Search Results (13,165)

Background: DEAD/H box 5 (DDX5) serves as a transcriptional coactivator for several transcription factors including E2F1, the primary target of the tumor suppressor pRB. E2F1 physiologically activated by growth stimulation activates growth-related genes and promotes cell proliferation. In contrast, upon loss of pRB function due to oncogenic changes, E2F1 is activated out of restraint by pRB (deregulated E2F1) and stimulates tumor suppressor genes such as ARF, which activates the tumor suppressor p53, to suppress tumorigenesis. We have recently reported that DDX5 augments deregulated E2F1 activity to induce tumor suppressor gene expression and apoptosis. During the analyses, we noted that over-expression of E2F1 increased DDX5 expression, suggesting a feed forward loop in E2F1 activation through DDX5. Objective: We thus examined whether the DDX5 gene is a target of deregulated E2F1. Method: For this purpose, we performed promoter analysis and ChIP assay. Result: The DDX5 promoter did not possess typical E2F binding consensus but contained several GC repeats observed in deregulated E2F1 targets. Insertion of point mutations in these GC repeats decreased responsiveness to deregulated E2F1 induced by over-expression of E2F1, but scarcely affected responsiveness to growth stimulation. ChIP assays showed that deregulated E2F1 induced by over-expression of E2F1 or expression of E1a, which binds pRB and releases E2F1, bound to the DDX5 gene, while physiological E2F1 induced by growth stimulation did not. Conclusions: These results suggest that the DDX5 gene is a target of deregulated E2F1, generating a feed forward loop mediating tumor suppressive E2F1 activity. Full article

Emotion regulation is essential for mental health. However, many people ignore their own emotional regulation or are deterred by the high cost of psychological counseling, which poses significant challenges to making effective support widely available. This review systematically examines the convergence of multimodal sensing technologies and large language models (LLMs) for the development of Automated Emotional Regulation (AER) systems. The review draws upon a comprehensive analysis of the existing literature, encompassing research papers, technical reports, and relevant theoretical frameworks. Key findings indicate that multimodal sensing offers the potential for rich, contextualized data pertaining to emotional states, while LLMs provide improved capabilities for interpreting these inputs and generating nuanced, empathetic, and actionable regulatory responses. The integration of these technologies, including physiological sensors, behavioral tracking, and advanced LLM architectures, presents the improvement of application, moving AER beyond simpler, rule-based systems towards more adaptive, context-aware, and human-like interventions. Opportunities for personalized interventions, real-time support, and novel applications in mental healthcare and other domains are considerable. However, these prospects are counterbalanced by significant challenges and limitations. In summary, this review synthesizes current technological advancements, identifies substantial opportunities for innovation and application, and critically analyzes the multifaceted technical, ethical, and practical challenges inherent in this domain. It also concludes that while the integration of multimodal sensing and LLMs holds significant potential for AER, the field is nascent and requires concerted research efforts to realize its full capacity to enhance human well-being. Full article

Soil salinization severely limits plant growth and productivity. Mulberry (Morus alba L.), an economically and ecologically important tree, is widely cultivated, yet its salt-tolerance mechanisms at the seedling stage remain insufficiently understood. This study investigated the physiological and biochemical responses of two-year-old mulberry (‘Tailai Sang’) seedlings subjected to six NaCl treatments (0, 50, 100, 150, 200, and 300 mmol L⁻¹) for 28 days. Results showed that growth parameters and photosynthetic gas exchange exhibited dose-dependent declines. The reduction in net photosynthetic rate (Pn) was attributed to both stomatal limitations (decreased stomatal conductance) and non-stomatal limitations, as evidenced by a significant decrease in the maximum quantum efficiency of photosystem II (Fv/Fm) under high salinity. To cope with osmotic stress, seedlings accumulated compatible solutes, including soluble sugars, proteins, and proline. Critically, mulberry seedlings demonstrated effective ion homeostasis by sequestering Na⁺ in the roots to maintain a high K⁺/Na⁺ ratio in leaves, a mechanism that was compromised above 150 mmol L⁻¹. Concurrently, indicators of oxidative stress—malondialdehyde (MDA) and H₂O₂—rose significantly with salinity, inducing the activities of antioxidant enzymes (SOD, CAT, APX, and GR), which peaked at 150 mmol L⁻¹ before declining under extreme stress. A biomass-based LC₅₀ of 179 mmol L⁻¹ NaCl was determined. These findings elucidate that mulberry salt tolerance is a coordinated process involving three key mechanisms: osmotic adjustment, selective ion distribution, and a robust antioxidant defense system. This study establishes an indicative tolerance threshold under controlled conditions and provides a physiological basis for further field-based evaluations of ‘Tailai Sang’ mulberry for cultivation on saline soils. Full article

Piezo1 is a mechanosensitive non-selective cation channel. Genetic alterations of the channel result in a hematologic phenotype named Hereditary Xerocytosis. With Yoda1 and, more recently, Yoda2, compounds to increase the activity of Piezo1 have become available. However, their concrete effect depends on the nano environment of the channel and hence on the cell type. Here we compare the potency of Yoda1 and Yoda2 in red blood cells (RBCs). We investigate the effect of the compounds on direct channel activity using automated patch clamp, as well as the secondary effects of channel activation on signalling molecules and cellular response. In terms of signalling, we investigate the temporal response of the second messenger Ca²⁺, and in terms of cellular response, the activity of the Gárdos channel. The opening of the Gárdos channel leads to a hyperpolarisation of the RBCs, which is measured by the Macey–Bennekou–Egée (MBE) method. Although the interpretation of the data is not straightforward, we discuss the results in a physiological context and provide recommendations for the use of Yoda1 and Yoda2 to investigate RBCs. Full article

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse—including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring—are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life. Full article

Prolonged inundations are altering coastal forest ecosystems of the southeastern US, causing extensive tree die-offs and the development of ghost forests. This hydrological stressor also alters carbon fluxes, threatening the stability of coastal carbon sinks. This study was conducted to investigate the interactions between hydrological drivers and ecosystem responses by analyzing daily eddy covariance flux data from a wetland forest in North Carolina, USA, spanning 2009–2019. We analyzed temporal patterns of net ecosystem exchange (NEE), gross primary productivity (GPP), and ecosystem respiration (RE) under both flooded and non-flooded conditions and evaluated their relationships with observed tree mortality. Generalized Additive Modeling (GAM) revealed that groundwater table depth (GWT), leaf area index (LAI), NEE, and net radiation (Rn) were key predictors of mortality transitions (R² = 0.98). Elevated GWT induces root anoxia; declining LAI reduces productivity; elevated NEE signals physiological breakdown; and higher Rn may amplify evapotranspiration stress. Receiver Operating Characteristic (ROC) analysis revealed critical early warning thresholds for tree mortality: GWT = 2.23 cm, LAI = 2.99, NEE = 1.27 g C m⁻² d⁻¹, and Rn = 167.54 W m⁻². These values offer a basis for forecasting forest mortality risk and guiding early warning systems. Our findings highlight the dominant role of hydrological variability in ecosystem degradation and offer a threshold-based framework for early detection of mortality risks. This approach provides insights into managing coastal forest resilience amid accelerating sea level rise. Full article

The soil-borne fungal pathogen Verticillium dahliae causes devastating vascular wilt disease in numerous crops, including cotton. In this study, we reveal that VdSOX1, a highly conserved sarcosine oxidase gene, is significantly upregulated during host infection and plays a multifaceted role in fungal physiology and pathogenicity. Functional deletion of VdSOX1 leads to increased fungal virulence, accompanied by enhanced microsclerotia formation, elevated carbon source utilization, and pronounced upregulation of effector genes, including over 50 predicted secreted proteins genes. Moreover, the VdSOX1 knockout strains suppress the expression of key defense-related transcription factors in cotton, such as WRKY, MYB, AP2/ERF, and GRAS families, thereby impairing host immune responses. Transcriptomic analyses confirm that VdSOX1 orchestrates a broad metabolic reprogramming that links nutrient acquisition to immune evasion. Our findings identify VdSOX1 as a central regulator that promotes V. dahliae virulence by upregulating effector gene expression and suppressing host immune responses, offering novel insights into the molecular basis of host–pathogen interactions and highlighting potential targets for disease management. Full article

Urochloa brizantha (Brizantha) is cultivated under varying altitudinal and management conditions. Twelve full-sun (monoculture) plots and twelve shaded (silvopastoral) plots were established, proportionally distributed at 170, 503, 661, and 1110 masl. Evaluations were conducted 15, 30, 45, 60, and 75 days after establishment. The conservation and integration of trees in silvopastoral systems reflected a clear anthropogenic influence, evidenced by the preference for species of the Fabaceae family, likely due to their multipurpose nature. Although the altitudinal gradient did not show direct effects on soil properties, intermediate altitudes revealed a significant role of CaCO₃ in enhancing soil fertility. These edaphic conditions at mid-altitudes favored the leaf area development of Brizantha, particularly during the early growth stages, as indicated by significantly larger values (p < 0.05). However, at the harvest stage, no significant differences were observed in physiological or productive traits, nor in foliar chemical components, underscoring the species’ high hardiness and broad adaptation to both soil and altitude conditions. In Brizantha, a significant reduction (p < 0.05) in stomatal size and density was observed under shade in silvopastoral areas, where solar radiation and air temperature decreased, while relative humidity increased. Nonetheless, these microclimatic variations did not lead to significant changes in foliar chemistry, growth variables, or biomass production, suggesting a high degree of adaptive plasticity to microclimatic fluctuations. Foliar ash content exhibited an increasing trend with altitude, indicating greater efficiency of Brizantha in absorbing calcium, phosphorus, and potassium at higher altitudes, possibly linked to more favorable edaphoclimatic conditions for nutrient uptake. Finally, forage quality declined with plant age, as evidenced by reductions in protein, ash, and In Vitro Dry Matter Digestibility (IVDMD), alongside increases in fiber, Neutral Detergent Fiber (NDF), and Acid Detergent Fiber (ADF). These findings support the recommendation of cutting intervals between 30 and 45 days, during which Brizantha displays a more favorable nutritional profile, higher digestibility, and consequently, greater value for animal feeding. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Potato (Solanum tuberosum L.) crop yields may be reduced by nitrogen deficiency stress tolerance. An evaluation of 144 tetraploid potato genotypes was carried out during two consecutive seasons (2019 and 2020), with the objective of characterizing their variability in key physiological and agronomic parameters. Physiological parameters included chlorophyll content and fluorescence, stomatal conductance, NDVI, leaf area, and perimeter, while agronomic characteristics such as yield, tuber fresh weight, tuber number, starch content, dry matter, and reducing sugars were evaluated. To genotype the population, the GGP V3 Potato array was used, generating 18,259 high-quality SNP markers. Marker–trait association analysis was conducted using the GWASpoly package in R, applying Q + K linear mixed models to enhance precision. This methodology enabled the identification of 18 SNP markers that exhibited statistically significant associations with the traits analyzed in both trials and periods, relating them to genes whose functional implication has already been described. Genetic loci associated with chlorophyll content and tuber number were detected across non-stress and stress treatments, while markers linked to leaf area and leaf perimeter were identified specifically under nitrogen deficiency stress. The genomic distribution of these markers revealed that genetic markers or single-nucleotide polymorphisms (SNPs) correlated with phenotypic traits under non-stress conditions were predominantly located on chromosome 11, whereas SNPs linked to stress responses were mainly identified on chromosomes 2 and 3. These findings contribute to understanding the genetic mechanisms underlying potato tolerance to nitrogen deficiency stress, offering valuable insights for the development of future marker-assisted selection programs aimed at improving nitrogen use efficiency and stress resilience in potato breeding. Full article

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions influenced both latewood width and earlywood vessel size in the first row. Latewood was positively correlated with precipitation and temperature, with the long-term positive effect of winter water supply supported by SPEI. In contrast, vessel size showed negative correlations, also reflecting a long-term negative effect of winter precipitation. Consequently, conditions that enhanced latewood width and overall tree-ring growth appear to be associated with the formation of smaller earlywood vessels. Although ample winter precipitation replenishes soil water reserves and supports prolonged wood formation, it may also induce anaerobic soil conditions that promote root fermentation, depleting carbohydrates needed for cell turgor and expansion, and ultimately regulating earlywood vessel size. This physiological decoupling may help explain the lack of a significant correlation between latewood width and earlywood vessel size, underscoring their independent responses to environmental influences. Our findings highlighted the complex interplay between various climatic conditions affecting Q. faginea, with implications for understanding its adaptive capacity in changing climates. Full article

Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient levels on maize seedling growth and primary metabolite profiles. Methods: Seedlings were treated with N-modified nutrient solution, which contained 0% to 120% of the standard nitrogen level (8.5 mM). Results: Nitrogen starvation (N0) significantly reduced plant height (by 11–14%), shoot fresh weight (over 30%) compared to the optimal N supply (N100). Total leaf nitrogen content under N0–N20 was less than half of that in N100, whereas moderate N deficiency resulted in moderate reductions in growth and nitrogen content. Metabolite analysis revealed that N deficiency induced the accumulation of soluble sugars and organic acids (up to threefold), while sufficient N promoted the synthesis of amino acids related to nitrogen assimilation and protein biosynthesis. Statistical analyses (PCA and ANOVA) showed that both genotypes (MB and TYC) and tissue type (upper vs. lower leaves) influenced the metabolic response to nitrogen, with MB displaying more consistent shifts and TYC exhibiting greater variability under moderate stress. Conclusions: These findings highlight the sensitivity of maize seedlings to early nitrogen deficiency, with severity influenced by nitrogen level, tissue-specific position, and genotype; thus underscore the close coordination between physiological growth and primary metabolic pathways in response to nitrogen availability. These findings expand current knowledge of nitrogen response mechanisms and offer practical insights for improving nitrogen use efficiency in maize cultivation. Full article

This study measured eight key phenotypic traits across 259 fresh maize inbred lines, including plant height and spike length. A total of 82 single nucleotide polymorphisms (SNPs) significantly associated with these phenotypes were identified by applying a mixed linear model to calculate the best linear unbiased prediction (BLUP) values and integrating genome-wide genotypic data through genome-wide association analysis (GWAS). A further analysis of significant SNPs contributed to the identification of 63 candidate genes with functional annotations. Notably, 11 major candidate genes were identified from multi-trait association loci, all of which exhibited highly significant P-values (<0.0001) and explained between 7.21% and 12.78% of phenotypic variation. These 11 genes, located on chromosomes 1, 3, 4, 5, 6, and 9, were functionally involved in signaling, metabolic regulation, structural maintenance, and stress response, and are likely to play crucial roles in the growth and physiological processes of fresh maize inbred lines. The functional genes identified in this study have significant implications for the development of molecular markers, the optimization of breeding strategies, and the enhancement of quality in fresh maize. Full article

Aronia melanocarpa (black chokeberry) is a medicinally valuable small fruit species, yet its commercial propagation remains limited by low rooting and genotype-specific responses. This study developed an efficient, callus-free micropropagation and rooting protocol using a Shrub Plant Medium (SPM) supplemented with 5 mg/L BAP in large 660 mL jars, which yielded up to 27 shoots per explant. Optimal rooting (100%) was achieved with 0.5 mg/L NAA + 0.25 mg/L IBA in half-strength SPM. In the second phase, supervised machine learning models, including Random Forest (RF), XGBoost, Gaussian Process (GP), and Multilayer Perceptron (MLP), were employed to predict morphogenic traits based on culture conditions. XGBoost and RF outperformed other models, achieving R² values exceeding 0.95 for key variables such as shoot number and root length. These results demonstrate that data-driven modeling can enhance protocol precision and reduce experimental workload in plant tissue culture. The study also highlights the potential for combining physiological understanding with artificial intelligence to streamline future in vitro applications in woody species. Full article