Model Membranes Research Articles

Classical Simulations on Quantum Computers: Interface-Driven Peptide Folding on Simulated Membrane Surfaces

Background:Antimicrobial peptides (AMPs) are crucial in the fight against infections and play significant roles in various health contexts, including cancer, autoimmune diseases, and aging. A key aspect of AMP functionality is their selective interaction with pathogen membranes, which often exhibit altered lipid compositions. These interactions are thought to induce a conformational shift in AMPs from random coil to alpha-helical structures, essential for their lytic activity. Traditional computational approaches have faced challenges in accurately modeling these structural changes, especially in membrane environments, thereby opening and opportunity for more advanced approaches. Method:This study extends an existing quantum computing algorithm, initially designed for peptide folding simulations in homogeneous environments, to address the complexities of AMP interactions at interfaces. Our approach enables the prediction of the optimal conformation of peptides located in the transition region between hydrophilic and hydrophobic phases, resembling lipid membranes. The new method was tested on three 10-amino-acid-long peptides, each characterized by distinct hydrophobic, hydrophilic, or amphipathic properties, across different media and at interfaces between solvents of different polarity. Results:The developed method successfully modeled the structure of the peptides without increasing the number of qubits required compared to simulations in homogeneous media, making it more feasible with current quantum computing resources. Despite the current limitations in computational power and qubit availability, the findings demonstrate the significant potential of quantum computing in accurately characterizing complex biomolecular processes, particularly AMP folding at membrane models. Conclusions:This research highlights the promising applications of quantum computing in biomolecular simulations, paving the way for future advancements in the development of novel therapeutic agents. We aim to offer a new perspective on enhancing the accuracy and applicability of biomolecular simulations in the context of AMP interactions with membrane models.

Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats.

This study was performed to evaluate the regenerative capacity of demineralized bone matrix vs fat graft, both guided by pericardium membrane in alveolar cleft model in albino rats. A total of 72 rats were required in this study. A surgical bone defect with a 7 mm length × 4 mm width × 3 mm depth was created as a model of an alveolar cleft, then the rats were divided randomly into four equal groups each group contained 18 rats: control group (defect only), the membrane group (the defect was covered by the pericardium membrane), the demineralized bone matrix (DBM) group (the defect was filled with DBM guided by pericardium membrane) and fat group (the defect was filled with a fat graft guided by the pericardium membrane). Around 6 rats from each group were euthanized after 2, 4, and 8 weeks. Skulls were scanned with cone beam computed tomography (CBCT) and harvested for histological evaluation with routine H&E immunohistochemical stains (Anti-osteocalcin and Anti-Wnt5a). The data was recorded and statistically analyzed by a two-way ANOVA. The study showed a notable formation of new bone, and expression of OCN and Wnt5a were notably increased by time in the fat group. However, the density of bone grafts and OCN and Wnt5a expression decreased with time in the DBM group. Control and membrane groups showed negative OCN and Wnt5a immune-reactivity in the cleft site. Fat graft results were superior to DBM results with regard to mucosal closure and accelerated bone regeneration, and may represent an effective treatment for alveolar cleft reconstruction. Finding an inexpensive, accessible, biocompatible and easily manipulated treatment for craniofacial reconstruction and fat graft fulfilled the desired aims. Further investigations with prolonged evaluation periods are needed. How to cite this article: Abdel Raouf E, Elsherbini AM, Abdel Salam Yousef Y, et al. Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats. J Contemp Dent Pract 2024;25(6):554-562.

Exploring the influence of acetylenic acetogenin unsaturation patterns on lipid interface interactions: Insights from surface chemistry, rheology, and spectroscopy

This study explores how the unsaturation patterns of three acetogenins from Porcelia macrocarpa (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11′-yn-19′-enyl)-butanolide (1), (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11′-ynyl)-butanolide (2), and (2S,3R,4R)-3-hydroxy-4-methyl-2-eicosyl-butanolide (3)—affect their interactions with lipid interfaces, using Langmuir monolayers of dipalmitoyl-phosphoethanolamine (DPPE) as a model for protozoal membranes. The hypothesis posits that unsaturated acetogenins (1 and 2) will exhibit distinct behaviors compared to the saturated acetogenin (3) due to structural differences. Experiments incorporated each acetogenin into DPPE monolayers, employing techniques like tensiometry, dilatational rheology, infrared spectroscopy, and Brewster angle microscopy (BAM) to assess interactions and changes in film properties. Results showed that unsaturated acetogenin 1, active against Leishmania infantum and Trypanosoma cruzi, destabilized the film and induced rapid molecular reorganization, while acetogenin 2, inactive against these parasites, uniquely increased the viscous contribution to viscoelasticity. Saturated acetogenin 3 did not integrate into the film. All acetogenins enhanced fluidity, reducing elasticity and viscosity, with BAM revealing phase separation only in acetogenin 2. Infrared spectroscopy underscored the impact of drug-lipid interactions, leading to the conclusion that unsaturated acetogenins 1 and 2 have a more significant influence on thermodynamic and structural properties than acetogenin 3, offering insights into their potential therapeutic mechanisms.

Raft-like lipid mixtures in the highly coarse-grained Cooke membrane model.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane.

The influence of blackcurrant extract–based cosmetic antimicrobial agent on skin cells and skin model membranes

The components of blackcurrant extract are known for their antimicrobial properties and the lipid membrane is the important target in terms of the activity of these compounds. In this work, a commercially available product that is PhytoCide Black Currant Powder (BCE), which can be used as a soothing, conditioning and antimicrobial agent in cosmetics, was investigated. The aim of this study was to explore its effect on skin cells and gain insight into the mechanism of its selectivity. The influence of this formulation on keratinocyte and fibroblast cells in in vitro tests was studied and the effect of BCE on model keratinocyte and fibroblast membranes was investigated. As model systems, the lipid monolayers of different compositions were used. The experiments involved the surface pressure/area measurement, penetration studies and Brewster angle microscopy experiments. The BCE formulation was shown to be non-toxic to the skin cells at the concentrations applied. Model membrane experiments confirmed that BCE components do not incorporate into keratinocyte and fibroblast membranes at membrane-related conditions. However, they alter morphology of the studied systems by acting in the region of polar head. Significant differences were found in the affinity of the BCE formulation for bacteria compared to skin lipids, consistent with the proven antibacterial effect of the preservative while lacking toxicity to skin cells. Thus, the membrane of the cell may be critical to the selectivity of the chemicals being tested.

Impact of compliant electrodes on the dynamics of electromagnetoactive membranes

The dynamics of electromagnetoactive polymer (EMAP) membranes have attracted much attention recently because of their wide range of modern robotic applications. Such applications majorly centered on how the dynamics of this novel class of membranes are affected by the mechanical behavior of the compliant electrode. This article presents the dynamic modeling and analysis of EMAP membranes, examining how the inertia of the electrode, coupled with its inherent viscoelastic properties, impacts its dynamic performance. Both the compression and suspension stages of the membrane are covered here in broad terms. An Euler–Lagrange equation of motion is implemented to deduce the governing dynamic model equation of the membrane system. The findings of the model solutions provide preliminary insights to characterize the dynamic response, instability analysis, periodic behavior, and resonance properties across varying parameters such as inertia, electric field, magnetic field, and prestress. Moreover, the study also evaluates the periodicity and stability of the nonlinear oscillations using Poincaré maps and phase portraits, facilitating an assessment of quasi-periodic to periodic transitions.

Thermodynamic Study on Biomimetic Legionella gormanii Bacterial Membranes.

The presented studies were aimed at determining the interactions in model membranes (Langmuir monolayers) created of phospholipids (PL) isolated from Legionella gormanii bacteria cultured with (PL + choline) or without (PL - choline) choline and to describe the impact of an antimicrobial peptide, human cathelicidin LL-37, on PL's monolayer behavior. The addition of choline to the growth medium influenced the mutual proportions of phospholipids extracted from L. gormanii. Four classes of phospholipids-phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), cardiolipin (CL), and their mixtures-were used to register compression isotherms with or without the LL-37 peptide in the subphase. Based on them the excess area (Ae), excess (ΔGe), and total (ΔGm) Gibbs energy of mixing were determined. The thermodynamic analyses revealed that the PL - choline monolayer showed greater repulsive forces between molecules in comparison to the ideal system, while the PL + choline monolayer was characterized by greater attraction. The LL-37 peptide affected the strength of interactions between phospholipids' molecules and reduced the monolayers stability. Accordingly, the changes in interactions in the model membranes allowed us to determine the difference in their susceptibility to the LL-37 peptide depending on the choline supplementation of bacterial culture.

Process design and optimization of membrane-based CO2 capture process with experimental performance data for a steam methane reforming hydrogen plant and a coal-fired power plant

Membrane-based separation is one of the promising next-generation carbon capture technologies. High degrees of freedom in process design for multi-stage membrane networks, make it difficult to fully understand the impact of network configuration on the economics of capture and separation performance. Furthermore, the optimality in process design is heavily influenced by the levels of membrane performance and the characteristics of feed gas. Membrane model utilized for the study is validated and tuned with 183 experimental data measured at various operating conditions, having 2.45 % of overall prediction error. The superstructure-based framework for the optimization of multi-stage membrane networks is used, with which design interactions between network configurations, flue gas characteristics and membrane performance are systematically investigated. Techno-economic analysis is embedded in the optimization framework, which performs rigorous trade-off between capital and operating costs, as well as allows simultaneous determination of optimal process network configuration and operating variables. Flue gas streams emitted from a coal-fired power plant and a steam methane reforming hydrogen production plant are selected as CO2 capture sources for the analysis of flue gas characteristics. Case study shows capture cost ranged from 30.2 $/tCO2 to 79.9 $/tCO2, depending on the network configuration and design specifications, and clearly improves our techno-economic understanding on the network configuration of membrane capture process. In addition, cryogenic-hybridized membrane capture process is examined and the optimal level of enriched CO2 stream concentration between membrane capture and cryogenic distillation processes is determined. Study suggests how network configuration of membrane capture process can impact capture cost.

HOCl forms lipid N-chloramines in cell membranes of bacteria and immune cells

Neutrophils orchestrate a coordinated attack on bacteria, combining phagocytosis with a potent cocktail of oxidants, including the highly toxic hypochlorous acid (HOCl), renowned for its deleterious effects on proteins. Here, we examined the occurrence of lipid N-chloramines in vivo, their biological activity, and their neutralization. Using a chemical probe for N-chloramines, we demonstrate their formation in the membranes of bacteria and monocytic cells exposed to physiologically relevant concentrations of HOCl. N-chlorinated model membranes composed of phosphatidylethanolamine, the major membrane lipid in Escherichia coli and an important component of eukaryotic membranes, exhibited oxidative activity towards the redox-sensitive protein roGFP2, suggesting a role for lipid N-chloramines in protein oxidation. Conversely, glutathione a cellular antioxidant neutralized lipid N-chloramines by removing the chlorine moiety. In line with that, N-chloramine stability was drastically decreased in bacterial cells compared to model membranes. We propose that lipid N-chloramines, like protein N-chloramines, are involved in inflammation and accelerate the host immune response.

Interactions between gamma-aminobutyric capped silver nanoparticles and large unilamellar vesicles (LUVs) and their antimicrobial activities

Multidrug-resistant bacteria (MDR) and bacterial virulence pose significant challenges to global health. Nanotechnology offers exciting possibilities for developing innovative strategies to combat these issues. This study investigates the synergistic effects of silver nanoparticles (AgNPs) and gamma-aminobutyric acid (GABA) to address antibiotic resistance and bacterial virulence. We report the synthesis and characterization of GABA-coated AgNPs (GABAAgNPs) using UV–VIS and infrared spectroscopies, zeta potential, X-ray diffraction, and transmission electron microscopy. The interaction between GABAAgNPs and model membranes (large unilamellar vesicles, LUVs) was assessed, revealing the formation of liposomal-bound GABAAgNPs (LPGABAAgNPs). Antimicrobial activity against E. coli ATCC 25922 demonstrated that LPGABAAgNPs exhibit enhanced antibacterial efficacy compared to free GABAAgNPs. These findings suggest that liposomal delivery of GABAAgNPs is a promising approach for optimizing their antibacterial properties. Moreover, incorporating GABA into the nanoparticle system offers the potential to modulate bacterial virulence, providing a multifaceted strategy to combat infection.

Selective actuation of higher-order modes of an electromagnetically driven micro drum

In this paper, we experimentally investigate selective actuation of the first few higher-order modes of a micromachined silicon nitride circular membrane (micro drum), which is actuated by electromagnetic forces. A novel design of electrodes is proposed to enable selective actuation for portions of the membrane with the Lorentz force, which excites efficiently the higher-order modes. With different electrode configurations, we show that the (0, 1) mode, the degenerate (1, 1) modes, and the (2, 1) mode can be selectively activated or deactivated using the orthogonality between the actuation force and the mode shapes. A reduced-order model for the circular membrane is established and used to explain the results.

Capillary-Assisted Assembly of Polymer Gel-Supported Lipid Bilayers.

The polymer-supported lipid bilayer represents an attractive supramolecular assembly in numerous biophysical and bioanalytical applications. The assembly of polymer-supported membranes with a polymer layer thickness of just a few nanometers is now well-established, but bilayer properties in such a membrane architecture are still influenced by the nearby solid substrate. Polymer-supported lipid bilayer systems with a several micrometers thick polymer layer will overcome this shortcoming. However, formation of a fluid lipid bilayer on a fully hydrated, micrometer thick polymer film using traditional methods (e.g., vesicle fusion and lipid monolayer deposition techniques) remains a challenging task due to the rather unfavorable interfacial conditions for bilayer formation in such a system. Here, we report for the first time on the facile capillary-assisted formation of a lipid bilayer on the surface of a fully hydrated, several micrometers thick polyacrylamide (PAA) gel, in which forced molecular crowding of lipids at the air-water interface of the capillary results in monolayer instability and collapse, thereby forming a lipid bilayer on the top of the polymer gel inside the capillary. Stable bilayer attachment on the surface of the polymer gel can be achieved via physisorption or specific chemical linkages (tethering) on both cross-linked and non-cross-linked PAA films. Unlike the traditional solid-supported lipid bilayer (SLB), the lipid lateral diffusion in the polymer gel-supported lipid bilayer is not anymore perturbed by a solid substrate. Instead, more like a plasma membrane, it is mainly influenced by the properties of the underlying polymer and the nature/distribution of polymer-bilayer attachments. Polymer gel-supported lipid bilayers built using the capillary-assisted assembly approach show attractive self-healing properties, resulting in superior long-term stability relative to the SLB. We hypothesize that the described capillary-assisted assembly method can be applied to a wide range of polymeric materials and lipid compositions, opening exciting opportunities as an advanced model membrane system.

Effect of concrete cover on the pure torsional behavior of reinforced concrete beams: Analytical model

Experimental data on RC members subjected to pure torsion is compiled from published studies so far. Interestingly, the past studies have concentrated largely on members with small to moderate concrete covers, with handful data on members with thick concrete cover. Widely accepted torsion models including the diagonal compression field theory (CFT), softened truss model (STM) and softened membrane model for torsion (SMMT) are verified on the domains of experimental data missing-in specimens with thick concrete cover. With increasing demand for durability design of RC structures use of thick concrete cover, say up to 75 mm, is being introduced in practice. Recent experimental investigation by the authors demonstrated that spalling of concrete cover, particularly in cases of thick covers, significantly impacts the torsional behavior of RC members. The present study uses these set of experiments to look at the response prediction capability of the existing advanced models and assess the reliability of existing concrete cover spalling theories. For cases with thick cover, the existing models either did not adequately capture the ultimate capacity or erroneously predicted the torsional behavior of the members due to the different mechanics between RC beams with thin and thick covers. Similarly, the spalling theories failed to fully explain the physically observed spalling behavior. Guided by the recent experimental observations and the apparent gaps, the study provides a rational theory for the spalling of concrete cover. The initiation and gradual evolution of concrete cover spalling is traced by observing the acting spalling moment and spalling resistance formulated in the proposed spalling model. The proposed spalling model inherently assumes members susceptibility to spalling of cover concrete and is governed by, the thickness of the concrete cover, tensile strength of concrete, presence of rebar cage and their location, and size of the member. The theory is unified and can explain the spalling of cover due to torsion as well as shear. Its capability is examined by integrating the approach into existing truss model. When compared with state-of-the-art models, the proposed method provides consistent prediction with a relatively smaller scatter, for cases with thick concrete cover as well.

Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering

Conserved signaling cascades monitor protein-folding homeostasis to ensure proper cellular function. One of the evolutionary conserved key players is IRE1, which maintains endoplasmic reticulum (ER) homeostasis through the unfolded protein response (UPR). Upon accumulation of misfolded proteins in the ER, IRE1 forms clusters on the ER membrane to initiate UPR signaling. What regulates IRE1 cluster formation is not fully understood. Here, we show that the ER lumenal domain (LD) of human IRE1α forms biomolecular condensates in vitro. IRE1α LD condensates were stabilized both by binding to unfolded polypeptides as well as by tethering to model membranes, suggesting their role in assembling IRE1α into signaling-competent stable clusters. Molecular dynamics simulations indicated that weak multivalent interactions drive IRE1α LD clustering. Mutagenesis experiments identified disordered regions in IRE1α LD to control its clustering in vitro and in cells. Importantly, dysregulated clustering of IRE1α mutants led to defects in IRE1α signaling. Our results revealed that disordered regions in IRE1α LD control its clustering and suggest their role as a common strategy in regulating protein assembly on membranes.

Simulating Bacterial Membrane Models at the Atomistic Level: A Force Field Comparison.

Molecular dynamics (MD) simulations are currently an indispensable tool to understand both the dynamic and nanoscale organization of cell membrane models. A large number of quantitative parameters can be extracted from these simulations, but their reliability is determined by the quality of the employed force field and the simulation parameters. Much of the work on parametrizing and optimizing force fields for biomembrane modeling has been focused on homogeneous bilayers with a single phospholipid type. However, these may not perform effectively or could even be unsuitable for lipid mixtures commonly employed in membrane models. This work aims to fill this gap by comparing MD simulation results of several bacterial membrane models using different force fields and simulation parameters, namely, CHARMM36, Slipids, and GROMOS-CKP. Furthermore, the hydrogen isotope exchange (HIE) method, combined with GROMOS-CKP (GROMOS-H2Q), was also tested to check for the impact of this acceleration strategy on the performance of the force field. A common set of simulation parameters was employed for all of the force fields in addition to those corresponding to the original parametrization of each of them. Furthermore, new experimental order parameter values determined from NMR of several lipid mixtures are also reported to compare them with those determined from MD simulations. Our results reveal that most of the calculated physical properties of bacterial membrane models from MD simulations are substantially force field and lipid composition dependent. Some lipid mixtures exhibit nearly ideal behaviors, while the interaction of different lipid types in other mixtures is highly synergistic. None of the employed force fields seem to be clearly superior to the other three, each having its own strengths and weaknesses. Slipids are notably effective at replicating the order parameters for all acyl chains, including those in lipid mixtures, but they offer the least accurate results for headgroup parameters. Conversely, CHARMM provides almost perfect estimates for the order parameters of the headgroups but tends to overestimate those of the lipid tails. The GROMOS parametrizations deliver reasonable order parameters for entire lipid molecules, including multicomponent bilayers, although they do not reach the accuracy of Slipids for tails or CHARMM for headgroups. Importantly, GROMOS-H2Q stands out for its computational efficiency, being at least 3 times faster than GROMOS, which is already faster than both CHARMM and Slipids. In turn, GROMOS-H2Q yields much higher compressibilities compared to all other parametrizations.

Polyoxometalate inhibition of SOX2-mediated tamoxifen resistance in breast cancer

BackgroundIncreased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells.MethodsVarious POM derivatives were synthesised and characterised by infrared spectra, powder X-ray diffraction pattern and nuclear magnetic resonance spectroscopy. Estrogen receptor (ER) positive breast cancer cells, and their counterparts, which have developed resistance to the hormone therapy tamoxifen, were treated with POMs and their consequences assessed by gel retardation and chromatin immunoprecipitation to determine SOX2 binding to DNA. Effects on proliferation, migration, invasion and tumorigenicity were monitored and quantified using microscopy, clone formation, transwell, wound healing assays, flow cytometry and in vivo chick chorioallantoic membrane (CAM) models. Generation of lentiviral stable gene silencing and gene knock-out using CRISPR-Cas9 genome editing were applied to validate the inhibitory effects of the selected POM. Cancer stem cell subpopulations were quantified by mammosphere formation assays, ALDEFLUOR activity and CD44/CD24 stainings. Flow cytometry and western blotting were used to measure reactive oxygen species (ROS) and apoptosis.ResultsPOMs blocked in vitro binding activity of endogenous SOX2. [P2W18O62]6− (PW) Wells-Dawson-type anion was the most effective at inhibiting proliferation in various cell line models of tamoxifen resistance. 10 µM PW also reduced cancer cell migration and invasion, as well as SNAI2 expression levels. Treatment of tamoxifen-resistant cells with PW impaired tumour formation by reducing CSC content, in a SOX2-dependent manner, which led to stem cell depletion in vivo. Mechanistically, PW induced formation of reactive oxygen species (ROS) and inhibited Bcl-2, leading to the death of tamoxifen-resistant cells. PW-treated tamoxifen-resistant cells showed restored sensitivity to tamoxifen.ConclusionsTogether, these observations highlight the potential use of PW as a SOX2 inhibitor and the therapeutic relevance of targeting SOX2 to treat tamoxifen-resistant breast cancer.

Study on heat transfer performance of cooling channels in proton exchange membrane fuel cells based on topology optimization

Based on topology optimization method, a dual-objective function topology optimization model containing minimum average temperature and minimum flow power dissipation was established in this study. Coupled with the uneven heat generation model of proton exchange membrane fuel cells, the optimal layout scheme under the target operating conditions was adaptively obtained. The effects of volume fraction, objective function weight, and parabolic inlet velocity on the flow channel structure and cooling performance of topological cooling plates were studied. The results indicate that with the increase of volume fraction, the area of fluid region increases, the average temperature and the pressure drop of cooling plate gradually decrease. At the volume fraction of 0.5, the cooling plate has the best cooling performance. The temperature difference and maximum temperature reach the minimum values of 5.45 K and 347.58 K, respectively. When the volume fraction increases from 0.4 to 0.6, the pressure difference decreases by 67.64 %. With the increase of temperature weight coefficient, the area of high-temperature area gradually decreases, and the temperature uniformity is significantly improved. When the inlet velocity of coolant is 0.025 m/s and the temperature weight coefficient is 0.9, the average and maximum temperatures of cooling plate reach the lowest values, which are 343.53 K and 344.51 K, respectively. The maximum temperature of cooling plate under parabolic inlet velocity is of 347.87 K, which is 0.29 K higher than that under uniform inlet velocity. Non-uniform coolant inlet velocity will lead to a decrease in heat transfer capacity of cooling plate and an increase in coolant power consumption.

Oxidation of lipid membrane cholesterol by cholesterol oxidase and its effects on raft model membrane structure

The effects of a peripheral protein – cholesterol oxidase (3β-hydroxysteroid oxidase, ChOx) on the characteristics of model lipid membranes composed of cholesterol, cholesterol:sphingomyelin (1:1), and the raft model composed of DOPC:Chol:SM (1:1:1) were investigated using two membrane model systems: the flat monolayer prepared by the Langmuir technique and the curved model consisting of liposome of the same lipids. The planar monolayers and liposomes were employed to follow membrane cholesterol oxidation to cholestenone catalyzed by ChOx and changes in the lipid membrane structure accompanying this reaction. Changes in the structure of liposomes in the presence of the enzyme were reflected in the changes of hydrodynamic diameter and fluorescence microscopy images, while changes of surface properties of planar membranes were evaluated by grazing incidence X-ray diffraction (GIXD) and Brewster angle microscopy. UV-Vis absorbance measurements confirmed the activity of the enzyme in the tested systems. A better understanding of the interactions between the enzyme and the cell membrane may help in finding alternative ways to decrease excessive cholesterol levels than the common approach of treating hypercholesterolemia with statins, which are not free from undesirable side effects, repeatedly reported in the literature and observed by the patients.

Glucose Oxidase-Coated Calcium Peroxide Nanoparticles as an Innovative Catalyst for In Situ H2O2-Releasing Hydrogels.

In situ forming and hydrogen peroxide (H2O2)-releasing hydrogels have been considered as attractive matrices for various biomedical applications. Particularly, horseradish peroxidase (HRP)-catalyzed crosslinking reaction serves efficient method to create in situ forming hydrogels due to its advantageous features, such as mild reaction conditions, rapid gelation rate, tunable mechanical strength, and excellent biocompatibility. Herein, a novel HRP-crosslinked hydrogel system is reported that can produce H2O2 in situ for long-term applications, using glucose oxidase-coated calcium peroxide nanoparticles (CaO2@GOx NPs). In this system, CaO2 gradually produced H2O2 to support the HRP-mediated hydrogelation, while GOx further catalyzed the oxidation of glucose for in situ H2O2 generation. As the hydrogel is formed rapidly is expected and the H2O2 release behavior is prolonged up to 10 days. Interestingly, hydrogels formed by HRP/CaO2@GOx-mediated crosslinking reaction provided a favorable 3D microenvironment to support the viability and proliferation of fibroblasts, compared to that of hydrogels formed by either HRP/H2O2 or HRP/CaO2/GOx-mediated crosslinking reaction. Furthermore, HRP/CaO2@GOx-crosslinked hydrogel enhanced the angiogenic activities of endothelial cells, which is demonstrated by the in vitro tube formation test and in ovo chicken chorioallantoic membrane model. Therefore, HRP/CaO2@GOx-catalyzed hydrogels is suggested as potential in situ H2O2-releasing materials for a wide range of biomedical applications.

Expansion of T follicular helper cells is associated with disease progression in rat experimental membranous nephropathy model.

T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses, but the functional role of Tfh cells in the pathogenesis of idiopathic membranous nephropathy (IMN) remains unclear. This study aimed to establish a rat experimental membranous nephropathy model, investigate the phenotypic characteristics of Tfh cells, and analyze a clinically significant correlation between Tfh cells. Passive Heymann nephritis (PHN) rats were induced by immunizing Sprague Dawley rats with anti-Fx1A serum. The frequency of Tfh and B cell subsets was analyzed with flow cytometry (FC). The serum concentration of interleukin-21 (IL-21), the relative mRNA expression levels of IL-21 and B cell lymphoma 6 (Bcl-6) in spleen mononuclear cells (MNCs), and the kidney infiltration of CD4+ T cells and IL-21 were assessed. The potential correlations among these measures were analyzed. In comparison with the control group, significantly increased percentages of Tfh cells, inducible T cell co-stimulator-positive (ICOS+) Tfh cells, and mRNA expression of Bcl-6 were detected in the spleen of PHN rats. Elevated IL-21 expression was detected in the serum and kidneys. Remarkably, the percentage of splenic ICOS+ Tfh cells was positively correlated with 24 h urine protein concentrations (r = 0.676, p = 0.011) in PHN rats. These data indicate that ICOS+ Tfh cells contribute to development of IMN, and they might be potential therapeutic targets for IMN.