Search Results (234)

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial–mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma. Full article

While pipecolic acid (Pip) mediates morpho-physiological and molecular responses during biotic stress, its roles under drought remain an inexpressible mystery. The investigation aimed to elucidate the roles of a 30μM Pip pretreatment in alleviating drought injury on barley (Hordeum vulgare L. cv, Bülbül89) seedlings. Pip pretreatment under normal or drought conditions lowered the osmotic potential (Ψs) and water saturation deficit (WSD), while optimizing the relative water content (RWC), triggered osmotically energetic molecules (OEM) and salicylic acid (SA) accumulation, improving osmotic adjustment (OA), and boosting water retention and uptake capacity (WTC, and WUC), alongwith a considerable improvement in seedling growth over non-treated plants under such conditions. Additionally, Pip pretreatment improved chlorophyll (Chl), the chlorophyll stability index (CSI), pheophytin_a, chlorophyllide_a (chlide_a), chlorophyllide_b (chlide_b), chl_a/chlide_a, chl_b/chlide_b, protoporphyrin, Mg-protoporphyrin, protochlorophyllide, and photosynthetic performance over non-treated plants under such conditions. Pip pretreatment preserves redox homeostasis in drought-stressed plants by accumulating antioxidant solutes alongside the activation of superoxide dismutase and glutathione reductase over non-treated plants. Drought distinctly reduced Ψs (more negative), RWC, photosynthetic pigment, CSI, chlorophyll assimilation intermediate, and photosynthetic performance, with an increment in chlorophyll degradation intermediate and nonenzymatic antioxidant solutes. Drought maintains OA capacity via a hyper-accumulation of OEM and SA, which results in higher WSD, WTC, and WUC. Drought triggered an oxidative burst, which was associated with a decline in the membrane stability index. These findings highlight Pip’s capability for lessening drought stress-induced restriction in barley seedlings via bolstering oxidative homeostasis, OA capacity, and stabilizing chlorophyll biosynthesis. Future research must elucidate the precise molecular mechanisms underlying Pip’s action in alleviating drought injury. Full article

Small molecule inhibitors that target the E3 ligase activity of MDM2-MDM4 have been explored to inhibit the oncogenic activity of MDM2-MDM4 complex. MMRi62 is a small molecule that was identified using an MDM2-MDM4 E3 ligase-based high throughput screen and a cell-death-based secondary screen. Our previous studies showed that MMRi62 promotes MDM4 degradation in cells and induces p53-independent apoptosis in cancer cells. However, MMRi62 activity in solid tumor cells such as melanoma cells, especially in BRAF inhibitor resistant melanoma cells, have not been explored. Although its promotion of MDM4 degradation is clear, the direct MMRi62 targets in cells are unknown. In this report, we show that MMRi62 is a much more potent p53-independent apoptosis inducer than conventional MDM2 inhibitors in melanoma cells. A brief structure-activity study led to development of SC-62-1 with improved activity. SC-62-1 potently inhibits and eliminates clonogenic growth of melanoma cells that acquired resistance to BRAF inhibitors. We developed a pair of active and inactive SC-62-1 probes and profiled the cellular targets of SC-62-1 using a chemical biology approach coupled with IonStar/nano-LC/MS analysis. We found that SC-62-1 covalently binds to more than 15 hundred proteins in cells. Pathways analysis showed that SC-62-1 significantly altered several pathways including carbon metabolism, RNA metabolism, amino acid metabolism, translation and cellular response to stress. This study provides mechanistic insights into the mechanisms of action for MMRi62-like quinolinols. This study also suggests multi-targeting compounds like SC-62-1 might be useful for overcoming resistance to BRAF inhibitors for improved melanoma treatment. Full article

Foxtail millet (Setaria italica L.), a representative C4 species, is recognized for its efficient nutrient utilization and robust abiotic stress responses. However, the molecular mechanisms mediating its tolerance to biotic stresses are poorly understood. In this study, we investigated the root transcriptomic response of foxtail millet to the damage-associated molecular pattern (DAMP), the plant elicitor peptide 1 (Pep1). Transcriptome analysis of Pep1-treated roots identified 401 differentially expressed genes (DEGs), comprising 144 up-regulated and 257 down-regulated genes. Gene Ontology (GO) enrichment analysis revealed a significant enrichment of ‘peroxidase activity’. This finding was corroborated by DAB staining, which confirmed H₂O₂ accumulation, along with elevated malondialdehyde (MDA) levels, collectively indicating oxidative stress. Notably, Pep1 treatment also resulted in a marked up-regulation of the pathogenesis-related protein 1 (PR1) gene in leaves, suggesting the activation of systemic acquired resistance. Together, these results demonstrate that Pep1 triggers substantial transcriptional reprogramming in roots, induces oxidative stress, and activates systemic defense signaling in foxtail millet. Full article

Cancer cell spheroids autonomously form in the ascites fluid and are considered a conduit for epithelial ovarian cancer metastasis within the peritoneal cavity. Spheroids are homotypic, avascular 3D structures that acquire resistance to anoikis to remain viable after cellular detachment. We used in vitro spheroid model systems to interrogate pathways critical for spheroid cell proliferation, distinct from those driving monolayer cancer cell proliferation. Using the 105C and KOC-7c human ovarian clear cell carcinoma (OCCC) cell lines, which have distinct proliferative phenotypes as spheroids but the same prototypical OCCC gene mutation profile of constitutively activated AKT signaling with the loss of ARID1A, we revealed therapeutic targets that efficiently kill cells in spheroids. RNA-seq analyses compared the transcriptome of 3-day monolayer and spheroid cells from these lines and identified the characteristics of dormant spheroid cell survival, which included the G2/M checkpoint, autophagy, and other stress pathways induced in 105C spheroids, in sharp contrast to the proliferating spheroid cells of the KOC-7c cell line. Next, we assessed levels of various G2/M checkpoint regulators and found a consistent reduction in steady-state levels of checkpoint regulators in dormant spheroid cells, but not proliferative spheroids. Our studies showed that proliferative spheroid cells were sensitive to Wee1 inhibition by AZD1775, but the dormant spheroid cells showed a degree of resistance to AZD1775, both in terms of EC50 values and spheroid reattachment abilities. Thus, we identified biomarkers of dormant spheroids, including the G2/M checkpoint regulators Wee1, Cdc25c, and PLK1, and showed that, when compared to proliferating spheroid cells, the transcriptome of dormant OCCC spheroids is a source of therapeutic targets. Full article

Reactive oxygen species (ROS) are toxic by-products of aerobic cellular metabolism. However, ROS conduct multiple functions, and specific ROS sources can have beneficial or detrimental effects on plant health. This review explores the complex dynamics of ROS in plant defense mechanisms, focusing on their involvement in basal resistance, hypersensitive response (HR), and systemic acquired resistance (SAR). ROS, including superoxide anion (O²⁻), singlet oxygen (¹O₂), hydroxyl radicals (OH), and hydrogen peroxide (H₂O₂), are generated through various enzymatic pathways. They may serve to inhibit pathogen growth while also activating defense-related gene expression as signaling molecules. Oxidative damage in cells is mainly attributed to excess ROS production. ROS produce metabolic intermediates that are involved in various signaling pathways. The oxidative burst triggered by pathogen recognition initiates hyper-resistance (HR), a localized programmed cell death restricting pathogen spread. Additionally, ROS facilitate the establishment of SAR by inducing systemic signaling networks that enhance resistance across the plant. The interplay between ROS and phytohormones such as jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) further complicates this regulatory framework, underscoring the importance of ROS in orchestrating both local and systemic defense responses. Grasping these mechanisms is essential for creating strategies that enhance plant resilience to biotic stresses. Full article

The control of bacterial plant diseases is very challenging and often relies on the application of copper compounds, although the frequent emergence and spread of resistant bacterial strains compromise their efficacy. Additionally, copper-based compounds raise environmental and human health concerns, leading to their inclusion in the European Commission’s list of candidates for substitution. As a promising and sustainable alternative, we investigated the efficacy of biogenic zinc oxide nanoparticles (ZnO-NPs) in protecting tomato plants against Pseudomonas syringae pv. tomato (Pst), the causal agent of bacterial speck disease. ZnO-NPs exhibited significant in vitro antibacterial activity (EC₉₅ = 17.0 ± 1.1 ppm) against the pathogen. Furthermore, when applied to the foliage of tomato plants at 100 ppm before or following Pst inoculation, they induced significant reductions in symptom severity and bacterial growth in planta, which were comparable to those shown by plants treated with acibenzolar-S-methyl, a plant defense inducer. Gene expression assessed by qPCR revealed the involvement of the systemic acquired resistance (SAR) pathway in tomato plants treated with ZnO-NPs before inoculation, suggesting that the observed protection could be due to a priming effect. Finally, infected plants showed oxidative stress, with higher H₂O₂ and malondialdehyde (MDA) contents. ZnO-NPs reverted this effect, containing the content of the above molecules, and stimulated the production of metabolites involved in dealing with oxidative perturbations (carotenoids and phenols), while unaffecting flavonoids and anthocyanins. Full article

The approval of immunotherapy has revolutionized the management of hepatocellular carcinoma (HCC) patients. However, sorafenib remains a first-line therapeutic option for advanced patients and, in particular, for patients not eligible for immune checkpoint inhibitors, but its efficacy is limited by the onset of acquired resistance, highlighting the urgent need for predictive biomarkers. This study investigates the role of miR-22 in metabolic reprogramming and its potential as a biomarker in HCC. The analysis of miR-22 expression was performed in HCC patients and preclinical models by qPCR. Functional analyses in HCC cells evaluated GLUT1 as a direct miR-22 target. Cellular and metabolic assays evaluated the miR-22/GLUT1 axis’s role in metabolic changes, tumor aggressiveness, and sorafenib response. Circulating miR-22 was analyzed in sorafenib-treated HCC patients and rats. MiR-22 was downregulated in HCCs and associated with aggressive tumor features. Functionally, miR-22 modulated the HIF1A pathway, enhanced survival in stressful conditions, promoted a glycolytic shift, and enhanced cancer cell plasticity and sorafenib resistance via GLUT1 targeting. In addition, high serum miR-22 levels were associated with sorafenib resistance in HCC patients and rats. GLUT1 inhibition sensitized low miR-22-expressing HCC cells to sorafenib in preclinical models. These findings suggest that circulating miR-22 deserves attention as a predictive biomarker of sorafenib response. GLUT1 inhibition may represent a therapeutic strategy to combine with sorafenib, particularly in patients exhibiting high circulating miR-22 levels. Full article

Cassava mosaic disease (CMD) is caused by viruses such as Sri Lankan cassava mosaic virus (SLCMV). It poses a significant threat to the cassava (Manihot esculenta) yield in Southeast Asia. Here, we investigated the expression of WRKY transcription factors (TFs) in SLCMV-infected cassava cultivars KU 50 (tolerant) and R 11 (susceptible) at 21, 32, and 67 days post-inoculation (dpi), representing the early, middle/recovery, and late infection stages, respectively. The 34 identified WRKYs were classified into the following six groups based on the functions of their homologs in the model plant Arabidopsis thaliana (AtWRKYs): plant defense; plant development; hormone signaling (abscisic, salicylic, and jasmonic acid); reactive oxygen species production; basal immune mechanisms; and other related hormones, metabolites, and abiotic stress responses. Regarding the protein interactions of the identified WRKYs, based on the interactions of their homologs (AtWRKYs), WRKYs increased reactive oxygen species production, leading to salicylic acid accumulation and systemic acquired resistance (SAR) against SLCMV. Additionally, some WRKYs were involved in defense-related mitogen-activated protein kinase signaling and abiotic stress responses. Furthermore, crosstalk among WRKYs reflected the robustly restricted viral multiplication in the tolerant cultivar, contributing to CMD recovery. This study highlights the crucial roles of WRKYs in transcriptional reprogramming, innate immunity, and responses to geminivirus infections in cassava, providing valuable insights to enhance disease resistance in cassava and, potentially, other crops. Full article

Exogenous abscisic acid (ABA) and brassinosteroid (BR) play important roles in alleviating cold stress in maize. In this study, two maize inbred lines with differing cold tolerance were treated with exogenous ABA, BR, and their combined solution under cold stress conditions at 10 °C to investigate the effects of these treatments on the physiological characteristics of maize seedlings. The results indicated that cold stress significantly inhibited the growth of maize seedlings. Exogenous hormone treatments enhanced antioxidant enzyme activities and promoted the synthesis of osmolytes, thereby alleviating cold stress; however, the combined treatment (AR) did not significantly improve maize cold tolerance. Transcriptomic analysis revealed that pathways including plant hormone signal transduction, fatty acid elongation, and phenylpropanoid biosynthesis were involved in the interaction between ABA and BR. Weighted gene co-expression network analysis (WGCNA) identified four key candidate genes responsive to exogenous ABA and BR under cold stress, namely Zm00001eb343270, Zm00001eb401890, Zm00001eb206790, and Zm00001eb199820. Based on the gene annotation results, we speculate that ubiquitin-conjugating enzyme E2 O, tubulin–tyrosine ligase-like protein 12, the negative regulator of systemic acquired resistance SNI1, and mRNA stability regulators in response to DNA damage may be involved in regulating maize cold tolerance. These findings provide further evidence for the regulatory mechanisms by which exogenous ABA and BR affect maize cold tolerance and elucidate their interaction under cold stress. Full article

Plants adapt to biotic and abiotic stresses through physiological, morphological, and genetic changes. In recent years, the fundamental roles of epigenetic mechanisms as regulators of various immune–biological processes in nematode–plant interactions have been increasingly recognized. Epigenetic control mechanisms include non-coding RNAs (ncRNAs), DNA methylation, and histone modifications. Gene expression and gene silencing play crucial roles in activated induced resistance during pathogen attacks. DNA methylation and histone modifications are linked to defense priming or immune memory, such as systemic acquired resistance (SAR). In addition, epigenetic processes play important roles in long-term defense priming, contributing to the development of immunological memory under future stress conditions. Therefore, advances in understanding epigenetic mechanisms hold considerable potential for future research on plant–nematode interactions. However, further development in the basic understanding of interactions among various stresses, the expansion of markers for epigenetic changes, and the permanence of priming are necessary to optimize its utilization in crop protection programs. In this paper, we focus on the function of epigenetic mechanisms in plant defense responses to nematode infection, specifically root-knot nematodes (RKNs). Understanding the adaptive ability of RKNs is important for developing suitable control methods. Additionally, we explore the role of epigenetic mechanisms in plant interactions with biological control agents. Full article

Biosensors are innovative and cost-effective analytical devices that integrate biological recognition elements (bioreceptors) with transducers to detect specific substances (biomolecules), providing a high sensitivity and specificity for the rapid and accurate point-of-care (POC) quantitative detection of selected biomolecules. In the meat production chain, their application has gained attention due to the increasing demand for enhanced food safety, quality assurance, food fraud detection, and regulatory compliance. Biosensors can detect foodborne pathogens (Salmonella, Campylobacter, Shiga-toxin-producing E. coli/STEC, L. monocytogenes, etc.), spoilage bacteria and indicators, contaminants (pesticides, dioxins, and mycotoxins), antibiotics, antimicrobial resistance genes, hormones (growth promoters and stress hormones), and metabolites (acute-phase proteins as inflammation markers) at different modules along the meat chain, from livestock farming to packaging in the farm-to-fork (F2F) continuum. By providing real-time data from the meat chain, biosensors enable early interventions, reducing the health risks (foodborne outbreaks) associated with contaminated meat/meat products or sub-standard meat products. Recent advancements in micro- and nanotechnology, microfluidics, and wireless communication have further enhanced the sensitivity, specificity, portability, and automation of biosensors, making them suitable for on-site field applications. The integration of biosensors with blockchain and Internet of Things (IoT) systems allows for acquired data integration and management, while their integration with artificial intelligence (AI) and machine learning (ML) enables rapid data processing, analytics, and input for risk assessment by competent authorities. This promotes transparency and traceability within the meat chain, fostering consumer trust and industry accountability. Despite biosensors’ promising potential, challenges such as scalability, reliability associated with the complexity of meat matrices, and regulatory approval are still the main challenges. This review provides a broad overview of the most relevant aspects of current state-of-the-art biosensors’ development, challenges, and opportunities for prospective applications and their regular use in meat safety and quality monitoring, clarifying further perspectives. Full article

In the natural environment, plants are simultaneously exposed to multivariable abiotic and biotic stresses. Typical abiotic stresses are changes in temperature, light intensity and quality, water stress (drought, flood), microelements availability, salinity, air pollutants, and others. Biotic stresses are caused by other organisms, such as pathogenic bacteria and viruses or parasites. This review presents the current state-of-the-art knowledge on programmed cell death in the cross-tolerance phenomena and its conditional molecular and physiological regulators, which simultaneously regulate plant acclimation, defense, and developmental responses. It highlights the role of the absorbed energy in excess and its dissipation as heat in the induction of the chloroplast retrograde phytohormonal, electrical, and reactive oxygen species signaling. It also discusses how systemic- and network-acquired acclimation and acquired systemic resistance are mutually regulated and demonstrates the role of non-photochemical quenching and the dissipation of absorbed energy in excess as heat in the cross-tolerance phenomenon. Finally, new evidence that plants evolved one molecular system to regulate cell death, acclimation, and cross-tolerance are presented and discussed. Full article

Optical microscope (OM), energy dispersive spectrometer (EDS), electron backscatter diffractometer (EBSD), electrochemical test, and transmission electron microscope (TEM) were employed to conduct interface microstructure observation and cladding corrosion resistance analysis on 304 SS/CS clad plates that have four different reduction ratios. The increase in rolling reduction ratio leads to larger grain size, gradually refined microstructure, and a decreased thickness of the interfacial martensite area. As the concentration disparity of the C element between carbon steel (CS) and 304 stainless steel (SS) is small, no evident carburization layer or decarburization layer can be detected. The ferrite microstructure on the CS side has greater stress distribution and greater local orientation deviation, and deformed grains are dominant. Austenite undergoes strain-induced martensitic transformation with the transformation mechanism of γ→twinning→a’-martensite. The martensite microstructure within the interface region grows in the direction of the interior of austenite grains. The reduction ratio increases sharply, leading to an increase in dislocation density, which promotes the nucleation, growth, and precipitation of carbides and seriously reduces the corrosion resistance of the cladding. Subsequently, the reduction ratio keeps on increasing. However, the degree of change in the reduction ratio diminishes. High temperature promotes the dissolution of carbides and improves the corrosion resistance. From this, it can be understood that by applying the process conditions of raising the reduction ratio and keeping a high temperature at the carbide dissolution temperature, a clad plate that has excellent interface bonding and remarkable corrosion resistance can be acquired. Full article