Search Results (13,394)

Reactive oxygen species (ROS), inevitable by-products of aerobic metabolism, act both as regulators of signaling pathways and as mediators of oxidative stress and aging-related damage. Protein oxidative post-translational modifications (Ox-PTMs) are recognized hallmarks of aging and metabolic decline, yet the persistence of protein oxidation under different physiological conditions, such as age and diet, remains unclear. Here, we applied proteomics to mitochondrial and membrane-enriched fractions of male Fischer 344 rat cerebrum and heart, comparing Ox-PTMs across young and aged animals subjected to ad libitum nutrition (AL) or calorie restriction (CR). We identified 139 mitochondrial and membrane-associated proteins consistently exhibiting high levels of oxidation, including tricarboxylic acid (TCA) cycle enzymes, respiratory chain subunits, ATP synthase components, cytoskeletal proteins, and synaptic vesicle regulators. Functional enrichment and network analyses revealed that oxidized proteins clustered in modules related to mitochondrial energy metabolism, membrane transport, and excitation–contraction coupling. Notably, many proteins remained persistently oxidized, predominantly as mono-oxidation, without significant changes during aging or CR. Moreover, the enzymatic activity of mitochondrial complexes was not only preserved but significantly enhanced in specific contexts, and the structural integrity of the respiratory chain was maintained. These findings indicate a dual strategy for coping with oxidative stress: CR reduces ROS production to limit oxidative burden, while protein and network robustness enable functional adaptation to persistent oxidation, collectively shaping mitochondrial function and cellular homeostasis under differing physiological conditions. Full article

Climate change necessitates a deeper understanding of plant tolerance mechanisms to dual water stresses. This study investigated the distinct physiological and genetic responses of Longleaf Speedwell (Pseudolysimachion longifolium) to drought and waterlogging using RNA-Seq. Physiological data showed a rapid and comparable reduction in photosynthetic efficiency after one week and a reduction in biomass under both stresses after two weeks. However, transcriptomic analysis revealed fundamentally distinct strategies: Drought induced a massive transcriptional response characterized by the strong upregulation of defense and stress-tolerance pathways and the severe shutdown of growth-related metabolism. In contrast, waterlogging triggered a constrained hypoxic response, prioritizing energy conservation by downregulating synthesis processes and activating ethylene signaling. The reliability of the RNA-Seq data was confirmed by qRT-PCR, which also crucially identified Alcohol dehydrogenase (ADH), Ethylene Responsive Factor (ERF), and Peroxidase (POD) as common candidate genes highly induced under both drought and waterlogging conditions, suggesting a shared genetic module for general water stress tolerance. These findings provide valuable insights into the adaptation mechanisms of non-model plants to complex environmental changes. Full article

With the increasing adoption of virtual reality (VR) in research and training applications, reliable stress detection in naturalistic settings remains challenging, particularly when hardware complexity must be minimized. This study presents an enhanced framework for real-time stress recognition in VR environments that integrates behavioral interactions with selectively derived physiological signals. Building upon previous architectures, the proposed framework incorporates pre-task baseline measurements to account for subject-specific and session-initial variability. While the comprehensive analysis employs a three-class affective framework, the practical implementation focuses on binary stress detection for real-world VR applications. Stress detection is achieved through VR-based behavioral signals, complemented by minimal input from a Galvanic Skin Response (GSR) sensor. The experimental evaluation demonstrates that baseline calibration improves separation across stress conditions. Quantitatively, the proposed Weighted Baseline Detector (WBD) achieved a classification accuracy of 94.17% and an Area Under the Curve (AUC) of 0.9993, outperforming the fixed global baseline approach (85.0% accuracy, AUC 0.9067), which demonstrates the effectiveness of the proposed calibration method. Rigorous cross-validation confirms that the approach achieves stable performance with statistical significance across stress conditions. These findings highlight the potential of combining behavioral analysis with physiological support to develop practical, low-hardware VR platforms for live stress recognition. Full article

Aberrant activation of innate immunity promotes the development of pulmonary arterial hypertension (PAH); however, the role of pattern recognition by Toll-like receptors (TLRs) within the pulmonary vasculature remains unclear. To consolidate knowledge (as of June 2025) about TLRs and their interactions with viruses in PAH and to identify therapeutic implications. A narrative review of experimental and clinical studies investigating ten TLRs in the context of the pulmonary vascular microenvironment and viral infections. Activation of TLR1/2, TLR4, TLR5/6, TLR7/8, and TLR9 converges on the MyD88–NF-κB/IL-6 axis, thereby enhancing endothelial-mesenchymal transition, smooth muscle proliferation, oxidative stress, thrombosis, and maladaptive inflammation, ultimately increasing pulmonary vascular resistance. Conversely, TLR3, through TRIF–IFN-I, preserves endothelial integrity and inhibits vascular remodeling; its downregulation correlates with PAH severity, and poly (I:C) restitution has been shown to improve hemodynamics and right ventricular function. HIV-1, EBV, HCV, endogenous retrovirus K, and SARS-CoV-2 infections modulate TLR circuits, either amplifying pro-remodeling cascades or attenuating protective pathways. The “TLR rheostat” is shaped by polymorphisms, ligand biochemistry, compartmentalization, and biomechanical forces. The balance between MyD88-dependent signaling and the TRIF–IFN-I axis determines the trajectory of PAH. Prospective therapeutic strategies may include TLR3 agonists, MyD88/NF-κB inhibitors, modulation of IL-6, and combination approaches integrating antiviral therapy with targeted immunomodulation in a precision approach. Full article

Studies that correlate the structure of a molecule with its biological function or activity are useful in identifying the structural components that determine how the molecule interacts with binding proteins. This enables the synthesis of structural analogs with desirable properties, such as agrochemicals that improve plant developmental traits or adaptations to environmental stress. This review highlights a group of plant defense-inducing small signaling molecules characterized by a fatty acid-derived molecular skeleton with different functional groups. These include medium chain 3-hydroxy fatty acids (mc-3-OH-FAs) derived from the bacterial cell wall; green leaf volatiles (GLVs), which comprise primary aldehydes, alcohols, and esters derived from plant membranes; insect-derived fatty acid-amino acid conjugates (FACs), caeliferins, and bruchins; and sphingoid bases from oomycete pathogens. These molecules are typically lipophilic, and their mechanism of action is likely determined by both specific structural hallmarks and physicochemical properties. They activate defense responses via signaling pathways and are therefore presumed to interact with extra- or intracellular receptor proteins. However, classical receptors have only been characterized for mc-OH-FAs, sphingoid bases, and FACs. Structure–function studies may reveal structural features of these molecules that are critical for binding to receptors and relevant to the specificity of these interactions. This is particularly significant for GLVs, which have been extensively investigated for their roles in plant stress signaling and interplant communication, yet no specific receptor has been identified to date. This comparative review aims to shed light on perception of GLVs and other small molecules. Full article

Homogalacturonan (HG) methylesterification is a key determinant of plant cell wall (CW) structure and function, shaping growth, morphogenesis, and responses to biotic and abiotic stresses. This review highlights recent advances in the regulation of homogalacturonan (HG) methylesterification, focusing on the coordinated roles of pectin methylesterases (PMEs), pectin methylesterase inhibitors (PMEIs), transcription factors (TFs), and hormonal signals. We examine how these regulators interact within the CW microenvironment to modulate elasticity, porosity, and remodeling dynamics. Insights from immunolocalization and biomechanical studies reveal the spatiotemporal patterning of HG de-esterification and its integration with developmental and stress-adaptive signaling. Beyond basic biology, HG methylesterification dynamics directly influence traits such as fruit firmness, pathogen resistance, and stress tolerance, positioning HG methylesterification-related genes as promising targets for molecular breeding and biotechnological interventions. By integrating mechanistic understanding with genomic and phenotypic selection approaches, breeders can precisely tailor CW properties to enhance crop resilience and quality. A comprehensive view of HG methylesterification—from enzymatic control to mechanical feedback—offers a conceptual and practical framework for guiding crop improvement and sustainable agricultural practices. Full article

Pressure-overload-induced heart failure is characterized by pathological ventricular remodeling, including hypertrophy and fibrosis, which compromise cardiac function and worsen outcomes. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has shown therapeutic promise in heart failure with reduced ejection fraction (HFrEF). This study evaluated its antihypertrophic, antifibrotic, and metabolic effects in a murine pressure-overload model. Male C57BL/6 mice (~25 g) underwent transverse aortic constriction (TAC) and received oral Vericiguat (10 mg/kg/day) for 14 days. Cardiac hypertrophy was assessed by gross morphology and heart weight; fibrosis was quantified using Masson’s trichrome and Picrosirius red staining. Collagen deposition and wall stress indices were measured by image analysis. Proteomic profiling of fibroblast- and myocyte-enriched tissues identified differentially expressed proteins (DEPs) across metabolic, structural, mitochondrial, and signaling pathways. Vericiguat significantly reduced heart weight and attenuated TAC-induced hypertrophy. Histological staining revealed marked reductions in myocardial fibrosis and collagen accumulation in the Vericiguat-treated TAC group compared to untreated TAC controls. Quantitative analysis demonstrated improved wall stress indices. Proteomic data showed consistent modulation of DEPs, with restoration of mitochondrial and energy-regulating proteins suppressed by TAC, indicating enhanced bioenergetic support. Collectively, Vericiguat mitigates pressure-overload-induced remodeling through coordinated antihypertrophic, antifibrotic, and metabolic reprogramming mechanisms. These findings support its potential as a therapeutic strategy for heart failure and warrant further clinical investigation. Full article

Molecular chaperones HSP70 and HSP90 represent a critical, yet conflict-ridden, node in plant physiology, particularly under the dual impact of heat stress and viral infection. As key components of both thermotolerance (maintaining proteostasis) and innate immunity (stabilization of NLR receptors), they are simultaneously exploited by viruses to facilitate their own life cycle. This review critically analyzes this “trilemma,” focusing on the hypothesis of competition for a limited chaperone pool. We present mechanistic insights indicating that during heat stress, cellular priority shifts towards maintaining global proteostasis, thereby diverting chaperones from immune functions. This resource-based competition mechanism potentially explains the collapse of ETI-immunity, as NLR receptors, deprived of support from the HSP90-SGT1-RAR1 complex, are destabilized and targeted for degradation. We also integrate adjacent signaling pathways into this model, including hormonal cross-talk (SA, JA) and autophagy. Understanding this trade-off opens new perspectives for molecular breeding and the biotechnological engineering of stress-resilient crop varieties. Full article

The interaction between human salivary alpha-amylase (HSAmy) and amylase-binding oral streptococci (ABS) helps determine the bacteria that colonize the oral cavity by establishing dental biofilms. Streptococci are important pioneer species of the oral cavity and influence oral health as well as common diseases such as dental caries. Various oral streptococcal species express distinct amylase-binding proteins, among which amylase-binding protein A (AbpA), encoded by the abpA gene in Streptococcus gordonii and several other species, which is the most extensively studied. Amylase binding facilitates microbial adhesion to host surfaces and biofilm formation and enables bacteria to harness the host’s amylase enzymatic activity at their cell surface, enhancing their capacity to metabolize dietary starch for nutritional gain. Additionally, amylase binding may also influence bacterial cell division and stress tolerance by engaging novel bacterial signaling pathways. From an evolutionary perspective, both Neanderthals and modern humans exhibit functional adaptations in nutrient metabolism, including selection for salivary amylase-binding oral streptococci, highlighting the importance of microbial co-adaptation in response to host diet. Further research is warranted to elucidate the broader roles of amylase binding to bacteria in host-bacterial signaling, bacterial cell division and fitness and the evolutionary trajectory of the oral microbiome. Full article

The global rise in cancer incidence and mortality represents a major challenge for modern healthcare. Although current screening programs rely mainly on histological or immunological biomarkers, cancer is a multifactorial disease in which biological, psychological, and behavioural determinants interact. Psychological dimensions such as stress, anxiety, and depression may influence vulnerability and disease evolution through neuro-endocrine, immune, and behavioural pathways, especially by affecting adherence to therapeutic recommendations. However, these dimensions remain underexplored in current screening workflows. This review synthesizes current evidence on the integration of biological markers (tumor and inflammatory biomarkers), psychometric profiling (stress, depression, anxiety, personality traits), and behavioural digital phenotyping (facial micro-expressions, vocal tone, gait/posture metrics) for potential early cancer risk evaluation. We examine recent advances in computational sciences and artificial intelligence that could enable multimodal signal harmonization, structured representation, and hybrid data fusion models. We discuss how structured computational information management may improve interpretability and may support future AI-assisted screening paradigms. Finally, we highlight the relevance of digital health infrastructure and telemedical platforms in strengthening accessibility, continuity of monitoring, and population-level screening coverage. Further empirical research is required to determine the true predictive contribution of psychological and behavioural modalities beyond established biological markers. Full article

With the aim of developing a new tool to meet the increasing demand for food safety, a whole-cell-based system able to detect the presence of cobalt contamination along the pasta production chain was constructed. This system is based on bacterial cells engineered with a plasmid containing the eGFP gene under the control of a promoter sequence, and is able to elicit a fluorescence signal when activated. The promoters of four stress-responsive genes (DnaK, GroE, UspA, and ZntA) were used to test their responsiveness to cobalt; the promoter of the UspA gene, coding for a universal stress protein, was chosen. The UspA promoter was activated by cobalt, and the system described was highly sensitive, successfully detecting low concentrations of cobalt within complex food matrices derived from durum wheat seeds when exogenous cobalt was added. In food matrices tested alone, a fluorescence signal was present only in bran and fine bran, confirming that these parts of the wheat seed are the ones in which contaminants accumulate. Conversely, in the other matrices derived from the inner part of grains, no signal was detected. The findings reported contribute to the development a new, effective and sensitive tool for monitoring cobalt contamination, offering a valuable approach to enhance food safety control. Full article

Thigmomorphogenesis denotes a suite of anatomical, physiological, biochemical, biophysical, and molecular responses of plants to mechanical stimulation. This phenomenon is evolutionarily conserved among diverse plant lineages; however, the magnitude and character of the response are strongly determined by both the frequency and intensity of the applied stimulus. In angiosperms, thigmomorphogenetic reactions typically occur gradually, reflecting a complex interplay of morphological alterations, biochemical adjustments, and genetic reprogramming. In dicotyledonous plants, thigmomorphogenesis is commonly expressed as a reduction in leaf blade surface area, shortening of petioles, decreased plant height, radial thickening of stems, and modifications in root system architecture. In monocotyledons, in turn, mechanical stress frequently results in stem rupture below the inflorescence, with concomitant shortening and increased flexibility of younger internodes. These specific traits can be explained by structural features of monocot secondary walls as well as by the absence of vascular cambium and lateral meristems. Mechanical stimulation has been shown to initiate a cascade of responses across multiple levels of plant organization. The earliest events involve activation of mechanoresponsive genes (e.g., TCH family), followed by enzymatic activation, biochemical shifts, and downstream physiological and molecular adjustments. Importantly, recent findings indicate that prolonged mechanical stress may significantly suppress auxin biosynthesis, while leaving auxin transport processes unaffected. Moreover, strong interdependencies have been identified between thigmostimulation, gibberellin biosynthesis, and flowering intensity, as well as between mechanical stress and signaling pathways of other phytohormones, including abscisic acid, jasmonic acid, and ethylene. At the molecular scale, studies have demonstrated a robust correlation between the expression of specific calmodulin isoforms and the GH3.1 gene, suggesting a mechanistic link between mechanosensing, hormone homeostasis, and regulatory feedback loops. The present study consolidates current knowledge and integrates novel findings, emphasizing both morphological and cellular dimensions of thigmomorphogenesis. In particular, it provides evidence that mechanical stress constitutes a critical modulator of hormonal balance, thereby shaping plant growth, development, and adaptive potential. Full article

Reef restoration is the major way to compensate the loss of scleractinian corals, which requires huge amounts of transplantation donors. Previous study revealed that some species of corals can conduct polyp bailout and reattachment under environmental stress, which contributes to the living of coral communities and offer a novel way to produce numerous coral colonies for reef restoration. In the present study, physiological and transcriptomic approaches were conducted to illustrate the effects and molecular mechanisms of brine shrimp feeding on the newly attached polyps of coral Poccillopora damicornis. It was observed that brine shrimp feeding significantly prompted the growth of reattached polyps by elevating polyp diameter, number of new polyps, weight of the calcified skeleton, symbiont density, chlorophyll a + c₂ content and Ea values. Transcriptomic analysis also inferred that signaling pathways responsive for energy metabolism, cell growth and biomineralization were dramatically activated. Furthermore, brine shrimp feeding enhanced the immunity of the reattached polyps by suppressing caspase-3 activation level and elevating antioxidant capacity. These results collectively reveals the influence and detailed molecular mechanisms of brine shrimp feeding on the growth of newly reattached coral polyps, which shed light on the potential application of such methods in the cultivation of coral transplantation donors. Full article

The Receptor for Advanced Glycation End-Products (RAGE) is a cell surface receptor of the immunoglobulin-like receptor superfamily. RAGE is a pattern-recognition, multi-ligand receptor that binds glycated proteins, specific non-glycated proteins, and nucleic acids. RAGE ligands are typically part of the group of damage-associated molecular patterns (DAMPs) or alarmins. As such, RAGE is a receptor for molecular products of cellular stress, abnormal metabolism, and inflammation. Activation of RAGE by its ligands leads to pro-inflammatory signaling, often resulting in persistent RAGE activation in various disease states. Consequently, RAGE has been investigated as a potential drug target in the treatment of diabetic complications, vascular disease, Alzheimer’s disease, and multiple types of cancer. An underexplored aspect of RAGE is its role in cell adhesion. Structural comparison of the extracellular domain of RAGE has revealed structural similarity to the activated leukocyte cell adhesion molecule (ALCAM). The present study reveals the role and mechanism of RAGE in regulating cell adhesion. We investigated the role of individual RAGE domains in cell adhesion to extracellular matrix proteins and the changes in protein expression resulting from RAGE upregulation. Key findings include that RAGE displays substrate-specific adhesion to extracellular matrix proteins, that the intracellular domain of RAGE is required for modulating cell spreading, and that regulation of ITGA8 depends on the cytoplasmic domain of RAGE. Full article

Hypoxia is a major global health concern, particularly in premature infants and cancer, where it promotes intracellular calcium accumulation and cell death. The transient receptor potential vanilloid 1 (TRPV1) channel has been implicated in calcium dysregulation and oxidative stress under hypoxic conditions, while estrogen (17β-estradiol, E₂) is known to modulate TRPV1 activity and redox balance. This study aimed to investigate the impact of E₂ on TRPV1 expression, hypoxia-inducible factor-1α (HIF-1α), and calcium signaling in MCF-7 breast cancer cells (ERα-positive) and TRPV1-transfected CHO cells (ERα-negative). Four experimental groups were established: normoxia, E₂, hypoxia, and hypoxia + E₂. Hypoxia was induced by CoCl₂ (200 µM, 24 h), while E₂ treatment was applied at 10 nM for 24 h. Western blot analysis revealed that both TRPV1 and HIF-1α expression were upregulated under hypoxia but significantly reduced by E₂. Fura-2 fluorescence assays revealed that hypoxia increased cytosolic Ca²⁺ levels, whereas E₂ reversed this elevation. Moreover, TRPV1 activation by capsaicin induced marked Ca²⁺ influx under hypoxia, which was attenuated by E₂ treatment. These findings demonstrate that E₂ mitigates hypoxia-induced toxicity by modulating TRPV1-mediated Ca²⁺ signaling and HIF-1α expression, underscoring the protective role of E₂ and identifying TRPV1 as a potential therapeutic target in estrogen-responsive tumors. Full article