Search Results (2,645)

Insufficient vascularization remains a major limitation in tissue engineering, restricting the survival and maturation of larger bioengineered constructs. While candidate hydrogels are commonly characterized with regard to physicochemical properties, gelation behavior, mechanical performance, and cytocompatibility, simple functional assays that assess their capacity to support vascular sprouting are less frequently integrated into early-stage biomaterial evaluation. Here, we investigated the established ex vivo aortic ring assay (ARA) as an exploratory functional approach for the initial comparison of selected hydrogel formulations. Murine aortic rings were embedded in collagen I (Col I), alginate (Alg), or gelatin methacryloyl (GelMA) and cultured under control conditions or with vascular endothelial growth factor A (VEGF-A) stimulation. These hydrogels were intentionally selected as a proof-of-concept panel of representative, non-equivalent material classes with distinct expected cell-interactive properties. After five days, Col I supported robust capillary-like outgrowth that was further enhanced by VEGF-A, whereas the tested GelMA formulation supported only limited cellular migration and the tested unmodified Alg formulation showed no detectable sprouting under the conditions examined. Cluster of differentiation 31 (CD31) immunostaining supported the presence of an endothelial component within the Col I-supported sprouting structures. These findings demonstrate that the ARA can detect pronounced formulation-dependent differences among the specific hydrogels tested using straightforward morphological and immunostaining readouts. Within the scope of the formulations tested, these findings support the ARA as a complementary functional readout alongside conventional biomaterial characterization before more complex tissue engineering or biofabrication studies are performed. Full article

Cryopreserved mesenchymal stem cells (MSCs) are widely used as off-the-shelf therapeutics. However, conventional manufacturing workflows typically include a post-thaw 2D monolayer recovery step before 3D spheroid formation. This study evaluated whether immediate spheroid formation following thawing (Direct-3D) could replace the conventional 2D-to-3D workflow while maintaining or improving chondrogenic potential. Using passage 5 Wharton’s jelly MSCs (WJ-MSCs), spheroid morphology, early chondrogenic priming, differentiation, and extracellular matrix (ECM) formation were systematically compared between the two strategies. The Direct-3D group exhibited faster and more uniform spheroid compaction and significantly increased SOX9 expression as early as 3 h, indicating enhanced early priming. This response was accompanied by higher COL2A1 expression and an increased COL2A1/COL1A1 ratio during early differentiation while maintaining minimal collagen type X expression. These findings demonstrate that the post-thaw monolayer recovery step is not essential for producing high-quality chondrogenic spheroids from WJ-MSCs. By simplifying the manufacturing workflow while preserving—and potentially enhancing—early chondrogenic performance, the Direct-3D strategy represents a practical and scalable approach for WJ-MSC-based cartilage tissue engineering and cell therapy. Full article

Macroscopic and microscopic aggregation patterns of reconstituted poly-L-lactic acid (PLLA) products may vary with product formulation, diluent, preparation protocol, and time. This descriptive in vitro pilot study compared two commercial formulations, StiCol Volume (150 mg PLLA reconstituted to 9 mL) and StiCol Soft (50 mg PLLA reconstituted to 6 mL), under 11 diluent conditions and 2 composite preparation protocols: roller mixing for 30 min and manual shaking for 3 min followed by 3 h of hydration. One preparation was evaluated for each formulation–diluent–protocol combination. Gross appearance was documented immediately and at 15, 30, 45, and 60 min and 24 h; microscopy was performed at ×40 and ×100 from 15 min onward. Two evaluators applied an ordinal visual aggregation scale, and the findings were analyzed descriptively. In the observed preparations, the StiCol Soft formulation generally showed lower aggregation grades than StiCol Volume; however, the products differed in nominal PLLA concentration, particle size, and excipient composition, so this pattern cannot be attributed to concentration alone. SWFI-based conditions tended to show fewer microscopic clusters than NSS-based conditions. The roller/30 min protocol also tended to show lower grades than the manual/3 h protocol, although mixing mode and hydration duration were inseparable. Macroscopic upper-layer accumulation was interpreted as vertical phase separation with creaming/flotation-like behavior rather than sedimentation. These exploratory findings generate hypotheses for replicated studies incorporating standardized sampling, redispersibility, particle size, rheological, and injectability testing; they do not establish an administration window or improved clinical safety. Full article

Skin is a highly specialized barrier organ, which serves essential barrier, immune, and sensory functions and exhibits conserved structure. In addition, each species exhibits a unique skin transcriptional profile for adapting distinct environmental conditions and physiological demands. However, these transcriptional profiles across mammals remain incompletely understood. In this study, we integrated 61 publicly available skin RNA-seq datasets from eight mammalian species: human (Homo sapiens), macaque (Macaca fascicularis), mouse (Mus musculus), sheep (Ovis aries), goat (Capra hircus), donkey (Equus asinus), rabbit (Oryctolagus cuniculus), and pig (Sus scrofa). We identified a large number (2286 to 4588) of differentially expressed genes (DEGs) based on 10,504 one-to-one orthologous genes in all pairwise species comparisons. A total of 44 conserved genes were identified by integrating tissue specificity, expression variability, and mean expression level, which were enriched in epidermal development, keratinocyte differentiation, and desmosome organization. We also identified species-specific genes and transcription factors, such as STMN1 (donkey), COL1A1 (goat), and ACTN2 (mouse), which are associated with the cell cycle, extracellular matrix, and muscle contraction pathways, respectively. WGCNA further revealed goat-associated module 2 (M2) enriched in the negative regulation of angiogenesis. Collectively, this study provides a comprehensive cross-species transcriptional profile resource for mammalian skin, providing a valuable resource for understanding the regulatory plasticity underlying skin evolution across mammals. Full article

Carbapenem-resistant Enterobacterales (CRE) are a major public health concern, yet genomic data from Bulgaria remain limited. We investigated the genomic epidemiology and genomic characteristics of clinically significant CRE recovered at University Hospital “Lozenetz”, Sofia, between 2022 and 2025. Antimicrobial susceptibility testing, phenotypic carbapenemase characterization, and PCR were combined with whole-genome sequencing of 23 purposively selected isolates chosen to capture temporal, species, carbapenemase, specimen, ward, and resistance-phenotype diversity. The proportion of CRE among all Enterobacterales remained broadly stable over the study period, and Klebsiella pneumoniae was the predominant species throughout. NDM-type carbapenemases were the most frequent overall, although VIM-, KPC-, and OXA-48-like enzymes were also detected. Among the sequenced isolates K. pneumoniae ST6260 (n = 16) was predominant. The remaining isolates included single K. pneumoniae isolates belonging to ST11, ST101, and ST258; two Enterobacter hormaechei ST114; one Proteus mirabilis ST93; and one Providencia stuartii ST46. All ST6260 isolates carried chromosomal blaNDM-5 within a conserved multidrug-resistance module with variable downstream regions, whereas blaOXA-232 was situated on a small ColKP3 plasmid within a defined subcluster. Overall, the data indicate that ST6260 is an emerging hospital-associated multidrug-resistant lineage. Full article

Introduction. Statins’ established cardiovascular benefits are often undermined by hepatic adverse effects in obese diabetic patients with suspected non-alcoholic fatty liver disease. We evaluated whether cannabis plant treatment is a safe and effective alternative to atorvastatin in a metabolically challenged rodent model. Methods. Fourteen obese and diabetic Wistar rats received either atorvastatin for 30 days or cannabis plant extract for 30 days. Main outcome: lipid profile; secondary outcomes: renal function, glycemia and endothelial health assessed through atherogenic indices. Safety was assessed using plasma liver enzyme concentrations. Results. Baseline biochemical profiles were similar between groups. Atorvastatin increased HDL-Col more than cannabis plant (MD: 44.3; IQR [33, 57.5] mg/dL, Hedges’ g 2.713 vs. MD: 14.3; IQR [14, 17] mg/dL, Hedges’ g 5.049), and cannabis plant did not change LDL-Col. Atherogenic index of plasma and Castelli Risk Index 1 improved with both interventions, more so with atorvastatin. Liver enzymes increased with atorvastatin (ALAT, MD: 15.9; IQR [12.5, 19.5] U/L; ASAT, MD: 33; IQR [26.5, 38] U/L) but remained virtually unchanged with cannabis. Serum creatinine increased with cannabis plant, with moderate effect size (Hedges’ g 0.798), but negligibly with statins (Hedges’ g 0.122). Conclusions. Cannabis plant extract modestly improved the lipid profile and atherogenic indices, with differences often not exceeding the change in control groups. Despite apparent liver safety, the undesired renal and neurological consequences limit applicability in humans. Further studies should prioritize addiction development and renal function. Full article

Background: Renal cell carcinomas (RCCs) represent neoplasms with variable biological behaviour, some of which remain difficult to classify within the current diagnostic framework. Clear cell papillary renal cell tumor (CCPRCT) is now recognised as an indolent entity, whereas RCC with fibromyomatous stroma (RCCFMS) remains a provisional subtype with partially overlapping morphological features. Methods: We analysed a multifocal RCC with clear cell morphology and prominent fibromyomatous stroma via whole-genome and RNA sequencing. The obtained molecular profile was compared with The Cancer Genome Atlas (TCGA) pan-cancer dataset, which includes 885 RCC cases, and histological re-evaluation of 10 identified similar cases was performed. Transcriptional data were mined for potential markers, which were validated in an independent cohort. Results: The 10 TCGA cases with similar transcriptomic features were characterised by diploid genomes, absence of recurrent chromosomal alterations, and lack of VHL mutations. Reduced VHL mRNA expression was observed, with increased methylation at selected CpG sites consistent with possible epigenetic down-regulation. Diagnostic variability was identified during histological re-evaluation of the 10 similar cases by three urological pathologists. Differential expression analysis highlighted cytokeratin 17 (CK17) and collagen 17A1 (COL17A1) as candidate markers. Immunohistochemical evaluation in a small (n = 6) independent CCPRCT cohort demonstrated expression of both markers, whereas tissue microarrays from 257 clear cell and 68 papillary RCC cases were found to be negative. Conclusions: These findings suggest that a subset of renal tumors with overlapping morphological features of CCPRCT and RCCFMS may share common molecular characteristics. CK17 and COL17A1 emerged as candidate markers for recognising these tumors, although their diagnostic sensitivity and specificity require validation across a broader spectrum of renal neoplasms. These observations are exploratory and hypothesis-generating, and further studies in large, well-characterised cohorts are required to clarify the biological and diagnostic significance of this subgroup. Full article

Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based on a carboxymethyl chitosan (CMCS)/Carbomer 940 (Carb940) composite gel loaded with hydroxypropyl-β-cyclodextrin inclusion complexes of paeonol (Pae-CD) was developed. Pae-CD was prepared using an ultrasound-assisted saturated aqueous solution method, and the physicochemical properties, sustained-release behavior, transdermal permeation, antioxidant activity, and safety of Pae-CD/gel were evaluated. Furthermore, a mouse model of skin photoaging induced by combined ultraviolet A (UVA)/ultraviolet B (UVB) irradiation was established to investigate its reparative effects in vivo. The results showed that Pae-CD/gel exhibited a homogeneous three-dimensional porous structure, favorable sustained-release characteristics, enhanced skin retention capacity, and good cellular compatibility. In vivo experiments demonstrated that Pae-CD/gel markedly ameliorated ultraviolet-induced skin dryness, abnormal epidermal thickening, and dermal collagen loss. It also reduced oxidative stress and inflammatory factor levels, down-regulated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) expression, and promoted the restoration of collagen type I (COL-1) and hydroxyproline (HYP) levels. Systemic safety evaluation revealed no obvious toxicity. In summary, Pae-CD/gel exerts antioxidant and anti-inflammatory effects and regulates collagen metabolism by enhancing transdermal delivery and local retention, thereby providing a safe and effective topical delivery strategy for the repair of skin photoaging. Full article

Background: The clinical translation of cell-based therapies for knee articular cartilage repair is fundamentally restricted by the severe biological unpredictability of autologous cell sources, inherent manufacturing bottlenecks, and the rapid phenotypic dedifferentiation of cells expanded in conventional 2D monolayers. To overcome these translational hurdles, this study engineered a scaffold-free, 3D formulation of highly characterized allogeneic FE002-Cart chondroprogenitor spheroids. Methods: We systematically investigated the specific microenvironmental cues and Good Manufacturing Practice (GMP) formulation parameters required to direct functional chondrogenesis. The structural and biochemical performance of this allogeneic formulation was benchmarked against multiple primary adult autologous chondrocyte types. Finally, we evaluated the phenotypic resilience of the microtissues in simulated osteoarthritic (OA) environments and investigated both short-term liquid storage and advanced terminal preservation strategies to establish off-the-shelf logistical viability. Results: Precise microenvironmental regulation proved to be a critical biological prerequisite. The synergistic combination of physiological hypoxia (2% O₂) and stringent glucocorticoid limitation (10 nM dexamethasone) induced robust glycosaminoglycan (GAG) deposition and a > 200-fold upregulation of ACAN and COL2, while suppressing the terminal hypertrophic drift observed in adult chondrocytes. Benchmarking revealed that the allogeneic FE002-Cart formulation substantially mitigates the profound morphological and biochemical unpredictability inherent to adult autologous cell sources. Furthermore, the scaffold-free spheroid geometry yielded a 10-fold increase in GAG production per cell compared to traditional matrix-seeded (MACI) platforms. Transitioning to a GMP-compatible manufacturing process revealed extreme cellular sensitivities; excipients within standard pharmaceutical-grade dexamethasone severely aborted chondrogenic differentiation, emphasizing the necessity of rigorous raw-material qualification. Functionally, the 3D architecture acted as a protective physical shield, sustaining high cellular viability when subjected to severe inflammatory stress and 100% OA patient synovial fluid. Logistically, the viable spheroids maintained matrix integrity and inter-spheroid fusion potential for up to 7 days at ambient temperature in transport medium. Finally, advanced spheroid preservation via lyophilization and high-dose gamma irradiation eliminated biological viability but successfully transitioned the microtissues into highly organized, terminally irradiated matrices capable of heterologous in vitro structural merging. Conclusions: These findings define the critical biological thresholds for manufacturing, demonstrate the enhanced in vitro biosynthetic efficiency of 3D allogeneic microtissues compared to specific autologous and matrix-dependent baselines, and establish a highly practical, off-the-shelf logistical framework for the regenerative treatment of large knee chondral defects. Full article

Centella asiatica (L.) Urb. (Apiaceae) is widely incorporated into dermatological and wound-healing formulations, where dechlorophylization is commonly used to improve extract stability, although its biological consequences are not fully understood. In this study, an ethanolic extract of C. asiatica leaves (CAE) was compared with a dechlorophylized C. asiatica extract (DCAE) in terms of cytotoxicity, wound-healing, anti-inflammatory, and antimicrobial activities, complemented by network pharmacology analysis. DCAE exhibited improved cytocompatibility, remaining non-cytotoxic up to 100 µg/mL, whereas CAE showed cytotoxic effects above 25 µg/mL. In contrast, CAE demonstrated superior wound-healing performance, reducing the residual wound area to 21.77% compared with 36.81% for DCAE and inducing higher Ki67 expression (1.94-fold versus 1.58-fold). These findings suggest that chlorophyll-associated constituents may contribute to keratinocyte proliferation and re-epithelialization. Although DCAE was enriched in pentacyclic triterpenes, including asiatic acid, asiaticoside, madecassic acid, and madecassoside, it showed stronger anti-inflammatory effects by more effectively suppressing CXCL10, IL-6, TNF-α, and IL-8 expression. Both extracts displayed weak antibacterial activity but moderate antifungal effects against Candida albicans, likely mediated through membrane disruption. Network pharmacology further indicated that wound-healing activity is associated with the regulation of COL1A1 and VEGFA through quercetin, kaempferol, and asiatic acid by way of the PI3K-Akt and MAPK signaling pathways, whereas anti-inflammatory effects involve modulation of PTGS2 and TNF through the NF-κB and IL-17 pathways. Overall, DCAE enhances cytocompatibility and anti-inflammatory activity, while CAE retains stronger regenerative capacity. These findings support the rational design of tailored formulations for specific dermatological applications, such as promoting wound repair or alleviating chronic skin inflammation. Full article

Growth and body conformation traits are key determinants of meat production efficiency and economic performance in sheep. However, the genetic architecture underlying these complex traits remains incompletely understood, particularly across multi-breed populations. In this study, we performed a genome-wide association study (GWAS) for seven growth and developmental traits in a combined population of 401 sheep, including Qira Black, Kyrgyz, Dorset × Hu crossbred, and Suffolk × Karakul crossbred sheep. After genotype harmonization and quality control, 47,674 autosomal SNPs were retained for analysis. Population structure was assessed using principal component analysis, and association testing was conducted using a mixed linear model incorporating breed, principal components, and a kinship matrix. A total of 44 independent loci were detected at a nominal significance threshold, encompassing 112 candidate genes. The strongest association was identified for cannon bone circumference near RPS6KA5 (Chr7; p = 1.40 × 10⁻⁷). Several biologically relevant genes involved in osteogenesis, cartilage development, and metabolic regulation were detected, including STEAP3, SLC26A2, PPARGC1B, COL11A1, CALN1, and CITED2. Two genomic regions exhibited pleiotropic effects, which were identified as being associated with multiple traits, suggesting shared genetic regulation of correlated skeletal characteristics. These findings are consistent with a polygenic architecture underlying growth trait in sheep and highlight candidate genomic regions potentially involved in skeletal development and body conformation. Although further validation is required, the identified loci provide preliminary evidence for regions that may influence growth-related phenotypes and offer a reference for future molecular breeding efforts in indigenous and crossbred sheep populations. Full article

Background: Prophylaxis in children with hemophilia B (HB) lacks quantitative approaches that integrate both plasma exposure and tissue distribution. This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model of factor IX (FIX) for pediatric HB. The model incorporated the binding of FIX to type IV collagen (Col4) to characterize its distribution in both plasma and extravascular tissues. Methods: A total of 20 children with severe HB were included, contributing 219 plasma samples. The base PBPK model was first established and verified using adult and plasma-derived FIX (pdFIX) data. It was subsequently extrapolated to children by integrating FIX-CTBB parameters and pediatric observations for model calibration. The validated model was used to characterize plasma pharmacokinetics, predict tissue distribution and target attainment, and simulate alternative prophylactic dosing regimens. Results: The model adequately described the plasma pharmacokinetics of FIX in children and predicted substantial extravascular distribution. Total extravascular exposure was approximately sixfold higher than plasma exposure. Marked heterogeneity in target attainment was identified across tissues. Lower target attainment was observed in the colon, pancreas, and brain, whereas delayed attainment occurred in bone and muscle. Simulations of prophylactic dosing regimens suggested that 75 IU/kg twice weekly may provide a favorable balance among sustained FIX exposure, tissue-level target attainment, and treatment burden. Conclusions: This PBPK model provides a mechanistic and quantitative framework for characterizing plasma and tissue exposure to FIX in children with HB and may support individualized optimization of FIX prophylactic dosing. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

This study aimed to investigate the effect of hesperidin (HSP) at two different doses on deltamethrin (DLM)-induced testicular damage. The study comprised four groups of Wistar Albino rats (n = 8 per group): Control, DLM, DLM + HSP 100 mg/kg, and DLM + HSP 300 mg/kg. At the end of the study, oxidative stress markers and CRP were measured in serum samples. Testicular tissues were assessed histopathologically. Expression of Bcl-2, Bax, and Nrf-2 were determined by immunofluorescence staining. RT-qPCR assessed tissue collagen (COL1A1, COL3A1) and apoptotic () expressions. HSP at both doses lowered the DLM-induced increase in total oxidant status, oxidative stress index (total oxidant status/total antioxidant capacity), and CRP levels. Nrf-2 was increased by a high dose of HSP (300 mg/kg). Whereas HSP normalized other apoptotic parameters at both doses, it partially normalized Bax expression in immunofluorescence and Bcl-2 expression in RT-qPCR only at 300 mg/kg. HSP reduced the increased fibrosis in DLM exposure, as revealed by the expressions of COL1A1 and COL3A1 at both doses. HSP partially ameliorated DLM-associated histological alterations, including Johnsen’s score, tubule diameter, and thickness of the tunica albuginea. HSP may exert protective effects against DLM-induced testicular injury by modulating systemic oxidative status, apoptosis-associated signaling, and profibrotic gene expression. Full article

Background: Histone 3 lysine 27 tri-methylation (H3K27me3) is a chromatin mark typically associated with transcriptional repression. Histone demethylation, and particularly the removal of H3K27me3, has been linked to abiotic stress tolerance in plants. However, less is known about its role in biotic stress responses. Methods: We exploited immunity-related transcriptomics data combined with chromatin-state data to identify an association between chromatin modifications and plant immunity in Arabidopsis thaliana. We also measured the expression and H3K27me3 levels at immune-responsive loci, at Col-0 and at histone deacetylase mutants. Results: We identified H3K27me3 as a mark correlated with the silencing of defence gene loci. Moreover, we showed that the expression of a subset of flg22-induced genes is repressed by H3K27me3 prior to elicitation, and that expression negatively correlates with the mark upon activation of immunity. Notably, our studies also revealed a role for the H3K27 demethylase REF6 in plant defence. Loss of REF6 allows ectopic H3K27me3 deposition at target genes, revealing that these loci are actively regulated by the demethylase. Conclusions: Our data provide insight into the regulation of plant immune responses through chromatin dynamics. Full article