Search Results (736)

This study numerically investigates the effects of red blood cell (RBC) volume fraction (hematocrit) and RBC diameter on cell distribution, cell-free layer (CFL) thickness and pressure drop in a microchannel with sudden expansion. Hematocrit levels of 0.2, 0.3, 0.4 and 0.5, together with RBC diameters of 4, 8 and 11 µm, are considered, where deviations from the physiological diameter of 8 μm represent pathological conditions. An Euler–Euler approach is employed to model the multiphase flow, treating RBCs as rigid spherical particles, while the non-Newtonian viscosity of blood is represented using a modified Carreau–Yasuda model. The numerical predictions are validated against existing experimental and numerical data. The effect of volumetric flow rate on RBC distribution is found to be limited; therefore, a representative flow rate of 100 μL/min is adopted for the subsequent analysis. The results show that RBC migration and the resulting cell distribution are strongly governed by RBC size and hematocrit. The pressure drop is primarily influenced by hematocrit, while the effect of RBC size is relatively weak. A minimum value for pressure drop is observed at a hematocrit of 0.3, indicating an optimal hematocrit level for minimizing flow resistance. A parabolic correlation is proposed for predicting the pressure drop as a function of hematocrit, with a maximum relative error of 1.13%. This study contributes to the understanding of pathological RBC size variations and their impact on microscale hemodynamics. Full article

This study develops a novel Locally Rib-Reinforced Rotational Hexagonal Honeycomb (LRRH) model. The objective is to systematically enhance the model’s mechanical performance and energy absorption efficiency through geometric morphology construction. The structure combines triangular and hexagonal units through a rotational arrangement, forming a rotating rigid structure (RRH), upon which re-entrant parallelogram units are embedded. A Finite Element simulation was developed in Abaqus/Explicit. Its reliability was validated by comparing the numerical predictions against the outcomes of quasi-static compression experiments. The axial impact response and energy absorption attributes of the configuration were thoroughly evaluated by adjusting the hexagonal cell angles and applying a symmetric design approach. The experimental outcomes indicate that the SEA of the RRH-Type I-180°-180° model surpasses that of the RRH-Type I-105°-105° by 43.68%, and the SEA of the LRRH-Type I-105°-105° achieved a significant 97.88% increase compared to the LRRH-Type I-180°-180° variant. Meanwhile, the SEA of the RRH-Type I-180°-180° honeycomb increased by 121.2% and 11.79% compared with the LRRH-Type I-180°-180° and LRRH-Type I-105°-105° structures. Parametric analysis results indicate that wall thickness and impact velocity are critical factors influencing energy absorption performance. The enhancement of structural thickness considerably strengthens its flexural resistance and pressure tolerance. Full article

Diabetes mellitus is increasingly recognized as a biologically heterogeneous disorder that extends beyond traditional phenotype-based classifications. Advances in human genetics have revealed that monogenic and polygenic forms of diabetes are not discrete entities, but rather represent points along a continuum of genetic architectures that converge on shared molecular pathways governing pancreatic β-cell identity, function, and survival. Rare monogenic forms, including maturity-onset diabetes of the young and neonatal diabetes, arise from highly penetrant single-gene defects that directly impair transcriptional regulation, glucose sensing, insulin biosynthesis, or stimulus–secretion coupling. Although individually uncommon, these disorders provide high-resolution models of β-cell dysfunction and have demonstrated the clinical value of genotype-guided diagnosis and therapy. At the opposite end of the spectrum, type 1 and type 2 diabetes result from complex interactions between multiple genetic variants and environmental factors, with genome-wide association studies highlighting a central role for genetically determined β-cell vulnerability alongside immune-mediated and metabolic stress pathways. Importantly, intermediate phenotypes such as latent autoimmune diabetes in adults further illustrate the overlap between autoimmune and metabolic mechanisms, challenging rigid diagnostic boundaries. This review synthesizes current evidence on the genetic architecture of diabetes across monogenic and polygenic forms, emphasizing convergent molecular mechanisms and their translational implications. By integrating insights from rare genetic disorders with findings from large-scale population studies, we propose a continuum-based framework that supports a shift from phenotype-driven labels toward a mechanistic, biology-informed approach to diabetes classification, risk stratification, and personalized care. Full article

Frankliniella occidentalis (Pergande) is a globally invasive pest that inflicts significant damage on economically important vegetable crops such as cucumbers (Cucumis sativus L.) and cowpeas (Vigna unguiculata L. Walp). To elucidate the interactions between host plants and F. occidentalis and to support the development of sustainable management strategies, this study evaluated the host selectivity and life history parameters of F. occidentalis living on these plant species to assess its adaptability. Transcriptome–metabolome profiles and associated metabolites were analyzed in healthy plants and in those infested by F. occidentalis for 48 h to characterize the defense responses of both host species. The results showed that both plant species are attractive to F. occidentalis, with a stronger preference observed for cowpeas. However, the reproductive output of F. occidentalis was significantly higher on cucumbers (16.99 ± 0.43 eggs/female) than on cowpeas (12.00 ± 0.38 eggs/female) plants, indicating a mismatch between host preference and performance. Feeding by F. occidentalis strongly induced the brassinolide and jasmonic acid signaling pathways, activated the phenylpropanoid metabolic pathway, increased the accumulation of the lignin precursor sinapyl alcohol, and promoted lignin biosynthesis, thereby enhancing cell wall rigidity as a physical defense barrier. These findings demonstrate that cucumbers and cowpeas coordinately regulate lignin synthesis through hormone–metabolism crosstalk as a defensive strategy against thrips attack. In response, F. occidentalis adjusts its host selection and reproductive investment to overcome plant defenses, reflecting an adaptive counter-strategy in host–herbivore interactions. This study provides new insights into the molecular mechanisms underlying plant–thrips interactions and supports the development of environmentally friendly pest control approaches. Full article

Tubulin is a heterodimeric protein composed of α- and β-subunits, which polymerize to form the cell’s microtubules. The latter are key components in mitotic spindle formation and essential targets in anticancer therapy. Compounds such as paclitaxel, tubulysins, dolastatins and synthetic analogues of these latter compounds, including cemadotin, exert their cytotoxic effects by disrupting microtubule dynamics. Previously, we reported the production and anticancer activity of a library of cemadotin analogues featuring a C-terminal tertiary amide functionalized with a variety of N-substituents, thus resulting in compounds occurring as a mixture of amide rotamers. Here we describe a comprehensive NMR and conformational study that provides new insights into the effect of the conformational equilibrium on the binding mode of the novel cemadotin analogues to the tubulin target. The conformational behavior of the isomer equilibrium of cemadotin’s terminal amide bond was investigated by TOCSY and ROESY NMR experiments, which allowed the identification and quantification of individual rotamer populations. A slow interconversion between the s-cis and s-trans amide rotamers was observed under standard NMR conditions (25 °C), indicating a significant energy barrier and conformational rigidity. Molecular docking and saturation transfer difference (STD) NMR experiments were performed with a representative analogue and tubulin to assess the binding mode. The results revealed that the s-trans rotamer is the predominant conformer in solution and exhibits a more favorable interaction with tubulin compared to the s-cis isomer, thus helping to understand the conformational requirements for an improved tubulin binding and the inhibition of the polymerization process. Full article

Background: Sickle cell disease (SCD) is a hereditary blood disorder marked by the production of abnormally shaped, rigid red blood cells that obstruct blood flow, resulting in pain, organ damage, and increased infection risk. SCD poses a significant public health challenge in Nigeria, which has the highest global burden, with about 150,000 affected children born annually. The high prevalence is exacerbated by limited healthcare infrastructure, low public awareness, and socio-economic barriers, making effective disease management difficult. Understanding the knowledge of home-based caregivers is essential to identify gaps that may impact care quality. This study was performed within the African Research and Innovative Initiative for Sickle Cell Education (ARISE, EC GA No 824021) project to develop best practice in the clinical management of SCD. Aim: This study explores the knowledge, experiences, and educational needs of home-based caregivers of children with SCD attending the Paediatric Haematology Clinic, ABUTH, Zaria. Methods: A qualitative case study design was used, involving in-depth interviews with ten purposively selected caregivers. Interviews were conducted in Hausa, transcribed, and translated into English. Thematic analysis was performed. Results: Four themes emerged: 1. Understanding of SCD aetiology 2. Knowledge of symptoms 3. Awareness of complications and 4. Knowledge of SCD type. Conclusions: Home-based caregivers had limited knowledge of the genetic basis of the disease, but possess some knowledge of SCD key symptoms, enabling basic disease management and healthcare seeking. However, there is a need to enhance caregiver education to improve care quality and health-seeking behaviour for children with SCD. Full article

The significant disparity between the size and electronegativity of N and group-V (P, As, Sb) atoms in dilute III–V-Ns remains a cornerstone for developing the next-generation electronics. Variations in the structural, optical, and phonon properties of the quaternary GaAs_1−x−ySb_yN_x alloys are being used for improving the high-performance photovoltaic energy and optoelectronic technologies. Bandgap ${\mathrm{E}}_{\mathrm{g}}$ tunability has assisted efficient light emission/detection to cover the crucial optical fiber wavelengths for the low-cost integrated chips in data communications and sensing devices. The lattice dynamical properties of these materials are critical for assessing the reliability to evaluate the performance of long-wavelength lasers, photodetectors, and multi-junction solar cells. Our systematic Raman measurements on high-quality MBE grown $\mathrm{G}\mathrm{a}{\mathrm{A}\mathrm{s}}_{0.946}{\mathrm{S}\mathrm{b}}_{0.032}{\mathrm{N}}_{0.022}$/GaAs samples have detected ${\mathsf{\omega }}_{\mathrm{T}\mathrm{O}\left(\mathsf{\Gamma }\right)}^{\mathrm{G}\mathrm{a}\mathrm{A}\mathrm{s}}$ and ${\mathsf{\omega }}_{\mathrm{T}\mathrm{O}\left(\mathsf{\Gamma }\right)}^{\mathrm{G}\mathrm{a}\mathrm{A}\mathrm{s}}$ phonons along with a high frequency N_As local mode near ~476 cm⁻¹. Weak phonon structures on both sides of the broad 476 cm⁻¹ band are interpreted forming a complex N_As–Ga–Sb_As defect center. Using a realistic rigid-ion model in the Green’s function framework, the simulations of impurity modes for isolated and complex defects have provided corroboration to the experimental data. Full article

Exocytosis is a fundamental biological process in all eukaryotes involving the vesicular transport of cellular cargo to the plasma membrane or extracellular space. However, in walled organisms such as plants, fungi, and certain archaea, the rigid cell wall presents a unique barrier to vesicular secretion. The dense, structured matrix of the mature cell wall restricts the passage of macromolecules and vesicles, raising the fundamental question of how vesicle secretion operates in this constrained environment. In the present study, we integrate transmission electron microscopy (TEM), cryo-electron tomography (cryo-ET), and serial section electron tomography (SS-ET) to investigate the structural mechanisms underlying cell wall-related exocytosis. We demonstrate that secretory vesicles do not undergo fusion with the plasma membrane in cell wall-related vesicle secretion in Arabidopsis thaliana (A. thaliana) and Saccharomyces cerevisiae (S. cerevisiae). Furthermore, in the floral nectary of A. thaliana, we identify the details of vesicles inside the multivesicular body (MVB)-like structure in cell wall. Collectively, these results reveal distinct vesicle secretion pathways adapted to the presence of a cell wall, expanding our understanding of how secretory vesicles traverse and deliver cargo beyond the plasma membrane in walled eukaryotic cells. Full article

Soybean (Glycine max) is a globally important crop valued for its high seed oil and protein content. However, lodging remains a major abiotic constraint that causes substantial yield losses. Lodging resistance is primarily determined by stem strength and toughness, which are governed by stem anatomical organization, vascular tissue development, and the composition and architecture of secondary cell walls (SCWs). This review synthesizes current knowledge on anatomical, structural, and genetic factors that are implicated in stem mechanical performance in dicotyledonous plants, with particular emphasis on vascular cambium activity, xylem and phloem differentiation, and the biosynthesis of major SCW components, including cellulose, hemicellulose, and lignin. These processes collectively determine stem rigidity, flexibility, and resistance to mechanical stress. By integrating insights from model species, especially Arabidopsis thaliana, and non-soybean dicots, this review highlights conserved regulatory pathways controlling stem development and SCW formation that are directly relevant to soybean improvement. The synthesis provides a translational framework for understanding how conserved anatomical and genetic mechanisms can be leveraged to enhance soybean stem strength, toughness, and lodging resistance. Overall, this review provides a conceptual foundation for future functional studies and breeding strategies to improve soybean yield stability and adaptability across diverse agronomic conditions. Full article

Cancer metastasis, the spread of tumour cells from the primary site to distant organs, is responsible for over 90% of cancer deaths, yet effective treatments remain elusive due to incomplete understanding of the molecular drivers involved. Podocalyxin (PODXL), a protein overexpressed in many aggressive cancers, links the cell membrane to the internal skeleton through its interaction with Ezrin, an actin cytoskeleton cross-linker. Despite its therapeutic relevance, the PODXL–Ezrin interface remains structurally uncharacterised and pharmacologically intractable. Here, we employed an integrated computational approach combining protein–protein docking, molecular dynamics (MD) simulations, and virtual screening to investigate the structural basis of the PODXL–Ezrin interaction. Using AlphaFold-predicted structures, we modelled PODXL and Ezrin complexes, revealing that PODXL’s cytoplasmic domain stabilises upon Ezrin binding, with Arg495 mediating temporally distinct electrostatic interactions essential for initial complex assembly. Particularly, we characterised the R495W missense mutation in PODXL’s Ezrin-binding domain, demonstrating that substitution of arginine with bulky, hydrophobic tryptophan may allosterically destabilise Ezrin’s dormant conformation. This mutation slightly increases the intramolecular distance between the F3 subdomain and C-terminal domain from 2.59 Å to 3.40 Å, thus leading to potential partial unmasking of the Thr567 phosphorylation site that could plausibly prime Ezrin for activation. Molecular dynamics simulations in the WT state with a total simulation time of 100 ns revealed enhanced structural rigidity and reduced radius of gyration fluctuations in the mutant complex, consistent with a potential “locked,” activation-prone state that amplifies oncogenic signalling. Through virtual screening, we identified NSC305787 as a selective destabiliser of the R495W mutant complex by disrupting key Trp495–pre-C-terminal loop Ezrin interactions and causing steric hindrance to PIP2 recruitment. Our findings identified mutation-dependent changes in drug binding that can guide the development and repurposing of compounds for targeting PODXL-related cancers and improve patient outcomes in PODXL-altered malignancies. Full article

Background/Objectives: Imatinib, the first tyrosine kinase inhibitor, marks the beginning of a revolution in clinical oncology. Disrupting oncogenic kinase-dependent signaling pathways represents a key strategy for advancing targeted cancer therapies. Terpene analogues of imatinib were developed to probe the influence of terminal ring modifications on BCR-ABL inhibition and downstream oncogenic signaling. Methods: Nine novel imatinib analogues bearing bulky aliphatic moieties were designed, synthesised, and structurally characterized by ¹H/¹³C NMR spectroscopy and high-resolution mass spectrometry (HRMS). Molecular docking calculations were performed to assess the binding modes and intermolecular interactions. The cytotoxicity of the newly synthesized imatinib derivatives was evaluated across a panel of BCR-ABL+ leukemia cell lines. Results: Molecular docking analyses demonstrated conserved interactions within the ATP-binding site of BCR-ABL for all derivatives, with calculated docking scores ranging between 123 and 128, while modifications at the terminal ring introduced subtle changes in electrostatic and steric profiles. Biological evaluation using MTT-based cytotoxicity assays in BCR-ABL+ leukemic cell lines revealed enhanced antiproliferative activity compared with imatinib, with compounds 6a (flexible cyclohexyl) and 6d (rigid camphane-type (+)-isopinocampheyl) exhibiting the lowest micromolar activity in the AR-230 model (IC₅₀ values of 1.1 and 1.2 μM, respectively). Proteome-wide phosphokinase profiling demonstrated shared suppression of STAT5/3/6, RSK1/2, S6K1/p70, and Pyk2, confirming effective disruption of canonical BCR-ABL pathways. Critically, the terpene moiety dictated downstream pathway bias: 6a preferentially attenuated CREB activation, whereas 6d more effectively suppressed the PI3K/Akt oncogenic axis and strongly activated proapoptotic p53-mediated stress responses. Conclusions: Our findings establish terpene-engineered imatinib analogues as tunable modulators and promising candidates for targeting downstream BCR-ABL signaling pathways in leukemia treatment. Full article

Multifunctional wound dressings integrating moisture retention, antibacterial activity, and bioactive delivery are in demand, yet balancing structural stability and functional synergy in polysaccharide hydrogels remains a challenge. This study focused on developing such advanced dressings. Poria cocos glucan (PCG) hydrogels were fabricated via annealing, with PCG-4 (4 wt.%) identified as the optimal matrix. PCG-tannic acid (TA) composite hydrogels were subsequently prepared via TA loading, followed by systematic property characterization and in vivo wound healing evaluation in a rat full-thickness wound model. The composite hydrogel exhibited balanced porosity (56.7 ± 3.4%) and swelling (705.5 ± 11.3%), along with enhanced mechanical rigidity. It enabled temperature-responsive TA release, coupled with high antioxidant activity and antibacterial efficacy. Additionally, it showed excellent biocompatibility (hemolysis rate <2%; NIH-3T3 cell viability >98%) and accelerated rat wound closure with enhanced collagen deposition, suggesting a beneficial combined effect of the composite’s components. PCG-TA holds promise as an advanced wound dressing, and the scalable annealing fabrication strategy supports its translational application potential. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, resulting in cardinal motor symptoms such as tremor, rigidity, and bradykinesia. Neuroinflammation is increasingly recognized as a central driver of PD onset and progression in which oligodendrocytes, astrocytes, and microglia engage in complex bidirectional crosstalk that shapes the inflammatory milieu of the central nervous system. Pathological activation of glial cells triggers the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, thereby exacerbating neuronal injury and contributing to sustained disease progression. Modulating maladaptive glial activation states and their intercellular communication represents a promising therapeutic avenue aimed at mitigating neuroinflammation and slowing PD pathology. This review synthesizes current knowledge on neuroinflammation in PD, focusing on the distinct roles of microglia, astrocytes, and oligodendrocytes, their interaction networks, and emerging therapeutic strategies. Full article

Extracellular polymeric substances (EPSs) produced by actinomycetes of the genus Rhodococcus play crucial roles in their ecological success, metabolic versatility, and biotechnological value. This review summarizes existing studies of Rhodococcus EPSs, emphasizing the biochemical composition, functional attributes, and practical significance of EPSs, as well as their importance in biomedicine, bioremediation, and other applications (food industry, biomineralization) with respect to the EPS chemical composition and biological roles. Rhodococcus species synthesize complex EPSs composed primarily of polysaccharides, proteins and lipids that, like in other bacteria, support cell adhesion, aggregation, biofilm formation, and horizontal gene transfer (and can prevent exogenous DNA binding) and are highly important for resistance against toxicants and dissolution/assimilation of hydrophobic compounds. EPSs produced by different species of Rhodococcus exhibit diverse structures (soluble EPSs, loosely bound and tightly bound fractions, capsules, linear and branched chains, amorphous coils, rigid helices, mushroom-like structures, extracellular matrix, and a fibrillar structure with a sheet-like texture), leading to variations in their properties (rheological features, viscosity, flocculation, sorption abilities, compression, DNA binding, and interaction with hydrophobic substrates). Notably, the EPSs exhibit marked emulsifying and flocculating properties, contributing to their recognized role in bioremediation. Furthermore, EPSs possess antiviral, antibiofilm, anti-inflammatory, and anti-proliferating activities and high viscosity, which are valuable in terms of biomedical and food applications. Despite extensive industrial and environmental interest, the molecular regulation, biosynthetic pathways, and structural diversity of Rhodococcus EPSs remain insufficiently characterized. Advancing our understanding of these biopolymers could expand new applications in biomedicine, bioremediation, and biotechnology. Full article

Chitin–glucan complex (CGC) is a naturally occurring heteropolysaccharide in which chitin chains are covalently integrated with β-glucans, forming a rigid structural framework in fungal and yeast cell walls. CGC exhibits a broad spectrum of functional properties, including antimicrobial, antioxidant, adsorption, and tissue-regenerative activities; however, its technological exploitation has been severely constrained by its intrinsic insolubility in water and most common solvents. In this work, CGC was isolated from Aspergillus niger mycelial biomass and, for the first time, completely dissolved in a precooled aqueous NaOH/urea solvent system (12 wt.% NaOH, 8 wt.% urea) within 5 min at ambient temperature, yielding a clear and stable solution. The influence of alkali concentration on dissolution efficiency and solution stability was systematically examined. Structural integrity and covalent linkage between chitin/chitosan and glucan segments were confirmed using FTIR spectroscopy, two-dimensional NMR, and electron microscopy. The degree of deacetylation determined by NMR was approximately 25%. Rheological analysis revealed concentration- and temperature-dependent sol–gel transitions, with well-defined storage and loss moduli during gelation. Crosslinking with epichlorohydrin enabled the fabrication of lightweight, highly porous three-dimensional CGC aerogels. In vitro cytocompatibility studies using NIH 3T3 fibroblasts demonstrated no detectable cytotoxicity over 72 h. These results establish a green, efficient route for CGC dissolution and processing and highlight the promise of CGC aerogels as sustainable biomaterials for biomedical and environmental applications. Full article