Search Results (53)

Maintaining the required relative humidity values in the vehicle cabin is an important HVAC task, along with considerations related to the temperature, velocity, air pressure and noise. Deviation from the optimal values worsens the psycho-physiological state of the driver and affects the energy efficiency of the train. In this study, a model of liquid film formation on and removal from various cabin surfaces was constructed using the fundamental Navier–Stokes hydrodynamic equations. A special transport model based on the liquid vapor diffusion equation was used to simulate the air environment inside the cabin. The evaporation and condensation of surface films were simulated using the Euler film model, which directly considers liquid–gas and gas–liquid transitions. Numerical results were obtained using the RANS equations and a turbulence model by means of the finite volume method in Ansys CFD. Conjugate fields of temperature, velocity and moisture concentration were constructed for various time intervals, and the dependence values for the film thicknesses on various surfaces relative to time were determined. The verification was conducted in comparison with the experimental data, based on the protocol for measuring the microclimate indicators in workplaces, as applied to the train cabin: the average ranges encompassed temperature changes from 11% to 18%, and relative humidity ranges from 16% to 26%. Comparison with the results of other studies, without considering the phase transition and condensation, shows that, for the warm mode, the average air temperature in the cabin with condensation is 12.5% lower than without condensation, which is related to the process of liquid evaporation from the heated walls. The difference in temperature values for the model with and without condensation ranged from −12.5% to +4.9%. We demonstrate that, with an effective mode of removing condensate film from the window surface, including recirculation modes, the energy consumption of the climate control system improves significantly, but this requires a more accurate consideration of thermodynamic parameters and relative humidity. Thus, considering the moisture condensation model reveals that this variable can significantly affect other parameters of the microclimate in cabins: in particular, the temperature. This means that it should be considered in the numerical modeling, along with the basic heat transfer equations. Full article

Viral lung infections are a never-ending threat to public health due to the emergence of new variants and their seasonal nature. While vaccines offer some protection, the need for effective antiviral drugs remains high. The existing research methods using 2D cell culture and animal models have their limitations. Human cell-based tissue engineering approaches hold great promise for bridging this gap. Here, we describe a microextrusion bioprinting approach to generate three-dimensional (3D) lung models composed of four cell types: endothelial cells, primary fibroblasts, macrophage cells, and epithelial cells. A549 and Calu-3 cells were selected as epithelial cells to simulate the cells of the lower and upper respiratory tract, respectively. Cells were bioprinted in a hydrogel consisting of alginate, gelatin, hyaluronic acid, collagen, and laminin-521. The models were cultured under air–liquid interface (ALI) conditions to further enhance their physiological relevance as lung cells. Their viability, metabolic activity, and expression of specific cell markers were analyzed during long-term culture for 21 days. The constructs were successfully infected with both a seasonal influenza A virus (IAV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, demonstrating their potential for studying diverse viral infections. Full article

Cholesterol plays an essential role in biological membranes and is crucial for maintaining their stability and functionality. In addition to biological membranes, cholesterol is also used in various synthetic lipid-based structures such as liposomes, proteoliposomes, and nanodiscs. Cholesterol regulates membrane properties by influencing the density of lipids, phase separation into liquid-ordered (Lo) and liquid-disordered (Ld) areas, and stability of protein–membrane interactions. For planar bilayers, cholesterol thickens the membrane, decreases permeability, and brings lipids into well-ordered domains, thereby increasing membrane rigidity by condensing lipid packing, while maintaining lateral lipid mobility in disordered regions to preserve overall membrane fluidity. It modulates membrane curvature in curved bilayers and vesicles, and stabilizes low-curvature regions, which are important for structural integrity. In liposomes, cholesterol facilitates drug encapsulation and release by controlling bilayer flexibility and stability. In nanodiscs, cholesterol enhances structural integrity and protein compatibility, which enables the investigation of protein–lipid interactions under physiological conditions. In proteoliposomes, cholesterol regulates the conformational stability of embedded proteins that have implications for protein–lipid interaction. Developments in molecular dynamics (MD) techniques, from coarse-grained to all-atom simulations, have shown how cholesterol modulates lipid tail ordering, membrane curvature, and flip-flop behavior in response to concentration. Such simulations provide insights into the mechanisms underlying membrane-associated diseases, aiding in the design of efficient drug delivery systems. In this review, we combine results from MD simulations to provide a synoptic explanation of cholesterol’s complex function in regulating membrane behavior. This synthesis combines fundamental biophysical information with practical membrane engineering, underscoring cholesterol’s important role in membrane structure, dynamics, and performance, and paving the way for rational design of stable and functional lipid-based systems to be used in medicine. In this review, we gather evidence from MD simulations to provide an overview of cholesterol’s complex function regulating membrane behavior. This synthesis connects the fundamental biophysical science with practical membrane engineering, which highlights cholesterol’s important role in membrane structure, dynamics, and function and helps us rationally design stable and functional lipid-based systems for therapeutic purposes. Full article

The development of alternatives to animal models and traditional cell cultures has led to the emergence of organ-on-chip (OoC) systems, which replicate organ functions under both physiological and pathological conditions. These microfluidic platforms simulate key tissue interfaces—such as tissue–air, tissue–liquid, and tissue–tissue interactions—while incorporating biomechanical stimuli to closely resemble in vivo environments. This makes OoC systems particularly suitable for modeling biological barriers such as the skin, the placenta, and the blood–brain barrier, which play essential roles in maintaining homeostasis. This review explores various biological barrier models that can be replicated using the OoC technology, discussing the integration of induced pluripotent stem cells (iPSCs) to advance personalized medicine. Additionally, we examine the methods for assessing barrier formation, including real-time monitoring through integrated sensors, and discuss the advantages and challenges associated with these technologies. The potential of OoC systems in disease modeling, drug discovery, and personalized therapeutic strategies is also highlighted. Full article

This study investigated the role of synthetic mucus coatings in enhancing the physiological relevance of in vitro nasal spray deposition assessments using 3D-printed nasal cavity models. Synthetic mucus solutions, representing normal (0.25% w/v xanthan gum) and diseased (1% w/v xanthan gum) nasal conditions, were developed to mimic the viscoelastic properties of human nasal mucus. Their physical properties, including viscosity, surface tension, contact angle, and adhesivity on dry and synthetic mucus-coated stereolithography (SLA) surfaces, were systematically characterized. Comparative experiments evaluated the behavior of saline drops and liquid films on dry versus synthetic mucus-coated SLA surfaces at inclinations of 30°, 45°, and 60°. Observational deposition experiments using anatomically accurate nasal models were conducted under a 45° backward-tilted head position with gentle sniff airflow across uncoated, 0.25% w/v mucus-coated, and 1% w/v mucus-coated surfaces. Synthetic mucus coatings significantly influenced saline spray deposition patterns. On uncoated surfaces, deposition consisted of scattered droplets and limited film formation, mainly in the anterior and turbinate regions. In contrast, synthetic mucus coatings facilitated broader and more uniform liquid distribution due to diffusion and lubrication effects. These findings highlight the value of synthetic mucus coatings for better simulating nasal environments, offering insights to optimize nasal spray formulations and delivery devices. Full article

Background: Surface-enhanced Raman spectroscopy (SERS) analysis of urine is a promising liquid biopsy technique for cancer detection. However, its clinical translation is hindered by two major challenges that impact classification efficacy. First, the SERS signal of urine is confounded by fluctuations induced by physiological differences in urine composition such as pH and dilution. Second, the molecular origin of the SERS signal of urine is incompletely understood, limiting the interpretability of machine learning classifiers in terms of specific biochemical markers. Methods: In this pilot study, we analyzed urine samples from breast cancer patients (n = 18) and control subjects (n = 10) at three pH levels (5, 7, and 9). Additionally, we analyzed simulated urine mixtures consisting of uric acid, hypoxanthine, xanthine, and creatinine in physiological concentrations to explain the variation in the SERS spectra at different pH values. Results: Urine at pH 9 yielded the most detailed spectral features. The SERS spectral pattern under alkaline pH reflected greater contributions from hypoxanthine, uric acid, and creatinine, while xanthine contributions diminished due to competitive interactions at the SERS substrate surface. Normalizing SERS signals to the creatinine band at 1420 cm⁻¹ effectively mitigated the confounding effects of urine dilution. Conclusions: Optimizing the pH to 9 and normalizing to creatinine significantly enhances the interpretability and accuracy of SERS-based urine analysis for cancer detection. These findings offer important theoretical and practical advancements for the development of SERS-based liquid biopsy tools for cancer detection. Full article

The evaluation of soft tissue biomechanical properties is of paramount importance not only for a comprehensive understanding of human physiology and physiopathology, but also in the research and development of bio-compatible artificial tissues with viscoelastic properties. Contrarily to standard tensile testing devices, a system intended for biomaterials testing should consider low stress and high strain ranges, characteristic of human tissues; moreover, such a system should enable the ex vivo simulation of biological environmental conditions. Commercial solutions address these challenges, although they are expensive for most academic and research institutions. This study presents a low-cost open-source design solution for soft tissue tensile testing, offering an affordable solution, yet without compromising the high quality and precision of the results. The proposed uniaxial tensile system allows for sample testing at room temperature as well as in a temperature-controlled liquid environment. Moreover, custom clamps ensure the fixation of tissue samples without slipping or tearing. System validation is performed using the tensile testing of springs and 3D-printed soft polymeric samples, demonstrating accurate results compared to the available data. The system is suitable for educational, research, and development applications. Full article

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone (CORT), dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to the baseline. Downstream effects of these catecholamines and CORT appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to the baseline by the final measurement. DHEA, which is used in a ratio with CORT, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to our understanding of crocodilian stress and potentially informing improved farming practices for conservation and sustainable management. Full article

Simulated body fluid (SBF) and artificial saliva (AS) are used in biomedical and dental research to mimic the physiological conditions of the human body. In this study, the biomimetic precipitation of double-doped amorphous calcium phosphate in SBF and AS are compared by thermodynamic modelling of chemical equilibrium in the SBF/AS-CaCl₂-MgCl₂-ZnCl₂-K₂HPO₄-H₂O and SBF/AS-CaCl₂-MgCl₂-ZnCl₂-K₂HPO₄-Glycine/Valine-H₂O systems. The saturation indices (SIs) of possible precipitate solid phases at pH 6.5, close to pH of AS, pH 7.5, close to pH of SBF, and pH 8.5, chosen by us based on our previous experimental data, were calculated. The results show possible precipitation of the same salts with almost equal SIs in the two biomimetic environments at the studied pHs. A decrease in the saturation indices of magnesium and zinc phosphates in the presence of glycine is a prerequisite for reducing their concentrations in the precipitates. Experimental studies confirmed the thermodynamic predictions. Only X-ray amorphous calcium phosphate with incorporated Mg (5.86–8.85 mol%) and Zn (0.71–2.84 mol%) was obtained in the experimental studies, irrespective of biomimetic media and synthesis route. Solid-state nuclear magnetic resonance (NMR) analysis showed that the synthesis route affects the degree of structural disorder of the precipitates. The lowest concentration of dopant ions was obtained in the presence of glycine. Further, the behaviour of the selected amorphous phase in artificial saliva was studied. The dynamic of Ca²⁺, Mg²⁺, and Zn²⁺ ions between the solid and liquid phases was monitored. Both direct excitation ³¹P NMR spectra and ¹H-³¹P CP-MAS spectra proved the increase in the nanocrystalline hydroxyapatite phase upon increasing the incubation time in AS, which is more pronounced in samples with lower additives. The effect of the initial concentration of doped ions on the solid phase transformation was assessed by solid-state NMR. Full article

For the progress of point-of-care medicine, where individual health status can be easily and quickly monitored using a handheld sensor, saliva serves as one of the best-suited body fluids thanks to its availability and abundance of physiological indicators. Salivary biomarkers, combined with rapid and highly sensitive detection tools, may pave the way to new real-time health monitoring and personalized preventative therapy branches using saliva as a target matrix. Saliva is increasing in importance in liquid biopsy, a non-invasive approach that helps physicians diagnose and characterize specific diseases in patients. Here, we propose a proof-of-concept study combining the unique specificity in biomolecular recognition provided by surface-enhanced Raman spectroscopy (SERS) in combination with molecular dynamics (MD) simulations, which give leave to explore the biomolecular absorption mechanism on nanoparticle surfaces, in order to verify the traceability of two validated salivary indicators, i.e., interleukin-8 (IL-8) and lysozyme (LYZ), implicated in oropharyngeal squamous cell carcinoma (OSCC) and oral infection. This strategy simultaneously assures the detection and interpretation of protein biomarkers in saliva, ultimately opening a new route for the evolution of fast and accurate point-of-care SERS-based sensors of interest in precision medicine diagnostics. Full article

Ionic liquids (ILs) are a class of low-melting molten salts (<100 °C) constituted entirely of ions, and their research has gained tremendous attention in line with their remarkably growing applications (>124,000 publications dated 30 August 2023 from the Web of Science^TM). In this review, we first briefly discussed the recent developments and unique characteristics of ILs and zwitterionic liquids (ZILs). Compared to molecular solvents and other conventional organic compounds, (zwitter) ionic liquids carry negligible volatility and are potentially recyclable and reusable. For structures, both ILs and ZILs can be systematically tailor-designed and engineered and are synthetically fine-tunable. As such, ionic liquids, including chiral, supported, task-specific ILs, have been widely used as powerful ionic solvents as well as valuable additives and catalysts for many chemical reactions. Moreover, ILs have demonstrated their value for use as polymerase chain reaction (PCR) enhancers for DNA amplification, chemoselective artificial olfaction for targeted VOC analysis, and recognition-based affinity extraction. As the major focus of this review, we extensively discussed that small-molecule thermoresponsive ILs (TILs) and ZILs (zwitterionic TILs) are new types of smart materials and can be expeditiously discovered through the structure and phase separation (SPS) relationship study by the combinatorial approach. Using this SPS platform developed in our laboratory, we first depicted the rapid discovery of N,N-dialkylcycloammonium and 1,3,4-trialkyl-1,2,3-triazolium TILs that concomitantly exhibited LCST (lower critical solution temperature) phase transition in water and displayed biochemically attractive T_c values. Both smart IL materials were suited for applications to proteins and other biomolecules. Zwitterionic TILs are ZILs whose cations and anions are tethered together covalently and are thermoresponsive to temperature changes. These zwitterionic TIL materials can serve as excellent extraction solvents, through temperature change, for biomolecules such as proteins since they differ from the common TIL problems often associated with unwanted ion exchanges during extractions. These unique structural characteristics of zwitterionic TIL materials greatly reduce and may avoid the denaturation of proteins under physiological conditions. Lastly, we argued that both rational structural design and combinatorial library synthesis of small-molecule TIL materials should take into consideration the important issues of their cytotoxicity and biosafety to the ecosystem, potentially causing harm to the environment and directly endangering human health. Finally, we would concur that before precise prediction and quantitative simulation of TIL structures can be realized, combinatorial chemistry may be the most convenient and effective technology platform to discover TIL expeditiously. Through our rational TIL design and combinatorial library synthesis and screening, we have demonstrated its power to discover novel chemical structures of both TILs and zwitterionic TILs. Undoubtedly, we will continue developing new small-molecule TIL structures and studying their applications related to other thermoresponsive materials. Full article

The anthropogenic release of Hg is associated with an increased human exposure risk. Since Hg²⁺ and MeHg⁺ have a high affinity for thiols, their interaction with L-glutathione (GSH) within mammalian cells is fundamentally involved in their toxicological chemistry and excretion. To gain insight into the interaction of these mercurials with multiple small molecular weight thiols, we have investigated their competitive interactions with GSH and N-acetylcysteine (NAC) at near-physiological conditions, using a liquid chromatographic approach. This approach involved the injection of each mercurial onto a reversed-phase (RP)-HPLC column (37 °C) using a PBS buffer mobile phase containing 5.0 mM GSH to simulate cytosolic conditions with Hg being detected in the column effluent by an inductively coupled plasma atomic emission spectrometer (ICP-AES). When the 5.0 mM GSH mobile phase was amended with up to 10 mM NAC, gradually increasing retention times of both mercurials were observed. To explain this behavior, the experiment with 5.0 mM NAC and 5.0 mM GSH was replicated using 50 mM Tris buffer (pH 7.4), and the Hg-containing fractions were analyzed by electrospray ionization mass spectrometry. The results revealed the presence of Hg(GS)(NAC) and Hg(NAC)₂ for Hg²⁺ and MeHg(GS) and MeHg(NAC) for MeHg⁺, which suggests that the coordination/displacement of GS-moieties from each mercurial by the more hydrophobic NAC can explain their retention behavior. Since the biotransformations of both mercurials were observed at near-physiological conditions, they are of toxicological relevance as they provide a biomolecular explanation for some results that were obtained when animals were administered with each mercurial and NAC. Full article

With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin’s low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine–curcumin derivatives is reported. The compounds were fully characterized (¹H/¹³C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells. Full article

Background and Objectives: This numerical analysis investigated the biomechanical behavior of the mandibular bone as a structure subjected to 0.5 N of orthodontic force during periodontal breakdown. Additionally, the suitability of the five most used failure criteria (Von Mises (VM), Tresca (T), maximum principal (S1), minimum principal (S3), and hydrostatic pressure (HP)) for the study of bone was assessed, and a single criterion was identified for the study of teeth and the surrounding periodontium (by performing correlations with other FEA studies). Materials and Methods: The finite element analysis (FEA) employed 405 simulations over eighty-one mandibular models with variable levels of bone loss (0–8 mm) and five orthodontic movements (intrusion, extrusion, tipping, rotation, and translation). For the numerical analysis of bone, the ductile failure criteria are suitable (T and VM are adequate for the study of bone), with Tresca being more suited. S1, S3, and HP criteria, due to their distinctive design dedicated to brittle materials and liquids/gas, only occasionally correctly described the bone stress distribution. Results: Only T and VM displayed a coherent and correlated gradual stress increase pattern for all five movements and levels of the periodontal breakdown. The quantitative values provided by T and VM were the highest (for each movement and level of bone loss) among all five criteria. The MHP (maximum physiological hydrostatic pressure) was exceeded in all simulations since the mandibular bone is anatomically less vascularized, and the ischemic risks are reduced. Only T and VM displayed a correlated (both qualitative and quantitative) stress increase for all five movements. Both T and VM displayed rotation and translation, closely followed by tipping, as stressful movements, while intrusion and extrusion were less stressful for the mandibular bone. Conclusions: Based on correlations with earlier numerical studies on the same models and boundary conditions, T seems better suited as a single unitary failure criterion for the study of teeth and the surrounding periodontium. Full article

To guide therapeutic strategies and to monitor the state changes in the disease, a low-cost, portable, and easily fabricated microfluidic-chip-integrated three-dimensional (3D) microchamber was designed for capturing and analyzing breast cancer cells. Optimally, a colorimetric sensor array was integrated into a microfluidic chip to discriminate the metabolites of the cells. The ultraviolet polymerization characteristic of poly(ethylene glycol) diacrylate (PEGDA) hydrogel was utilized to rapidly fabricate a three-layer hydrogel microfluidic chip with the designed structure under noninvasive 365 nm laser irradiation. 2-Hydroxyethyl methacrylate (HEMA) was added to the prepolymer in order to increase the adhesive capacity of the microchip’s surface for capturing cells. 1-Vinyl-2-pyrrolidone (NVP) was designed to improve the toughness and reduce the swelling capacity of the hydrogel composite. A non-toxic 3D hydrogel microarray chip (60 mm × 20 mm × 3 mm) with low immunogenicity and high hydrophilicity was created to simulate the real physiological microenvironment of breast tissue. The crisscross channels were designed to ensure homogeneous seeding density. This hydrogel material displayed excellent biocompatibility and tunable physical properties compared with traditional microfluidic chip materials and can be directly processed to obtain the most desirable microstructure. The feasibility of using a PEGDA hydrogel microfluidic chip for the real-time online detection of breast cancer cells’ metabolism was confirmed using a specifically designed colorimetric sensor array with 16 kinds of porphyrin, porphyrin derivatives, and indicator dyes. The results of the principal component analysis (PCA), the hierarchical cluster analysis (HCA), and the linear discriminant analysis (LDA) suggest that the metabolic liquids of different breast cells can be easily distinguished with the developed PEGDA hydrogel microfluidic chip. The PEGDA hydrogel microfluidic chip has potential practicable applicability in distinguishing normal and cancerous breast cells. Full article