Cellular Layers Research Articles

Impact of temperature-reliant thermal conductivity and viscosity variations on the convection of Jeffrey fluid in a rotating cellular porous layer

In this analysis, the collective impact of temperature-dependent thermal conductivity and viscosity variations on the convective instability of a Jeffrey fluid in a rotating layer of cellular porous material is examined using an improved Jeffrey–Darcy model. This study has significant implications for cellular foams made from plastics, ceramics and metals, in which radiative heat transmission can be taken as a diffusion practice. Utilizing the linear stability concept and Galerkin method, approximate analytical and numerical solutions accurate to one decimal place are offered. The analysis reveals that the effect of the thermal conductivity variation factor and the rotation factor is to postpone the convective wave, whereas the viscosity variation factor and the Jeffrey factor have a dual effect in the form of rotation. The range of the convective cell is reduced with cumulating thermal conductivity variation factor, viscosity variation factor, Jeffrey factor and rotation factor. In the absence of rotation, the range of the convective cell is not dependent on the Jeffrey factor or the viscosity variation factor. Furthermore, the outcomes are matched with the existing literature for the specific case of this investigation.

Memory B Cells Provide Long-Term Protection to Vaccinated Kidney Transplant Recipients Against SARS-CoV-2 Variants.

Kidney transplant recipients (KTRs) are highly vulnerable to COVID-19. An intensified scheme of vaccination offers short-term protection to the 50%-75% of KTRs able to develop a germinal center reaction, required for the generation of neutralizing titers of antibodies (NAbs). However, the duration of this vaccinal protection is unknown. In-depth longitudinal analysis of the immune response to vaccination of 33 KTRs demonstrates that the low peak of IgGs, the progressive decline in antibody titers, and the emergence of a variant of concerns (VOC) of SARS-CoV2, synergize to let 2/3 of responders to vaccine without NAbs after only a few months. Yet, a retrospective study of an independent cohort of 274 KTRs, revealed that the risk of severe COVID-19 in the latter was low, similar to that of patients with serum neutralizing capacity against VOC. Our work links this late vaccine protection with the presence of memory B cells, which are generated during the initial vaccine-induced germinal center reaction, have a wide repertoire directed against conserved spike epitopes, and rapidly differentiate into IgG-producing plasma cells upon antigenic rechallenge. We conclude that in contrast with a serological layer that goes fading rapidly, the cellular layer of humoral memory provides an efficient long-term protection against VOC to KTRs. This illustration of the complementary roles of the two layers of the humoral memory has implications in immunopathology beyond the COVID-19 in KTRs.

Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation.

The mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.

Feasibility of Nondestructive Soluble Sugar Monitoring in Tomato: Quantified and Sorted through ATR-FTIR Coupled with Chemometrics

As a fast detection method, Fourier transform infrared attenuated total reflection (ATR-FTIR) spectroscopy is seldom used for monitoring soluble sugars in crops. This study aimed to demonstrate the feasibility of leveraging ATR-FTIR coupled with chemometrics to quantify and sort the contents of soluble sugar in tomatoes. Firstly, 192 tomato samples were scanned using ATR-FTIR; subsequently, a quantitative model was developed using PLSR with selected wavelength variables as inputs. Finally, a classification model was estimated through probabilistic neural network (PNN) to determine the samples. The results indicated that ATR-FTIR had successfully captured the spectra from the cellular layers of tomatoes, resulting in a robust PLSR model created by 468 selected variables with a R² value of 0.86, a RMSEP of 0.71%, a ratio of performance to relative percent deviation (RPD) of 1.87, and a ratio of prediction to interquartile range (RPIQ) of 2.1. Meanwhile, the PNN model demonstrated a high rate correct (RC) of 92.17% in identifying whether the samples with a higher soluble sugar content than the limit of detection (LOD at 2.1%). Overall, ATR-FTIR coupled with chemometrics has proven effective for non-destructive determination of soluble sugars in tomatoes, offering new insights into internal monitoring techniques for crop quality assurance.

Histological assessment of the effect of 50mW red laser on retina at variable time intervals: animal model.

To assess the histopathological effect of 50milliWatt red laser pointer on mice retinal tissue at variable exposure times. The experimental study was conducted in the Postgraduate Laboratory of the Unit of Medical Physics, Department of Physiology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from November 2020 to April 2021, and comprised albino mice. Histopathological effects on the retinal tissues were evaluated microscopically using conventional haematoxylin and eosin stain just after being exposed to commercially available 50 milliWatt red laser pointers with 630nm wavelength at 1, 2 and 3 minutes, grouped as R1, R2 and R3, respectively. The laser beam was focussed on the right eye of the mice sedated with sodium pentobarbital, reserving the left eye for use as a control group. Data was analysed using SPSS 24. Of the 12 mice, 4(33.3%) were in each of the 3 groups. There was significantly destructive effect of red laser on retinal outer cellular layers in all the groups compared to the controls (p<0.05). The effect was significant between R1 and R2 (p=0.0001), and between R2 and R3 (p=0.02). The handheld commercial red laser pointers could harmfully affect a wide range of mice retina and choroid.

Enteroids to Study Pediatric Intestinal Drug Transport.

Intestinal maturational changes after birth affect the pharmacokinetics (PK) of drugs, having major implications for drug safety and efficacy. However, little is known about ontogeny-related PK patterns in the intestine. To explore the accuracy of human enteroid monolayers for studying drug transport in the pediatric intestine, we compared the drug transporter functionality and expression in enteroid monolayers and tissue from pediatrics and adults. Enteroid monolayers were cultured of 14 pediatric [median (range) age: 44 weeks (2 days-13 years)] and 5 adult donors, in which bidirectional drug transport experiments were performed. In parallel, we performed similar experiments with tissue explants in Ussing chamber using 11 pediatric [median (range) age: 54 weeks (15 weeks-10 years)] and 6 adult tissues. Enalaprilat, propranolol, talinolol, and rosuvastatin were used to test paracellular, transcellular, and transporter-mediated efflux by P-gp and breast cancer resistance protein (BCRP), respectively. In addition, we compared the expression patterns of ADME-related genes in pediatric and adult enteroid monolayers with tissues using RNA sequencing. Efflux transport by P-gp and BCRP was comparable between the enteroids and tissue. Efflux ratios (ERs) of talinolol and rosuvastatin by P-gp and BCRP, respectively, were higher in enteroid monolayers compared to Ussing chamber, likely caused by experimental differences in model setup and cellular layers present. Explorative statistics on the correlation with age showed trends of increasing ER with age for P-gp in enteroid monolayers; however, it was not significant. In the Ussing chamber setup, lower enalaprilat and propranolol transport was observed with age. Importantly, the RNA sequencing pathway analysis revealed that age-related variation in drug metabolism between neonates and adults was present in both enteroids and intestinal tissue. Age-related differences between 0 and 6 months old and adults were observed in tissue as well as in enteroid monolayers, although to a lesser extent. This study provides the first data for the further development of pediatric enteroids as an in vitro model to study age-related variation in drug transport. Overall, drug transport in enteroids was in line with data obtained from ex vivo tissue (using chamber) experiments. Additionally, pathway analysis showed similar PK-related differences between neonates and adults in both tissue and enteroid monolayers. Given the challenge to elucidate the effect of developmental changes in the pediatric age range in human tissue, intestinal enteroids derived from pediatric patients could provide a versatile experimental platform to study pediatric phenotypes.

Biotransformation of nanoplastics in human plasma and their permeation through a model in vitro blood-brain barrier: An in-depth quantitative analysis

Challenges in characterizing and quantifying nanoplastics within the human body hinder understanding of their transport, biotransformation, and potential for cellular penetration and barrier crossing. By implementing an innovative analytical workflow, including incorporation of gadolinium (Gd) as a tracer into the polymer matrix of nanoplastics, the fate of nanoplastics relative to an in vitro blood-brain barrier (BBB) model is elucidated in the absence or presence of a biomomolecule corona. The nanoplastics were incubated in human plasma for 5 min, 1 h, 6 h, and 24 h, after which the absorbed proteins and lipids (biocorona) were determined. A total of 268 proteins were identified in the biological coronas on polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics, with the initial compositions being broadly similar on both PS and PVC. Both nanoplastics exhibited a strong affinity for phosphatidylcholines (PC) and lysophosphocholines (LPC) from human plasma. The inherent chemical composition of the nanoplastics plays a pivotal role in the corona’s evolution over time. Human induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs) and astrocytes were exposed for 2 h to 5 µg L−1 of pristine nanoplastics or nanoplastics covered with a biological corona (following incubation in plasma for 6 h). A relatively low concentration of PS and PVC nanoplastics was determined to be present within the cellular layer of the BBB. The number of PVC nanoplastics crossing the BBB was higher than the number of PS nanoplastics. The presence of a biological corona on these particles decreases their uptake and transcytosis. This understanding might further the development of preventive measures or therapeutic strategies to counteract potential nanoplastic-induced neurotoxicity, and provide a foundation for development of in silico models to predict the neurotoxic implications of nanoplastics.

TME-NET: an interpretable deep neural network for predicting pan-cancer immune checkpoint inhibitor responses.

Immunotherapy with immune checkpoint inhibitors (ICIs) is increasingly used to treat various tumor types. Determining patient responses to ICIs presents a significant clinical challenge. Although components of the tumor microenvironment (TME) are used to predict patient outcomes, comprehensive assessments of the TME are frequently overlooked. Using a top-down approach, the TME was divided into five layers-outcome, immune role, cell, cellular component, and gene. Using this structure, a neural network called TME-NET was developed to predict responses to ICIs. Model parameter weights and cell ablation studies were used to investigate the influence of TME components. The model was developed and evaluated using a pan-cancer cohort of 948 patients across four cancer types, with Area Under the Curve (AUC) and accuracy as performance metrics. Results show that TME-NET surpasses established models such as support vector machine and k-nearest neighbors in AUC and accuracy. Visualization of model parameter weights showed that at the cellular layer, Th1 cells enhance immune responses, whereas myeloid-derived suppressor cells and M2 macrophages show strong immunosuppressive effects. Cell ablation studies further confirmed the impact of these cells. At the gene layer, the transcription factors STAT4 in Th1 cells and IRF4 in M2 macrophages significantly affect TME dynamics. Additionally, the cytokine-encoding genes IFNG from Th1 cells and ARG1 from M2 macrophages are crucial for modulating immune responses within the TME. Survival data from immunotherapy cohorts confirmed the prognostic ability of these markers, with p-values <0.01. In summary, TME-NET performs well in predicting immunotherapy responses and offers interpretable insights into the immunotherapy process. It can be customized at https://immbal.shinyapps.io/TME-NET.

Machine learning of metabolite-protein interactions from model-derived metabolic phenotypes.

Unraveling metabolite-protein interactions is key to identifying the mechanisms by which metabolism affects the function of other cellular layers. Despite extensive experimental and computational efforts to identify the regulatory roles of metabolites in interaction with proteins, it remains challenging to achieve a genome-scale coverage of these interactions. Here, we leverage established gold standards for metabolite-protein interactions to train supervised classifiers using features derived from genome-scale metabolic models and matched data on protein abundance and reaction fluxes to distinguish interacting from non-interacting pairs. Through a comprehensive comparative study, we explore the impact of different features and assess the effect of gold standards for non-interacting pairs on the performance of the classifiers. Using data sets from Escherichia coli and Saccharomyces cerevisiae, we demonstrate that the features constructed by integrating fluxomic and proteomic data with metabolic phenotypes predicted from genome-scale metabolic models can be effectively used to train classifiers, accurately predicting metabolite-protein interactions in the context of metabolism. Our results reveal that the high performance of classifiers trained on these features is unaffected by the method used to generate gold standards for non-interacting pairs. Overall, our study introduces valuable features that improve the performance of identifying metabolite-protein interactions in the context of metabolism.

Light-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography

Phototransduction involves changes in concentration of ions and other solutes within photoreceptors and in subretinal space, which affect osmotic pressure and the associated water flow. Corresponding expansion and contraction of cellular layers can be imaged using optoretinography (ORG), based on phase-resolved optical coherence tomography (OCT). Until now, ORG could reliably detect only photoisomerization and phototransduction in photoreceptors, primarily in cones under bright stimuli. Here, by employing a phase-restoring subpixel motion correction algorithm, which enables imaging of the nanometer-scale tissue dynamics during minute-long recordings, and unsupervised learning of spatiotemporal patterns, we discover optical signatures of the other retinal structures’ response to visual stimuli. These include inner and outer segments of rod photoreceptors, retinal pigment epithelium, and subretinal space in general. The high sensitivity of our technique enables detection of the retinal responses to dim stimuli: down to 0.01% bleach level, corresponding to natural levels of scotopic illumination. We also demonstrate that with a single flash, the optoretinogram can map retinal responses across a 12° field of view, potentially replacing multifocal electroretinography. This technique expands the diagnostic capabilities and practical applicability of optoretinography, providing an alternative to electroretinography, while combining structural and functional retinal imaging in the same OCT machine.

Improvement of broadband low-frequency sound insulation of sandwich plates with negative Poisson's ratio butterfly-shaped auxetic cellular

The novel cellular cores auxetic metamaterials with negative Poisson's ratio (NPR) exhibit unique mechanical deformation characteristics compared to conventional cellular cores, which can be further exploited in modeling lightweight sandwich structures. The butterfly-shaped auxetic cellular is not only an improvement upon the traditional re-entrant auxetic cellular with NPR, but also a kind of bionic design, which possesses higher stiffness and thus offers greater potential for sound insulation. Based on this, the present article explores a study of the sound transmission characteristics exhibited by sandwich plates with butterfly-shaped auxetic cellular core layers. Firstly, the motion equation is derived based on the first-order shear deformation theory and Hamilton's principle, which is further solved analytically based on fluid-structure coupling conditions and combined with Navier method. Then, the sound transmission loss (STL) is analytically described. The correctness of the theoretical model is verified by comparing the theoretical solution with the calculation results of the commercial software COMSOL and the experimental results of impedance tube sound insulation tests. Based on the theoretical model, it is calculated that the sound insulation effect of butterfly-shaped auxetic cellular core is better than that of traditional re-entrant cellular with NPR. An analysis is subsequently conducted to explore the impact of key parameters on the STL of the butterfly-shaped cellular sandwich plates.

Dissecting Acute Drug-Induced Hepatotoxicity and Therapeutic Responses of Steatotic Liver Disease Using Primary Mouse Liver and Blood Cells in a Liver-On-A-Chip Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based liver sinusoid model to mimic MASLD pathomechanisms and investigate the therapeutic effects of drug candidates lanifibranor and resmetirom. Mouse liver primary hepatocytes, hepatic stellate cells, Kupffer cells, and endothelial cells are seeded in a dual-chamber biocompatible liver-on-a-chip (LoC). The LoC is then perfused with circulating immune cells (CICs). Acetaminophen (APAP) and free fatty acids (FFAs) treatment recapitulate acute drug-induced liver injury and MASLD, respectively. As a benchmark for the LoC, multiplex immunofluorescence on livers from APAP-injected and dietary MASLD-induced mice reveals characteristic changes on parenchymal and immune cell populations. APAP exposure induces cell death in the LoC, and increased inflammatory cytokine levels in the circulating perfusate. Under FFA stimulation, lipid accumulation, cellular damage, inflammatory secretome, and fibrogenesis are increased in the LoC, reflecting MASLD. Both injury conditions potentiate CIC migration from the perfusate to the LoC cellular layers. Lanifibranor prevents the onset of inflammation, while resmetirom decreases lipid accumulation in hepatocytes and increases the generation of FFA metabolites in the LoC. This study demonstrates the LoC potential for functional and molecular evaluation of liver disease drug candidates.

Machine learning algorithms integrate bulk and single-cell RNA data to unveil oxidative stress following intracerebral hemorrhage

BackgroundIncreased oxidative stress (OS) activity following intracerebral hemorrhage (ICH) had significantly impacting patient prognosis. Identifying optimal genes associated with OS could enhance the understanding of OS after ICH. MethodsWe employed single-cell RNA sequencing (scRNA-seq) to investigate the heterogeneity of OS across various cellular tiers following ICH, aiming to acquire biological insights into ICH. We utilized AUCell, Ucell, singscore, ssgsea, and AddModuleScore algorithms, along with correlation analysis, to identify hub genes influencing high OS post-ICH. Furthermore, we employed four machine learning algorithms, eXtreme Gradient Boosting, Boruta, Random Forest, and Least Absolute Shrinkage and Selection Operator, to identify the optimal feature genes. To validate the accuracy of our analysis, we conducted validation in ICH animal experiments. ResultsAfter analyzing the scRNA-seq dataset using various algorithms, we found that OS activity exhibited heterogeneity across different cellular layers following ICH, with particularly heightened activity observed in monocytes. Further integration of bulk data and machine learning algorithms revealed that ANXA2 and COTL1 were closely associated with high OS after ICH. Our animal experiments demonstrated an increase in OS expression post-ICH. Additionally, the protein expression of ANXA2 and COTL1 was significantly elevated and co-localized with microglia. Pearson correlation coefficient analysis revealed a significant correlation between ANXA2 and OS, indicating strong consistency (r = 0.84, p < 0.05). Similar results were observed for COTL1 and OS (r = 0.69, p < 0.05). ConclusionsFollowing ICH, ANXA2 and COTL1 might penetrate the brain via monocytes, localize within microglia, and enhance OS activity. This might help us better understand OS after ICH.

Rheology of a suspension of deformable spheres in a weakly viscoelastic fluid

In this work, we consider a suspension of weakly deformable solid particles within a weakly viscoelastic fluid. The fluid phase is modelled as a second-order fluid, and particles within the suspended phase are assumed linearly elastic and relatively dilute. We apply a cell model as a proxy for mean field flow, and solve analytically within a cellular fluid layer and its enclosed particle. We use an ensemble averaging process to derive analytical results for the bulk stress in suspension, and evaluate the macroscopic properties in both shear and extensional flow. Our viscometric functions align with existing literature over a surprisingly broad range of fluid and solid elasticities.The suspension behaves macroscopically as a second-order fluid, and we give simple formulae by which the reader can calculate the parameters of this effective fluid, for use in more complex simulations. We additionally calculate the particle shape and orientation, and in simple shear flow show that the leading-order modifications to the angle of inclination ζ act to align the particle towards the flow direction, giving ζ=π/4−3Cae/4+α0Wi/2α1 where Cae is the elastic capillary number, Wi is the Weissenberg number, and αi are material properties of the suspending second-order fluid, for which the ratio α0/α1 is negative.

Structural and functional characterization of retinal impairment in T1DM patients without diabetic retinopathy: a 3-year longitudinal study.

To analyze the progression of structural and functional retinal impairment in type 1 diabetes mellitus (T1DM) patients with no clinical signs of diabetic retinopathy (DR) during a 3-year follow-up. This was an observational longitudinal study. Post-pediatric T1DM patients without clinical signs of DR, and sex- and age-matched healthy subjects were recruited at San Raffaele Hospital (Milan, Italy). Each patient underwent a comprehensive ophthalmological evaluation, including optical coherence tomography (OCT), OCT-angiography (OCT-A), retinal static and dynamic vessel analysis (DVA), and microperimetry. 21 eyes of 21 T1DM patients (10 females; 24 ± 2years old), and 21 age and sex-matched healthy subjects were enrolled. At baseline, T1DM eyes revealed a significantly decreased vessel length density using OCT-A (p < 0.001 and p = 0.046 in 3 × 3 and 6 × 6mm images) and a significantly increased vessel density index (p = 0.013 and p = 0.087 in 3 × 3 and 6 × 6mm images) of deep capillary plexus. DVA detected a significantly decreased vessel response to flicker light (p = 0.002). A significantly increased thickness of ganglion cellular layer 6-mm-diameter subfields in inferior and superior quadrants was found in diabetic patients (p < 0.001 in both subfields). At 3-years-follow-up no significant longitudinal changes were disclosed in all analyses. Concomitant subclinical microvascular and neurodegenerative damages could be early signs of DR onset that precede functional alterations and clinical signs of DR development. These alterations demonstrated a stable trend over time.

Neuron mapping in the Molly fish optic tectum: An emphasis on the adult neurogenesis process.

Teleost fish exhibit the most pronounced and widespread adult neurogenesis. Recently, functional development and the fate of newborn neurons have been reported in the optic tectum (OT) of fish. To determine the role of neurogenesis in the OT, this study used histological, immunohistochemical, and electron microscopic investigations on 18 adult Molly fish specimens (Poecilia sphenops). The OT of the Molly fish was a bilateral lobed structure located in the dorsal part of the mesencephalon. It exhibited a laminated structure made up of alternating fiber and cellular layers, which were organized into six main layers. The stratum opticum (SO) was supplied by optic nerve fibers, in which the neuropil was the main component. Radial bipolar neurons that possessed bundles of microtubules were observed in the stratum fibrosum et griseum superficiale (SFGS). Furthermore, oligodendrocytes with their processes wrapped around the nerve fibers could be observed. The stratum album centrale (SAC) consisted mainly of the axons of the stratum griseum centrale (SGC) and the large tectal, pyriform, and horizontal neurons. The neuronal cells of the SO and large tectal cells of the SAC expressed autophagy-related protein-5 (APG5). Interleukin-1β (IL-1β) was expressed in both neurons and glia cells of SGC. Additionally, inducible nitric oxide synthase (iNOS) was expressed in the neuropil of the SAC synaptic layer and granule cells of the stratum periventriculare (SPV). Also, transforming growth factor beta (TGF-β), SRY-box transcription factor 9 (SOX9), and myostatin were clearly expressed in the proliferative neurons. In all strata, S100 protein and Oligodendrocyte Lineage Transcription Factor 2 (Olig2) were expressed by microglia, oligodendrocytes, and astrocytes. In conclusion, it was possible to identify different varieties of neurons in the optic tectum, each with a distinct role. The existence of astrocytes, proliferative neurons, and stem cells highlights the regenerative capacity of OT. RESEARCH HIGHLIGHTS: The OT of the Molly fish exhibited a laminated structure made up of alternating fiber and cellular layers, which were organized into six main layers. Radial bipolar neurons that possessed bundles of microtubules were observed in the stratum fibrosum et griseum superficiale (SFGS). The stratum album central (SAC) consisted mainly of the axons of the stratum griseum centrale (SGC) and the large tectal, pyriform, and horizontal neurons. Inducible nitric oxide synthase (iNOS) was expressed in the neuropil of the SAC synaptic layer and granule cells of the stratum periventricular (SPV). Also, transforming growth factor beta (TGF-β), SRY-box transcription factor 9 (SOX9), and myostatin were clearly expressed in the proliferative neurons. The existence of astrocytes, proliferative neurons, and stem cells highlights the regenerative capacity of OT.

Mechanical and piezoresistive performance of additively manufactured carbon fiber/PA12 hybrid honeycombs

This study investigates a novel self-sensing honeycomb composite structure composed of two distinct cellular layers with differing unit cell architectures, specifically hexagonal and re-entrant designs. Short carbon fiber (CF)/polyamide 12 (PA12) composite filaments with 0, 5 or 15 wt.% CF content were utilized to additively manufacture the honeycomb structures via Fused Filament Fabrication (FFF), and their mechanical and piezoresistive self-sensing characteristics were experimentally investigated under quasi-static in-plane and out-of-plane compression at both room temperature and elevated temperatures. The results reveal that the hybrid hexagonal/re-entrant (HR) honeycombs mechanically outperform their non-hybrid double-layer and single-layer counterparts under in-plane loading, reporting an increase in collapse strength and energy absorption by factors of 1.64 and 2.25, respectively. These improvements are attributed to the mechanical interactions occurring at the interface between the auxetic and non-auxetic layers within the hybrid structure, effectively enhancing its structural attributes. Furthermore, the double-layer honeycombs display excellent strain-sensing capabilities within the elastic regime, with gauge factors reaching values as high as 146. Mechanical tests conducted at elevated temperatures reveal that the CF/PA12 honeycombs retain a significant portion of their elastic modulus, strength and energy absorption even at 125 °C, while maintaining high gauge factors of up to 72.4. These honeycombs also exhibit pronounced thermoresistive behavior, evidenced by a decrease in electrical resistance of up to 41.3 % with increasing temperatures from 25 to 125 °C. Considering their exceptional combination of thermo-mechanical, thermoresistive and piezoresistive characteristics, these hybrid double-layered CF/PA12 honeycombs hold promise for potential applications in multifunctional lightweight structures, offering integrated temperature and strain-sensing capabilities.

An in vitro 3-dimensional Collagen-based Corneal Construct with Innervation Using Human Corneal Cell Lines

To develop a 3-dimensional corneal construct suitable for invitro studies of disease conditions and therapies. Invitro human corneal constructs were created using chemically crosslinked collagen and chondroitin sulfate extracellular matrix and seeded with 3 human corneal cell types (epithelial, stromal, and endothelial) together with neural cells. The neural cells were derived from hybrid neuroblastoma cells and the other cells used from immortalized human corneal cell lines. To check the feasibility and characterize the constructs, cytotoxicity, cell proliferation, histology, and protein expression studies were performed. Optimized culture condition permitted synchronized viability across the cell types within the construct. The construct showed a typical appearance for different cellular layers, including healthy appearing, phenotypically differentiated neurons. The expected protein expression profiles for specific cell types within the construct were confirmed with western blotting. An invitro corneal construct was successfully developed with maintenance of individual cell phenotypes with anatomically correct cellular loci. The construct may be useful in evaluation of specific corneal disorders and in developing different corneal disease models. Additionally, the construct can be used in evaluating drug targeting and/or penetration to individual corneal layers, testing novel therapeutics for corneal diseases, and potentially reducing the necessity for animals in corneal research at the early stages of investigation. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

In vitro mRNA-S maternal vaccination induced altered immune regulation at the maternal-fetal interface.

Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology. This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs). We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs). Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1β remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs. In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications.

Associations of cartilage intermediate layer protein 1 and hypoxia-inducible factor-1-alpha with transthoracic echocardiography results in patients with heart failure with preserved ejection fraction

Aim. To evaluate the relationship of serum concentrations of myocardial remodeling and cellular hypoxia biomarkers cartilage intermediate layer protein 1 (CILP-1) and hypoxia-inducible factor-1-alpha (HIF-1α) with paraclinical parameters in patients with heart failure with preserved ejection fraction (HFpEF) and in the control group.Material and methods. The study included 47 patients diagnosed with HFpEF, aged from 47 to 79 years, who were treated from May 2018 to December 2019 in the hospital of the National Medical Research Center for Therapy and Preventive Medicine. The control group consisted of 32 people without a diagnosis of HFpEF, matched by sex and age. All participants underwent transthoracic echocardiography with assessment of diastolic function. Serum concentrations of CILP-1 and HIF-1α were determined by enzyme immunoassay using standardized test systems (RayBio and Clone-Cloud, USA).Results. In patients with HFpEF, the median serum concentrations of CILP-1 (3,24 ng/ml) and HIF-1α (14,3 pg/ml) were not significantly different from the values obtained in the control group (3,6 ng/ml and 7,5 pg/ml, respectively). Significant correlations of CILP-1 with echocardiographic indicators of the left ventricular interstitial fibrosis severity were revealed, while echocardiographic markers of HFpEF positively correlated with the HIF-1α level.Conclusion. Although the serum concentrations of CILP-1 and HIF-1α do not differ depending on HFpEF presence, it demonstrates an association with a number of echocardiographic parameters both in subgroups of patients with HFpEF and in subgroups of controls with different body mass index.