The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking, chemo and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to 1) optimize delivery of oncolytic viruses beyond the blood brain barrier; 2) trigger inflammatory immune responses in and around tumors; and 3) use of multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

Abstract: Radiation-induced skin injury can be a serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on the skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH-1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment.

UV-digital printing belongs to the commonly used method for custom large-area substrate decoration. Despite low surface energy and adhesion, transparent polymer materials, such as polymethylmethacrylate (PMMA) and polycarbonate (PC), represent an ideal substrate for such purposes. The diffuse coplanar surface barrier discharge (DCSBD) in a novel compact configuration was used for substrate activation to improve ink adhesion to the polymer surface. This industrially applicable version of DCSBD was prepared, tested, and successfully implemented for the UV-digital printing process. Furthermore, wettability and surface free energy measurement, X-ray photoelectron spectroscopy, atomic force and scanning electron microscopy evaluated the surface chemistry and morphology changes. The changes in adhesion of the surface and of ink were analyzed by a peel-force and a crosscut test, respectively. A short plasma treatment (1-5 s) enhanced the substrate's properties of PMMA and PC while providing the pre-treatment suitable for further in-line UV-digital printing. Furthermore, we did not observe damage or significant change of roughness affecting the substrate's initial transparency.

Petrosamine (1) – a colored pyridoacridine alkaloid from the Belizean sponge, Petrosia sp. that is also a potent inhibitor of acetylcholine esterase (AChE) – was investigated by spectroscopic and computational methods. Analysis of the petrosamine free energy landscapes, pKa and tautomerism revealed an accurate electronic depiction of the molecular structure of 1 as the di-keto form, with net charge of q = +1, rather than a dication (q = +2) under ambient conditions of isolation-purification. The pronounced solvatochromism (UV-vis) reported for 1, and related analogs, was investigated in detail and is best explained by charge delocalization and stabilization of the ground state (HOMO) of 1 rather than an equilibrium of competing tautomers. Refinement of the molecular structure of 1 by QM methods complements published computational docking studies to define the contact points in the enzyme active site that may improve design of new AChE inhibitors based on the pyridoacridine alkaloid molecular skeleton.

More than twenty-five years ago the Global Solar UV index (UVI) has been introduced as a simple means of visualizing the intensity of ultraviolet radiation and to alert people to the need for sun protection. In our survey among directors of 436 kindergartens in southern Germany we investigated the level of awareness and knowledge about the UVI as well as the practical consequences for sun protection in kindergartens. Less than half of the directors (n=208, 47.7%) had ever heard of the UVI, and only a small minority of them (n=34, 8.7%) used the daily UVI information to adapt sun protective measures in their kindergartens. Detailed knowledge about the UVI was a rarity among the respondents. The proportion of respondents with self-perceived detailed UVI knowledge was five times higher than actual knowledge assessed by an in-depth structured interview using open-ended questions about the UVI (14.2% vs. 2.8%). No clear relationship of UVI awareness, knowledge, and use to directors' age and gender was found. The UVI-related variables also showed no association with directors' knowledge of risk factors for skin cancer and their attitudes towards tanned skin. Overall, the results paint a sobering picture regarding the penetration of the UVI into sun protection policies of German kindergartens. Future public health campaigns should target increasing awareness and understanding of the UVI as well as its importance for sun protection of children.

In this experimental report the biocompatibility of elastomeric scaffold structures made via stereolithography employing table-top 3D printer (Ember, Autodesk) and commercial resin FormLabs Flexible (FormLabs) was studied. The samples were manufactured using standard printing and development protocol, which is known to inherit cytotoxicity due to remaining non-polymerized remaining monomers, despite the polymerized material being fully biocompatible. Additional steps were taken to remedy this problem: the fabricated structures were soaked in isopropanol and methanol for different conditions (temperature, duration) in order to leach out the non-polymerized monomers. Also printed structures were UV exposed to assure maximum polymerization degree of the material. Post-processed structures were seeded with myogenic stem cells and the number of live cells was evaluated as an indicator for the material biocompatibility. The straightforward post-processing protocol enhances the biocompatibility by 7 times after 7 days soaking in isopropanol and methanol and is comparable to control (glass and polystyrene) samples. This proposes the approach as a novel and simple method to be widely applicable for dramatic cytotoxicity reduction of optically 3D printed micro-/nano-scaffolds for biomedical applications.

As one of GEO-constellation for environmental monitoring in the next decade, Geostationary Environment Monitoring Spectrometer (GEMS) is designed to observe the Asia Pacific region to provide the information on the atmospheric chemicals, aerosol and cloud properties. For the continuous monitoring of the sensor performance after its launch in early 2020, here we suggest deep convective clouds (DCCs) as a possible target for the vicarious calibration of GEMS, the first UV/VIS hyperspectral sensor onboard a geostationary satellite. Tropospheric Monitoring Instrument (TROPOMI) and Ozone Monitoring Instrument (OMI) are used as a proxy of GEMS, and a conventional DCC detection approach applying the thermal threshold test is used for the DCC detection based on the collocations with Advance Himawari-8 Imager (AHI) onboard Himawari-8 geostationary satellite. DCCs are frequently detected over the GEMS observation area on average over 200 pixels in a single observation scene. Considering the spatial resolution of GEMS, 3.5 km×7 km which is similar to TROPOMI, and its temporal resolution (8 times a day), availability of DCCs for vicarious calibration of GEMS is expected to be sufficient. Inspection of the DCC reflectivity spectra estimated from the OMI and TROPOMI data also shows a promising result. Even though, their observation geometry and sensor characteristics are quite a different, the estimated DCC spectra agree quite a well within a known uncertainty range with comparable spectral features. When the DCC detection is further improved by applying both visible and infrared tests, the variability of DCC reflectivity from the TROPOMI data is reduced by half, from 10% to 5%. This is mainly due to the efficient screening of cold thin cirrus with the visible test and of bright warm clouds with the infrared test. The precise DCC detection is also expected to contribute to the accurate characterization of the cloud reflectivity, which will be further investigated.

Coffee and caffeine have been used as solar absorbers and also to increase the thermal stability and efficiency of perovskite solar cells. In this work, we report the sensing of extremely alkaline pH by colloidal coffee solution aided by generation of an optical absorption band in the near-UV region. This generation of absorption band could be explained by the orientation induced dipole-dipole interactions arising from differing caffeine-solvent interactions with varying pH. Such a generation leads to the lowering of direct as well as indirect bandgaps from 4 eV-->2.8 eV& 3.4 eV-->2.5 eV, respectively. We also estimate the changes in optical energy storage efficiency, inferring it to be highest for pH 11 having the highest intensity of the generated absorption band (λ_abs≈360 nm). With these observations and further deductions, the work reported in this paper would be of immense interest to the researchers working in the field of development of chemical pH sensors and also in the development of novel UV absorbers.

The aim of the study was the evaluation of the efficiency of selected abiotic elicitors, i.e. silver and cadmium ions, ultrasound, and UV-C irradiation, in the stimulation of triterpenoid biosynthesis, accumulation, and saponin secretion in Calendula officinalis hairy root cultures. Apart from the possible enhancement of triterpenoid production, the relationship between primary and secondary metabolism (represented respectively by sterols and pentacyclic triterpenes), modifications of the sterol compositional profile, and fluctuations in the total triterpenoid content were monitored in the performed experiments. The main phenomenon observed as a response to heavy metal treatment was the stimulation (up to 12-fold) of the secretion of saponins, accompanied by significant changes in sterol composition. Ultrasound stimulated the secretion of saponins (up to 11-fold); however, it exerted diverse influences on the triterpenoid content in hairy root tissue (stimulating or decreasing) depending on the duration of the exposure to the elicitor. UV-C radiation caused a slight increase in the content of both sterols and saponins in hairy root tissue, and stimulated saponin secretion up to 8.5-fold. The expected symptoms of the competition between the biosynthetic pathways of sterols and pentacyclic triterpenoids were less evident in reactions to abiotic stressors than those reported previously for biotic elicitors

In the past few years, micromodels have become a useful tool for visualizing flow phenomena in porous media with pore structures, e.g., the multifluid dynamics in soils or rocks with fractures in natural geomaterials. Micromodels fabricated using glass or silicon substrates incur high material cost; in particular, the microfabrication-facility cost for making a glass or silicon-based micromold is usually high. This may be an obstacle for researchers investigating the two-phase-flow behavior of porous media. A rigid thermoplastic material is a preferable polymer material for microfluidic models because of its high resistance to infiltration and deformation. In this study, cyclic olefin copolymer (COC) was selected as the substrate for the micromodel because of its excellent chemical, optical, and mechanical properties. A delicate micromodel with a complex pore geometry that represents a two-dimensional (2D) cross-section profile of a fractured rock in a natural oil or groundwater reservoir was developed for two-phase-flow experiments. Using an optical visualization system, we visualized the flow behavior in the micromodel during the processes of imbibition and drainage. The results show that the flow resistance in the main channel (fracture) with a large radius was higher than that in the surrounding area with small pore channels when the injection or extraction rates were low. When we increased the flow rates, the extraction efficiency of the water and oil in the mainstream channel (fracture) did not increase monotonically because of the complex two-phase-flow dynamics. These findings provide a new mechanism of residual trapping in porous media.

Regenerative capacity of well-preserved blood clot may be enhanced by biologics like enamel matrix derivative (EMD). This retrospective analysis compares outcomes reported by three centers using different heterografts. Center 1 (C1) treated intrabony defects combining cross-linked heavy weight hyaluronic acid (xHyA) with a xenograft, Center 2 (C2) used EMD with an allograft combination to graft residual pocket. Center 3 (C3) combined xHyA with placement of resorbable polymer membrane for defect cover. Clinical parameters, BoP reduction and radiographically observed defect fill at 12-months examination are reported. The 12-months evaluation yielded significant improvement in PPD and CAL at each center (p<0.001, respectively). Analyses of Covariance revealed significant improvement of all parameters, significantly greater CAL gain disclosed C2 vs. C1 (p=0.006). Radiographic defect fill presented with significantly higher scores for C2 and C3 vs. C1 (P=.003 and =.014; C2 vs. C3 P=1.00). Gingival recession increased in C1 and C3 (P=1.00), while C2 reported no GR after 12-months (C2:C1 P=.002; C2:C3 P=.005). BoP tendency and pocket closure rate shared similar rates. Within limitations of the study, data comparison indicated that xHyA showed similar capacity to enhance regenerative response, as known for EMD. Radiographic follow-up underlined xHyA staying alone role in new attachment formation.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone-graft displacement and report the clinical application of long-term resorbable GMEM-B-2 (L-lactic acid/-caprolactone [P(LA/CL)]) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1W) and 5–6 months (5M) post-MSA, bone height changes, bone height reduction rates at 1W and 5M post-MSA, bone-graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p < 0.005). However, no difference was observed between 1W and 5M post-MSA. Bone-graft displacement was observed in eight patients; the reduction rate from 1W to 5M post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–natural mouth distance were associated with bone-graft displacement (p < 0.05). Height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation amount (p < 0.05). The L-lactic acid/ε-caprolactone [P(LA/CL)] membrane compared favourably with other membranes and may be useful as a barrier membrane for the MSA open window.

Astragaloside IV (AIV) – triterpenoid saponin from the Astragalus mongholicus roots with the proved acetylcholinesterase (AChE)-inhibitory capability was used as the substance with the potential to attenuate memory impairment. Scopolamine (SCOP), antagonist of muscarinic cholinergic receptors and lipopolysaccharide (LPS), neuroinflammation inducer were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in the SCOP-treated mice was attenuated by the earlier intraperitoneal (ip) administration of AIV in the dose of 25 mg/kg. The reduction of memory impairment by LPS was not observed, therefore AIV does not reverse memory impairments through the anti-inflammatory mechanisms. All the studied doses of AIV did not affect basic locomotor activity of mice. As a result of the post-mortem analysis of mice body tissues, the largest content of AIV was determined in the kidneys, then in the spleen, liver and the smallest one in brain by mass spectrometry.

Barrier coverage is a fundamental application in wireless sensor networks, which is widely used to protect a region through intruder detection for smart city. In this paper, we study a new branch of barrier coverage, named warning barrier coverage (WBC). Different from the classic barrier coverage, WBC has the inverse protect direction, which protects unexpected visitors by warning them away from the region enclosed by sensor barriers. The WBC holds a promising prospect in many danger keep out applications for smart city. For example, a WBC can enclose the debris area in the sea and alarm any approaching ships in order to avoid their damaging propellers. One special feature of WBC is that the target region is usually dangerous and its boundary is previously unknown. Hence, the scattered mobile nodes need to detect the boundary and form the barrier coverage themselves. It is challenging to form these distributed sensor nodes into a barrier because a node can sense only the local information and there is no global information of the unknown region or other nodes. To this end, we propose a novel solution AutoBar for mobile sensor nodes to automatically form a WBC for smart city. To pursue the high coverage quality, we theoretically derive the optimal distribution pattern of sensor nodes using convex theory. Based on the analysis, we design a fully distributed algorithm that enables nodes to collaboratively move towards the optimal distribution pattern. In addition, AutoBar is able to reorganize the barrier even any node is broken. To validate the feasibility of AutoBar, we develop the prototype of the specialized mobile node, which consists of two kinds of sensors: one for boundary detection and another for visitor detection. Based on the prototype, we conduct extensive real trace driven simulations in various smart city scenarios. Performance results demonstrate that AutoBar outperforms the existing barrier coverage strategies in terms of coverage quality, formation duration, and communication overhead.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

The importance of PAs for CNS functions are well known. Less clear is, however, where PAs in the brain are derived from. Principally, there are three possibilities: (i) intake by nutrition, release into the bloodstream, and subsequent uptake from CNS capillaries, (ii) products of parenchymatous organs as the liver, and again uptake from CNS capillaries, and (iii) uptake of precursors such as arginine from the blood and subsequent local biosynthesis of polyamines within the CNS.The present investigation aimed to unequivocally answer the question, whether PAs, especially the higher ones like SPD and SPM can or cannot be taken up into the brain from the bloodstream. For this purpose a biotin-labelled analogue of SPM was synthesized, characterized, and used to visualize its uptake into brain cells subsequent to application to surviving brain slices, to the intraventricular space, or to the bloodstream.In surviving slices uptake of B-X-SPM is massive into protoplasmic and absent in fibrous type astrocytes. It is also taken up by neurons but to a lesser degree. Under in-vivo conditions astrocyte uptake of biotinylated SPM also is massive from the brain interstitial fluid subsequent to intraventricular application. In contrast, following intracardial injection there is no uptake from the bloodstream, indicating that the brain is completely dependent on the local synthesis of polyamines.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

This paper studied the combined influences of the hot streak and swirl on the cooling performances of the NASA C3X guide vane coated with or without TBCs. The results show that: (1) Even under uniform velocity inlet conditions, the hot streak core can be stretched as it impinges the leading edge which causes higher heat load on the suction side of the forward portion. (2) The swirl significantly affects circumferential and radial migration of the hot streak core in the NGV passage. On the passage inlet plane, positive swirl leads to a hotter tip region on the suction side. In comparison, negative swirl leads to a hotter hub region on the pressure side. (3) Under the influence of swirl, migration of coolant improve the coverage of film cooling close to the midspan, while in the regions close to the hub and tip end-wall, the overall cooling performance decrease simultaneously. (4) In the regions with enough internal cooling, the cooling effectiveness increment is always larger than that in other regions. Besides, the overall cooling effectiveness increment decreases on the region covered by film cooling for the coated vane, especially in the region with negative local heat flux.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We will discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs) and hemichannels (HCs) which are composed of hexamer of connexin 43 (Cx43) protein. In particular, we will discuss how GJ intercellular communication (GJIC) in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are "hijacked" by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent by what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, will need to be re-visited and understood together with new findings on Cx proteins and HC activities.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Target detection of defense technology is being rapidly upgraded with modern surveillance technologies. The latest techniques of surveillance are already being implemented for defense applications. Self-protection and hiding from opposing forces are the key principle for protection of special team in defense. Camouflage textiles aims to create confusing objects for target detection of military personnel. These textiles are applied for military protection such as clothing, weapon, vehicle and location hiding nets/tents, etc. The urgent need of camouflage textiles have been formulated with a technical solution and implementation of right camouflage materials for concealment of defense target signature against dry leaves, green leaves, tree bark-woodland combat background; water-marine combat background; sand-desertland combat background; stone-stoneland combat background; snow-snowland combat background; sky combat background and ice-iceland combat background, concrete-concreteland combat background (DGTWSICB) in ultraviolet-visible-infrared (UV-Vis-IR) spectrums. This hypothesis of optical & surveillance engineering has been coalesced for advancement of UV-Vis-IR-DGTWSICB camouflage textiles technology. The principle of camouflage engineering has been approached by broader spectrum probe in UV-Vis-IR rather than Vis ranges only. Furthermore, single formulation of camouflage textiles has been proposed for multidimensional CBs-DGTWSICB. Electromagnetic spectrum, reflection, electron energy, photonic signal and imaging mechanism in UV-Vis-IR have been presented for optical engineering of concealment, detection, recognition and identification of target signature against DGTWSICB. Spectrum relationship of camouflage materials and DGTWSICB materials have been illustrated and compared in UV-Vis-IR spectrums. Camouflage material design, method design & spectral design; adaptive camouflage; techniques for camouflage textile assessment for digital camera and hyperspectral camera imaging; image processing techniques and a hierarchical model have been demonstrated for augmentation of camouflage textiles in UV-Vis-IR illumination. Therefore, anticipated design of camouflage textiles may enhance high-performance innovation for modern surveillance of military protection related to digital camera, hyperspectral camera and radar. This hypothesis includes advance guideline for camouflage textiles design for CBs-DGTWSICB.

A variety of bioactive substances present in fruits and vegetables processed products have health-promoting properties. Consumption of nutrient-rich plant-based products is essential to address undernutrition and micronutrient deficiencies. Preservation is paramount in manufacturing plant-based non-solid foods such as juices, purees, and sauces. Thermal processing has been widely used to preserve fruit and vegetable-based products by reducing enzymatic and microbial activities, thereby ensuring safety and prolonged shelf life. However, the nutritional value of products is compromised due to the deleterious effects of thermal treatments on essential nutrients and bioactive compounds. To prevent the loss of nutrients associated with thermal treatment, alternative technologies are being researched extensively. In studies conducted on non-solid food, UV-C treatment has been proven to preserve quality and minimize nutrient degradation. This review compiles information on the use of UV-C technology in preserving the nutritional attributes of non-solid foods derived from fruit and vegetables. Legislation, market potential, consumer acceptance, and limitations of UV-C are reviewed.

The drug delivery systems receive more and more attention for the control and treatment of many diseases due to their increased number in recent years. The main aims of this study were to develop and to characterize a polyurethane drug delivery system that it is intended to be used for the transmembrane transport of nucleosides. Three different samples have been synthesized based on aliphatic diisocyanates (hexamethylene diisocyanate, isophorone diisocyanate and lysine diisocyanate) as organic phase, respectively a mixture of polyethylene glycol, polycaprolactone diol and low molecular weight diols as aqueous phase. The samples were characterized by pH, refractivity index and solubility measurements, drug loading efficacy and release investigations, thermal behavior, Zetasizer, cells viability and irritation tests on mice skin. The results indicate the obtaining of different populations of neutral acido-basic particles with size between 132 and 190 nm; the Zeta potential values and SEM images show a medium tendency to form clusters, while UV-Vis evaluations indicate an almost 70% encapsulation efficacy, a prolonged release (45% of encapsulated substance is released in the first 5 days) and around 70% of particles have penetrated an artificial membrane in the first 24h. The synthesized products can be tested in further clinical trials, the currently tests on cells culture and mice skin revealing no side effects.

Current methods for the hardening step of functional coatings over different materials imply the use of high temperatures, high energy consumption or long periods of time, which have repercussions on the speed and cost of the product. We report here a simple and low cost methodology for the functionalization of low cost stainless steel, which is modular, depending of the functionality pursued: a levelling layer for smooth the surface of the material, an “easy to clean” property, or both of them. The research is based on sol-gel coatings cured under UV light without requiring high thermal hardening processes making it applicable to plastics and other sensible materials and possessing high chemical and thermal stability. The film ensures lower processing costs, and higher rates of hardening if the adequate medium-pressure lamps are employed. This formulation is also well defined for scaling up the process, so it is possible to perform a continuous coating in large areas by employing mild processing conditions (low temperature, atmospheric pressure). In addition, the sol gel solution was fully characterized and studied in order to guarantee a long service life before deposition, with a focus on industrial applications in the domestic sector.

The self-organization properties of C70 fullerene molecules in a xylene/tetrahydrofuran binary mixture were studied for the first time by optical absorption, refractometry, and dynamic light scattering. A correlation has been established between the change in the refractive index of the C70/xylene/tetrahydrofuran solution and the degree of self-organization of C70 molecules in the medium at various concentrations and storage periods of the solution. It is shown that the features of the optical absorption spectrum of C70/xylene/tetrahydrofuran at a fixed low concentration of the fullerene are sensitive to its storage time. It was determined that the beginning time of the formation of C70 nanoclusters and their final size depend on the concentration of fullerene and the time of keeping the solution. The observed nature of the C70 fullerene solution in a binary mixture may help to elucidate the mechanism of self-organization in the future.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat and remove toxins; and served as a folk medicine to deal with diabetes, obesity, and hypertension. Trans-p-hydroxycinnamic acid and its esters, which were isolated from the leaves of L. robustum, might be a new resource to prevent diabetes and its complications because of their strong -glucosidase and fatty acid synthase (FAS) inhibitory activities and antioxidant effect. However, the quantitative analytical method for trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum hasn’t been reported so far. In addition, it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. Therefore, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum was developed in the present study. The optimal hydrolyzation conditions were as follows: 1 mL sodium hydroxide aqueous solution (1 M) was added into 1 mL the extract of L. robustum and incubated at 80 °C for 2 h , and then 1 mL hydrochloride (1 M) solution was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL/min, and detecting at 310 nm. The analytical method was simple and rapid, which simplified greatly the analytical process. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy. High linearity was demonstrated with correlation coefficient of 1.000 for trans-p-hydroxycinnamic acid. The LOD and LOQ values were 1.55 and 4.69 μg/mL, respectively. The relative standard deviations (RSD) of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 101.2% ± 0.8%. Finally, the proposed method was applied successfully to the determination and comparison of the contents of trans-p-hydroxycinnamic acid and its esters in various extracts of the leaves of L. robustum. The 60%-70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96-3.99 mg/g), and the 50%-80% ethanol extracts of L. robustum displayed the highest contents of trans-p-hydroxycinnamic acid esters (202.6-210.6 mg/g). The method can be applied also to the quality control of the products of L. robustum.

Using optical characterization, it is evident that the spin state of the spin crossover molecular complex [Fe{H2B(pz)2}2(bipy)] (pz = tris (pyrazol-1-1y)-borohydride, bipy = 2,2’-bipyridine) depends on the ferroelectric polarization of an adjacent thin film of the polymer ferroelectric polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP). The UV-Vis spectroscopy reveals that room temperature switching of [Fe{H2B(pz)2}2(bipy)] molecules in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] as a function of ferroelectric polar polarization. The electric polarity dependence of bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] shows a strong dependence on the thickness of the PVDF-HFP layer. The PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] interface may affect polarization retention in the PVDF-HFP thin film limit.

(1) Background: Investigating the characteristics of photosynthetic physiological changes of leaves in Mangifera indica L. cv. 'GuIfei' under enhanced UV-B radiation, natural light exposed trees were regarded as control, and 96 kJ·m-2·d-1enhanced UV-B radiation was artificially simulated in the field; (2) Methods: The changes of fruit maturity and fruit quality, leaf net photosynthetic rate (Pn), photosynthetic pigments contents, photochemical reaction, activities of photosynthetic enzymes and their genes expressions were determined; (3) Results: Compared with CK, the percentage of mature fruits of the treatment was significantly increased, and fruit quality was better. The net photosynthetic rate (Pn), the contents of photosynthetic pigment, Hill reaction activity and photochemical quenching coefficient (qP) of the treatment leaves showed a significantly higher trend than CK. The activities of Rubisco and RCA, and the expression of Rubisco genes rbcL and rbcS were significantly increased; (4) Conclusions: 96 kJ·m-2·d-1 enhanced UV-B radiation treatment improved Rubisco activity through increasing the expression of Rubisco genes rbcL and rbcS, thereby enhancing the CO2-fixing capacity and dark reaction capacity of leaves. Based on this, it raised the net photosynthetic rate of leaves, which promoted the early maturity of 'Guifei' mango by the fast accumulating photosynthetic products.

Chymotrypsin is an important proteolytic enzyme in human digestion system that cleaves milk proteins, through hydrolysis reaction, which makes it interesting subject to study activity of milk proteases. In this work, we compared detection of chymotrypsin by spectrophotometric, dynamic light scattering (DLS) and quartz crystal microbalance (QCM) methods and determined the limit of chymotrypsin detection (LOD), 0.15 ± 0.01 nM for spectrophotometric, 0.67 ± 0.05 nM for DLS and 1.40 ± 0.30 nM for QCM methods, respectively. We discuss peculiarities and give perspective for implementation of detection methods and note that while the optical detection methods are simple to implement, the QCM method is more robust for sample preparation. We give an overview on methods and instruments for detection of chymotrypsin and other milk proteases.

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

One-dimensional shape memory polymer fibers (SMPFs) have obvious advantages in mechanical properties, dispersion properties and weavability. In this work, a method for fabricating semi-crystallization ethylene-vinyl acetate copolymer (EVA) fiber with two-way shape memory effect by melt spinning and ultraviolet (UV) curing was developed. Here, the effect of crosslink density on its performance was systematically analyzed by gel fraction measurement, tensile tests, DSC and TMA analysis. The results showed that the crosslink density and shape memory properties of EVA fiber could be facilely adjusted by controlling UV curing time. The resulting EVA fiber with cylindrical structure had a diameter of 247.13 ± 10.07 μm, and its mechanical strength and elongation at break were 64.46 MPa and 114.33%, respectively. The critical impact of the crosslink density and applied constant stress on the two-way shape memory effect were analyzed. Moreover, the single EVA fiber could lift more than 143 times its own weight and achieve 9% reversible actuation strain. The reversible actuation capability was significantly enhanced by a simple winding design of the single EVA fiber, which provided great potential applications in smart textiles, flexible actuators and artificial muscles.

Today, more than 70 million tons of lignin are produced by the pulp and paper industry every year. However, the utilization of lignin as a source for chemical synthesis is still limited due to the complex and heterogeneous lignin structure. The purpose of this study was a selective photodegradation of industrially available kraft lignin in order to obtain appropriate fragments and building block chemicals for further utilization, e.g. polymerization. Thus, kraft lignin obtained from soft wood black liquor by acidification was dissolved in sodium hydroxide and irradiated at a wavelength of 254 nm with and without the presence of titanium dioxide in various concentrations. Analyses of the irradiated products via SEC showed decreasing molar masses and decreasing polydispersity indices over time. At the end of the irradiation period the lignin was depolymerised to form fragments as small as the lignin monomers. TOC analyses showed minimal mineralisation due to the depolymerisation process.

UV SO₂ cameras have become a common tool to measure and monitor SO₂-emission-rates, mostly from volcanoes but also from anthropogenic sources (e.g. power plants or ships). In the past years, the analysis of UV SO₂ camera data has seen many improvements. As a result, for many of the required analysis steps, several alternatives exist today. This inspired the development of Pyplis, an open-source software toolbox written in Python 2.7, which aims to unify the most prevalent methods from literature within a single, cross-platform analysis framework. Pyplis comprises a vast collection of algorithms relevant for the analysis of UV SO₂ camera data. These include several routines to retrieve plume background radiances as well as routines for cell and DOAS based camera calibration. The latter includes two independent methods to identify the DOAS field-of-view within the camera images. Plume velocities can be retrieved using an optical flow algorithm as well as signal cross-correlation. Furthermore, Pyplis includes a routine to perform a first order correction of the signal dilution effect. All required geometrical calculations are performed within a 3D model environment allowing for distance retrievals to plume and local terrain features on a pixel basis. SO₂-emission-rates can be retrieved simultaneously for an arbitrary number of plume intersections. Pyplis has been extensively and successfully tested using data from several field campaigns. Here, the main features are introduced using a dataset obtained at Mt. Etna, Italy on 16 September 2015.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

The Baltic Sea coast is one of the geographical areas of Europe most threatened by the current climate change. This issue concerns erosional processes, groundwater flows affecting sea-shore settings. Long term hydrological investigations within the western sector of the Łeba Barrier, northern Poland, based on a network of monitoring stations, coupled with the meteorology records of the past 12 years, revealed significant fluctuations in ground water fluxes from the Baltic Sea on the adjoining mainland. Groundwater resources are negatively affected by sea-level drops in the coastal areas along the southern Baltic coast. The low sea levels strengthen the effects of low precipitation and high temperatures, causing altogether the occurrence of hydrogeological drought in the coastal sandbar areas. Drought periods are characterized by lowering of water-tables in the Slowinski National Park. The obtained results have direct relevance to a long-term assessment of water resources, environmental protection of the climatically most susceptible ecosystems, as well as the tourism management of this popular visitors’ destination.

Aging is a major risk factor for Alzheimer's disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood-brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.

Insulin receptors are internalized by endothelial cells; however, the impact of hyperinsulinemia on this process is not known. Thus, the aim of this study is to determine the role of hyperinsulinemia on insulin receptor function and internalization, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). To this end, hippocampal microvessels were isolated from male C57Bl/6J mice on either a control or high-fat diet and assessed for insulin receptor signaling. Cell surface insulin receptors in brain microvascular endothelial cells were labelled with biotin to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without Claramine treatment, a potent PTP1B antagonist. Our results indicated that insulin receptor levels increased in tandem with insulin receptor dysfunction in the high-fat diet mouse hippocampal microvessels. Hyperinsulinemic cell-receptors demonstrate a shift in splice variation towards decreased IR-A/IR-B ratios and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling, however, Claramine restored signaling and receptor internalization in hyperinsulinemic cells. In conclusion, hyperinsulinemia negatively impacts brain microvascular endothelial cell insulin receptor function and internalization, likely through both alternative splicing and increased negative feedback from PTP1B.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

The synergistic efficacy of combined treatment mild heat (MH) and dielectric barrier discharge (DBD) plasma in Bacillus cereus-contaminated red pepper powder was tested. A cocktail of three strains of B. cereus (NCCP 10623, NCCP 14579, ATCC 11778) was inoculated onto red pepper powder and then treated with MH (60 ℃ for 5-20 min) and DBD plasma (5-20 min). Treatment with MH and DBD plasma alone for 5~20 min resulted in reductions of 0.23~1.43 and 0.12~0.96 log CFU/g, respectively. Combined treatment with MH and DBD plasma was the most effective at reducing B. cereus counts on red pepper powder and resulted in log-reductions of ≥ 6.0 log CFU/g. The largest synergistic values (4.24-4.42 log) against B. cereus in red pepper powder were obtained by the combination of 20 min MH and 5~15 min DBD plasma. Hunter color ‘‘L’’, ‘‘a’’, and ‘‘b’’ values of the combination-treated samples were not significantly different from those of non-treated samples. Also, no significant (p > 0.05) differences in pH values between samples were observed. Therefore, these results suggest that the combination of MH treatment and DBD plasma can be potentially utilized in the food industry to effectively inactivate B. cereus without incurring quality deterioration of red pepper powder.

The controls of depositional environments on reservoir quality have been evaluated in terms of porosity and permeability of the Gabo Field, Niger Delta, Nigeria. Data used in this research include Well logs, Core data and photos, and grain size analysis for Wells 51 and 52 in the study area. Standard methods as applicable in petrophysical and sedimentological analysis has been adopted. Thirteen reservoir units have been identified in wells 51 and 52 which had 5 reservoirs cored each. The lithofacies units of the identified reservoirs across the study area, comprise pebbly sands, coarse -, medium -, fine- and very fine-grained sands, sandy mud, silty sands and heteroliths. The heteroliths – very fine-grained silty muds are highly bioturbated. Ophiomorpha and skolithos are the major trace fossils with sedimentary structures (ripple lamination, wavy lenticular and planar beds, cross bedded sands, coarsening and fining upward). The facies associations interpreted for the study area are Channel and Coastal barrier systems and the environment of deposition as distributary channel, upper and lower shoreface. The sedimentary processes that deposited facies ranged from high energy regimes, reworking by waves to low energy with periodic influx of silts and muds. The average porosity and permeability for reservoirs in Well 51 is 16.7% and 1317 Md, reservoirs in Well 52 is 28.2% and 2330Md whereas porosity range for the study area is 2% - 32% and permeability is 1.2 – 10600 Md. The reservoir quality reservoir of the sand units in Well 51 (7, 9 and 13) and Well 52 (5, 7, 9, 11 and 13) is excellent - good, this is because of the dynamics environments of deposition (upper shoreface and distributary channel) as well as the mechanisms that play out during deposition such as bioturbation, sorting, sedimentary structures formed. Whereas the poor quality across the reservoirs especially the lower shoreface and prodelta facies is as result of lack bioturbation, connectivity, multiplicity of burrows that may have been plugged by clay and intercalation of shale and sand (heteroliths). This research has shown that environments of deposition have direct influence the reservoir quality in terms of porosity and permeability.

The scene for regional biogeography and human settlements in Central Amazonia is set by the river network, which presumably consolidated in the Pliocene. However, we present geomorphological and sediment chronological data showing that the river network has been anything but stable. Even during the last 50 kyr, the tributary relationships have repeatedly changed for four major rivers, together corresponding to one third of the discharge of the Amazon. The latest major river capture event converted the Japurá from a tributary of the Rio Negro to a tributary of the Amazon only 1000 years ago. Such broad-scale lability implies that rivers cannot have been as efficient biogeographical dispersal barriers as has generally been assumed, but that their effects on human societies can have been even more profound. Climate change and deforestation scenarios predict increasing water levels during peak floods, which will likely increase the risk of future river avulsions. This may have disastrous consequences for the local human societies, especially in those areas where the current floodplains are at only marginally lower elevations than the nearest water divide. We suggest that the prevailing paradigm of rivers as principal structuring elements of Amazonian biogeography needs to be re-evaluated, and that land use planning and civil risk assessment should take the possibility of river avulsions into account.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

The development of photocurable compositions is in high demand for the manufacture of func-tional materials for electronics, optics, medicine, energy, etc. The properties of the final pho-to-cured material are primarily determined by the initial mixture, which needs to be tuned for each application. In this study we propose to use simple systems based on di(meth)acrylate, polyimide and photoinitiator for the preparation of new photo-curable compositions. It was es-tablished that a fluorinated cardo copolymide (FCPI) based on 2,2-bis-(3,4-dicarboxydiphenyl)hexafluoropropane dianhydride, 9,9-bis-(4-aminophenyl)fluorene and 2,2-bis-(4-aminophenyl)hexafluoropropane (1.00:0.75:0.25 mol) has excellent solubility in di(met)acrylates. This made it possible to prepare solutions of FCPI in such monomers, to study the effect of FCPI on the kinetics of their photopolymerization in situ and the properties of the resulting polymers. According to the obtained data, the solutions of FCPI (23 wt.%) in 1,4-butanediol diacrylate (BDDA) and FCPI (15 wt.%) in tetraethylene glycol diacrylate were tested for the formation of the primary protective coatings of the silica optical fibers. It was found that the new coating of poly(BDDA–FCPI23%) can withstand prolonged annealing at 200°C (72 h), which is comparable or superior to the known most thermally stable photo-curable coatings. The proposed approach can be applied to obtain other functional materials.

In our study we investigated the accelerated aging process of PLA under 253.7 nm UV-C irradiation with the use of GPC, NMR, FTIR, DSC methods and formal kinetic analysis. The results of GPC and DSC indicated a significant degree of destructive changes in PLA macromol-ecules, while spectroscopic methods NMR and FTIR showed maintenance of PLA main structural elements even after a long time of UV exposure. In addition to that, the GPC method displayed the formation of a high-molecular fraction starting from 24 hours of irradiation, and an increase in its content after 144 hours of experiment. It has been showed for the first time that a distinctive feature of prolonged UV exposure is the occurrence of intra- and intermolecular radical recom-bination reactions, leading to the formation of a high-molecular fraction of PLA decomposition products. This causes the observed slowdown of the photolysis process. It was concluded that photolysis of PLA is a complex of physicochemical processes, the mechanism of which depends on morphological changes in a solid phase of the polymer under UV radiation.

An ultraviolet (UV) nanosecond pulsed laser with a wavelength of 355 nm was applied to anneal amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFT) at various laser beam powers ranging from 0 to 280 mW. Laser irradiation was selectively carried out on the a-IGZO channel area using the beam scanning method after the a-IGZO TFT was formed through indium-tin oxide (ITO) electrode patterning and a subsequent lift-off process. After laser annealing, negative shifts in the threshold voltages and enhanced on-currents were observed at laser-beam powers ranging from 54 to 120 mW. No meaningful parameters were investigated for laser beams higher than 200 mW. By extracting the energy band gap and work function of a-IGZO from the transmittance and ultraviolet photoelectron spectroscopy (UPS) results, the ITO electrode/a-IGZO channel energy band structures were established under different laser annealing conditions, and the electron injection mechanism from the ITO to the a-IGZO channel was analyzed and optimized at a laser beam power of 120 mW. The results show that the electrical characteristics of the a-IGZO TFTs can be improved without any heat damage to the substrate because of the selective annealing process.

The use of covers to protect blueberry orchards from adverse weather events has increased due to the variability in climate patterns, but the effects of rain cover and netting materials on yield and fruit quality have not been studied yet. This research evaluated the simultaneous effect of LDPE plastic cover, woven cover and netting materials on environmental components (UV light, PAR, NIR and growing degree days, GDD), plant performance (light interception, leaf area index, LAI, yield and flower development), and fruit quality traits (firmness, total soluble solids and acidity) in two blueberry cultivars. On average, UV transmission under netting was 11% and 43% higher compared to that under woven and LDPE plastic covers, while NIR was 8 -13% higher with both types of rain covers, with an increase in fruit air temperature and GDD. Yield was 27% higher under woven cover with respect to netting, but fruit firmness values under netting were 12% higher than those of LDPE plastic cover. Light interception, LAI and flower development explained 64% (p=0.0052) of the yield variation due to the cover material effect. The obtained results suggest that the type of cover differentially affects yield and fruit quality in blueberries due to the specific light and temperature conditions generated under these materials.

The purpose of this investigation was to prepare a water-soluble complex by encapsulation of propolis extract with the carrier 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and to examine the influence of in vitro simulated gastrointestinal digestion (GID) on the content of the main polyphenolic groups when administered as aqueous suspension. The research was conducted on two continental samples of propolis from Croatia and a mixture of selected polyphenol standards. By applying UAE followed by a lyophilization procedure, it was possible to obtain a powder with a high content of polyphenols. The content of total phenols (TPs), total flavonols/flavones (TFFs) and total flavanones/dihydroflavonols (TFDs) in the fractions of oral and gastric phase and small intestinal phase performed with two models: centrifugation and dialysis through a semi-permeable membrane, was determined by three UV/Vis spectrophotometric methods: Folin-Ciocalteu, aluminium complexation and 2,4-dinitrophenylhydrazine method. The obtained results for both propolis complexes showed stability in the polyphenol content and high bioaccessibility during all three phases of digestion. The bioaccessibility of TPs, TFFs and TFDs under in vitro conditions after dialysis through a semipermeable membrane was lower compared to the intestinal phase model with centrifugation.

The natural compounds of boron have many applications, including as dietary supplement. Communication is based on the discovery that diester chlorogenoborate complex can be detected and quantified from green coffee bean. The study reports that such diester molecule can also be synthesized in stable form by direct reaction of boric acid and chlorogenic acid, in a mixture of acetonitrile–water (1:1, v/v), left to evaporate over a period of 48 hours, at room temperature, resulting a spirocyclic form (diester complex). The diester complex, with its molecular structure and digestibility attributes has potential application as prebiotic in gut health, oral health and as micronutrient essential for microbiota to human and animals.

It is essential to mitigate gaseous emissions that result from poultry and livestock production to increase industry sustainability. Odorous volatile organic compounds (VOCs), ammonia (NH3), hydrogen sulfide (H2S), and greenhouse gases (GHGs) have detrimental effects on the quality of life in rural communities, the environment, and climate. This study's objective was to evaluate the photocatalytic UV treatment of gaseous emissions of odor, odorous VOCs, NH3, and other gases (GHGs, O3 – sometimes considered as by-products of UV treatment) from stored swine manure on a pilot-scale. The manure emissions were treated in fast-moving air using a mobile lab equipped with UV-A and UV-C lights and TiO2-based photocatalyst. Treated gas airflow (0.25 to 0.76 m3/s) simulates output from a small ventilation fan in a barn. Through controlling the light intensity and airflow, UV dose was tested for techno-economic analyses. The treatment effectiveness depended on the UV dose and wavelength. Under UV-A (367 nm) photocatalysis, the percent reduction of targeted gases was up to i) 63% of odor, ii) 51%, 51%, 53%, 67%, and 32% of acetic acid, propanoic acid, butanoic acid, p-cresol, and indole, respectively, iii) 14% of nitrous oxide (N2O), iv) 100% of O3, and 26% generation of CO2. Under UV-C (185+254 nm) photocatalysis, the percent reductions of target gases were up to i) 54% and 47% for p-cresol and indole, respectively, ii) 25% of N2O, iii) 71% of CH4, and 46% & 139% generation of CO2 & O3, respectively. The results proved that the UV technology was sufficiently effective in treating odorous gases, and the mobile lab was ready for farm-scale trials. The UV technology can be considered for the scaled-up treatment of emissions and air quality improvement inside livestock barns.

Given the high prevalence of cutaneous genus beta human papillomavirus (β-HPV) infections, it is important to understand how they are manipulating their host cells. This is particularly true for cellular responses to UV damage, since our skin is continually exposed to UV. The E6 protein from β-HPV (β-HPV E6) decreases the abundance of two essential UV-repair kinases (ATM and ATR). Since β-HPV E6 reduces their availability, the impact on downstream signaling events has been uncertain. We demonstrate that β-HPV E6 decreases ATM and ATR activation. This inhibition extended to XPA, an ATR target necessary for UV repair, lowering both its phosphorylation and accumulation. β-HPV E6 hinders POLη phosphorylation and foci formation, critical steps in translesion synthesis. ATM’s phosphorylation of BRCA1 is also attenuated by β-HPV E6. However, β-HPV E6’s hindrance of ATM/ATR signaling during UV-associated cell cycle arrest was incomplete. While there was less phosphorylation of immediate downstream targets (CHK1), events further down the cascade were not decreased. These observations are consistent with β-HPV infections making UV radiation more deleterious and support the proposed role of β-HPV in early stages of non-melanoma skin cancer development.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Recent in-vitro studies have investigated the effects of CytoSorb hemoadsorption on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but to this day there is a lack of clinical studies showing whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We analyzed the data on administered fluid volumes and catecholamines to determine the potential benefit of CytoSorb hemoadsorption therapy on endothelial function in a clinical scenario. We performed a retrospective analysis of 124 septic shock patients who had undergone adjunctive treatment with CytoSorb hemadsorption therapy. We collected volume requirements, and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. We also calculated catecholamine requirements. With regard to the entire study cohort our findings revealed a significant reduction in fluid balance at 72 hours (T72) compared to both baseline (T0) and the 24-hour mark (T24). Fluid balances from T72 – T0 were significantly lower in hospital survivors compared to non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings showed that use of hemoadsorption therapy results in a reduced positive fluid balance paralleled by reductions in vasopressor needs suggesting a positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights that may greatly improve our understanding of the multiple effects of hemoadsorption treatment in septic shock patients.

The growing adoption of distributed energy production technologies, and the potential of energy underutilization when it is produced by non-connected groups, has raised interest in ‘sharing economy’ concepts in the electricity sector. We suggest that mechanisms, such as peer-to-peer (P2P) energy trading, will allow users to exchange their surplus energy for mutual benefits, stimulate the adoption of renewable energy, encourage communities to ‘democratically’ control their own energy supplies for local development, and improved energy efficiency, and create many other benefits This approach is receiving increasing attention across the world, particularly in Germany, the Netherlands and Australia. Nevertheless, the actual development and implementation of these platforms is slow and mostly limited to trial activities. This study investigates the challenges and barriers facing P2P energy trading developments based on previous academic and industry studies. We provide a comprehensive multidimensional barrier analysis through a PESTLE approach to assess the barriers from a variety of perspectives, including the political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) aspects. This approach clarifies the many intersecting problem fields of P2P trading in renewable energy, and the paper identifies a list of such barriers, and discusses the prospects for addressing these issues. We also elaborate on the importance of incentive-based P2P market design.

Reproductive isolating barriers are a crucial element in the speciation process. There are various types of barriers, and within those that act early in the speciation process, the behavioral one can play an important role in isolating populations or closely related species. It has been shown that the high diversity of some taxa correlates with the variation of sexual signals, which facilitate isolation. Here it is explored whether chemical signals may contribute to the high diversity of Liolaemus lizards, which has more than 290 species. Population chemical discrimination was investigated in two co-distributed species, L. tenuis and L. lemniscatus. The studied populations were closely located and likely belonged to the same genetic lineages. Lizards of both species discriminated between scents of their own and different populations, and in most cases, scents from their population were preferred. Results suggest a fast evolution of scents, and their recognition, and there for the ethological barriers associated with the chemical modality may evolve fast. However, because the studied species differed in the strength of the exhibited population chemical discrimination, ethological barriers evolve at different rates across species. It can be concluded that ethological barriers involving the chemical modality may disrupt species' cohesion, contributing to Liolaemus diversification, in synergy or not with geographical barriers.

Purpose: Inducible Slc4a11 KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH3-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study is to investigate the link between oxidative stress and failure of pump and barrier functions and test different approaches to revert the process. Methods: Mice homozygous for Slc4a11 Flox and Estrogen receptor –Cre Recombinase fusion protein alleles at 8 weeks of age were fed Tamoxifen (Tm) enriched chow (0.4 g/Kg) for 2 weeks, and controls were fed normal chow. During the initial 14 days, Slc4a11 expression, corneal thickness (CT), stromal [lactate], Na+-K+ ATPase activity, mitochondrial superoxide levels, expression of lactate transporters, and activity of key kinases were assessed. In addition, barrier function was assessed by fluorescein permeability, ZO-1 tight junction integrity, and cortical cytoskeleton F-actin morphology. Results: Tm induced a rapid decay in Slc4a11 expression that was 84% complete at 7 days and 96% at 14 days of treatment. Superoxide levels increased significantly by day 7; CT and fluorescein permeability by day 14. Tight junction ZO-1 distribution and cortical cytoskeleton were disrupted at day 14 concomitant with decreased expression of Cldn1 yet an increase in tyrosine phosphorylation. Stromal lactate increased by 60%, Na+-K+ATPase activity decreased by 40%, and expression of lactate transporters MCT2 and MCT4 significantly decreased, but MCT1 was unchanged at 14 days. Src kinase was activated but not Rock, PKCα, JNK, or P38Mapk. Mitochondrial antioxidant Visomitin (SkQ1, mitochondrial targeted antioxidant) or Src kinase inhibitor eCF506 significantly slowed the increase in CT, with concomitant decreased stromal lactate retention, improved barrier function, reduced Src activation and Cldn1 phosphorylation, and rescued MCT2 and MCT4 expression. Conclusions: Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that results in perturbation of pump components and barrier function of the CE.

Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). In murine models, chronic SF can impair endothelial function and induce cognitive declines. These deficits are likely mediated, at least in part, by alterations in Blood-Brain Barrier (BBB) integrity. Male C57Bl/6J mice were randomly assigned to SF or sleep control (SC) conditions for 4 or 9 weeks, and in a subset 2 or 6 weeks of normal sleep recovery. Presence of inflammation and microglia activation were evaluated. Explicit memory function was assessed with the novel object recognition (NOR) test, while BBB permeability was determined by systemic dextran-4kDA-FITC injection and Claudin 5 expression. SF exposures resulted in decreased NOR performance and in increased inflammatory markers and microglial activation as well as enhanced BBB permeability. Explicit memory and BBB permeability were significantly associated. BBB permeability remained elevated after 2 weeks of sleep recovery (p<0.01) and returned to baseline values only after 6 weeks. Chronic SF exposures mimicking the fragmentation of sleep that characterizes patient with OSA elicits evidence of inflammation in brain regions and explicit memory impairments in mice. Similarly, SF is also associated with increased BBB permeability, the magnitude of which is closely associated with cognitive functional losses. Despite normalization of sleep patterns, BBB functional recovery is a protracted process that merits further investigation.

In kidney, epithelial barrier has diverse functions in body fluid and electrolyte homeostasis, and urine production. Maintaining epithelial integrity fundamentally builds up physiological functionality of the renal epithelial barrier (REB). Specially, the REB) states regularly in osmotic dynamics. The osmotic dynamics gives rise of osmotic pressure that is a physical force. Overloading of osmotic pressure can crack epithelial integrity and damage REB. How REB endures the osmotic pressure force yet remains enigmatic. LMO7 (LIM domain only 7) is a protein associated with cell-cell junctional complex and cortical F-actin. LMO7 upregulation was observed in cells cultured in hypertonic condition. In kidney, LMO7 predominantly distributes in epithelial cells in renal tubules. Hypertonic stimulation leads to assembly of LMO7 and F-actin in cortical stress fibers in renal epithelial cells. Hypertonic-isotonic alternation as pressure force pushing plasma membrane inward/outward was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. Along with junctional integrity, LMO7 depleted cells resulted in loss of junctional integrity in the epithelial sheet cultured hypertonic medium or hypertonic-isotonic alternation. On the other hand, FAK inhibited by PF-573228 leads to failure in robust cortical F-actin assembly and association of LMO7 with cortical F-actin in epithelial cells responding upon hypertonic stress. Epithelial integrity in context of osmotic stress, LMO7 and FAK signaling both involves in assembling robust cortical F-actin and maintaining junctional integrity. The LMO7 elaborately manages FAK activation in renal epithelial cells, which was evidently demonstrated in NRK-52E cells who have excessive FAK activation and lost epithelial integrity when cells with LMO7 depletion exposed to hypertonic environment. Our data suggests that LOM7 manages FAK activation and is responsible for maintaining REB under osmotic disturbance.

The electrical performance of the back-channel etched Indium–Gallium–Zinc–Oxide (IGZO) thin-film transistors (TFTs) with copper (Cu) source and drain (S/D) which are patterned by a selective etchant was investigated. The Cu S/D were fabricated on molybdenum (Mo) layer to prevent the Cu diffusion to the active layer (IGZO). We deposited the Cu layer using thermal evaporation and performed the selective wet etching of Cu using non-acidic special etchant without damaging the IGZO active layer. We fabricated the IGZO TFTs and compare the performance in terms of linear and saturation region mobility, threshold voltage and ON current (ION). The IGZO TFTs with Mo/Cu S/D exhibits good electrical properties as the linear region mobility is 12.3 cm2/V-s, saturation region mobility is 11 cm2/V-s, threshold voltage is 1.2 V and ION is 3.16 x 10-6 A. We patterned all the layers by photolithography process. Finally, we introduced SiO2-ESL layer to protect the device from the external influence. The results show that the prevention of Cu and introduced ESL layer enhances the electrical properties of IGZO TFTs.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

Focal cerebral ischemia can lead to blood-brain barrier (BBB) breakdown, which is implicated in neuroinflammation and elevation of matrix metalloproteinases (MMPs). The role of the anti-inflammatory protein, monocyte chemotactic protein–induced protein 1 (MCPIP1) plays in the injury of BBB in stroke has not yet been reported. This study was conducted to identify and characterize the role MCPIP1 plays in BBB breakdown. Transient middle cerebral artery occlusion (MCAO) is induced in both wild-type and Mcpip1^-/- mice for 2 hours of occlusion periods followed by reperfusion for 24 or 48 hours. BBB permeability was measured by FITC-dextran extravasation, MMP-9/3 expression was analyzed by western blot, and claudin-5 and zonula occludens-1 (ZO-1) were analyzed by immunohistochemistry and western blot. After MCAO in wild type mouse is induced, there is significantly increase in MCPIP1 mRNA and protein levels. Absence of MCPIP1 leaded to significant increase in FITC-dextran leakage in peri-infarct brain, significant upregulation of MMP-9, MMP-3 and reduced levels of tight junction components, claudin-5 and ZO-1 in the brain after MCAO. Our data demonstrate that absence of MCPIP1 exacerbates ischemia-induced blood-brain barrier disruption by enhancing the expression of matrix metalloproteinases and degradation of tight junction proteins. Overall data indicate that MCPIP1 is important protective role against BBB disruption in cerebral ischemia.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

Geological disposal facilities for radioactive waste pose significant challenges for robust monitoring of environmental conditions within the engineered barriers that surround the waste canister. Temperatures are elevated, due to the presence of heat generating waste, relative humidity varies from 20% to 100%, and swelling pressures within the bentonite barrier can typically be 2-10 MPa. Here, we test the robustness of a bespoke design MEMS sensor-based monitoring system, which we encapsulate in polyurethane resin. We place the sensor within an oedometer cell and show that despite a rise in swelling pressure to 2 MPa, our relative humidity (RH) measurements are unaffected. We then test the sensing system against a traditional RH sensor, using saturated bentonite with a range of RH values between 50% and 100%. Measurements differ, on average, by 2.87% RH, and are particularly far apart for values of RH greater than 98%. However, bespoke calibration of the MEMS sensing system using saturated solutions of known RH, reduces the measurement difference to an average of 1.97% RH, greatly increasing the accuracy for RH values close to 100%.

Water pollution is the main problem in the current scenario which is being faced by mankind due to the industrial and commercial effects. Industrial effluents contain heavy metals and inorganic ions like nitrates and phosphate ions. These ions are being included in waterways through industrial runoff. When the concentration of these hazardous pollutants increases in aquatic flora and fauna causes severe health problems. So remediation of these toxicants from water reserves is of chief importance. Conventional processes along with modern processes are being used for the treatment of industrial wastes. Photo-degradation is a modern method used for the degradation of inorganic ions due to its environmentally friendly nature and cost-effectiveness. In a recent study Aluminum oxide (Al2O3) nanoparticles were synthesized via a green approach at different pH by using Cymbopogan citratus (lemongrass) plant extract and these nanoparticles were used for the removal of inorganic ions from wastewater. The nanoparticles of different pH showed different % degradation of the inorganic ions in acidic medium removal of inorganic waste was less, in basic media % degradation was more as compared to acidic media but maximum % degradation was observed in neutral media like that average % degradation 91% and 81% was observed for nitrate and phosphate ions. The maximum absorbance occurred at 212nm and Al2O3 nanoparticles showed absorbance from 210nm-217nm. The R2 values of pseudo1st, 2nd, and BMG models were 0.956, 0.837, 0.7007 0.95, 0.896, and 0.756 for the nitrate and phosphate ions. Characterizations of synthesized particles were investigated by using UV-visible spectroscopy and other analytical methods like X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The statistical analyses were done using Simple Linear regression (SLR).

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode for transmission. In addition to tools like vaccination and testing, counter-measures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model. Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to un-treated air. Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a muti-day exposure period during peak viral shedding from hamsters. Conclusion: These findings demonstrate the efficacy of the UV-C light to mitigate airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool to reduce infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

The uneven immunogenicity of the attenuated tetravalent dengue vaccine has created the diffi-culty to achieve a balanced protection against all four serotypes of dengue virus (DENV). To overcome this problem, non-replicative-based vaccines have come into focus as their immuno-genicity is adjustable. This approach is excellent for multivalent vaccines but commonly faces the issue of low immunogenicity. In this present study, we developed a non-replicating dengue vaccine composing of UV-inactivated dengue-2 virus (UV-DENV2) and DENV-2 NS1-279 protein encapsidated within nanoparticles. This vaccine candidate was administered in the presence of BCG cell wall cytoskeleton (BCG-CWS) as an adjuvant. We revealed, here, that encapsidated immunogens with BCG-CWS exerted potent activities on both B and T cells and elicited Th-1/Th-2 responses in mice. This was evidenced by strong neutralizing antibody activity with an unde-tectable antibody enhancing activity in a group of mice receiving encapsidated immunogens with BCG-CWS. Importantly, BCG-CWS significantly augmented antibody-mediated comple-ment-fixing activity, strongly stimulated the antigen-specific polyfunctional T cell responses as well as activated mixed Th-1/Th-2 responses specific to DENV2- and NS1-279 antigens. In conclu-sion, BCG-CWS potently adjuvanted the inactivated DENV-2 and subunit DENV immunogens. The mechanism of adjuvanticity remains unclear. This study revealed the potential use of BCG-CWS in vaccine development.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

A new strategy to nanoengineer gold/fluorocarbon multilayer (ML) nanostructures is reported. We have investigated the morphological changes occuring at the metal-polymer interface in multilayer structures with varying volume fraction of gold (Au) and the kinetic growth aspect of the microscale properties of nano-sized Au in plasma polymer fluorocarbon (PPFC). Investigations were carried out at various temperatures and annealing time by means of grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS). We have fabricated a series of multilayers with variying volume fraction (0.12, 0.27, 0.38) of Au and bilayer periodicity in ML structure. They show an interesting granular structure consisting of nearly spherical shaped nanoparticles within the polymer layer. The nanoparticle (NP) morphology changes due to the collective effects of NPs diffusion within ensembles in the in-plane vicinity and inter-layer with increasing temperature. The in-plane NPs size distinctly increases (from 1.9 to 4 nm) with increasing temperature. The NPs become more spherical thus reducing the surface energy. Linear growth of NPs with temperature and time shows diffusion-controled growth of NPs in the ML structure. The structural stability of the multilayer is controlled by the volume ratio of the metal in polymer. At room temperature UV-Vis shows a blueshift of the plasmon peak from 560 nm in ML Au/PTFE_1 to 437 nm in Au/PTFE_3. We have identified the fabrication and post-deposition annealing conditions to limit the Local Surface Plasmon resonance (LSPR) shift (from 〖∆λ〗_LSPR=180 nm (Au/PTFE_1) to 〖∆λ〗_LSPR=67 nm (Au/PTFE_3 ML)) and their optical response over a wide visible wavelength range. A variation in the dielectric constant of the polymer in precence of varying Au inclusion is found to be the main factor affecting the LSPR frequency. Our finding may provide insights in Nano engineering ML structure can be useful to systematically control the growth of NPs in polymer matrix.

Wasted Green tuff powder produced by cutting Towada stone is recycled as environmental cleaning material. The optimum temperature for green tuff powder calcination to reduce the hydroxyl radical produced in hydrogen peroxide decomposition with ultraviolet light (UV) and no light. The green tuff calcined at 800 °C shows the large decomposition rate of hydrogen peroxide with no UV light when measured by using ESR. With UV light, the optimum temperature for calcinating the green tuff powder in order to reduce hydroxyl radical is also 800 °C. Next, the powder calcined at 800 °C is used to produce the tile by compression and heating, and then the formaldehyde adsorption rate was measured. The green tuff powder calcined at 800 °C showed a high adsorption rate, similar to that of the activated carbon. The tiles formed at 40 MPa and heated st 1100 °C were the strongest and also adsorbed formaldehyde. The adsorbed formaldehyde on the green tuff tile and powder might have a possibility to decompose by photocatalytic.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from the Terminalia arjuna (Combreatceae) bark, i.e. arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid, and arjunetin, is presented. The studies are based on the in silico pharmacokinetic and biomimetic studies, the acetylcholinesterase (AChE) inhibitory activity tests, and the molecular docking research. Based on the calculated pharmacokinetic parameters, arjunetin and arjunglucoside I are indicated as able to cross the blood-brain barrier. The compounds of interest exhibit marked acetylcholinesterase inhibitory potential, which was tested in the TLC bioautography test. The longest time to reach brain equilibrium is observed for both the arjunic and arjunolic acids and the shortest one for arjunetin. All compounds exhibit high and relatively similar magnitude of binding energies, varying from ca. -15 to -13 kcal/mol. The superposition of the most favorable positions of all ligands interacting with AChE is analyzed. The correlation between the experimentally determined IC50 values and the steric parameters of the molecules is investigated. The inhibition of the enzyme by the analyzed compounds shows their potential to be used as cognition enhancing agents. For the most potent compound (arjunglucoside I; ARG), the kinetics of AChE inhibition is tested. The Michaelis–Menten constant (Km) for the hydrolysis of the acetylthiocholine iodide substrate was calculated to be 0.011 mM.

With the increment of the aging population in recent years, neurodegenerative diseases exert a major global disease burden, essentially as a result of the lack of treatments that can stop the disease progression. Alzheimer’s Disease (AD) is an example of a neurodegenerative disease, that affects millions of people globally, with no effective treatment. Natural compounds have emerged as a viable therapy to fill a huge gap in AD management, and in recent years, mostly fuelled by the Covid-19 pandemic, RNA-based therapeutics have become a hot topic in the treatment of several diseases. Treatments of neurodegenerative diseases face significant limitations due to the complex and interconnected pathways that lead to their hallmarks and, also due to the necessity to cross the blood–brain barrier. Nanotechnology has contributed to surpass this bottleneck in the treatment of AD, by promoting safe and enhanced drug delivery to the brain. In particular, exosome-like nanoparticles, a hybrid delivery system combining exosomes and liposomes' advantageous features, are demonstrating great potential in the treatment of central nervous system diseases.

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

The idea of using the lytic power of viruses against the malignant cells has been entertained for many decades. However, oncolytic viruses (OV) gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of the oncolytic herpesvirus to treat advanced melanoma. OVs offer an attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, yet the latter effect is less well studied. Nevertheless, OVs can be envisaged as potential in situ tumor vaccines. The therapeutic potential of OVs can be instigated further by using the molecular biological and biotechnological tools to modify the existing viruses for their optimal tumor selectivity and enhanced immune stimulation. Furthermore, OVs can be readily combined with other therapeutic agents to increase the efficacy of the existing therapeutic schemes. In this review, we discuss biotechnological advances in the development of therapeutic applications of OVs in Russia. Particular emphasis is made on the OV-mediated treatment of glioblastoma. In addition, we highlight the challenges of oncolytic virotherapy, and describe the strategies to optimize current approaches to improve clinical outcomes.

Lead-acid batteries utilised in electrical substations release hydrogen and oxygen when these are charged. These gases could be dangerous and cause a risk of fire if they are not properly ventilated. Therefore, this research seeks to design and implement a network control panel for heating, ventilation, and air-conditioning systems (HVACS). This is done using a specific range of controllers, which have more than thirty loops of proportional, integral and derivative (PID) control to achieve a cost-effective design. It performs the required function of extracting hydrogen, oxygen, and maintaining the desired temperature of the battery storage room within the recommended limits (i.e. 25°C ±1°C tolerance) without compromising quality as set out in the user requirement specification in Appendix-A. The system control panel allows the user to access control parameters such as changing temperature set-points, fan-speed, sensor database amongst others. The hardware is configured to detect extreme hydrogen and oxygen gas content in the battery room and ensure that the HVACS extract the gas content to the outside environment. The results of the system show that the network control panel effectively operates as per the recommended system requirements. Therefore, the effective operation of the HVACS ensures sufficient gas ventilation, thus mitigating the risk of fire in a typical battery storage room. Furthermore, the effective operation of HVACS enhances battery lifespan because of regulated operating temperature, which is conducive to minimise the effect of sulfation in lead acid Batteries (LABs).

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

In our previous study, a novel barrier processing on a porous low-dielectric constant (low-k) film was developed: an ultrathin Mn oxide on a nitrogen-stuffed porous carbon-doped organosilica film (p-SiOCH(N)) as a barrier of the Cu film was fabricated. To form a better barrier Mn₂O_3-xN film, an additional annealing at 450°C was implemented. In this study, the electrical characteristics and reliability of this integrated Cu/Mn₂O_3-xN/p-SiOCH(N)/Si structure is investigated. The proposed Cu/Mn₂O_3-xN/p-SiOCH(N)/Si capacitors exhibited poor dielectric breakdown characteristics in the as-fabricted stage, although, less degradation was found after thermal stress. Moreover, its time-dependence-dielectric-breakdown electric-field acceleration factor slightly increased after thermal stress, leading to a larger dielectric lifetime in a low electric-field as compared to other MIS capacitors. Furthermore, its Cu barrier ability under electrical or thermal stress was improved. As a consequent, the proposed Cu/Mn₂O_3-xN/p-SiCOH(N) scheme is a promising integrity for back-end-of-line interconnects.

Using co-precipitation to synthesize (CeO2)0.95(Y2O3)0.05 (YDC) and solid reaction method to synthesize (CeO2)0.75(ZrO2)0.25 (ZDC), and the characterization for both crystal structure and micro-structure of the two materials was conducted with X-ray diffraction (XRD) and scanning electron microscope (SEM) methods. Prepare the YDC and ZDC based limited current O2 sensor by employing platinum pasting bonding method. Sensing characteristics of the sensor were obtained at different conditions and study on the impact of temperature, O2 concentration as well as water vapor pressure on the sensing characteristics had been conducted. XRD results show that the phase structure of both YDC and ZDC is cubic phase. SEM results show that both YDC and ZDC layers are dense layers, which are then qualified to be the composition materials of the sensor. This limited current O2 sensor shows good sensing performance and conforms to the Knudsen model. Log(IL•T) depends linearly on 1000/T with R2 of 0.9904, IL depends linearly on x(O2) with R2 of 0.9726 and sensing characteristics are not affected by p(H2O).

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species. The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

In the literature, the chemical composition of Rhododendron tomentosum is mainly represented by the study of isoprenoid compounds of essential oil. In contrast, the study of the content of flavonoids will contribute to the expansion of the pharmacological action and the use of the medicinal plant for medical purposes. The paper deals with the technology of extracts from Rhododendron tomentosum shoots using ethanol of various concentrations and purified water as an extractant. Extracts from Rhododendron tomentosum were obtained by a modified method that combined the effects of ultrasound and temperature to maximize the extraction of biologically active substances from the raw material. By the method of high-performance thin-layer chromatography in the system of solvents ethyl acetate: formic acid: water (15:1:1) the following substances have been separated and identified: rutin, hyperoside, quercetin, and chlorogenic acid in all the extracts obtained. To quantify the total flavonoids content, a method of spectrophotometric determination based on the reaction of complexation with aluminum chloride has been developed. It has been proved that the course of the complexation reaction and, accordingly, the quantification of the flavonoid structure substances by the spectrophotometric method is influenced by some factors, including the environment, pH, the structure of the complexes, etc. Regardless of the chosen method, for the further production of Rhododendron tomentosum extracts with a higher content of flavonoid structure substance, it is advisable to use 60%, 70%, and 80% ethyl alcohol as extractant.