Search Results (2,784)

Background/Objectives: Calcium hydroxyapatite (CaHA)-based injectable materials are widely used as dermal biostimulators. In vitro models allow for controlled comparison of cellular responses and particle characteristics across formulations. This study aimed to compare two commercially available CaHA-based materials in terms of fibroblast metabolic activity, extracellular matrix-related gene expression, and microsphere morphology. Methods: Primary human dermal fibroblasts were exposed to two CaHA-based materials (Sample R and Sample S) at 10 mg/mL. Metabolic activity was assessed using the MTT assay at 24, 36, 48, and 72 h. Type I collagen and elastin gene expression were evaluated by RT-qPCR at 72 h. Microsphere morphology was analyzed by scanning electron microscopy (SEM). Results: Both materials increased fibroblast metabolic activity compared with the control at all time points. Early responses were similar, whereas Sample S showed higher activity at 48 and 72 h. At 72 h, both materials increased collagen and elastin gene expression versus the control, with greater responses observed for Sample S. SEM analysis showed predominantly spherical microspheres in both materials, with qualitative differences in surface microtopography. Conclusions: Under controlled in vitro conditions, both CaHA-based materials were biocompatible and modulated fibroblast metabolic activity and extracellular matrix-related gene expression. Differences in particle surface characteristics may contribute to the observed biological profiles. These findings support further studies incorporating extended incubation periods and protein-level analyses. Full article

Organophosphate flame retardants (OPFRs) are widely used as flame-retardant additives in plastics, electronics, and building materials. However, growing evidence suggests these compounds may pose significant neurotoxic risks. This study evaluated phenotypic alterations, such as cell viability, reactive oxygen species generation, and acetylcholinesterase activity, induced by seven widely detected OPFRs in SH-SY5Y human neuroblastoma cells. Aromatic OPFRs such as triphenyl phosphate (TPhP), 2-ethylhexyldiphenyl phosphate (EHDPhP) and tricresyl phosphate (TCP) exhibited the strongest effects, including decreased cell viability, increased oxidative stress and AChE inhibition. Therefore, 3D brain organoid models were used to further explore the potential lipidomic alterations induced by aromatic OPFRs. Lipidomic analysis of brain organoids exposed to aromatic OPFRs (TPhP, EHDPhP and TCP) showed significant alterations across major lipid classes, especially glycerophospholipids, sphingolipids, and glycerolipids. The depletion of bis(monoacylglycerol)phosphate (BMP) species suggests perturbations in endolysosomal lipid homeostasis and membrane trafficking pathways. Increased levels of ether-linked lysophosphatidylcholine (LPC-O) species, together with altered phosphatidylethanolamine (PE) and phosphatidylserine (PS) species, indicate extensive membrane lipid remodeling and changes in cellular signaling. Furthermore, the accumulation of diacylglycerol (DG) and triacylglycerol (TG) species points to disturbances in lipid storage and metabolism. Overall, these findings indicate that aromatic OPFRs induce cytotoxicity, oxidative stress, and alteration of cholinergic function, and are associated with lipid dysregulation linked to neurotoxicity in brain organoids. Future research should explore chronic low-dose exposure and long-term neurological effects. Full article

The transition towards carbon-neutral construction materials requires innovative solutions that combine reduced embodied energy, enhanced durability and improved building energy efficiency. This study investigates and compares two novel bioaerated low-density composites—BAAC and BIOAERMAC—developed through biologically driven aeration processes incorporating industrial byproducts. BAAC is produced using Saccharomyces cerevisiae and hydrogen peroxide, replacing conventional aluminum powder and improving safety while enabling the valorization of waste-derived yeast. BIOAERMAC is a gypsum-based composite incorporating synthetic anhydrite, microorganisms, peroxides, and recycled rubber from end-of-life tires. The materials were characterized in terms of hygrothermal behavior and dimensional stability, and compared with commercial autoclaved aerated concrete under equivalent mechanical strength conditions. The results highlight significant differences in moisture transport and shrinkage, primarily governed by pore structure and connectivity. BAAC exhibits behavior comparable to conventional AAC, whereas BIOAERMAC shows reduced capillary and hygroscopic absorption, indicating limited pore connectivity, but higher drying shrinkage. These findings demonstrate the effectiveness of bioaeration in tailoring pore structure and controlling the trade-off between moisture transport, durability, and dimensional stability, highlighting the potential of bioaerated composites for low-carbon and energy-efficient building applications. Full article

Among a broad range of promising applications, the use of cellular solids as lightweight structural components is an important field of research that requires reliable predictions of their stiffness and strength. Predictive and general models should not depend on extensive parameter-fitting experiments and should not rely on computationally intensive numerical calculations for each new set of geometric parameters and loading conditions. An overview of models for 2D, 2.5D, and three-dimensional structures will be presented. Most 2D and 2.5D models neglect out-of-plane behaviour and the face sheets used in sandwich panels. 3D studies, mainly by finite element models (FEMs), are often limited to a narrow set of geometries and simple loading conditions. Elastic anisotropy is well covered, but calculating yield surfaces remains a challenge. Simplified models based on structural mechanics are rare and often limited in scope. They offer a flexible, computationally efficient approach for simulating truss-based materials. For more advanced designs, parameter-based FEMs must be developed for any loading condition to facilitate the generalised incorporation of 3D cellular solids in mechanical design. Artificial intelligence and machine learning are promising approaches for making optimal use of experimental and FEM results across multidimensional parameter spaces. Full article

The safety profile for bio-derived phenols post-oxidation and their related antioxidant/redox potential remain largely under-explored. Oxidation by fungi, in terms of environmental impacts via fungal oxidation by enzymes, remains an attractive strategy under milder conditions, since it is one route by which many naturally occurring lignocellulosic phenols are modified; thus, an immediate need still exists for characterizing the effects that these modified phenolic compounds may have. Methodology: We examined four different biomass-derived phenolics—vanillin, ferulic acid, syringaldehyde and guaiacol—that were oxidized with fungal laccase and characterized their effects on normal human lung fibroblasts and levels of cellular oxidative stress. Laccase activity was evaluated via the ABTS method and through simple observation and UV-Vis spectroscopic scanning of the phenolics in question, and compared with the untreated version of each phenolic. In addition to assessing the cytotoxic effect and oxidative stress generated by the phenols alone, an ELISA-based measurement assay was used to investigate the relative abundance of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in the human normal lung fibroblast cell line under varying treatment regimes, complemented by phase-contrast microscopy. Scores integrating the biomarkers were analyzed via clustering, PCA, radar and Pearson correlation analyses, to discern distinct trends in antioxidant potential after laccase conversion. Observations: Each of the four tested phenolics demonstrated the presence of laccase activity, leading to substantial differences in visible appearance compared with the control and characteristic absorbance shifts at differing wavelengths from the original molecule. Cell viability dropped dramatically as phenol concentration was increased and the untreated phenolics resulted in diminished confluence and induced greater levels of oxidative damage, from guaiacol and syringaldehyde. Laccase treatment resulted in higher MTT reduction activity and improved cellular morphology compared with the corresponding untreated phenolic compounds. Untreated phenols induced the highest levels of MDA, while decreasing SOD, CAT, GPx and GSH levels. Post-oxidation with laccase, there were lower amounts of lipid peroxidation, along with improved levels of antioxidant activity compared with the control phenol. Multi-technique analyses show clear distinctness between the untreated and laccase-converted phenolic groups. Clustering with multivariate techniques separated all cell groups in line with control samples, grouping the laccase-converted treatments towards the middle and displaying an inverse relationship between MDA and the antioxidant markers. Conclusions: Laccase conversion markedly decreases the adverse effects that bio-derived phenols have on normal cell viability and induces fewer detrimental effects on the cellular redox balance. This is a critical discovery in terms of finding greener methods by which to upgrade bio-derived substances as we research these lignocellulosic phenols. By employing ELISA-based measurements along with multiple analysis techniques, we present a suitable paradigm for studying biological effects in all bio-based goods intended for pharmaceuticals, packaging materials, nutraceuticals or a host of different applications. Full article

Arrhythmogenic cardiomyopathy (ACM/ARVC) is an inherited myocardial disease characterized by progressive fibro-fatty replacement, ventricular arrhythmias, and an increased risk of sudden cardiac death. In addition to mutations in desmosomal genes, growing evidence suggests that microRNAs (miRNAs) actively contribute to disease pathogenesis by regulating key processes such as fibrosis, cell adhesion, and cardiac remodeling. This systematic review analyzed the main miRNAs identified in studies of human cardiac tissue and animal models of ARVC. Materials and Methods: Studies based on human myocardial tissue analysis (including autopsy and biopsy samples) and animal models of arrhythmogenic cardiomyopathy were included, using RNA sequencing, small RNA sequencing, miRNA arrays, and RT-qPCR. Studies on circulating miRNAs and narrative reviews were excluded. miRNAs were analyzed in relation to their functional pathways and their role in disease pathogenesis. Results: The synthesis of studies on human and animal cardiac tissue reveals a consistent miRNA signature associated with arrhythmogenic cardiomyopathy. MiR-21-5p and miR-29b-3p are associated with fibrosis and extracellular matrix remodeling, whereas miR-133a-b and miR-130a are linked to cardiomyocyte integrity loss and desmosomal dysfunction. A second group of miRNAs, including miR-217-5p, miR-708-5p, and miR-135b, regulates key pathways such as Wnt/β-catenin and Hippo signaling, contributing to structural remodeling and loss of cellular identity. Furthermore, downregulation of miR-499-5p is associated with mitochondrial dysfunction and cellular vulnerability, while the miR-142-3p, miR-182-5p, and miR-183-5p clusters contribute to differential molecular signatures compared with other cardiomyopathies. Overall, miRNAs converge on three main pathogenic axes: myocardial fibrosis, desmosomal impairment, and remodeling of cellular signaling pathways. Conclusions: The available evidence indicates that arrhythmogenic cardiomyopathy is regulated by a coordinated network of miRNAs that actively drives myocardial damage progression. These miRNAs represent not only biomarkers but also functional mediators of disease, suggesting potential diagnostic and therapeutic applications based on tissue-specific molecular signatures, including in post-mortem settings. Full article

Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article

This study evaluates the intrinsic osteogenic potential of β-tricalcium phosphate (β-TCP)-containing composite scaffolds (PLCL–TCP, PLGA–TCP, and ZnO–TCP) on chorion-derived mesenchymal stem cells (CMSCs) under non-osteogenic in vitro conditions. CMSCs were cultured on the three biomaterials for 35 days without osteogenic supplements to isolate the material-driven cellular response. Cell viability was assessed via MTT assay, while osteogenesis-associated markers (alkaline phosphatase, type I collagen, and osteocalcin) were quantified using ELISA. Scaffold surface morphology and elemental composition were characterized before and after cultivation utilizing SEM and EDX. All investigated scaffolds supported long-term CMSC viability and induced measurable osteogenic responses. PLCL–TCP demonstrated a consistently strong biological response, characterized by sustained metabolic activity, elevated ALP and COL I production, and increased osteocalcin levels at later stages of cultivation. ZnO–TCP also exhibited favorable osteogenesis-associated responses, particularly with respect to late-stage osteocalcin production, while maintaining high structural stability. In conclusion, β-TCP composites can intrinsically modulate CMSC behavior without biochemical supplements. Osteogenic outcomes depend on a complex interplay of surface chemistry, scaffold architecture, and degradation profiles, with PLCL–TCP demonstrating favorable overall performance among the investigated biomaterials. Full article

The mechanical response of cellular structures is governed not only by relative density and average cell geometry but also by the spatial arrangement of cells. However, the manner in which arrangement-dependent effects evolve with increasing cell number has not been systematically clarified. In this study, the compressive behavior of closed-cell structures with varying cell numbers was investigated using finite element analysis under dynamically equilibrated compression conditions while maintaining constant relative density and identical material parameters. Cellular models were generated using hierarchical Poisson disk sampling combined with Voronoi tessellation. The number of cells was increased through three distinct approaches: mirror replication of a reference structure, enlargement of the overall specimen size, and refinement of cell size under fixed external dimensions. To characterize arrangement-dependent effects, two distinct features of the compressive response were introduced: averaging, defined as a reduction in variability across responses from different initial cell arrangements, and smoothing, defined as the suppression of abrupt stress fluctuations within an individual response. Quantitative metrics were employed to evaluate both effects. Averaging was observed in plate-type models compressed in the z-direction and in fixed-size models, whereas mirror-connected models retained strong arrangement dependence despite large cell numbers. Smoothing occurred predominantly in plate-type models compressed in the z-direction and was strongly correlated with the number of cell layers aligned along the compression direction rather than with total cell number alone. The simulations were conducted in a dynamically equilibrated regime in which internal stress equilibrium was achieved during deformation. These results demonstrate that compressive behavior is governed not only by cell number but also by structural arrangement and directional cell-layer alignment, providing mechanistic insight into the transition from arrangement-dependent variability to stable macroscopic response under dynamic compression. Full article

Photodynamic therapy (PDT) represents a promising non-antibiotic strategy for addressing bacterial and fungal infections, particularly in the context of increasing antimicrobial resistance and biofilm-associated disease. PDT is based on the light-induced activation of photosensitizers, leading to the generation of reactive oxygen species (ROS), including singlet oxygen (¹O₂), which induce oxidative damage to multiple microbial targets. Unlike conventional antimicrobial drugs that often act through specific molecular pathways, antimicrobial PDT produces simultaneous damage to membranes, proteins, nucleic acids, and extracellular biofilm components, thereby reducing the probability of resistance development. This review critically analyzes the cellular, biochemical, and biophysical determinants that govern PDT selectivity toward bacterial and fungal cells in comparison with mammalian host tissues. Particular attention is given to photosensitizer localization, membrane interactions, photobleaching, oxygen dependence, light penetration, and the balance between Type I and Type II photochemical mechanisms. The review provides a comparative overview of major molecular photosensitizer classes, including phenothiazines, porphyrins, chlorins, phthalocyanines, xanthene dyes, natural polyphenols, endogenous compounds, and advanced targeted photosensitizers. In addition, this review distinguishes molecular photosensitizers from nanotechnology-based platforms and delivery systems. Nanoparticles, polymeric carriers, hydrogels, and light-activated coatings are discussed not only as photosensitizer delivery tools, but also as systems that modulate aggregation, improve localization, enhance biofilm penetration, and enable surface-confined ROS generation. ROS are capable of causing phototoxic effects wherever they are located. Unless selectively accumulated by target organisms, there can be systemic phototoxicity. Overall, PDT should be regarded as a modular antimicrobial platform in which photosensitizer chemistry, formulation, light delivery, oxygen availability, and infection biology must be co-optimized. Although further studies are required to address clinical translation, regulatory complexity, material safety, and standardized treatment protocols, PDT offers a scientifically robust and clinically relevant approach that may complement conventional antibacterial and antifungal therapies, especially in localized, biofilm-associated, and device-related infections. Full article

Surface engineering is a key strategy for modulating the biological behavior of TiO₂-based nanomaterials, with potential relevance for future localized or adjuvant approaches targeting residual cancer cells. This study evaluated whether amine functionalization and subsequent gold decoration modify the effects of TiO₂ nanoparticles (TiO₂NPs) on MCF7 and MDA-MB-231 breast cancer cells. The synthesized materials preserved the anatase TiO₂ framework, while surface modification altered their physicochemical and optical properties. After 24 h of exposure, pristine TiO₂NPs produced minimal changes in cell viability, whereas NH₂-functionalized TiO₂NPs (TiO₂NPs-NH₂) and gold-decorated NH₂-functionalized TiO₂NPs (Au@TiO₂NPs-NH₂) reduced viability in a concentration-dependent and cell line-dependent manner. These effects were more evident in the MTT assay than in Trypan Blue exclusion counting, suggesting changes in metabolic activity before extensive membrane integrity loss. Overall, the findings indicate that surface modification, rather than the TiO₂ core alone, is a major determinant of the cellular response to these nanomaterials. These results provide an initial in vitro basis for further mechanistic studies evaluating surface-engineered TiO₂NPs as candidate platforms for future adjuvant breast cancer strategies. Full article

This study develops an integrated computational framework to assess the passage efficiency of a dam crest serving as a critical inter-regional corridor following a severe explosion event. The framework combines a physics-based damage model with an agent-based cellular automata (CA) approach that incorporates pedestrian behavioral heterogeneity. The damage model conceptualizes three concentric zones: a complete fragmentation zone (0–1.5 m) with total material disintegration, a primary damage zone (1.5–5 m) following an exponential decay in structural integrity, and a secondary damage zone (5–20 m) governed by a power-law attenuation of fragmentation effects. Pedestrian behavior is parameterized by the Allowable Conflict Coefficient (ACC), the inverse of interpersonal friction, and the Emergency Level (EL), which scales the desired velocity. Extensive simulations under stochastic and targeted impact scenarios reveal a consistent evacuation performance hierarchy: Center (C) > Bottom-Left (BL) > Top-Left (TL) > Bottom-Right (BR) ≈ Top-Right (TR). Exit-proximal damage (TR, BR) increased evacuation time by up to 85% compared with central impacts. Results demonstrate a strong coupling between physical friction and urgency: the “faster-is-faster” effect is maximized under low friction (high ACC), while high friction not only suppresses the benefits of elevated EL but can also induce “faster-is-slower” phenomena under extreme conditions. These findings underscore that optimal evacuation strategies depend critically on both impact location and crowd behavior management, providing actionable insights for emergency planning and highlighting the importance of conflict mitigation in enhancing infrastructure resilience. The proposed framework thus offers a versatile and validated simulation tool for emergency planners to proactively assess and optimize evacuation strategies under various damage scenarios. Full article

Neuroimmune interactions in the intestine are essential for maintaining tissue homeostasis, yet they remain poorly understood in teleost fish. This study investigated the structural and cellular organization of enteric neurons and immune cells in the intestine of goldfish (Carassius auratus) using semithin histology, transmission electron microscopy (TEM), and confocal immunofluorescence. Histological observations revealed a well-organized epithelium composed of enterocytes and goblet cells, with numerous lymphocytes located in the basal epithelium. Prominent gut-associated lymphoid tissue (GALT) was identified in both scattered and aggregated forms within the lamina propria and submucosa. Macrophages were widely distributed throughout all intestinal layers and were consistently found in close proximity to enteric neurons and nerve fibers. Ultrastructural analysis confirmed direct contacts between macrophages and neuronal elements. These macrophages exhibited typical phagocytic features, including lysosomes, vacuoles, and engulfed material, particularly in association with myenteric nerve fibers. Immunofluorescence analysis revealed strong expression of toll-like receptor 2 (TLR2) and major histocompatibility complex class II (MHC II) in macrophages and enterocytes, suggesting an active role in antigen recognition. Langerin-positive dendritic-like cells were identified in the submucosa, while CD4-positive lymphocytes showed partial colocalization with serotonin (5-HT). S100-positive cells also exhibited partial overlap with 5-HT, and goblet cells demonstrated serotonin immunoreactivity. In addition, inducible nitric oxide synthase (iNOS) colocalized with TLR2 in submucosal immune cells. These findings demonstrate a close structural and functional association between enteric neurons and immune cells, highlighting an integrated neuroimmune network in the goldfish intestine. Full article

The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article

High-performance thermal protection materials are urgently required in harsh thermal environments, such as hypersonic vehicles, the thermal runaway of energy batteries and high-temperature equipment. Conventional aerogels only exhibit passive thermal insulation and fail to resist instantaneous high-temperature attack. Herein, a cooling material of ammonium oxalate (AO) was introduced to achieve efficient, active endothermic protection. A cellular isolation effect induced by graphene nanosheets combined with anti-solvent crystallization was adopted to significantly decrease the size of AO crystals by over 93%. Based on superfine morphology and the constructed conduction network, the decomposition rate and heat absorption capacity of obtained graphene-doped AO powders (GdAPs) are improved by 41.2% and 30.4%, respectively. The mechanisms of morphology regulation and enhanced heat absorption are explored specifically in this study. Furthermore, GdAPs are embedded in phenolic resin to prepare thermal protection composite materials. Benefiting from their nearly complete thermal decomposition, GdAPs serve as a sacrificial template to generate discrete micropores in pyrolyzed resin. So, the as-prepared carbon aerogels (CAs) with a regulable microstructure exhibit an extremely low thermal conductivity of 0.056 W/(m·K), which is lower than those of reported CAs with the same density. Based on the above advantages, a synergistic endothermic-insulating thermal protection material is reported for the first time, and its heating rate is only 28.6% of that of commercial silica aerogel under identical high-temperature shock. Therefore, a new accessible strategy is demonstrated to provide high-efficiency thermal protection for resisting both abrupt and prolonged high temperature. Full article