Search Results (141)

To investigate the impermeability characteristics of composite geomembranes in rigid landfills, a three-dimensional finite element seepage analysis model, which incorporates a composite geomembrane, was established based on a case study of a rigid landfill project in Tongling. Utilizing the seepage mechanism of the composite geomembrane, the seepage distribution patterns of the hazardous waste leachate within the unit cell were computed under representative operating conditions. Different thickness amplification factor schemes for the equivalent treatment of the composite geomembrane were comparatively analyzed, considering both isotropic and anisotropic seepage conditions. The relationships between the seepage flow rate, velocity, and thickness amplification factor were determined. The results showed that the leachate experiences a rapid drop in the water head as it passes through the composite geomembrane, with a low seepage flow rate and velocity, highlighting the membrane’s significant impermeability effect. The finite element analysis indicated that thickness amplification of the composite geomembrane based on the flow equivalence is feasible to some degree, but treating the geomembrane as an anisotropic material during the equivalent process better approximates the actual conditions. Full article

In the context of the circular economy, the valorization of bio-derived waste has become a priority across various production sectors, including food processing and packaging. Gelatin (Gel), a protein which can be recovered from meat industry byproducts, offers a sustainable solution in this regard. In this study, pork-derived gelatin was used to develop novel edible active packaging films, designed for meat products. Glycerol (Gl) was used as a plasticizer. Two types of montmorillonite-based nanohybrids were employed as both reinforcing agents and carriers of antioxidant/antibacterial compounds: eugenol-functionalized montmorillonite (EG@Mt) and citral-functionalized montmorillonite (CT@Mt). The active films were formulated as Gel/Gl/xEG@Mt and Gel/Gl/xCT@Mt, where x = 5, 10, or 15 wt.%. Controlled-release kinetics showed that EG@Mt released up to 95% of its adsorbed eugenol, whereas CT@Mt released up to 55% of its adsorbed citral. The films were evaluated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and tested for antibacterial activity against Escherichia coli and Listeria monocytogenes. Results demonstrated that the Gel/Gl/xEG@Mt films exhibited superior antioxidant and antibacterial performance compared to the Gel/Gl/xCT@Mt films. All formulations were impermeable to oxygen. Although the incorporation of EG and CT slightly reduced cell viability, values remained above 80%, indicating non-toxicity. In conclusion, the film containing 15 wt.% EG@Mt achieved an oxygen transmission rate of zero, an effective concentration (EC₆₀) of 9.9 mg/L to reach 60% antioxidant activity, and reduced E. coli and L. monocytogenes populations by at least 5.8 log CFU/mL (p < 0.05), bringing them below the detection limit. Moreover, it successfully extended the shelf life of fresh minced pork by two days. Full article

Solid oxide electrolysis cells (SOECs) represent a promising technology because they have the potential to achieve greater efficiency than existing electrolysis methods, making them a strong candidate for sustainable hydrogen production. SOECs utilize a solid oxide electrolyte, which facilitates the migration of oxygen ions while maintaining gas impermeability at temperatures between 600 °C and 900 °C. This review provides an overview of the recent advancements in research and development at the intersection of machine learning and SOECs technology. It emphasizes how data-driven methods can improve performance prediction, facilitate material discovery, and enhance operational efficiency, with a particular focus on materials for cathode-supported cells. This paper also addresses the challenges associated with implementing machine learning for SOECs, such as data scarcity and the need for robust validation techniques. This paper aims to address challenges related to material degradation and the intricate electrochemical behaviors observed in SOECs. It provides a description of the reactions that may be involved in the degradation mechanisms, taking into account thermodynamic and kinetic factors. This information is utilized to construct a fault tree, which helps categorize various faults and enhances understanding of the relationship between their causes and symptoms. Full article

Vascular smooth muscle cells (VSMCs) can dynamically change their phenotype between contractile and synthetic forms in response to environmental stress, which is pivotal in maintaining vascular homeostasis and mediating pathological remodeling of blood vessels. We previously reported that suppression of canonical transient receptor potential 6 (TRPC6) channel-mediated cation entry sustains VSMCs contractile phenotype and promotes the blood flow recovery after hindlimb ischemia in mice. We also reported that Zn²⁺, a metal biomolecule mobilized by TRPC6 channel activation, exerts potential beneficial effects on cardiac contractility and remodeling. Therefore, we hypothesized that TRPC6-mediated Zn²⁺ influx participates in phenotype switching of VSMCs and vascular remodeling. We established rat aortic smooth muscle cells (RAoSMCs) stably expressing wild type (WT) and Zn²⁺ only impermeable TRPC6 (KYD) mutant. Although the resting phenotypes were similar in both RAoSMCs, pharmacological TRPC6 activation by PPZ2 prevented the transforming growth factor (TGF) β-induced reduction in the intracellular Zn²⁺ amount and contractile differentiation in RAoSMCs (WT), but failed to prevent them in RAoSMCs (KYD). There were no significant differences in TRPC6-dependent cation currents among all RAoSMCs pretreated with or without TGFβ and/or PPZ2, suggesting that TRPC6 channels are functionally expressed in RAoSMCs regardless of their phenotype. Treatment of mice with PPZ2 attenuated the progression of vascular remodeling caused by chronic angiotensin II infusion. These results suggest that Zn²⁺ influx through TRPC6 channels negatively regulates the TGFβ-induced contractile differentiation of VSMCs and the progression of vascular remodeling in rodents. Full article

The global burden of liver metastases from different primary lesions is increasing, resulting in significant challenges for public health systems. Accordingly, colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with a high incidence of liver metastases. Although surgical resection is considered the standard curative treatment, it is only viable for a limited subset of patients. This review aims to describe a potential alternative nonsurgical intervention, such as electrochemotherapy (ECT), in the treatment of CRC oligometastatic liver disease. ECT has been largely used for the treatment of cutaneous and subcutaneous lesions, while its visceral use is currently a novel approach. ECT consists of the administration of intravenous anticancer drugs, followed by the application of intralesional electrode needles, which release localized electrical pulses to induce electroporation, a process that transiently increases cell membrane permeability, thereby facilitating the intracellular delivery of otherwise membrane-impermeable drugs. The main topics of this review focus on the technical and clinical applications, efficacy, safety, and possible complications of ECT for CRC liver metastases. A comparison with other locoregional treatments is also performed, highlighting possible advantages and disadvantages. Full article

The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is a promising biotechnology tool for genome editing. However, in living organisms, several pharmacokinetic challenges arise, including off-target side effects due to incorrect distribution, low bioavailability caused by membrane impermeability, and instability resulting from enzymatic degradation. Therefore, innovative delivery strategies must be developed to address these issues. Modified nanoparticles offer a potential solution for the non-invasive delivery of CRISPR/Cas9 ribonucleoproteins (Cas9 RNPs). Cas9 RNPs encapsulated in nanoparticles are protected from enzymatic degradation, similar to how microRNAs are shielded within exosomes. It is well-established that certain materials, including proteins, are expressed selectively in specific cell types. For example, the α-7 nicotinic receptor is expressed in endothelial and neuronal cells, while the αvβ3 integrin is expressed in cancer cells. These endogenous materials can facilitate receptor-mediated endocytosis or transcytosis. Nanoparticles encapsulating Cas9 RNPs and coated with ligands targeting such receptors may be internalized through receptor-mediated mechanisms. Once internalized, Cas9 RNPs could perform the desired gene editing in the nucleus after escaping the endosome through mechanisms such as the proton sponge effect or membrane fusion. In this review, I discuss the potential and advantages of delivering Cas9 RNP-encapsulated nanoparticles coated with ligands through receptor-mediated endocytosis or transcytosis. Full article

The ability of a cell to keep its volume constant irrespective of intra- and extracellular conditions is essential for cellular homeostasis and survival. The purpose of this study is to elaborate a theoretical model of cell volume homeostasis and to apply it to a simulation of human aqueous humor (AH) production. The model assumes a cell with a spherical shape and only radial deformation satisfying the property that the cell volume in rest conditions equals that of the cell couplets constituting the ciliary epithelium of the human eye. The cytoplasm is described as a homogeneous mixture containing fluid, ions, and neutral solutes whose evolution is determined by net production mechanisms occurring in the intracellular volume and by water and solute exchange across the membrane. Averaging the balance equations over the cell volume leads to a coupled system of nonlinear ordinary differential equations (ODEs) which are solved using the $\theta$-method and the Matlab function ode15s. Simulation tests are conducted to characterize the set of parameters corresponding to baseline conditions in AH production. The model is subsequently used to investigate the relative importance of (a) impermeant charged proteins; (b) sodium–potassium (Na+/K+) pumps; (c) carbonic anhydrase (CA) in the AH production process; and (d) intraocular pressure. Results suggest that (a) and (b) play a role; (c) lacks significant weight, at least for low carbon dioxide values; and (d) plays a role for the elevated values of intraocular pressure. Model results describe a higher impact from charged proteins and Na+/K+ ATPase than CA on AH production and cellular volume. The computational virtual laboratory provides a method to further test in vivo experiments and machine learning-based data analysis toward the prevention and cure of ocular diseases such as glaucoma. Full article

Hexagonal boron nitride (h-BN) has emerged as a promising dielectric material for protecting metallic substrates such as copper and steel under ambient conditions. The layered structure of h-BN offers significant potential in preventing the oxidation and corrosion of these substrates. Due to their impermeability, boron nitride nanosheets (BNNSs) do not form a galvanic cell with the underlying metals, enhancing their effectiveness as protective coatings. BNNSs are both thermally and chemically stable, making them suitable for coatings that protect against environmental degradation. Additionally, BNNSs have demonstrated excellent fire resistance, hydrophobicity, and oxidation resistance when applied to wood, functioning as a binder-free, retardant coating that remains effective up to 900 °C in air. This review focuses on the anti-corrosion properties of BNNSs, particularly on copper and steel substrates, and discusses various methods for their application. This article also discusses future perspectives in this field, including the innovative concept of wooden satellites designed for short- and long-term missions. Full article

Background: Microorganisms are a known source of antibiotics. The study aimed to identify and screen antibiotic-producing microbes isolated from seawater. Method: Three of the fifty (50) bacteria isolated from seawater showed positive for antibiotic activity. The antimicrobial activity of Pseudomonas guguanensis (KD1) was screened against the ESKAPE pathogens using agar-well diffusion assays. P. guguanensis (KD1) was selected for the fermentation and extraction of antimicrobial compounds using solvent extraction assays. Results: P. guguanensis (KD1) produced the highest antibacterial activity after 36 h of cultivation, inhibiting S. aureus, E. faecium, A. baumannii and E. cloacae. According to sensitization assay, K. pneumoniae was impermeable to all the cell-free supernatants of P. guguanensis (KD1). Using agar-well diffusion assays, ethyl acetate extracts from the supernatant recorded zones of inhibition against S. aureus, E. faecium, and E. cloacae, producing zones of 20.1 ± 0.432, 17.8 ± 0.121 and 16 ± 0.162 mm, respectively. Acetonitrile extract from the supernatant inhibited A. baumannii and S. aureus, forming zones of inhibition 18.2 ± 0.323 mm and 18 ± 0.234. The minimum inhibitory concentration and minimum bactericidal concentration recorded for the ethyl acetate extract and acetonitrile extract ranged from 1.56 to 6.25 mg/mL and 12.5–25 mg/mL, respectively. Conclusions: P. guguanensis (KD1) offers a potential source of antibiotics for infections caused by multidrug-resistant bacteria. Full article

The cytosolic calcium concentration ([Ca²⁺]_cyt) in yeast cells is maintained at a low level via the action of different transporters sequestrating these cations in the vacuole. Among them, the vacuolar Ca²⁺ ATPase Pmc1 crucially contributes to this process. Its inactivation in Ogataea yeasts was shown to cause sodium dodecyl sulfate (SDS) hypersensitivity that can be alleviated by the inactivation of the plasma membrane high-affinity Ca²⁺ channel Cch1. Here, we show that SDS at low concentrations induces a rapid influx of external Ca²⁺ into cells, while the plasma membrane remains impermeable for propidium iodide. The inactivation of Pmc1 disturbs efficient adaptation to this activity of SDS. The inactivation of Cch1 partially restores the ability of pmc1 mutant cells to cope with an increased [Ca²⁺]_cyt that correlates with the suppression of SDS hypersensitivity. At the same time, Cch1 is unlikely to be directly involved in SDS-induced Ca²⁺ influx, since its inactivation does not decrease the amplitude of the rapid [Ca²⁺]_cyt elevation in the pmc1-Δ mutant. The obtained data suggest that the effects of CCH1 inactivation on SDS sensitivity and coping with increased [Ca²⁺]_cyt are related to an additional Cch1 function beyond its direct involvement in Ca²⁺ transport. Full article

Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate. However, the intracellular delivery of exogenous PCr is challenging as it does not readily cross the plasma membrane. This complicates the use of PCr as a therapeutic agent to maintain energy homeostasis or to treat conditions like cerebral creatine deficiency syndrome (CDS), which results from defective creatine transporters. Methods: This study employs the use of fusogenic liposomes to deliver PCr directly into the cytosol, bypassing membrane impermeability issues. We engineered various 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based fusogenic liposomes, incorporating phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with phospholipid-aromatic dye components to facilitate membrane fusion and to enhance the delivery of the PCr cargo. Liposomal formulations were co-loaded with membrane-impermeable chromophores and PCr and studied on live cells using confocal microscopy. Conclusions: We demonstrated the successful intracellular delivery of these agents and observed a 23% increase in intracellular ATP levels in cells treated with PCr-loaded liposomes. This increase was not observed with free PCr, confirming the effectiveness of the liposome-based delivery system. Additionally, cell viability assays showed minimal toxicity from the liposomes. Our results indicate that fusogenic liposomes are a promising method for the delivery of PCr (and potentially other cell-impermeable therapeutic agents) to the cellular cytosol. The approach demonstrated here could be advantageous for treating energy-related disorders and improving cellular energy homeostasis. Full article

Sonoporation stimulates cell growth as it improves the permeability of the membrane and increases the uptake of impermeable molecules in the extracellular matrix. We evaluated the effects of substrates (whey, whole, and skim milk) and ultrasonic treatments (ultrasonication and thermosonication) on the antioxidant activity (AA) of water-soluble kefir postbiotics (WSKPs). The samples were evaluated in terms of antioxidant activity (ABTS, DPPH, FRAP, and ORAC), water-soluble protein content, proteolysis (SDS-PAGE profiles), and cell membrane permeability. The levels of AA in all WSKPs depended on the substrate and method of obtaining them. However, the WSKPs from whey had higher antioxidant activity with DPPH (11.11 mg TE/100 mL), ABTS (12.77 mg TE/100 mL), and FRAP (5.18 mg TE/100 mL). Also, the WSKPs from whey had the highest values for water-soluble protein (1.45–1.32 mg/mL) and proteolysis degree and the lowest percentage of dead cells (11.4–28%). These results suggest that the production of WSKPs from whey might add value to whey production. Furthermore, WSKPs have potential as a functional ingredient in the production of beverages or foods with antioxidant activity. Full article

Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood–tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, ¹²⁵I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases. Full article

The membrane impermeability of a drug poses a significant challenge in drug research and development, preventing effective drug delivery to the target site. Specifically, the blood-brain barrier (BBB) presents a formidable obstacle to the delivery of drugs targeting the central nervous system (CNS) into the brain, whereas the blood-retinal barrier (BRB) presents a tremendous obstacle to the delivery of drugs targeting the ocular diseases into the eyes. The development of drugs for Alzheimer’s or Parkinson’s disease targeting the CNS and for diabetic retinopathy and age-related macular degeneration targeting the eyes remains an unmet medical need for patients. Transporters play a crucial physiological role in maintaining homeostasis in metabolic organs. Various types of solute carrier (SLC) transporters are expressed in the capillary endothelial cells of the BBB, facilitating the delivery of nutrients from the blood flow to the brain. Therefore, carrier-mediated transport across the BBB can be achieved using SLC transporters present in capillary endothelial cells. It is well-known that CNS drugs typically incorporate N-containing groups, indicating that cation transporters facilitate their transport into the brain. In fact, carrier-mediated transport across the BBB can be accomplished using glucose transporter type 1 (Glut1) as a glucose transporter, L-type amino acid transporter 1 (LAT1) as a large neutral amino acid transporter, and H⁺/cation antiporter as a cation transporter. Surprisingly, although organic cation transporter novel type 2 (OCTN2) is expressed in the capillary endothelial cells, there has been limited investigation into OCTN2-mediated substance delivery into the brain across the BBB. Furthermore, it is suggested that OCTN2 is expressed at the BRB. In this prospective review, I present the advantages and possibilities of substance delivery into the brain across the BBB or into the eyes across the BRB, mediated by OCTN2 via carrier-mediated transport or receptor-mediated transcytosis. Full article

Signal transduction and homeostasis are regulated by complex protein interactions in the intracellular environment. Therefore, the transportation of impermeable macromolecules (nucleic acids, proteins, and drugs) that control protein interactions is essential for modulating cell functions and therapeutic applications. However, macromolecule transportation across the cell membrane is not easy because the cell membrane separates the intra/extracellular environments, and the types of molecular transportation are regulated by membrane proteins. Cell-penetrating peptides (CPPs) are expected to be carriers for molecular transport. CPPs can transport macromolecules into cells through endocytosis and direct translocation. The transport mechanism remains largely unclear owing to several possibilities. In this review, we describe the methods for investigating CPP conformation, translocation, and cargo transportation using artificial membranes. We also investigated biomolecular transport across living cell membranes via CPPs. Subsequently, we show not only the biochemical applications but also the synthetic biological applications of CPPs. Finally, recent progress in biomolecule and nanoparticle transportation via CPPs into specific tissues is described from the viewpoint of drug delivery. This review provides the opportunity to discuss the mechanism of biomolecule transportation through these two platforms. Full article