The expression patterns and potential regulatory correlates of CLDN3 in cancers remain insufficiently characterised, necessitating further investigation. We employed R software alongside bioinformatics platforms to analyse the aberrant expression of CLDN3. Experiments in vitro, including proliferation, wound healing, cell cycle progression and apoptosis assays, were conducted to evaluate the role of CLDN3 in CRC. Co-immunoprecipitation (CO-IP) and immunofluorescence analyses were conducted to investigate the interaction between CLDN3 and TRIM28. Western blotting was employed to evaluate the effect of TRIM28 on CLDN3 SUMOylation and protein stability. CLDN3 was found to be overexpressed in several cancers. Genomic alterations and promoter hypomethylation were identified as key contributors to CLDN3 dysregulation. Bioinformatic analysis suggests that CLDN3 is associated with tumour progression and poor prognosis by influencing pathways, it also contributes to immune dysregulation and chemo-resistance mechanisms. Knockdown of CLDN3 in CRC cells decreased proliferation and migration. CLDN3 overexpression was shown to reduce the sensitivity to 5-FU in CRC cells. CO-IP and immunofluorescence confirmed a direct interaction between CLDN3 and TRIM28. Western blot analysis demonstrated that TRIM28 mediates CLDN3 SUMOylation and degradation. CLDN3 influences the growth and chemotherapy resistance of CRC cells, its interaction with TRIM28 makes the TRIM28/CLDN3 axis as a promising therapeutic target for CRC.

MT mitigates Cd toxicity by enhancing photosystem and antioxidant system activities, and related gene expression in GCC. NAC, HSF, and MYB-related families may play key roles in MT-induced Cd tolerance. Cadmium (Cd), a toxic heavy metal non-essential to plants, has detrimental impacts on both the environment and human health. Melatonin (MT) plays an important protective role in plants against stresses such as heavy metal toxicity. However, the detailed mechanism underlying MT alleviating Cd toxicity remains unclear in ground-cover chrysanthemum (Chrysanthemum morifolium Ramat., GCC). GCC seedlings were pre-treated with MT solution (150 μM) via foliar spraying and subsequently grown under Cd stress, after which the growth, physiological, and transcriptomic responses of the plant were investigated. The results demonstrated that MT pre-treatment inhibited the Cd-induced chlorophyll degradation in GCC seedlings, while it enhanced chlorophyll synthesis and related gene expression by promoting electron transfer efficiency and maintaining the integrity of the oxygen-evolving complex in photosynthesis. Furthermore, MT + Cd treatment upregulated 11 photosystem I (PSI), 13 PSII, eight light-harvesting complex I (LHCI), and 20 LHCII-related genes as compared with Cd treatment alone. MT also alleviated oxidative stress and boosted antioxidant capacity by conserving the activities and gene expression levels of superoxide dismutase, peroxidase, and key enzymes in the ascorbate-glutathione cycle and thioredoxin-peroxiredoxin pathway. In addition, MT reduced the generation rate of O2·- by 27.64%, malondialdehyde by 68.36%, and H2O2 by 44.97%, alleviating the Cd-induced damage. Weighted gene co-expression network analysis provided additional evidence that MT improved GCC tolerance to Cd by modulating the expression of transcription factors (e.g., NAC, HSF, and MYB-related families) related to abiotic stress.

Polyploid rice exhibits superior cadmium tolerance via enhanced antioxidant activity, reduced Cd accumulation, and transporter regulation, with zinc nanoparticles further mitigating toxicity and modulating stress-responsive genes. Cadmium (Cd) contamination poses a serious threat to rice production by impairing plant growth and yield. To investigate the mechanisms of Cd tolerance, we compared diploid rice (E22) and its polyploid counterpart (T42) under Cd stress (50 mg kg-1 soil) with or without zinc supplementation (25 mg kg-1 soil). Upon Cd exposure, E22 exhibited a 7.8% decline in plant weight and seed set, while T42 experienced only a 4.71% reduction in plant weight, demonstrating its enhanced tolerance to Cd toxicity. Consistently, Cd accumulation was markedly lower in T42 across multiple tissues. Under Cd stress, T42 maintained lower levels of H₂O₂ and malondialdehyde while exhibiting enhanced antioxidant activity, including elevated peroxidase, superoxide dismutase, catalase, and glutathione, compared to E22. The more complete organelles in T42 likely contributed to its improved Cd tolerance. Notably, supplementation with ZnO-NPs reduced Cd accumulation in both diploid and polyploid rice. Transcriptomic analysis revealed that starch metabolism-related genes (OsISA1 and OsISA2) were strongly expressed in T42, whereas tubulin genes (OsTB16 and OsTB50) were strongly expressed in T42 under Zn treatment. In contrast, photosynthesis-related genes show remarkable differential expressions between E22 and T42, suggesting different adaptive strategies in E22 and T44, as evidenced by impaired photosynthesis in E22 under stress. Overall, these findings demonstrate that polyploid rice possesses enhanced resilience to Cd stress through coordinated regulation of tubulin, metal transporters, and antioxidant systems, with ZnO-NPs further mitigating Cd toxicity.

Drug-induced liver injury (DILI) from acetaminophen (APAP) overdose involves ER stress, oxidative damage, apoptosis, and inflammation.

Aberrant DNA methylation patterns are increasingly recognized as contributors to a wide range of conditions, including metabolic, oncogenic, and neurodevelopmental disorders. Nutritional factors, such as choline, can shape methylation potential via methyl group donation. The purpose of this narrative review is to synthesize current evidence on the DNA methylation landscapes underlying health and disease paradigms, with a focus on the role of choline as a compelling target for modulating epigenetic states. A comprehensive literature review search was conducted in PubMed to identify relevant studies, with additional articles retrieved from review papers.

Lineage plasticity has emerged as an important mechanism of treatment resistance in prostate cancer, increasingly associated with loss of androgen receptor (AR) signaling, and in many cases induction of stemness phenotypes and neuroendocrine features. However, targeted therapies for this stage of the disease are currently lacking. In this study, we demonstrated the critical role of the epigenetic regulator UHRF1 in the enzalutamide resistance development of prostate cancer. We have shown that UHRF1 is highly expressed in enzalutamide-resistant prostate cancer cells and its expression correlates with the loss of AR-dependent glandular features. Knocking down UHRF1 led to increased AR expression and enhanced the activity of canonical AR signaling pathway in prostate cancer cells. The combination of UHRF1 knockdown with enzalutamide treatment demonstrated synergistic tumor inhibitory effects both in vitro and in vivo. Mechanistically, UHRF1 was found to bind to AR and promote its ubiquitination and degradation. Furthermore, inhibition of UHRF1 restored AR pathway activity and re-sensitized resistant prostate cancer cells to enzalutamide. Therefore, our findings elucidate an intracellular molecular mechanism that promotes prostate cancer lineage plasticity and suggest that UHRF1 may serve as a potential therapeutic target for overcoming resistance to AR-targeted therapies.

Endometrial cancer (EC) incidence is increasing globally, highlighting the need for novel therapies targeting molecular drivers of malignancy. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase implicated in tumor progression, is overexpressed in EC; however, its precise role and therapeutic potential remain unclear. In this study, we aimed to investigate EZH2 expression, its functional role, and the efficacy of EZH2 inhibitors in EC cell lines.

Glioblastoma constitutes a major subset of brain cancers and is characterized by a high recurrence rate and a low five-year survival rate. Ginsenoside compound K (GCK), a bioactive component derived from traditional Chinese medicine, exhibits anti-allergic, anti-aging, and notable anti-tumor properties. Although previous studies have shown that GCK can inhibit glioblastoma, its precise role and underlying mechanisms remain unclear. In this study, we demonstrated the effects of GCK on glioma initiation and progression, as well as its associated mechanisms. In vitro experiments revealed that GCK markedly inhibited the proliferation and migration of glioblastoma cells and significantly disrupted their cell cycle. In vivo, intragastric administration of GCK substantially reduced the growth rate of transplanted glioblastoma and prolonged the survival of nude mice. Furthermore, RNA sequencing and Western blot analyses showed that GCK suppresses glioblastoma progression by dephosphorylating p-ERK1/2 via upregulation of DUSP5 expression. These findings highlight the critical role of GCK in glioblastoma inhibition and suggest its potential as a promising therapeutic agent for clinical treatment, underscoring the value of traditional Chinese medicine in modern oncology.

Oxytocin, a neuropeptide predominantly produced in the hypothalamus, has garnered significant attention for its multifaceted roles extending beyond social bonding and reproduction to therapeutic applications in neurodegenerative and neuropsychiatric disorders. This review explores oxytocin's neuroprotective properties, including anti-inflammatory, antioxidant and anti-apoptotic effects, which counteract pathological mechanisms underlying diseases like Alzheimer's, Parkinson's and Epilepsy. Oxytocin's ability to modulate key neurotransmitter systems GABAergic, dopaminergic, and serotonergic pathways enhances synaptic plasticity, neurogenesis, and emotional regulation. These mechanisms have positioned oxytocin as a promising intervention for neuropsychiatric conditions such as autism, schizophrenia, depression, and anxiety. Preclinical and clinical studies have shown that intranasal administration of oxytocin improves social cognition, reduces symptom severity, and is well-tolerated, though challenges remain in standardizing dosages and measuring oxytocin levels due to individual variability. Emerging technologies, such as nanoparticle-based drug delivery systems, offer solutions to enhance oxytocin's bioavailability and brain penetration, making targeted, patient-specific therapies feasible. Epigenetic modifications of the oxytocin receptor gene including DNA methylation have been associated with variability in social and stress-related behaviors. While these findings offer insight into inter-individual differences, their application to precision medicine remains speculative and will require rigorous clinical validation. Combination therapies, integrating oxytocin with agents targeting neuroinflammation and synaptic plasticity, hold potential for synergistic effects. Despite methodological and translational challenges, oxytocin represents a transformative therapeutic agent with broad applications across neurological, psychiatric, and systemic disorders. Future research focusing on nanotechnology, epigenetics, and long-term clinical trials will be pivotal in realizing the full potential of oxytocin-based interventions for complex, multifactorial diseases.

Silicon dioxide nanoparticles (SiO2 NPs) have been shown to alleviate cadmium (Cd) toxicity in plants, but the mechanisms regarding SiO2 NPs-mediated Cd uptake and detoxification on hyperaccumulators are unknown. In this study, physiological and transcriptomic analyses were performed to investigate the impact of SiO2 NPs on the growth and Cd accumulation of the Cd-hyperaccumulator Sedum alfredii. The results showed that SiO2 NPs significantly increased root fresh weight (32.71% to 121.50%) and shoot fresh weight (22.72% to 86.36%). Simultaneously, SiO2 NPs enhanced the Cd uptake and accumulation by S. alfredii (with maximum increases of 232.14%). In the leaves, the Cd content in the phloem of the Si treatment group increased by 1.24 to 1.79-fold, indicating that SiO2 NPs enhanced the transport of Cd to the shoots. Furthermore, SiO2 NPs improved the photosynthetic parameters, with the net photosynthetic rate, transpiration rate and stomatal conductance increasing by 2.86-fold, 1.14-fold, and 1.84-fold of the control, respectively. Furthermore, SiO2 NPs significantly strengthened the antioxidative enzymes activities (SOD, CAT, POD). Transcriptomic analysis revealed that SiO2 NPs enhanced the Cd tolerance and accumulation capacity of S. alfredii by upregulating the expression of genes encoding photosynthesis-related functions (PSI, PSII), antioxidant enzymes, cell wall synthesis functions, heavy metal-responsive transcription factors (WRKY, NAC, bZIP, MYB), and Cd chelation and transport protein functions. Combining physiological and transcriptomic analyses, our findings provide the mechanisms of SiO2 NPs in promoting Cd accumulation and enhancing Cd tolerance in S. alfredii, highlighted the potential of SiO2 NPs to enhance phytoremediation efficiency.

Cytochrome P450s (CYPs) 2C subfamily (eg, 2C8, 2C9, and 2C19) and phase II enzymes such as uridine 5'-diphospho-glucuronosyltransferases (UGTs) are increasingly relevant in drug development and key targets for enzymatic induction. However, for these enzymes, weak induction signals in standard in vitro tools, such as sandwich-cultured human hepatocytes, challenge drug-drug interaction (DDI) risk assessment. This study evaluated an all-human hepatocyte coculture system (TruVivo) as a more sensitive model for CYP2Cs and UGT1A1 induction. After treatment of cells with rifampicin, carbamazepine, and phenytoin, we demonstrated robust mRNA and activity-fold-induction exceeding or meeting the 2-fold threshold in the coculture system, allowing for estimation of CYP2Cs and UGT1A1 induction parameters (IndC50, Indmax), unlike sandwich culture. Using TruVivo IndC50, Indmax of these precipitants in physiologically based pharmacokinetic (PBPK) modeling resulted in high predictive accuracy. In rifampicin studies, using TruVivo mRNA-derived data from the most sensitive donor 1 and average parameters across donors, was essential to properly predict in vivo DDI, particularly for object drugs mainly metabolized by CYP2Cs and UGT1A1, or with moderate to low CYP3A4 contribution (fm ≤ 0.5) in multipathway metabolism. For object drugs metabolized by CYP3A4 beyond 2Cs and UGTs, carbamazepine and phenytoin PBPK predictions highlighted the applicability of TruVivo uncalibrated CYP3A4 data for accurate assessment, whereas parameters calibrated against rifampicin showed a conservative trend in estimating DDI. Overall, the all-human coculture system, paired with PBPK, offers a breakthrough for CYP2Cs and UGT1A1 preclinical DDI induction risk assessment. SIGNIFICANCE STATEMENT: Cryopreserved human hepatocytes in sandwich culture show limited sensitivity toward cytochrome P450s 2C and uridine 5' -diphospho-glucuronosyltransferases induction, challenging in vitro-in vivo translation of the drug-drug interaction risk. This study confirms that TruVivo is a more sensitive in vitro model. By using physiologically based pharmacokinetic modeling, we investigated the impact of the measured induction parameters on predictive accuracy, showing TruVivo as a useful tool for cytochrome P450s 2C and uridine 5' -diphospho-glucuronosyltransferases risk assessment.

The purpose of this study was to investigate whether mitochondrial unfolded protein response (UPRmt) was induced in Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)-treated osteoblasts and to study the relationship among UPRmt, mitochondrial function and bone resorption in periodontitis.

Postoperative cognitive dysfunction is a type of cognitive impairment that occurs after surgery. Here, this experiment investigated the role of PLCG1 in sevoflurane-induced model and the molecular mechanisms underlying its regulation of ferroptosis. Single-cell RNA sequencing data and bioinformatic analyses were performed using GEO datasets (GSE196239). Mice were exposed to 2.3% sevoflurane for 2 h daily for 3 consecutive days. PLCG1 expression was up-regulation in patients exposed to sevoflurane. Specifically, blood samples from these patients exhibited elevated levels of PLCG1 mRNA. Consistently, in a mouse model of sevoflurane exposure, both mRNA and protein levels of PLCG1 were significantlyincreased in brain tissue. Single-cell RNA sequencing analysis revealed that PLCG1 was predominantly expressed in astrocytes (marked by AQP4, GFAP, LUZP2, and SLC25A28) and neurons (marked by B3GAT2, ENO2, GNG2, and SLC1A1) in sevoflurane-exposed patients. In contrast, PLCG1 expression was undetectable in B cells (CD74, CD79B, CD80, CD86), T cells (CD4, CD8B, CD69, CD247), or macrophages (CD36, CD68, CD83, CD163). In conclusion, PLCG1 drives neuronal ferroptosis in the context of sevoflurane exposure by enhancing mitochondrial oxidative stress and facilitating LAMP2A ubiquitination, thereby impairing the LAMP2A/HSPA8 pathway. These findings position PLCG1 as a promising biomarker and potential therapeutic target for monitoring and mitigating sevoflurane-induced neurotoxicity. In conclusion, PLCG1 drives neuronal in the context of sevoflurane exposure by enhancing mitochondrial oxidative stress and facilitating LAMP2A Ubiquitination, thereby impairing the LAMP2A/HSPA8 pathway. These findings position PLCG1 as a promising biomarker and potential therapeutic target for monitoring and mitigating sevoflurane-induced neurotoxicity.

Graphene oxide (GO), a two-dimensional nanomaterial, has shown potential for improving plant stress tolerance. However, its involvement in, and mechanism of, regulating the drought stress response in apple plants remains unclear. In this study, we investigated the effects of GO on drought tolerance of M9-T337 plants under both short-term and long-term drought conditions. Results revealed that under short-term drought conditions, 0.1 and 1 mg L-1 GO significantly alleviated drought-induced damage by reducing electrolytic leakage and MDA contents, while enhancing antioxidant enzyme activities and ROS scavenging. Under long-term drought conditions, 0.1 and 1 mg L-1 GO improved photosynthetic rate and promoted root system development, thereby enhancing plant drought tolerance. Additionally, in M9-T337 plants, GO elevated the levels of γ-aminobutyric acid, proline, phenylalanine, arginine, and histidine, and upregulated the expression of MdCAT2, MdPOD2, MdDREB2A, MdERF1, and MdABI1. Taken together, this study connects GO with drought tolerance in apple plants, providing evidence that GO effectively enhances the drought tolerance of M9-T337 plants. These findings offer a promising strategy for the sustainable cultivation of apple in water-scarce regions through the application of nanomaterials.

A number of published studies suggest that HIV infection accelerates epigenetic ageing. The main aim of this study was to ascertain if HIV infection is an independent factor leading to DNA hypomethylation and accelerating epigenetic ageing in men successfully treated with integrase inhibitor (INSTI)-based combined antiretroviral therapy (cART). Forty-eight (48) men living with HIV receiving INSTI-based cART and fifty (50) uninfected men in the control group were included. All participants filled out a questionnaire probing into lifestyle factors. Global and site-specific DNA methylation and expression of methyltransferase genes were examined in all participants. As well, all patients underwent basic laboratory blood tests. The results were analysed using statistical and machine learning methods. We found a strong association between HIV infection and global DNA hypomethylation as well as significant association with higher expression of the methyltransferase gene DNMT1. However, there was no association with DNA methylation levels of CNOT2, DPP6, FOXG1 and NPTX2 genes or expression levels of DNMT3a and DNMT3b. The results confirm that in men successfully treated with INSTI-based cART, HIV infection is an independent factor causing global DNA hypomethylation and increased DNMT1 expression and thus accelerating epigenetic ageing.

TP53 is a tumor-suppressor gene involved in regulating apoptosis, DNA repair, and genomic stability. Mutations in TP53 are implicated in approximately half of all detected cancers, including breast, lung, colorectal, and ovarian cancers, making it a significant target for therapeutic interventions. Many pharmaceutical drugs aim to restore TP53 function, and there is a need for predictive tools to assess how compounds may affect TP53 expression. In this study, we propose a new ensemble machine-learning model to predict the direction of TP53 relative gene expression in response to pharmaceutical compounds. Our model utilizes molecular fingerprints, descriptors, and scaffold-based features extracted from SMILES representations of compounds concatenated into a single feature vector. Trained using our newly generated benchmark dataset based on the Connectivity Map (CMap) database and addressing class imbalance with the Synthetic Minority Over-sampling Technique (SMOTE), our model achieves 62.9%, 93.9%, 40.3%, and 0.39 in terms of accuracy, sensitivity, specificity, and Matthews Correlation Coefficient (MCC), respectively. As the first-of-its-kind TP53 gene regulation prediction, our study serves as a convincing proof-of-concept that paves the way for future investigation. GenReP as a stand-alone predictor, its source code, and our newly generated benchmark dataset are publicly available.

Adult glioblastoma multiforme (GBM) is the most common primary malignant brain tumour caused by multiple molecular factors. N6-methyl-adenosine (m6A) is an abundant RNA modification that governs cellular RNA metabolism. We hypothesise that changes in m6A-modified RNA and regulatory machinery such as the writer proteins, Methyltransferase 3 (METTL3) and WT1-associating protein (WTAP), the demethyltransferase protein, and Alpha-ketoglutarate dependent dioxygenase (FTO), are driving factors of GBM development and treatment resistance. Here, we investigated m6A-RNA spatial and quantitative abundance and expression of m6A effector proteins directly in GBM tissue and patient-derived low-passage primary adult GBM and low-grade glioma (LGG) cells, and explored the consequences of m6A-RNA disruption on GBM invasive capabilities, self-renewal and responsiveness to temozolomide (TMZ). We observed that METTL3, WTAP and FTO transcript and protein expression were significantly increased in cells derived from invasive regions of GBM tumours, and elevated WTAP and FTO expression significantly correlated with poor GBM patient survival. We further found that the abundance of m6A-modified RNA in GBM tumours was significant higher in rim and invasive tissue, as well as significantly higher in patient-derived cells from GBM tumour invasive regions. Functional depletion of these effector proteins significantly altered m6A levels on and the expression of the pluripotency stem cell marker SOX2 while also impairing self-renewal and cell invasion behaviour and increasing sensitivity to TMZ. The targeting of RNA modification regulatory mechanisms reveals novel therapeutic strategies aimed at improving clinical outcomes for GBM patients.

Because prostate cancer proliferates in an androgen-dependent manner, various inhibitors of androgen production and antagonists of the androgen receptor (AR) are used as therapeutic agents. However, the emergence of castration-resistant prostate cancer has prompted the development of additional treatment strategies. In this study, we focused on the antiprostate cancer effects of vitamin D3 and examined novel antiproliferative effects through the crosstalk with androgen signaling. In human prostate cancer LNCaP cells, homeobox C9 (HOXC9) was identified as a common regulated target gene by dihydroxytestosterone and 1α,25-dihydroxyvitamin D3, but in opposite directions. Ligand-stimulated AR and vitamin D receptor competitively shared binding sites in the HOXC9 regulatory region, but dihydroxytestosterone stimulation preferentially suppressed HOXC9 expression due to the stronger binding properties of AR and the induction of DNA methylation. Forced expression of HOXC9 inhibited androgen signaling to eliminate the androgen-dependent proliferation by associating with the AR transcription complex, in part due to interference with AR binding to some of its targets in LNCaP cells. In summary, this study provides evidence for the involvement of HOXC9 in antiproliferative effects through a regulatory mechanism mediated by a crosstalk between vitamin D receptor and AR.

Lavender essential oil (LEO) is commonly used in aromatherapy for stress reduction, relaxation and recovery from (muscle) fatigue. However, molecular mechanisms underlying its potential physiological effects on the skeletal muscle remain unclear. This study investigates whether LEO affects the intracellular signaling pathways in skeletal muscle cells that respond to physical activity. Prior to the experiment, GC-MS analysis confirmed linalyl acetate and linalool as the main components of LEO used in this study. Transdermal permeability was assessed using a reconstructed human epidermis model, which showed that linalool permeated the epidermal layer, while linalyl acetate showed minimal permeation. Following this confirmation, the differentiated C2C12 myotubes were treated with LEO in an in vitro muscle contraction model using electrical pulse stimulation (EPS). LEO significantly increased Interleukin 6 (IL-6) mRNA expression under EPS, and DNA whole-genome microarray analysis showed that LEO induced different gene expression profiles depending on the contraction state of the muscle cells. These results provide the first molecular evidence that LEO modulates skeletal muscle gene networks in a stimulation-dependent manner and may indicate its potential use as an aid to recovery (from fatigue) after exercise. Notably, the skin permeation of LEO components showed a saturation trend at concentrations above 5%, suggesting the presence of an optimal concentration range for topical application in sports aromatherapy.

DNA methylation is a conserved regulatory mechanism of gene expression, genome stability, and development, and is highly associated with the effective induction of defense responses for plant priming. In the Green Deal era, the use of plant defense inducers (PDIs), compounds that activate defense and prime plants against imminent pathogen attacks, is a safe and environmentally sustainable approach to support plants against pathogens. Though efforts have succeeded at deciphering part of the mode of action of PDIs, more information is needed to understand the underlying pathways of their effectiveness. Here, salicylic acid (SA), loaded in chitosan nanoparticles, increased hypomethylation by more than 25% for 56 genomic regions that corresponded to defense-related genes, such as pectin lyases, defensins and leucine-rich repeat transmembrane protein kinases against the biotrophic fungal pathogen Podosphaera xanthii. A genomic region of the promoter of SKP1A, which is a core member of the SCF E3 ubiquitin ligase complex, was found to be a differentially methylated region (DMR), with 60% hypomethylation, both after PDI application and pathogen inoculation, possibly indicating a similar activation mechanism. Examination of this DMR revealed the presence of SA-, auxin-, and defense-related cis-elements. Investigation of the proteins associated with the above cis-elements showed significant upregulation in expression after PDI. Moreover, association of the identified DMR with transcriptomics showed enrichment of the SA pathway. Overall, these findings shed light on the epigenetic mechanisms that underlie SA-related defense priming in plants.