × 10⁻⁷ A·cm⁻². It also exhibited the highest low-frequency impedance modulus. When the ZrO₂ concentration was further increased, the coating porosity increased and the improvements gradually weakened. Overall, a suitable ZrO₂ concentration promoted coating growth and reduced structural defects. It also improved the hardness, wear behavior and corrosion protection of the coating. Therefore, these findings provide a reference for the concentration design of ZrO₂-modified MAO coatings. They also clarify the nonmonotonic relationship between coating growth, structural defects and performance. Full article

(This article belongs to the Special Issue Heterogeneous Nanostructured Coatings: Design, Preparation, and Application)

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20 pages, 2234 KB

Open AccessArticle

Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K⁺ Retention During MR Antagonism in Female Spontaneously Hypertensive Rats

by Irina Baranovskaya, Iryna Bilous, Sati Alexander, Bianca Tubalinal, Alena Cherezova, Vadym Buncha, Mikhail Fomin, Celso Gomez-Sanchez and Mykola Mamenko

Int. J. Mol. Sci. 2026, 27(15), 6953; https://doi.org/10.3390/ijms27156953 (registering DOI) - 2 Aug 2026

Abstract

Mineralocorticoid receptor (MR) blockade exerts sex-specific effects in hypertension and cardiovascular disease; however, its role in blood pressure regulation in spontaneously hypertensive rats (SHRs) remains unclear. We assessed the effects of MR antagonism on blood pressure and electrolyte balance in male and female [...] Read more.

Mineralocorticoid receptor (MR) blockade exerts sex-specific effects in hypertension and cardiovascular disease; however, its role in blood pressure regulation in spontaneously hypertensive rats (SHRs) remains unclear. We assessed the effects of MR antagonism on blood pressure and electrolyte balance in male and female SHRs aged 10–15 weeks. Higher serum K⁺ levels in spironolactone-treated female SHRs were accompanied by transiently reduced urinary K⁺ excretion and a fourfold increase in aldosterone at the study’s end. These differences were not observed in male SHRs. Plasma renin activity and circulating corticosterone were 19% and 41% lower in females than in males but were unaffected by spironolactone in either sex. Plasma renin activity in SHRs was comparable to that of normotensive Wistar–Kyoto rats. Females exhibited approximately twofold higher renal MR and 1.7-fold greater renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) protein levels. MR antagonism did not alter ENaC activity, α-ENaC protein abundance, blood pressure, or amiloride-sensitive urinary electrolyte excretion in either sex. Collectively, the upregulation of renal MR and 11β-HSD2 in females was associated with elevated circulating potassium in response to MR blockade, an effect that was likely counterbalanced by a compensatory rise in aldosterone. Low renin–angiotensin–aldosterone system activity in SHRs may limit the antihypertensive efficacy of MR antagonists. Full article

(This article belongs to the Special Issue 25th Anniversary of IJMS: Advances in Molecular Endocrinology and Metabolism)

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23 pages, 748 KB

Open AccessArticle

Relationship of Vitamin D, Spondyloarthritis Activity and Left Ventricular Systolic and Diastolic Function

by Silvija Miletić Gršković, Iva Uravić Bursać, Vedrana Tudor Špalj, Vedrana Drvar, Vlatka Sotošek, Tatjana Kehler, Viktor Peršić, Tamara Sinožić and Gordana Laškarin

J. Clin. Med. 2026, 15(15), 6017; https://doi.org/10.3390/jcm15156017 (registering DOI) - 2 Aug 2026

Abstract

Background/Objectives: Vitamin D insufficiency is common in patients with spondyloarthritis (SpA). We analyzed the relationship between vitamin D, disease activity, and left ventricular (LV) function in patients with SpA. Methods: A total of 298 patients with SpA and 57 healthy controls were enrolled. [...] Read more.

Background/Objectives: Vitamin D insufficiency is common in patients with spondyloarthritis (SpA). We analyzed the relationship between vitamin D, disease activity, and left ventricular (LV) function in patients with SpA. Methods: A total of 298 patients with SpA and 57 healthy controls were enrolled. Serum vitamin D and laboratory cardiovascular risk factors were analyzed, and LV function was assessed by echocardiography. Vitamin D, the Ankylosing Spondylitis Disease Activity Score (ASDAS), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) were examined for mutual correlations using univariate and multivariate linear regression models and were compared between groups. Results: Vitamin D levels did not differ between the SpA group and controls, although vitamin D supplementation was more frequent among SpA patients. Vitamin D was not associated with SpA activity. ASDAS and DAPSA were positively correlated with isovolumic relaxation time, and DAPSA was inversely correlated with peak early diastolic mitral annular velocity (e′), after adjustment for age, sex, metabolic factors, and/or therapy. Patients with insufficient serum vitamin D levels (<75 nmol/L) showed greater impairment of systolic and diastolic LV function and a diabetic-like lipid profile compared with those with sufficient vitamin D levels. The e′ wave was positively correlated with vitamin D after controlling for confounding factors. These findings in patients with SpA are consistent with those previously reported in patients with psoriatic arthritis (PsA). Conclusions: Patients with SpA were characterized by vitamin D supplementation, increased disease activity parameters, and impaired LV function. SpA activity, independent of vitamin D, was associated with LV functional impairment, and vitamin D was associated with an increase in the e′ wave after adjustment for confounding factors. However, causal inferences cannot be drawn from correlational analyses. Full article

(This article belongs to the Section Immunology & Rheumatology)

28 pages, 7919 KB

Open AccessArticle

A Multi-Feature Early Fusion Network with Domain-Specific Contrastive Representation and Attention Mechanism for Side-Scan Sonar Target Detection

by Junhui Zhu, Houpu Li, Shaofeng Bian, Xueshen Li, Lei Liu, Guojun Zhai and Ye Peng

Appl. Sci. 2026, 16(15), 7683; https://doi.org/10.3390/app16157683 (registering DOI) - 2 Aug 2026

Abstract

Accurate target detection in side-scan sonar imagery is important for marine resource investigation, underwater infrastructure inspection, and maritime security. However, Side-scan sonar images are often affected by low contrast, acoustic speckle, weak target boundaries, and cluttered seabed backgrounds, which make target detection particularly [...] Read more.

Accurate target detection in side-scan sonar imagery is important for marine resource investigation, underwater infrastructure inspection, and maritime security. However, Side-scan sonar images are often affected by low contrast, acoustic speckle, weak target boundaries, and cluttered seabed backgrounds, which make target detection particularly challenging, especially under limited training data conditions. To improve the representation of sonar-specific structures, this study proposes a multi-feature early fusion detection network, referred to as MFEF-Det, for side-scan sonar target detection. The method combines multiple handcrafted features with data-driven representations to provide complementary information. In particular, a directional contrast core response feature (DCCR) is introduced to better emphasize the echo–shadow structure commonly observed in side-scan sonar imagery. An adaptive fusion strategy is then adopted to combine multiple feature maps before feeding them into a detection network, and an attention refinement module is further employed for complex scenes to improve the discrimination between target-related regions and cluttered backgrounds. Experiments were conducted on two publicly available sonar datasets. Experiments on the KLSG and SSS-Bottom datasets demonstrate that MFEF-Det achieves 0.933 ± 0.016 mAP@0.5 and 0.866 ± 0.052 mAP@0.5, respectively. The results indicate that the proposed feature representation can improve detection performance in both relatively clean and more challenging noisy scenes. These findings suggest that incorporating sonar-specific priors can be beneficial for side-scan sonar detection in marine survey and maritime-security applications. Full article

16 pages, 998 KB

Open AccessArticle

Outcomes of Low Vision Rehabilitation Programs for Children: A Prospective Observational Cohort Study

by Areej Okasheh-Otoom

Children 2026, 13(8), 1030; https://doi.org/10.3390/children13081030 (registering DOI) - 2 Aug 2026

Abstract

Purpose: To evaluate the visual, functional, educational, and mobility outcomes of a comprehensive pediatric low vision rehabilitation (LVR) program and determine whether electronic low vision aids (LVAs) provide additional benefit. Methods: A multicenter prospective observational cohort study was conducted across three [...] Read more.

Purpose: To evaluate the visual, functional, educational, and mobility outcomes of a comprehensive pediatric low vision rehabilitation (LVR) program and determine whether electronic low vision aids (LVAs) provide additional benefit. Methods: A multicenter prospective observational cohort study was conducted across three tertiary low vision rehabilitation centers in Jordan. Two hundred children aged 6–16 years with moderate-to-severe visual impairment were enrolled. The intervention group (n = 150) received comprehensive multidisciplinary rehabilitation, including optical LVAs, rehabilitation training, educational support, and electronic LVAs when indicated, while the comparison group (n = 50) received routine low vision care without participation in the structured multidisciplinary rehabilitation program. Primary outcomes were LogMAR distance visual acuity (VA) and LV Prasad Functional Vision Questionnaire (FVQ) scores. Secondary outcomes included near VA, reading speed, mathematics performance, and mobility independence. Results: At 12 months, the intervention group demonstrated significant improvement in distance VA from 0.87 ± 0.13 to 0.65 ± 0.11 LogMAR (mean change −0.22; 95% confidence interval [CI], −0.25 to −0.19; p < 0.001), whereas the comparison group showed only minimal improvement. FVQ scores increased significantly from 42.3 ± 8.7 to 76.5 ± 9.1 (+34.2 points; p < 0.001). Within the intervention group, reading speed improved by 25.3 words/minute, mathematics scores by 15.7%, and mobility independence by 32% (all p < 0.001), whereas only minimal changes were observed in the comparison group. Multivariate regression analysis identified electronic LVA use as the strongest independent predictor of functional improvement (β = 0.41, p < 0.001). Conclusions: Comprehensive pediatric low vision rehabilitation improved visual, educational, and mobility outcomes. In an exploratory subgroup analysis, children using electronic low vision aids demonstrated greater functional improvement than those using non-electronic low vision aids. Full article

22 pages, 4533 KB

Open AccessReview

The Vicious Cycle of Biofilm, Host Inflammation and Microvascular Insufficiency in Venous Leg Ulcers

by Diana Tatarciuc, Irina Mihaela Esanu, Iolanda Foia, Teodor Flaviu Vasilcu, Ana Maria Raluca Pauna, Ilinca Foia, Roxana Ionela Vasluianu, Nicoleta Ioanid, Marius Constantin Moraru, Elena-Roxana Avadanei and Mioara-Florentina Trandafirescu

Med. Sci. 2026, 14(4), 453; https://doi.org/10.3390/medsci14040453 (registering DOI) - 2 Aug 2026

Abstract

Chronic venous leg ulcers (VLUs) affect approximately 1% of adults, and up to 30% remain unhealed by 12 months of standard therapy, with rates of recurrence approaching 70%. The chronicity and treatment resistance cannot be explained by the traditional view that venous hypertension [...] Read more.

Chronic venous leg ulcers (VLUs) affect approximately 1% of adults, and up to 30% remain unhealed by 12 months of standard therapy, with rates of recurrence approaching 70%. The chronicity and treatment resistance cannot be explained by the traditional view that venous hypertension alone causes the pathogenesis of VLUs. This narrative review synthesizes evidence from PubMed, Web of Science, and Scopus (2016–April 2026), including original research, systematic reviews, meta-analyses, and clinical trials on the pathophysiology, diagnosis, and treatment of VLU, with a focus on biofilm, inflammation, and microvascular dysfunction. The reviewed studies were critically appraised. The current integrated framework offers a potential mechanistic roadmap for understanding the pathogenesis of VLUs and may help justify integrated therapeutic strategies. This review evaluates the existing evidence, identifies controversies, and highlights areas of knowledge that require further investigation. We analyze emerging data to propose a unified, conceptually distinct framework focused on the reciprocal, self-perpetuating interactions between biofilm, inflammation, and microvascular dysfunction, a triad that may offer a more comprehensive explanation for clinical heterogeneity and therapeutic resistance than venous hypertension alone. Future research should focus on the development of clinically available biofilm diagnostics, rigorous studies of combination therapies and elucidation of molecular links between components of the triad. We suggest that a transition to mechanism-based approaches targeting simultaneously may hold promise for transforming outcomes for millions of people affected by this debilitating condition. Full article

(This article belongs to the Section Cardiovascular Disease)

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24 pages, 2069 KB

Open AccessArticle

Biological Evaluation, Molecular Docking, and in Ovo Hatchability Assessment of Selected Mannich-Type 1,2,4-Triazol-5-one Derivatives

by Songül Ulufer Bulut, Özlem Durna, Songül Boy, Fevzi Aytemiz, Gül Özdemir Toraman, Önder Albayrak, Murat Beytur, Ahmet Harmankaya, Haydar Yüksek and Gültekin Yildiz

Int. J. Mol. Sci. 2026, 27(15), 6948; https://doi.org/10.3390/ijms27156948 (registering DOI) - 2 Aug 2026

Abstract

1,2,4-Triazole derivatives are widely investigated as bioactive heterocyclic compounds with diverse biological properties; however, their potential effects on avian embryonic development remain insufficiently characterized. This study aimed to synthesize selected Mannich-type 1,2,4-triazol-5-one derivatives and evaluate their in vitro biological activities, predicted enzyme interactions, [...] Read more.

1,2,4-Triazole derivatives are widely investigated as bioactive heterocyclic compounds with diverse biological properties; however, their potential effects on avian embryonic development remain insufficiently characterized. This study aimed to synthesize selected Mannich-type 1,2,4-triazol-5-one derivatives and evaluate their in vitro biological activities, predicted enzyme interactions, and in ovo hatchability outcomes in broiler embryos. Three derivatives (3a–3c) were synthesized and structurally characterized using Fourier-transform infrared (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and carbon-13 nuclear magnetic resonance (¹³C-NMR) spectroscopy. Their reducing capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, metal-chelating capacity, and antimicrobial activity were evaluated. Molecular docking analyses were performed against carbonic anhydrase II and catalase, using acetazolamide and 3-amino-1,2,4-triazole as reference inhibitors, respectively. For the in ovo assessment, fertilized Ross 308 eggs were allocated to non-injected control, vehicle control, and compound-treated groups. Compounds 3a, 3b, and 3c were administered on incubation day 17 at 20, 10, and 5 mg/egg, respectively, as literature-supported, compound-specific exploratory exposure levels. The compounds exhibited weak reducing capacity, negligible DPPH radical-scavenging activity, pronounced metal-chelating capacity, and selective antimicrobial activity against several bacterial strains, whereas no inhibition was observed against Escherichia coli. Docking analysis predicted favorable interactions with both enzyme targets, with compound 3c showing the most favorable binding energies. Baseline egg weights were comparable among groups, indicating that initial egg weight was unlikely to influence hatchability outcomes. Complete hatch failure occurred in all compound-treated groups, whereas hatchability was observed in the control groups. These findings suggest that the tested derivatives may adversely affect embryonic development under the applied in ovo conditions. Their pronounced metal-chelating capacity, together with the predicted interactions with carbonic anhydrase II and catalase, provides a plausible mechanistic framework for interpreting the observed embryonic outcomes. The molecular docking results complement the experimental findings and provide supportive in silico evidence for these potential interactions. These findings contribute to the limited literature on the in ovo evaluation of synthetic Mannich-type 1,2,4-triazol-5-one derivatives and provide preliminary evidence regarding their embryotoxic potential. Further dose-dependent, mechanistic, histopathological, and enzyme-based studies are required to clarify the biological basis of the observed effects and to guide future evaluation of these compounds in in ovo, biomedical, and veterinary applications. Full article

(This article belongs to the Special Issue Azoles and Fused Heterocycles in Antimicrobial Drug Discovery: Synthesis, Mechanisms, and Applications)

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29 pages, 9390 KB

Open AccessArticle

Conserved Core and Species-Specific Signatures in the Milk Exosomal microRNA Targetome: A Preliminary Comparative In Silico Analysis of Human, Cow, Goat and Donkey Milk

by Maksym Zoziuk, Abel Dafogo Djibagaou, Alessandro Terrinoni, Dimitri Koroliouk and Vittorio Colizzi

Int. J. Mol. Sci. 2026, 27(15), 6952; https://doi.org/10.3390/ijms27156952 (registering DOI) - 2 Aug 2026

Abstract

Milk-derived extracellular vesicles (EVs) transport microRNAs (miRNAs) that are unusually stable and have been proposed to survive digestion and modulate gene expression in the consumer, although their dietary bioavailability and physiological relevance remain debated. How the predicted regulatory potential of these miRNAs differs [...] Read more.

Milk-derived extracellular vesicles (EVs) transport microRNAs (miRNAs) that are unusually stable and have been proposed to survive digestion and modulate gene expression in the consumer, although their dietary bioavailability and physiological relevance remain debated. How the predicted regulatory potential of these miRNAs differs among the milks of different animals most relevant to human nutrition has not been systematically compared. Here, we performed an integrative in silico analysis of publicly available small-RNA sequencing data from 29 milk and milk-cell samples of human, cow, goat, and donkey origin. miRNAs were quantified against human (hsa) miRBase references—thereby restricting the analysis to evolutionarily conserved miRNAs with human orthologs—and their predicted effect on the human transcriptome was modeled by integrating predicted (mirDIP database) and experimentally supported (TarBase v9 database) miRNA–target interactions into a per-gene, per-species weighted targeting score. Because miRNAs act predominantly as repressors, this score is read as a prediction of which genes would be post-transcriptionally down-regulated in a recipient. miR-148a-3p dominated the exosomal spectrum of all four species (human, cow, goat, and donkey; ≈21.5% of pooled abundance), and the twenty most abundant miRNAs accounted for roughly three quarters of the signal. Of 4577 robustly targeted genes, a 1809-gene conserved “pan-milk” core showed the highest cross-species targeting and was enriched for transcriptional regulation, PI3K–Akt, MAPK, and TGF-β/SMAD signaling, autophagy and—strikingly—the components of the RNA-interference machinery itself. Species-restricted gene sets recapitulated biologically plausible programs, including a human-biased neuronal/axon-guidance and chromatin module, a donkey-biased transcriptional, epithelial, and immune (CD47) module, and a ruminant lipid/cholesterol and insulin–mTOR module. Across categories, we observed a reproducible confidence–exclusivity trade-off. We emphasize that these results are computational predictions that assume dietary miRNA uptake and do not constitute experimental validation. We provide the complete targetome as a hypothesis-generating resource to prioritize candidate genes, pathways, and milk types for future functional, nutritional, and epigenetic investigation. Across the 29 samples from the four species, miRNA composition segregated by species (silhouette width = 0.82, a cluster-separation measure ranging from −1 to 1, with values near 1 indicating well-separated groups) and the category structure exceeded a permutation null, indicating that the between-species signal is robust to differences in dataset origin and milk state. Full article

(This article belongs to the Special Issue Harnessing Bioinformatics for miRNA Research: Methods, Insights and Applications)

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28 pages, 24257 KB

Open AccessArticle

Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial–Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes

by Zhonglu Ren, Zhuangchang Li, Jie Wang, Yuchen Liu, Lidan Chen, Yuxin Su, Limin Zhao and Xi Liu

Int. J. Mol. Sci. 2026, 27(15), 6951; https://doi.org/10.3390/ijms27156951 (registering DOI) - 2 Aug 2026

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate below 10%. Cancer-associated fibroblasts (CAFs) promote epithelial–mesenchymal transition (EMT) and metastasis, yet the specific CAF subtypes and molecular axes driving PDAC progression remain incompletely understood. Here, using multi-omics data [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate below 10%. Cancer-associated fibroblasts (CAFs) promote epithelial–mesenchymal transition (EMT) and metastasis, yet the specific CAF subtypes and molecular axes driving PDAC progression remain incompletely understood. Here, using multi-omics data from PDAC samples, we identified a malignant ductal subpopulation, termed Ductal-T0, characterized by the highest EMT activity and prominent acquisition of myofibroblastic CAF (myCAF)-like transcriptional programs. Computationally, we predicted that myCAF-secreted THBS2 and FN1 engage the ITGA3/ITGB1/SDC1/SDC4 receptor axes in Ductal-T0 cells, which could activate TNF, NF-κB, TGF-β, and PI3K-AKT-signaling pathways to promote EMT. Pseudotime trajectory and velocity analyses suggested that Ductal-T0 cells exhibited the highest propensity to acquire myCAF-like features among all ductal subpopulations. Survival analysis revealed that an increased proportion of Ductal-T0 cells and elevated abundance of THBS2-ITGA3/ITGB1 and THBS2-SDC1 ligand–receptor pairs were significantly associated with poor prognosis. Spatial transcriptomics further revealed that myCAFs and Ductal-T0 cells co-localized at the tumor margin, which may contribute to reduced immune cell presence via dense extracellular matrix (ECM) barrier formation—a computationally inferred model of EMT-associated immune exclusion and metastatic progression—and identify THBS2 as a promising candidate for future therapeutic investigation to disrupt CAF–tumor crosstalk in PDAC. Full article

(This article belongs to the Special Issue Deciphering Molecular Complexity of Pancreatic Cancer)

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