Search Results (45)

Background: Encapsulation of siRNA fragments inside liposome vesicles has emerged as an effective method for delivering siRNAs in vitro and in vivo. However, the liposome’s fluid-phospholipid bilayer of liposomes allows siRNA fragments to diffuse out of the liposome, decreasing the dose concentration and therefore the effectiveness of the carrier. We have previously reported that β-cyclodextrins formulated in liposomes help increase the stability of siRNAs in cell culture medium. Here, we continued that study to include α, γ, methyl-β-cyclodextrins and β-cyclodextrin-modified gold and selenium nanoparticles. Methods: We used Isothermal Titration Calorimetry to study the binding thermodynamics of siRNAs to the cyclodextrin-modified nanoparticles and to screen for the best adamantane derivative to modify the siRNA fragments, and we used gel electrophoresis to study the stabilization effect of siRNA by cyclodextrins and the nanoparticles. Results: We found that only β- and methyl-β-cyclodextrins increased siRNA serum stability. Cyclodextrin-modified selenium nanoparticles also stabilize siRNA fragments in serum, and siRNAs chemically modified with an adamantane moiety (which forms inclusion complexes with the cyclodextrin-modified-nanoparticles) show a strong stabilization effect. Conclusions: β-cyclodextrins are good additives to stabilize siRNA in cell culture medium, and the thermodynamic data we generated of the interaction between cyclodextrins and adamantane analogs (widely used in drug delivery studies), should serve as a guide for future studies where cyclodextrins are sought for the delivery and solvation of small organic molecules. Full article

Cell membranes are crucial elements in living organisms, serving as protective barriers and providing structural support for cells. They regulate numerous exchange and communication processes between cells and their environment, including interactions with other cells, tissues, ions, xenobiotics, and drugs. However, the complexity and heterogeneity of cell membranes—comprising two asymmetric layers with varying compositions across different cell types and states (e.g., healthy vs. diseased)—along with the challenges of manipulating real cell membranes represent significant obstacles for in vivo studies. To address these challenges, researchers have developed various methodologies to create model cell membranes or membrane fragments, including mono- or bilayers organized in planar systems. These models facilitate fundamental studies on membrane component interactions as well as the interactions of membrane components with external agents, such as drugs, nanoparticles (NPs), or biomarkers. The applications of model cell membranes have extended beyond basic research, encompassing areas such as biosensing and nanoparticle camouflage to evade immune detection. In this review, we highlight advancements in the engineering of planar model cell membranes, focusing on the nanoarchitectonic tools used for their fabrication. We also discuss approaches for incorporating challenging materials, such as proteins and enzymes, into these models. Finally, we present our view on future perspectives in the field of planar model cell membranes. Full article

A phospholipid bilayer is a typical structure that serves crucial functions in various cells and organelles. However, it is not unusual for it to take part in pathological processes. The cell membrane may be a binding target for amyloid-forming proteins, becoming a factor modulating the oligomerization process leading to amyloid deposition—a hallmark of amyloidogenic diseases—e.g., Alzheimer’s disease. The information on the mechanisms governing the oligomerization influenced by the protein–membrane interactions is scarce. Therefore, our study aims to describe the interactions between DPPA, a cell membrane mimetic, and amyloidogenic protein human cystatin C. Circular dichroism spectroscopy and differential scanning calorimetry were used to monitor (i) the secondary structure of the human cystatin C and (ii) the phase transition temperature of the DPPA, during the protein–membrane interactions. NMR techniques were used to determine the protein fragments responsible for the interactions, and molecular dynamics simulations were applied to provide a molecular structure representing the interaction. The obtained data indicate that the protein interacts with DPPA, submerging itself into the bilayer via the AS region. Additionally, the interaction increases the content of α-helix within the protein’s secondary structure and stabilizes the whole molecule against denaturation. Full article

Polyene antibiotics have been used in antifungal therapy since the mid-twentieth century. They are highly valued for their broad spectrum of activity and the rarity of pathogen resistance to their action. However, their use in the treatment of systemic mycoses often results in serious side-effects. Recently, there has been a renewed interest in the development of new antifungal drugs based on polyenes, particularly due to the emergence of highly dangerous pathogenic strains of fungi, such as Candida auris, and the increased incidence of mucormycosis. Considerable understanding has been established regarding the structure–biological activity relationships of polyene antifungals. Yet, no previous studies have examined the effect of introducing quaternized fragments into their molecular structure. In this study, we present a series of amides of amphotericin B, nystatin, and natamycin bearing a quaternized group in the side chain, and discuss their biological properties: antifungal activity, cytotoxicity, and effects on lipid bilayers that mimic fungal and mammalian cell membranes. Our research findings suggest that the nature of the introduced quaternized residue plays a more significant role than merely the introduction of a constant positive charge. Among the tested polyenes, derivatives 4b, 5b, and 6b, which contain a fragment of N-methyl-4-(aminomethyl)pyridinium in their structure, are particularly noteworthy due to their biological activity. Full article

RNA-based therapeutics, including siRNA, have obtained recognition in recent years due to their potential to treat various chronic and rare diseases. However, there are still limitations to lipid-based drug delivery systems in the clinical use of RNA therapeutics due to the need for optimization in the design and the preparation process. In this study, we propose adaptive focused ultrasound (AFU) as a drug loading technique to protect RNA from degradation by encapsulating small RNA in nanoliposomes, which we term nanoplexes. The AFU method is non-invasive and isothermal, as nanoplexes are produced without direct contact with any external materials while maintaining precise temperature control according to the desired settings. The controllability of sample treatments can be effectively modulated, allowing for a wide range of ultrasound intensities to be applied. Importantly, the absence of co-solvents in the process eliminates the need for additional substances, thereby minimizing the potential for cross-contaminations. Since AFU is a non-invasive method, the entire process can be conducted under sterile conditions. A minimal volume (300 μL) is required for this process, and the treatment is speedy (10 min in this study). Our in vitro experiments with silencer CD44 siRNA, which performs as a model therapeutic drug in different mammalian cell lines, showed encouraging results (knockdown > 80%). To quantify gene silencing efficacy, we employed quantitative polymerase chain reaction (qPCR). Additionally, cryo-electron microscopy (cryo-EM) and atomic force microscopy (AFM) techniques were employed to capture images of nanoplexes. These images revealed the presence of individual nanoparticles measuring approximately 100–200 nm in contrast with the random distribution of clustered complexes observed in ultrasound-untreated samples of liposome nanoparticles and siRNA. AFU holds great potential as a standardized liposome processing and loading method because its process is fast, sterile, and does not require additional solvents. Full article

The life stories of older adults encapsulate an array of personal experiences that reflect their care needs. However, due to inherent fuzzy features, fragmented natures, repetition, and redundancies, the practical application of the life story approach poses challenges for caregivers in acquiring and comprehending these narratives. Addressing this challenge, our study introduces a novel approach called Life Story Hierarchies with Graph-Enhanced Event Feature Refinement (LSH-GEFR). LSH-GEFR constructs a bilayer graph. Firstly, the event element map leverages intricate relationships between event elements to extract environmental features, providing a detailed context for understanding each event element. Secondly, the event map explores the complex web of relationships between the events themselves, allowing LSH-GEFR to generate a comprehensive understanding of each event and enhance its representation. Subsequently, we conducted experiments on different datasets and found that, in comparison with four advanced event tree generation methods, the proposed LSH-GEFR method outperformed them in terms of path coherence, branch reasonableness, and overall readability when generating life story hierarchies. Over 84.91% of the structured life narratives achieved readability, marking a 5.96% increase over the best-performing approach at the baseline. Full article

Advanced two-dimensional spin-polarized heterostructures based on twisted (TBG) and nanoporous (NPBG) bilayer graphenes doped with Eu ions were theoretically proposed and studied using Periodic Boundary Conditions Density Functional theory electronic structure calculations. The significant polarization of the electronic states at the Fermi level was discovered for both Eu/NPBG(AA) and Eu/TBG lattices. Eu ions’ chemi- and physisorption to both graphenes may lead to structural deformations, drop of symmetry of low-dimensional lattices, interlayer fusion, and mutual slides of TBG graphene fragments. The frontier bands in the valence region at the vicinity of the Fermi level of both spin-polarized 2D Eu/NPBG(AA) and Eu/TBG lattices clearly demonstrate flat dispersion laws caused by localized electronic states formed by TBG Moiré patterns, which could lead to strong electron correlations and the formation of exotic quantum phases. Full article

A synthesis procedure and aggregation properties of a new homologous series of dicationic gemini surfactants with a dodecane spacer and two carbamate fragments (N,N′-dialkyl-N,N′-bis(2-(ethylcarbamoyloxy)ethyl)-N,N′-dimethyldodecan-1,6-diammonium dibromide, n-12-n(Et), where n = 10, 12, 14) were comprehensively described. The critical micelle concentrations of gemini surfactants were obtained using tensiometry, conductometry, spectrophotometry, and fluorimetry. The thermodynamic parameters of adsorption and micellization, i.e., maximum surface excess (Г_max), the surface area per surfactant molecule (A_min), degree of counterion binding (β), and Gibbs free energy of micellization (∆G_mic), were calculated. Functional activity of the surfactants, including the solubilizing capacity toward Orange OT and indomethacin, incorporation into the lipid bilayer, minimum inhibitory concentration, and minimum bactericidal and fungicidal concentrations, was determined. Synthesized gemini surfactants were further used for the modification of liposomes dual-loaded with α-tocopherol and donepezil hydrochloride for intranasal treatment of Alzheimer’s disease. The obtained liposomes have high stability (more than 5 months), a significant positive charge (approximately + 40 mV), and a high degree of encapsulation efficiency toward rhodamine B, α-tocopherol, and donepezil hydrochloride. Korsmeyer-Peppas, Higuchi, and first-order kinetic models were used to process the in vitro release curves of donepezil hydrochloride. Intranasal administration of liposomes loaded with α-tocopherol and donepezil hydrochloride for 21 days prevented memory impairment and decreased the number of Aβ plaques by 37.6%, 40.5%, and 72.6% in the entorhinal cortex, DG, and CA1 areas of the hippocampus of the brain of transgenic mice with Alzheimer’s disease model (APP/PS1) compared with untreated animals. Full article

Background: BFSP1 (beaded filament structural protein 1) is a plasma membrane, Aquaporin 0 (AQP0/MIP)-associated intermediate filament protein expressed in the eye lens. BFSP1 is myristoylated, a post-translation modification that requires caspase cleavage at D433. Bioinformatic analyses suggested that the sequences 434–452 were α-helical and amphipathic. Methods and Results: By CD spectroscopy, we show that the addition of trifluoroethanol induced a switch from an intrinsically disordered to a more α-helical conformation for the residues 434–467. Recombinantly produced BFSP1 fragments containing this amphipathic helix bind to lens lipid bilayers as determined by surface plasmon resonance (SPR). Lastly, we demonstrate by transient transfection of non-lens MCF7 cells that these same BFSP1 C-terminal sequences localise to plasma membranes and to cytoplasmic vesicles. These can be co-labelled with the vital dye, lysotracker, but other cell compartments, such as the nuclear and mitochondrial membranes, were negative. The N-terminal myristoylation of the amphipathic helix appeared not to change either the lipid affinity or membrane localisation of the BFSP1 polypeptides or fragments we assessed by SPR and transient transfection, but it did appear to enhance its helical content. Conclusions: These data support the conclusion that C-terminal sequences of human BFSP1 distal to the caspase site at G433 have independent membrane binding properties via an adjacent amphipathic helix. Full article

Cationic and hydrophilic coatings based on casting and drying water dispersions of two different nanoparticles (NPs) onto glass are here described and evaluated for antimicrobial activity. Discoid cationic bilayer fragments (BF) surrounded by carboxy-methylcellulose (CMC) and poly (diallyl dimethyl ammonium) chloride (PDDA) NPs and spherical gramicidin D (Gr) NPs dispersed in water solution were cast onto glass coverslips and dried, forming a coating quantitatively evaluated against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. From plating and colony forming units (CFU) counting, all strains interacting for 1 h with the coatings lost viability from 10⁵ to 10⁶, to zero CFU, at two sets of Gr and PDDA doses: 4.6 and 25 μg, respectively, or, 0.94 and 5 μg, respectively. Combinations produced broad spectrum, antimicrobial coatings; PDDA electrostatically attached to the microbes damaging cell walls, allowing Gr NPs interaction with the cell membrane. This concerted action promoted optimal activity at low Gr and PDDA doses. Further washing and drying of the deposited dried coatings showed that they were washed out so that antimicrobial activity was no longer present on the glass surface. Significant applications in biomedical materials can be foreseen for these transient coatings. Full article

Hybrid structures based on graphene and carbon nanotubes (CNTs) are one of the most relevant modern nanomaterials for applications in various fields, including electronics. The variety of topological architectures of graphene/CNT hybrids requires a preliminary study of their physical properties by in silico methods. This paper is devoted to the study of the electronic and electrical properties of graphene/CNT hybrid 2D structures with an island topology using the self-consistent charge density functional-based tight-binding (SCC-DFTB) formalism and the Landauer–Buttiker formalism. The island-type topology is understood as the atomic configuration of a graphene/CNT hybrid film, in which the structural fragments of graphene and nanotubes form “islands” (regions of the atomic structure) with an increased density of carbon atoms. The island-type graphene/CNT hybrid structures are formed by AB-stacked bilayer graphene and (6,3)/(12,8) chiral single-walled carbon nanotubes (SWCNT). The bilayer graphene is located above the nanotube perpendicular to its axis. Based on the binding energy calculations, it is found that the atomistic models of the studied graphene/SWCNT hybrid structures are thermodynamically stable. The peculiarities of the band structure of graphene/SWCNT (6,3) and graphene/SWCNT (12,8) hybrid structures are analyzed. It is shown that the electronic properties of graphene/SWCNT hybrid structures are sensitive to the orientation and size of the graphene layers with respect to the nanotube surface. It is found that an energy gap of ~0.1 eV opens in the band structure of only the graphene/SWCNT (6,3) hybrid structure, in which the graphene layers of the same length are arranged horizontally above the nanotube surface. We revealed the electrical conductivity anisotropy for all considered atomistic models of the graphene/SWCNT (12,8) hybrid structure when bilayer graphene sheets with different sizes along the zigzag and armchair directions are located at an angle with respect to the nanotube surface. The obtained knowledge is important to evaluate the prospects for the potential application of the considered atomic configurations of graphene/SWCNT hybrid structures with island-type topology as connecting conductors and electrodes in electronic devices. Full article

It is of extreme importance to develop a reliable numerical prediction technique to simulate the ballistic response of ceramic armor subjected to high-velocity impact (HVI) to economize the test cost and shorten the design period. In the present manuscript, a series of experiments on tungsten heavy alloy (WHA) fragment’s penetration into 99.5% alumina (AD995) armors are systematically simulated by employing the FE-converting-SPH technique. The numerical results are compared with the experimental counterparts to find that the FE-converting-SPH method is fairly efficient in predicting the depth of penetration, the residual velocity, length and mass of fragment, and reproducing the crack forms of ceramic. The applicability and accuracy of the numerical model in terms of the algorithm, material model parameters and contact definitions are validated. Then, the relevant parameters of the calibrated numerical model are incorporated to explore the influence of cover-layer thickness on the armor performance. A few mechanisms regarding the cover plate have been identified to act on the armor performance, such as the alteration of fracture cone half-angle, proportion of energy absorbed by ceramic, mushrooming deformation of fragment, etc. The result of multi-mechanism superposition is that the best ballistic performance is endued with 1 mm cover-layer armor, which demonstrates a 24.6% improvement over the bi-layer armor with 4.96 g/cm² area density, only at the cost of 15.7% increase in areal density, when back-plate thickness is held as 2 mm; for a constant area density of 4.96 g/cm², a 1 mm cover-layer is also expected to be the best choice, with 10.7% improvement in armor performance. Full article

Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections. Full article

Many novel physical properties of twisted bilayer graphene have been discovered and studied successively, but the physical mechanism of the chiral modulation of BLG by a twisted angle lacks theoretical research. In this work, the density functional theory, the wavefunction analysis of the excited state, and the quantum theory of atoms in molecules are used to calculate and analyze the anti-symmetric chiral characteristics of zigzag-edge twisted bilayer graphene quantum dots based on periodic complementary twisted angles. The analysis of the partial density of states shows that Moiré superlattices can effectively adjust the contribution of the atomic basis function of the fragment to the transition dipole moment. The topological analysis of electron density indicates that the Moiré superlattices structure can enhance the localization of the system, increasing the electron density of the Moiré central ring, reducing the electron surge capacity in general and inducing the reversed helical properties of the top and underlying graphene, which can be used as the origin of the chiral discrimination; it also reveals the mole in the superlattice chiral physical mechanism. On this basis, we will also study the nonlinear optical properties of twisted bilayer graphene based on a twisted angle. Full article

Two-dimensional molybdenum disulfide (MoS₂) has attracted significant attention for next-generation electronics, flexible devices, and optical applications. Chemical vapor deposition is the most promising route for the production of large-scale, high-quality MoS₂ films. Recently, the chemical vapor deposition of MoS₂ films on soda-lime glass has attracted great attention due to its low cost, fast growth, and large domain size. Typically, a piece of Mo foil or graphite needs to be used as a buffer layer between the glass substrates and the CVD system to prevent the glass substrates from being fragmented. In this study, a novel method was developed for synthesizing MoS₂ on glass substrates. Inert Al₂O₃ was used as the buffer layer and high-quality, uniform, triangular monolayer MoS₂ crystals with domain sizes larger than 400 μm were obtained. To demonstrate the advantages of glass/Al₂O₃ substrates, a direct comparison of CVD MoS₂ on glass/Mo and glass/Al₂O₃ substrates was performed. When Mo foil was used as the buffer layer, serried small bilayer islands and bright core centers could be observed on the MoS₂ domains at the center and edges of glass substrates. As a control, uniform MoS₂ crystals were obtained when Al₂O₃ was used as the buffer layer, both at the center and the edge of glass substrates. Raman and PL spectra were further characterized to show the merit of glass/Al₂O₃ substrates. In addition, the thickness of MoS₂ domains was confirmed by an atomic force microscope and the uniformity of MoS₂ domains was verified by Raman mapping. This work provides a novel method for CVD MoS₂ growth on soda-lime glass and is helpful in realizing commercial applications of MoS₂. Full article