Search Results (8,732)

Fruit coloration is a key determinant of tomato quality, yet how light and temperature interact to regulate pigmentation during ripening remains unclear. Using a semi-in-fruit experimental system, we demonstrate that while high light accelerates chlorophyll degradation and lycopene accumulation at 25 °C, supra-optimal temperature (40 °C) completely abolishes lycopene biosynthesis irrespective of light conditions, primarily through transcriptional suppression of SlPSY1 and SlGGPS2. Elevated postharvest temperatures (≥30 °C) not only change the carotenoid composition but also reduce the antioxidant capacity and vitamin C content in fruit. Temperature-switch experiments revealed a critical developmental window, days 2–4 after ethylene treatment, during which temperature exerts dominant control over carotenoid metabolism. Exposure to high temperature within this window irreversibly shifts pigment accumulation from lycopene to yellow/orange carotenoids. These findings identify a temporally precise regulatory nexus integrating environmental signals with the ripening program, offering a framework for targeted temperature management to optimize tomato color and nutritional quality. Full article

Soil salinization is increasingly threatening global agricultural productivity and food security, currently affecting over 6% of the world’s land and one-third of irrigated areas. Tomato (Solanum lycopersicum L.), a major vegetable crop worldwide, exhibits moderate sensitivity to salinity, which limits both its yield and fruit quality. In recent years, epigenetic regulation has gained attention as a key mechanism enabling flexible and reversible control of gene expression without altering DNA sequences. This review synthesizes current knowledge on the epigenetic control of salt stress responses in tomato, focusing on three interconnected levels: DNA methylation dynamics, RNA-directed DNA methylation (RdDM), and histone modifications. We explore how DNA methyltransferases reshape the methylome under salinity, using examples such as PKE1 and SlGI to illustrate functional gene-body methylation. The RdDM pathway is discussed with emphasis on the unexpected role of SlAGO4A as a negative modulator of stress tolerance and the growing evidence for RdDM-mediated regulation of transcription factors. We also examine the balanced regulation of histone acetylation and deacetylation, highlighting the conserved role of GCN5 in maintaining cell wall integrity and the diverse functions of histone deacetylases, such as SlHDA1, SlHDA3, and SlHDA5, in stress adaptation. Additionally, insights from wild tomato species and grafting-induced epigenetic changes are presented, revealing new dimensions of stress memory. Collectively, these epigenetic mechanisms constitute a complex regulatory framework that integrates stress responses with growth and development, providing potential targets for epigenetic breeding of salt-tolerant tomatoes. Full article

To maintain homeostatic conditions and optimal function during stressors, mitochondria initiate retrograde signaling. The mitochondrial integrated stress response (ISR) and unfolded protein response (UPR^mt) are critical quality control mechanisms activated during instances of mitochondrial perturbations. Restoration of mitochondrial homeostasis is orchestrated by three transcription factors, ATF4, CHOP, and ATF5, which upregulate protective genes to counteract stress. As the health and function of skeletal muscle are heavily dependent on a highly adaptive mitochondrial network, defining how mitochondrial health is maintained across various conditions is essential. Although several studies demonstrate the importance of these responses following instances of stress, the signaling mechanisms required to initiate such pathways remain poorly characterized in skeletal muscle. This review examines how the mitochondrial ISR/UPR^mt and related transcription factors respond to organellar stress by emphasizing the molecular events that occur during exercise, aging and muscle disuse. By consolidating the literature, this work aims to highlight the current understanding of mitochondrial stress response signaling within skeletal muscle and thus emphasize areas for future research and potential therapeutic strategies during divergent metabolic conditions. Full article

Fruit shape is determined by patterns of cell division and expansion during early development, yet the upstream transcription factors coordinating cell wall dynamics and cytoskeletal organization remain largely unknown. Here, we report that SlbHLH113, a bHLH transcription factor, positively regulates tomato fruit elongation. Overexpression (OE) of SlbHLH113 produced elongated fruits with increased length/width ratio, whereas RNAi lines exhibited flattened fruits. Histological analysis revealed that SlbHLH113 alters columella cell polarity—promoting elongated cell morphology without affecting cell area—and reduces columella–placenta width and locule width, without altering pericarp thickness. Transcriptomic profiling identified 87 differentially expressed genes in OE lines, with enrichment in cell wall-related processes. Notably, a pectate lyase gene (PL5) and an expansin gene (EXT90) were down-regulated, while genes involved in oriented cellulose deposition (COBRA4) and ethylene signaling were up-regulated. Importantly, SlbHLH113 physically interacts with the microtubule-associated protein SlIQD21a, as demonstrated by yeast two-hybrid and luciferase complementation assays. Finally, SlbHLH113 did not affect major nutrient contents in red-ripe fruits. Collectively, our findings identify SlbHLH113 as a novel regulator of tomato fruit shape that might act through cell polarity control, cell wall remodeling, and interaction with a microtubule-associated protein, offering a potential target for improving fruit morphology without compromising nutritional quality. Full article

The two NFAT transcription factors NFATc1 and NFATc2 are the most prominent Ca⁺⁺-dependent TFs in the nuclei of activated peripheral lymphocytes. They control the activity of thousands of genes during immune responses. Although their structure and function show numerous things in common, their expression and activity differ markedly in most types of lymphocytes. Over the last 40 years, the work of our laboratory revealed a strong inducible transcription of the Nfatc1 gene upon lymphocyte (co-)activation, compared to the ‘tonic’ transcription of Nfatc2. This leads to the inducible expression of a short NFATc1 isoform that we designated as NFATc1/αA, which differs from longer NFATc1 proteins and NFATc2 by an individual N-terminal ‘α’ peptide and the absence of a C-terminal peptide of approximately 250 amino acid residues. While comprehensive experimental studies led to the conclusion that NFATc2 supports (i) apoptosis, (ii) the induction of anergy, and (iii) the ‘exhaustion’ of peripheral T cells, opposite conclusions can be derived from our studies of NFATc1/αA. This view on the ‘two faces’ of NFAT transcription factors will be presented in this review and discussed in the role of NFATs in cancerogenesis. Full article

Paclobutrazol (PBZ) is a triazole-type plant growth regulator that interferes with gibberellin (GAs) biosynthesis by blocking the oxidation step that converts ent-kaurene into ent-kaurenoic acid; however, the developmental mechanisms linking GAs restriction with storage organ enlargement remain poorly understood. In potato, PBZ induces compact growth while promoting microtubers (MTs) expansion, suggesting that GAs depletion triggers coordinated developmental reprogramming rather than simply suppressing elongation. Here, we evaluated the phenotypic, histological, and transcriptomic responses associated with PBZ-induced MTs development in Solanum tuberosum L. PBZ treatment, which increased MTs size, suppressed stolon growth, and enhanced starch accumulation, indicating a shift toward storage tissue development. Transcriptomic analysis identified broad PBZ-responsive changes, including enrichment of pathways related to metabolism, ribosome function, carbon metabolism, plant hormone signaling, and cell cycle regulation. Network analyses revealed ATH1-associated modules connected with receptor-like kinases, transcriptional regulators, mitotic regulators, replication-licensing factors and condensin components, supporting coordinated regulation among growth control, localized proliferation, asymmetric division, endoreduplication, and chromatin stability. These patterns were further supported by the absence of a detectable gibberellic acid (GA₃) peak in PBZ-treated samples. These findings support a model in which PBZ-responsive signaling is associated with developmental reprogramming toward radial expansion and reinforcement of storage tissue, providing a regulatory mechanism by which growth repression is coupled to microtube enlargement in potato. Full article

GRAS transcription factors are essential for plant growth and stress adaptation, yet they remain uncharacterized in the medicinal herb Coptis chinensis. To address this gap, we performed a genome-wide identification of the GRAS family and investigated its transcriptional responses to temperature and light stress, integrating comparative transcriptomics with promoter analysis to explore potential co-expression with bZIP factors. A total of 48 CcGRAS genes were identified and found to be unevenly distributed across nine chromosomes. Expression profiling revealed that CcGRAS genes are markedly more responsive to varying light intensities (476, 8340 lx) than to temperature stresses (15, 35 °C), relative to controls (2060 lx for light, 25 °C for temperature). Co-expression analysis uncovered an underground tissue-specific module in which CcbZIP16 is upregulated with four CcGRAS genes (CcGRAS11, CcGRAS12, CcGRAS43, CcGRAS48) that are coordinately upregulated specifically under low-light conditions. The promoters of these co-expressed genes are significantly enriched in canonical light-responsive cis-elements, providing correlative evidence for their coordinated transcriptional control. Together, these findings identify a tissue-specific GRAS-bZIP co-expressed gene set under light stress and suggest a candidate regulatory framework for dissecting light adaptation mechanisms. This work also provides a foundation for targeted genetic improvements in stress tolerance and alkaloid biosynthesis in this important medicinal plant. Full article

Energy homeostasis requires precise coordination between brain-derived appetitive signals and peripheral nutrient-handling mechanisms. Although Neuropeptide F (NPF) and its mammalian homolog NPY are well-established central stimulators of feeding, whether and how they regulate nutrient assimilation in the gut remains unknown. Here, using Drosophila, we identify a previously unrecognized transcriptional circuit between NPF and the purine synthesis enzyme GART trifunctional enzyme (Gart) that governs feeding by controlling gut absorptive efficiency. We show that NPF signaling acts via its receptor NPFR to positively regulate Gart expression specifically within the intestine. Conversely, Gart activity exerts negative feedback on NPF expression, forming a reciprocal regulatory loop. Functionally, gut-specific, but not glial or fat body-specific, Gart is necessary and sufficient for promoting food absorption and consumption. Genetic epistasis experiments demonstrate that Gart acts downstream of NPF to execute its function. Strikingly, peripheral NPF from the fat body and gut, rather than brain-derived NPF, serves as the primary systemic signal driving this loop. Our findings reveal a gut-centered homeostatic module where NPF activates Gart to boost nutrient absorption, while the resultant feeding activity in turn curbs the signal, ensuring calibrated energy intake. This work redefines a canonical neuropeptide’s role from a pure behavioral driver to a key regulator of peripheral metabolic efficiency, and establishes a novel framework for understanding gut–brain communication in energy balance. Full article

Background/Objectives: Yes-associated protein 1 (YAP1) is a transcriptional cofactor that coordinates the complex interplay between cell proliferation, survival, differentiation, metabolism, biomechanics, and tissue regeneration. Previous studies have shown that YAP1 activity is reduced during aging, and replacing YAP1 function has been shown to rejuvenate old cells by mitigating senescence and its associated inflammation. Methods: As YAP1 is now confirmed to exert a profound regenerative influence on multiple organs, we wanted to gain more insight into the molecular signature of YAP1 expression relevant to brain cells. Since proteomics is a very powerful tool for discoveries, we generated SH-SY5Y cells stably expressing GFP-YAP1 and screened 8000 human proteins using multiplex arrays that utilize biotin-label-based antibody arrays. Results: We found YAP1 expression in astrocytes, microglia, neuronal and neuroblastoma cell lines, as well as human neurons. Importantly, YAP1 protein levels were significantly reduced selectively in the nuclear fractions of the brains of patients with Alzheimer’s disease (AD) relative to normal control (NC) subjects. The screen resulted in the identification of 283 differentially expressed proteins. In line with YAP1’s known role in the regulation of actin and cytoskeleton, we found a 2.53-fold upregulated level of Rho guanine nucleotide exchange factor 1 (ARHGEF1), a guanine nucleotide exchange factor (GEF) for the RhoA GTPase, which is crucial for dendritic spine regulation. A 6.19-fold upregulated level of NECAP endocytosis-associated 2 (NECAP2), the highest known increase for any protein in this screen, plays an essential role in clathrin-mediated endocytosis. Most importantly, another upregulated protein was Neudesin Neurotrophic Factor (NENF) (3.07-fold increase), also known as Neudesin, which primarily acts as a neurotrophic factor, and it promotes neuronal survival, enhances cell proliferation, and neurogenesis in neural progenitor cells. Neural Precursor Cell Expressed, Developmentally Down-Regulated 9(NEDD9) levels were also upregulated by 2.46-fold, and it affects neuronal cell number and synaptic connections through its role in neurite formation. However, it should be noted that these proteomic results are preliminary in nature as they are derived from single-sample data. The upregulated levels of ARHGEF1 and NEDD9 were confirmed by immunoblots. We also found a drastic reduction in the levels of p16INK4a, a marker of senescence. Conclusions: Thus, the anti-senescence effect of YAP1 may be mediated through p16INK4a, which in turn may be crucial for YAP1’s regenerative functions through NENF and NEDD9. Full article

Aims: Coronary heart disease (CHD) associated with rheumatoid arthritis (RA) is a primary driver of mortality in RA patients. In this study, we sought to establish a combined rat model of CHD and RA by integrating cardiac ischemia/reperfusion (I/R), high-fat diet (HFD), and intradermal administration of bovine type II collagen emulsified in complete Freund’s adjuvant. The aim of constructing this model is to investigate and analyze the pathogenesis of RA-induced CHD under the modulation of HFD and cardiac I/R exposure. Methods and Results: Sixty-four male Sprague–Dawley rats were randomly categorized into eight groups (n = 8 per group): control, I/R, HFD, collagen-induced arthritis (CIA), I/R + CIA, HFD + CIA, I/R + HFD, and I/R + HFD + CIA groups (n = 8 per group). We applied Synchrotron radiation-based X-ray micro-computed tomography (micro-CT) to observe the structural changes within the model over time. To further elucidate molecular mechanisms, transcriptome RNA-seq analysis was carried out to identify key signaling pathways, with particular emphasis on the homeostasis of Toll-like receptor 4 (TLR4)/Myd88 signaling in the ischemic myocardium. Furthermore, we conducted in vivo shRNA-mediated knockdown of polymerase I and transcription release factor (PTRF) and evaluated the co-localization of PTRF and TLR4 through immunofluorescence experiments. It is worth mentioning that our rat model of RA-induced (CHD) under a high-fat diet effectively manifested the relevant pathological features that align with the Traditional Chinese Medicine (TCM) definition of “bi” syndrome. The results indicate that the combined stimulation of HFD and CIA significantly elevated cardiac injury markers (CK-MB, LDH, CRP, and c-TNT) and was accompanied by a more severe expansion of the infarct area and increased cardiomyocyte apoptosis compared to the I/R group alone. In addition, the histopathological evaluation revealed significantly aggravated myocardial inflammation and fibrosis deposition, accompanied by extensive areas of tissue damage, further indicating a state of heightened inflammation and severe cardiac degenerative changes. Consistently, myocardial tissues from rats in the I/R + CIA + HFD group exhibited robust activation of the TLR4/MyD88 signaling pathway and a pronounced elevation in the p-JNK/JNK ratio. Moreover, pronounced co-localization between PTRF and TLR4 was evident in small vessels surrounding the infarcted myocardium. Importantly, AAV-mediated knockdown of PTRF attenuated the HFD- and CIA-induced exacerbation of myocardial injury in I/R rats. Conclusions: We successfully established a rat model of CHD with rheumatic syndrome using I/R in combination with RA and HFD. The present findings suggest that the PTRF-related TLR4/MyD88-JNK signaling pathway may act as an important regulatory mechanism underlying myocardial injury aggravated by combined HFD and CIA stimulation. Full article

The NAC transcription factor superfamily is one of the most prominent plant-specific regulatory gene families, extensively participating in multiple metabolic processes that govern plant growth, tissue development and stress adaptation. Masson pine (Pinus massoniana Lamb.) is a native dominant conifer widely cultivated across South China, whose timber resources possess great exploitation potential in pulp manufacturing and the paper industry. In this study, a total of 98 non-redundant NAC family members were mined at the genome-wide level. Functional validation revealed that PmNAC82, a member belonging to the VND evolutionary subgroup, acts as a core regulatory factor controlling wood formation. Subcellular localization tests confirmed PmNAC82 exclusively resides in the cell nucleus. Heterologous genetic transformation in poplar demonstrated that this gene positively regulates the accumulation of lignin and cellulose. Furthermore, through RT-qPCR, yeast one-hybrid assays, and EMSA, we confirmed that PmNAC82 can bind to the promoters of PtrMYB3, PtrMYB21 and PmCesA7. These findings provide a solid foundation for further investigation into the molecular functions of NAC genes in Masson pine as well as their potential application towards molecular breeding strategies aimed at improving wood quality. Full article

Verticillium wilt, caused by Verticillium dahliae, is a devastating disease that severely threatens cotton production worldwide. The long-term survival of the pathogen in soil and the limited availability of resistant cultivars make effective control strategies challenging. Although the fungal cross-kingdom RNA VdsR-1 has been reported to delay floral transition and prolong vegetative growth, the underlying plant regulatory mechanisms remain largely unclear. Here, we show that the transcription factor AtTOE1, a target of ath-miR172b-3p, displays altered expression in response to changes in ath-miR172b-3p levels during V. dahliae inoculation, coinciding with coordinated changes in plant immune-related and developmental responses. Increased AtTOE1 expression is correlated with enhanced disease resistance, reduced pathogen colonization, and delayed floral transition. Furthermore, our results indicate that the VdsR-1/AtSPL13A module is associated with modulation of AtTOE1 expression via ath-miR172b-3p, suggesting the involvement of a cross-kingdom RNA-related regulatory framework linking plant immunity and development. Notably, this regulatory relationship is also observed in cotton, indicating evolutionary conservation across plant species. Together, our findings highlight TOE1 as a potential integrator of defense and growth-related processes during pathogen challenge and provide insights that may inform strategies to improve resistance to V. dahliae in cotton and other crops. Full article

Ovarian endometriosis (OE) is a chronic, inflammatory gynecological disorder associated with sterility and an elevated risk of ovarian cancer. Despite its high prevalence, the complex molecular mechanisms governing OE pathogenesis remain poorly investigated. We conducted a comprehensive histopathological and molecular investigation of OE in a cohort of 188 Saudi women (88 patients with OE and 100 healthy controls) using histopathological, qRT-PCR, immunostaining, and Western blot techniques. Histopathological analysis confirmed significant stromal fibrosis and chronic inflammation in endometriotic lesions. Gene expression profiling revealed a pro-proliferative, anti-apoptotic signature, marked by the upregulation of PTTG1 and the downregulation of TNFRSF10D, CDK4, and CDKN1A. Interestingly, we identified a post-transcriptional regulatory paradox in the inflammatory response: while IL-6 mRNA was significantly upregulated, its corresponding protein level was downregulated, suggesting a novel, tightly controlled mechanism to limit excessive local inflammation. Besides the increased autophagic activity and decreased Ubiquitin mRNA levels, epigenetic dysregulation was prominent, characterized by the upregulation of DNA methyltransferase DNMT3B and the downregulation of the histone variant H3.1. These findings elucidate novel molecular pathways underlying OE pathogenesis as evidenced by a post-transcriptional paradox in IL-6 expression, and uncover key dysregulations spanning cell proliferation, apoptosis, inflammation, autophagy, and epigenetic regulation. Full article

Staphylococcus aureus (S. aureus) bovine mastitis is a significant public health issue. Despite enormous efforts, important gaps remain regarding host–microenvironmental factors. How intramammary reduced oxygen modulates S. aureus transcription in bovine mammary epithelial cells (MECs) remains unclear. We examined oxygen-associated transcriptional changes in a bovine-mammary adapted S. aureus clone following internalization into MECs and identified functional category enrichments under Normal-O₂ and Reduced-O₂ exposures. Bovine MAC-T monolayers were infected with a dominant bovine mastitis isolate under Normal-O₂ or Reduced-O₂ conditions. Triplicate infection experiments were performed for each oxygen condition. Each condition included matched non-reacted bacterial controls maintained under the same gas condition but without MAC-T exposure serving as the reference condition for expression calling. RNA was extracted and profiled using a high-throughput qRT-PCR platform covering genome-wide loci. Expression calls were mapped to curated BioQT roles and interpreted descriptively. Results indicated 211 loci were upregulated and 99 were downregulated under Normal-O₂ conditions, versus 53 upregulated and 35 downregulated under Reduced-O₂ conditions, relative to their non-reacted controls. Under Normal-O₂ conditions, regulated loci covered multiple functional roles, including cellular processes, transport/binding proteins, regulatory functions, and energy metabolism with downregulated loci enriched in transport/binding and cell-envelope categories. Under Reduced-O₂ conditions, upregulated loci were abundant in cellular process annotations dominated by pathogenesis/toxin-related functions, whereas downregulated loci were enriched in nucleotide biosynthetic and DNA/cell division categories. Thus, this reveals oxygen-associated shifts in the transcriptional response of intramammary S. aureus in MAC-T cells. Normal-O₂ conditions were associated with broader category representation, whereas Reduced-O₂ conditions yielded a narrower distribution enriched for selected toxin/pathogenesis- and iron/cation-associated annotations. These oxygen-linked transcriptional-shifts highlight candidate pathways for the intramammary adaptation of S. aureus, potential diagnostic markers, anti-virulence strategies, and targeted therapeutics. Full article

Background/Objectives: Gliomas are among the most aggressive primary brain tumors in adults, characterized by profound molecular heterogeneity and poor response to conventional therapies. Immunotherapy has transformed outcomes in several cancers, yet glioma remains largely refractory, due in part to an immunosuppressive tumor microenvironment. Post-transcriptional regulation of gene expression is increasingly recognized as a key mechanism controlling immune cell function in tumors. Regnase-1, an endoribonuclease regulating the stability of inflammation- and immunity-related mRNAs, is a central modulator of immune responses; however, its role in glioma progression and immune modulation remains poorly understood. This study aimed to evaluate Regnase-1 expression in glioma and investigate its association with tumor grade, prognosis, and immune microenvironment characteristics. Methods: Regnase-1 transcript levels were evaluated by RT-PCR in tumor samples from 40 Moroccan glioma patients and validated using transcriptomic data from The Cancer Genome Atlas (TCGA, n = 672) and the Chinese Glioma Genome Atlas (CGGA, n = 959). Bioinformatic analyses and statistical assessments were performed using established pipelines. Results: Regnase-1 expression was significantly elevated in glioblastoma, IDH-wildtype tumors, and higher tumor grades, correlating with poorer overall survival, and emerging as an independent prognostic factor in the CGGA cohort. High Regnase-1 expression was associated with enrichment of pathways related to angiogenesis, hypoxia, invasion, and immune evasion. Tumors with elevated Regnase-1 showed reduced infiltration of effector immune cells (CD8⁺ T cells, Th1 cells) and increased presence of immunosuppressive populations, including regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages. Single-cell analyses further highlighted exhausted CD8⁺ T cells and regulatory T cells as major populations linked to Regnase-1 expression. Notably, Regnase-1 expression also exhibited strong positive correlations with multiple inhibitory immune checkpoint pathways. Conclusions: Elevated Regnase-1 expression defines an aggressive, immunosuppressive glioma phenotype and is associated with poor prognosis, supporting its potential as a prognostic biomarker and a target for immunomodulatory strategies. Full article