Search Results (13,670)

Preeclampsia (PE) is associated with systemic oxidative stress and vascular dysfunction, yet its effects on red blood cell (RBC) stability and mechanics remain incompletely understood. Here, we investigate the structural and nanomechanical alterations of RBCs in third-trimester pregnancies complicated by non-severe and severe PE, compared with normotensive controls. RBCs are analyzed using differential scanning calorimetry (DSC) to assess protein thermal stability and atomic force microscopy (AFM) to determine membrane elasticity (Young’s modulus) during in vitro aging. Linear mixed-effects models аre applied to evaluate the effects of disease severity, storage time, and their (group × storage time) interaction. DSC reveals that Band 3 and hemoglobin exhibited pronounced destabilization in PE, with severe cases showing earlier and larger reductions in transition temperatures and heat capacities, indicative of disrupted membrane–cytoskeletal interactions. AFM confirms that these molecular changes translate into functional consequences: control and non-severe PE RBCs show physiological softening over time, whereas severe PE RBCs undergo pathological stiffening. Statistical modeling demonstrates strong time, group, and interaction effects for both thermodynamic and mechanical parameters. Together, these findings identify the Band 3–hemoglobin macrocomplex as a primary target of PE-induced RBC alterations and suggest that combined thermodynamic–nanomechanical profiling can serve as a sensitive approach to detect early subclinical RBC damage not detectable by routine hematological tests. Full article

Given the rapid mutation and high transmissibility of coronaviruses, especially SARS-CoV-2, comparative genomic studies are crucial for understanding viral evolution, transmission dynamics, and therapeutic development. In prior work, we analyzed and compared the spectral distribution patterns of various k-mer subsets across 920 genome sequences, spanning from primates to prokaryotes. This revealed an evolutionary mechanism in genome sequences, indicating the presence of both CG and TA-specific selection modes. In the present study, we further investigate the specific selection modes in coronavirus genomic sequences by examining the intrinsic distribution rules of 32 XYi 6-mer subset spectra. Our results show that coronavirus genomes exhibit only the CG-specific selection mode, with no evidence of TA-specific selection. Using the CG-specific selection mode, we identified CG1 6-mers as the fundamental subset underlying coronavirus genome evolution. To validate the CG1 subset, we constructed phylogenetic relationships for a set of coronaviruses and SARS-CoV-2 variant genomes. Comparative analysis confirmed that the resulting phylogenetic relationships align more closely with established knowledge. This study thus provides a theoretical framework for inferring phylogenetic relationships at the whole-genome level. Full article

Soleus muscle fibres display modest changes in tetanic force and [Ca²⁺]_i during repeated contractions. In this study, we investigate whether increasing mitochondrial Ca²⁺ load during repeated contractions could induce premature fatigue. Intact, single fibres were dissected from the soleus muscles of adult mice. Mitochondrial Ca²⁺ was measured with rhod-2 in intact fibres. Fatigue was induced by 70 Hz, 350 ms tetani given at 2 s intervals in the absence and presence of 10 µM CGP-37157, a potent inhibitor of the mitochondrial Na⁺-Ca²⁺ exchanger. In soleus fibres fatigued in the absence of CGP-37157, tetanic force was significantly reduced by about 30% at the end of the fatiguing stimulation, while mitochondrial [Ca²⁺] increased to a maximum after about 50 tetani and returned to its resting level within 20 min after the end of the stimulation. In the presence of CGP-37157, the maximal mitochondrial [Ca²⁺] increase was more than twice that in control fibres. In addition, fatigue developed more rapidly and force remained depressed after the end of the stimulation. No difference in mitochondrial membrane potential or ROS production was seen between control and CGP-37157 conditions. We conclude that while modest increases in mitochondrial Ca² may be beneficial, excessive mitochondrial Ca² loading depresses muscle function. Full article

Bone marrow(BM) is the primary site of hematopoiesis, supporting the self-renewal and differentiation of hematopoietic stem cells (HSCs). Its function depends on a highly complex microenvironment composed of stromal cells, vascular networks, extracellular matrix components, and dynamic biophysical signals. Traditional two-dimensional culture systems and animal models fail to adequately recapitulate the spatial architecture and dynamic regulatory processes of the human bone marrow niche, thereby limiting in-depth investigations into hematopoietic regulatory mechanisms, disease pathogenesis, and drug-induced bone marrow toxicity. In recent years, advances in microphysiological systems (MPS) have provided novel engineering approaches for the in vitro reconstruction of the bone marrow microenvironment. This review systematically summarizes current construction strategies for bone marrow MPS, including three-dimensional self-organized bone marrow organoids and microfluidic bone marrow-on-a-chip platforms. Particular attention is given to the roles of key cellular components, biomaterial scaffolds, vascularized architectures, and dynamic perfusion systems in biomimetic bone marrow engineering. In addition, we discuss strategies for constructing more complex models, such as vascular niches, vascularized bone tissue constructs, and bone metastasis models. Bone marrow MPS more faithfully recapitulate the hematopoietic microenvironment and provide a physiologically relevant in vitro platform for hematopoietic research, disease modeling, and drug evaluation, thereby supporting future advances in precision and regenerative medicine. Full article

Background/Objectives: Tumor–stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) were suggested as prognostic markers in oral squamous cell carcinoma (OSCC). Identification of markers assessable in preoperative biopsies that could guide treatment planning is of great importance. This study aimed to evaluate the concordance and prognostic impact of TSR and TILs in preoperative biopsies and matched resection specimens of OSCC. Methods: This study included 100 patients with OSCC. TSR and stromal TILs were evaluated on hematoxylin and eosin-stained slides of biopsies and paired resection specimens and categorized (into low TSR and high TSR; high TILs and low TILs). The agreement between resections and biopsies, and the prognostic significance and clinicopathological correlations of TSR and TILs, were investigated. Results: For TSR, substantial agreement between preoperative biopsies and surgical specimens (kappa correlation coefficient 0.713) was demonstrated. The assessment of TILs showed poor concordance between biopsies and resections (kappa correlation coefficient 0.372). For both biopsies and resections, Cox regression showed an independent negative prognostic impact of low TSR on disease-free, disease-specific, and overall survival. Independent prognostic value of TILs evaluated in biopsies was not found, and the negative prognostic impact of low TILs on disease-free and overall survival was observed only in the main resection specimens. Conclusions: TSR evaluated in preoperative biopsies was highly concordant with results in main resection specimens and may provide significant information for OSCC prognostication, risk stratification, and treatment decisions. In contrast, TILs evaluated in biopsies showed poor concordance with main resection specimens and failed to demonstrate prognostic significance. Full article

Human adipose biology is strongly influenced by three-dimensional (3D) architecture, cell–cell interactions, and local oxygen availability maintained over a long-term culture period, features that are not reproduced in traditional two-dimensional (2D) culture systems. To address this gap, we established a long-term human adipose-derived stem cell (hASC) spheroid model using elastin-like polypeptide–polyethyleneimine (ELP-PEI) coating. The ELP-PEI coating facilitated stable spheroid formation and sustained adipogenic differentiation over 56 days. As spheroids enlarged and matured, they exhibited hallmark features of adipocytes, including lipid accumulation, morphological compaction, and transition out of the proliferative state. Glucose uptake increased during maturation and declined as spheroids became larger. This reduction coincided with a marked rise in hypoxia-inducible factor-1α (HIF-1α) expression, indicating the emergence of a hypoxic microenvironment within larger spheroids. Notably, inhibiting HIF-1α restored insulin-stimulated glucose uptake, demonstrating that hypoxia was the primary driver of impaired insulin responsiveness in late-stage spheroids. These findings position ELP-PEI-supported hASC spheroids as a practical and physiologically relevant platform for studying human adipocyte biology, particularly the development and reversibility of hypoxia-associated metabolic dysfunction. This model offers new opportunities for mechanistic studies and for evaluating therapeutic strategies targeting insulin resistance and adipose tissue pathology. Full article

Fungal decay fundamentally alters moisture transport in wood through complex bio-physical coupling mechanisms that remain poorly understood. Brown-rot fungi such as Coniophora puteana (Schumach.: Fr.) P. Karst. degrade wood through chelator-mediated Fenton (CMF) chemistry, producing hydroxyl radicals that depolymerise cellulose and hemicellulose before significant mass loss. This diffusion-dependent process requires elevated moisture content and leads to structural degradation. However, existing models fail to capture the interaction between boundary-driven fungal colonization, decay-induced property changes, and multi-phase multi-Fickian moisture redistribution, particularly the separate evolution of bound- and free-water phases during decay. Here, we present a transport-response bio-hygrothermal finite element model that couples boundary-driven Monod-type fungal colonization kinetics with multi-phase moisture transport (free water, bound water, vapor) in decaying wood. Although fungal biomass evolution is simulated via a reaction–diffusion equation, decay progression is not derived from biomass–substrate interaction but prescribed independently as an experimentally informed input. The model incorporates decay-modified sorption isotherms, permeability evolution, and boundary-driven biomass influx, along with associated moisture transport, into the governing equations. The model is validated against low-field nuclear magnetic resonance (LF-NMR) measurements of C. puteana decay in Scots pine over 35 days. The model successfully reproduces the experimentally observed moisture evolution: a peak free-water content of 50%–70% during weeks 1–2, followed by a progressive decline, while bound water remains remarkably constant despite advancing decay. Monte Carlo uncertainty quantification demonstrates hierarchical parameter control: bound water is governed solely by thermodynamic factors, while free water responds to interacting biological and physical processes. Time-resolved correlation analysis shows a fundamental transition from colonization-dominated (weeks 1–2) to transport-dominated (weeks 3–5) moisture control, quantitatively explaining the experimentally observed shift from accumulation to depletion. This transport-response framework for analyzing moisture behavior under externally defined decay progression establishes quantitative parameter hierarchies that may inform the development of future substrate-coupled bio-hygrothermal models. Full article

This study quantifies how confinement changes the orientational phase space of proteins by comparing hanging-drop (HD) with Langmuir–Blodgett (LB) conditions within a unified probabilistic framework grounded in structural data from the Protein Data Bank (PDB). For each protein, principal moments of inertia are computed from atomic coordinates, trace-normalized, and used to define a geometry-based benchmark for the probability of occupying a predefined productive-orientation set. In parallel, a Hamiltonian-weighted probability is obtained within a classical statistical–mechanical treatment by reconstructing the orientational distribution over the polar–azimuthal domain under a fixed global confinement protocol. The analysis is carried out on a ten-protein panel spanning diverse sizes and anisotropies, and the HD→LB contrast is characterized through probability gains, distributional distances, and an energy-basin decomposition that distinguishes basin depth from basin measure. Under identical parameterization, LB globally produces higher productive-orientation probabilities than HD across all proteins, establishing a uniform direction of the confinement effect while preserving protein-dependent magnitudes. The inertia-based benchmark exhibits broader dispersion in LB/HD amplification, whereas the Hamiltonian construction yields a more regular cross-protein gain, consistent with LB acting as a global reweighting of orientational phase space rather than a protein-specific re-tuning. By integrating PDB-derived structural descriptors with a statistical–mechanical operator, the framework provides a transparent bridge between molecular geometry and confinement-driven ordering and offers a compact basis for comparing crystallization-relevant confinement protocols across structurally heterogeneous proteins. Full article

The annual occupational personal ultraviolet radiation (UVR) exposure of outdoor workers is vital for several purposes, including non-melanoma skin cancer risk assessment and the recognition of UVR-related pathologies as occupational diseases. Estimations of annual personal exposure (PE) are based on measurements, which are influenced by the measuring period respectively by the start and end time of the measurements, and PEs gained from different periods may differ noticeably. Therefore, we present a method that recalculates PE measurements to any other period (time and duration) during the day, and which is also applicable for measured ambient UVR to determine the relative personal UVR exposure (ERTA). The application shows the necessity of considering not only duration but especially time, as noon hours contribute differently than morning and evening hours. The uncertainties of recalculations are within ±5% if the measuring or target periods last at least 5 h and noon hours are covered. Furthermore, we propose a method to calculate annual PE using ERTA. The application for Austria shows that depending on the work-time model (working hours, working times) and date of holidays, annual PE may differ by up to 30%. Additionally, interannual variability of 16% within a ten-year period suggests avoiding a single year for consideration. Full article

Deforestation in unprotected areas (UPAs) within the Brazilian Amazon affects environmental sustainability and regional climate. This study quantifies shifts in near-surface air temperature, precipitation, and evapotranspiration (ET) during the dry season resulting from UPA loss. Utilizing a five-year ensemble (2015–2019) to isolate the climatic response from interannual variability, simulations indicate a warmer (+1.0 ± 0.4 °C) and drier climate, characterized by a basin-wide 12 ± 8% reduction in precipitation and a 12 ± 4% reduction in ET following UPA removal. This shifted climate state extends to Rondônia, a southwestern state where detailed risk mapping was developed by integrating changes in climate variables with socio-economic, agricultural, and demographic. UPA deforestation, largely external to Rondônia, is associated with a simulated decrease in precipitation by 20 ± 7% and ET by 11 ± 9% coupled with an increase in air temperature by 1.2 ± 0.4 °C. These shifts indicate increased vulnerability for municipalities, including the capital, potentially affecting agricultural productivity. Findings suggest that to protect remaining forests these biophysical risks must be mitigated. This study establishes a spatial framework for identifying municipalities most suceptible to the climatic shifts triggered by UPA loss. Full article

The central role of YB-1 in messenger ribonucleoprotein particle (mRNP) metabolism and stress-granule biology highlights the importance of defining the determinants of its self-assembly. YB-1 fibrillogenesis has been attributed primarily to the cold shock domain (CSD). Here, we show that the YB-1 fragment spanning residues 1–129 (AP–CSD) form amyloid fibrils under near-physiological ionic strength (0.12–0.15 M KCl). Fibrillization proceeds without a pronounced exponential growth phase and increases approximately linearly over 45–50 h. Far-UV circular dichroism (CD) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) indicate no substantial change in overall secondary-structure content during aggregation. In parallel, ¹H nuclear magnetic resonance (NMR) spectroscopy reveals the depletion of soluble species, and oriented fiber X-ray diffraction displays the hallmark cross-β reflections at approximately 4.7 Å and 10 Å. The prolonged formation time implies an activation barrier that is unlikely to require global refolding. Instead, it may reflect early association events such as dimerization or other local rearrangements required for primary nucleation, followed by consolidation into stable intermolecular contacts. Aggregation that preserves a largely native-like fold while establishing cross-β order may reduce recognition by cellular quality-control systems that preferentially target globally unfolded or strongly destabilized states. This provides a plausible framework for how YB-1 derived assemblies could persist under stress and during age-associated proteostasis decline. Full article

Oxidative stress generates oxidized phospholipids (OxPLs) that alter membrane structure and inflammatory lipid signaling, yet the underlying biophysical mechanisms remain poorly understood. Here, we examine how two structurally distinct truncated oxidized phosphatidylcholines (OxPCs), 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC), remodel membrane lateral organization and regulate secretory phospholipase A₂ (sPLA₂) activity. Large unilamellar vesicles composed of sphingomyelin, cholesterol, and either monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or polyunsaturated 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC) were used to reconstitute the liquid-ordered/liquid-disordered (L_o/L_d) phase coexistence characteristic of eukaryotic plasma membranes. Fluorescence spectroscopy revealed that OxPLs modulate lipid packing and nanodomain organization in a structure- and composition-dependent manner. POVPC promoted pronounced membrane ordering and L_o domain stabilization compared with PGPC, particularly in monounsaturated membranes with low cholesterol content. In contrast, PDPC-containing membranes, especially at elevated cholesterol, exhibited enhanced structural resilience to OxPL-induced perturbations. These biophysical changes were associated with distinct functional outcomes. Notably, the relationship between membrane structural parameters and sPLA₂ activity was not linear, indicating a decoupling between bulk membrane properties and enzymatic response. sPLA₂ activity was linked to membrane lateral organization: the size of L_o domains modulate hydrolysis by influencing the physicochemical properties of L_o/L_d interfaces, which may represent preferential sites for enzyme activation. Consistent with this, POVPC reduced sPLA₂ activity through stabilization of ordered domains at both low and high cholesterol, while PGPC enhanced hydrolysis at high cholesterol. Importantly, PDPC-containing membranes attenuated sPLA₂ activity and exhibited a protective effect against OxPC-induced enzymatic activation. Together, these findings identify membrane lateral organization as a key regulator of sPLA₂ function and provide mechanistic insight into how oxidative stress can differentially modulate inflammatory lipid signaling depending on membrane composition. This work highlights membrane organization as an active determinant of enzyme activity and a potential target in pathologies associated with oxidative stress, including atherosclerosis, neuroinflammation, and metabolic disease. Full article

Neural network-based visual identification of animals has significant potential for livestock farming and herd management. Real farm environments rarely provide controlled visual conditions for high-quality dataset collection, which often leads to reduced model performance on out-of-distribution inputs and makes confidence estimation essential for reliable application. This work introduces a conformal prediction framework for animal identification based on pretrained neural network embeddings (ResNet-50 and Swin Transformer), enabling the generation of prediction sets with formal confidence guarantees. By calibrating a nonconformity score derived from cosine distances in the embedding space, the method ensures that the true identity is included in the prediction set at a user-defined confidence level. Three nonconformity scoring functions are evaluated to determine which produces the most compact prediction sets. Experiments on cow and goat datasets demonstrate that the framework achieves empirical coverage close to the target confidence levels across different embedding models. The ratio-based nonconformity measure consistently outperforms others, reducing mean set sizes by up to 79% compared to alternative measures. Swin-T embeddings outperform ResNet-50 by up to 14 percentage points in singleton prediction rate. The proposed framework preserves formal validity guarantees, improving robustness and interpretability in practical livestock applications where standard identification methods return only the nearest match without reliability estimates. Full article

Pitahaya (Hylocereus spp.) production is increasingly affected by climatic factors, as well as by phytopathogens and abiotic stress, leading to delays in agronomic interventions and reduced productivity. The objective was to design, implement, and validate a multimodal system (CARYPAR) that enables early disease detection and agile decision-making, characterized by low latency and reduced dependence on cloud connectivity. The methodology integrates climate reanalysis from NASA POWER, biophysical remote sensing variables derived from Sentinel-1/2, and proximal computer vision captured via mobile devices using a late fusion architecture and an optimized convolutional neural network, EfficientNet-V2B0, which discriminates between optimal and pathological conditions in vegetative tissues and fruit. The results of the experimental validation carried out in 160 georeferenced units achieved an overall accuracy of 80.0% and an F1 score of 0.8645 for Bad Fruit. The McNemar test and the operational agreement with agro-industrial experts yielded a Cohen’s Kappa index of κ = 0.6831, with an inference latency reduced to 22.00 ms. It is concluded that the multimodal integration of satellite bio-environmental data with edge computer vision achieves substantial agreement with agronomic expert judgment under heterogeneous field conditions (Cohen’s κ = 0.6831), supporting its role as a decision-support tool rather than a replacement for expert assessment. Therefore, its adoption can enhance real-time irrigation management and crop protection, while contributing to traceability and sustainable resource management in agricultural regions with limited connectivity. Full article

Polysialic acid (PSA), a highly negatively charged glycan attached mainly to the neural cell adhesion molecule (NCAM), is emerging as a critical but underrecognized extracellular regulator of glutamatergic neurotransmission. While previous literature has focused on PSA’s developmental roles, increasing evidence indicates that PSA–NCAM also contributes to synaptic plasticity mechanisms in the mature brain. This review integrates evidence from structural biophysics, single-channel electrophysiology, and disease models to explain how PSA modulates glutamate receptor gating to control learning and memory. We synthesize findings from biochemical reconstitution, electrophysiological recordings, and in vivo studies to show that PSA can modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor open probability, burst duration, and cooperative gating without affecting conductance, thereby promoting long-term potentiation. Conversely, PSA selectively suppresses GluN2B-containing extrasynaptic N-methyl D-Aspartate (NMDA) receptor activity by lowering open probability and calcium influx, maintaining an optimal balance between potentiation and depression while providing neuroprotection. Disruption of PSA–NCAM signaling in developmental and disease models, including prenatal cannabinoid exposure and neurodegeneration, produces cognitive deficits reversible by PSA restoration. Notably, much of the current evidence derives from in vitro systems, with relatively few studies conducted in vivo, and studies employing PSA mimetics mostly, which should be considered when interpreting physiological relevance. Collectively, the available evidence suggests that PSA functions as an extracellular modulator linking synaptic glycans to glutamate receptor regulation and plasticity related signaling pathways, highlighting the potential importance of extracellular glycan mechanisms in the control of synaptic function. Full article