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18 pages, 1331 KB

Open AccessArticle

Infraorbital–Infratrochlear Versus Transnasal Sphenopalatine Ganglion Block for Septorhinoplasty: A Prospective, Randomized, Double-Blind, Clinical Trial

by Andaç Dedeoğlu, Fatma Acil, Mehmet Özkılıç, Hülya Tosun Soner and Cem Kıvılcım Kaçar

J. Clin. Med. 2026, 15(16), 6321; https://doi.org/10.3390/jcm15166321 (registering DOI) - 15 Aug 2026

Abstract

Background/Objectives: Regional anesthesia techniques are increasingly being incorporated into multimodal analgesia for septorhinoplasty. This study compared the postoperative analgesic efficacy and recovery profiles of infraorbital–infratrochlear (ION–ITN) nerve block and transnasal sphenopalatine ganglion (SPG) block techniques. Methods: In this prospective, randomized, double-blind [...] Read more.

Background/Objectives: Regional anesthesia techniques are increasingly being incorporated into multimodal analgesia for septorhinoplasty. This study compared the postoperative analgesic efficacy and recovery profiles of infraorbital–infratrochlear (ION–ITN) nerve block and transnasal sphenopalatine ganglion (SPG) block techniques. Methods: In this prospective, randomized, double-blind trial, 93 patients undergoing septorhinoplasty received bilateral ION–ITN block (n = 45) or transnasal SPG block (n = 48). The primary outcome was postoperative pain assessed using the Numerical Rating Scale (NRS). Peak postoperative NRS scores at the predefined assessment intervals were evaluated with a linear mixed-effects model adjusted for relevant covariates. Continuous variables are presented as medians (first quartile–third quartile [Q1–Q3]), and categorical variables as numbers (percentages). Secondary outcomes included emergence agitation (Riker Sedation–Agitation Scale (RSAS)), rescue tramadol use, patient satisfaction, and adverse events. Results: Pain scores decreased significantly over time in both groups (p < 0.001). No significant group effect was observed (p = 0.726), and adjusted between-group differences were not significant at any postoperative interval (all p > 0.05). Although the group-by-time interaction showed a trend toward statistical significance (p = 0.053), no meaningful differences in postoperative pain trajectories were observed between the two groups. Median RSAS scores were lower in the SPG group (3 [2,3,4] vs. 4 [3,4], p = 0.04), whereas emergence agitation incidence, tramadol use, patient satisfaction, and adverse events were similar. Conclusions: Within the multimodal analgesic regimen, no statistically significant differences in postoperative pain outcomes were detected between ION–ITN and transnasal SPG block. Because this study was not designed as an equivalence or non-inferiority trial, these findings should be interpreted as an absence of detected differences rather than proof of equivalent analgesic efficacy. Although SPG block was associated with lower agitation scores, this finding suggests reduced agitation severity rather than superior overall analgesic efficacy. Full article

(This article belongs to the Section Anesthesiology)

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16 pages, 1199 KB

Open AccessReview

Systemic Inflammatory Biomarkers and Cancer-Associated Cachexia: A Narrative Review

by Shawna Landon, Jaclyn M. Hall and Saunjoo L. Yoon

Curr. Oncol. 2026, 33(8), 483; https://doi.org/10.3390/curroncol33080483 (registering DOI) - 15 Aug 2026

Abstract

Cancer-associated cachexia (CAC) is a multifactorial syndrome characterized by systemic inflammation, muscle wasting, and progressive functional decline, affecting up to 80% of patients with advanced cancer. The inconsistent diagnostic criteria limit comparability across studies and hinder translation into clinical practice. Inflammatory biomarkers, including [...] Read more.

Cancer-associated cachexia (CAC) is a multifactorial syndrome characterized by systemic inflammation, muscle wasting, and progressive functional decline, affecting up to 80% of patients with advanced cancer. The inconsistent diagnostic criteria limit comparability across studies and hinder translation into clinical practice. Inflammatory biomarkers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and serum albumin, have been studied as markers of the presence, severity, and progression of CAC. This review synthesizes evidence linking these five biomarkers to key manifestations of CAC, including weight- loss, muscle depletion, fatigue, quality of life, and survival. A structured search of PubMed, Embase, and Web of Science studies published between 2000 and 2025, yielding 20 articles for final synthesis to evaluate biomarker patterns and their potential utility for early detection and risk stratification. IL-6 and CRP show consistent associations with muscle wasting and systemic inflammatory burden. Albumin and NLR demonstrate enhanced prognostic value when incorporated into composite indices such as the Cachexia index. TNF-α remains mechanistically relevant but shows limited predictive utility when assessed independently. CRP, Albumin, and NLR are derived from routine, low-cost tests, whereas IL-6 and TNF-α require specialized cytokine assays. Future research is warranted to standardize diagnostic criteria and validate biomarker thresholds to develop an accessible, multi-biomarker panel for improved detection and monitoring of CAC. Full article

(This article belongs to the Special Issue Role of Inflammation in Cancer)

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24 pages, 2537 KB

Open AccessReview

Proline: A Reliable Biochemical Marker of Plant Abiotic Stress Tolerance?

by Delia Maria Luca, Marius-Nicuşor Grigore and Oscar Vicente

Plants 2026, 15(16), 2478; https://doi.org/10.3390/plants15162478 (registering DOI) - 15 Aug 2026

Abstract

Climate change is placing global agriculture under growing pressure, as plants must withstand extreme environmental conditions such as drought and high salinity, both inducing osmotic and oxidative stress. As part of their survival strategies, plants accumulate protective molecules (osmolytes), including the amino acid [...] Read more.

Climate change is placing global agriculture under growing pressure, as plants must withstand extreme environmental conditions such as drought and high salinity, both inducing osmotic and oxidative stress. As part of their survival strategies, plants accumulate protective molecules (osmolytes), including the amino acid proline. For decades, plant biology has largely assumed that high proline accumulation under stress signals strong stress tolerance. However, this review challenges that “proline-centric” perspective. Analyses across a wide range of plant species reveal a more complex picture. Stress-induced proline accumulation is not universal: in some species, proline levels remain relatively unchanged, with other metabolites acting as functional osmolytes, or increase only in response to artificially applied severe stress conditions. Even when proline increases, its absolute concentrations may be too low to contribute significantly to osmotic adjustment. Nevertheless, proline may still be involved in stress tolerance mechanisms through its additional roles, detoxifying reactive oxygen species (ROS), directly stabilising proteins or acting as a stress signalling molecule. Comparative analyses of genetically related taxa with varying degrees of stress tolerance sometimes show negative correlations between proline accumulation and tolerance, with higher proline concentrations measured in the most sensitive genotypes. Overall, the evidence indicates that proline‘s role in plant survival is highly context-dependent and strongly influenced by genetic background and must therefore be evaluated on a case-by-case basis. Distinguishing whether proline acts as an adaptive defence or merely as a biochemical marker of physiological strain under stress is essential for accurately assessing plant stress tolerance. Full article

(This article belongs to the Special Issue Plants 2025—from Seeds to Food Security)

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15 pages, 7174 KB

Open AccessArticle

Long-Term Survival and Maturation of Transplanted Cerebral Organoids Derived from Human Induced Pluripotent Stem Cells

by Xiaoli Ji, Zhongmeng Xiong and Wanxing Li

Cells 2026, 15(16), 1466; https://doi.org/10.3390/cells15161466 (registering DOI) - 15 Aug 2026

Abstract

Human cerebral organoids have emerged as a promising new therapeutic strategy for cell transplantation after brain injury. Researchers have explored the short-term survival and maturation of human cerebral organoids derived from human embryonic stem cells (hESCs) in animal models. However, the long-term survival [...] Read more.

Human cerebral organoids have emerged as a promising new therapeutic strategy for cell transplantation after brain injury. Researchers have explored the short-term survival and maturation of human cerebral organoids derived from human embryonic stem cells (hESCs) in animal models. However, the long-term survival and maturation of cerebral organoids derived from human induced pluripotent stem cells (hiPSCs) have not been studied in depth. In this study, we generated cerebral organoids from hiPSCs in a feeder-free culture system. Then, the cerebral organoids were digested into small clusters and transplanted into the frontal cerebral cortex of postnatal day 0 (P0) SCID mice. The long-term survival and maturation of the grafted cerebral organoids were evaluated at 12 months post-transplantation. Our results indicate that grafted cerebral organoids survive well and maintain their forebrain identity in vivo over a long period. The transplanted cerebral organoids showed reduced proliferative capacity, indicating a low risk of tumor formation. The majority of transplanted cells differentiated into cortical neuronal subtypes in different cortical layers in anatomical lamination at 12 months post-transplantation. In addition, a small population of grafted cerebral organoids matured into GABAergic neurons and gliocytes, including astrocytes, microglia and oligodendrocytes. Furthermore, the grafts formed synapses with the host cells and achieved vascularization in the host brain. Our study demonstrates the long-term survival and maturation of cerebral organoids derived from hiPSCs in vivo and provides evidence for the feasibility of cerebral organoids derived from hiPSCs as a potential cell transplantation therapy. Full article

(This article belongs to the Section Stem Cells)

41 pages, 21329 KB

Open AccessReview

Phytochemistry and Pharmacological Potential of the Genus Dalea: Current Evidence and Future Directions

by Renata Solis-Peña, Vanessa Lizbeth Correa-Macias, Hania Lizeth Peralez-Olguin, Dalia Lizbeth Martínez-Medellín, Andrea Melissa González-Rodríguez, Lizeth Guadalupe Campos-Muzquiz, Lissethe Palomo-Ligas and Sendar Daniel Nery-Flores

Pharmaceuticals 2026, 19(8), 1294; https://doi.org/10.3390/ph19081294 (registering DOI) - 15 Aug 2026

Abstract

The genus Dalea (Fabaceae) comprises approximately 188 recognized species distributed mainly in arid and semi-arid regions of the American continent, where several species have been traditionally used in folk medicine for the treatment of gastrointestinal disorders, infections, inflammation, and other ailments. In recent [...] Read more.

The genus Dalea (Fabaceae) comprises approximately 188 recognized species distributed mainly in arid and semi-arid regions of the American continent, where several species have been traditionally used in folk medicine for the treatment of gastrointestinal disorders, infections, inflammation, and other ailments. In recent years, Dalea species have attracted considerable scientific interest due to their remarkable diversity of secondary metabolites, particularly prenylated flavonoids, isoflavonoids, rotenoids, chalcones, stilbenes, and terpenoid-rich essential oils. Among these compounds, prenylated and geranylated flavonoids represent some of the most characteristic metabolites of the genus and are strongly associated with its reported biological activities. This review summarizes current knowledge regarding the taxonomy, distribution, traditional uses, phytochemical profile, pharmacological activities, and toxicological aspects of the genus Dalea. Although only about 19 species (approximately 10% of currently recognized species) have been subjected to phytochemical investigation, substantial knowledge gaps remain within the genus. Special emphasis is placed on prenylated phenolic compounds because of their structural diversity and broad spectrum of biological activities, including antibacterial, antifungal, antiparasitic, anti-inflammatory, neuroprotective, anticancer, anti-tyrosinase, and xanthine-oxidase-inhibitory effects. Despite promising pharmacological findings, most available evidence remains limited to in vitro evaluations, with relatively few studies including in vivo validation or mechanistic investigations. Furthermore, important challenges remain regarding toxicity, pharmacokinetics, metabolomic characterization, and sustainable production of bioactive metabolites. Overall, the available evidence highlights Dalea as a valuable source of bioactive compounds with potential pharmaceutical applications and supports the need for further interdisciplinary research focused on drug discovery and development. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods: From Traditional Medicine to Modern Applications in Nutrition and Health)

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17 pages, 2734 KB

Open AccessArticle

Hand Gesture Recognition Based on Multi-Scale Attention Graph Convolutional Network

by Xiaowei Han, Tingshan Yan, Yunjing Lu, Ruize Liang, Honghui Zhang and Wei Chen

Electronics 2026, 15(16), 3649; https://doi.org/10.3390/electronics15163649 (registering DOI) - 15 Aug 2026

Abstract

Advances in artificial intelligence have made hand gesture recognition an important human–computer interaction modality. Graph convolutional networks (GCNs) are widely used for skeleton-based hand gesture recognition, yet their performance can be limited by weak semantic topology modeling, underused feature channels, and shallow spatio-temporal [...] Read more.

Advances in artificial intelligence have made hand gesture recognition an important human–computer interaction modality. Graph convolutional networks (GCNs) are widely used for skeleton-based hand gesture recognition, yet their performance can be limited by weak semantic topology modeling, underused feature channels, and shallow spatio-temporal fusion. We propose a Multi-scale Attention Graph Convolutional Network (MA-GCN) that combines three components within one skeleton framework: a hybrid topology that augments physiological connections with semantic priors; a Gaussian Multi-Scale Channel Attention (GMCA) module for coordinate denoising and adaptive channel weighting; and a Local-Global Fusion Module (LGFM) that combines local convolutional features with channel-wise global attention. Ablation studies quantify the independent and joint contributions of these components. MA-GCN obtains Top-1 accuracies of 97.50%/95.95% on SHREC’17 Track and 94.29%/92.86% on DHG14/28 for the 14-/28-class settings. In a SHREC’17 Track-to-FPHA pre-train-then-fine-tune evaluation, it reaches 94.09% Top-1 accuracy, providing preliminary evidence that the proposed framework maintains effectiveness under cross-dataset transfer. Full article

(This article belongs to the Special Issue Deep Learning Applications on Human Activity Recognition)

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20 pages, 4143 KB

Open AccessArticle

Effects of Roasting Degree and Concentration of Ethiopian Coffee Extract on the Quality Characteristics of Yanggaeng

by Minseo Cho, Taehyung Yun, Jisu Lee, Bong-Hyun Kim, Miae Doo, Hyun-Joo Lee and Jung-Heun Ha

Appl. Sci. 2026, 16(16), 8149; https://doi.org/10.3390/app16168149 (registering DOI) - 15 Aug 2026

Abstract

The present study evaluated the effects of Ethiopian coffee extract (E) on the physicochemical, antioxidant, textural, and sensory properties of Yanggaeng according to the roasting degree (light, medium, and dark) and extract concentration (0% for the control group [CON] and 2%, 4%, and [...] Read more.

The present study evaluated the effects of Ethiopian coffee extract (E) on the physicochemical, antioxidant, textural, and sensory properties of Yanggaeng according to the roasting degree (light, medium, and dark) and extract concentration (0% for the control group [CON] and 2%, 4%, and 6% for each roasted coffee extract). The proximate composition varied significantly according to the roasting degree and E concentration, with dark-roasted samples generally showing higher moisture content, and L6 and M6 exhibiting higher carbohydrate content. Colorimetric analysis revealed that the addition of E decreased lightness while increasing redness, yellowness, and total color difference. The pH values increased in all extract-added samples compared with that of the CON group, whereas Brix values varied according to the roasting degree and extract concentration without showing a clear concentration-dependent trend. The total polyphenol content remained comparable to that of the CON group, while the DPPH radical scavenging activity increased significantly in the dark-roasted group, with D6 showing the highest activity. Textural properties, particularly hardness, gumminess, and chewiness, were modified after the addition of E, with responses differing depending on roasting degree and extract concentration, indicating changes in the measured texture profile of Yanggaeng. Sensory acceptance testing revealed significant effects of concentration and interaction on preferences for color, aroma, and chewiness, whereas overall acceptance was comparable to that of the CON in most formulations. These findings indicate that Ethiopian coffee extract has potential as an ingredient for coffee-infused Yanggaeng with modified visual, textural, aroma-related sensory, and radical-scavenging properties. Full article

(This article belongs to the Special Issue Physicochemical, Sensory and Nutritional Properties of Foods)

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5 pages, 996 KB

Open AccessInteresting Images

Pelvic Actinomycosis Mimicking Gynecologic Malignancy: CT and Histopathologic Correlation

by Jia Yi Kow and Yi-Wen Su

Diagnostics 2026, 16(16), 2586; https://doi.org/10.3390/diagnostics16162586 (registering DOI) - 15 Aug 2026

Abstract

A healthy 65-year-old postmenopausal woman with a 15-year history of copper intrauterine device use presented to the emergency room with several days of lower abdominal pain and diarrhea. Laboratory testing revealed leukocytosis (white blood cell count, 26.15 × 10³/µL) and elevated [...] Read more.

A healthy 65-year-old postmenopausal woman with a 15-year history of copper intrauterine device use presented to the emergency room with several days of lower abdominal pain and diarrhea. Laboratory testing revealed leukocytosis (white blood cell count, 26.15 × 10³/µL) and elevated C-reactive protein (19.81 mg/dL). Contrast-enhanced computed tomography demonstrated multiple cystic and heterogeneous abdominopelvic lesions, including extension across the abdominal wall fascia and muscles, with involvement of the uterus and urinary bladder, raising suspicion for advanced gynecologic malignancy with peritoneal dissemination. Tumor markers were within normal limits. Persistent lower abdominal pain and inflammatory markers without fever and negative blood culture after a week of empirical antibiotics (Flomoxef Sodium 2000 mg) prompted exploratory laparotomy to evaluate for possible ovarian malignancy or abscess. Total hysterectomy, right salpingo-oophorectomy, partial excision of the abdominal abscess, and drainage of the left ovarian abscess were performed. Histopathology later confirmed the diagnosis of diffuse pelvic actinomycosis. The patient recovered after surgical drainage and antibiotics penicillin G for 4 weeks, followed by doxycycline (200 mg) twice daily for 3 months. This case highlights the important radiologic features of pelvic actinomycosis mimicking gynecologic malignancy, particularly in women with prolonged intrauterine device use and the management in refractory pelvic actinomycosis. Full article

(This article belongs to the Special Issue Imaging for the Diagnosis of Obstetric and Gynecological Diseases—2nd Edition)

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26 pages, 4888 KB

Open AccessArticle

Performance and Overflow Analysis of Polynomial Multiplication with Lazy Reduction in LightSaber

by Suchart Khummanee, Chanwit Suwannapong, Sarutte Atsawaraungsuk, Chalida Sanemueang, Thipwimon Chompookham and Kritsanapong Somsuk

Electronics 2026, 15(16), 3647; https://doi.org/10.3390/electronics15163647 (registering DOI) - 15 Aug 2026

Abstract

Polynomial multiplication is the main operation in lattice-based cryptography. Modular reduction is required to maintain the correctness within finite rings. In this study, the application of lazy reduction is chosen to reduce the frequency of modular operations in the LightSaber cryptosystem. Four polynomial [...] Read more.

Polynomial multiplication is the main operation in lattice-based cryptography. Modular reduction is required to maintain the correctness within finite rings. In this study, the application of lazy reduction is chosen to reduce the frequency of modular operations in the LightSaber cryptosystem. Four polynomial multiplication algorithms, including Schoolbook, Karatsuba (128 and 64 splits), and Toom-3, are evaluated under both conventional and lazy reduction settings within the same polynomial ring domain. The experimental results show that lazy reduction reduces execution time across all evaluated algorithms. The reductions range from 44.52% to 59.15%. When the number of modular reduction operations is considered, they are reduced by more than 99% for Schoolbook and Karatsuba-based methods, and by 57.14% for Toom-3. Under lazy reduction, the number of modular reductions becomes identical across all algorithms. Among the evaluated coefficient-domain methods, Toom-3 achieved the lowest execution time. Karatsuba-based methods provide a more balanced trade-off between performance, memory usage, and structural complexity. This study further examines coefficient growth and evaluates the risk of overflow to ensure numerical reliability. All intermediate values remain within the range of signed 32-bit integers. Furthermore, lazy reduction leads to an increase in peak memory usage across all algorithms, with the most significant increase observed in Schoolbook, while more advanced methods exhibit only modest growth. Since this study focuses on coefficient-domain polynomial multiplication, transform-based approaches such as the Number Theoretic Transform (NTT) are beyond the scope of this work. NTT operates in a different computational domain and involves distinct implementation trade-offs. Accordingly, the reported performance comparisons are restricted to the coefficient-domain methods evaluated in this study. In addition, hardware-specific evaluations are beyond the scope of this work, because the primary objective is to provide an algorithm-level analysis of computational efficiency, modular reduction behavior, and numerical safety under controlled conditions. Under the evaluated Python implementation and the LightSaber parameter configuration, the results show that lazy reduction is an effective technique for reducing computational overhead in coefficient-domain polynomial multiplication. The observed performance remains dependent on the structural characteristics of each multiplication algorithm. Full article

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13 pages, 9452 KB

Open AccessArticle

Feasibility and Safety of Rapid Drug Desensitization for Chemotherapy-Induced Maculopapular Eruptions

by Meryem Demir, Nilay Duman, Haydar Soydaner Karakus, Sercan On, Kasim Okan, Hatice Serpil Akten, Sinem Inan, Su Ozgur, Tuncay Goksel, Erdem Goker and Ozlem Goksel

J. Clin. Med. 2026, 15(16), 6320; https://doi.org/10.3390/jcm15166320 (registering DOI) - 15 Aug 2026

Abstract

Background/Objectives: Chemotherapy drug (ChD)-induced maculopapular eruptions (MPEs) may interrupt optimal cancer treatment when no equally effective alternative therapy is available. Evidence supporting rapid drug desensitization (RDD) for delayed-type MPE remains scarce. We aimed to evaluate the feasibility and safety of RDD in [...] Read more.

Background/Objectives: Chemotherapy drug (ChD)-induced maculopapular eruptions (MPEs) may interrupt optimal cancer treatment when no equally effective alternative therapy is available. Evidence supporting rapid drug desensitization (RDD) for delayed-type MPE remains scarce. We aimed to evaluate the feasibility and safety of RDD in patients with ChD-induced MPE. Methods: Adult patients with ChD-induced MPE who underwent RDD between January 2021 and January 2024 were evaluated. Delayed MPE recurrence was assessed until the subsequent chemotherapy cycle. Results: A total of 63 RDD procedures were performed in 10 patients with ChD-induced MPE, most commonly triggered by taxanes and platinum agents. The median onset of the index reaction was 60.0 h (24.0–336.0), and delayed intradermal tests were positive in 2 of 9 tested patients (22.2%). No delayed MPE recurrences were observed during the predefined follow-up period until the subsequent chemotherapy cycle. Immediate breakthrough reactions occurred in 3 of 10 patients (30.0%), corresponding to 17 of 63 RDD procedures (27.0%), and were limited to mild flushing and pruritus that resolved with antihistamines with or without low-dose corticosteroids. All RDD procedures were successfully completed without severe systemic reactions, and all patients were discharged on the same day. Conclusions: In carefully selected patients with delayed-type MPE, RDD appears to be a feasible and safe short-term strategy for enabling continuation of essential chemotherapy within the predefined observation period. As this pilot study includes a small and heterogeneous patient population with limited follow-up, the findings should be considered preliminary and hypothesis-generating and warrant confirmation in larger prospective studies with longer follow-up. Full article

(This article belongs to the Special Issue Translational Immunology in Clinical Medicine: From Preclinical Insights to Therapeutic Impact)

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23 pages, 3906 KB

Open AccessArticle

Ellagic Acid Mitigates Lead (Pb)-Induced Toxicity in Cyprinus Carpio: A Multi-Biomarker Assessment of Hematological, Immunological, and Oxidative Stress Responses Supported by Molecular Docking

by Mücahit Eroğlu, Mehmet Nuri Cakmak, Ayşegül Pala, Harun Uslu, Serpil Mişe Yonar, Ünal İspir, Cemal Orhan and Muhammet Enis Yonar

Antioxidants 2026, 15(8), 1020; https://doi.org/10.3390/antiox15081020 (registering DOI) - 15 Aug 2026

Abstract

Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) [...] Read more.

Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) using a multi-biomarker approach and molecular docking. Fish were assigned to six experimental groups: control, EA-treated, Pb-I, Pb-I + EA, Pb-II, and Pb-II + EA. Fish in the Pb-I and Pb-II groups were exposed to 2.5 and 5 mg/L Pb, respectively, while EA was administered via diet at 100 mg/kg for 14 days. At the end of the exposure period, hematological indices, innate immune parameters, and oxidative stress biomarkers were assessed in blood, liver, kidney, and gill tissues. Pb exposure caused marked hematological impairment, suppressed immune responses, increased malondialdehyde levels, and disrupted antioxidant defense by reducing SOD, CAT, GSH-Px, and GSH levels while increasing GST activity. In contrast, dietary EA supplementation significantly mitigated Pb-induced alterations, improved hematological and immunological responses, reduced lipid peroxidation, restored antioxidant capacity, and normalized GST activity to control levels. Molecular docking analyses further showed that EA interacts with hemoglobin and immunoglobulin M, supporting its potential role in preserving oxygen transport and immune functions under Pb-induced stress. Overall, the findings demonstrate that Pb-induced toxicity involves coordinated disruption of redox homeostasis and immune function, whereas EA exerts a multi-target protective effect through biochemical and molecular mechanisms. This study provides mechanistic insight into chemical–biological interactions and supports the potential application of natural bioactive compounds in mitigating heavy metal-induced toxicity. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

23 pages, 423 KB

Open AccessArticle

Efficient Methods for Dynamic Correlation in Atoms

by Kenneth G. Dyall

Atoms 2026, 14(8), 70; https://doi.org/10.3390/atoms14080070 (registering DOI) - 15 Aug 2026

Abstract

An algorithm for large-scale correlated calculations on atoms is presented that significantly reduces the scaling of these calculations with the number of single-particle functions used to construct the N-particle states. The reduction is provided in the stage in which the Hamiltonian matrix is [...] Read more.

An algorithm for large-scale correlated calculations on atoms is presented that significantly reduces the scaling of these calculations with the number of single-particle functions used to construct the N-particle states. The reduction is provided in the stage in which the Hamiltonian matrix is contracted with the coefficients or amplitudes of the basis states in an iterative procedure such as the Davidson method. The algorithm relies on the representation of the radial one-particle functions on a grid, and it makes use of the multipole expansion of the electron–electron interaction in a sequence of transformations on the spinors, coefficients, and potentials. It also uses prototyping for the angular integrals and evaluation of recoupling coefficients for the configuration state functions (CSFs) separately rather than for pairs of CSFs. The scaling is verified with calculations on two-electron atoms and analyzed in terms of the number of operations required for each stage of both the proposed algorithm and the conventional methods. Full article

(This article belongs to the Special Issue Future Directions in Atomic Physics Inspired by the Pioneering Work of Charlotte Froese Fischer and Ian Philip Grant)

36 pages, 1943 KB

Open AccessReview

Extruded Pseudocereal Snacks Mathematical Modelling Approaches for Prediction and Optimisation: A Review

by Biljana Lončar, Miloš Radosavljević, Jelena Filipović, Ivica Djalović, Milenko Košutić, Vladimir Filipović and Milica Nićetin

Foods 2026, 15(16), 2854; https://doi.org/10.3390/foods15162854 (registering DOI) - 15 Aug 2026

Abstract

Pseudocereals such as quinoa, amaranth, and buckwheat have attracted increasing attention as ingredients for extruded snack products because of their nutritional value, gluten-free status, and content of bioactive compounds. The quality of extruded products is governed by complex interactions among processing variables, including [...] Read more.

Pseudocereals such as quinoa, amaranth, and buckwheat have attracted increasing attention as ingredients for extruded snack products because of their nutritional value, gluten-free status, and content of bioactive compounds. The quality of extruded products is governed by complex interactions among processing variables, including barrel temperature, screw speed, feed moisture content, and formulation characteristics. As a result, mathematical modelling has become an important tool for predicting product properties and identifying suitable processing conditions. This review summarizes modelling approaches applied to extruded food products with a focus on pseudocereal extrusion. Particular emphasis is placed on response surface methodology (RSM), artificial neural networks (ANNs), adaptive neuro-fuzzy inference systems (ANFIS), support vector regression (SVR), and hybrid optimisation strategies. Published studies indicate that RSM remains the most commonly used approach because of its simplicity and interpretability, while ANN-based models generally provide much higher predictive accuracy when strong nonlinear relationships are present. The widespread use of small experimental datasets and limited external validation remains a major challenge for the practical implementation of advanced machine-learning models. This review examines the strengths and limitations of current modelling approaches and discusses future opportunities for integrating predictive models with digital manufacturing frameworks. Full article

(This article belongs to the Section Grain)

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15 pages, 2405 KB

Open AccessReview

Pathogen Effector-Mediated Reprogramming of Plant Alternative Splicing: From Immune Regulation to Crop Disease Resistance

by Yunyun Li, Junru Mao and Song Kou

Plants 2026, 15(16), 2477; https://doi.org/10.3390/plants15162477 (registering DOI) - 15 Aug 2026

Abstract

Plants have evolved sophisticated immune systems to defend against diverse pathogens, whereas pathogens deploy effectors to manipulate host cellular processes for successful infection. Recent studies have revealed that pathogen effectors can target host RNA processing, particularly pre-mRNA alternative splicing (AS), to reshape transcript [...] Read more.

Plants have evolved sophisticated immune systems to defend against diverse pathogens, whereas pathogens deploy effectors to manipulate host cellular processes for successful infection. Recent studies have revealed that pathogen effectors can target host RNA processing, particularly pre-mRNA alternative splicing (AS), to reshape transcript isoform profiles and modulate plant immunity. However, the common principles and specific differences among pathogen effector-mediated regulation of host AS and their impacts on plant immunity have not been systematically summarized. In this review, we summarize recent advances in pathogen effector-mediated regulation of plant AS, focusing on three major mechanisms: targeting host splicing factors, altering RNA regulatory elements, and interfering with RNA-processing pathways. We discuss how effector-induced AS reprogramming affects immune-related gene expression and contributes to pathogen virulence. Furthermore, we highlight the emerging potential of AS regulation in disease resistance and disease-resistant crop breeding, and propose future directions for dissecting effector-specific splicing targets and translating AS-based regulatory mechanisms into crop improvement strategies. This review emphasizes host RNA splicing as an important regulatory layer in plant-pathogen interactions and provides new perspectives for understanding pathogen manipulation of plant immunity. Full article

(This article belongs to the Collection Feature Papers in Plant Protection)

70 pages, 30761 KB

Open AccessReview

Innovative Hydroxyapatite–Hydrogel Composites for Cartilage Regeneration

by Anita Ioana Visan, Liviu Duta and Irina Negut

Gels 2026, 12(8), 727; https://doi.org/10.3390/gels12080727 (registering DOI) - 15 Aug 2026

Abstract

Articular cartilage defects remain a significant clinical challenge due to the limited intrinsic regenerative capacity of cartilage and the inability of many current therapeutic approaches to restore the structure and function of native hyaline tissue. As a result, considerable research efforts have been [...] Read more.

Articular cartilage defects remain a significant clinical challenge due to the limited intrinsic regenerative capacity of cartilage and the inability of many current therapeutic approaches to restore the structure and function of native hyaline tissue. As a result, considerable research efforts have been directed toward the development of tissue-engineering and biomaterial-based strategies capable of promoting more effective regeneration. Among these, hydroxyapatite–hydrogel (HAp–hydrogel) composites have emerged as particularly promising candidates because they combine the biological functionality of HAp with the structural versatility of hydrogel networks. Hydrogels provide a highly hydrated, extracellular matrix-like environment that supports cell survival, facilitates matrix deposition, and enables the localized delivery of therapeutic agents. At the same time, their physicochemical properties can be tailored through a variety of crosslinking approaches and advanced responsive design strategies. The incorporation of HAp, either in nano- or microscale form, contributes to mechanical reinforcement, supports subchondral bone regeneration, and influences cellular behavior through both biochemical and mechanotransductive mechanisms. Beyond promoting chondrogenic differentiation, HAp–hydrogel composites have also been investigated for their capacity to modulate inflammation, stimulate angiogenesis within the subchondral region, provide antibacterial protection, and maintain a microenvironment conducive to tissue repair. This review critically examines recent advances in the development and application of HAp–hydrogel composites for cartilage regeneration, highlighting material design principles, fabrication strategies, healing mechanisms, and the key challenges that continue to influence their clinical translation. Full article

(This article belongs to the Special Issue Innovative Gels: Structure, Properties, and Emerging Applications)

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22 pages, 1647 KB

Open AccessArticle

AI-Supported Functional Pain Phenotyping in Low Back Pain Using Sensor-Based Gait and Neuromuscular Biomarkers

by Jan Jens Koltermann, Philipp Floessel, Freya Charlotte Wunderlich, Jil-Justin Funke, Hannes Kaplick and Alexander C. Disch

Sensors 2026, 26(16), 5178; https://doi.org/10.3390/s26165178 (registering DOI) - 15 Aug 2026

Abstract

Low back pain (LBP) is associated with altered motor control that may be reflected in sensor-derived features. This exploratory development study analysed 3567 gait-analysis variables from 36 participants using a 15-feature pipeline and leave-one-subject-out evaluation. The primary outcome contrasted pain-free with high pain [...] Read more.

Low back pain (LBP) is associated with altered motor control that may be reflected in sensor-derived features. This exploratory development study analysed 3567 gait-analysis variables from 36 participants using a 15-feature pipeline and leave-one-subject-out evaluation. The primary outcome contrasted pain-free with high pain intensity after 11 participants in the intermediate mild-pain stratum were excluded by design (25 participants; 50 trials). Stacking achieved an accuracy of 0.780 (95% CI 0.620–0.920) and balanced accuracy of 0.731 (95% CI 0.573–0.893). Recurrent features involved the feet, left thigh and multifidus-specific EMG asymmetry. An exploratory two-cluster analysis showed clinical associations but weak separation (silhouette 0.172). As model configuration and comparison were developed within the available cohort, the estimates represent internal exploratory performance rather than validation of a clinical prediction model. The findings are hypothesis-generating and require independent external validation. Full article

(This article belongs to the Topic Advanced Functional Materials for Environmental and Health Applications)

36 pages, 3381 KB

Open AccessArticle

Towards a Regionally Grounded Theoretical Model of East African Built Heritage as a Layered System: Implications for Architectural Education

by Rweyemamu Valentine Vedasto, Koenraad Van Cleempoel, Els Hannes, Shubira Leonidas Kalugila and Sarah Phoya

Heritage 2026, 9(8), 321; https://doi.org/10.3390/heritage9080321 (registering DOI) - 15 Aug 2026

Abstract

Built cultural heritage in East Africa is often interpreted and taught through monument-based, stylistic, or externally derived frameworks that insufficiently account for the region’s overlapping environmental, cultural, historical, and socio-spatial processes. Responding to this theoretical and pedagogical gap, this article develops a regionally [...] Read more.

Built cultural heritage in East Africa is often interpreted and taught through monument-based, stylistic, or externally derived frameworks that insufficiently account for the region’s overlapping environmental, cultural, historical, and socio-spatial processes. Responding to this theoretical and pedagogical gap, this article develops a regionally grounded theoretical model of East African built heritage as a layered system, with particular attention to Kenya, Tanzania, and Uganda. Methodologically, the study adopts a qualitative, interpretive approach, combining a critical literature review, analysis of selected built heritage layers, and expert perspectives from East African and European/international respondents. The findings show that East African built heritage is shaped by five interrelated layers: environmental foundations, indigenous and vernacular systems, Swahili/coastal Indian Ocean urbanism, colonial reconfiguration, and postcolonial/contemporary transformation. These layers do not form a linear historical sequence; rather, they overlap, interact, are disrupted, and are reinterpreted through material practices, spatial transformation, memory, environmental knowledge, and everyday use. The article argues that East African built heritage is defined by a layered system that is hybrid, fragile, unevenly recognized, partly intangible, and negotiated. It concludes that architectural education must move beyond object-based conservation knowledge transfer toward competency building in historical interpretation, environmental understanding, community engagement, adaptive reuse, and critical design intervention. Full article

(This article belongs to the Section Architectural Heritage)

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26 pages, 4049 KB

Open AccessArticle

Optimization and Comparative Evaluation of Green Extraction Techniques for Polyphenol Recovery from Aronia melanocarpa By-Products

by Georgios Triantafyllou, Vassilis Athanasiadis, Dimitrios Kalompatsios, Stavros I. Lalas and Paraskevi Mitlianga

Foods 2026, 15(16), 2853; https://doi.org/10.3390/foods15162853 (registering DOI) - 15 Aug 2026

Abstract

Due to its high content of bioactive constituents and associated health benefits, Aronia melanocarpa is considered a superfood, and its consumption has increased substantially in recent years. This growing demand has led to the generation of large quantities of processed by-products, which remain [...] Read more.

Due to its high content of bioactive constituents and associated health benefits, Aronia melanocarpa is considered a superfood, and its consumption has increased substantially in recent years. This growing demand has led to the generation of large quantities of processed by-products, which remain rich in valuable phytochemicals and require sustainable utilization. In this study, four extraction techniques—conventional solvent extraction (CSE), pressurized liquid extraction (PLE), pulsed electric field extraction (PEF), and ultrasound-assisted extraction (UAE)—were comparatively evaluated and optimized for the recovery of bioactive compounds from aronia pomace. A second-order polynomial model (Fit Least Squares) was applied to determine the optimal conditions for each technique. The optimized extracts exhibited distinct phytochemical profiles: total polyphenol content reached 71.5 (UAE), 70.0 (CSE), 67.0 (PLE), and 48.0 (PEF) mg GAE/g dw, while total anthocyanins were 15.5 (UAE), 13.0 (CSE), 11.0 (PEF), and 3.5 (PLE) mg CyE/g dw. Antioxidant capacity ranged from 538.0 to 800.0 µmol AAE/g dw (FRAP) and 17.0 to 39.0 mmol AAE/g dw (DPPH). HPLC analysis confirmed cyanidin-3-O-glucoside as the predominant compound, with concentrations of 5.0 (UAE), 4.6 (CSE), 3.2 (PEF), and 0.8 mg/g dw (PLE). Overall, ultrasound-assisted extraction under optimal conditions provided the highest recovery of bioactive constituents, highlighting its suitability for the valorization of aronia by-products. Full article

(This article belongs to the Special Issue Food By-Products as a Source of Active Ingredients for a Sustainable Food Industrial Sector)

14 pages, 1523 KB

Open AccessArticle

Dynamics of Hyper-Reflective Foci and Hard Exudates in Diabetic Macular Edema Treated with Faricimab

by Paul Widmann-Sedlnitzky, Kim Lien Huber, Irene Steiner, Markus Gumpinger, Heiko Stino, Tilman Schmoll, Ursula Schmidt-Erfurth, Stefan Sacu and Andreas Pollreisz

J. Clin. Med. 2026, 15(16), 6319; https://doi.org/10.3390/jcm15166319 (registering DOI) - 15 Aug 2026

Abstract

Background/Objectives: Diabetic macular edema is caused by disruptions in the blood–retinal barrier, resulting in leakage and inflammation, appearing in optical coherence tomography as retinal fluid, hard exudates, and hyper-reflective foci. This study aimed to assess volumetric changes in hyper-reflective foci and hard exudates [...] Read more.

Background/Objectives: Diabetic macular edema is caused by disruptions in the blood–retinal barrier, resulting in leakage and inflammation, appearing in optical coherence tomography as retinal fluid, hard exudates, and hyper-reflective foci. This study aimed to assess volumetric changes in hyper-reflective foci and hard exudates in faricimab-treated diabetic macular edema in real-world practice. Methods: This retrospective longitudinal study included forty-four eyes with faricimab-treated diabetic macular edema and follow-up of ≥40 weeks. Optical coherence tomography scans were analyzed at baseline, post-loading, 6 months and 1 year. Hyper-reflective foci and hard exudates were quantified across macular subfields using a machine-learning algorithm with manual correction. Outcomes included volumetric changes, best-corrected visual acuity, and central subfield thickness. Early morphologic responders were defined post-loading by ≥20% central subfield thickness reduction and/or central subfield thickness below 280 µm. Results: At 1 year, hyper-reflective foci and hard exudate volumes significantly decreased in the central subfield (median differences: −0.025 nL, p = 0.00028; −0.119 nL, p = 0.00025) and outer ring (−0.178 nL, p = 0.00041; −0.612 nL, p = 0.014). Hard exudate volume significantly decreased in the inner ring (−0.740 nL, p < 0.0001). Best-corrected visual acuity and central subfield thickness improved significantly (−0.10 logarithm of the minimum angle of resolution (logMAR), p = 0.0018; −48 µm, p < 0.0001). Total hyper-reflective foci volumes were similar between responders and non-responders. In contrast, hard exudate burden remained numerically higher in non-responders. Conclusions: During the year following the switch to faricimab, HRF and HE burden decreased alongside visual and anatomical improvement. HRF volumes were descriptively similar between early CST responders and non-responders, whereas HE burden remained numerically higher in non-responders. Full article

(This article belongs to the Section Ophthalmology)

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35 pages, 5110 KB

Open AccessArticle

Balancing Rapid Urbanization and Ecological Security on a Tropical Island: Multi-Objective Land Use Optimization and Simulation Based on Non-Linear Driving Thresholds

by Yaobin Fang, Yeqing Cheng, Yan Chen and Jinping Zhang

Land 2026, 15(8), 1479; https://doi.org/10.3390/land15081479 (registering DOI) - 15 Aug 2026

Abstract

Subjected to high-intensity development, enclosed tropical islands frequently face severe spatial resource constraints and acute risks of ecological degradation. To seek a comprehensive solution to multidimensional spatial conflicts, this study selected Hainan Island—a region facing development pressure from the Free Trade Port construction—as [...] Read more.

Subjected to high-intensity development, enclosed tropical islands frequently face severe spatial resource constraints and acute risks of ecological degradation. To seek a comprehensive solution to multidimensional spatial conflicts, this study selected Hainan Island—a region facing development pressure from the Free Trade Port construction—as the study area. By coupling the XGBoost-SHAP, NSGA-II, and PLUS models, we constructed an integrated modular spatial planning framework of “mechanism interpretation—macro optimization—micro reconstruction”. The main findings are as follows. (1) Over the past 15 years, the fragile ecosystem of the island has faced immense pressure. Lacking an external buffer hinterland, land-use transitions exhibited a distinct chain transmission characteristic of “built-up land occupying agricultural land, and agricultural land squeezing forest”. This internal spatial cascading substitution constituted the core mechanism of ESV decline. (2) The reconstruction of the spatial pattern is governed by dual thresholds of natural constraints and economic pulling. A rigid ecological defense baseline (NDVI ≥ 0.40) restricts disorderly urban sprawl, while spatial inflection points (8.46 km from the coastline and 271 m from roads) precisely delineate the coastal and traffic-oriented agglomeration boundaries for built-up land. (3) Among the predefined scenarios, the Sustainable Development (SD) scenario emerges as the optimal pathway. By proactively reducing inefficient agricultural land space at the macro level and strictly implementing identified threshold controls alongside “infill” urban agglomeration at the micro level, the SD scenario is expected to successfully achieve a Pareto-optimal synergy between socioeconomic growth and the restoration of regional ESV. This study not only establishes an objective benchmark for the refined multi-objective spatial governance of the Hainan Free Trade Port, but also provides a referential planning paradigm for vulnerable enclosed islands globally facing high-intensity anthropogenic stress. Full article

(This article belongs to the Topic Biophilic Cities and Communities: Human-Environment Interaction and Sustainable Governance)

13 pages, 553 KB

Open AccessArticle

Symptom Burden, Depressive Symptoms, Resilient Coping, and Pretreatment Health-Related Quality of Life with Breast, Gynecological and Genitourinary Cancer

by Caterina Calderon, Patricia Cruz-Castellanos, Asia Ferrandez-Arias, Lucía Roncero-Sánchez, Valle Rodríguez-Morón, Rocío Galán-Moral, David Gómez-Sánchez, María Nevado-Rodríguez, Marina Gustems and Paula Jiménez-Fonseca

Curr. Oncol. 2026, 33(8), 482; https://doi.org/10.3390/curroncol33080482 (registering DOI) - 15 Aug 2026

Abstract

Pretreatment health-related quality of life (HRQoL) may identify supportive care needs, but the joint contribution of symptom burden, depressive symptoms, and resilient coping remains insufficiently characterized. This multicenter baseline analysis included 194 adults with breast (n = 86), gynecological (n = [...] Read more.

Pretreatment health-related quality of life (HRQoL) may identify supportive care needs, but the joint contribution of symptom burden, depressive symptoms, and resilient coping remains insufficiently characterized. This multicenter baseline analysis included 194 adults with breast (n = 86), gynecological (n = 77), or genitourinary (n = 31) cancer from six Spanish hospitals before systemic therapy. Global HRQoL was assessed with the EuroQol visual analogue scale EQ-VAS; symptom burden with EORTC QLQ-C30 symptom scales/items; depressive symptoms with the Brief Symptom Inventory-18 depression subscale; and resilient coping with the Brief Resilient Coping Scale. EQ-VAS scores did not differ by tumor site (p = 0.369). Symptom burden was strongly inversely associated with HRQoL (r = −0.827, p < 0.001). In the moderated mediation model, higher symptom burden was associated with higher depressive symptoms (B = 0.275, 95% CI 0.118 to 0.431); symptom burden (B = −0.642, 95% CI −0.715 to −0.569) and depressive symptoms (B = −0.529, 95% CI −0.743 to −0.316) were associated with lower HRQoL scores. Indirect effects through depressive symptoms were statistically different from zero, but resilient coping did not significantly moderate this indirect association. These cross-sectional findings support pretreatment screening for symptoms and depressive symptoms to guide early supportive oncology care. Full article

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16 pages, 3857 KB

Open AccessReview

The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances

by Mina Kolahdouzmohammadi, Nicholas Tjandra, Kevan Wu, Raha Nikoumaram and Graziano Oldani

Cells 2026, 15(16), 1465; https://doi.org/10.3390/cells15161465 (registering DOI) - 15 Aug 2026

Abstract

The adult liver exhibits remarkable regenerative capacity in vivo; however, primary hepatocytes (PHs), the principal functional cells of the liver, swiftly forfeit their proliferative potential and specialized hepatic functions when isolated from their native microenvironment and cultured in vitro. While PHs are the [...] Read more.

The adult liver exhibits remarkable regenerative capacity in vivo; however, primary hepatocytes (PHs), the principal functional cells of the liver, swiftly forfeit their proliferative potential and specialized hepatic functions when isolated from their native microenvironment and cultured in vitro. While PHs are the benchmark for studying hepatic physiology, xenobiotic metabolism, and toxicological responses, their rapid dedifferentiation resulting in the loss of hepatic functions significantly limits their further application. Recent studies suggest three converging strategies to address the challenge of long-term maintenance and expansion of PHs. First, defined chemical and growth factor-based protocols can temporarily induce hepatocytes into a proliferative, progenitor-like state, followed by a maturation phase that restores differentiated hepatic functions. In addition, the inhibition of signaling pathways linked to cellular stress responses and identity loss can postpone dedifferentiation and preserve drug-metabolizing activity for prolonged durations, thereby enhancing disease modeling and toxicology studies. Finally, three-dimensional (3D) culture platforms generally improve hepatocyte maturation and functional stability, but these are often not scalable due to matrix dependence, technical complexity, handling requirements, and cost. This review thoroughly examines innovative methodological advancements designed to facilitate the proliferation and prolonged viability of healthy PHs, focusing on their translational relevance and clinical applicability. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms Behind Liver Inherited Metabolic Diseases and Novel Therapeutic Strategies)

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21 pages, 1587 KB

Open AccessArticle

A Metabolomics-Driven Integrated Machine Learning Framework for Early Prediction of Recurrent Acute Pancreatitis

by Qing Huang, Xiaoyan Shen, Ying Li, Haoxi Wu, Xiangxiang Huang, Guangming Li and Di Wang

Metabolites 2026, 16(8), 575; https://doi.org/10.3390/metabo16080575 (registering DOI) - 15 Aug 2026

Abstract

Background/Objective: Recurrent acute pancreatitis (RAP) can progress to chronic pancreatitis and ultimately pancreatic ductal adenocarcinoma; therefore, early identification of patients at high recurrence risk is clinically important. However, the high dimensionality, inherent variability, and susceptibility to outliers of metabolomic data pose challenges [...] Read more.

Background/Objective: Recurrent acute pancreatitis (RAP) can progress to chronic pancreatitis and ultimately pancreatic ductal adenocarcinoma; therefore, early identification of patients at high recurrence risk is clinically important. However, the high dimensionality, inherent variability, and susceptibility to outliers of metabolomic data pose challenges for reliable biomarker identification. Methods: Here, we propose an integrated framework that combines Isolation Forest-based outlier handling to systematically assess the influence of aberrant samples, a dual-pathway adaptive Lasso feature selection strategy incorporating stability-oriented and sparsity-oriented pathways, and statistical significance filtering to reduce false positives. Results: When applied to a cohort of 63 patients, Random Forest (RF) achieved the highest mean outer-fold area under the receiver operating characteristic curve (AUC) among the five classifiers evaluated (0.933 ± 0.133). In an exploratory modality analysis incorporating 11 prespecified baseline clinical covariates, the clinical-only, metabolomics-only, and combined clinical–metabolomic RF models achieved mean outer-fold AUCs of 0.712 ± 0.265, 0.933 ± 0.133, and 0.986 ± 0.029, respectively. Although the combined model showed the highest numerical AUC, it did not significantly outperform the metabolomics-only model based on pooled out-of-fold predictions. Notably, in this small-sample setting, the dual-pathway selection strategy recurrently identified orotic acid as a candidate metabolite with the most consistent fold-wise statistical support across outer training partitions. Re-execution of the workflow on a public gastric cancer metabolomics dataset demonstrated its technical portability to a distinct classification task. Conclusions: Together, these findings provide a framework that distinguishes internal predictive performance and feature stability from biochemical validation, offering a reproducible basis for prioritizing RAP-associated metabolic signals and guiding future multicenter targeted validation studies. Full article

(This article belongs to the Topic Metabolomics: Evaluating the Metabolic Profile of Biological Samples)

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14 pages, 2333 KB

Open AccessArticle

Lysophosphatidic Acid Receptor 5 (LPA₅) Antagonist AS2717638 Attenuates Allergic Asthma by Reducing Mast Cell Degranulation and Th2 Inflammation in Mice

by Seung-Won Jeong and Dong-Soon Im

Int. J. Mol. Sci. 2026, 27(16), 7296; https://doi.org/10.3390/ijms27167296 (registering DOI) - 15 Aug 2026

Abstract

Lysophosphatidic acid receptor 5 (LPA₅, formerly designated GPR92) is a G protein-coupled receptor that recognizes lysophosphatidic acid. Previous studies have indicated that the absence of LPA₅ confers protection against the development of neuropathic pain. Although LPA₅ expression has been [...] Read more.

Lysophosphatidic acid receptor 5 (LPA₅, formerly designated GPR92) is a G protein-coupled receptor that recognizes lysophosphatidic acid. Previous studies have indicated that the absence of LPA₅ confers protection against the development of neuropathic pain. Although LPA₅ expression has been identified in mast cells, macrophages, and microglia, its specific contribution to allergic responses remains insufficiently characterized. In this study, we evaluated the therapeutic potential of LPA₅ inhibition in allergic asthma. To this end, the effects of the selective LPA₅ antagonist 6,7-dimethoxy-2-(5-methyl-1,2-benzisoxazol-3-yl)-4-(1-piperidinylcarbonyl)-1(2H)-isoquinolinone (AS2717638) were examined using both an in vitro mast cell degranulation model and an in vivo ovalbumin-induced asthma model in BALB/c mice. In RBL-2H3 cells expressing the lpar5 gene, AS2717638 treatment attenuated antigen-induced degranulation. In vivo, administration of AS2717638 reduced airway resistance triggered by ovalbumin exposure. Furthermore, treatment with AS2717638 led to a decrease in eosinophil and lymphocyte infiltration, as well as reduced levels of inflammatory cytokines in bronchoalveolar lavage fluid. Histopathological analysis additionally demonstrated diminished pulmonary inflammation following AS2717638 administration, accompanied by significant reductions in cytokine expression within lung tissue. Collectively, these findings suggest that pharmacological inhibition of LPA₅ using AS2717638 mitigates key features of allergic asthma, supporting LPA₅ as a potential therapeutic target for this condition. Full article

(This article belongs to the Special Issue Allergic Diseases: Molecular Insights into Immunotherapy)

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25 pages, 997 KB

Open AccessArticle

Just as I Expected: Experimentally Testing the Influence of Expectancies on Perceptions of Interrogations

by Christopher J. Normile and Kyle C. Scherr

Behav. Sci. 2026, 16(8), 1401; https://doi.org/10.3390/bs16081401 (registering DOI) - 15 Aug 2026

Abstract

Expecting that a future consequence will occur has a meaningful and powerful influence on people’s behavior, regardless of whether the expected event actually occurs. However, most people do not appreciate the substantial impact that expectations have on human behavior. In this series of [...] Read more.

Expecting that a future consequence will occur has a meaningful and powerful influence on people’s behavior, regardless of whether the expected event actually occurs. However, most people do not appreciate the substantial impact that expectations have on human behavior. In this series of studies, we investigated people’s ability to grasp the power of expectations on suspects’ confession decisions. In Experiment 1 (N = 253), mock-jurors failed to appreciate the power of expectation and believed that a defendant who confessed after being induced with an expectation regarding the length of an interrogation was more likely to be guilty than a defendant who actually experienced a lengthy interrogation. In Experiment 2 (N = 261), online participants were less likely to support reintegration services for an exoneree who falsely confessed after being induced with expectations during his interrogation compared to an exoneree who actually experienced a lengthy interrogation. Collectively, the results of Experiments 1 and 2 further our understanding of people’s difficulty in appreciating situational influences and, in particular, suspects’ decision-making and the subsequent effects of false confession evidence. Full article

(This article belongs to the Special Issue Psychological and Behavioral Processes in Legal Decision-Making)

36 pages, 17071 KB

Open AccessReview

Merging Galaxy Clusters and the Search for New Physics of Dark Matter: A Review

by Rogério Monteiro-Oliveira

Universe 2026, 12(8), 249; https://doi.org/10.3390/universe12080249 (registering DOI) - 15 Aug 2026

Abstract

Merging galaxy clusters represent one of the most powerful macroscopic laboratories in the Universe for searching for new physics within the dark sector. High-velocity cosmic collisions inherently separate the dark matter and stellar components from the highly collisional, X-ray-emitting intracluster gas. These massive [...] Read more.

Merging galaxy clusters represent one of the most powerful macroscopic laboratories in the Universe for searching for new physics within the dark sector. High-velocity cosmic collisions inherently separate the dark matter and stellar components from the highly collisional, X-ray-emitting intracluster gas. These massive systems provide an ideal environment to probe the fundamental nature of dark matter, specifically testing whether it behaves as a strictly collisionless particle or exhibits non-zero self-interactions. While pioneering systems like the Bullet Cluster historically demonstrated the macroscopic decoupling of dark and ordinary matter, the field has evolved into a sophisticated discipline driven by multi-disciplinary methodologies. This review synthesizes recent theoretical and empirical advances in interpreting post-collision dynamics. It examines how the synergy of combined approaches—integrating multi-wavelength observations from gravitational lensing and X-ray mapping with high-fidelity N-body hydrodynamical simulations—allows the translation of macroscopic spatial observables into stringent constraints on microscopic particle properties. Through this synthesis, the work evaluates how leveraging heterogeneous merger ensembles can reliably advance the ongoing search for physics beyond the standard cosmological model. Full article

(This article belongs to the Special Issue Search for New Physics Through Combined Approaches)

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