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20 pages, 4064 KB  
Article
Elevational Metabolic Reprogramming Optimizes Flavonoid Accumulation and Antioxidant Capacity in Chimonobambusa utilis Leaves
by Jingkai Wu, Yingying Dai, Boqian Qin, Songming Li, Jianjun Zhang, Fanfan He, Guohua Liu and Changlai Liu
Plants 2026, 15(9), 1290; https://doi.org/10.3390/plants15091290 (registering DOI) - 22 Apr 2026
Abstract
Chimonobambusa utilis is a dominant bamboo species in China, yet its leaves remain an underutilized resource despite their significant bioactive potential. To elucidate the metabolic reprogramming of Ch. utilis leaves across an elevational gradient and its link to antioxidant phenotypes, we integrated widely [...] Read more.
Chimonobambusa utilis is a dominant bamboo species in China, yet its leaves remain an underutilized resource despite their significant bioactive potential. To elucidate the metabolic reprogramming of Ch. utilis leaves across an elevational gradient and its link to antioxidant phenotypes, we integrated widely targeted metabolomics with redox profiling of leaves collected from 1150, 1600, and 2000 m in the Qingba Mountains. The mid-elevation (1600 m) group exhibited the most robust antioxidant capacity and the highest total flavonoid content. Metabolomic analysis identified 3113 metabolites across 13 classes, with flavonoids (604 compounds, 22.7% of total abundance) emerging as the predominant secondary metabolites. Pairwise comparisons revealed 1716 differentially accumulated metabolites (DAMs). KEGG enrichment indicated that while the low-elevation (1150 m) group prioritized primary metabolism and upstream phenylpropanoid branches, the high-elevation (2000 m) group was associated with photoprotection and defense responses. In contrast, the mid-elevation environment optimized the flux toward flavonoid biosynthesis while maintaining steady metabolic supply. HPLC quantification further confirmed that key markers—vitexin, hyperoside, orientin, and luteoloside—peaked at 1600 m. Correlation analysis between 423 differential flavonoids and antioxidant indices demonstrated that distinct radical-scavenging activities are driven by specific flavonoid structural motifs. Overall, altitude-driven metabolic remodeling, characterized by a mid-elevation advantage for flavonoid accumulation, dictates the antioxidant plasticity of Ch. utilis leaves. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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15 pages, 712 KB  
Review
Intersecting Roles of Estrogens and Neutrophils in Modulating Innate Immunity in Cancer
by Mary Wines-Samuelson, Thomas R. Henson, Raegan J. Myers and Stephen R. Hammes
Biomolecules 2026, 16(5), 617; https://doi.org/10.3390/biom16050617 - 22 Apr 2026
Abstract
Steroid-sensitive cancers (e.g., breast, ovarian, uterine, and prostate cancers) are difficult to control and frequently metastasize to lymph nodes, bone, or lung. Although endocrine research has greatly advanced our identification of the direct roles of steroid sex hormones such as androgens and estrogens [...] Read more.
Steroid-sensitive cancers (e.g., breast, ovarian, uterine, and prostate cancers) are difficult to control and frequently metastasize to lymph nodes, bone, or lung. Although endocrine research has greatly advanced our identification of the direct roles of steroid sex hormones such as androgens and estrogens on tumor cells in promoting metastasis or recurrence (e.g., treatment with gonadotropin releasing hormone agonists/antagonists, aromatase inhibitors, and estrogen and androgen receptor antagonists), mechanistic insight regarding indirect effects of steroid hormones, including how the innate immune system responds to cancer and is influenced by steroid hormones, is lacking. Despite technological advances in engineering more robust adaptive immunity to combat tumor growth (e.g., CART or checkpoint inhibitors), there remains a relative lack of investigation into the role of innate immunity as a key defense system. Here we discuss recent studies that highlight the significance of neutrophils and their response to tumorigenic conditions with or without steroid hormones in animal models of cancer. We will describe relationships between steroid hormones and neutrophils, with a specific focus on neutrophil extracellular traps (NETs), and how these interactions modulate tumor growth and invasion. Together, these data indicate that combinatorial regulation of both innate and adaptive immunity in the context of tumorigenesis may improve outcomes in cancer therapies. Full article
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19 pages, 1675 KB  
Article
The Effect of Gold Nanoparticles in Sodium Alginate on the Biochemical Characteristics of Garden Cress
by Miłosz Rutkowski, Damian Duda, Ewa Godos, Wojciech Makowski, Emilia Bernaś, Karen Khachatryan, Andrzej Kalisz, Agnieszka Sękara and Gohar Khachatryan
Molecules 2026, 31(8), 1373; https://doi.org/10.3390/molecules31081373 - 21 Apr 2026
Abstract
Gold nanoparticles (AuNPs) have numerous applications in science and industry. Therefore, their potential phytotoxicity should be investigated. Garden cress (Lepidium sativum L.) is a useful model plant for assessing the effects of chemicals released into the environment. The aim of this study [...] Read more.
Gold nanoparticles (AuNPs) have numerous applications in science and industry. Therefore, their potential phytotoxicity should be investigated. Garden cress (Lepidium sativum L.) is a useful model plant for assessing the effects of chemicals released into the environment. The aim of this study was to prepare alginate gels containing AuNPs for plant exposure experiments, evaluate their physicochemical properties, and determine their effects on selected biochemical parameters of garden cress seedlings. Gold nanoparticles were synthesized in sodium alginate at an initial concentration of 50 mg/L, using xylose and maltose as reducing agents. The gels were diluted with distilled water to obtain AuNP concentrations of 5 and 25 mg/L. Garden cress seeds were placed on filter paper soaked with the tested formulations, while distilled water and sodium alginate solutions without AuNPs served as controls. After 5 days of incubation at 20 °C under light conditions, the plant material was collected and selected bioactive compounds were determined. AuNP-containing gels significantly affected the biochemical status of the seedlings. In particular, AuNPs synthesized with xylose at 25 mg/L significantly increased the contents of photosynthetic pigments and total polyphenolic compounds. All tested AuNP formulations increased the antioxidant activity of seedlings, suggesting the activation of abiotic stress-related defense responses, however, direct markers of oxidative damage were not assessed in the present study. Overall, the results indicate that alginate-based AuNPs can modify selected biochemical parameters in garden cress seedlings, and these effects depend on nanoparticle concentration and reducing sugar used during synthesis, which may be relevant for the future development of plant-targeted nanomaterials for agricultural applications. Full article
(This article belongs to the Special Issue Bioactive Compounds in Plants: Extraction and Application)
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17 pages, 8622 KB  
Article
Biochemical Signatures Linked to Rice Blast Severity Under Acibenzolar-S-Methyl, Jasmonic Acid and Combined Treatments in Upland Rice
by Eugenio Miranda Sperandio, Helson Mario Martins do Vale, Marcio Vinícius de Carvalho Barros Cortes and Marta Cristina Corsi de Filippi
Agronomy 2026, 16(8), 839; https://doi.org/10.3390/agronomy16080839 (registering DOI) - 21 Apr 2026
Abstract
Acibenzolar-S-methyl (ASM), a salicylic acid (SA) analog, and jasmonic acid (JA) are chemical inducers of plant defenses, yet crosstalk between SA- and JA-associated pathways may result in antagonistic outcomes. Here, we assessed how ASM and JA, applied alone or in combination, are associated [...] Read more.
Acibenzolar-S-methyl (ASM), a salicylic acid (SA) analog, and jasmonic acid (JA) are chemical inducers of plant defenses, yet crosstalk between SA- and JA-associated pathways may result in antagonistic outcomes. Here, we assessed how ASM and JA, applied alone or in combination, are associated with rice blast severity and defense-related responses in an upland rice cultivar. Plants of rice (Oryza sativa L., cv. Primavera) were treated with JA, ASM or JA + ASM and subsequently challenged with Magnaporthe oryzae. ASM treatment was associated with reduced leaf blast severity (LBS), whereas JA treatment was associated with increased LBS. Antagonistic outcomes were observed in the combined treatment: LBS in JA + ASM plants was higher than in ASM-treated plants but lower than in JA-treated plants. Lipoxygenase (LOX) activity was induced by JA and positively correlated with LBS, indicating that higher LOX activity aligned with greater susceptibility under the tested conditions. In contrast, ASM-treated plants showed higher peroxidase (POX) activity, which was associated with lower LBS. Disease outcomes were also linked to secondary defense metabolism and phenylpropanoid-related components, including phenylalanine ammonia-lyase (PAL), salicylic acid (SA) and phenolic compounds (PC). Overall, these results provide an integrated biochemical profile of how ASM, JA and their combination are associated with contrasting blast outcomes in upland rice, consistent with antagonistic interactions between JA- and SA-associated defense responses. These findings may inform the use of defense inducers and the interpretation of defense markers in upland rice systems where blast management is a major constraint. Full article
(This article belongs to the Section Agricultural Biosystem and Biological Engineering)
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21 pages, 442 KB  
Review
Role of Donor Unrestricted T Cells (DURTs) in TB Host Defense: Implications for Novel TB Vaccine Development
by Dylan Kain, David Michael Lewinsohn and Deborah Anne Lewinsohn
Vaccines 2026, 14(4), 365; https://doi.org/10.3390/vaccines14040365 - 21 Apr 2026
Abstract
Tuberculosis (TB) is the leading cause of infectious disease-related death globally. Most TB vaccine strategies have focused on conventional CD4 T cell responses, but to date, these have failed to deliver durable sterilizing protection. Donor unrestricted T cells (DURTs), including CD1-restricted T cells, [...] Read more.
Tuberculosis (TB) is the leading cause of infectious disease-related death globally. Most TB vaccine strategies have focused on conventional CD4 T cell responses, but to date, these have failed to deliver durable sterilizing protection. Donor unrestricted T cells (DURTs), including CD1-restricted T cells, HLA-E-restricted T cells, MR1-restricted T cells and γδ T cells represent an attractive complementary target for future TB vaccine development. They recognize antigens through conserved, non-polymorphic restricting elements and are therefore broadly targetable across genetically diverse populations. They are also enriched at mucosal sites, have rapid effector and cytotoxic capacities and recognize conserved mycobacterial ligands. Emerging human and animal data support their participation in antimycobacterial immunity and suggest they can be shaped by BCG vaccination and other immunization strategies. Here, we review the evidence for DURT involvement in TB host defense, assess their strengths and current limitations as vaccine targets, and discuss how DURT-directed approaches may help to enable faster, broader, and more durable protection against Mycobacterium tuberculosis. Full article
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27 pages, 1216 KB  
Systematic Review
Antifungal Efficacy of Essential Oils and Nanoformulations Against Fusarium Wilt of Tomato: Systematic Review (2000–2025)
by Salam Y. Abuzaitoun, Mazen N. Salman, Yamen Y. Hamdan, Rana M. Jamous and Mohammed S. Ali-Shtayeh
Plants 2026, 15(8), 1268; https://doi.org/10.3390/plants15081268 - 21 Apr 2026
Abstract
Fusarium oxysporum f. sp. lycopersici (FOL) is one of the most destructive soil-borne pathogens affecting tomato production worldwide, causing substantial yield losses and persisting in soil for extended periods. The increasing regulatory restrictions on chemical fungicides and the emergence of resistant pathogen strains [...] Read more.
Fusarium oxysporum f. sp. lycopersici (FOL) is one of the most destructive soil-borne pathogens affecting tomato production worldwide, causing substantial yield losses and persisting in soil for extended periods. The increasing regulatory restrictions on chemical fungicides and the emergence of resistant pathogen strains have intensified the search for sustainable and environmentally friendly alternatives. This systematic review synthesizes studies published between 2000 and 2025 that evaluated the antifungal efficacy of essential oils (EOs), their bioactive constituents, and EO-based nanoformulations against FOL in tomato. A total of 40 studies were included, following the PRISMA 2020 guidelines, encompassing in vitro, greenhouse, and limited field evaluations. Many EOs rich in phenolic compounds and oxygenated monoterpenes, such as thymol, carvacrol, eugenol, citral, and menthol, consistently inhibited FOL growth and spore germination, with reported mycelial growth inhibition ranging from 60 to 100% and minimum inhibitory concentrations (MICs) between 0.05 and 1.5 µL ml−1. However, the use of EOs is often limited because they evaporate quickly, do not mix well with water, can harm plants, and do not persist under field conditions. Nano-delivery systems, including nanoemulsions, polymeric nanoparticles, chitosan-based carriers, and lipid-based nanostructures, have been shown to enhance the stability, bioavailability, and antifungal efficacy of EOs. This has led to improved disease management and reduced pesticide application rates. In addition, several EO-based treatments have been reported to activate plant defense responses, including the induction of defense-related genes, antioxidant enzymes, and epigenetic modifications. Overall, EO-based nanoformulations show promise as next-generation biopesticides for the sustainable management of tomato Fusarium wilt. Nevertheless, large-scale field validation, standardized formulation protocols, and regulatory assessments are required before these technologies can be widely implemented in agriculture. Full article
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24 pages, 3486 KB  
Article
Mining and Analysis of Salt Tolerance Genes in Maize at the Seedling Stage
by Zhenping Ren, Zelong Zhuang, Jianwen Bian, Wanling Ta, Xiaojia Hao, Lei Zhang and Yunling Peng
Curr. Issues Mol. Biol. 2026, 48(4), 423; https://doi.org/10.3390/cimb48040423 - 20 Apr 2026
Abstract
Salt stress represents a significant abiotic stress factor that adversely affects plant growth and development. It directly inhibits both vegetative and reproductive growth, resulting in substantial reductions in crop yield and quality. Consequently, the identification of salt tolerance genes and the elucidation of [...] Read more.
Salt stress represents a significant abiotic stress factor that adversely affects plant growth and development. It directly inhibits both vegetative and reproductive growth, resulting in substantial reductions in crop yield and quality. Consequently, the identification of salt tolerance genes and the elucidation of their underlying molecular mechanisms are crucial for improving crop salt tolerance and ensuring agricultural productivity. To investigate the molecular basis underlying differential salt tolerance between Zheng58 and PH4CV, we employed pooled sequencing (BSA-seq) using extreme phenotypic individuals from their F2 population and conducted a comparative transcriptome analysis at the seedling stage of the two genotypes. Phenotypic, physiological, biochemical, and ion content analyses revealed that Zheng58 exhibited significantly superior performance compared to PH4CV under salt stress conditions. BSA-seq analysis identified six genomic regions associated with salt tolerance, encompassing a total of 391 genes. Functional annotation enabled the screening of 151 candidate genes potentially involved in salt stress responses. Transcriptome profiling indicated that differentially expressed genes were significantly enriched in biological processes, particularly plant hormone signal transduction and MAPK signaling pathways. Integrating BSA-seq and transcriptome data, key candidate gene ZmACC2 (Zm00001eb419400) was identified as potentially involved in the regulation of salt tolerance in maize. This gene may modulate Na+/K+/Ca2+ homeostasis and reactive oxygen species metabolism through defense responses mediated by ethylene (ETH) and hydrogen peroxide, as well as through ion homeostasis regulatory pathways. This study provides valuable candidate genes and a theoretical foundation for further dissection of the molecular mechanisms governing salt tolerance in maize. Full article
(This article belongs to the Special Issue Plant Hormones, Development, and Stress Tolerance)
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25 pages, 6172 KB  
Article
Transcriptional and Alternative Splicing Regulation of Autophagy and Vesicle Transport Pathways in Large Yellow Croaker Cells During Megalocytivirus Infection
by Zaiyu Zheng, Hongshu Chi, Xiaodong Liu, Xiuxia Chen, Ying Pan and Hui Gong
Animals 2026, 16(8), 1259; https://doi.org/10.3390/ani16081259 - 20 Apr 2026
Abstract
Infection of the large yellow croaker (Larimichthys crocea) embryo cell line YCE1 with megalocytivirus strain FD201807 leads to accumulation of capsid-deficient viral intermediates within intracellular vesicles at 48 h post-infection (a phenotype associated with non-lytic egress), which coincides with the initial [...] Read more.
Infection of the large yellow croaker (Larimichthys crocea) embryo cell line YCE1 with megalocytivirus strain FD201807 leads to accumulation of capsid-deficient viral intermediates within intracellular vesicles at 48 h post-infection (a phenotype associated with non-lytic egress), which coincides with the initial peak of viral genomic copies. To characterize the host molecular response during this critical stage, we performed time-course RNA sequencing at 24, 48, 96, and 144 hpi. Integrated analysis identified 6661 differentially expressed genes (DEGs) and 1138 differential alternative splicing (DAS) events affecting 892 genes, with DAS event abundance peaking at 48 h. DAS genes in autophagy and Golgi vesicle transport pathways, both integral to animal innate immunity, were significantly enriched exclusively at this timepoint, featuring novel mutually exclusive exon (MXE) isoforms in gopc (Golgi-associated PDZ and coiled-coil motif containing) and rint1 (RAD50 interactor 1). Weighted gene co-expression network analysis (WGCNA) of DEGs identified mapk9 (mitogen-activated protein kinase 9) and map1lc3a (microtubule-associated protein 1 light chain 3 alpha) as hub genes within modules enriched for autophagy-related functions. Separate co-expression analysis of DAS genes revealed rnf5, rimoc1, and golga4 as hub genes, with gopc exhibiting only a single linkage to rnf5. These findings implied concurrent transcriptional and virus-induced host splicing regulation of vesicle-associated innate defense pathways and suggest that splicing-derived features may serve as potential candidates for diagnostics or prevention against megalocytivirus disease in L. crocea. Full article
(This article belongs to the Special Issue Innate Host Defence Mechanisms of Aquatic Animals)
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17 pages, 14561 KB  
Article
The bZIP Transcription Factor LkbZIP4 Enhances Drought Tolerance in Hybrid Larch (Larix kaempferi × L. gmelinii)
by Chan Zhang, Xuhui Wang, Yang Xu, Runze Liu, Lijing Yu, Ming Wei and Chenghao Li
Forests 2026, 17(4), 507; https://doi.org/10.3390/f17040507 - 19 Apr 2026
Viewed by 149
Abstract
Drought stress critically impacts plant growth and productivity. The bZIP transcription factor family is crucial for abiotic stress responses, yet its role in larch drought tolerance remains unclear. This study identified 19 bZIP genes in Larix kaempferi (Lamb.) Carr. and characterized LkbZIP4. [...] Read more.
Drought stress critically impacts plant growth and productivity. The bZIP transcription factor family is crucial for abiotic stress responses, yet its role in larch drought tolerance remains unclear. This study identified 19 bZIP genes in Larix kaempferi (Lamb.) Carr. and characterized LkbZIP4. Bioinformatics analysis classified it into the A subgroup. Subcellular localization and yeast two-hybrid assays confirmed that it is a nucleus-localized transactivator. Expression pattern analysis revealed that LkbZIP4 was highly specifically expressed in roots and was significantly induced by drought stress. A series of transgenic overexpression lines was successfully established through Agrobacterium tumefaciens-mediated method, using embryogenic callus of hybrid larch (L. kaempferi × L. gmelinii). Under 7% PEG-induced drought stress, LkbZIP4-overexpressing transgenic calli displayed enhanced drought tolerance relative to wild-type. This was evidenced by better growth, higher biomass, and reduced membrane damage, indicated by lower malondialdehyde content and relative electrolyte leakage. Meanwhile, these transgenic calli accumulated higher levels of osmoregulatory substances, including proline and soluble sugars, along with enhanced activities of antioxidant enzymes including superoxide dismutase and peroxidase. Our results indicate that LkbZIP4 functions to promote drought tolerance in larch, likely through the enhancement of osmotic adjustment and oxidative defense mechanisms. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Responses in Trees Species—2nd Edition)
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27 pages, 3695 KB  
Review
Plant Immunometabolism: Metabolic Reprogramming Linking Developmental Signaling and Defense Metabolites
by Wajid Zaman, Asma Ayaz and Adnan Amin
Int. J. Mol. Sci. 2026, 27(8), 3635; https://doi.org/10.3390/ijms27083635 - 19 Apr 2026
Viewed by 238
Abstract
Plant metabolism is essential for coordinating growth, development, and defense under changing environmental conditions. Plants continuously adjust their metabolic pathways to balance resource allocation between growth and immune responses. Under stress, metabolic reprogramming redirects energy and resources toward the production of defense compounds [...] Read more.
Plant metabolism is essential for coordinating growth, development, and defense under changing environmental conditions. Plants continuously adjust their metabolic pathways to balance resource allocation between growth and immune responses. Under stress, metabolic reprogramming redirects energy and resources toward the production of defense compounds and activation of immune signaling pathways. These changes involve complex interactions among primary metabolism, specialised metabolites, and regulatory networks, including calcium signaling, reactive oxygen species, and phytohormones. Advances in metabolomics and multi-omics technologies have improved understanding of the metabolic control of plant immunity; however, knowledge remains fragmented, and an integrated framework linking metabolism, development, and defense is still emerging. This review examines plant immunometabolism by highlighting the dynamic relationships between metabolic networks and immune functions during development and stress. It discusses pathways that influence growth, stress-induced metabolic shifts linked to defense, and how signaling interacts with metabolism. Progress in metabolomics, transcriptomics, proteomics, and computational modeling that supports systems-level analysis of plant metabolism is also summarized. In addition, potential applications in agriculture and biotechnology, including metabolic engineering, genome editing, and metabolomics-based breeding, are considered in relation to crop resilience. By integrating metabolism, signaling, and systems biology, this review provides a broad perspective on how metabolic reprogramming shapes the growth–defense trade-off in plants and outlines future directions for developing climate-resilient crops. Full article
(This article belongs to the Collection Advances in Molecular Plant Sciences)
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32 pages, 1928 KB  
Article
Physiological and Proteomic Analysis of Sorghum Bicolor Seedling Leaves Reveals Molecular Responses to PEG-Induced Drought Stress
by Hongbing Li, Qilong Han, Zhao Yang, Meijing Cheng, Qingbo Ke, Sang-Soo Kwak, Xiping Deng and Suiqi Zhang
Plants 2026, 15(8), 1255; https://doi.org/10.3390/plants15081255 - 18 Apr 2026
Viewed by 248
Abstract
Drought stress significantly constrains crop productivity and yield stability. Sorghum (Sorghum bicolor L. Moench), a C4 cereal widely cultivated in arid and semi-arid regions, exhibits high water-use efficiency and remarkable drought tolerance. Understanding both the impacts of drought and the plant’s response [...] Read more.
Drought stress significantly constrains crop productivity and yield stability. Sorghum (Sorghum bicolor L. Moench), a C4 cereal widely cultivated in arid and semi-arid regions, exhibits high water-use efficiency and remarkable drought tolerance. Understanding both the impacts of drought and the plant’s response mechanisms is essential for enhancing drought resilience in this crop. In this study, physiological changes and differential protein accumulation were analyzed in leaves of the sorghum inbred line BT × 623 under 10% PEG-6000-induced drought stress. The physiological adaptation to drought was characterized by improved water retention and mitigation of oxidative damage through the synergistic action of antioxidant enzymes. Using two-dimensional electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometry, 43 protein spots were successfully identified, corresponding to 38 unique proteins differentially expressed under osmotic stress. These proteins function in diverse biological processes, including protein synthesis, processing, and degradation; photosynthesis; carbohydrate and energy metabolism; transcriptional regulation; stress and defense; lipid and membrane metabolism; and amino acid metabolism. Proteomic profiling revealed that the coordinated modulation of multiple functional groups, such as those involved in photosynthesis, energy metabolism, transcriptional adjustment, ROS scavenging, and protein turnover, underpins sorghum’s osmotic stress adaptation. These findings provide key insights into the drought resistance mechanisms of sorghum at both physiological and proteomic levels. Full article
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19 pages, 8753 KB  
Article
Interferon-β Modulates Early Viral Replication Kinetics and Innate Responses to Non-Fatal Alphavirus Encephalomyelitis
by Benjamin H. Nguyen, Elise Stanley, Victoria K. Baxter and Diane E. Griffin
Pathogens 2026, 15(4), 441; https://doi.org/10.3390/pathogens15040441 - 18 Apr 2026
Viewed by 200
Abstract
Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and [...] Read more.
Alphaviruses are mosquito-borne viruses that can infect the central nervous system (CNS) and cause encephalomyelitis, which is a rare but dangerous complication from infection. In mice, this can be studied in a model of infection with Sindbis virus (SINV), which infects neurons and causes neurological disease. Due to the non-renewable nature of neurons, the immune response in the CNS is specialized to prevent neuronal damage or death, even if they are infected. Therefore, insights into the nuances of antiviral immunity in the CNS provide a better understanding of disease pathogenesis and mechanisms of recovery. Type I interferons (IFNs) are critically important for survival; they are an innate antiviral defense mechanism that consists mainly of IFNα and IFNβ. Although both use the same receptor, type-specific differences between IFNα and IFNβ have been described in other contexts. To this end, Ifnb−/− mice were used to elucidate the role of IFNβ in recovery from alphavirus encephalomyelitis. IFNβ-deficient mice have intact IFNα expression and downstream signaling, but symptomatic disease occurs earlier and is more severe. This is accompanied by increased virus replication in the early stages of infection. Microgliosis is reduced in Ifnb−/− mice compared to wildtype, but inflammatory cytokine/chemokine levels are higher and associated with alterations in monocyte and NK cell recruitment into the CNS. Ifnb−/− mice have no deficiencies in the expression of factors known to be required for viral clearance. Therefore, IFNβ modulates the early stages of the immune response and facilitates restriction of virus replication, contributing to delayed disease onset. Full article
(This article belongs to the Special Issue Arboviruses Infections and Pathogenesis)
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18 pages, 5215 KB  
Article
Histone Demethylase JMJD2D Suppresses Influenza A Virus Infection by Promoting RIG-I Expression
by Xiaochun Xia, Jiadi Liang, Hanshi Guo, Fudong Zhang, Junjie Zhang, Chundong Yu, Pingli Mo and Yilin Hong
Biomolecules 2026, 16(4), 604; https://doi.org/10.3390/biom16040604 - 18 Apr 2026
Viewed by 165
Abstract
The efficacy of the host antiviral response against Influenza A virus (IAV), a leading cause of global pandemics, hinges upon the rapid recognition of the pathogen and the prompt activation of immune mechanisms. Nevertheless, the epigenetic landscape that orchestrates this antiviral response remains [...] Read more.
The efficacy of the host antiviral response against Influenza A virus (IAV), a leading cause of global pandemics, hinges upon the rapid recognition of the pathogen and the prompt activation of immune mechanisms. Nevertheless, the epigenetic landscape that orchestrates this antiviral response remains largely elusive. Here, we identify histone demethylase JMJD2D as a critical regulator in defense against IAV infection. A significant upregulation of JMJD2D expression was observed clinically in response to IAV infection, indicating that JMJD2D may play a role in regulating IAV infection. Indeed, JMJD2D-deficient mice exhibit increased susceptibility to IAV, characterized by elevated viral loads, severe lung tissue damage, and reduced survival rates, suggesting that JMJD2D plays an essential role in defense against IAV infection. Consistently, knockdown or pharmacological inhibition of JMJD2D in lung cells suppressed IAV replication and the IAV-triggered innate immune response. Mechanistically, JMJD2D suppressed IAV infection by removing H3K9me3 at the promoter region of retinoic acid inducible gene-I (RIG-I) and cooperating with NF-κB to enhance the expression of RIG-I, a critical sensor for IAV RNA. This study identifies JMJD2D as an epigenetic rheostat that governs RIG-I-mediated antiviral signaling, highlighting its potential as a therapeutic target for mitigating severe IAV infection. Full article
(This article belongs to the Section Cellular Biochemistry)
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22 pages, 6017 KB  
Article
RdDM-Dependent Epigenetic Regulation Coordinates Systemic Immunity and Compatibility with Trichoderma atroviride in Arabidopsis thaliana
by Maria Montserrat Rosendo-Vargas, Valeria Ávila-Castillo, Kumari Rashmi and Sergio Casas-Flores
Microorganisms 2026, 14(4), 914; https://doi.org/10.3390/microorganisms14040914 - 18 Apr 2026
Viewed by 164
Abstract
Epigenetic regulation plays a central role in modulating plant immune responses and interactions with beneficial microbes. In this study, we investigated the contribution of RNA-directed DNA methylation (RdDM) components—DCL3; AGO9; DCL1; and the de novo DNA methyltransferases CMT3, DRM1, and DRM2—to the interaction [...] Read more.
Epigenetic regulation plays a central role in modulating plant immune responses and interactions with beneficial microbes. In this study, we investigated the contribution of RNA-directed DNA methylation (RdDM) components—DCL3; AGO9; DCL1; and the de novo DNA methyltransferases CMT3, DRM1, and DRM2—to the interaction between Arabidopsis thaliana, Trichoderma atroviride, and foliar pathogens. We show that DCL3 and AGO9 differentially regulate basal and inducible immunity, negatively affecting resistance to the necrotrophic fungus Botrytis cinerea, while promoting defense against the hemibiotrophic bacterium Pseudomonas syringae pv. tomato DC3000. Transcriptional analyses revealed that RdDM components modulate the balance between jasmonic acid/ethylene (JA/ET) and salicylic acid (SA) signaling pathways, influencing the amplitude and coordination of defense responses. In addition, DCL3 and DCL1 appear to be required for the full expression of T. atroviride-mediated systemic resistance, whereas AGO9 and DNA methyltransferases contribute to efficient root colonization. Notably, mutants in these pathways displayed enhanced basal resistance but impaired responsiveness to beneficial microbial signals, revealing a trade-off between constitutive defense activation and inducible systemic protection. Consistent with this, alterations in RdDM components were also associated with changes in plant growth dynamics under specific conditions, supporting a role for epigenetic regulation in coordinating growth–defense trade-offs. Together, our findings support a model in which epigenetic regulation controls defense responsiveness, enabling plants to balance immune activation, growth and compatibility toward beneficial microbes. Full article
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23 pages, 825 KB  
Review
From Chronic Inflammation to Cancer: The Role of Trained Immunity in IBD-Associated Colorectal Carcinogenesis
by Ferenc Sipos and Györgyi Műzes
Med. Sci. 2026, 14(2), 202; https://doi.org/10.3390/medsci14020202 - 17 Apr 2026
Viewed by 108
Abstract
Trained immunity is a concept that is currently in development and refers to the long-term functional reprogramming of innate immune cells in response to microbial or inflammatory stimuli. This process serves a dual purpose in the gastrointestinal tract, contributing to chronic inflammatory conditions [...] Read more.
Trained immunity is a concept that is currently in development and refers to the long-term functional reprogramming of innate immune cells in response to microbial or inflammatory stimuli. This process serves a dual purpose in the gastrointestinal tract, contributing to chronic inflammatory conditions like inflammatory bowel disease and maintaining host defense. The production of pro-inflammatory mediators is augmented by epigenetic and metabolic changes that are induced by the persistent activation of innate immune cells, which is triggered by microbial components and damage-associated signals. Although this increased responsiveness may initially be protective, sustained activation leads to tissue damage, epithelial barrier dysfunction, and chronic inflammation. These mechanisms are significant contributors to colorectal carcinogenesis, particularly in colitis-associated cancer. Through the activation of oncogenic signaling pathways, the establishment of a pro-tumorigenic microenvironment, and an increase in oxidative stress, trained immunity also influences tumor development. Additionally, the systemic reprogramming of hematopoietic progenitor cells has the potential to exacerbate inflammation and facilitate the progression of tumors. The identification of epigenetic and metabolic biomarkers associated with trained immunity can lead to novel diagnostic opportunities. Targeting metabolic and epigenetic pathways, as well as regulating the intestinal microbiota, is a promising therapeutic approach that could enhance the effectiveness of treatments for colorectal cancer while minimizing adverse effects on the immune system. Nevertheless, it is necessary to maintain a delicate equilibrium to suppress pathological inflammation without compromising protective immune responses. In general, trained immunity may represent a potentially relevant mechanistic link between chronic inflammation and colorectal cancer; however, its role remains context-dependent and not yet fully defined. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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