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Toxins May 2024α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer...
α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection map. At this resolution, no major conformational changes between the crystalline and solution states of α-LTX tetramers were observed. Electrophysiological studies showed that, under the conditions of crystallization, α-LTX simultaneously formed multiple channels in biological membranes that displayed coordinated gating. Two types of channels with conductance levels of 120 and 208 pS were identified. Furthermore, we observed two distinct tetramer conformations of tetramers both when observed as monodisperse single particles and within the 2D crystals, with pore diameters of 11 and 13.5 Å, suggestive of a flickering pore in the middle of the tetramer, which may correspond to the two states of toxin channels with different conductance levels. We discuss the structural changes that occur in α-LTX tetramers in solution and propose a mechanism of α-LTX insertion into the membrane. The propensity of α-LTX tetramers to form 2D crystals may explain many features of α-LTX toxicology and suggest that other pore-forming toxins may also form arrays of channels to exert maximal toxic effect.
Topics: Cryoelectron Microscopy; Animals; Spider Venoms; Cell Membrane; Protein Multimerization; Crystallization
PubMed: 38922143
DOI: 10.3390/toxins16060248 -
Toxins May 2024A major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, binding membrane cholesterol and producing permanent lytic or transient pores. During...
A major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, binding membrane cholesterol and producing permanent lytic or transient pores. During brain infections, vascular damage with variable ischemia occurs. The role of ischemia on pneumolysin's pore-forming capacity remains unknown. In acute brain slice cultures and primary cultured glia, we studied acute toxin lysis (via propidium iodide staining and LDH release) and transient pore formation (by analyzing increases in the intracellular calcium). We analyzed normal peripheral tissue glucose conditions (80 mg%), normal brain glucose levels (20 mg%), and brain hypoglycemic conditions (3 mg%), in combinations either with normoxia (8% oxygen) or hypoxia (2% oxygen). At 80 mg% glucose, hypoxia enhanced cytolysis via pneumolysin. At 20 mg% glucose, hypoxia did not affect cell lysis, but impaired calcium restoration after non-lytic pore formation. Only at 3 mg% glucose, during normoxia, did pneumolysin produce stronger lysis. In hypoglycemic (3 mg% glucose) conditions, pneumolysin caused a milder calcium increase, but restoration was missing. Microglia bound more pneumolysin than astrocytes and demonstrated generally stronger calcium elevation. Thus, our work demonstrated that the toxin pore-forming capacity in cells continuously diminishes when oxygen is reduced, overlapping with a continuously reduced ability of cells to maintain homeostasis of the calcium influx once oxygen and glucose are reduced.
Topics: Streptolysins; Glucose; Animals; Bacterial Proteins; Oxygen; Cholesterol; Streptococcus pneumoniae; Brain; Calcium; Cells, Cultured; Neuroglia
PubMed: 38922127
DOI: 10.3390/toxins16060232 -
Toxics Jun 2024Bisphenol A (BPA), a typical endocrine disruptor, is known to have various adverse effects on the male reproductive system. However, the toxic effects and mechanisms of...
Bisphenol A (BPA), a typical endocrine disruptor, is known to have various adverse effects on the male reproductive system. However, the toxic effects and mechanisms of low-dose BPA have not yet been fully explored. In this study, male Kunming mice were orally administered low-dose BPA (0.03, 0.3 and 3 mg/kg/d) for ten consecutive weeks. Pathological sections of testicular tissue showed no significant morphological differences after BPA exposure. An analysis of the functional parameters of sperm revealed that exposure to low-dose BPA significantly decreased sperm motility, chemotaxis, and the acrosome reaction. An in vitro BPA exposure model combined with an omics data analysis showed that the olfactory receptor-related pathway was significantly enriched after BPA treatment. Subsequent experiments verified the reduced mRNA level of a novel olfactory receptor gene, , in vivo and in vitro exposure models. Meanwhile, exposure to low-dose BPA reduced the intracellular calcium ion concentration and the mRNA levels of pore-forming subunits of the CatSper channel in sperm. Importantly, the knockdown of Olfr25 inhibited calcium ion levels and CatSper subunit expression in GC-2 cells. Olfr25 overexpression attenuated the BPA-induced downregulation of CatSper subunit expression in GC-2 cells. These findings indicate that Olfr25 might participate in low-dose BPA-induced sperm dysfunction by affecting the CatSper-Ca signaling pathway. This study reveals a new mechanism underlying the effects of low-dose BPA on sperm function and provides a reference for assessing the safety of low-dose BPA exposure.
PubMed: 38922122
DOI: 10.3390/toxics12060442 -
Toxics Jun 2024Fly ash, a type of solid waste generated in power plants, can be utilized as a catalyst carrier to enhance its value-added potential. Common methods often involve using...
Fly ash, a type of solid waste generated in power plants, can be utilized as a catalyst carrier to enhance its value-added potential. Common methods often involve using a large amount of alkali for preprocessing, resulting in stable quartz and mullite forming silicate dissolution. This leads to an increased specific surface area and pore structure. In this study, we produced a catalyst composed of MnO/NiOOH supported on fly ash by directly employing nickel hydroxide and potassium permanganate to generate metal active sites over the fly ash surface while simultaneously creating a larger specific surface area and pore structure. The ozone catalytic oxidation performance of this catalyst was evaluated using sodium acetate as the target organic matter. The experimental results demonstrated that an optimal removal efficiency of 57.5% for sodium acetate was achieved, surpassing even that of MnO/NiOOH supported catalyst by using γ-AlO. After loading of MnO/NiOOH, an oxygen vacancy is formed on the surface of fly ash, which plays an indirect oxidation effect on sodium acetate due to the transformation of ozone to •O and •OH over this oxygen vacancy. The reaction process parameters, including varying concentrations of ozone, sodium acetate, and catalyst dosage, as well as pH value and the quantitative analysis of formed free radicals, were examined in detail. This work demonstrated that fly ash could be used as a viable catalytic material for wastewater treatment and provided a new solution to the added value of fly ash.
PubMed: 38922092
DOI: 10.3390/toxics12060412 -
Nanomaterials (Basel, Switzerland) Jun 2024Fluidization bed reactor is an attractive method to synthesize and process quantities of functional nanoparticles, due to the large gas-solid contact area and its...
Fluidization bed reactor is an attractive method to synthesize and process quantities of functional nanoparticles, due to the large gas-solid contact area and its potential scalability. Nanoparticles fluidize not individually but as a form of porous agglomerates with a typical porosity above 90%. The porous structure has a significant effect on the hydrodynamic behavior of a single nanoparticle agglomerate, but its influence on the flow behavior of nanoparticle agglomerates in a fluidized bed is currently unclear. In the present study, a drag model was developed to consider the porous structure effects of nanoparticle agglomerates by incorporating porous-structure-based drag laws in the Eulerian-Eulerian two-fluid model. Numerical simulations were performed from particulate to bubbling fluidization state to evaluate the applicability of porous-structure-based drag laws. Results obtained for the minimum fluidization and bubbling velocities, bed expansion ratio, and agglomerate dispersion coefficient show that, compared with the drag law of solid sphere, the porous-structure-based drag laws, especially the drag law of fractal porous spheres, provide a closer fit to the experimental data. This indicates that the pore structures have a great impact on gas-solid flow behavior of nanoparticle agglomerates, and the porous-structure-based drag laws are more suitable for describing flows in nanoparticle agglomerate fluidized beds.
PubMed: 38921933
DOI: 10.3390/nano14121057 -
Nanomaterials (Basel, Switzerland) Jun 2024Monodisperse and semi-faceted ultra-small templated mesoporous silica nanoparticles (US-MSNs) of 20-25 nm were synthesized using short-time hydrolysis of...
Monodisperse and semi-faceted ultra-small templated mesoporous silica nanoparticles (US-MSNs) of 20-25 nm were synthesized using short-time hydrolysis of tetraethoxysilane (TEOS) at room temperature, followed by a dilution for nucleation quenching. According to dynamic light scattering (DLS), a two-step pH adjustment was necessary for growth termination and colloidal stabilization. The pore size was controlled by cetyltrimethylammonium bromide (CTAB), and a tiny amount of neutral surfactant F127 was added to minimize the coalescence between US-MSNs and to favor the transition towards internal ordering. Flocculation eventually occurred, allowing us to harvest a powder by centrifugation (~60% silica yield after one month). Scanning transmission electron microscopy (STEM) and 3D high-resolution transmission electron microscopy (3D HR-TEM) images revealed that the US-MSNs are partially ordered. The 2D FT transform images provide evidence for the coexistence of four-, five-, and sixfold patterns characterizing an "on-the-edge" crystallization step between amorphous raspberry and hexagonal pore array morphologies, typical of a protocrystalline state. Calcination preserved this state and yielded a powder characterized by packing, developing a hierarchical porosity centered at 3.9 ± 0.2 (internal pores) and 68 ± 7 nm (packing voids) of high potential for support for separation and catalysis.
PubMed: 38921929
DOI: 10.3390/nano14121052 -
Nanomaterials (Basel, Switzerland) Jun 2024With the rapid development of electronic technology and large-scale integrated circuit devices, it is very important to develop thermal management materials with high...
With the rapid development of electronic technology and large-scale integrated circuit devices, it is very important to develop thermal management materials with high thermal conductivity. Silicon carbide whisker-reinforced copper matrix (Cu/SiCw) composites are considered to be one of the best candidates for future electronic device radiators. However, at present, most of these materials are produced by high-temperature and high-pressure processes, which are expensive and prone to interfacial reactions. To explore the plating solution system suitable for SiCw and Cu composite electroplating, we tried two different Cu-based plating solutions, namely a Systek UVF 100 plating solution of the copper sulfate (CuSO) system and a Through Silicon Via (TSV) plating solution of the copper methanesulfonate (Cu(CHSO)) system. In this paper, Cu/SiCw composites were prepared by composite electrodeposition. The morphology of the coating under two different plating liquid systems was compared, and the mechanism of formation of the different morphologies was analyzed. The results show that when the concentration of SiCw in the bath is 1.2 g/L, the surface of the Cu/SiCw composite coating prepared by the CuSO bath has more whiskers with irregular distribution and the coating is very smooth, but there are pores at the junction of the whiskers and Cu. There are a large number of irregularly distributed whiskers on the surface of the Cu/SiCw composite coating prepared with the copper methanesulfonate (Cu(CHSO)) system. The surface of the composite is flat, and Cu grows along the whisker structure. The whisker and Cu form a good combination, and there is no pore in the cross-section of the coating. The observation at the cross-section also reveals some characteristics of the toughening mechanism of SiCw, including crack deflection, bridging and whisker pull-out. The existence of these mechanisms indicates that SiCw plays a toughening role in the composites. A suitable plating solution system was selected for the preparation of high-performance Cu/SiCw thermal management materials with the composite electrodeposition process.
PubMed: 38921919
DOI: 10.3390/nano14121043 -
Nanomaterials (Basel, Switzerland) Jun 2024Compared to traditional biochar (BC), nano-biochar (NBC) boasts superior physicochemical properties, promising extensive applications in agriculture, ecological...
Compared to traditional biochar (BC), nano-biochar (NBC) boasts superior physicochemical properties, promising extensive applications in agriculture, ecological environments, and beyond. Due to its strong adsorption and migration properties, NBC may carry nutrients or pollutants to deeper soil layers or even groundwater, causing serious environmental risks. Nevertheless, the migration rules and mechanisms of NBC in soil are still unclear. Therefore, this study employed soil column migration experiments to systematically explore the migration rules and mechanisms of NBC under various flow rates, initial soil water contents, soil depths, and soil textures. The results showed that regulated by smaller particle size differences and greater surface charges, NBC exhibited a stronger migration ability compared with traditional BC. As the soil texture transitioned from fine to coarse, the migration capability of NBC significantly improved, driven by both pore structure and interaction forces as described by the DLVO theory. The migration ability of NBC was also greatly boosted as the soil transitioned from saturated to unsaturated conditions, primarily because of preferential flow. When the flow rate increased from 70% KS to 100% KS and 130% KS, the migration ability of NBC also increased accordingly, as changes in injection flow rates altered the velocity distribution of pore water. NBC in 25 cm soil columns was more prone to shallow retention compared with 10 cm soil columns, resulting in weaker overall migration ability. In addition, through fitting of the two-site kinetic model and related parameters, the penetration curves of NBC under various variable conditions were effectively characterized. These findings could offer valuable insights for NBC's future efficient, rational, and sustainable utilization, facilitating the evaluation and mitigation of its potential environmental risks.
PubMed: 38921911
DOI: 10.3390/nano14121035 -
Pathogens (Basel, Switzerland) Jun 2024Thermophilic / is reported to be the first bacterial cause of gastroenteritis worldwide and the most common zoonosis in Europe. Although non-/ sp. are increasingly...
Thermophilic / is reported to be the first bacterial cause of gastroenteritis worldwide and the most common zoonosis in Europe. Although non-/ sp. are increasingly suspected to be responsible for diarrhoea or to be involved in inflammatory bowel disease, they remain poorly isolated due to their fastidious and non-thermophilic nature. Additionally, they are not targeted by commercial syndromic PCR assays. In this study, we present routine diagnostic results over 6 years (2017-2019 and 2021-2023) of sp. and related species, obtained by optimised culture from 51,065 stools by both 0.65 µm pore filtration on antibiotic-free agar, incubated in an H-enriched atmosphere at 37 °C (also known as the Cape Town protocol), and the use of selective inhibitory Butzler medium incubated at 42 °C. This allowed the isolation of 16 species, 2 species, and 2 species, providing a completely different view of the epidemiology of Campylobacterales, in which / represents only 30.0% of all isolates, while represents 44.4%. , representing only 5.5% of all Campylobacterales pre-COVID-19, represented 20.6% of all strains post-COVID-19 (218% increase; < 0.05). At the same time, the proportions of , , and decreased by 37, 53, and 28%, respectively ( < 0.05).
PubMed: 38921773
DOI: 10.3390/pathogens13060475 -
Pathogens (Basel, Switzerland) May 2024alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of and is the major virulence...
alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of and is the major virulence determinant of type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.
PubMed: 38921752
DOI: 10.3390/pathogens13060454