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21 pages, 14932 KB  
Communication
Allelopathic Activity of Ginseng-Cultivated Soil: Extracts on Seed Germination and Growth of Five Vegetables in China
by Jun Lei, Tianyi Wang, Wei Lin, Zhengwu Liu, Jiaqi Yang, Wanting Niu, Zichu Zhao, Jiarui Chen, Ping Chen and Yi Wang
Plants 2026, 15(11), 1607; https://doi.org/10.3390/plants15111607 (registering DOI) - 23 May 2026
Abstract
Allelopathy means that one plant produces chemical substances to affect the growth of other plants. Crop rotation is considered as a potential strategy to alleviate the allelopathic inhibition. So, it is important to identify rotation crops with wide availability and low inhibitory effects. [...] Read more.
Allelopathy means that one plant produces chemical substances to affect the growth of other plants. Crop rotation is considered as a potential strategy to alleviate the allelopathic inhibition. So, it is important to identify rotation crops with wide availability and low inhibitory effects. In this study, the allelopathic potential of soil extracts was investigated on the germination, seedling growth, biomass, and biochemical parameters (malondialdehyde, photosynthetic pigments, and antioxidant enzyme activities) of five crops, by a series of laboratory experiments. Firstly, both soil water extracts (SWE) and soil ethanol extracts (SEE) exhibited allelopathic inhibition on the seed germination and the root length of all seedlings in a dose-dependent relationship. The SWE significantly promoted the shoot length of bok choy and Chinese lettuce, while the SEE had no significant effect in bok choy. The application of SEE resulted in a significant increase in the dry weight of bok choy and rocket. In contrast, SWE had a negligible effect on bok choy and lettuce. Both of them caused decrease in the dry weight of the other seedlings. Then, the allelopathic synthetic effect index of water/ethanol extracts was chemo-inhibitory, and the inhibitory effect increased with increasing extract concentration. The SWE had the strongest inhibition on rocket and the SEE on lettuce. Both of them had the weakest effect on bok choy. The extracts significantly inhibited the photosynthetic capacity in five crops, manifested as decrease in photosynthetic pigments and dose-dependent effects. The malondialdehyde (MDA) content in all crops increased in a dose-dependent manner, confirming that the extracts caused lipid peroxidation. However, the defense strategies of different crops vary significantly. There is crop with active defense, such as bok choy treated with SWE. It delayed oxidative damage by continuously upregulating the activities of superoxide dismutase (SOD) and catalase (CAT). This is the key physiological mechanism for tolerance. There is also the oxidative stress failure type, as follows: CAT activity of rocket and cabbage increased, but the SOD activity did not increase by SEE. This reveals the physiological essence of their sensitivity—the lack of persistent scavenging ability for reactive oxygen species. Based on the inhibition of peroxidase (POD) and ascorbic acid peroxidase (APX), it is speculated that the extracts may inhibit the hydrogen peroxide scavenging pathway, which centered on the ascorbate–glutathione cycle. It is the fundamental reason why the continuous accumulation of MDA though SOD/CAT is up. This study confirmed the allelopathic effects of the water and ethanol extracts on five vegetable crops, and found that bok choy was less affected by them. The soil extracts affected the growth and development of seedlings by regulating their oxidative metabolism and photosynthetic capacity. These results support recommending pak choi as a rotation crop. This provides crops for subsequent field experiments and a new direction for next-step research on continuous cropping obstacles. Full article
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20 pages, 1477 KB  
Review
Glutamine-Linked Cellular Stress Responses in Viral Infection: Mechanisms, Crosstalk, and Future Perspectives
by Ngan Thi Kim Pham, Quang Duy Trinh, Hiroshi Ushijima, Shihoko Komine-Aizawa and Kazuaki Yoshimune
Int. J. Mol. Sci. 2026, 27(11), 4717; https://doi.org/10.3390/ijms27114717 (registering DOI) - 23 May 2026
Abstract
Glutamine is the most abundant amino acid in human plasma and tissues and plays essential roles in cellular metabolism, biosynthesis, and redox homeostasis. Beyond these canonical functions, glutamine availability and utilization have emerged as key regulators of multiple cellular stress responses, including the [...] Read more.
Glutamine is the most abundant amino acid in human plasma and tissues and plays essential roles in cellular metabolism, biosynthesis, and redox homeostasis. Beyond these canonical functions, glutamine availability and utilization have emerged as key regulators of multiple cellular stress responses, including the integrated stress response, endoplasmic reticulum stress, metabolic checkpoint signaling, and autophagy. During viral infection, host glutamine metabolism is frequently reprogrammed to meet the energetic and biosynthetic demands of viral replication, thereby inducing or reshaping glutamine-linked stress pathways. Increasing evidence indicates that these stress responses are not merely secondary consequences of infection but actively influence key stages of the viral life cycle, including viral entry, genome replication, protein synthesis, and host antiviral responses. In this review, we summarize current advances in understanding how glutamine metabolism regulates cellular stress responses in the context of both viral and non-viral infections, and how these pathways, in turn, modulate viral pathogenesis and host defense. We discuss the context-dependent roles of glutamine-linked stress signaling in either promoting viral replication or restricting infection, depending on viral species, host cell type, and metabolic conditions. Finally, we highlight emerging concepts and unresolved questions, including the potential of targeting glutamine metabolism and associated stress pathways as host-directed antiviral strategies. A deeper understanding of the interplay between glutamine metabolism, cellular stress responses, and viral infection may provide new insights into disease mechanisms and inform the development of novel therapeutic approaches. Full article
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19 pages, 2273 KB  
Article
Multi-Feature Incremental Scheduling for TSN Cyclic Queuing and Forwarding via a Triple-Mode Cooperative Optimizer
by Jianning Zhan, Hangu Zhang, Changsheng Chen, Wentao Zhang, Chao Fan, Xu Han and Shizhuang Deng
Electronics 2026, 15(11), 2252; https://doi.org/10.3390/electronics15112252 - 22 May 2026
Abstract
Time-Sensitive Networking (TSN) with Cyclic Queuing and Forwarding (CQF) is a critical mechanism for ensuring deterministic forwarding. However, existing incremental schedulers typically rely on single-dimensional heuristics, which fail to address the coupled impact of traffic characteristics and spatiotemporal resource distribution. This limitation leads [...] Read more.
Time-Sensitive Networking (TSN) with Cyclic Queuing and Forwarding (CQF) is a critical mechanism for ensuring deterministic forwarding. However, existing incremental schedulers typically rely on single-dimensional heuristics, which fail to address the coupled impact of traffic characteristics and spatiotemporal resource distribution. This limitation leads to suboptimal scheduling success, especially under complex topologies and high network loads. To address this, we propose TMCOA–MFS, a joint incremental scheduling framework that integrates the Triple-Mode Cooperative Optimization Algorithm (TMCOA) with a Multi-Feature Scheduling (MFS) strategy. The logic of our approach is twofold: First, to balance spatial resource distribution, we introduce the TMCOA—inspired by table-tennis offensive–defensive behaviors—to optimize path selection by minimizing port-load variance and escaping local optima through a three-mode population partition. Second, building upon the optimized spatial paths, the MFS strategy is employed to resolve temporal scheduling conflicts. By computing a composite priority score that accounts for path hops, offset configuration difficulty, and flow size, MFS enables a robust incremental offset search with integrated feasibility checking. Extensive simulations on benchmark functions and diverse TSN scenarios demonstrate that the TMCOA offers superior convergence and stability. More importantly, the integrated TMCOA–MFS framework significantly enhances scheduling success rates and load balancing, effectively overcoming the bottlenecks of high-load and topologically complex environments. Full article
(This article belongs to the Special Issue Real-Time Networks and Systems)
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20 pages, 3657 KB  
Article
Elicitor-Induced Modulation of Biomass, Antioxidant Enzyme Activities, and Phenolic Profiles in Adventitious Root Cultures of Gypsophila paniculata
by Hebat-Allah Ali Hussein
Horticulturae 2026, 12(6), 651; https://doi.org/10.3390/horticulturae12060651 - 22 May 2026
Abstract
Elicitation is a powerful strategy for increasing bioactive metabolites in plant systems. This study is among the first to integrate growth responses, antioxidant enzyme activities, and metabolite profiling in G. paniculata adventitious roots (ARs). The study aims to evaluate the effects of yeast [...] Read more.
Elicitation is a powerful strategy for increasing bioactive metabolites in plant systems. This study is among the first to integrate growth responses, antioxidant enzyme activities, and metabolite profiling in G. paniculata adventitious roots (ARs). The study aims to evaluate the effects of yeast extract (YE) and salicylic acid (SA) on biomass traits, antioxidant enzymes (peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase), and phenolic metabolite profiles. ARs were exposed to YE (0.25–2 g L−1) and SA (50–400 µM) for 28 days. Yeast extract significantly enhanced antioxidant capacity by promoting enzyme activities, phenolics, and flavonoids. In contrast, SA exhibited concentration-dependent effects. Moderate concentrations improved antioxidant activity, while higher concentrations promoted the accumulation of specific flavonoids. Maximum biomass production was achieved with 1 g L−1 YE, which also resulted in the highest metabolite productivity. Conversely, SA treatments caused a progressive reduction in biomass with increasing concentration, although they enhanced the accumulation of selected bioactive compounds. Notably, 100 µM SA resulted in the highest phenolic content and antioxidant activity, whereas 400 µM SA markedly increased flavonoids such as rutin and quercetin. HPLC analysis identified seventeen phenolic compounds, demonstrating that YE acts as a broad-spectrum elicitor, whereas SA functions as a selective metabolic modulator. The differential enzymatic responses further highlight elicitor-specific regulatory patterns in antioxidant defense and secondary metabolism. Overall, these findings demonstrate that elicitor type and concentration differentially influence the balance between growth and secondary metabolism, providing a framework for optimizing metabolite production in controlled in-vitro systems. Full article
36 pages, 1273 KB  
Article
A New Many-Objective Optimization Approach to Association Rule Mining: The NSGA-II/DE-ARM Algorithm
by Zulfukar Aytac Kisman, Gokhan Demir, Hande Yuksel and Bilal Alatas
Biomimetics 2026, 11(6), 362; https://doi.org/10.3390/biomimetics11060362 - 22 May 2026
Abstract
Association rule mining is a fundamental data mining technique for uncovering latent relationships among variables in large-scale datasets. However, conventional approaches rely on single-metric filtering strategies, which are insufficient for capturing the inherent multi-criteria nature of rule quality. To address this limitation, this [...] Read more.
Association rule mining is a fundamental data mining technique for uncovering latent relationships among variables in large-scale datasets. However, conventional approaches rely on single-metric filtering strategies, which are insufficient for capturing the inherent multi-criteria nature of rule quality. To address this limitation, this study formulates ARM as a many-objective optimization problem and proposes a hybrid algorithm, NSGA-II/DE-ARM, that simultaneously optimizes four rule-quality measures: support, confidence, lift, and NetConf. The proposed algorithm enhances the NSGA-II framework by integrating binary differential evolution operators, an adaptive operator selection mechanism, lift-weighted tournament selection, and a constraint-domination principle combined with a dynamic minimum support threshold. Its performance was evaluated using two datasets: a SIPRI–World Bank panel dataset consisting of defense industry and macroeconomic indicators covering 46 items over the 2002–2023 period, and the UCI Mushroom benchmark dataset consisting of 118 items. Across 30 independent runs on the SIPRI–World Bank dataset, NSGA-II/DE-ARM outperformed the Apriori baseline in all four metrics (mean lift = 4.748, confidence = 0.853, support = 0.146, NetConf = 0.789), with large effect sizes (Cohen’s d = 1.77–5.77, p < 0.001 in each case). On the Mushroom benchmark dataset, the proposed method also achieved substantial improvements, with Cohen’s d values ranging from 0.93 to 6.16. NSGA-II/DE-ARM generated 68 Pareto-optimal rules in a representative run and achieved the highest hypervolume values on both datasets, with HV = 3.231 for SIPRI–World Bank and HV = 6.262 for Mushroom. These results suggest that NSGA-II/DE-ARM offers decision-makers a broader and more balanced multi-criteria solution set than single-metric filtering approaches. Full article
(This article belongs to the Section Biological Optimisation and Management)
21 pages, 1386 KB  
Article
The Biocontrol Effect and Induced Disease Resistance Mechanism of Bacillus velezensis FJ17-4 on Cucumber Fusarium Wilt
by Chengzhong Lan, Lin Gan, Yuli Dai, Xiaofei Liu, Xiujuan Yang, Zhenhua Lei and Hongchun Ruan
Agronomy 2026, 16(11), 1028; https://doi.org/10.3390/agronomy16111028 - 22 May 2026
Abstract
Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum Owen (FOC) is a major disease affecting cucumber production. Developing environmentally friendly prevention and control strategies is essential for managing cucumber Fusarium wilt (CFW). Bacillus velezensis is a beneficial microorganism with biocontrol potential against [...] Read more.
Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum Owen (FOC) is a major disease affecting cucumber production. Developing environmentally friendly prevention and control strategies is essential for managing cucumber Fusarium wilt (CFW). Bacillus velezensis is a beneficial microorganism with biocontrol potential against plant diseases. To investigate the biocontrol efficacy and induced disease resistance mechanism of B. velezensis FJ17-4 against CFW, the biocontrol effect of FJ17-4 on CFW was determined through indoor pot cultivation experiments, and the transcriptome of cucumber root samples treated with FJ17-4 was sequenced and analyzed by RNA-Seq technology. The results showed that CFW incidence was significantly reduced after FJ17-4 treatment, with 68.75% control efficacy, higher than that of Kasugamycin. A total of 1041 differentially expressed genes (DEGs) were induced, including 477 upregulated and 564 downregulated genes. DEGs associated with plant–pathogen interaction pathways (such as carbon metabolism, phenylpropanoid biosynthesis and amino acid biosynthesis), calcium (Ca2+) signaling pathway, and plant hormone signaling pathways [such as salicylic acid (SA), ethylene (ET), and jasmonic acid (JA)] were induced. These responses activated the disease resistance system of cucumber against CFW. Quantitative RT-PCR validation of 10 annotated DEGs confirmed consistent expression trends with the transcriptomic data. The results indicate that FJ17-4-induced disease resistance involves multiple genes and coordinated regulation of metabolisms, with hormone-mediated defense signaling pathways playing important roles. The transcriptome sequencing data provides a scientific basis for exploring the induced disease resistance mechanism of FJ17-4 and developing environmentally friendly biocontrol strategies. Full article
(This article belongs to the Special Issue Interaction Mechanisms Between Crops and Pathogens)
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19 pages, 1202 KB  
Article
Antimicrobial Activity of Micrurus Venoms and Bioactive Films Functionalized with Purified L-Amino Acid Oxidase
by Vitelbina Núñez Rangel, Paola Rey-Suárez, Daniel Buitrago-Chinchilla, Laura Reyes-Méndez, Leidy Gómez-Sampedro, Alejandro Carmona-Jiménez, Mateo Rivillas-Ochoa and Adriana Muñoz-Bravo
Toxins 2026, 18(6), 240; https://doi.org/10.3390/toxins18060240 - 22 May 2026
Abstract
Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized [...] Read more.
Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized components with potent antimicrobial properties as part of a defense mechanism against prey-borne microorganisms. This study evaluated the inhibitory potential of Micrurus venoms against pathogens of agricultural interest and developed bioactive gelatin-based films incorporated with purified L-amino acid oxidases (LAAOs) as a novel biocontrol strategy. Venoms from M. ancoralis, M. mipartitus, and M. dumerilii exhibited significant growth inhibition against Xanthomonas and Fusarium strains. The primary active component was identified as LAAO through biological activity and mass spectrometry. Biofilms were formulated by incorporating M. ancoralis venom and its purified LAAO into a gelatin matrix. Physicochemical and microbiological characterization, alongside in situ assays on strawberries, demonstrated that the functionalized biofilms retained potent antimicrobial activity. Furthermore, LAAO incorporation did not significantly alter the physicochemical properties of the fruit but effectively extended shelf life by reducing weight loss and maintaining sensory appearance. These findings highlight the biotechnological potential of elapid venom components in the development of alternatives for phytopathogen control and active food packaging. Full article
(This article belongs to the Special Issue Venoms and Drugs)
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19 pages, 7444 KB  
Article
Locust cGAS-like Receptors Recognize Derivatives of a Gypsy Retrotransposon to Synergize with RNAi Against Viral Invasion
by Yi-Lan Li, Ma-Cheng Zhang, Shuo Yang, Peng Wang, Yao Xu and He-Ying Qian
Insects 2026, 17(6), 539; https://doi.org/10.3390/insects17060539 - 22 May 2026
Abstract
Transposable elements (TEs) are increasingly recognized as modulators of innate immunity, yet their antiviral functions remain poorly understood outside mammals and dipterans. Here, we identify a long terminal repeat retrotransposon, LmGypsy, as a key regulator of antiviral defense in Locusta migratoria. [...] Read more.
Transposable elements (TEs) are increasingly recognized as modulators of innate immunity, yet their antiviral functions remain poorly understood outside mammals and dipterans. Here, we identify a long terminal repeat retrotransposon, LmGypsy, as a key regulator of antiviral defense in Locusta migratoria. The infection of Acrididae reovirus (ARV) induces rapid upregulation of LmGypsy, and its inhibition compromises antiviral resistance. Mechanistically, LmGypsy promotes viral-derived DNA (vDNA) production, which drives Dicer-2-dependent biogenesis of virus-derived small interfering RNAs (vsiRNAs) to enhance RNA interference-mediated viral clearance. Notably, vDNA persists throughout infection, suggesting a role in sustaining antiviral responses. In parallel, LmGypsy activity is positively associated with induction of cyclic GMP-AMP synthase (cGAS)-like receptors (LmcGAS1/2/4) and their downstream effector Stimulator of Interferon Genes (STING). Together, these findings support a dual-layer antiviral strategy and indicate that TE-mediated immunity represents a widespread antiviral mechanism across taxa. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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30 pages, 1668 KB  
Systematic Review
Nasal Epithelial Organoids as Translational Platforms in Inflammatory, Infectious, and Precision Medicine Applications: A Systematic Review
by Veronica Scocca, Lorenzo Lauda, Riccardo Nocini and Giovanni Dell'Aversana Orabona
J. Clin. Med. 2026, 15(11), 4016; https://doi.org/10.3390/jcm15114016 - 22 May 2026
Abstract
Background/Objectives: The airway epithelium plays a central role in host defense, inflammatory signaling, and disease progression across infectious, inflammatory, and genetic respiratory disorders. Human nasal epithelial organoids have emerged as accessible and patient-specific in vitro platforms with increasing translational relevance. This systematic review [...] Read more.
Background/Objectives: The airway epithelium plays a central role in host defense, inflammatory signaling, and disease progression across infectious, inflammatory, and genetic respiratory disorders. Human nasal epithelial organoids have emerged as accessible and patient-specific in vitro platforms with increasing translational relevance. This systematic review aimed to critically evaluate the current evidence on nasal epithelial organoid models, focusing on donor characteristics, culture methodologies, differentiation strategies, and translational applications. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Ovid MEDLINE, and Cochrane Library was conducted for studies published between 1990 and April 2026. The review followed PRISMA guidelines and was structured according to the PICOTS framework. Eligible studies included in vitro experimental investigations using human-derived nasal epithelial organoids in infectious, inflammatory, or precision medicine contexts. Risk of bias was assessed using the QUIN tool. Results: Seventeen studies met the inclusion criteria. Applications clustered into three principal domains: infectious disease modeling, inflammatory and epithelial remodeling research, and cystic fibrosis precision medicine. Most studies employed expandable three-dimensional Matrigel-embedded organoids or organoid-derived air–liquid interface systems. Infection-focused studies demonstrated variant-specific viral replication dynamics and epithelial immune responses, while inflammatory models reproduced disease-associated differentiation and remodeling phenotypes. Cystic fibrosis oriented studies showed that organoid swelling and electrophysiological assays correlate with CFTR functional rescue and, in selected cases, clinical response. Methodological heterogeneity across protocols and outcome reporting precluded quantitative synthesis. Conclusions: Human nasal epithelial organoids represent versatile translational platforms bridging accessible patient-derived tissue and advanced airway disease modeling. Although variability in culture protocols and functional benchmarks limits standardization, these models hold significant promise for mechanistic investigation, therapeutic stratification, and precision medicine applications. Full article
(This article belongs to the Special Issue New Technologies for Personalized Medicine in Head and Neck Surgery)
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18 pages, 1826 KB  
Article
Comparative Biocontrol Efficacy and Mechanisms of Indirect and Direct Application Methods Against Leaf Spot Caused by Pseudomonas syringae pv. aptata in Sugar Beet
by Tamara Krstić Tomić, Marija Nedeljković, Aleksandra Mesaroš, Jovana Todorović, Marijana Pešaković, Slaviša Stanković and Jelena Lozo
Int. J. Mol. Sci. 2026, 27(11), 4672; https://doi.org/10.3390/ijms27114672 - 22 May 2026
Abstract
Using beneficial bacteria from the plant microbiome to combat pathogens is an environmentally friendly strategy for biological control. Although significant progress has been made in characterizing microorganisms with biocontrol potential, the optimal methods for applying such biological preparations to achieve maximum effectiveness against [...] Read more.
Using beneficial bacteria from the plant microbiome to combat pathogens is an environmentally friendly strategy for biological control. Although significant progress has been made in characterizing microorganisms with biocontrol potential, the optimal methods for applying such biological preparations to achieve maximum effectiveness against plant pathogens remain insufficiently defined. Our goal was to select rhizobacteria from the sugar beet microbiome and analyze their biocontrol capacity in both indirect and direct applications to protect the plant from Pseudomonas syringae pv. aptata P21. The methodological approach differed: indirect application involved seed priming with selected strains, Bacillus safensis MRh275, B. pseudomycoides JRh226, Stenotrophomonas maltophilia JRh266, or the T2 consortium (MRh275 and JRh266), while direct application involved simultaneous treatment of both the pathogen and the biocontrol strain. Although the direct approach resulted in a greater reduction in lesions and a lower concentration of H2O2, the indirect approach showed higher activity of peroxidase and superoxide dismutase as antioxidant enzymes, as well as phenylalanine ammonia-lyase, which is involved in the phenylpropanoid pathway and plant defense mechanisms. Infected plants showed higher expression of NPR1, MYC2, and LOX defense-related genes only under indirect biocontrol with all three strains, except in the T2 application. The T2 consortium performed best in direct biocontrol, where it most effectively reduced lesions. Since encounters between plants and pathogens cannot be accurately predicted, and the application of biological preparations should be easy and accessible for farmers, this study highlights the use of indirect biocontrol through seed priming to enhance the plant’s intrinsic defense capacity. Full article
(This article belongs to the Special Issue Molecular Insights into Rhizospheric Microbial Interactions)
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29 pages, 3251 KB  
Review
Beyond Inflammation: The Role of Oxidative Stress and Gut–Skin Axis Dysbiosis in the Pathogenesis of Immune-Mediated Skin Disorders and Potential Therapeutic Implications
by Maria Clara Gama de Souza Silva, Lucrezia De Pietro, Carla Ruffino San Cataldo, Antonio Bisaccia, Federica Nuccio, Federica Li Pomi and Sebastiano Gangemi
Int. J. Mol. Sci. 2026, 27(11), 4656; https://doi.org/10.3390/ijms27114656 - 22 May 2026
Abstract
The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized [...] Read more.
The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila, has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments. Full article
(This article belongs to the Special Issue Molecular Insights into Skin Health and Disease)
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21 pages, 5160 KB  
Article
Prophylactic and Therapeutic Anti-Hyperglycemic Effects of Heat-Killed Mycobacterium aurum in STZ-Induced Diabetic Mice
by Ali Ali, Hanin-Khaula Hakam, Alaa Eter, Samer Bazzi, Amani Chahine, Charles Akle, Georges M. Bahr and Karim S. Echtay
Nutrients 2026, 18(11), 1652; https://doi.org/10.3390/nu18111652 - 22 May 2026
Abstract
Background/Objectives: Exploiting the metabolic properties of postbiotics is a novel strategy for managing metabolic disorders, including diabetes. Inactivated microorganisms, a major class of postbiotics, improve glycemic control in preclinical and clinical studies. Here, we examined whether heat-killed (HK) Mycobacterium aurum (M. [...] Read more.
Background/Objectives: Exploiting the metabolic properties of postbiotics is a novel strategy for managing metabolic disorders, including diabetes. Inactivated microorganisms, a major class of postbiotics, improve glycemic control in preclinical and clinical studies. Here, we examined whether heat-killed (HK) Mycobacterium aurum (M. aurum) exerts prophylactic or therapeutic anti-hyperglycemic effects in diabetic mice. Methods: Diabetes was induced in male BALB/c mice by streptozotocin (STZ; 150 mg/kg) injection. HK M. aurum (1 mg) was given orally (three prophylactic doses before STZ) or intradermally (six weekly therapeutic doses after STZ). We assessed glycemic parameters, serum C-peptide/insulin (ELISA), and tissue protein expression (Western blot). Results: Neither route altered body weight or glucose homeostasis in non-diabetic mice. In STZ-diabetic mice, oral prophylactic treatment significantly attenuated hyperglycemia (39–60% reduction weeks 5–8 post-STZ) and showed a trend toward improved serum C-peptide, but did not affect dysregulated expression of skeletal muscle (SM), hepatic, pancreatic and renal proteins involved in glucose transport (GLUT2, GLUT4, and SGLT2), glycolysis (α-LDH), mitochondrial uncoupling (UCP2 and UCP3), and antioxidant defense (CAT). Therapeutic intradermal administration significantly decreased blood glucose (~30% at week 5, ~40% at week 6) and modestly enhanced insulin secretion. Hepatic UCP2 and α-LDH and SM UCP3 protein levels were normalized toward non-diabetic levels, whereas hepatic GLUT2 and SM GLUT4 remained largely unchanged. These correlative findings suggest effects independent of insulin-dependent glucose transport, but do not demonstrate direct functional improvement in mitochondrial or redox status. Conclusions: HK M. aurum exerts partial anti-hyperglycemic effects in STZ-induced diabetic mice, but the associated protein changes require functional validation before its role as a postbiotic in β-cell dysfunction can be established. Full article
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27 pages, 1050 KB  
Review
A Two-Stage In Silico-Guided Workflow for Forensic Toxicology: Empirical Validation via Capillary Zone Electrophoresis Prior to Mass-Spectrometric Confirmation
by Ivan Šoša
Toxics 2026, 14(5), 451; https://doi.org/10.3390/toxics14050451 - 21 May 2026
Abstract
Medium-throughput forensic toxicology laboratories are increasingly expected to detect highly polar metabolites while working under tight resource and time constraints. To meet these requirements, a workflow is proposed that includes two stages: The first is computational metabolite prediction, followed by capillary zone electrophoresis [...] Read more.
Medium-throughput forensic toxicology laboratories are increasingly expected to detect highly polar metabolites while working under tight resource and time constraints. To meet these requirements, a workflow is proposed that includes two stages: The first is computational metabolite prediction, followed by capillary zone electrophoresis (CZE), and the second stage is mass spectrometry (MS). The predictive step generates plausible metabolites and relevant physicochemical properties, which help guide early separation strategies. CZE then provides a rapid, low-cost way to test these predictions, identify informative samples, and exclude those unlikely to yield meaningful findings. Only samples that warrant further investigation proceed to targeted LC–MS/MS or high-resolution MS for confirmation. This approach shifts analytical effort toward the least resource-intensive stages, reducing unnecessary MS runs and improving turnaround time without compromising evidentiary standards. In practice, the workflow also improves day-to-day laboratory efficiency by overcoming equipment limitations and helping analysts focus on samples with genuine interpretive value. This stepwise combination of techniques is therefore suitable for routine forensic casework, where analytical decisions must be transparent, reproducible, and defensible. Full article
(This article belongs to the Special Issue Forensic and Post-Mortem Toxicology)
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24 pages, 3284 KB  
Review
Plant-Derived Bioactive Metabolites from the Sonoran Desert: Redox Regulation, Nrf2/NF-κB Signaling, and Emerging Therapeutic Applications
by Lidianys Maria Lewis-Luján, Annette Pulcherie Iloki-Lewis, Diego Emmanuel Guerrero-Magaña, Mikhail A. Osadchuk, Maxim V. Trushin, Juan Carlos Galvez-Ruiz, Judas Tadeo Vargas Durazo, Cinthia Jhovanna Perez-Martinez, Maria Guadalupe Burboa-Zazueta, Ana V. Torres-Figueroa, Sergio Trujillo Lopez and Simon Bernard Iloki-Assanga
Int. J. Mol. Sci. 2026, 27(10), 4634; https://doi.org/10.3390/ijms27104634 - 21 May 2026
Abstract
Plant-derived bioactive metabolites have emerged as promising modulators of oxidative stress and inflammation, two interconnected processes involved in the pathogenesis of numerous chronic diseases. Arid ecosystems, particularly the Sonoran Desert, constitute an underexplored source of structurally diverse phytochemicals with significant pharmacological potential. This [...] Read more.
Plant-derived bioactive metabolites have emerged as promising modulators of oxidative stress and inflammation, two interconnected processes involved in the pathogenesis of numerous chronic diseases. Arid ecosystems, particularly the Sonoran Desert, constitute an underexplored source of structurally diverse phytochemicals with significant pharmacological potential. This review provides a comprehensive overview of major classes of plant-derived bioactives, including polyphenols, flavonoids, terpenoids, and alkaloids, with emphasis on their molecular mechanisms of antioxidant and anti-inflammatory action. These compounds exert cytoprotective effects through direct reactive oxygen species (ROS) scavenging and indirect regulation of endogenous defense systems, primarily via activation of the Nrf2/Keap1 pathway and suppression of NF-κB signaling. Additional pathways, including MAPK, PI3K/Akt, AMPK, and mitochondrial regulatory networks, are discussed as critical mediators of redox balance and inflammatory control. Particular attention is given to Sonoran Desert plant species such as Bucida buceras, Phoradendron californicum, Larrea tridentata, Opuntia spp., and Agave deserti, all of which demonstrate promising biological activities associated with enhanced adaptation to environmental stress. Experimental approaches used to evaluate phytochemical bioactivity, including chemical assays, cellular models, omics technologies, and translational strategies, are also examined. Furthermore, this review discusses current limitations related to bioavailability, phytochemical variability, and clinical validation, highlighting emerging nanodelivery systems and precision medicine approaches as potential solutions. Collectively, the evidence supports the therapeutic relevance of Sonoran Desert plant bioactives as multi-target agents for modulating oxidative stress, inflammation, and chronic disease progression Full article
(This article belongs to the Special Issue Plant-Origin Bioactive Substances)
31 pages, 756 KB  
Tutorial
A Dual-Stage Ransomware Defense Framework Combining an Artificial Immune System and Honeyfile Traps
by Xiang Fang, Huseyn Huseynov and Tarek Saadawi
Electronics 2026, 15(10), 2223; https://doi.org/10.3390/electronics15102223 - 21 May 2026
Abstract
The escalating sophistication of ransomware requires defensive strategies that are both proactive against zero-day attacks and operationally efficient. Existing solutions often force a trade-off—sacrificing low false-positive rates for broad detection, or vice versa. This work introduces an integrated framework designed to transcend this [...] Read more.
The escalating sophistication of ransomware requires defensive strategies that are both proactive against zero-day attacks and operationally efficient. Existing solutions often force a trade-off—sacrificing low false-positive rates for broad detection, or vice versa. This work introduces an integrated framework designed to transcend this limitation. Our dual-stage approach synergizes pre-encryption behavioral analysis with definitive post-encryption confirmation. The first stage employs a specialized artificial immune system (AIS) that monitors a curated set of 47 features, including API-call n-grams and file entropy dynamics, to identify malicious activity before file encryption begins. This pre-emptive analysis is complemented by an enhanced, cross-platform R-Locker mechanism, which uses Windows named pipes and symbolic links to deploy honeyfiles that trap ransomware during I/O operations, providing a high-fidelity trigger for automated containment. We subjected this framework to a rigorous evaluation against 3500 real-world ransomware samples and 12,000 benign applications. The results demonstrate a 98.2% detection rate with a 0.8% false-positive rate, achieving a mean response time of 1.3 s. A key finding is the framework’s efficiency on both Windows and Linux (the only platforms tested), with the AIS and R-Locker modules consuming a combined 101 MB of memory. While the system excels in real-time detection, we note that its current memory forensics capability for key recovery is incompatible with certain ransomware families due to architectural obfuscations. Our findings suggest that the integrated approach performs well under laboratory conditions; further real-world validation is required to confirm robustness in diverse environments. Full article
(This article belongs to the Special Issue Cryptography and Computer Security, 2nd Edition)
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