Search Results (630)

Methyl farnesoate (MF) is a sesquiterpenoid hormone that controls a variety of physiological processes in crustaceans, including morphogenesis, development, reproduction, and molting. MF action is mediated by a transcriptional signaling cascade consisting of Methoprene-tolerant (Met), Steroid receptor coactivator (Src), Krüppel homolog 1 (Kr-h1), and Ecdysone response gene 93 (E93) transcription factors (TFs), and transcriptional co-regulators CREB-binding protein (CBP) and C-terminal-binding protein (CtBP). Phylogenetic and sequence analyses revealed that these genes were highly conserved across pancrustacean species. Met and Src were characterized as basic helix-loop-helix, Period (Per)-Aryl Hydrocarbon Nuclear Translocator (ARNT)-Single-minded (Sim) protein (bHLH-PAS) TFs; Kr-h1 was characterized as a C₂H₂ zinc finger TF with seven zinc finger motifs; E93 was characterized as a helix-turn-helix, pipsqueak (HTH_Psq) TF. CBP was identified by several zinc finger-binding regions with Transcription Adaptor Zinc Finger 1 and 2, Really Interesting New Gene, Plant homeodomain, and Z-type zinc finger domains; the Kinase-inducible Domain Interacting-transcription factor docking site; the Bromodomain-acetylated lysine recognition and binding site; the histone acetyltransferase domain; and a C-terminal CREB-binding region containing a nuclear receptor co-activator-binding domain. CtBP had a dehydrogenase domain with arginine-glutamate-histidine catalytic triad. 81 Met contigs, 45 Src contigs, 136 Kr-h1 contigs, 66 E93 contigs, 60 CBP contigs, and 172 CtBP contigs were identified across pancrustacean taxa, including decapod crustaceans. Bioinformatic identification and annotation of these TFs and co-regulators in brachyuran Y-organ (YO) transcriptomes suggests that MF signaling influences YO ecdysteroidogenesis; functional tests in the YO are needed to establish causality. Full article

Background/Objectives: Trace metals, including copper (Cu) and zinc, are associated with the development and prognosis of hepatocellular carcinoma (HCC). However, their interference with magnetic resonance imaging (MRI) limits their use as potential biomarkers. This study investigated the usefulness of Synchrotron Radiation–excited X-ray Fluorescence (SR-XRF) imaging in studying the distribution of trace metals in HCC. Methods: This case–control study analyzed 33 specimens from 32 patients with HCC who underwent surgical resection (n = 29) or biopsy (n = 3) at Kobe University Hospital between December 1999 and November 2002. The findings of SR-XRF were compared with those of MRI and histopathology. Results: SR-XRF provided two-dimensional mapping of trace metal distribution with high spatial resolution (1.0 µm). The mean tumor-to-liver ratio (TLR) of Cu content was significantly higher in well-differentiated HCCs than in moderately and poorly differentiated HCCs (p < 0.05). Moreover, the mean TLRs of Cu content were significantly higher in high-intensity lesions than in iso- or low-intensity lesions on T1-weighted imaging (p < 0.05). Conclusions: This study supports previous evidence of the involvement of Cu in HCC development, suggesting its potential as a clinical biomarker for diagnosis and disease progression. Additionally, the results demonstrate that SR-XRF has potential for clinical application due to its ability to map trace metal distribution at high resolution. These findings suggest, rather than demonstrate, the association among Cu accumulation, tumor differentiation, and MRI signal characteristics. Full article

Acid-sensing ion channels (ASICs), activated under acidic conditions, play a critical role in ischemic brain injury, but the detailed mechanisms and signaling pathways remain unclear. Our previous studies have shown that activation of ASIC1a channels contributes to acidosis-induced neuronal injury, partially mediated by increased calcium influx. In this study, we provide evidence that activation of ASIC2a-containing channels induces zinc influx. In cultured mouse cortical neurons, ASIC currents that were insensitive to PcTx1 inhibition were potentiated by extracellular zinc. In Chinese Hamster Ovary cells transfected with different ASIC subunits, large inward currents were recorded upon a pH drop from 7.4 to 5.0 in cells expressing homomeric ASIC1a, ASIC2a, or heteromeric ASIC1a/2a channels when normal Na⁺-rich extracellular fluid (ECF) was used. However, when ECF was modified to one containing zinc as the primary cation, the same pH drop induced an inward current only in cells expressing homomeric ASIC2a or heteromeric ASIC1a/2a, but not homomeric ASIC1a. Fluorescence imaging revealed rapid zinc influx in cells expressing ASIC2a but not ASIC1a when zinc was applied with the acidic ECF. Additionally, at pH values where ASIC2a-containing channels were activated, acid-mediated neurotoxicity was exacerbated by zinc. Thus, ASIC2a-containing channels may represent a novel pathway for zinc entry and activation of these channels might contribute to zinc-mediated neurotoxicity. Full article

Micronutrients, particularly boron (B), iron (Fe), manganese (Mn), and zinc (Zn), are pivotal for cotton (Gossypium spp.) growth, reproductive success, and fiber quality. However, their critical roles are often overlooked in fertility programs focused primarily on macronutrients. This review synthesizes recent advances in the physiological, molecular, and agronomic understanding of B, Fe, Mn, and Zn in cotton production. The overarching goal is to elucidate their impact on cotton nutrient use efficiency (NUE). Drawing from the peer-reviewed literature, we highlight how these micronutrients regulate essential processes, including photosynthesis, cell wall integrity, hormone signaling, and stress remediation. These processes directly influence root development, boll retention, and fiber quality. As a result, deficiencies in these micronutrients contribute to significant yield gaps even when macronutrients are sufficiently supplied. Key genes, including Boron Transporter 1 (BOR1), Iron-Regulated Transporter 1 (IRT1), Natural Resistance-Associated Macrophage Protein 1 (NRAMP1), Zinc-Regulated Transporter/Iron-Regulated Transporter-like Protein (ZIP), and Gossypium hirsutum Zinc/Iron-regulated transporter-like Protein 3 (GhZIP3), are crucial for mediating micronutrient uptake and homeostasis. These genes can be leveraged in breeding for high-yielding, nutrient-efficient cotton varieties. In addition to molecular hacks, advanced phenotyping technologies, such as unmanned aerial vehicles (UAVs) and single-cell RNA sequencing (scRNA-seq; a technology that measures gene expression at single-cell level, enabling the high-resolution analysis of cellular diversity and the identification of rare cell types), provide novel avenues for identifying nutrient-efficient genotypes and elucidating regulatory networks. Future research directions should include leveraging microRNAs, CRISPR-based gene editing, and precision nutrient management to enhance the use efficiency of B, Fe, Mn, and Zn. These approaches are essential for addressing environmental challenges and closing persistent yield gaps within sustainable cotton production systems. Full article

Seed vigor is a key agronomic trait that integrates germination capacity and seedling establishment, critically influencing rice productivity. Inositol hexakisphosphate (IP₆) serves as a major phosphorus reservoir in seeds, yet its regulatory mechanism in seed vigor remains unclear. Here, we demonstrate that exogenous IP₆ application inhibited seed germination and seedling growth of japonica rice (Oryza sativa L. ssp. japonica cv. Zhonghua11) in a dose-dependent manner; 10 mM IP₆ reduced seed germination by 100%, while 100 μM IP₆ suppressed primary root length by 33.6% compared to the control. This inhibitory effect is likely mediated by antagonizing auxin signaling, as supported by suppressed DR5::GUS expression and altered transcription of auxin-responsive genes. OsIPK2, a key enzyme in IP₆ biosynthesis, showed high expression during early development in rice. RNA interference of OsIPK2 led to a 40.8–61.7% reduction in seed IP₆ content, 45.3–65% higher zinc (Zn) and iron (Fe) accumulation, and a 35.4–53.5% lower germination rate compared to wild-type (WT). Conversely, OsIPK2-RNAi seedlings exhibited enhanced growth and resistance to IP₆, which was associated with misregulation of auxin-responsive genes and a decrease in the repressive histone mark H3K27me3 at their loci. Furthermore, endogenous indole-3-acetic acid (IAA) levels significantly reduced in Ri-1 but unchanged in Ri-2, while abscisic acid (ABA) content and the IAA/ABA ratio remained unaltered compared to wild-type. Our findings reveal that OsIPK2 balances seed vigor and seedling development by modulating inositol phosphate metabolism, auxin responses, and epigenetic regulation, providing insights for improving seed quality in cereals. Whether the regulatory role of OsIPK2 in seed vigor is conserved across other rice subspecies requires further investigation. Full article

Iron (Fe), as one of the essential micronutrients for plants, plays a pivotal role in regulating growth and development through homeostatic balance. Fe deficiency is a common agricultural stress that causes visible leaf chlorosis and impairs plant growth. In this study, Arabidopsis thaliana seedlings grown under Fe deficiency for 4 days were subjected to 6 h Fe resupply via foliar spray or root supply, followed by measurements of chlorophyll fluorescence and metal ion contents in leaves and roots. Fe deficiency significantly reduced Fe levels and the maximum quantum yield of fluorescence (Fv/Fm), while increasing copper (Cu) accumulation in roots. Zinc (Zn) and manganese (Mn) levels were also altered, depending on tissue type. Fe resupply restored Fv/Fm, increased Mn levels, and rebalanced micronutrient content. MicroRNA (miRNA) mediates adaptation to Fe deficiency via post-transcriptional regulation in plants. However, the involved regulatory networks of miRNAs under stress conditions during Fe resupply following deficiency remain poorly understood. These physiological changes prompted us to explore the underlying regulatory networks using miRNA-seq and mRNA-seq. The bioinformatics analysis identified differentially expressed miRNAs responsive to Fe stress, with the Fe-deficiency-specific cis-element IDE1 characterized in their promoter regions. By integrating miRNA-seq and mRNA-seq datasets, we constructed a regulatory network and identified 13 miRNAs harboring IDE1 motifs alongside their functional target genes. Three critical Fe homeostasis modules were proposed—miR396b-LSU2, miR401-HEMA1, and miR169b-NF-YA2—that link Fe homeostasis to chlorophyll synthesis, sulfur (S) responses, and developmental signaling. This study integrates physiological phenotyping with transcriptomic insights to provide a comprehensive view of Fe deficiency and recovery in Arabidopsis. Full article

Background: Melanin protects skin and hair from the effects of ultraviolet (UV) radiation damage, which contributes to all forms of skin cancer, including melanoma. Human melanocytes produce two main types of melanin: eumelanin provides effective photoprotection, and pheomelanin offers less protection against UV-induced skin damage. The agouti signaling protein (ASIP) antagonizes the melanocortin-1 receptor (MC1R), hinders melanocyte signaling, and shifts pigmentation toward pheomelanin, promoting UV vulnerability. In this study, we aim to discover compounds that inhibit ASIP–MC1R interaction and effectively preserve eumelanogenic signaling. Methods: The ASIP–MC1R interface-based pharmacophore model from ASIP is implicated in MC1R receptor protein engagement. We performed virtual screening with a validated pharmacophore model for ~4000 compounds curated from ZINCPharmer and applied drug-likeness filters, viz. ADMET and toxicity profiling tests. Further, the screened candidates were targeted for docking to the ASIP C-terminal domain corresponding to the MC1R-binding moiety. Top compounds underwent a 100-nanosecond (ns) run of molecular dynamics (MD) simulations to assess complex stability and persistence of key contacted residues. Results: Sequential triage, including pharmacophore, ADME–toxicity (ADMET), and docking/ΔG, yielded a focused group of candidates against ASIP antagonists with a favorable fit value. The MD run for 100 ns supported pose stability at the targeted pocket. Based on these predictions and analyses, compound ZINC14539068 was screened as a new potent inhibitor of ASIP to preserve α-MSH-mediated signaling of MC1R. Conclusions: Our in silico pipeline identifies ZINC14539068 as a potent inhibitor of ASIP at its C-terminal interface. This compound is predicted to disrupt ASIP–MC1R binding, thereby maintaining eumelanin-biased signaling. These findings motivate experimental validation in melanocytic models and in vivo studies to confirm pathway modulation and anti-melanoma potential. Full article

Amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistors (TFTs) have emerged as promising candidates for next-generation large-area and low-power electronics due to their high mobility, low leakage current, and compatibility with low-temperature fabrication on flexible or transparent substrates. In this work, we report the fabrication of bottom-gate a-IGZO NMOS TFTs using HfO₂ as high-k gate dielectric and Mo top contacts. The devices were electrically characterized through capacitance–voltage (C–V) and current–voltage (I–V) measurements, from which key parameters were extracted. Based on these transistors, we designed, fabricated, and characterized inverters employing four different load configurations: resistive, diode, depletion, and pseudo-CMOS. A comparative analysis was performed in terms of voltage transfer characteristics (VTCs), gain, and noise margins, highlighting that depletion-load inverters offer the highest gain and robust noise margins. Finally, a two-channel multiplexer was designed and fabricated. The multiplexer was characterized under both square and sinusoidal input signals up to 1 kHz, demonstrating correct channel selection and robust switching behavior. These results confirm the potential of a-IGZO TFT-based circuits as building blocks for low-power and high-reliability digital and mixed-signal electronics. Full article

GATA transcription factors, defined by their zinc finger DNA-binding domains, are central regulators of tissue development. They modulate gene expression by activating or repressing transcription, thereby coordinating cellular differentiation and cell cycle exit to maintain homeostasis. In progenitor cells, GATA factors promote proliferation, whereas in differentiating cells, they drive maturation and induce cell cycle arrest. Dysregulation of GATA factors has been linked to tumorigenesis and contributes significantly to cancer progression and metastasis. Mutations in GATA factor genes correlate with poor prognosis in multiple cancers, where they influence key oncogenic processes, including sustained proliferative signaling, activation of epithelial–mesenchymal transition, angiogenesis, resistance to cell death, and immune escape. Importantly, their context-dependent roles across tumor types highlight the complexity of their functions in malignancies. Meanwhile, non-coding RNAs have emerged as critical regulators of gene expression, acting as either tumor suppressors or oncogenes by modulating chromatin dynamics, transcription factor activity, and mRNA stability. Despite this, the regulation of GATA transcriptional activity by non-coding RNAs remains largely unexplored. This review highlights the role of GATA factors in regulating EMT and metastasis and focuses on the interplay between non-coding RNAs and GATA transcription factors in cancer progression, proposing a novel regulatory axis with potential implications for biomarker discovery and therapeutic targeting. Full article

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article

Protein S-palmitoylation is a pivotal yet poorly integrated research field in dermatology. This reversible post-translational lipid modification primarily occurs on cysteine residues and is principally catalyzed by zinc finger and Asp-His-His-Cys DHHC-domain containing proteins (zDHHCs). The S-palmitoylation/depalmitoylation cycle directly affects protein localization, trafficking, stability, and protein–protein interaction, thereby regulating a variety of signaling pathways, including those mediating inflammation and immune reaction. Accumulating evidence has indicated that S-palmitoylation regulates various skin biological functions, including skin inflammation, skin barrier function, hair growth, and melanin synthesis, and is ultimately implicated in the initiation and development of massive dermatoses, such as alopecia and psoriasis. The recent development of new research tools, coupled with S-palmitoylation’s therapeutic potential, makes the timely synthesis of its role in skin pathophysiology both critical and opportune. Here, we summarize recent advances in understanding the mechanistic roles of S-palmitoylation in dermatological conditions and evaluate its potential as a therapeutic target for innovative treatment strategies. Full article

Dynamic environmental changes significantly affect trace element balance and exposure to toxic metals, influencing vascular homeostasis. The endothelium, as a key regulator of vascular tone and inflammation, is highly sensitive to fluctuations in micronutrient and heavy metal concentrations. This review summarizes current evidence on the molecular mechanisms by which essential trace elements, such as zinc, selenium, copper, and magnesium, support endothelial function through antioxidant defense, nitric oxide regulation, and anti-inflammatory signaling. Conversely, exposure to heavy metals including cadmium, lead, mercury, and arsenic induces oxidative stress, disrupts nitric oxide bioavailability, and promotes endothelial dysfunction, accelerating the pathogenesis of many diseases. The paper examines how these alterations contribute to the development of major cardiovascular diseases and outlines preventive measures to reduce associated risks. Understanding these interactions is crucial for society’s health amid growing environmental challenges. Full article

Exercise acts as a physiological stimulus, requiring precise coordination among endocrine, microbial, and mitochondrial systems to maintain metabolic stability through allostatic regulation. The goal of the article is to integrate multidisciplinary evidence to characterize the thyroid–microbiome–mitochondrial axis as a key regulator of the allostatic state in athletic physiological response. During acute, chronic, and overload training phases, the thyroid–microbiome–mitochondrial axis operates bidirectionally, coupling microbial signaling with endocrine and mitochondrial networks to mediate metabolic response to exercise. This response shows interindividual variability driven by sex, age, genetics, and nutritional status, shaping the boundaries between adaptive efficiency and allostatic overload. Microbial metabolites, such as short-chain fatty acids (SCFA) and secondary bile acids, modulate deiodinase activity, bile acid recycling, and mitochondrial biogenesis through AMPK–SIRT1–PGC1α signaling, optimizing substrate use and thermogenic capacity. Thyroid hormones reciprocally regulate gut motility, luminal pH, and bile secretion, maintaining microbial diversity and mineral absorption. Under excessive training load, caloric restriction, or inadequate recovery, this network becomes transiently unbalanced: SCFA synthesis decreases, D3 activity increases, and a reversible low-T₃/high-rT₃ pattern emerges, resembling early Hashimoto- or Graves-like responses. Selenium-, zinc-, and iron-dependent enzymes form the redox link between microbial metabolism, thyroid control, and mitochondrial defense. In conclusion, the thyroid–microbiome–mitochondrial axis provides the physiological basis for the allostatic state, a reversible phase of dynamic recalibration that integrates training, nutrition, environmental stress, and circadian cues to sustain thyroid activity, mitochondrial efficiency, and microbial balance. This integrative perspective supports precision interventions to optimize recovery and performance in athletes. Full article

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1’s role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell fate. Retinoic acid-induced differentiation downregulated INSM1 and N-Myc, linking INSM1 to tumor cell immaturity. INSM1 overexpression in SH-SY-5Y cells upregulated neuroendocrine and thyroid hormone-related genes (CHGA, CHGB, DDC, NCAM1, DIO3, TH), while suppressing genes involved in cell cycle (RRM, CDC25A), methionine metabolism (AHCY, MAT2A), transcriptional regulation (MYBL2, EZH2), and oncogenic signaling (ALK, LINC011667). These findings suggest that INSM1 promotes NB aggressiveness by sustaining a neuroendocrine progenitor-like phenotype through metabolic-epigenetic coupling. Full article

Efficient synthesis routes for zinc oxide nanoparticles (ZnO NPs) that are rapid and non-toxic and operate at room temperature (RT) are essential to expand accessibility, minimize environmental impact, and enable integration with temperature-sensitive substrates. In this work, ZnO NPs were synthesized by probe ultrasonication at RT for durations from 30 s to 10 min and benchmarked against our previously reported water bath sonication method. A 10-min probe treatment yielded highly uniform ZnO NPs with particle sizes of 60–550 nm and a specific surface area of up to 75 m² g⁻¹, compared to ~38 m² g⁻¹ for bath sonication. These features were largely preserved after calcination at 500 °C. When integrated into chemiresistive devices, the resulting ZnO (P(10))-based sensors exhibited pronounced selectivity toward styrene, showing reversible responses at low concentrations (10–50 ppm) and stronger signals at higher levels (up to 200 ppm, with resistance changes reaching 2930%). The sensors demonstrated stable operation across 10–90% relative humidity, and consistent performance from −20 °C to 180 °C. Flexibility tests confirmed reliable sensing after 100 bending cycles at 30°. Overall, RT-probe ultrasonication offers a rapid, scalable, and eco-friendly route to ZnO NPs with tunable properties, opening new opportunities for flexible gas sensing. Full article