Search Results (38,070)

Postharvest shiitake mushrooms (Lentinus edodes) often undergo browning under low-temperature, high-humidity storage conditions, which significantly reduces their commercial value and constrains industry development. However, the molecular mechanisms regulating this process remain unclear. In this study, we used ‘Nongxiang No. 1’ as the experimental material and observed that during storage, the L* value of caps and stipes decreased continuously, shifting from light brown to dark brown-black. Concurrently, the relative electrical conductivity increased by approximately 3.07-fold, and the membrane lipid peroxidation product malondialdehyde (MDA) content increased by approximately 7.9-fold. Superoxide dismutase (SOD) activity initially increased then declined, indicating that elevated membrane permeability accelerates senescence. Peroxidase (POD) activity exhibited a significant upward then downward trend and improved 75.83% at day 22 of postharvest storage, with LEHP1, LEHP2, and LEHP3 gene expression patterns closely aligning with these changes. Specifically, LEHP2 and LEHP3 expression was upregulated by 23.8-fold and 2.35-fold on day 22 than day 0. Cis-element analysis identified MYB binding sites in all three LEHP genes. Genome-wide screening combined with qRT-PCR revealed two MYB transcription factors, LeMYB2 and LeMYB5, whose expression synchronized with LEHP genes. Transient expression assays in tobacco leaves confirmed their nuclear localization, consistent with transcription factor characteristics. Electrophoretic Mobility Shift Assay (EMSA) and Dual-Luciferase Reporter Assay (DLR) experiments further demonstrated that LeMYB2 and LeMYB5 directly activate LEHP2 and LEHP3 promoters, highlighting their key regulatory roles in postharvest browning of shiitake mushrooms. Full article

Radiation resistance presents a significant challenge in the treatment of triple-negative breast cancer (TNBC). To investigate the molecular adaptations associated with radiation therapy resistance, MDA-MB-231 cells were subjected to a repeated radiation (RR) regimen totaling 57 Gy over 11 weeks, followed by clonal selection. The resulting radiation-adapted cells (MDA-MB-231^RR) were analyzed using whole-transcriptome RNA sequencing, revealing substantial dysregulation of pathways related to cell adhesion, mitochondrial function, and epithelial–mesenchymal transition (EMT). These transcriptional changes were corroborated by functional assays. MDA-MB-231^RR cells exhibited reduced expression of adhesion receptors (ITGB1, ITGA2, ITGA6) and extracellular matrix proteins (fibronectin, collagen, laminins), accompanied by significantly impaired cell adhesion to fibronectin, collagen, and laminin substrates. Mitochondrial dysfunction was supported by downregulation of oxidative phosphorylation genes (MTCO1, MTND1) and confirmed by JC-1 dye assays demonstrating a marked reduction in mitochondrial membrane potential. EMT-associated changes included increased mesenchymal markers and loss of epithelial markers (CTNNB1, SNAI2, CK19), consistent with enhanced migratory potential. Taken together, this study delineates key molecular features of radiation adaptation in TNBC, providing a foundation for the development of targeted therapies to overcome treatment resistance. Full article

Cannabidiol (CBD) and other phytocannabinoids are gaining attention for their therapeutic potential in cardiovascular disease (CVD), the world’s leading cause of death. This review highlights advances in understanding the endocannabinoid system, including CB1 and CB2 receptors, and the mechanisms by which CBD exerts anti-inflammatory, antioxidative, vasoprotective, and immunomodulatory effects. Preclinical and translational studies indicate that selective activation of CB2 receptors may attenuate atherogenesis, limit infarct size in ischemia–reperfusion injury, decrease oxidative stress, and lessen chronic inflammation, while avoiding the psychotropic effects linked to CB1. CBD also acts on multiple molecular targets beyond the CB receptors, affecting redox-sensitive transcription factors, vascular tone, immune function, and endothelial integrity. Early clinical trials and observational studies suggest that CBD may lower blood pressure, improve endothelial function, and reduce sympatho-excitatory peptides such as catestatin, with a favorable safety profile. However, limited bioavailability, small sample sizes, short study durations, and uncertainty about long-term safety present challenges to its clinical use. Further research is needed to standardize dosing, refine receptor targeting, and clarify the role of the endocannabinoid system in cardiovascular health. Overall, current evidence supports CBD’s promise as an adjunct in CVD treatment, but broader clinical use requires more rigorous, large-scale studies. Full article

Evidence indicates that light can trigger an increase in triacylglycerol (TAG) accumulation in eukaryotic microalgae without reducing cell division. In connection with this, we have recently reported that the expression of the chloroplast enzyme diacylglycerol acyltransferase 3 (DGAT3) is induced by light in concert with TAG accumulation in Chlamydomonas reinhardtii. In this work, we report the identification of two phytyl ester synthases (PES) in C. reinhardtii, named PESα and PESβ. These are homologous to chloroplast PES1 and PES2 of Arabidopsis thaliana, which play a role in the synthesis of fatty acid phytyl esters (FAPEs) and TAGs. We demonstrate that PESα and PESβ transcript levels are transiently induced upon transferring cell cultures from a growth condition of low light to high light, and this occurs in parallel to an increase in TAG levels. In a pesα knockdown mutant, DGAT3 transcripts and TAG levels are significantly higher than in the parental strain at the end of the low-light period, and remain elevated after shifting pesα cells to the high-light condition. On the contrary, in a pesβ knockdown mutant, TAG levels, as well as DGAT3 expression, are similar to those of the control strain. These results suggest that PESα and PESβ are non-redundant in TAG metabolism and that PESα is functionally related to DGAT3. Full article

Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to fresh-frozen specimens of one HCC and one liver metastasis (>16,000 genes per sample, >97% mapping rates) as a proof-of-principle two-specimen study, cross-validated in human proteomics and patients’ survival datasets. Transcriptional clustering revealed spatially distinct compartments, rare cell states, and pathway alterations, which were further compared against an independent systemic dataset. Results: HCC displayed an ordered lineage architecture, with transformed hepatocyte-like tumor cells broadly dispersed across the tissue and more differentiated hepatocyte-derived cells restricted to localized zones. By contrast, liver metastases showed two sharply compartmentalized domains: an invasion zone, where proliferative stem-like tumor cells occupied TAM-rich boundaries adjacent to hypoxia-adapted tumor-core cells, and a plasticity zone, which formed a heterogeneous niche of cancer–testis antigen–positive germline-like cells. Across both tumor types, we detected a conserved metabolic program of “porphyrin overdrive,” defined by reduced cytochrome P450 expression, enhanced oxidative phosphorylation gene expression, and upregulation of FLVCR1 and ALOX5, reflecting coordinated rewiring of heme and lipid metabolism. Conclusions: In this pilot study, HCC and liver metastases demonstrated fundamentally different spatial architectures, with metastases uniquely harboring a germline/neural-like plasticity hub. Despite these organizational contrasts, both tumor types converged on a shared program of metabolic rewiring, highlighting potential therapeutic targets that link local tumor niches to systemic host–tumor interactions. Full article

This study aims to elucidate the molecular mechanisms underlying cyanogenic glycoside accumulation in flax. As an important oil and fiber crop, the nutritional value of flax is compromised by the toxicity of cyanogenic glycoside. To clarify the key genetic regulators and temporal patterns of cyanogenic glycoside biosynthesis, transcriptomic sequencing was performed on seeds from high- and low-cyanogenic glycoside flax varieties (‘MONTANA16’ and ‘Xilibai’) at three developmental stages: bud stage, full flowering stage, and capsule-setting stage. A total of 127.25 Gb of high-quality data was obtained, with an alignment rate exceeding 87.80%. We identified 31,623 differentially expressed genes (DEGs), which exhibited distinct variety- and stage-specific expression patterns. Principal component analysis (PCA) and hierarchical clustering demonstrated strong reproducibility among biological replicates and revealed the seed pod formation stage as the period with the most significant varietal differences, suggesting it may represent a critical regulatory window for cyanogenic glycoside synthesis. GO and KEGG enrichment analyses indicated that DEGs were primarily involved in metabolic processes (including secondary metabolism and carbohydrate metabolism), oxidoreductase activity, and transmembrane transport functions. Of these, the cytochrome P450 pathway was most significantly enriched at the full bloom stage (H2 vs. L2). A total of 15 LuCYP450 and 13 LuUGT85 family genes were identified, and their expression patterns were closely associated with cyanogenic glycoside accumulation: In high-cyanogenic varieties, LuCYP450-8 was continuously upregulated, and LuUGT85-12 was significantly activated during later stages. Conversely, in low-cyanogenic varieties, high expression of LuCYP450-2/14 may inhibit synthesis. These findings systematically reveal the genetic basis and temporal dynamics of cyanogenic glycoside biosynthesis in flax and highlight the seed pod formation stage as a decisive regulatory window for cyanogenic glycoside synthesis. This study provides new insights into the coordinated regulation of cyanogenic pathways and establishes a molecular foundation for breeding flax varieties with low CNG content without compromising agronomic traits. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Clinical studies have linked glyphosate exposure to substantial morbidity, with acute kidney injury occurring in some cases. Although the toxic effects of glyphosate-based herbicides (GBHs) have been reported in several studies, their molecular impact on renal function remains poorly understood. Given the kidney’s critical role in excretion, it is particularly susceptible to damage from xenobiotic exposure. In this study, we aim to identify N-glycomics and proteomics change in the kidney following chronic GBH exposure, to better understand the mechanisms behind glyphosate-induced kidney damage. Kidney tissues from female and male rats were analyzed using liquid chromatography–tandem mass spectrometry. The results revealed notable changes in the N-glycan composition, particularly in the fucosylated and sialofucosylated N-glycan types. The proteomic analysis revealed the activation of immune signaling and inflammatory pathways, including neutrophil degranulation, integrin signaling, and MHC class I antigen presentation. Transcription regulators, such as IL-6, STAT3, and NFE2L2, were upregulated, indicating a coordinated inflammatory and oxidative stress response. Sex-specific differences were apparent, with female rats exhibiting more pronounced alterations in both the N-glycan and protein expression profiles, suggesting a higher susceptibility to GBH-induced nephrotoxicity. These findings provide new evidence that chronic GBH exposure may trigger immune activation, inflammation, and potentially carcinogenic processes in the kidney. Full article

Acute lung injury (ALI) is a severe pulmonary disorder characterized by the disruption of the alveolar–capillary barrier, leading to impaired oxygenation and pulmonary edema. Current pharmacological interventions primarily involve the use of steroid drugs, oxygen radical scavengers, and bronchodilators. However, the therapeutic efficacy of these interventions remains inconsistent. Canthin-6-ones, a class of tryptophan-derived alkaloids, exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, we synthesized a novel Canthin-6-one derivative, namely HCX3, and evaluated its potential beneficial effects and underlying mechanisms on ALI. Prior to the experimental study, network pharmacology analysis revealed that HCX3 may exert anti-inflammatory effects in the context of ALI through the regulation of multiple signaling pathways, including the NF-κB pathways. To validate these findings, Lipopolysaccharide (LPS) was employed to stimulate RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) to construct cellular models of inflammatory response associated with ALI. Our data demonstrated that exposure to HCX3 significantly inhibited the transcription and the secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner. Additionally, HCX3 reduced LPS-induced phosphorylation levels of p65 and IκB-α in macrophages, indicating an inhibitory effect of the compound on the activation of NF-κB signaling pathway. Collectively, our data suggest that HCX3 exhibits significant anti-inflammatory effects by inhibiting NF-κB-related signaling pathways, providing new insights for ALI treatment. Full article

TCP transcription factors represent a crucial family of plant regulators that contribute significantly to growth and developmental processes. Although the TCP gene family has been extensively studied in various plant species, research on Chimonanthus praecox (wintersweet) remains limited. Here, we performed genome-wide identification and analysis of the TCP gene family in C. praecox and identified 22 CpTCP genes. We further systematically examined the associated physicochemical properties, evolutionary relationships, gene structures, and regulatory features. Analysis revealed that all CpTCP proteins possess a conserved TCP domain, and subcellular localization prediction indicated their localization in the nucleus. Promoter analysis revealed that multiple cis-elements are associated with abiotic stress responses and plant growth regulation. Further analysis revealed high CpTCP2 expression in the leaves and stamen, with significantly increased levels during flower senescence. CpTCP2 expression was upregulated in response to methyl jasmonate (MeJA), salicylic acid, abscisic acid, and shade. CpTCP2 overexpression in Arabidopsis thaliana resulted in a reduced leaf area, delayed flowering, and increased rosette leaf numbers. Moreover, MeJA treatment accelerated leaf senescence in CpTCP2 transgenic Arabidopsis. These findings provide insights into the evolutionary characteristics of the TCP family in C. praecox, highlighting the functional role of CpTCP2 in regulating leaf development and flowering time in Arabidopsis, thereby offering valuable genetic resources for wintersweet molecular breeding. Full article

Background: Metabolic flexibility, the ability to efficiently switch between fuel sources in response to changing nutrient availability and energy demands, is recognized as a key determinant of metabolic health. In a recent randomized controlled human feeding trial, overweight individuals receiving American black elderberry juice (EBJ) demonstrated improvements in multiple clinical indices of metabolic flexibility, but the mechanisms of action were unexplored. The objective of this study was to utilize RNA sequencing to examine how EBJ modulates the transcriptional response to fasting and feeding, focusing on pathways related to metabolic flexibility. Methods: Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. RNA sequencing was performed on peripheral blood mononuclear cells from 10 participants to assess transcriptomic responses collected at fasting (pre-meal) and postprandial (120 min post-meal) states during a meal-challenge test. Results: The fasted-to-fed transition for EBJ showed 234 differentially expressed genes following EBJ consumption compared to 59 genes following PL, with 44 genes shared between interventions. EBJ supplementation showed significantly higher enrichment of several metabolic pathways including insulin, FoxO, and PI3K–Akt signaling. KEGG pathway analysis showed 27 significant pathways related to metabolic flexibility compared to 7 for PL. Conclusions: Our findings indicate that short-term elderberry juice consumption may promote metabolic flexibility in overweight adults. Full article

Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors show therapeutic potential in triple-negative breast cancer (TNBC), but resistance through compensatory signaling limits their efficacy. We previously identified the secretory carrier membrane protein 3 (SCAMP3) as a regulator of TNBC progression and ERK1/2 activation. Here, we investigated the role of SCAMP3 in ERK1/2 signaling and therapeutic response using TMT-based LC-MS/MS phosphoproteomics of wild-type (WT) and SCAMP3 knockout (SC3KO) SUM-149 cells under basal conditions, after epidermal growth factor (EGF) stimulation, and during ERK1/2 inhibition with MK-8353. A total of 4408 phosphosites were quantified, with 1093 significantly changed. SC3KO abolished residual ERK activity under MK-8353 and affected the compensatory activation of oncogenic pathways observed in WT cells. SC3KO reduced the phosphorylation of ERK feedback regulators RAF proto-oncogene serine/threonine-protein kinase Raf-1 (S43) and the dual-specificity mitogen-activated protein kinase kinase 2 (MEK2) (T394), affected other ERK targets, including nucleoporins, transcription factors, and metabolic enzymes triosephosphate isomerase (TPI1) (S21) and ATP-citrate lyase (ACLY) (S455). SCAMP3 loss also impaired the mammalian target of rapamycin complex I (mTORC1) signaling and disrupted autophagic flux, evidenced by elevated sequestosome-1 (SQSTM1/p62) and microtubule-associated protein light chain 3 (LC3B-II) with reduced levels of the autophagosome lysosome maturation marker, Rab7A. Beyond ERK substrates, SC3KO affected phosphorylation events mediated by other kinases. These findings position SCAMP3 as a central coordinator of ERK signaling and autophagy. Our results support SCAMP3 as a potential therapeutic target to enhance ERK1/2 inhibitor clinical efficacy and overcome adaptive resistance mechanisms in TNBC. Full article

Antimicrobial resistance (AMR) is traditionally discussed in the context of horizontally acquired resistance genes and point mutations at target loci. However, this gene-centred model fails to account for a large number of clinically important modalities of resistance. There is now substantial evidence implicating bacteria in the ability to escape the effects of antibiotics in a variety of non-canonical ways, which are not considered in traditional diagnostic and surveillance pipelines. Among these factors, we can list those arising from global regulatory networks, phase variability, epigenetic tuning, small RNAs, genome structural variability, and phenotypic states like tolerance and persistence. This review will blend the current knowledge on these alternative pathways of resistance and underscore how they intersect with canonical genetic determinants. We will highlight cases where resistance emerges in the absence of known resistance genes, analyse the role of regulatory plasticity in efflux pump expression and membrane remodelling, and examine the contributions of bacterial stress responses and post-transcriptional control. Additionally, we will address methodological gaps in the detection of these mechanisms and their implications for clinical treatment failure, resistance surveillance, and drug development. By integrating insights from molecular microbiology, systems biology, and genomics, this review aims to offer a framework for understanding AMR as a multifaceted, context-dependent phenotype, not merely a genotype. We conclude by identifying knowledge gaps and suggesting priorities for research and diagnostic innovation in this evolving field. Full article

The inclusion of meat quality traits in breeding programs is a promising strategy to improve beef by selecting animals based on both growth and meat quality. This study aimed to estimate genetic parameters for average daily gain (ADG) and Warner–Bratzler shear force (WBSF), as well as to perform genome-wide association studies (GWAS) to identify genomic regions and transcription factor (TF) binding sites associated with both traits in Nelore cattle. Genetic parameters were estimated using a bi-trait Bayesian model, and GWAS identified key SNPs explaining over 1% of variance in genomic estimated breeding values. Candidate genes near these SNPs were annotated, TF binding sites predicted, and gene–TF networks constructed. Genetic estimates indicated moderate heritability for ADG, low heritability for WBSF, and a small negative genetic correlation between traits. Genomic regions contained 116 and 151 candidate genes for ADG and WBSF, respectively, with 35 shared between traits. Functional analyses highlighted MYBPC1 and PENK for WBSF, and GHRS and NPY for ADG. TF analysis identified 25 TFs, with 3 key ones highlighted. Gene–TF networks revealed candidates including CAPN1 and LTBP3 for WBSF, and CARM1 and GH1 for ADG. Shared candidate genes identified in the combined network provide valuable insights into the genetic architecture of growth and tenderness in Nelore cattle. Full article

Lilac (Syringa spp.) is a widely cultivated ornamental plant prized for its fragrant aroma and attractive flower colors. However, the molecular mechanisms governing its flower pigmentation remain poorly understood. In this study, we performed integrated transcriptomic and metabolomic analyses on purple (Syringa oblata) and white (Syringa oblata var. alba) lilacs at the P1 stage, the point of deepest pigmentation. Compared with W1, P1 has a total of 918 differentially expressed genes, including 614 up-regulated genes and 304 down-regulated genes. And S. oblata exhibited significant upregulation of key anthocyanin biosynthesis genes, including the rate-limiting enzyme gene ObDFR, ObF3’H and transcriptional regulators such as ObWPA, which encodes a WD40 repeat protein. This transcriptional activation was accompanied by a substantial accumulation of 27 anthocyanins, including Petunidin Chloride, Cyanidin Chloride, Delphinidin and so on, while the Petunidin-3-O-rutinoside, Petunidin-3-O-(6-O-p-coumaroyl)-glucoside and Malvidin-3-O-sambubioside-5-O-glucoside were only detected in S. oblata. Furthermore, ATAC-seq analysis revealed that, in comparison to white lilac, purple lilac exhibited 3522 and 805 genes with increased and decreased chromatin accessibility, respectively. Integrative analysis with the transcriptome identified 135 genes that were both more accessible and transcriptionally upregulated in purple lilac, including ObWPA, Ob0214386, and Ob0227194 which belong to WD40 members. Subsequent qRT-PCR validation confirmed ObWPA as the most significantly upregulated gene in purple lilac, a finding consistent with the specific chromatin accessibility detected in its promoter region. To validate its function, we knocked down ObWPA expression in purple lilac using Virus-Induced Gene Silencing (VIGS). This intervention resulted in a dramatic color shift from purple to white, concomitant with a significant decrease in key anthocyanin metabolites such as Cyanidin-3-(6-O-p-caffeoyl)-glucoside, Cyanidin Chloride, Pelargonidin, Cyanidin-3-O-rutinoside, Dihydrokaempferol, and Petunidin Chloride. Collectively, our findings demonstrate that ObWPA is an indispensable positive regulator of purple color formation in S. oblata. Full article