Microscopic Architecture Research Articles

Neonatal Hemochromatosis Secondary to an Inborn Error of Metabolism (Mitochondrial Disorder): Post- mortem Diagnosis in the Fetus of a Young Primipara

Abstract Introduction/Objective Neonatal hemochromatosis (NH), an extremely rare congenital phenotype of acute hepatic failure with hepatic and extrahepatic siderosis, is primarily (98%) caused by gestational alloimmune liver disease (GALD) and, rarely (2%), by infection, metabolic disorders, bile acid defects, and mitochondrial hepatopathy. This report presents an extremely rare case of NH caused by an inborn error of metabolism (suspected mitochondrial dysfunction). This low-birth-weight female was born with acute liver failure, metabolic acidosis, multisystem failure, and progressive lactate acidosis, and expired on day 7. On autopsy, liver was less than 50% of normal size and without nodularity. Microscopic architecture was preserved with erythropoiesis, canalicular bile plugs, microvesicular steatosis (oil red O stain) and abundant coarsely granular siderosis (iron stain). GALD was unlikely because of the absence of the typical hepatocytic injury, fibrosis or biliary destruction, and the negative immunohistochemistry for MAC (C5b-C9). Extrahepatic siderosis was demonstrated in thyroid follicles, thymic Hassall corpuscles, myocardium, and adenohypophysis. Sanger sequencing and deletion testing of mitochondrial genome on a maternal buccal biopsy identified a homoplasmic variant (m.15482 T>C p.(S246P) in maternal MT-CYB gene but without molecular diagnosis of a mitochondrial DNA disorder. Infant plasma had increased C6DC, C5, C12-OH acylcarnitine, alanine, and proline. Urine contained elevated organic acids (lactate/pyruvate, 2-ketoacids, 3-methylglutarate, 3-methylglutaconate), concerning acute mitochondrial respiratory chain dysfunction. Methods/Case Report: Case Study Results (if a Case Study enter NA) NA Conclusion Diagnosis of NH warrants exclusion of the most common etiology, GALD. Mitochondrial genetic mutations are the most difficult to diagnosis because of heterogeneity and typically undiagnosed maternal defects. This is the first report of NH with a homoplasmic maternal variant of uncertain significance. Neonatal lactic acidosis is the strongest clinical clue for mitochondrial dysfunction and should trigger phenotyping, maternal mitochondrial genetic variants (mtDNA, nuDNA), functional, biochemical, and genetic studies.

Enhanced sensitivity and broadband response in porous triple periodic minimal surface piezoresistive sensors for telemedicine applications

Wearable pressure sensors with outstanding performance have garnered significant attention in fields such as telemedicine. However, the development of sensors that achieve both adjustable high sensitivity and a wide response range remains a formidable challenge. To address these issues, we propose the development of a flexible piezoresistive sensor featuring simultaneous macro- and microstructures. This is achieved by constructing a complex macro-topological skeleton using Fused Deposition Molding (FDM) technology and integrating supercritical carbon dioxide (ScCO2) foaming technology for microscopic pore creation. The unique conductive network structure, coupled with the Triple Periodic Minimal Surface (TPMS) metamaterial framework and microscopic pore architecture, endows the piezoresistive sensors with exceptional sensing performance, including high sensitivity (12.13 MPa−1), a broad response range (exceeding 30 MPa), and long-term fatigue resistance (over 26,000 s cycles). In addition, the sensors are shielded from electromagnetic interference, with a maximum EMI shielding effectiveness of 53.2 dB for the TMFM with a thickness of 2.3 mm. The effects of varying porosities and foaming pressures on sensitivity were analyzed using finite element simulations. Owing to these remarkable features, multiple foot movement recognition was successfully demonstrated with volunteer participants by assembling sensing unit array modules. Based on this, an intelligent fall warning recognition system is developed using machine learning. This system accurately distinguishes four types of activity behaviors—standing, walking, spraining foot, and falling—with accuracy rates of 98.9 %, 97.1 %, 98.9 %, and 95.1 %, respectively. The system automatically generates an alarm pattern for detected fall behaviors. These findings suggest that the combination of TPMS skeleton and micropores structure offers a promising strategy for developing sensors with adjustable sensitivity and wide detection range for wearable devices. This technology holds significant potential for applications in telemedicine assistance, particularly for the elderly and other vulnerable populations.

FICTURE: scalable segmentation-free analysis of submicron-resolution spatial transcriptomics.

Spatial transcriptomics (ST) technologies have advanced to enable transcriptome-wide gene expression analysis at submicron resolution over large areas. However, analysis of high-resolution ST is often challenged by complex tissue structure, where existing cell segmentation methods struggle due to the irregular cell sizes and shapes, and by the absence of segmentation-free methods scalable to whole-transcriptome analysis. Here we present FICTURE (Factor Inference of Cartographic Transcriptome at Ultra-high REsolution), a segmentation-free spatial factorization method that can handle transcriptome-wide data labeled with billions of submicron-resolution spatial coordinates and is compatible with both sequencing-based and imaging-based ST data. FICTURE uses the multilayered Dirichlet model for stochastic variational inference of pixel-level spatial factors, and is orders of magnitude more efficient than existing methods. FICTURE reveals the microscopic ST architecture for challenging tissues, such as vascular, fibrotic, muscular and lipid-laden areas in real data where previous methods failed. FICTURE's cross-platform generality, scalability and precision make it a powerful tool for exploring high-resolution ST.

Choke Anastomosis: A Key Element Acting as a Shunt Converter Between Adjacent Angiosomes.

Choke anastomosis is commonly recognized as a resistance factor that detrimentally affects the hemodynamics of the skin flap; however, its additional potential physiological roles in normal skin function are currently not fully understood. Ten cadaveric forehead flap specimens pedicled with unilateral STAs were perfused with lead oxide-gelatin mixture, and then dissected into 3 layers, including the super temporal fascia-frontalis-galea aponeurotica layer, the subcutaneous adipose tissue layer, and the "super-thin flap" layer. The forehead flap and stratified specimens underwent molybdenum target x-ray and subsequent transparent processing to effectively visualize the microscopic spatial architecture of arterial vessels across all levels. Based on the different anastomoses near the midline area of the flap, 2 types of arterial perfusion were identified: choke anastomosis type (8/10) and true anastomosis type (2/10). The former formed multiple choke anastomoses near the midline. In the "super-thin flap" layer, arterial perfusion density on the ipsilateral side was significantly higher compared to that on the contralateral side. The arterioles on the ipsilateral side exhibited a dense and uninterrupted distribution, whereas those on the contralateral side appeared sparse and dispersed. The latter exhibited an alternative perfusion pattern; the bilateral arterial vessels were connected with 3 to 5 true anastomoses near the midline. Furthermore, the microscopic architecture confirmed a uniform distribution of arterioles that remained continuous from ipsilateral to contralateral sides in the "super-thin flap" layer. This study demonstrated that choke anastomosis not only impairs blood perfusion in the adjacent angiosomes but also acts as a shunt converter to impact the blood supply of distal skin flaps at different levels through the "trans-territory diversion phenomenon." This results in necrosis of the superficial dermis while preserving survival of the deep subcutaneous adipose tissue.

Micro‐Ring Morphology of Ag7NCs and Light‐Induced Reversible Interconversion of FCC Ag14NCs via Cu2+ ions‐Mediated Particle‐Assisted Reversible Interconversion

AbstractDespite the remarkable progress made on intercluster conversion in atomically precise metal nanoclusters (MNCs) and their self‐organization to develop microscopic molecular architecture with well‐defined size and shape, achieving light‐induced reversible structural transformation and the development of micro‐ring self‐assembly in MNCs have, so far, remained elusive. The present investigation touches on these two long‐standing quests by showcasing a new route, light‐induced Particle‐Assisted Reversible Interconversion (PARI) for the reversible transformation from Face Centered Cubic (FCC) Ag14NCs to Ag7NCs. Our studies reveal that the lack of plasmonic silver nanoparticles (AgNPs) in the system results in the formation of Ag7NCs with metallic kernels having centrosymmetric crystal packing. The molecular self‐organization of Ag7NCs through various non‐covalent interactions such as C−H⋅⋅⋅O, C−H⋅⋅⋅H−C, and C−H⋅⋅⋅π leads to the formation of micro‐ring morphology, a unique molecular architecture in MNCs. The in situ generated AgNPs due to the acceleration of the reaction kinetics by Cu2+ ions facilitate the growth of Ag14NCs with FCC metallic kernel. These two structural units of AgNCs show light‐induced reversible structural transformation which is also associated with the reversible tuning of their spectroscopic and morphological signatures. This PARI‐guided interconversion strategy put forward a most appropriate example of a structure–property relationship in MNCs.

Micro-Ring Morphology of Ag7NCs and Light-Induced Reversible Interconversion of FCC Ag14NCs via Cu2+ ions-Mediated Particle-Assisted Reversible Interconversion.

Despite the remarkable progress made on intercluster conversion in atomically precise metal nanoclusters (MNCs) and their self-organization to develop microscopic molecular architecture with well-defined size and shape, achieving light-induced reversible structural transformation and the development of micro-ring self-assembly in MNCs have, so far, remained elusive. The present investigation touches on these two long-standing quests by showcasing a new route, light-induced Particle-Assisted Reversible Interconversion (PARI) for the reversible transformation from Face Centered Cubic (FCC) Ag14NCs to Ag7NCs. Our studies reveal that the lack of plasmonic silver nanoparticles (AgNPs) in the system results in the formation of Ag7NCs with metallic kernels having centrosymmetric crystal packing. The molecular self-organization of Ag7NCs through various non-covalent interactions such as C-H⋅⋅⋅O, C-H⋅⋅⋅H-C, and C-H⋅⋅⋅π leads to the formation of micro-ring morphology, a unique molecular architecture in MNCs. The in situ generated AgNPs due to the acceleration of the reaction kinetics by Cu2+ ions facilitate the growth of Ag14NCs with FCC metallic kernel. These two structural units of AgNCs show light-induced reversible structural transformation which is also associated with the reversible tuning of their spectroscopic and morphological signatures. This PARI-guided interconversion strategy put forward a most appropriate example of a structure-property relationship in MNCs.

Lamiales epidermal dynamics: Unveiling antimicrobial resilience in a structural symphony.

This research on Lamiales epidermal anatomy not only provides in-depth understanding of their structural traits but also highlights the significance of uncovering the inherent antimicrobial resilience embedded within these plants. Such insights hold promise for advancing natural product-based approaches in medicine, potentially contributing to the development of novel antimicrobial agents inspired by Lamiales unique biological defense mechanisms. Scanning microscopic tools were utilized to conduct foliar epidermal anatomy of nine species that belong to seven genera and four families within the Lamiales order, Plantaginaceae, Scrophulariaceae, Verbenaceae, and Lamiaceae. This approach aimed to gather both qualitative and quantitative data, facilitating the assessment of taxonomic microanatomical significance. The shape of epidermal cells and their anticlinal walls; number of epidermal cells, stomata, and trichomes; type of stomata and trichomes; length and width of epidermal cells, trichomes, stomatal pore, guard cells, and subsidiary cells; and stomatal index were determined statistically. Most of the species examined were amphistomatous and showed extensive array of trichomes diversity. The exploration of Lamiales epidermal micromorphology and their antimicrobial potential were significant for their implications in multidisciplinary fields. The pharmacological research to utilize sustainable agricultural practices prompts avenues to strengths of Lamiales order for the development of novel antimicrobial solutions and ecological benefits. RESEARCH HIGHLIGHTS: Diverse trichome morphometry reveals a wide array of trichome structures across Lamiales species. Epidermal microscopic architecture variability of epidermal cell shapes and sizes signifies the interspecies variability. Secondary metabolite localization within microanatomical structures elucidates potential hotspots for antimicrobial compound production.

Single step grown porous polycrystalline nickel microstructures with ultra-thin defect rich surface oxide for alkaline water oxidation

Investigation on the intrinsic catalytic activity of structurally diverse polycrystalline nickel microstructures such as porous nickel sheets (PNS), porous folded/curled nickel structures (PFNS) and porous nickel balls (PNB) revealed the surface bounded electrocatalytic activities within an alkaline reaction environment for water oxidation. Nickel microstructures were grown via template/surfactant-free, single step solution combustion technique in air atmosphere. The distinct morphologies (porous nickel sheets, porous folded/curled nickel structures and porous nickel balls) were achieved through changing the quantity of HNO3 in the reaction mixture. The physicochemical characterisations were done with XRD, FESEM, EDS and XPS. Microscopic studies revealed the growth of nickel grains with numerous macro pores forming microstructures in distinct morphologies. The O ls spectra of XPS studies revealed the presence of O−/O2− sites and Ni 2p spectra were distinguished between the formation of Ni0/Ni2+/Ni3+ states, implied the existence of surface oxide with plenty of defects. The synergistic effect results from the formation of microscopic porous architectures with defect rich surface oxide on the electrochemical behaviour and OER activity of PNS, PFNS and PNB were discussed with electrochemical techniques such as CV, LSV, EIS and CP. The OER kinetics in terms of relatively low value of overpotential at 10 mA cm−2 and Tafel slope along with high specific activity of PNS/GCE with respect to PFNS/GCE and PNB/GCE were attributed to the combined effect of increase in electrochemical surface area, high roughness factor and fast charge transfer kinetics. The better electrochemical performance and OER activities of porous nickel sheets in comparison with folded/curled nickel structures and nickel balls is contributed to the unique 2D porous architecture with plenty of oxygen vacancies. This structure not only expose more surface for the formation of passive oxide layer in an alkaline reaction environment but also exhibit facile charge transport properties, causes the generation of numerous surface-active sites for electrocatalytic water oxidation. The outcome of our work gives new insights on the surface electrochemistry of polycrystalline nickel, enables micro-structuring as a prospective strategy towards the optimization of electrocatalysts as anode material for alkaline water oxidation.

Amanita amplivelata, (Amanitaceae, Agaricales), a remarkable new Eurasian species of the section Vaginatae

Amanita amplivelata is introduced as a new species, based on numerous collections from geographically distant areas of Europe and the Near East (Bulgaria, the Czech Republic, France and Türkiye). This new species is likely ectomycorrhizal with Populus spp. in natural poplar stands, urban settings, and plantations. Detailed description and illustrations of its morphological features are presented. Phylogenetic analysis of nrITS and combined nrITS, nrLSU and TEF-1α sequences placed it in a separate stirp in Clade 5 of section Vaginatae. The ample, saccate volva with a peculiar microscopic architecture confirms relatively close phylogenetic relationships with A. crocea and A. dryophila. The distinction of the new species from other phylogenetically related or morphologically similar taxa is outlined.

Modulating lipid bilayer permeability and structure: Impact of hydrophobic chain length, C-3 hydroxyl group, and double bond in sphingosine

Sphingosine, an amphiphilic molecule, plays a pivotal role as the core structure of sphingolipids, essential constituents of cell membranes. Its unique capability to enhance the permeability of lipid membranes profoundly influences crucial life processes. The molecular structure of sphingosine dictates its mode of entry into lipid bilayers and governs its interactions with lipids, thereby determining membrane permeability. However, the incomplete elucidation of the relationship between the molecular structure of sphingosine and the permeability of lipid membranes persists due to challenges associated with synthesizing sphingosine molecules. A series of sphingosine-derived molecules, featuring diverse hydrophobic chain lengths and distinct headgroup structure, were meticulously designed and successfully synthesized. These molecules were employed to investigate the permeability of large unilamellar vesicles, functioning as model lipid bilayers. With a decrease in the hydrophobic chain length of sphingosine from C15 to C11, the transient leakage ratio of vesicle contents escalated from ∼ 13 % to ∼ 28 %. Although the presence of double bond did not exert a pronounced influence on transient leakage, it significantly affected the continuous leakage ratio. Conversely, modifying the chirality of the C-3 hydroxyl group gives the opposite result. Notably, methylation at the C-3 hydroxyl significantly elevates transient leakage while suppressing the continuous leakage ratio. Additionally, sphingosines that significantly affect vesicle permeability tend to have a more pronounced impact on cell viability. Throughout this leakage process, the charge state of sphingosine-derived molecule aggregates in the solution emerged as a pivotal factor influencing vesicle permeability. Fluorescence lifetime experiments further revealed discernible variations in the effect of sphingosine molecular structure on the mobility of hydrophobic regions within lipid bilayers. These observed distinctions emphasize the impact of molecular structure on intermolecular interactions, extending to the microscopic architecture of membranes, and underscore the significance of subtle alterations in molecular structure and their associated aggregation behaviors in governing membrane permeability.

Characterization and morphological methods for oral biofilm visualization: where are we nowadays?

The oral microbiome represents an essential component of the oral ecosystem whose symbiotic relationship contributes to health maintenance. The biofilm represents a state of living of microorganisms surrounding themselves with a complex and tridimensional organized polymeric support and defense matrix. The substrates where the oral biofilm adhere can suffer from damages due to the microbial community metabolisms. Therefore, microbial biofilm represents the main etiological factor of the two pathologies of dental interest with the highest incidence, such as carious pathology and periodontal pathology. The study, analysis, and understanding of the characteristics of the biofilm, starting from the macroscopic structure up to the microscopic architecture, appear essential. This review examined the morphological methods used through the years to identify species, adhesion mechanisms that contribute to biofilm formation and stability, and how the action of microbicidal molecules is effective against pathological biofilm. Microscopy is the primary technique for the morphological characterization of biofilm. Light microscopy, which includes the stereomicroscope and confocal laser microscopy (CLSM), allows the visualization of microbial communities in their natural state, providing valuable information on the spatial arrangement of different microorganisms within the biofilm and revealing microbial diversity in the biofilm matrix. The stereomicroscope provides a three-dimensional view of the sample, allowing detailed observation of the structure, thickness, morphology, and distribution of the various species in the biofilm while CLSM provides information on its three-dimensional architecture, microbial composition, and dynamic development. Electron microscopy, scanning (SEM) or transmission (TEM), allows the high-resolution investigation of the architecture of the biofilm, analyzing the bacterial population, the extracellular polymeric matrix (EPS), and the mechanisms of the physical and chemical forces that contribute to the adhesion of the biofilm to the substrates, on a nanometric scale. More advanced microscopic methodologies, such as scanning transmission electron microscopy (STEM), high-resolution transmission electron microscopy (HR-TEM), and correlative microscopy, have enabled the evaluation of antibacterial treatments, due to the potential to reveal the efficacy of different molecules in breaking down the biofilm. In conclusion, evidence based on scientific literature shows that established microscopic methods represent the most common tools used to characterize biofilm and its morphology in oral microbiology. Further protocols and studies on the application of advanced microscopic techniques are needed to obtain precise details on the microbiological and pathological aspects of oral biofilm.

Exploring the Place of Fish Skin Grafts with Omega-3 in Pediatric Wound Management.

Wound healing in the pediatric population is known to be a challenge and poorly studied. Split-thickness skin grafts, full-thickness skin grafts, and flaps overlap their applications with the growing field of cellular and tissue-based therapies. However, their role in pediatric reconstruction has yet to be defined. The Kerecis® Omega-3 wound patch, derived from decellularized codfish skin, has garnered attention due to its preserved microscopic architecture resembling the human extracellular matrix. This acellular dermal matrix acts as a scaffold, fostering dermal cell and capillary adhesion while harnessing omega-3 polyunsaturated fatty acids for granulation acceleration and antimicrobial effects. This study presents a comprehensive review and surgical protocol for utilizing Kerecis® fish skin in pediatric wound care. The research embraces a case series involving five patients with diverse wound locations. The Kerecis® Omega-3 wound patch underwent meticulous application and careful monitoring. The results highlight an average time of 48.6 days for complete epithelialization, yielding favorable outcomes with no hypertrophic scarring and mild retraction. Kerecis® fish skin grafting stands as a tool that not only accelerates healing but also addresses the multifaceted challenges associated with wound management in the pediatric population: the avoidance of donor site morbidity and improved postoperative pain control.

Scale-invariant changes in corticospinal excitability reflect multiplexed oscillations in the motor output.

In the absence of disease, humans produce smooth and accurate movement trajectories. Despite such 'macroscopic' aspect, the 'microscopic' structure of movements reveals recurrent (quasi-rhythmic) discontinuities. To date, it is unclear how the sensorimotor system contributes to the macroscopic and microscopic architecture of movement. Here, we investigated how corticospinal excitability changes in relation to microscopic fluctuations that are naturally embedded within larger macroscopic variations in motor output. Participants performed a visuomotor tracking task. In addition to the 0.25Hz modulation that is required for task fulfilment (macroscopic scale), the motor output shows tiny but systematic fluctuations at ∼2 and 8Hz (microscopic scales). We show that motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) during task performance are consistently modulated at all (time) scales. Surprisingly, MEP modulation covers a similar range at both micro- and macroscopic scales, even though the motor output differs by several orders of magnitude. Thus, corticospinal excitability finely maps the multiscale temporal patterning of the motor output, but it does so according to a principle of scale invariance. These results suggest that corticospinal excitability indexes a relatively abstract level of movement encoding that may reflect the hierarchical organisation of sensorimotor processes. KEY POINTS: Motor behaviour is organised on multiple (time)scales. Small but systematic ('microscopic') fluctuations are engrained in larger and slower ('macroscopic') variations in motor output, which are instrumental in deploying the desired motor plan. Corticospinal excitability is modulated in relation to motor fluctuations on both macroscopic and microscopic (time)scales. Corticospinal excitability obeys a principle of scale invariance, that is, it is modulated similarly at all (time)scales, possibly reflecting hierarchical mechanisms that optimise motor encoding.

Understanding Osteoporosis: Human Bone Density, Genetic Mechanisms, Gut Microbiota, and Future Prospects.

Osteoporosis is a systemic condition of the skeleton that leads to diminished bone mass, a breakdown in the bone tissue's microscopic architecture, and an elevated risk of breaking a bone. The elderly and women particularly after menopause are disproportionately affected, and the condition generally stays undiagnosed until a broken bone causes severe pain and immobility. Causes of osteoporosis include low bone mass, more than normal bone loss, changes in hormone levels (decreased estrogen or testosterone), certain diseases and therapies, and lifestyle factors like smoking and inactivity. The spine, hip, and forearm are particularly vulnerable to osteoporosis-related fractures. The purpose of this article is to present a thorough understanding of osteoporosis, including the disease's connection to bone density in humans, and the major part played by genetic pathways and gut flora. The causes of osteoporosis, the effects of aging on bone density, and why some groups experience a higher incidence of the disease than others are investigated. The paper also includes animal and human experiments investigating the link between gut flora and osteoporosis. Finally, it looks to the future and speculates on possible developments in osteoporosis prevention and therapy.

Functional Connectome Hierarchy Distortions in Female Nurses With Occupational Burnout and Its Gene Expression Signatures.

Burnout has become a serious public health issue worldwide, particularly during the COVID-19 pandemic. Functional connectome impairments associated with occupational burnout were widely distributed, involving both low-level sensorimotor cortices and high-level association cortices. To investigate whether there are hierarchical perturbations in the functional connectomes and if these perturbations are potentially influenced by genetic factors in nurses who feel "burned out." Prospective, case control. Thirty-three female nurses with occupational burnout (aged 27-40, 32.42 ± 3.37) and 32 matched nurses who were not feeling burned out (aged 27-42, 32.50 ± 4.21). 3.0 T, gradient-echo echo-planar imaging sequence (GE-EPI). Gradient-based techniques were used to depict the perturbations in the multi-dimensional hierarchical structure of the macroscale connectome. Gene expression data were acquired from the Allen Human Brain Atlas. Cortex-wide multivariate analyses were used for between-group differences in gradients as well as association analyses between the hierarchy distortions and the MBI score (FDR corrected). Partial least squares, spin test and bootstrapping were utilized together to select the gene sets (FDR corrected). Gene enrichment analyses (GO, KEGG and cell-type) were further performed. Significance level: P < 0.05. There were significant gradient distortions, with strong between-group effects in the somatosensory network and moderate effects in the higher-order default-mode network, which were significantly correlated with the gene expression profiles (r = 0.3171). The most related genes were broadly involved in the cellular response to minerals, neuronal plasticity, and the circadian rhythm pathway (q value < 0.01). Significant enrichments were found in excitatory (r = 0.2588), inhibitory neurons (r = 0.2610), and astrocytes cells (r = 0.2633). Regions affected by burnout severity were mainly distributed in the association and visual cortices. By connecting in vivo imaging to genes, cell classes, and clinical data, this study provides a framework to understand functional impairments in occupational burnout and how the microscopic genetic architecture drive macroscopic distortions. 1 TECHNICAL EFFICACY: Stage 2.

MICROSCOPIC ARCHITECTURE OF THE LIVER OF EXPERIMENTAL RATS AFTER CANNABIDIOL OIL APPLICATIONS

Cannabidiol (CBD), found in Cannabis sativa (hemp), is a non-psychoactive phytochemical substance that has gained considerable popularity over the past decade. Cannabidiol is the main phytocannabinoid, its share in the plant extract can reach 40%. The aim of the study was to study and compare the microscopic architecture of the liver in normal and after 2 weeks cannabidiol oil applications in experimental rats. We conducted an experimental study of the effect of CBD on the liver 2 weeks after its use as a dietary supplement. The main group consisted of 18 rats to which 5 drops (3 mg 10%) of cannabidiol oil were added to the main feed once a day for 2 weeks. The control group consisted of 6 sexually mature white male rats, which were provided with water and food without any restrictions. Our research results showed that the use of CBD oil as a food supplement did not have a toxic effect on the liver, did not cause any damage.

On the origin of power-scaling exponents in silica aerogels

AbstractThe macroscopic properties of open-porous cellular materials hinge upon the microscopic skeletal architecture and features of the material. Typically, bulk material properties, viz. the elastic modulus, strength of the material, thermal conductivity, and acoustic velocity, of such porous materials are expressed in terms of power-scaling laws against their density. In particular, the relation between the elastic modulus and the density has been intensively investigated. While the Gibson and Ashby model predicts an exponent of 2 for ideally connected foam-like open-cellular solids, the exponent is found to lie between 3 and 4 for silica aerogels. In this paper, we investigate the origins of this scaling exponent. Particularly, the effect of the pearl-necklace-like skeletal features of the pore walls and that of the random spatial arrangement is extensively computationally studied. It is shown that the latter is the driving factor in dictating the scaling exponent and the rest of the features play a negligible or no role in quantifying the scaling exponent.Graphical Abstract

Tenofovir alone or combined with doxorubicin abrogates DMBA-induced mammary cell carcinoma: An insight into its modulatory impact on oxidative/Notch/apoptotic signaling

AimsBreast cancer incidence keeps on growing and emerging as one of the major global challenges, therefore, the introduction of new approaches is of great demand. Drug repurposing is crucial to faster and cheaper discovery of anti-cancer drugs. The antiviral tenofovir disproxil fumarate (TF) was reported to decrease hepatocellular carcinoma risk by interfering with cell cycle and proliferation. This study aimed to scrutinize the role of TF alone or combined with doxorubicin (DOX) in 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinoma rat model. Materials and methodsBreast carcinoma was induced by DMBA (7.5 mg/kg, twice/week, subcutaneous into mammary gland) for 4 successive weeks. TF (25 and 50 mg/kg/day) was given orally and DOX (2 mg/kg) was injected once/week by tail vein starting from day 1. Key findingsThe anti-cancerous effect of TF was mediated by suppression of oxidative stress markers and Notch signaling proteins (Notch1, JAG1, and HES1), attenuation of tumor proliferation markers (cyclin-D1 and Ki67), and boosting of apoptosis (P53 and Caspase3) and autophagy biomarkers (Beclin1 and LC3). In parallel, histopathological assessment displayed that mammary glands from animals treated with TF alone or combined with DOX showed better histopathological scores. Interestingly, TF and DOX co-treatment markedly decreased myocardial injury markers (AST, LDH, and CK-MB), restored the balance between GSH and ROS, prohibited lipid peroxidation, and preserved microscopic myocardial architecture. SignificanceTF elicited antitumor activity via multiple molecular mechanisms. Moreover, combining TF with DOX might be a potential novel strategy to enhance DOX-anticancer activity and decrease its cardiac side effects.

Empagliflozin inhibits autophagy and mitigates airway inflammation and remodelling in mice with ovalbumin-induced allergic asthma

Empagliflozin, a selective inhibitor of Na+-glucose cotransporter-2, has been reported to exert anti-inflammatory and anti-fibrotic effects in addition to autophagy modulation. Addressing the role of autophagy in allergic asthma revealed controversial results. The potential effect of empagliflozin treatment on airway inflammation and remodelling as well as autophagy modulation in a murine model of allergic asthma was investigated. Over a 7-week period, male BALB/c mice were sensitized and challenged by intraperitoneal injection and inhalation of ovalbumin, respectively. Animals were treated with empagliflozin (10 mg/kg; orally) and/or rapamycin (an autophagy inducer; 4 mg/kg; intraperitoneally) before every challenge. Methacholine-induced airway hyperresponsiveness was evaluated one day after the last challenge. After euthanasia, serum, bronchoalveolar lavage fluid, and lung tissues were collected for biochemical, histopathological, and immunohistochemical assessment. Results revealed that empagliflozin decreased airway hyperresponsiveness, serum ovalbumin-specific immunoglobulin E, and bronchoalveolar lavage total and differential leukocytic counts. Levels of inflammatory and profibrotic cytokines (IL-4, IL-5, IL-13, IL-17, and transforming growth factor-β1) were all inhibited. Moreover, empagliflozin preserved pulmonary microscopic architecture and alleviated bronchiolar epithelial thickening, goblet cell hyperplasia, fibrosis and smooth muscle hypertrophy. These effects were associated with inhibition of ovalbumin-activated autophagic flux, as demonstrated by decreased LC3B expression and LC3BII/I ratio, as well as increased P62 expression. However, the therapeutic potential of empagliflozin was inhibited when rapamycin was co-administered. In conclusion, this study demonstrates that empagliflozin has immunomodulatory, anti-inflammatory, and anti-remodelling properties in ovalbumin-induced allergic asthma and suggests that autophagic flux inhibition may play a role in empagliflozin's anti-asthmatic effects.

Technique for xenogeneic cross-circulation to support human donor lungs ex vivo.

Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and recover injured human donor lungs ex vivo. Human donor lungs (n=9) declined for transplantation were procured, cannulated, and subjected to 24 hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus) and complement-depleting cobra venom factor. Standard lung-protective perfusion and ventilation strategies, including periodic lung recruitment maneuvers, were used throughout xenogeneic XC. Every 6 hours, ex vivo donor lung function (gas exchange, compliance, airway pressures, pulmonary vascular dynamics, lung weight) was evaluated. At the experimental endpoint, comprehensive assessments of the lungs were performed by bronchoscopy, histology, and electron microscopy. Student's t-test and 1-way analysis of variance with Dunnett's post-hoc test was performed, and p < 0.05 was considered significant. After 24 hours of xenogeneic XC, gas exchange (PaO2/FiO2) increased by 158% (endpoint: 364 ± 142 mm Hg; p=0.06), and dynamic compliance increased by 127% (endpoint: 46 ± 20 ml/cmH2O; p=0.04). Airway pressures, pulmonary vascular pressures, and lung weight remained stable (p > 0.05) and within normal ranges. Over 24 hours of xenogeneic XC, gross and microscopic lung architecture were preserved: airway bronchoscopy and parenchymal histomorphology appeared normal, with intact blood-gas barrier. Xenogeneic cross-circulation is a robust method for ex vivo support, evaluation, and improvement of injured human donor lungs declined for transplantation.