Search Results (866)

Mercury ions (Hg²⁺) are highly toxic and pose severe risks to human health and ecosystems, necessitating sensitive detection methods for environmental monitoring. Here, we report a paper-based graphene sensor functionalized with single-stranded DNA (ssDNA) probes for Hg²⁺ detection based on T-Hg²⁺-T coordination chemistry. To elucidate the effect of probe structure on sensing performance, we designed DNA constructs with varying numbers of guanine (G) bases (3–6, designated DNA2–DNA5) in the bridging fragment and systematically evaluated their influence on hairpin stability, Hg²⁺ binding affinity, and sensor response. The DNA3-based sensor (four G bases) exhibited optimal electronic stability and sensitivity, achieving a detection limit of 0.673 pM with effective real-time monitoring capability in aqueous media. These findings highlight the critical role of DNA sequence design in T-Hg²⁺-T-based biosensors and provide a promising strategy for sensitive and selective Hg²⁺ detection in environmental samples. Full article

A quartz crystal microbalance-based biosensor for the specific detection of the first transgenic common bean (L.) cultivar (BRS FC401 RMD) with resistance to Bean golden mosaic virus (BGMV) was developed. The immobilization chemistry relies on the strong bond between the thiolated probe and the gold electrode surface. The probe sequence is internal to a region of the BGMV rep gene that was introduced into the common bean genome. The sensor’s analytical performance was determined using synthetic oligonucleotides. Real samples of transgenic and wild-type bean seeds were also tested. Sample pretreatment consisted only of enzymatic fragmentation, followed by a thermal denaturation step combined with blocking oligonucleotides. Different biosensor regeneration approaches were studied. Immobilization showed good reproducibility (CV% of 5.8%). The biosensor proved specific for both synthetic oligonucleotides and non-amplified genomic DNA. A linear detection range of 0–1.4 ng/µL was observed, with a detection limit of 0.18 ng/µL. Three sequential detections were performed without loss of surface activity. The results demonstrate the biosensor’s potential for direct, real-time, label-free detection of DNA samples for field screening of transgenic common bean cultivars. Full article

Genotoxic stress, which includes DNA damage and the mis-localization of DNA and RNA, is a defining feature of tauopathies, Alzheimer’s disease, and several other neurodegenerative disorders. Recent findings indicate that activation of the innate immune system in response to genotoxic stress can drive harmful neuroinflammation, compromise neuronal integrity, and promote neurodegeneration. Multiple innate immune sensors of genotoxic stress have recently been discovered, but the contributions of many of these emerging nucleic acid–sensing pathways in neurodegenerative disease pathogenesis remain largely unexplored. Z-DNA binding protein 1 (ZBP1) is one such recently discovered genotoxic stress sensor that has been shown to incite various forms of cell death as well as proinflammatory cytokine production in response to left-handed Z conformations of DNA (Z-DNA) and RNA (Z-RNA). Here, we show that ZBP1 deletion provides protection against tau pathology and neuronal loss in the PS19 mouse model of tauopathy. Moreover, we find that this rescue of tauopathy seen with ZBP1 ablation is associated with dampened activation of microglia and astrocytes. These findings identify ZBP1 as a pivotal genotoxic stress sensor that drives tau pathology, gliosis, and neuronal loss in tauopathy. This work further suggests that targeting ZBP1 may offer a therapeutic strategy to treat tau-mediated neurodegenerative disease. Full article

Obesity-associated carcinogenesis offers a model to explore the transition from metabolic dysregulation to genomic instability and carcinogenesis. Adenosine 5′-monophosphate-activated protein kinase (AMPK), the principal cellular energy sensor, coordinates adenosine triphosphate (ATP) production with metabolic demand; however, in obesity, AMPK activity is impaired, resulting in reduced ATP, elevated Adenosine Monophosphate (AMP), and cellular energy stress. Deoxyribonucleic Acid (DNA) polymerases ε (Pol ε) and δ (Pol δ) maintain replication fidelity via a 3′→5′ exonuclease proofreading activity that removes misincorporated nucleotides. Elevated AMP directly binds and selectively inhibits the exonucleases, conserving energy at the expense of genomic accuracy. As a result, replication errors escape correction and accumulate, some conferring a selective advantage and driving carcinogenic evolution. Therapeutic and lifestyle interventions that activate AMPK—including weight loss, exercise, metformin, and aspirin—restore ATP production, lower AMP, and relieve inhibition of exonuclease proofreading, thereby preserving genomic integrity and slowing mutation-driven carcinogenesis. This framework reveals two core biological principles: 1. Energy metabolism and DNAreplication fidelity are mechanistically coupled at the DNA polymerase active site. 2. The mutation rate is an adaptive metabolic phenotype, modulated by AMP levels. These concepts redefine the metabolic–genetic interface in carcinogenesis and highlight AMPK activation as a rational target for obesity-associated cancer prevention. Full article

Background: Gene expression and cellular identity are regulated by epigenetics that occurs through chromatin modifications, RNA changes, chromatin accessibility, and three-dimensional genome organization. Although DNA methylation has been the focus of most epigenetics studies in the past, other non-methyl epigenetic processes, including histone post-translational modifications (PTMs), epitranscriptomic marks, and chromatin remodeling, are dynamic, reversible, and context-dependent, and thus are difficult to accurately interrogate using endpoint sequencing-based assays, especially in heterogeneous tissues, developing systems, and therapeutic response environments. Scope and Approach: The present review discusses epigenetic modifications other than DNA methylation regarding sensor-based technologies that can measure live, dynamic, and spatially resolved measurements. Epigenetic sensors include any genetically encoded sensors (GECs) based on resonance energy transfer, CRISPR/dCas-derived sensors, or aptamer-based sensors, and hybrid biochemical/imaging sensors that can be used in live or semi-live settings. It lays emphasis on the technologies, which have been developed recently, that allow real-time kinetic measurements, working in three-dimensional and organoid models, and being applied to disease-relevant perturbations. On these platforms, performance properties such as specificity, sensitivity, spatial and temporal resolution, ability to perform dynamic versus locus-specific interrogation, and perturbed endogenous chromatin states are compared. Key Conclusions and Outlook: Together, these sensing strategies are complementary to the traditional methods of measuring epigenomics in that they show epigenetic dynamics unobservable with static measurements. We list the important technical issues, including specificity, quantitation, multiplexing, and chromatin perturbation, and report the barriers and solutions in development and design. Lastly, we provide a conceptual map of how live epigenetic sensing and multi-omics and translational models can be integrated, and how the two methodologies can be used to develop functional epigenetics and guide disease modeling and drug development. 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

A novel sensitive and selective electrochemiluminescence (ECL) sensor using nitrogen-doped graphyne as the platform was proposed for kanamycin (KAN) detection. First, nitrogen-doped graphyne nanomaterial (1N-GY) with high conductivity was synthesized using a high-energy ball milling method. Compared with ordinary graphyne, the addition of nitrogen atoms can improve the conductivity of the material and reduce the electronic migration energy barrier. Then it was used as a substrate material of the ECL sensor, not only increasing the conductivity of the biosensor but also improving the sensitivity of the ECL sensor by providing more immobilization space for the luminescent probe of Nafion-coated mesoporous silica adsorbed Ru(bpy)₃²⁺ (mSiO₂@Nafion@Ru(bpy)₃²⁺). On this basis, mSiO₂@Nafion@Ru(bpy)₃²⁺ functionalized DNA probes were used as luminescent and capture probes to specifically recognize different concentrations of KAN to produce ECL signals. Under optimal conditions, the proposed ECL sensor exhibited good linearity (10⁻¹²–10⁻⁶ M KAN) and a low detection limit of 1.08 pM. The prepared biosensor with good stability and selectivity successfully detected KAN in honey and milk samples, with spiked recovery rates ranging from 98% to 111.79%. This method not only expands the application of 1N-GY as a novel graphitic material in ECL biosensors but also provides an effective way to check antibiotics in dairy products. Full article

Crop fungal and viral diseases cause annual economic losses exceeding USD 150 billion globally, demanding rapid, sensitive, and field-deployable diagnostic technologies. This review critically evaluates recent advances in electrochemical biosensing platforms for early crop pathogen detection, focusing on immunosensors, genosensors, aptasensors, and VOC-based systems. Reported analytical performances demonstrate ultralow detection capabilities, including 0.3 fg mL⁻¹ for viral coat proteins, 15 DNA copies for bacterial pathogens, 0.5 fg µL⁻¹ RNA detection for viroids, and nanomolar-level VOC sensing (35–62 nM), with response times ranging from 2 to 60 min. Comparative analysis reveals that genosensors and aptasensors generally achieve the lowest LODs due to nucleic acid amplification or high-affinity recognition, while immunosensors provide robust protein-level specificity validated against ELISA. Volatile organic compound (VOC) sensors enable non-invasive, pre-symptomatic monitoring but face specificity challenges. Despite strong laboratory performance, practical adoption is limited by matrix-derived electrochemical interference, environmental instability of biorecognition elements, workflow complexity, and insufficient standardization across studies. Emerging innovations, including magnetic bead enrichment, nanoporous and graphene-based electrodes, microfluidic integration, AI-assisted impedance interpretation, and biodegradable substrates, are progressively addressing these bottlenecks. This review emphasizes that successful field translation requires holistic workflow engineering, matrix-matched validation, and harmonized performance metrics rather than incremental sensitivity improvements alone. By integrating analytical chemistry, nanomaterials engineering, and agricultural decision-support frameworks, electrochemical biosensing platforms hold significant potential to enable decentralized, rapid, and sustainable crop disease management. 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

The objective of this study is to develop a label-free fluorescent sensor for the quantitative detection of hypochlorite ions (ClO⁻) and validate its applicability in biological samples, particularly exploring the potential of ClO⁻ as a biomarker for stress-induced hypertension (SIH). Male Sprague-Dawley rats (8 weeks old, 250–300 g) were used to establish the SIH model. A guanine-rich (G-rich) signal DNA sequence (S-DNA) was rationally designed, with a ClO⁻-responsive phosphorothioate (PS) moiety integrated into the probe architecture. In the absence of ClO⁻, the S-DNA folds into a stable G-quadruplex structure, which specifically binds to ThT and triggers a significant enhancement of the dye’s fluorescence intensity. Upon introduction of ClO⁻, the specific hydrolysis reaction between the PS moiety and ClO⁻ induces cleavage of the S-DNA into two discrete fragments, thereby abrogating G-quadruplex formation and resulting in a remarkable quenching of ThT fluorescence. This proposed method exhibits excellent anti-interference capability against other reactive oxygen species (ROS) and achieves a low detection limit of 41.2 nM for ClO⁻. Furthermore, this strategy was successfully applied to the quantitative determination of endogenous ClO⁻ in human cells and the plasma of stress-induced hypertensive (SIH) rats, highlighting its substantial potential for clinical and physiological research. Full article

Sensitive quantitative detection of breast cancer gene synthetic sequences is crucial for related biosensing research. To address the limitations of traditional sensors for detecting ultra-low concentrations, this study developed a novel fiber-optic biosensor by combining nanomaterial sensitization with nanoparticle signal amplification strategies. A fiber optic sensor based on single-mode fiber-thin-core fiber-multimode fiber-single-mode fiber structure was fabricated and functionalized with black phosphorus (BP) nano-interface. The Au@cDNA complex was prepared by covalently immobilizing sulfhydryl-modified complementary DNA (cDNA) on the surface of gold nanoparticles (AuNPs). The complex specifically hybridized with the probe DNA (pDNA) immobilized on the surface of the sensor. The experimental results show that this sensor has a sensitivity of 0.793 nm/lgM and a detection limit of 20.27 fM in the concentration range of 100 fM to 100 nM. Specifically, the BP-functionalized sensor exhibits superior dynamic range, higher sensitivity, and lower detection limits for detecting Au@cDNA. The synergistic effect of interfacial sensitization by BP and signal amplification by AuNPs significantly enhances detection performance, providing a promising platform for ultra-sensitive biosensing applications. Full article

Marine renewable energy (MRE) systems operate in harsh marine environments where long-term exposure to seawater leads to biofouling, resulting in increased surface roughness, hydrodynamic drag, added mass, structural loading, sensor degradation, and reduced energy production. Despite its significant operational and economic impact, biofouling management in MRE devices has traditionally relied on manual inspections and empirical growth models, which offer limited predictive capability. This review provides a structured, data-centric synthesis of recent advances in machine learning (ML) and bioinformatics approaches for biofouling modeling, performance prediction, and maintenance planning in offshore wind turbines, tidal turbines, and wave energy converters. The study systematically examines key fouling locations and associated engineering impacts, and analyzes the major data streams used for predictive modeling, including SCADA and condition-monitoring time series, metocean variables, inspection imagery, laboratory and field experiments, and environmental DNA (eDNA) sequencing outputs. We compare modeling strategies ranging from physics-based simulations to classical ML, deep learning, computer vision, and hybrid physics-informed frameworks, and discuss how biological indicators such as microbial community profiles and eDNA-derived taxa abundances can be integrated as predictive features. The review further outlines emerging digital twin architectures for fouling-aware performance forecasting and maintenance decision support. Finally, we identify key challenges including data scarcity, cross-site generalization, validation practices, and uncertainty quantification, and propose future research directions toward integrated, proactive biofouling management systems in marine renewable energy infrastructure. Full article

Using disposable screen-printed electrodes faces major challenges when attempting to monitor a continuous process, especially in systems where there is pronounced adsorption, fouling, degradation, or in cases of irreversible electrochemical reactions. Methylene Blue (MB) exhibits some therapeutic properties and is commonly used as a redox reporter in DNA sensors, but is also considered a toxic pollutant in aquatic systems. MB demonstrates strong adsorption to carbon materials, which prevents its electroanalytical determination in multiple measurements with a single electrode. Our work details direct electrochemical determination of MB with only the native carbon screen-printed working electrode as sensing material and optimization of the analytical method. In batch mode, we significantly improved sensitivity and interelectrode reproducibility by introducing a prepolarization step, but successive measurements in lower concentrations were not feasible due to strong adsorption. A fully customizable, modular flow cell was 3D printed to allow in operando replacement of the planar screen-printed three-electrode system after measurement during continuous flow. As confirmed by mechanical properties testing, the rigid polyacrylate upper section of the flow cell provides structural stability, combined with a flexible TPU lower section which enables effortless sensor hot swapping and effective sealing during flow. With an optimized hot swapping flow detection method, MB was detected via square wave voltammetry with a sensitivity of 65.59 µA/µM and a calculated LOD of 7.75 nM, which outperforms similar systems from the literature. We envisage this approach can be integrated into low-cost continuous environmental monitoring systems or in-line quality control, especially in flow chemistry synthesis. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivation and excessive autoantibody production. Z-DNA binding protein 1 (ZBP1), an innate immune sensor involved in nucleic acid recognition and cell death signaling, has been implicated in antiviral and inflammatory responses. However, its role in B-cell dysregulation during SLE remains unclear. Methods: Integrative transcriptomic analyses were performed using public datasets (GSE61635, GSE235658, GSE136035, and GSE163497) to determine the expression pattern and biological functions of ZBP1 in SLE. Bulk RNA-seq and single-cell RNA-seq data were used to evaluate ZBP1 expression across B-cell subsets. Correlations between ZBP1 expression, disease activity, and immunological parameters were assessed. RNA-seq data following ZBP1 knockdown were analyzed to explore its potential downstream pathways and molecular networks. In addition, in vitro ZBP1 knockdown experiments were conducted to examine its effects on B-cell activation, plasma cell differentiation, and antibody production. Results: ZBP1 was significantly upregulated in peripheral blood and B cells from SLE patients and was enriched in pathways related to type I interferon signaling and cytokine-mediated immune responses. Single-cell transcriptomic profiling further revealed elevated ZBP1 expression across multiple B-cell subsets, including naïve B cells, memory B cells, age-associated B cells (ABCs), and plasma cells. Clinically, ZBP1 expression in peripheral B cells was positively correlated with CD86 mean fluorescence intensity (MFI), SLE Disease Activity Index (SLEDAI) scores, and serum IgG levels, suggesting a link between ZBP1 and B-cell activation. RNA-seq analysis following ZBP1 silencing demonstrated that ZBP1 regulates genes involved in the cell cycle, DNA replication, and p53 signaling, indicating its potential role in promoting B-cell proliferation and activation. Functionally, ZBP1 silencing impaired B-cell activation, reduced plasma cell differentiation, and decreased immunoglobulin production in vitro. Conclusions: Our study identifies ZBP1 as a molecule upregulated in SLE B cells and associated with B-cell activation and disease activity. Although direct causality remains to be established, the data indicate that ZBP1 may contribute to SLE pathogenesis by modulating cell cycle-related pathways and promoting aberrant B-cell responses, highlighting its potential as a biomarker and a candidate therapeutic target in SLE. Full article

Aortic diseases, including thoracic and abdominal aneurysms as well as aortic dissections, represent life-threatening vascular disorders characterized by progressive wall degeneration and inflammation. Increasing evidence indicates that oxidative stress is a central driver of aortic pathology through the induction of DNA damage in vascular smooth muscle cells and endothelial cells. Oxidative DNA lesions activate the DNA damage response (DDR), a highly coordinated network of damage sensors, signaling kinases, and repair effectors that determines cell fate decisions such as DNA repair, apoptosis, or cellular senescence. In aortic tissue, persistent or dysregulated DDR signaling contributes to chronic inflammation, extracellular matrix degradation, and loss of vascular integrity. Key molecular regulators, including base excision repair enzymes OGG1 and APE1, as well as DDR mediators such as ATM, ATR, p53, PARP, and NOTCH1, integrate oxidative stress signals with pro-inflammatory and pro-degenerative pathways. Aberrant activation of these mechanisms promotes vascular smooth muscle cell VSMC phenotypic switching from contractile to synthetic phenotype, endothelial dysfunction, and senescence-associated secretory responses, thereby accelerating aortic wall weakening and aneurysm progression. This review highlights the mechanistic links between oxidative stress-induced DNA damage, DDR pathway activation, and vascular remodeling in aortopathies. A deeper understanding of these molecular interactions may uncover novel biomarkers and therapeutic targets aimed at limiting inflammation, preserving genomic stability, and preventing catastrophic aortic events. This work represents a narrative review and therefore has inherent limitations in terms of systematic literature search and selection. Full article