Search Results (3,038)

Background/Objectives: Ribosome-inactivating proteins (RIPs) are plant-derived enzymes with potent cytotoxic activity, widely studied as anticancer agents, particularly as toxic payloads in immunoconjugates. Despite numerous encouraging results reported, their clinical application has been limited by their immunogenicity. RIPs from edible plants have been proposed as potentially more suitable candidates due to their possible improved tolerability. However, this aspect still requires validation in vivo in animal models. This study investigated the cytotoxic activity, mechanisms of action and translational potential of sodin 5 (a recently characterized type 1 RIP derived from the edible plant Salsola soda L.) in human colon cancer models, comparing it to the well-known type 1 RIP saporin-S6. Methods: The effects of sodin 5 and saporin-S6 on cell viability, cell death mechanisms and epithelial barrier integrity were assessed on HT29 and Caco-2 cell lines. Sodin 5 cross-reactivity with other anti-type 1 RIP sera was evaluated by ELISA. Finally, its structural characteristics were analyzed. Results: Sodin 5 showed a cytotoxic effect comparable to that of saporin-S6 in HT29 and Caco-2 colon cancer cells, with time- and concentration-dependent reductions in viability. Both type 1 RIPs disrupted the integrity of the intestinal epithelial barrier in mono- and co-culture models and predominantly activated the apoptotic pathway, without inducing necrosis. Sodin 5 exhibited limited immunological cross-reactivity and a conserved catalytic core, supporting its potential relevance as a therapeutic payload for intestinal cancer therapy. Conclusions: Our results indicate that sodin 5 possesses promising characteristics for anticancer applications, particularly in the treatment of intestinal malignancies, where local exposure and repeated administration are often required. Full article

Psychrophilic organisms are able to grow at temperatures down to −15 °C, while hyperthermophiles can multiply at temperatures up to 122 °C. What structural changes in extremophile proteins are needed to maintain stable and biochemically active structures under such conditions? Understanding how such extremophiles accomplish this is relevant for human health, biotechnology, and our search for life elsewhere in the universe. The purpose of the current study is to report and compare the structures of four rubredoxins (Rds), the first ever two experimental psychrophile bacteria structures (from Gram-positive Clostridium psychrophilum and Gram-negative Polaromonas glacialis) and two hyperthermophiles from the Gram-negative Thermotoga maritima bacterium and the archaeon Pyrococcus yayanosii, also a piezophile, as part of a program to understand structural variations that support both stability and function under extreme conditions. These structures were obtained using synchrotron radiation X-ray diffraction at 100 K. All four structures had the expected overall rubredoxin fold. Rubredoxin from the only aerobic psychrophilic bacterium Polaromonas glacialis had larger variations in sequence and structure, whereas the other psychrophilic bacterium showed properties closely related to hyperthermophile rubredoxins. Multi-subunit structures showed similar RMSD variability independent from their thermal adaptation status. We propose including functional information in the analysis since temperature optimization may not be the only determinant for a specific protein adaptation. Full article

X-ray free-electron lasers (XFELs) have revolutionized structural biology by enabling “diffraction-before-destruction” and capturing the ultrafast dynamics of life. However, the intrinsic sparsity and noise of XFEL diffraction snapshots, often complicated by multi-lattice overlaps, create a formidable computational bottleneck that limits data utilization and structural fidelity. Here, we present MCDPS-SFX, a robust indexing framework based on a reference-based, whole-pattern matching principle integrated with parallelized iterative refinement. By exhaustively sampling orientation space and progressively rejecting outliers, MCDPS-SFX significantly outperforms legacy algorithms—more than doubling crystal yields in heterogeneous datasets (e.g., 21,807 vs. 8792 for MOSFLM)—and achieves highly competitive yields comparable to state-of-the-art indexers, such as extracting over 90,000 lattices in the lysozyme benchmark. We demonstrate its efficacy on standard benchmarks and technically demanding G-protein-coupled receptor (GPCR) systems, including the rhodopsin–arrestin complex and the glucagon receptor. MCDPS-SFX consistently produces high-quality data statistics, enabling the high-resolution visualization of functionally critical, flexible regions such as phosphorylated receptor tails. Our results provide a powerful tool for enhancing the scientific output of XFEL experiments, offering a robust alternative for maximizing information recovery from weakly diffracting or overlapping crystalline samples. Full article

Streptococcus canis is an opportunistic pathogen that colonises the mucosal surfaces and skin of its host. Though predominantly a veterinary pathogen affecting cats and dogs, S. canis has also been identified as the causative agent in severe human disease. IdeC is a secreted cysteine protease of S. canis that has a high specificity for IgG, cleaving at the hinge region. We show here that the protein binds back to the surface of the bacteria. Additionally, the protein contains a conserved Arg-Gly-Asp (RGD) motif, the minimal peptide sequence required for integrin binding. Several bacterial proteins containing RGD motifs have been implicated in adhesion and invasion of host cells. This RGD motif along with the ability of IdeC to bind back to the bacterial surface after secretion is the basis for this study into a potential secondary function of IdeC in adhesion and/or invasion. We used protein-coated latex beads to investigate the interaction of IdeC with epithelial and endothelial cells and, further, the extent to which the RGD motif is involved in this interaction by utilising an RGD->RGE recombinant protein. We also report here that the deletion of IdeC in S. canis results in a significant reduction in invasion into epithelial cells. Full article

In the era of increasing generation of various waste streams, the possibility of utilizing them as secondary resources is of utmost importance and fully corresponds to the goals of the circular economy. Industrial residues from the pulp and paper industry, such as biomass combustion ash (FARP) and sludge from industrial wastewater treatment (PPWS), together with natural zeolite as a modifying additive, represent valuable sources enabling their integrated valorization. The present study aims to investigate the potential for their reuse through the development of sustainable material blends. A comprehensive analysis of the chemical composition and morphology of the obtained mixtures was carried out using inductively coupled plasma optical emission spectroscopy (ICP-OES), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results indicate a tendency for the formation of mineral matrices dominated by calcium–sulfur–oxygen (Ca–S–O) phases, with the presence of calcium sulfate and aluminosilicate structures. The blends are associated with the formation of stable crystalline structures exhibiting potential pozzolanic activity. In this way, carbon is captured and fixed in a stable mineral form. The obtained results suggest the potential of these blends for use in low-carbon systems focused on waste valorization and carbon retention. The materials may be suitable for applications in construction, soil remediation, and environmental technologies, contributing to closing the resource loop “from farm to table and back again”. Full article

We report here a thorough study concerning the acylation reaction products of 8-hydroxyquinoline with 2-chloroacyl chloride, with new insights and clarifications in respect to the obtained products brought by NMR and X-ray studies. According to the reaction conditions we employed, three compounds could be obtained: 1-(2-chloro-2-oxoethyl)pyridin-1-ium chloride 10, 8-hydroxyquinoline hydrochloride 11, and the acylated product 8-(2-chloroacetoxy)quinolin-1-ium chloride 12. A certain influence of the catalyst and the used solvent was observed, and feasible explanations for product formations were furnished. The structure of the compounds was proved by using ¹H- and ¹³C-NMR spectra as well as single-crystal X-ray diffraction studies for compounds 12 and 11. According to X-ray crystallography, compounds 11 and 12 have a planar structure and exhibit an ionic crystal structure crystallized as a hydrochloride salt of the corresponding organic base. The crystal structures of both compounds are stabilized by intermolecular hydrogen bonds and π-π stacking interactions. In the crystals of compounds 11 and 12, the structural components are interconnected by a system of intermolecular hydrogen bonding, and a similar one-dimensional array is formed via hydrogen bonding and π-π stacking. The further assembling of the structure for 12 and 11 occurs with the formation of a three-dimensional supramolecular network. Full article

The new compound Cs₂Cu₂[V₄O₁₂]Br₂ was synthesized by the chemical vapor transport reaction method. Structural data obtained by single-crystal X-ray diffraction in the temperature range 100–700 K revealed three successive (with decreasing temperature) structural phase transitions: from the high-temperature aristotype structure I4/mmm (>550 K) to the polymorph P4/mnc (550–340 K), then to P4/m (340–300 K), and finally to the low-temperature phase I4/m (<300 K). The crystal structure of the new compound is based upon the Cu₂[V₄O₁₂]⁰ layers, consisting of four-membered rings of corner-sharing vanadate tetrahedra linked by CuO₄ squares. Analysis of the structural evolution with increasing temperature shows that the entire sequence of phase transitions is governed by the rotation of the [V₄O₁₂]⁴⁻ rings about the z axis. Full article

Graphene oxide (GO)–lipid hybrid nanostructures represent a promising class of multifunctional platforms for drug delivery and fluorescence-guided cellular imaging. In this study, we developed a graphene oxide-supported lipid bilayer system composed of rhodamine-labeled phosphatidylcholine (POPC-Rhod) for the delivery of the repurposed antispasmodic drug alverine citrate (ALV) to neuroblastoma cells. The hybrid nanostructures were assembled using two drug-loading strategies and characterized by UV–Vis spectroscopy, fluorescence analysis, dynamic light scattering, and atomic force microscopy to evaluate molecular interactions, vesicle size distribution, and nanomechanical properties. In vitro studies were performed using human neuroblastoma SH-SY5Y cells and their retinoic acid-differentiated neuronal-like counterparts. Confocal microscopy confirmed efficient cellular uptake of the fluorescent lipid–graphene hybrids, while viability and mitochondrial reactive oxygen species assays revealed differentiation-dependent cellular responses. ALV-loaded hybrids induced cytotoxic effects in proliferating neuroblastoma cells, whereas differentiated neuron-like cells exhibited greater tolerance and, at moderate concentrations, preserved viability despite increased oxidative stress. These findings demonstrate that graphene oxide–lipid hybrids can act as fluorescence-traceable drug delivery platforms and highlight the potential of alverine as a candidate for repurposing in neural cancer models. The system presented here provides a proof-of-concept framework for the development of multifunctional nanocarriers integrating therapeutic delivery with imaging capabilities. Full article

Membrane technology is a highly efficient, cost-effective, and chemical-free process, leading to its widespread application across various fields. However, the high capital cost of traditional ceramic benchmarks remains a barrier. This study addresses this challenge by engineering a low-cost, waste-derived geopolymeric membrane functionalized with a silver molybdate (Ag₂MoO₄) catalytic coating for the removal of trimethoprim (TMP), a persistent emerging contaminant. Systematic filtration assays for the removal of TMP (100 mg·L⁻¹, pH 4) revealed the role of the Ag₂MoO₄ layer as a performance intensifier, yielding a 26% increase in initial permeate flux and a 33% improvement in the selectivity compared to the pristine support, while maintaining robust rejection efficiency. Comprehensive characterization attributes these enhancements to synergistic effects between increased surface hydrophilicity and favorable solute–catalyst interfacial interactions. Furthermore, a fouling analysis using Hermia’s models indicated the simultaneous operation of multiple blocking mechanisms, a phenomenon linked to the non-uniform nature of the coating and subsequent formation of preferential flow paths. Overall, the incorporation of the silver molybdate coating effectively improved the membrane’s flux performance and selectivity. These findings demonstrate that integrating catalytic coatings onto waste-based geopolymer frameworks provides a scalable, circular-economy-aligned strategy for advanced wastewater treatment, balancing high-flux performance with the efficient removal of recalcitrant pharmaceuticals. Full article

Basic zinc sulfate with an empirical formula of ZnSO₄∙3 Zn(OH)₂∙3.5 H₂O (or Zn₄SO₄(OH)₆∙3.5 H₂O) was precipitated using stoichiometric amounts of ZnSO₄ and NaOH, followed by drying and storage in air. The XRD pattern suggests that the product contains tri- and tetrahydrate of basic zinc sulfate. Penta-, mono-, and hemihydrates of basic zinc sulfate can be produced by storing the original material in air at various temperatures and humidity levels, and especially by immersion in aqueous solutions. The precipitate was characterized by its specific surface area and zeta potential, and it has an isoelectric point (IEP) at pH 8.9. Ion exchange with an excess of CuSO₄ results in conversion to brochantite Cu₄(OH)₆SO₄ (as detected by XRD) and in an increase in the specific surface area. The conversion was complete at room temperature with a sufficient excess of CuSO₄, but it was not complete at 50 or 60 °C. Apparently, the conversion into brochantite is exothermic. The IEP of brochantites obtained from ZnSO₄∙3 Zn(OH)₂∙3.5 H₂O by ion exchange was at a pH of about 10, which is higher than the previously reported IEP. Full article

Background: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD). Proteomic studies suggest that Lp(a)-associated proteins mediate inflammation, thrombosis, and vascular calcification, but methodological variability may influence proteome definition. Methods: Lp(a) was immunoprecipitated from human plasma using an apo(a)-specific monoclonal antibody and analyzed by mass spectrometry following either in-gel digestion or automated in-solution proteolysis. Proteins identified by ≥3 unique peptides and consistently detected across all samples by both methods were considered high confidence. Functional enrichment and interaction networks were assessed using STRING. Results: In-solution proteolysis identified 92 proteins and in-gel digestion identified 55 proteins, with 34 proteins shared between methods. These high-confidence proteins were enriched for pathways involved in lipoprotein remodeling, coagulation regulation, vesicle-mediated transport, lipid binding, and extracellular matrix organization, providing biological insight into mechanisms linking Lp(a) to inflammation, thrombosis, and calcification. Conclusions: Proteome composition of Lp(a) is method-dependent; however, a rigorously defined core proteome of 34 proteins was consistently identified across analytical approaches, highlighting biologically relevant pathways that may underlie Lp(a)-mediated ASCVD risk. Full article

The structural characterization of GG-rich DNA sequences in presence of metal ions provides essential insight into quadruplex stability and ion-dependent conformational specifics. We report the crystal structure of the GG-quadruplex formed by the sequence GGGGTTTTGGGG in the presence of Zn²⁺, K⁺, and Na⁺. It was deposited in the RCSB Protein Data Bank under the accession code 9FTA. The structure was determined by single-crystal X-ray diffraction at a resolution of 2.49 Å in the space group P2₁2₁2₁. It reveals a parallel-stranded, two-G-tetrad stabilized by K⁺ ions within the central channel, while Na⁺ and Zn²⁺ occupy peripheral and groove-associated sites. Zn²⁺ ions are engaged in noncanonical coordination interactions with phosphate oxygens and structured water molecules, contributing to lattice stabilization and subtle adjustments in groove dimensions. The T4 loop forms a compact, ordered motif that contributes to crystal packing rather than intramolecular G4 stabilization. The presence of mixed cations produces a sole lattice architecture mediated by ions that provides structural insight into how bivalent and monovalent metals mutually modulate G-quadruplex topology. These results suggest a basis for understanding the specific ion effects on G4 structures and may direct the design of metal open DNA architectures. Full article

The recent endeavor to establish a sustainable society, with respect to environmental protection and occupational health prevention, imposes the need for the development of environmentally friendly anodization electrolytes. In addition, these electrolytes should be composed of biocompatible organic acids derived from renewable sources. In response to these challenges, a need arises to seek environmentally conscious alternatives to the widely used sulfuric acid anodization electrolytes. Accordingly, a comparative study was performed on the anodic polarization of AA2024-T3 aircraft alloy samples for 30 min at 0 or 20 °C. The respective electrolytes were composed of 0.5 M solutions of oxalic, citric, tartaric acids, or glycine. The comparative analysis included optical metallographic microscopy (OMM), scanning electron microscopy (SEM), determination of color characteristics and wettability, chemical composition analysis by X-ray photoelectron spectroscopy (XPS), and assessment of the corrosion protective properties of the obtained layers. The latter were defined by the application of electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization scanning (PDS) after 24 h of exposure to a 0.5% NaCl solution. Among the most important conclusions is that the barrier properties of the layers obtained in citric and tartaric acid electrolytes remarkably exceed those of the film obtained in oxalic acid. The use of glycine does not result in film formation at all. The process temperature did not have as strong an effect as the electrolyte composition. Full article

Five previously undescribed steroids, chrysogenones A–E (1–5), were isolated from the deep-sea-derived Penicillium sp. MCCC 3A00121. Their chemical structures were unambiguously established through comprehensive spectroscopic analyses, density functional theory (DFT)-based electronic circular dichroism (ECD) calculations, and X-ray crystallography. Chrysogenones represent a class of oxidatively modified ergosterone-type derivatives, with 1, 2, and 5 featuring an uncommon malonyl substitution at C-12 of the ergosterone skeleton. Biologically, 1–5 exhibited varying degrees of inhibitory activity against renal fibrosis, as evidenced by the downregulation of the key fibrotic markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1). Among them, chrysogenone B (2) emerged as the most promising candidate, demonstrating superior potency and pronounced inhibition of activated NRK-49F cell proliferation. Integrated network pharmacology analysis and molecular docking studies further suggested that the anti-renal fibrotic effects of compound 2 may be mediated through its interaction with putative molecular targets, including AKT1, HSP90AA1, and MDM2. Full article