Saved Queries

by Alba Antúnez-Rodríguez, Sonia García-Rodríguez, Ana Pozo-Agundo, Jesús Gabriel Sánchez-Ramos, Eduardo Moreno-Escobar, José Matías Triviño-Juárez, María Jesús Álvarez-Cubero, Luis Javier Martínez-González and Cristina Lucía Dávila-Fajardo

Int. J. Mol. Sci. 2025, 26(19), 9766; https://doi.org/10.3390/ijms26199766 - 7 Oct 2025

Abstract

Clopidogrel is widely used as an antiplatelet therapy for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Genetic factors influence variability in clopidogrel response, with non-functional CYP2C19 alleles increasing the risk of major adverse cardiovascular events (MACEs). While CYP2C19 genotype-guided therapy after PCI improves outcomes, MACEs persist at variable rates. Pharmacogenomics (PGx) has primarily focused on genes related to drug metabolism, but therapeutic failure may stem from individual disease predisposition. This study aims to identify novel genetic variants underlying adverse events after PCI despite PGx-guided therapy. A custom sequencing panel was analyzed in 244 ACS-PCI-stent patients and 99 controls without cardiovascular (CV) disease. Association analysis was performed independent of treatment and by prescribed treatment (clopidogrel or prasugrel), complemented by random forest models to predict risk during antiplatelet therapy. No polymorphism reached genomic significance, but in clopidogrel-treated patients, rs2472434 in ABCA1, related to altered lipid metabolism, was strongly associated with secondary CV events (p = 1.7 × 10⁻³). Variants in the clopidogrel pathway, including CYP2C19, ABCB1, and UGT2B7, were also identified and may influence clopidogrel response. Predictive models incorporating these variants effectively discriminated patients with and without events (p = 0.02445). Our findings support combined genotyping of CYP2C19 loss-of-function and ABCB1 C3435T variants to guide antiplatelet therapy and suggest additional targets, such as rs2472434 (ABCA1) and rs7439366 (UGT2B7), to improve risk prediction of adverse CV events. Therefore, the unexplained variability in clopidogrel response may be due to disease pathogenesis itself, highlighting the need for a paradigm shift in PGx studies. Full article

(This article belongs to the Special Issue Molecular and Translational Research in Cardiovascular Endocrinology, Cardio-Metabolic Diseases and Non-Alcoholic Fatty Liver Disease (NAFLD): 2nd Edition)

17 pages, 1807 KB

Open AccessArticle

First-Principles Study on the Microheterostructures of N-GQDs@Si₃N₄ Composite Ceramics

by Wei Chen, Yetong Li, Yucheng Ma, Enguang Xu, Rui Lou, Zhuohao Sun, Yu Tian and Jianjun Zhang

Coatings 2025, 15(10), 1172; https://doi.org/10.3390/coatings15101172 - 7 Oct 2025

Abstract

In the previous research that aimed to enhance the toughness and tribological properties of silicon nitride ceramics, a lignin precursor was added to the ceramic matrix, which achieved conversion through pyrolysis and sintering, resulting in a silicon nitride-based composite ceramic containing nitrogen-doped graphene quantum dots (N-GQDs). This composite material demonstrated excellent comprehensive mechanical properties and friction-wear performance. Based on the existing experimental results, the first-principles plane wave mode conservation pseudopotential method of density functional theory was adopted in this study to build a microscopic heterostructure model of Si₃N₄-based composite ceramics containing N-GQDs. Meanwhile, the surface energy of Si₃N₄ and the system energy of the N-GQDs@Si₃N₄ heterostructure were calculated. The calculation results showed that when the distance between N-GQDs and Si₃N₄ in the heterostructure was 2.3 Å, the structural energy was the smallest and the structure was the steadiest. This is consistent with the previous experimental results and further validates the coating mechanism of N-GQDs covering the Si₃N₄ column-shaped crystals. Simultaneously, based on the results of the previous experiments, the stress of the heterostructure composed of Si₃N₄ particles coated with different numbers of layers of nitrogen quantum dots was calculated to predict the optimal lignin doping amount. It was found that when the doping amount was between 1% and 2%, the best microstructure and mechanical properties were obtained. This paper provides a new method for studying the graphene quantum dot coating structure. Full article

(This article belongs to the Special Issue Advanced Ceramic Materials and Coatings: Synthesis, Properties and Applications)

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25 pages, 998 KB

Open AccessArticle

Trust Formation, Error Impact, and Repair in Human–AI Financial Advisory: A Dynamic Behavioral Analysis

by Jihyung Han and Daekyun Ko

Behav. Sci. 2025, 15(10), 1370; https://doi.org/10.3390/bs15101370 - 7 Oct 2025

Abstract

Understanding how trust in artificial intelligence evolves is crucial for predicting human behavior in AI-enabled environments. While existing research focuses on initial acceptance factors, the temporal dynamics of AI trust remain poorly understood. This study develops a temporal trust dynamics framework proposing three phases: formation through accuracy cues, single-error shock, and post-error repair through explanations. Two experiments in financial advisory contexts tested this framework. Study 1 (N = 189) compared human versus algorithmic advisors, while Study 2 (N = 294) traced trust trajectories across three rounds, manipulating accuracy and post-error explanations. Results demonstrate three temporal patterns. First, participants initially favored algorithmic advisors, supporting “algorithmic appreciation.” Second, single advisory errors resulted in substantial trust decline (η² = 0.141), demonstrating acute sensitivity to performance failures. Third, post-error explanations significantly facilitated trust recovery, with evidence of enhancement beyond baseline. Financial literacy moderated these patterns, with higher-expertise users showing sharper decline after errors and stronger recovery following explanations. These findings reveal that AI trust follows predictable temporal patterns distinct from interpersonal trust, exhibiting heightened error sensitivity yet remaining amenable to repair through well-designed explanatory interventions. They offer theoretical integration of appreciation and aversion phenomena and practical guidance for designing inclusive AI systems. Full article

19 pages, 2433 KB

Open AccessArticle

Two-Dimensional Analytical Magnetic Field Calculation in a Brushless Doubly Fed Reluctance Machine

by Slimane Tahi, Cherif Guerroudj, Smail Mezani, Rachid Ibtiouen and Noureddine Takorabet

Actuators 2025, 14(10), 486; https://doi.org/10.3390/act14100486 - 7 Oct 2025

Abstract

This paper proposes a 2D semi-analytical model based on the subdomain method for the performance analysis of a brushless doubly fed reluctance machine (BDFRM) with a salient pole rotor. In particular, assuming an infinite magnetic permeability of the iron core and assuming a smooth stator, the field calculation region is divided into two solution subdomains, i.e., the rotor slot and air-gap. The magnetic vector potential in each subdomain is obtained by solving the governing PDE by the separation of variables method and employing the boundary conditions between adjacent interfaces. Moreover, based on the stored magnetic energy in the air-gap, the calculation of the three-phase windings’ self and mutual inductances is presented. Through a case study involving a 6/2 pole BDFRM, the accuracy of the developed subdomain model is confirmed by comparing its analytically predicted results with those obtained from two-dimensional finite element method (FEM) simulations. Full article

(This article belongs to the Special Issue Advanced Theory and Application of Magnetic Actuators—3rd Edition)

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15 pages, 3339 KB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of the SPL Gene Family in Phalaenopsis equestris

by Xule Zhang, Lei Feng, Qingdi Hu, Yaping Hu, Xiaohua Ma and Jian Zheng

Plants 2025, 14(19), 3090; https://doi.org/10.3390/plants14193090 - 7 Oct 2025

Abstract

The SQUAMOSA promoter-binding protein-like (SPL/SBP) family plays crucial roles in multiple developmental processes. Phalaenopsis equestris is a key ornamental and breeding species known for producing abundant colorful flowers on a single inflorescence. The SPL gene family in this species remains largely uncharacterized. In this study, 15 SPL genes were identified, all encoding proteins that are bioinformatically predicted to be nuclear-localized, hydrophilic, and unstable, with conserved SBP domains. Phylogenetic and collinearity analyses revealed a closer evolutionary relationship with rice SPLs than Arabidopsis SPLs. Conserved motif and gene structure analyses showed that subfamily II members possess more motifs and introns, implying functional complexity. Five PeqSPLs contained transmembrane domains, suggesting potential dual nuclear/cytoplasmic roles. Promoter analysis revealed abundant cis-elements responsive to light, stress, and phytohormones. Expression profiling across tissues showed that PeqSPL2, PeqSPL3, and PeqSPL5 exhibited broad expression and PeqSPL10 exhibited predominantly high expression in flowers, indicating possible roles in normal growth and floral development. This study provides a foundation for further functional exploration of PeqSPL genes in P. equestris. Full article

(This article belongs to the Special Issue Orchid Conservation and Biodiversity)

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13 pages, 2169 KB

Open AccessPerspective

The Spectrum of Consciousness on the Borders of Life and Death

by Calixto Machado and Gerry Leisman

Clin. Transl. Neurosci. 2025, 9(4), 48; https://doi.org/10.3390/ctn9040048 - 7 Oct 2025

Abstract

We here delve into the intricate and evolving concepts of brain death and consciousness, particularly at the end of life. We examine the historical and technological advancements that have influenced our understanding of death, such as mechanical ventilation and resuscitation techniques. These developments have challenged traditional definitions of death, leading to the concept of brain death, defined as the irreversible loss of all brain functions, including the brainstem. We emphasize that consciousness exists on a continuum, ranging from full alertness to deep coma and complete cessation of brain activity. It explores various disorders of consciousness, including coma, vegetative state, minimally conscious state, and locked-in syndrome, each with distinct characteristics and levels of awareness. Neuroimaging techniques, such as EEG, fMRI, and DTI, are highlighted for their crucial role in diagnosing and understanding disorders of consciousness. These techniques help to detect covert consciousness, assess brain activity, and predict recovery potential. The phenomenon of the “wave of death,” which includes a paradoxical surge in brain activity at the point of death, is also discussed. We address the challenges in defining and understanding both death and consciousness, calling for biologically grounded, ethically defensible, and culturally sensitive definitions. We advocate for standardized neuroimaging protocols, longitudinal studies, and the integration of artificial intelligence to improve diagnosis and treatment. In conclusion, the document underscores the importance of an integrated, evidence-based approach to understanding the gray zones between life and death, recognizing that consciousness and death are dynamic processes with both biological and experiential dimensions. Full article

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24 pages, 8385 KB

Open AccessArticle

Classification of Calcium-Dependent Protein Kinases and Their Transcriptional Response to Abiotic Stresses in Halophyte Nitraria sibirica

by Lu Lu, Ting Chen, Tiangui Yang, Chunxia Han, Jingbo Zhang, Jinhui Chen and Tielong Cheng

Plants 2025, 14(19), 3091; https://doi.org/10.3390/plants14193091 - 7 Oct 2025

Abstract

Calcium-dependent protein kinases (CDPKs) are key Ca²⁺ sensors in plants, mediating responses to abiotic stresses via phosphorylation signaling. In the halophyte Nitraria sibirica, which thrives in saline soils, we identified 19 CDPK genes (NsCDPKs) and classified them into four canonical angiosperm clades, highlighting conserved functional modules. Promoter analysis revealed diverse cis-acting elements responsive to light, hormones (ABA, MeJA, auxin, GA, SA), and abiotic stresses (drought, cold, wounding), along with numerous MYB binding sites, suggesting complex transcriptional regulation. Transcriptome profiling under salt stress (100 and 400 mM NaCl) showed induction of most NsCDPKs, with several genes significantly upregulated in roots and stems, indicating coordinated whole-plant activation. These salt-responsive NsCDPKs were also upregulated by cold but repressed under PEG-simulated drought, indicating stress-specific regulatory patterns. Fifteen MYB transcription factors, differentially expressed under salt stress, were predicted to interact with NsCDPK promoters, implicating them as upstream regulators. This study identified a potential salt- and cold-responsive CDPK regulatory module and a MYB-mediated transcriptional hierarchy in N. sibirica, providing insights into the molecular mechanisms of salinity adaptation and highlighting candidate genes that could be explored for improving salt tolerance in crop species. Full article

(This article belongs to the Special Issue Molecular Mechanisms Associated with Plant Tolerance upon Abiotic Stress—2nd Edition)

15 pages, 1671 KB

Open AccessArticle

In Silico Identification of DNMT Inhibitors for the Treatment of Glioblastoma

by Meyrem Osum, Louai Alsaloumi and Rasime Kalkan

Int. J. Transl. Med. 2025, 5(4), 48; https://doi.org/10.3390/ijtm5040048 - 7 Oct 2025

Abstract

Background/Objectives: Gliomas are the most common tumours of the central nervous system (CNS), classified into grades I to IV based on their malignancy. Genetic and epigenetic alterations play a crucial role in glioma progression. DNA methyltransferases (DNMTs) are vital enzymes responsible for DNA methylation, with DNMT1 and DNMT3 catalysing the addition of a methyl group to the 5-carbon of cytosine in CpG dinucleotides. Targeting DNMTs with DNA methyltransferase inhibitors (DNMTi) has become a promising therapeutic approach in tumour treatment. In this study, in silico screening tools were employed to evaluate potential inhibitors of DNMT1, DNMT3A, and DNMT3B for the treatment of glioblastoma multiforme (GBM). Methods: The Gene2Drug platform was used to screen compounds and rank them based on their capacity to dysregulate DNMT genes. PRISM viability assays were performed on 68 cell lines, and DepMap data were analyzed to assess the antitumor activities of these compounds and their target genes. Candidate drug similarity was evaluated using DSEA, and compounds with p < 1 × 10⁻³ were considered statistically significant. Gene-compound interactions for DNMT1, DNMT3A, and DNMT3B were confirmed using Expression Public 24Q2, while Prism Repositioning Public data were analyzed via DepMap. Results: Glioblastoma cell lines showed sensitivity to compounds including droperidol, demeclocycline, benzthiazide, ozagrel, pizotifen, tracazolate, norcyclobenzaprine, monocrotaline, dydrogesterone, 6-benzylaminopurine, and nifedipine. SwissTargetPrediction was utilised to identify alternative molecular targets for selected compounds, revealing high-probability matches for droperidol, pizotifen, tracazolate, monocrotaline, dydrogesterone, and nifedipine. Conclusions: Integrating computational approaches with biological insights and conducting tissue-specific and experimental validations may significantly enhance the development of DNMT-targeted therapies for gliomas. Full article

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16 pages, 1758 KB

Open AccessArticle

Predicting Biochemical Recurrence After Robot-Assisted Prostatectomy with Interpretable Machine Learning Model

by Tianwei Zhang, Hisamitsu Ide, Jun Lu, Yan Lu, Toshiyuki China, Masayoshi Nagata, Tsuyoshi Hachiya and Shigeo Horie

J. Clin. Med. 2025, 14(19), 7079; https://doi.org/10.3390/jcm14197079 - 7 Oct 2025

Abstract

Background: This study aimed to develop and evaluate machine learning (ML) models to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Methods: We retrospectively analyzed clinical data from 1125 patients who underwent RARP between July 2013 and December 2023. The dataset was divided into a training set (70%) and a testing set (30%) using a stratified sampling strategy. Five ML models were developed using the training set. Model performance was evaluated on the testing set using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 scores. Additionally, model interpretability was assessed using SHapley Additive exPlanations (SHAP) values to determine the contribution of individual features. Results: Among the five ML models, the LightGBM model achieved the best prediction ability with an AUC of 0.881 (95%CI: 0.840–0.922) in the testing set. For model interpretability, SHAP values explained the contribution of individual features to the model, revealing that pathological T stage (pT), positive surgical margin (PSM), prostate-specific antigen (PSA) nadir, initial PSA, systematic prostate biopsy positive rate, seminal vesicle invasion (SVI), pathological International Society of Urological Pathology Grade Group (pGG), and perineural invasion (PI) were the key contributors to the predictive performance. Conclusions: We developed and validated ML models to predict BCR following RARP and identified that the LightGBM model with 8 variables achieved promising performance and demonstrated a high level of clinical applicability. Full article

(This article belongs to the Section Nephrology & Urology)

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17 pages, 3914 KB

Open AccessArticle

Genomic and Functional Characterization of Acetolactate Synthase (ALS) Genes in Stress Adaptation of the Noxious Weed Amaranthus palmeri

by Jiao Ren, Mengyuan Song, Daniel Bimpong, Fulian Wang, Wang Chen, Dongfang Ma and Linfeng Du

Plants 2025, 14(19), 3088; https://doi.org/10.3390/plants14193088 - 7 Oct 2025

Abstract

Acetolactate synthase (ALS) is an important enzyme in plant branched-chain amino acid biosynthesis and the target of several major herbicide classes. Despite its agronomic importance, the role of ALS genes in stress adaptation in the invasive weed Amaranthus palmeri remains unstudied. In this study, four ApALS genes with high motif conservation were identified and analyzed in A. palmeri. Phylogenetic analysis classified ApALS and other plant ALS proteins into two distinct clades, and the ApALS proteins were predicted to localize to the chloroplast. Gene expression analysis demonstrated that ApALS genes are responsive to multiple stresses, including salt, heat, osmotic stress, glufosinate ammonium, and the ALS-inhibiting herbicide imazethapyr, suggesting roles in both early and late stress responses. Herbicide response analysis using an Arabidopsis thaliana ALS mutant (AT3G48560) revealed enhanced imazethapyr resistance, associated with higher chlorophyll retention. Furthermore, high sequence homology between AT3G48560 and ApALS1 suggests a conserved role in protecting photosynthetic function during herbicide stress. This study provides the first comprehensive analysis of the ALS gene family in A. palmeri and offers important insights into its contribution to stress resilience. These findings establish a vital foundation for developing novel strategies to control this pervasive agricultural weed and present potential genetic targets for engineering herbicide tolerance in crops. Full article

(This article belongs to the Special Issue Molecular, Biochemical and Developmental Adaptations of Plants Under Abiotic Stress)

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15 pages, 467 KB

Open AccessArticle

Elevated Alcohol Consumption and Chronic Inflammation Predict Cardiovascular Risk Among Black Americans: Examination of a Dual-Risk Model Using Epigenetic Risk Markers

by Steven R. H. Beach, Robert A. Philibert, Mei-Ling Ong, Man-Kit Lei and Kaixiong Ye

Epigenomes 2025, 9(4), 40; https://doi.org/10.3390/epigenomes9040040 - 7 Oct 2025

Abstract

Background: Heart disease may take a greater toll on Black Americans than White Americans despite similar levels of traditional risk factors. Elevated alcohol consumption (EAC) and chronic inflammation are two potentially important additional risk factors to consider. Both are relevant to understanding health disparities in cardiovascular health. Methods: Couples with a Black preadolescent or early adolescent child living in the home were recruited and followed. In waves 5 and 6 of data collection, biological samples were also collected allowing the characterization of elevated alcohol consumption, chronic inflammation, and cardiac risk using DNA methylation indices. 383 individual partners comprising 221 couples were examined across the two waves of data, yielding 661 person-wave observations from 383 individuals. Results: EAC at wave 5 forecast increased cardiac risk at W6 (R² change = 0.276), β = −0.193, p = 0.001. However, chronic inflammation at wave 5 did not add significantly to the baseline model, β = −0.042, p = 0.549. Conversely, the slope of change for chronic inflammation was associated with slope of change in cardiac risk (R² change = 0.111), b = −0.014, p = <0.001, but EAC change was not significantly associated with change in cardiac risk, b = −0.001, p = 0.185. Conclusions: Elevated alcohol consumption may be an important risk factor for increased cardiac risk over time in middle age. If so, it could be an important avenue for preventative intervention to decrease cardiac risk. Future research should examine whether similar associations are observed for other racial or minoritized groups and for non-minoritized groups. Full article

(This article belongs to the Collection Feature Papers in Epigenomes)

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17 pages, 2845 KB

Open AccessArticle

Quantitative Mechanisms of Long-Term Drilling-Fluid–Coal Interaction and Strength Deterioration in Deep CBM Formations

by Qiang Miao, Hongtao Liu, Yubin Wang, Wei Wang, Shichao Li, Wenbao Zhai and Kai Wei

Processes 2025, 13(10), 3183; https://doi.org/10.3390/pr13103183 - 7 Oct 2025

Abstract

During deep coalbed methane (CBM) drilling, wellbore stability is significantly influenced by the interaction between drilling fluid and coal rock. However, quantitative data on mechanical degradation under long-term high-temperature and high-pressure conditions are lacking. This study subjected coal cores to immersion in field-formula drilling fluid at 60 °C and 10.5 MPa for 0–30 days, followed by uniaxial and triaxial compression tests under confining pressures of 0/5/10/20 MPa. The fracture evolution was tracked using micro-indentation (µ-indentation), nuclear magnetic resonance (NMR), and scanning electron microscopy (SEM), establishing a relationship between water absorption and strength. The results indicate a sharp decline in mechanical parameters within the first 5 days, after which they stabilized. Uniaxial compressive strength decreased from 36.85 MPa to 22.0 MPa (−40%), elastic modulus from 1.93 GPa to 1.07 GPa (−44%), cohesion from 14.5 MPa to 5.9 MPa (−59%), and internal friction angle from 24.9° to 19.8° (−20%). Even under 20 MPa confining pressure after 30 days, the strength loss reached 43%. Water absorption increased from 6.1% to 7.9%, showing a linear negative correlation with strength, with the slope increasing from −171 MPa/% (no confining pressure) to −808 MPa/% (20 MPa confining pressure). The matrix elastic modulus remained stable at 3.5–3.9 GPa, and mineral composition remained unchanged, confirming that the degradation was due to hydraulic wedging and lubrication of fractures rather than matrix damage. These quantitative thresholds provide direct evidence for predicting wellbore stability in deep CBM drilling. Full article

(This article belongs to the Topic Exploitation and Underground Storage of Oil and Gas)

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28 pages, 1237 KB

Open AccessArticle

Counting Cosmic Cycles: Past Big Crunches, Future Recurrence Limits, and the Age of the Quantum Memory Matrix Universe

by Florian Neukart, Eike Marx and Valerii Vinokur

Entropy 2025, 27(10), 1043; https://doi.org/10.3390/e27101043 - 7 Oct 2025

Abstract

We present a quantitative theory of contraction and expansion cycles within the Quantum Memory Matrix (QMM) cosmology. In this framework, spacetime consists of finite-capacity Hilbert cells that store quantum information. Each non-singular bounce adds a fixed increment of imprint entropy, defined as the cumulative quantum information written irreversibly into the matrix and distinct from coarse-grained thermodynamic entropy, thereby providing an intrinsic, monotonic cycle counter. By calibrating the geometry–information duality, inferring today’s cumulative imprint from CMB, BAO, chronometer, and large-scale-structure constraints, and integrating the modified Friedmann equations with imprint back-reaction, we find that the Universe has already completed

N_{past} = 3.6 \pm 0.4

cycles. The finite Hilbert capacity enforces an absolute ceiling: propagating the holographic write rate and accounting for instability channels implies only

N_{future} = 7.8 \pm 1.6

additional cycles before saturation halts further bounces. Integrating Kodama-vector proper time across all completed cycles yields a total cumulative age

t_{QMM} = 62.0 \pm 2.5 Gyr

, compared to the

13.8 \pm 0.2 Gyr

of the current expansion usually described by

Λ

CDM. The framework makes concrete, testable predictions: an enhanced faint-end UV luminosity function at

z ≳ 12

observable with JWST, a stochastic gravitational-wave background with

f^{2 / 3}

scaling in the LISA band from primordial black-hole mergers, and a nanohertz background with slope

α ≃ 2 / 3

accessible to pulsar-timing arrays. These signatures provide near-term opportunities to confirm, refine, or falsify the cyclical QMM chronology. Full article

(This article belongs to the Special Issue Modified Gravity: From Black Holes Entropy to Current Cosmology, 4th Edition)

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16 pages, 1095 KB

Open AccessArticle

Inflammation-Based Cell Ratios Beyond White Blood Cell Count for Predicting Postimplantation Syndrome After EVAR and TEVAR

by Ebubekir Sönmez, İzatullah Jalalzai and Ümit Arslan

Int. J. Mol. Sci. 2025, 26(19), 9753; https://doi.org/10.3390/ijms26199753 - 7 Oct 2025

Abstract

Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; p = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0–1.3; p = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0–1.6; p = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2–6.3; p = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2–3.1; p = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1–3.2; p = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies. Full article

(This article belongs to the Special Issue Identification of Novel Biomarkers Towards Improved Diagnosis and Management of Peripheral Vascular Diseases)

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23 pages, 6082 KB

Open AccessArticle

A Bibenzyl from Dendrobium pachyglossum Exhibits Potent Anti-Cancer Activity Against Glioblastoma Multiforme

by Hnin Mon Aung, Onsurang Wattanathamsan, Kittipong Sanookpan, Aphinan Hongprasit, Chawanphat Muangnoi, Rianthong Phumsuay, Thanawan Rojpitikul, Boonchoo Sritularak, Tankun Bunlue, Naphat Chantaravisoot, Claudia R. Oliva, Corinne E. Griguer and Visarut Buranasudja

Antioxidants 2025, 14(10), 1212; https://doi.org/10.3390/antiox14101212 - 7 Oct 2025

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a potent antioxidant bibenzyl derivative isolated from Dendrobium pachyglossum. In U87MG cells, TDB reduced viability in a dose- and time-dependent manner, suppressed clonogenic growth, induced apoptosis via Bax upregulation and Bcl-xL/Mcl-1 downregulation, and inhibited both mTORC1 and mTORC2 signaling. TDB also impaired cell migration and downregulated epithelial–mesenchymal transition (EMT)-associated proteins. Notably, TDB enhanced the cytotoxicity of temozolomide (TMZ), the current standard of care for GBM. These TMZ-sensitizing properties were further confirmed in patient-derived xenograft (PDX) Jx22 cells. To assess its potential for central nervous system delivery, blood–brain barrier (BBB) permeability was predicted using four independent in silico platforms—ADMETlab 3.0, LogBB_Pred, LightBBB, and BBB Predictor (Tree2C)—all of which consistently classified TDB as BBB-permeable. This predicted CNS accessibility, together with its potent anticancer profile, underscores TDB’s translational promise. Collectively, our findings identify TDB as a plant-derived antioxidant with multifaceted anti-GBM activity and favorable BBB penetration potential, warranting further in vivo validation and preclinical development as a novel therapeutic candidate for GBM. Full article

(This article belongs to the Special Issue Anti-Cancer Potential of Plant-Based Antioxidants)

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