Search Results (1,637)

Plants are sessile organisms that use molecular oxygen to perform basic metabolic functions. However, when oxygen availability decreases to 1–5% (hypoxic stress), the plant responds transcriptionally to adjust its metabolism and survive the stress. It has been observed that during hypoxia, adenosine triphosphate (ATP) levels decrease drastically, which could trigger plant death. However, despite experiencing an energy deficit, it has been observed that during hypoxia, plants induce defense mechanisms against pathogens. Plants manage to evade pathogenic microorganisms during an energy deficit by using complex signaling networks and different levels of regulation (transcriptional, post-translational, physiological, metabolomic, etc.) that converge to respond to both types of stress (biotic and abiotic). Understanding this phenomenon would have potential applications for agriculture and crop improvement. Therefore, this review details the main mechanisms of plant response to hypoxia and how this affects immunity mechanisms, highlighting the participation of ERF-VII transcription factors as oxygen sensors and their ability to bind to the GCC-box present in promoter regions of defense genes, MAPK signaling pathways, hormonal pathways, ROS, and Ca²⁺. Full article

Molecularly imprinted polymers (MIPs) are widely employed for selective adsorption of target molecules in sensing and separation applications. The architecture of MIP films can influence adsorption behavior, interfacial stability, and reusability, yet systematic investigations of these effects are limited. This study aimed to evaluate how different polypyrrole (PPy) MIP film architectures affect the adsorption, stability, and regeneration characteristics of geraniol-imprinted layers on gold electrodes. Geraniol-imprinted and non-imprinted PPy films were electropolymerized onto quartz crystal microbalance (QCM) substrates. Two film architectures were compared: (i) a single-layer geraniol-imprinted PPy film, and (ii) a double-layer film consisting of a non-imprinted PPy underlayer followed by a geraniol-imprinted layer. Film characterization was performed using cyclic voltammetry (CV) and electrochemical quartz crystal microbalance (EQCM) measurements. Adsorption–desorption cycles were conducted to assess mass uptake, signal stability, and regeneration performance. EQCM analysis revealed that the double-layer architecture exhibited enhanced frequency signal stability during repeated adsorption–desorption cycles compared to single-layer films, suggesting a stabilizing effect of the underlying non-imprinted PPy layer at the electrode interface. Geraniol-imprinted films demonstrated significantly higher mass uptake than non-imprinted controls, confirming the sensitivity provided by molecular imprinting. Single-layer films showed more variability in signal response and less consistent regeneration performance. The architecture of MIP films significantly affects adsorption behavior, stability, and regeneration on electrode surfaces. Incorporating a non-imprinted PPy underlayer can improve signal reproducibility and enhance the robustness of MIP-based sensing interfaces. These findings provide guidance for the rational design of MIP coatings for electrochemical sensors and QCM-active platforms. Full article

Background: Tumor cells can reprogram their metabolism, constituting a hallmark of cancer that plays a crucial role in tumor progression. As tumor cells exhibit an increased demand for nutrients, e.g., amino acids, they rely on extracellular sources and show deregulation of transport proteins. Among these, SNAT1 (SLC38A1) is described as the loader for glutamine that is responsible for the main influx of this amino acid. The aim of this study was to assess the molecular function of SNAT1 in melanoma regarding its role in amino acid transport and regulation of cellular metabolism. Methods: siPool-mediated downregulation of SNAT1 expression in melanoma cell lines was used to investigate the molecular function of this protein. Glutamine transport was assessed by measuring the intracellular and extracellular concentrations of glutamine. Regulation of downstream effectors was evaluated with qRT-PCR and Western Blot. Metabolism was investigated by performing Seahorse flux analysis. Mitochondrial staining was examined via flow cytometry. Protein interaction was assessed with Co-IP, and in silico modeling of protein interaction was performed with AlphaFold3. Results: In this study, we uncovered the new finding that SNAT1 is not primarily implicated in glutamine influx into melanoma cells but in signaling in response to extracellular glutamine. We identified P62 and cMYC as downstream effectors of SNAT1. By activating the P62/cMYC-axis and target genes of cMYC, SNAT1 modulates the metabolism of melanoma cells depending on the glutamine level. SNAT1 and P62 are interaction partners. Conclusions: This finding newly suggests that SNAT1 may function as a sensor or receptor (“transceptor”) for glutamine rather than being a direct and primary glutamine transporter, and could open up new therapeutic options targeting melanoma cells. Full article

This study explored the electronic and structural tunability of fullerene (C₆₀) derivatives via functionalization with heteroatoms (O, S, Se) in mono-, di-, and tri-bridged configurations, including covalently modeled dimers. Calculations were performed using density functional theory (DFT) at the B3LYP/6-31G(d,p) level. Electronic descriptors such as total dipole moments (TDMs), HOMO–LUMO energy gaps (ΔE), global reactivity descriptors, total density of states (TDOS), molecular electrostatic potential (MESP) and non-covalent interactions (NCIs) were analyzed to elucidate how functionalization alters reactivity and stability. Key findings indicate that TDM increases and ΔE decreases in all functionalized C₆₀; for example, the TDM increased from 0 Debye for C₆₀ to 2.156 Debye for C₆₀–O–S–Se, and ΔE decreased from 2.762 eV (C₆₀) to 2.532 eV (C₆₀–Se), indicating enhanced reactivity. This aligns with global reactivity descriptors such as reduced ionization energy and hardness. Mapped MESP surfaces showed activation around heteroatom sites. Quantum theory of atoms in molecules (QTAIM) and NCI analyses revealed that while mono-bridged structures retain covalent linkages, dimeric systems such as C₆₀–O–C₆₀ and C₆₀–S–C₆₀ relax into weak, van der Waals-type interactions. OPDOS (overlap population density of states) highlighted antibonding character between the fragments in the conduction region. These results demonstrate that heteroatom functionalization enhances the electronic properties of C₆₀, making it a promising candidate for optoelectronic, organic photovoltaic, and sensor applications. Full article

Chronic Kidney Disease (CKD) is a global health crisis, projected to be the fifth leading cause of death by 2040. Its progression is driven by a reinforcing loop of mitochondrial dysfunction, oxidative stress, and chronic inflammation. The AMPK-NRF2–FOXO axis serves as a central “redox-metabolic rheostat” that maintains renal homeostasis but is commonly dysfunctional in CKD. Herein, we explore the molecular crosstalk within this network, where AMPK acts as a metabolic and redox sensor, NRF2 governs the cytoprotective response, and FOXO isoforms regulate autophagy, antioxidative defense, and senescence. We highlight the functional paradoxes within the axis and evaluate the benefits and drawbacks of nutraceuticals and pharmacological agents, such as NRF2 inducer bardoxolone methyl, underscoring the necessity for context-dependent modulation. Furthermore, we examine the AMPK–NRF2–FOXO axis within the current clinical management, according to the 2024/2026 KDIGO guidelines. These guidelines reflect a shift toward a multi-targeted pharmacological approach involving metformin, SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, and hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors. Full article

Electrochemical sensors are user-friendly devices designed for the rapid and straightforward detection of target analytes. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter and neuromodulator that regulates diverse neuronal processes. Using a custom-designed screen-printed carbon electrode (SPCE) incorporating ordered mesoporous carbon–bimetal oxides of Cu and Ni (CuO–NiO–OMC), rapid and real-time detection of 5-HT was achieved. The CuO–NiO–OMC structure featured highly active CuO and NiO catalytic sites that effectively promoted the irreversible oxidation of 5-HT (vs. Ag/AgCl reference electrode). The CuO–NiO–OMC/SPCE sensor, connected to a portable potentiostat, exhibited exceptional electrocatalytic performance for the oxidation of 5-HT, with a detection limit of 42.5 nM. The sensitivity was 1.56 A M⁻¹ cm⁻², and the linear dynamic range was 0.0–80.0 µM. The CuO–NiO–OMC/SPCE sensor also demonstrated outstanding selectivity in the presence of competing neurochemicals, including norepinephrine, epinephrine, dopamine, and glutamate, as well as high concentrations of tested biomolecules and inorganic ions. Furthermore, the practicality of the sensor was demonstrated using human serum and urine samples, with recovery percentages ranging from 91.1% to 98.3%. Thus, the CuO–NiO–OMC/SPCE sensor offers an effective approach for 5-HT sensing, thereby permitting molecular-level understanding of brain function. Full article

Background: Multiple myeloma (MM) is characterised by clonal expansion of plasma cells (PCs) in the bone marrow (BM). Disease assessment and monitoring typically rely on invasive, single-site procedures, such as BM biopsies (BMBs), which may inadequately capture intra- and extra-medullary spatial heterogeneity. Circulating plasma cells (CPCs), enriched from peripheral blood (PB), may represent a minimally invasive alternative or adjunct for molecular profiling. Objectives: This study aimed to evaluate the feasibility of using CPCs, enriched from PB, for mRNA analysis in plasma cell dyscrasia, including MM. A secondary objective was to assess whether mRNA expression levels of the endoplasmic reticulum (ER) stress sensors X-box-binding protein 1 (uXBP1) and activating transcription factor 6 (ATF6), and the chaperone-mediated autophagy marker Lysosomal-Associated Membrane Protein 2 (LAMP2A) by droplet digital PCR (ddPCR), were associated with resistance to the second-generation proteasome inhibitor (PI) carfilzomib (Cfz). Methods: Multiple myeloma (MM) cell lines (H929 and U266) and their carfilzomib-adapted derivatives were used to establish and validate droplet digital PCR (ddPCR) assays targeting ER stress (uXBP1, ATF6) and autophagy-related (LAMP2A) transcripts. Solid tumour cell lines, including serum-starved HeLa cells, served as biological controls to support assay specificity and sensitivity. Total RNA was extracted and reverse-transcribed to complementary DNA prior to analysis. Transcript levels were normalised to those of β-actin or GAPDH, as appropriate. ddPCR was performed using the BioRad QX200 system, with results reported as the normalised transcript copy number per microlitre of reaction. Matched bone marrow aspirate (BMA) and peripheral blood (PB) samples were collected at a single clinical time point from adults undergoing investigation for plasma cell dyscrasia between January 2021 and December 2023. Samples were obtained as part of standard clinical care and/or during treatment with Bortezomib (Btz) or Cfz. Mononuclear cells were isolated by density gradient centrifugation, and CD138⁺ plasma cells were enriched by fluorescence-activated cell sorting. Enrichment purity was assessed qualitatively by immunofluorescence microscopy using CD138 and CD117 markers. Samples yielding fewer than 1000 CD138⁺ plasma cells were excluded, resulting in 10 evaluable matched patient pairs. Results: Carfilzomib-adapted MM cell lines demonstrated reduced levels of uXBP1, ATF6, and LAMP2A mRNA compared to treatment-naïve cells. In matched BM and PB samples, uXBP1 mRNA levels were consistently lower in circulating PCs than in BM-derived PCs, whereas ATF6 mRNA levels were concordant between compartments. LAMP2A mRNA levels exhibited marked inter-patient heterogeneity. Conclusions: This study demonstrates the feasibility of using CPCs as a minimally invasive source for mRNA-based biomarker assessment and highlights ddPCR as a sensitive platform for quantifying ER stress and chaperone-mediated autophagy related transcripts in CPCs. Cfz adaptation was associated with reduced levels of uXBP1 and LAMP2A mRNA in MM cell lines. Future prospective studies evaluating the clinical utility of ER stress and chaperone-mediated autophagy associated transcripts in CPCs as predictors of resistance to PI are warranted. Full article

Novel, accurate molecular diagnostics are driving new advances across medicine, public health, and environmental monitoring. Surface-enhanced Raman spectroscopy (SERS) nanotags are powerful platforms for ultrasensitive, multiplexed, and quantitative detection of molecular targets. This review focuses on indirect sensing strategies, where SERS nanotags act as signal transducers, resulting in enhanced and unique Raman spectra upon binding of target analytes (high specificity) and allowing for ultralow limits of detection. These indirect SERS sensors typically consist of a plasmonic core, a Raman reporter molecule, and a ligand that targets the analyte of interest. Each of these components contributes to the sensitivity, stability, and selectivity of the system. Rational design of SERS nanotags requires balancing enhancement efficiency with reproducibility, biocompatibility, and assay integration. The choice of reporter molecules, for instance, governs spectral uniqueness and enables multiplexed detection of multiple analytes within a single sample. Recent advances in artificial intelligence and machine learning are accelerating nanotag development by enabling predictive control over nanostructure geometry, composition, and optical response. SERS nanotags are increasingly being integrated into diagnostic formats, such as lateral flow assays and microfluidic devices, offering both qualitative and quantitative analysis at the point of care. This review provides an overview of key design principles, common strategies for nanostructure functionalization and stabilization, and emerging biosensing applications, serving as a practical guide for researchers seeking to design and implement SERS nanotags. Full article

Candida albicans (C. albicans) is an opportunistic fungal pathogen and a major cause of nosocomial infections, especially in immunocompromised patients. Conventional diagnostic approaches such as blood culture and biochemical assays are accurate but require multi-step sample processing and prolonged turnaround times, limiting their applicability for rapid clinical screening. In the present study, we developed an electrochemical biosensor based on molecularly imprinted polymer (MIP) technology for the rapid and selective detection of intact C. albicans cells. The MIP layer was electropolymerized onto a screen-printed carbon electrode (SPCE), forming selective recognition cavities complementary to the fungal morphology. Electrochemical characterization and detection were performed using cyclic voltammetry in phosphate-buffered saline (PBS). The system demonstrated a wide linear detection range, enabling reliable quantification of C. albicans across concentrations spanning from 1 to 10⁴ CFU/mL and achieved an ultralow limit of detection (LOD) of 1.30 CFU/mL, demonstrating high sensitivity. High selectivity was confirmed against E. coli, S. aureus, and P. aeruginosa, demonstrating that the imprinted cavities effectively distinguish fungal cells from bacterial contaminants. These findings highlight the promise of MIP-based electrochemical biosensors as a simple, low-cost, and portable alternative for early fungal diagnostics. Full article

The hypothalamic–pituitary–adrenal (HPA) axis coordinates metabolic, immune, and behavioral responses to a changing environment. Its molecular effectors are the nuclear receptors for glucocorticoids and mineralocorticoids (the GRs/MRs), encoded by nr3c1/nr3c2. The MR serves as the high-affinity sensor of basal hormone concentrations, whereas the GR amplifies the stress response and mediates negative feedback. Despite their shared domain architecture, the receptors have diverged functionally: isoform composition, post-translational modifications, and the complement of co-regulators together determine which genes are activated or repressed in a given tissue at a given time. The regulation of the HPA axis activity is a major determinant of embryonic development. Pregnancy adds a placental control layer that meters maternal signals: 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the syncytiotrophoblast inactivates cortisol, whereas 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) can regenerate it, and systemic buffering by transcortin (cortisol-binding globulin, CBG) limits the free hormone fraction. Under stress, inflammation, or hypoxia, this barrier weakens, exposing the fetus to stronger glucocorticoid pulses during windows of heightened vulnerability for brain and immune development. Such overexposure not only reshapes ongoing transcription but is also epigenetically inscribed: the methylation of alternative nr3c1 promoters, the remodeling of histones, and the shifts in ncRNA profiles recalibrate the axis sensitivity for the long term. At the phenotypic level, this manifests as variability in stress reactivity, cognitive and affective trajectories, and an immune and metabolic risk across later ontogeny. In this review, we integrate evidence on the structure and functions of the GR, the mechanisms of its post-translational and epigenetic regulation, and the role of the placenta, to provide a coherent framework for understanding the multifaceted consequences of prenatal stress and to identify potential targets for early prevention. Full article

Root plasticity is vital for crop survival amid global warming. Yet, the molecular mechanisms governing wheat root thermotolerance remain largely unknown. In this study, we combined phenomics, transcriptomics, and metabolomics with machine learning to analyze the performance of heat-tolerant cultivar YM158 and heat-sensitive cultivar YM15 under varying heat stress. While high temperatures (35 °C) severely inhibited root growth and caused oxidative damage in YM15, YM158 maintained robust root architecture and redox balance. Using weighted gene co-expression network analysis (WGCNA) alongside the random forest feature selection algorithm, we identified the flavonoid biosynthesis pathway as central to thermotolerance. Protein–protein interaction network analysis revealed that wheat root adaptability to high temperatures involves maintaining protein homeostasis via the endoplasmic reticulum protein processing system, specifically activating the flavonoid biosynthesis pathway and enhancing the antioxidant enzyme system. Furthermore, we identified a potential regulatory hub involving the cell wall sensor FERONIA (FER) and heat shock factors (HSFs), highlighting a complex interaction between hormonal signaling and secondary metabolism. Our study offers a detailed map of root heat adaptation and positions the flavonoid-mediated antioxidant system as a promising target for breeding climate-resilient crops. Full article

In the context of research aimed at identifying the causes of the progressive decline in cellular and tissue functions characteristic of aging, in recent decades, increasing attention has been devoted to the sirtuin family. Sirtuins are named after the Sir2 protein of Saccharomyces cerevisiae, a product of the SIR gene family, known as “silent information regulator 2”. Sirtuins are NAD⁺-dependent protein deacetylases and deacylases characterized by a conserved catalytic domain of approximately 275 amino acids. The removal of acetyl groups from acetyl-lysine residues on proteins is critical in regulating a wide range of biological functions, including gene silencing, genome stability, longevity, metabolism, and cellular physiology. In humans, the sirtuin family comprises seven isoforms (SIRT1–SIRT7), each with specific substrate preferences and primarily, but not exclusively, localized in the nucleus (SIRT1, SIRT6, and SIRT7), cytoplasm (SIRT2), and mitochondria (SIRT3, SIRT4, and SIRT5). Sirtuins may regulate numerous cellular processes associated with survival and longevity, including transcription and DNA repair, inflammation, glucose and lipid metabolism, oxidative stress, mitochondrial function, apoptosis, autophagy, and stress resistance. Sirtuins’ dependence on NAD⁺ allows them to function as cellular energy sensors, linking metabolic demands to selective lysine deacylation in various subcellular organelles. The aim of this review is to provide an update on this family of molecules, describing their molecular structures, physiological functions, roles in aging processes, and potential to be modulated to serve as a strategy for promoting healthy aging. Full article

Cancer remains a significant global health burden, often requiring conventional treatments characterized by considerable side effects and limited tumor specificity. This review addresses the critical gap in understanding the non-thermal mechanisms by which Pulsed Electromagnetic fields (PEMFs) exert selective anti-tumor effects. Our primary objective is to analyze the molecular and cellular events through which low-intensity PEMF triggers stress responses and apoptosis in neoplastic cells without impacting normal cell viability. This comprehensive review synthesizes current evidence on the biological effects of PEMFs. Findings indicate that PEMFs disrupts intracellular homeostasis, induces reactive oxygen species-mediated oxidative stress, and activates endoplasmic reticulum stress, collectively driving malignant cells towards apoptosis or cell cycle arrest. Importantly, these effects are preferentially observed in cancer cells due to their inherent biophysical vulnerabilities—such as depolarized membrane potentials—and depend critically on specific PEMFs parameters. In conclusion, PEMFs acts as a multifaceted disruptor of cancer cell homeostasis, representing a promising non-invasive therapeutic modality. Further research is essential to optimize dosimetry and identify primary molecular sensors such as radical pair dynamics, to enhance clinical application and explore synergistic combinations with existing therapies. Full article

Haemophilus influenzae (H. influenzae) is an important respiratory pathogen that can cause various invasive and non-invasive bacterial infections requiring rapid and sensitive detection. In recent years, electrochemical biosensors have emerged as a practical alternative for pathogen detection due to their high sensitivity, portability and short analysis time. Molecularly imprinted polymers (MIPs) are a class of synthetic receptors designed to mimic biological recognition through template-directed polymerization. In this study, an electrochemical biosensor based on MIPs was developed for the selective detection of H. influenzae. The polymeric film composed of methacrylamide (MAM), acrylamide (AAM), and vinylpyrrolidone (VP) monomers was fabricated on a gold screen-printed electrode (gold-SPE). The results of cyclic voltammetry (CV) revealed a strong redox current shift corresponding to bacteria concentrations within an analytical range of 1–10,000 CFU/mL with LOD 1.03 CFU/mL, with relative standard deviation (RSD) values below 9% across the tested concentration range. The optimized composition yielded and exhibited excellent selectivity when tested against non-target bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Full article

Inflammatory bowel diseases (IBD) are chronic, relapsing, immune-mediated disorders that require regular and preferably noninvasive monitoring of inflammatory activity. Fecal biomarkers of neutrophilic inflammation, namely calprotectin and lactoferrin, therefore represent key analytical targets for diagnosis and longitudinal disease management. Despite their widespread clinical use, existing publications predominantly address either their clinical relevance or individual technical solutions, without establishing a comprehensive engineering-translational framework for their biosensor-based implementation. This review bridges this gap by providing an integrative analysis of the molecular and biological nature of calprotectin and lactoferrin, the mechanisms underlying their appearance in fecal matrices, and the analytical constraints that directly influence the design of hybrid point-of-care (PoC) biosensor systems. We systematically compare major biosensing platforms, emphasizing sensor architecture, signal transduction mechanisms, and sample preparation strategies as critical determinants of sensitivity, selectivity, reproducibility, and clinical relevance. The novelty of this review lies in combining the pathophysiological context of neutrophilic inflammation with physicochemical and technological aspects of biosensor development, enabling a transition from laboratory prototypes to evaluation of real translational readiness. The practical significance resides in establishing a methodological basis for rational design of next-generation hybrid-integrated biosensor systems and outlining perspectives for digital analytics and artificial intelligence in clinically interpretable IBD monitoring. Full article