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Quantum machine learning (QML) has emerged as a promising approach for enhancing image classification by exploiting quantum computational principles such as superposition and entanglement. However, practical applications on complex datasets like CIFAR-100 remain limited due to the low expressivity of shallow circuits and challenges in circuit optimization. In this study, we propose HQCNN–REGA—a novel hybrid quantum–classical convolutional neural network architecture that integrates data re-uploading and genetic algorithm optimization for improved performance. The data re-uploading mechanism allows classical inputs to be encoded multiple times into quantum states, enhancing the model’s capacity to learn complex visual features. In parallel, a genetic algorithm is employed to evolve the quantum circuit architecture by optimizing gate sequences, entanglement patterns, and layer configurations. This combination enables automatic discovery of efficient parameterized quantum circuits without manual tuning. Experiments on the MNIST and CIFAR-100 datasets demonstrate state-of-the-art performance for quantum models, with HQCNN–REGA outperforming existing quantum neural networks and approaching the accuracy of advanced classical architectures. In particular, we compare our model with classical convolutional baselines such as ResNet-18 to validate its effectiveness in real-world image classification tasks. Our results demonstrate the feasibility of scalable, high-performing quantum–classical systems and offer a viable path toward practical deployment of QML in computer vision applications, especially on noisy intermediate-scale quantum (NISQ) hardware. Full article

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16 pages, 2696 KiB

Open AccessArticle

Presence of Protozoan Viruses in Vaginal Samples from Pregnant Women and Their Association with Trichomoniasis

by Gegham Ghardyan, Lusine Abrahamyan, Karen Julhakyan, Hakob Davtyan, Norayr Martirosyan, Elina Arakelova, Hranush Avagyan, Sona Hakobyan, Tigranuhi Vardanyan, Naira Karalyan and Zaven Karalyan

Pathogens 2025, 14(8), 764; https://doi.org/10.3390/pathogens14080764 (registering DOI) - 1 Aug 2025

Abstract

This study was conducted in Armenia and included 32 pregnant women with TV infection and 30 healthy controls. The vaginal virome includes viruses that infect human cells and unicellular eukaryotes such as Trichomonas vaginalis (TV). Among these are Trichomonas vaginalis viruses (TVVs), double-stranded RNA viruses from the Totiviridae family, and giant DNA viruses that replicate in protozoa. This study investigated the presence of TVVs and giant protozoan viruses in pregnant women with trichomoniasis in Armenia and explored their potential associations with adverse pregnancy outcomes. Vaginal and urethral samples were collected from 32 pregnant women with confirmed TV infection and 30 healthy pregnant controls. TVVs and giant viruses (Marseilleviridae, Mimiviridae, Phycodnaviridae) were detected using qRT-PCR. Viral RNA and DNA were extracted from clinical samples and TV cultures, followed by quantification and gene expression analysis. Selected TVVs were visualized via scanning electron microscopy. All TV-positive women carried at least one TVV strain, with 94% harboring multiple TVV types and TVV4 being the most common. TV infection was significantly associated with preterm birth and premature rupture of membranes (PPROM). Giant viruses were identified in all TV-positive cases but in only 40% of controls. Marseilleviridae gene expression was observed in TV cultures, suggesting possible interactions. These findings highlight a potential role for protozoan viruses in reproductive complications and warrant further investigation. Full article

(This article belongs to the Section Viral Pathogens)

33 pages, 2015 KiB

Open AccessArticle

From Development to Regeneration: Insights into Flight Muscle Adaptations from Bat Muscle Cell Lines

by Fengyan Deng, Valentina Peña, Pedro Morales-Sosa, Andrea Bernal-Rivera, Bowen Yang, Shengping Huang, Sonia Ghosh, Maria Katt, Luciana Andrea Castellano, Lucinda Maddera, Zulin Yu, Nicolas Rohner, Chongbei Zhao and Jasmin Camacho

Cells 2025, 14(15), 1190; https://doi.org/10.3390/cells14151190 (registering DOI) - 1 Aug 2025

Abstract

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

(This article belongs to the Special Issue Advances in Understanding Skeletal Muscle Metabolism and Regeneration: From Mechanisms to Therapeutics)

25 pages, 830 KiB

Open AccessArticle

Writing Is Coding for Sustainable Futures: Reimagining Poetic Expression Through Human–AI Dialogues in Environmental Storytelling and Digital Cultural Heritage

by Hao-Chiang Koong Lin, Ruei-Shan Lu and Tao-Hua Wang

Sustainability 2025, 17(15), 7020; https://doi.org/10.3390/su17157020 (registering DOI) - 1 Aug 2025

Abstract

In the era of generative artificial intelligence, writing has evolved into a programmable practice capable of generating sustainable narratives and preserving cultural heritage through poetic prompts. This study proposes “Writing Is Coding ” as a paradigm for sustainability education, exploring how students engage with AI-mediated multimodal creation to address environmental challenges. Using grounded theory methodology with 57 twelfth-grade students from technology-integrated high schools, we analyzed their experiences creating environmental stories and digital cultural artifacts using MidJourney, Kling, and Sora. Data collection involved classroom observations, semi-structured interviews, and reflective journals, analyzed through systematic coding procedures (κ = 0.82). Five central themes emerged: writing as algorithmic design for sustainability (89.5%), emotional scaffolding for environmental awareness (78.9%), aesthetics of imperfection in cultural preservation (71.9%), collaborative dynamics in sustainable creativity (84.2%), and pedagogical value of prompt literacy (91.2%). Findings indicate that AI deepens environmental consciousness and reframes writing as a computational process for addressing global issues. This research contributes a theoretical framework integrating expressive writing with algorithmic thinking in AI-assisted sustainability education, aligned with SDGs 4, 11, and 13. Full article

(This article belongs to the Special Issue Generative Artificial Intelligence (GAI) and AI-Generated Content (AIGC) for Sustainable Futures: Innovations in Education, Culture, and Society)

21 pages, 1979 KiB

Open AccessArticle

A Comparative Analysis of Usual- and Gastric-Type Cervical Adenocarcinoma in a Japanese Population Reveals Distinct Clinicopathological and Molecular Features with Prognostic and Therapeutic Insights

by Umme Farzana Zahan, Hasibul Islam Sohel, Kentaro Nakayama, Masako Ishikawa, Mamiko Nagase, Sultana Razia, Kosuke Kanno, Hitomi Yamashita, Shahataj Begum Sonia and Satoru Kyo

Int. J. Mol. Sci. 2025, 26(15), 7469; https://doi.org/10.3390/ijms26157469 (registering DOI) - 1 Aug 2025

Abstract

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

(This article belongs to the Special Issue Genomics and Proteomics of Cancer)

24 pages, 2329 KiB

Open AccessArticle

Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway

by Xiaolin Zhu, Lulu Zhang, Xuan Ni, Jian Guo, Yizhuo Fang, Jianghan Xu, Zhuo Chen and Zhihui Hao

Nutrients 2025, 17(15), 2540; https://doi.org/10.3390/nu17152540 (registering DOI) - 1 Aug 2025

Abstract

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

(This article belongs to the Section Nutrition and Metabolism)

18 pages, 3267 KiB

Open AccessArticle

Sodium Caseinate Induces Apoptosis in Cytarabine-Resistant AML by Modulating SIRT1 and Chemoresistance Genes, Alone or in Combination with Cytarabine or Daunorubicin

by Daniel Romero-Trejo, Itzen Aguiñiga-Sánchez, Amanda Velasco-García, Katia Michell Rodríguez-Terán, Fabian Flores-Borja, Isabel Soto-Cruz, Martha Legorreta-Herrera, Víctor Manuel Macías-Zaragoza, Ernesto Romero-López, Benny Weiss-Steider, Karen Miranda-Duarte, Claudia Itzel Sandoval-Franco and Edelmiro Santiago-Osorio

Int. J. Mol. Sci. 2025, 26(15), 7468; https://doi.org/10.3390/ijms26157468 (registering DOI) - 1 Aug 2025

Abstract

Resistance to cytarabine (Ara-C) remains a major obstacle to the successful treatment of acute myeloid leukemia (AML). Therefore, modulating Ara-C resistance is indispensable for improving clinical outcomes. We previously demonstrated that sodium caseinate (SC), a salt derived from casein, the principal milk protein, inhibits proliferation and modulates the expression of Ara-C resistance-related genes in chemoresistant cells. However, it remains unclear whether the combination of SC with antineoplastic agents enhances apoptosis, modulates chemoresistance-related genes, and prolongs the survival of tumor-bearing mice implanted with chemoresistant cells. Here, we investigated the effects of SC in combination with Ara-C or daunorubicin (DNR) on cell proliferation, apoptosis, the expression of chemoresistance-associated genes, and the survival of tumor-bearing mice. Crystal violet assays, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, flow cytometry, and Kaplan–Meier survival curves were used to evaluate the effects of combinations in chemoresistant cells. We demonstrate that the IC₂₅ concentration of SC, when combined with antileukemic agents, increases the sensitivity of chemoresistant WEHI-CR50 cells to Ara-C by downregulating SIRT1 and MDR1, upregulating the expression of ENT1 and dCK, enhancing apoptosis, and prolonging the survival of WEHI-CR50 tumor-bearing mice. Our data suggest that SC in combination with antileukemic agents could be an effective adjuvant for Ara-C-resistant AML. Full article

(This article belongs to the Special Issue Molecular Diagnostics and Genomics of Tumors)

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20 pages, 2424 KiB

Open AccessArticle

Loss of SVIP Results in Metabolic Reprograming and Increased Retention of Very-Low-Density Lipoproteins in Hepatocytes

by Vandana Sekhar, Thomas Andl and Shadab A. Siddiqi

Int. J. Mol. Sci. 2025, 26(15), 7465; https://doi.org/10.3390/ijms26157465 (registering DOI) - 1 Aug 2025

Abstract

Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article

(This article belongs to the Section Molecular Endocrinology and Metabolism)

15 pages, 4562 KiB

Open AccessArticle

DNA Methylation-Associated Epigenetic Changes in Thermotolerance of Bemisia tabaci During Biological Invasions

by Tianmei Dai, Yusheng Wang, Xiaona Shen, Zhichuang Lü, Fanghao Wan and Wanxue Liu

Int. J. Mol. Sci. 2025, 26(15), 7466; https://doi.org/10.3390/ijms26157466 (registering DOI) - 1 Aug 2025

Abstract

Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article

(This article belongs to the Section Molecular Biology)

9 pages, 220 KiB

Open AccessCommunication

Characterisation of the Ovine KRTAP36-1 Gene in Chinese Tan Lambs and Its Impact on Selected Wool Traits

by Lingrong Bai, Huitong Zhou, Jinzhong Tao, Guo Yang and Jon G. H. Hickford

Animals 2025, 15(15), 2265; https://doi.org/10.3390/ani15152265 (registering DOI) - 1 Aug 2025

Abstract

Wool has distinctive biological, physical, and chemical properties that contribute to its value both for the sheep and in global fibre and textile markets. Its fibres are primarily composed of proteins, principally keratin and keratin-associated proteins (KAPs). To better comprehend the genes that underpin key wool traits, this study examined the keratin-associated protein 36-1 gene (KRTAP36-1) in Chinese Tan lambs. We identified three previously reported alleles of the gene (named A, B and C) that were present in the lambs studied, with genotype frequencies as follows: 2.0% (n = 5; AA), 6.9% (n = 17; AB), 13.8% (n = 34; AC), 8.9% (n = 22; BB), 33.4% (n = 82; BC) and 35.0% (n = 86; CC). The frequencies of the individual alleles in the Chinese Tan lambs were 12.4%, 29.1% and 58.5% for alleles A, B and C, respectively. The three alleles were in Hardy–Weinberg Equilibrium. In an association analysis, it was revealed that allele C was associated with variation in the mean fibre curvature of the fine wool of the Chinese Tan lambs, but this association was not observed in their heterotypic hair fibres. This finding suggests that KRTAP36-1 might be differentially expressed in the wool follicles that produce the two fibre types, and that along with other KRTAP genes, it may be involved in determining fibre curvature and the distinctive curly coat of the lambs. Full article

(This article belongs to the Special Issue Genetic Analysis of Important Traits in Domestic Animals)

23 pages, 1985 KiB

Open AccessArticle

Photobiomodulation of 450 nm Blue Light on Human Keratinocytes, Fibroblasts, and Endothelial Cells: An In Vitro and Transcriptomic Study on Cells Involved in Wound Healing and Angiogenesis

by Jingbo Shao, Sophie Clément, Christoph Reissfelder, Patrick Téoule, Norbert Gretz, Feng Guo, Sabina Hajizada, Stefanie Uhlig, Katharina Mößinger, Carolina de la Torre, Carsten Sticht, Vugar Yagublu and Michael Keese

Biomedicines 2025, 13(8), 1876; https://doi.org/10.3390/biomedicines13081876 (registering DOI) - 1 Aug 2025

Abstract

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

(This article belongs to the Section Cell Biology and Pathology)

14 pages, 2514 KiB

Open AccessArticle

The Transcriptional Coactivator DEAD/H Box 5 (DDX5) Gene Is a Target of the Transcription Factor E2F1 Deregulated from the Tumor Suppressor pRB

by Rinka Nakajima, Yaxuan Zhou, Mashiro Shirasawa, Mariana Fikriyanti, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki and Kiyoshi Ohtani

Genes 2025, 16(8), 929; https://doi.org/10.3390/genes16080929 (registering DOI) - 1 Aug 2025

Abstract

Background: DEAD/H box 5 (DDX5) serves as a transcriptional coactivator for several transcription factors including E2F1, the primary target of the tumor suppressor pRB. E2F1 physiologically activated by growth stimulation activates growth-related genes and promotes cell proliferation. In contrast, upon loss of pRB function due to oncogenic changes, E2F1 is activated out of restraint by pRB (deregulated E2F1) and stimulates tumor suppressor genes such as ARF, which activates the tumor suppressor p53, to suppress tumorigenesis. We have recently reported that DDX5 augments deregulated E2F1 activity to induce tumor suppressor gene expression and apoptosis. During the analyses, we noted that over-expression of E2F1 increased DDX5 expression, suggesting a feed forward loop in E2F1 activation through DDX5. Objective: We thus examined whether the DDX5 gene is a target of deregulated E2F1. Method: For this purpose, we performed promoter analysis and ChIP assay. Result: The DDX5 promoter did not possess typical E2F binding consensus but contained several GC repeats observed in deregulated E2F1 targets. Insertion of point mutations in these GC repeats decreased responsiveness to deregulated E2F1 induced by over-expression of E2F1, but scarcely affected responsiveness to growth stimulation. ChIP assays showed that deregulated E2F1 induced by over-expression of E2F1 or expression of E1a, which binds pRB and releases E2F1, bound to the DDX5 gene, while physiological E2F1 induced by growth stimulation did not. Conclusions: These results suggest that the DDX5 gene is a target of deregulated E2F1, generating a feed forward loop mediating tumor suppressive E2F1 activity. Full article

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

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16 pages, 1632 KiB

Open AccessArticle

Meloidogyne incognita Significantly Alters the Cucumber Root Metabolome and Enriches Differential Accumulated Metabolites Regulating Nematode Chemotaxis and Infection

by Naicun Chen, Qianqian Sun, Zhiqun Chen and Xu Zhang

Horticulturae 2025, 11(8), 892; https://doi.org/10.3390/horticulturae11080892 (registering DOI) - 1 Aug 2025

Abstract

Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to facilitate its parasitism. In this study, untargeted metabolomics was employed to analyze metabolic changes in cucumber roots following nematode inoculation, with the goal of identifying differentially accumulated metabolites that may influence M. incognita behavior. Metabolomic analysis revealed that M. incognita significantly altered the cucumber root metabolome, triggering an accumulation of lipids and organic acids and enriching biotic stress-related pathways such as alkaloid biosynthesis and linoleic acid metabolism. Among differentially accumulated metabolites, myristic acid and hexadecanal were selected for further study due to their potential roles in nematode inhibition. In vitro assays demonstrated that both metabolites suppressed egg hatching and reduced infectivity of M. incognita, while pot experiments indicated a correlation between their application and reduced root gall formation. Chemotaxis assays further revealed that both metabolites exerted repellent effects on the chemotactic migration of M. incognita J2 and suppressed the transcriptional expression of two motility-and feeding-related neuropeptides, Mi-flp-1 and Mi-flp-18. In conclusion, this study demonstrates the significant potential of differentially accumulated metabolites induced by M. incognita infection for nematode disease control, achieved by interfering with nematode chemotaxis and subsequent infection. This work also provides deeper insights into the metabolomic mechanisms underlying the cucumber-M. incognita interaction. Full article

(This article belongs to the Special Issue 10th Anniversary of Horticulturae—Recent Outcomes and Perspectives)

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27 pages, 872 KiB

Open AccessArticle

Effect of Monomer Mixture Composition on TiCl₄-Al(i-C₄H₉)₃ Catalytic System Activity in Butadiene–Isoprene Copolymerization: A Theoretical Study

by Konstantin A. Tereshchenko, Rustem T. Ismagilov, Nikolai V. Ulitin, Yana L. Lyulinskaya and Alexander S. Novikov

Computation 2025, 13(8), 184; https://doi.org/10.3390/computation13080184 (registering DOI) - 1 Aug 2025

Abstract

Divinylisoprene rubber, a copolymer of butadiene and isoprene, is used as raw material for rubber technical products, combining isoprene rubber’s elasticity and butadiene rubber’s wear resistance. These properties depend quantitatively on the copolymer composition, which depends on the kinetics of its synthesis. This work aims to theoretically describe how the monomer mixture composition in the butadiene–isoprene copolymerization affects the activity of the TiCl₄–Al(i-C₄H₉)₃ catalytic system (expressed by active sites concentration) via kinetic modeling. This enables development of a reliable kinetic model for divinylisoprene rubber synthesis, predicting reaction rate, molecular weight, and composition, applicable to reactor design and process intensification. Active sites concentrations were calculated from experimental copolymerization rates and known chain propagation constants for various monomer compositions. Kinetic equations for active sites formation were based on mass-action law and Langmuir monomolecular adsorption theory. An analytical equation relating active sites concentration to monomer composition was derived, analyzed, and optimized with experimental data. The results show that monomer composition’s influence on active sites concentration is well described by a two-step kinetic model (physical adsorption followed by Ti–C bond formation), accounting for competitive adsorption: isoprene adsorbs more readily, while butadiene forms more stable active sites. Full article

(This article belongs to the Special Issue Feature Papers in Computational Chemistry)

22 pages, 2050 KiB

Open AccessArticle

YAP/TAZ Promote GLUT1 Expression and Are Associated with Prognosis in Endometrial Cancer

by Masayuki Fujita, Makoto Orisaka, Tetsuya Mizutani, Yuko Fujita, Toshimichi Onuma, Hideaki Tsuyoshi and Yoshio Yoshida

Cancers 2025, 17(15), 2554; https://doi.org/10.3390/cancers17152554 (registering DOI) - 1 Aug 2025

Abstract

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

(This article belongs to the Section Clinical Research of Cancer)

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