Search Results (33)

Patients presenting with conditions attributed to environmental exposures face complex, multi-toxicant burdens, yet the stability of multivariate toxicant patterns under demographic adjustment remains poorly evaluated. This study assessed the sensitivity of principal component analysis (PCA) structures to demographic confounding and variable composition in 551 patients (aged <1–86 years) with environmentally related conditions. Nine urinary biomarkers were analysed using PCA with Varimax and Promax rotation on both raw data and residuals adjusted for age and sex. Among the identified patterns, the solvent/industrial cluster (xylene and styrene metabolites) was the most stable, persisting across both raw and residual analyses regardless of rotation method. However, overall component structures were sensitive to preprocessing: the clustering pattern of the herbicide 2,4-dichlorophenoxyacetic acid shifted markedly after demographic adjustment, illustrating indirect confounding whereby demographic effects on co-variables altered apparent biomarker associations. Notably, inclusion of an endogenous mitochondrial marker (tiglylglycine) alongside exogenous toxicant biomarkers produced Heywood cases (loadings > 1), violating factor analysis assumptions and indicating that mixing exposure and response variables destabilises the model. Cumulative variance explained was modest, consistent with the weak inter-biomarker correlations observed (KMO ≈ 0.52). These findings do not support the identification of robust, demographically stable clustering patterns in this cohort. Instead, they demonstrate that PCA-derived structures in heterogeneous clinical data are vulnerable to demographic confounding, variable selection and marker type, and caution against interpreting transient clustering patterns as definitive exposure signatures without rigorous validation. It should be noted that the absence of a non-clinical matched control group means that whether the identified co-exposure signatures are distinctive to symptomatic patients or reflective of general population exposure patterns cannot be determined; future studies should incorporate matched controls to address this directly. Full article

Since the synthesis of ferrocene in 1951, metallocenes have attracted attention, making the accurate prediction of their electronic structure and ionization energy crucial for understanding their photophysical and electrochemical behavior in materials and in biological systems. Here, we combined Density Functional Theory (DFT), Complete Active Space Self-Consistent Field (CASSCF), NEVPT2 (N-Electron Valence State Perturbation Theory) and Coupled Cluster approaches (CCSD, DLPNO-CCSD(T)) to study the electronic structure, ionization energies (IEs) and absorption spectra of metallocene and metallocenium complexes in the gas phase and in THF implicit solvent. DFT IEs agree closely with NEVPT2 and DLPNO-CCSD(T) values and with experiment values (deviations 0.02–0.3 eV). For CASSCF and NEVPT2, the minimal active space of the d electrons at six orbitals is not enough for the accurate prediction of the IEs, while an extended active space incorporating all 3d metal electrons plus four ligand valence electrons into 15 orbitals improves the calculated IE values. In solution, computed oxidation energies (OEs) in THF reproduce experimental values and follow the Fe > Ni > Co ordering. Substitution of metallocene complexes with chromophore units results in similar OEs. Overall, the substitution effects remain modest: the effect of substitution on OE values results in differences up to 0.2 eV. These results clarify the effect of the metal center on IE and OE values and UV–vis absorption behavior. Full article

Understanding Li⁺ solvation structure is critical for the rational design of high- and localized high-concentration electrolytes. Here, we present a systematic investigation of tetrahydrofuran (THF)-based electrolytes with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) using Raman spectroscopy and ⁷Li nuclear magnetic resonance to investigate the local solvation structures. By varying the THF:LiTFSI molar ratio, we observed a transition of Li⁺ solvation from solvent-separated ion pairs to contact ion pairs and aggregates, accompanied by increased structural heterogeneity and constrained local dynamics. Raman spectroscopy captures the evolution of Li⁺–anion coordination with increasing salt concentration, while ⁷Li NMR chemical shifts, line widths, and relaxation times provide complementary insight into changes in the electronic environment and symmetry of Li⁺ coordination. Electrolyte structure is further examined by introducing a hydrofluoroether co-solvent into a concentrated (THF)₂–LiTFSI electrolyte. Raman results show that the local Li⁺–TFSI⁻ coordination structure is preserved upon 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) addition, whereas NMR reveals subtle modifications of the ion-rich solvation clusters. These results provide fundamental insight into Li⁺ solvation and electrolyte localization, offering general design principles for advanced electrolyte systems. Full article

The highly chitinolytic marine bacterium Vibrio jasicida KMM 6832, which exhibits potent antifungal activity, possesses an atypical Glycosyl Hydrolase family 19 (GH19) chitinase (ChitVjs). This is the first report of a GH19 gene in V. jasicida, an enzyme generally absent in this species and rare within the Harveyi clade. Phylogenetically, ChitVjs-like enzymes from the genera Vibrio and Aeromonas form a distinct cluster, separate from typical plant and bacterial GH19 counterparts. Despite high sequence identity (80–94%) with characterized homologs from V. parahaemolyticus and V. cholerae, ChitVjs is distinguished by its obligate halophilicity (optimum 0.3–0.4 M NaCl), an acidic isoelectric point (pI 4.72), and a broader cation-activation profile (K⁺, Ni²⁺, Ca²⁺, Cu²⁺, Co²⁺). The recombinant ChitVjs was produced in E. coli as a soluble 63 kDa protein. It functions as a stable, salt-dependent endo-chitinase/chitosanase, exhibiting optimal activity at 40 °C and pH 7.0. The enzyme displays high affinity for colloidal chitin (K_M 0.377 mg·mL⁻¹), is activated by DTT and Tween 80, and shows moderate stability in organic solvents. Furthermore, unlike its primarily catabolic relatives, ChitVjs suppresses conidial germination in marine-derived Aspergillus strains. These findings suggest that ChitVjs significantly contributes to the competitive fitness of V. jasicida KMM 6832 in high-salinity marine environments through both nutrient acquisition and antagonism. Full article

Background: Rheumatoid arthritis (RA) is a systemic, pro-inflammatory, autoimmune disease that mainly affects the joints in a symmetrical manner. Differential proteomic profiling through Sequential Window Acquisition of all Theoretical Fragment Ion Mass Spectra (SWATH-MS/MS) helps in a better understanding of the RA pathogenesis. In this study, we compared the differentially upregulated proteins with those associated with fibrosis to gain a deeper understanding of the fibrotic aspect of RA. Methods: We analyzed plasma proteomics data, previously obtained by SWATH-MS/MS. Our focus was on proteins associated with Leucine Rich Alpha2glycoprotein1 (LRG1) and we employed an in silico method. Results: We identified common proteins between RA and fibrosis. Among them, LRG1 and Serine Protease Inhibitor Clade A, Member 1 (SERPINA1) showed a high co-expression score in the gene clusters. LRG1 is both pro-inflammatory and pro-fibrotic, while SERPINA1 is an anti-inflammatory protein that inhibits pro-inflammatory and pro-fibrotic molecules (Elastase). Further, docking studies and a simulation study of the docked complexes with the analysis of Hydrogen bonds, Solvent Accessible Surface Area (SASA), Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of gyration (Rg), suggested a strong interaction between the two partners, LRG1 and SERPINA1. Conclusions: Our study suggests that LRG1 may inhibit SERPINA1 and promote inflammation and fibrotic processes by disrupting SERPINA1’s primary function. Full article

Background/Objectives: Understanding the stabilization mechanisms of amino acid conformations in different solvent environments is crucial for elucidating biomolecular interactions and crystallization processes. This study presents a comprehensive computational investigation of glycine, the simplest amino acid, in both its canonical and zwitterionic forms when interacting with dimethyl sulfoxide (DMSO) molecules. Methods: Using density functional theory (DFT) calculations at the B3LYP/6-311++G(d,p) level with empirical dispersion corrections, we examined the conformational landscape of glycine–DMSO clusters with one and two DMSO molecules, as well as implicit solvent calculations, and compared them with analogous water clusters. Results: Our results demonstrate that while a single water molecule is insufficient to stabilize the zwitterionic form of glycine, one DMSO molecule successfully stabilizes this form through specific interactions between the S=O and the methyl groups of DMSO and the NH₃⁺ and the oxoanion group of zwitterionic glycine, respectively. Topological analysis of the electron density using QTAIM and NCI methods reveals the nature of these interactions. When comparing the relative stability between canonical and zwitterionic forms, we found that two DMSO molecules significantly reduce the energy gap to approximately 12 kJ mol⁻¹, suggesting that increasing DMSO coordination could potentially invert this stability. Implicit solvent calculations indicate that in pure DMSO medium, the zwitterionic form becomes more stable below 150 K, while remaining less stable at room temperature, contrasting with aqueous environments where the zwitterionic form predominates. Conclusions: These findings provide valuable insights into DMSO’s unique role in biomolecular stabilization and have implications for protein crystallization protocols where DMSO is commonly used as a co-solvent. Full article

This study evaluated the acute and developmental toxicity of selected hydrotropes, co-solvents, and surfactants commonly used in pharmaceutical and cosmetic formulations, using Artemia salina as a model organism. Two bioassays were employed: a lethality test and a hatching inhibition test. Compounds such as sodium lauryl sulfate (LC₅₀ < 0.05%), sodium xylenesulfonate (LC₅₀ = 0.79%), sodium p-toluensulfonate (LC₅₀ = 0.21%), N,N-dimethylbenzamide (LC₅₀ < 0.05%), and N,N-diethylnicotinamide (LC₅₀ = 0.05%) exhibited high toxicity at 48 h, inducing significant mortality and strong inhibition of hatching. Glycerin, propylene glycol, and dimethyl sulfoxide showed low toxicity across all concentrations. Lethal concentration values confirmed the high toxicity of sodium xylenesulfonate and N,N-dimethylbenzamide, with moderate effects observed for other compounds. The hatching inhibition test proved more sensitive than the lethality test, enabling the detection of embryotoxicity and developmental delays. Although more laborious, it provided detailed information into how the tested substances influenced developmental stage progression. Hierarchical clustering analysis grouped the substances based on toxicity patterns and clearly discriminated highly toxic surfactants from low-toxicity solvents. The results demonstrated that combining both bioassays offers a more comprehensive evaluation of toxicity, with the hatching test being particularly useful for identifying early developmental effects not evident in lethality testing alone. Full article

Nickel oxide (NiO) is one of the most popular hydrogenation catalysts. In heterogeneous catalysis, nickel oxide is used, for example, as a suitable methanation catalyst in the Fischer–Tropsch reaction not only for CO hydrogenation but also in the modified Fischer–Tropsch reaction with CO₂. However, CH₄ selectivity and CO₂ conversion strongly depend on NiO micro- (MPs) and nanoparticles’ (NPs) shape, size, and surface area. In this study, the synthesis of NiO micro- and nanoparticles was conducted using the simple solvothermal method. Different morphologies (microspheres, sheet clusters, hexagonal microparticles, and nanodiscs) were prepared using this method with different solvents and stabilizers. The prepared catalysts were tested in the hydrogenation of CO₂ in a gas phase with excellent conversion values and high selectivity to produce CH₄. The best results were obtained with the NiO with disc or sphere morphology, which produced methane with selectivity at a level near 100% and conversion close to 90%. 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

Incorporating two organic ligands with different functionalities into a titanium-oxo cluster entity simultaneously can endow the material with their respective properties and provide synergistic performance enhancement, which is of great significance for enriching the structure and properties of titanium-oxo clusters (TOCs). However, the synthesis of such TOCs is highly challenging. In this work, we successfully synthesized a TBC4A-functionalized TOC, [Ti₂(TBC4A)₂(MeO)₂] (Ti2; MeOH = methanol, TBC4A = tert-butylcalix[4]arene). By adjusting the solvent system, we successfully introduced 1,10-phenanthroline (Phen) and prepared TBC4A and Phen co-protected [Ti₂(TBC4A)₂(Phen)₂] (Ti2-Phen). Moreover, when Phen was replaced with bulky 4,7-diphenyl-1,10-phenanthroline (Bphen), [Ti₂(TBC4A)₂(Bphen)₂] (Ti2-Bphen), which is isostructural with Ti2-Phen, was obtained, demonstrating the generality of the synthetic method. Remarkably, Ti2-Phen demonstrates good stability and stronger light absorption, as well as superior photoelectric performance compared to Ti2. Density functional theory (DFT) calculations reveal that there exists ligand-to-core charge transfer (LCCT) in Ti2, while an unusual ligand-to-ligand charge transfer (LLCT) is present in Ti2-Phen, accompanied by partial LCCT. Therefore, the superior light absorption and photoelectric properties of Ti2-Phen are attributed to the existence of the unusual LLCT phenomenon. This study not only deeply explores the influence of Phen on the performance of the material but also provides a reference for the preparation of materials with excellent photoelectric performance. Full article

The organization of modifiable and functional building components into various superstructures is of great interest due to their broad applications. Supramolecular self-assembly, based on rationally designed building blocks and appropriately utilized driving forces, is a promising and widely used strategy for constructing superstructures with well-defined nanostructures and diverse morphologies across multiple length scales. In this study, two homogeneous organohydrogels with distinct appearances were constructed by simply mixing polyoxometalate (phosphomolybdic acid, HPMo) and a double-tailed zwitterionic quaternary ammonium amphiphile in a binary solvent of water and dimethyl sulfoxide (DMSO). The delicate balance between electrostatic attraction and repulsion of anionic HPMo clusters and zwitterionic structures drove them to co-assemble into homogeneous organohydrogels with diverse microstructures. Notably, the morphologies of the organohydrogels, including unilamellar vesicles, onion-like vesicles, and spherical aggregates, can be controlled by adjusting the ionic interactions between the zwitterionic amphiphiles and phosphomolybdic acid clusters. Furthermore, we observed an organohydrogel fabricated with densely stacked onion-like structures (multilamellar vesicles) consisting of more than a dozen layers at certain proportions. Additionally, the relationships between the self-assembled architectures and the intermolecular interactions among the polyoxometalate, zwitterionic amphiphile, and solvent molecules were elucidated. This study offers valuable insights into the mechanisms of polyoxometalate-zwitterionic amphiphile co-assembly, which are essential for the development of materials with specific structures and emerging functionalities. Full article

In this study, both practical and theoretical aspects of the solubility of edaravone (EDA) in Deep Eutectic Solvents (DESs) were considered. The solubility of edaravone in some media, including water, can be limited, which creates the need for new efficient and environmentally safe solvents. The solubility of EDA was measured spectrophotometrically and the complex intermolecular interactions within the systems were studied with the COSMO-RS framework. Of the four studied DES systems, three outperformed the most efficient classical organic solvent, namely dichloromethane, with the DES comprising choline chloride and triethylene glycol, acting as hydrogen bond donor (HBD), in a 1:2 molar proportion yielding the highest solubility of EDA. Interestingly, the addition of a specific amount of water further increased EDA solubility. Theoretical analysis revealed that in pure water or solutions with high water content, EDA stacking is responsible for self-aggregation and lower solubility. On the other hand, the presence of HBDs leads to the formation of intermolecular clusters with EDA, reducing self-aggregation. However, in the presence of a stoichiometric amount of water, a three-molecular EDA–HBD–water complex is formed, which explains why water can also act as a co-solvent. The high probability of formation of this type of complexes is related to the high affinity of the components, which exceeds all other possible complexes. Full article

In this report, the catalytic potential of chalcogen-stabilized iron carbonyl clusters [Fe₃E₂(CO)₉ (E = S, Se, Te)] for the photolytic hydration of alkynes has been explored. The iron chalcogenide clusters bring excellent transformations of terminal and internal alkynes to their respective keto products in just 25 min photolysis at −5 °C in inert free and aqueous conditions. After the completion of the reaction, the product can be extracted from organic solvent, and due to the lower solubility of the catalyst in water, it can also be isolated and further reused several times prior to any activation. The catalyst was also found to be active in thermal conditions and bring about the desired transformations with average to good catalytic efficiency. Moreover, during the thermal reaction, the catalyst decomposed and formed the nanoparticles of iron selenides, which worked as a single-source precursor for FeSe nanomaterials. The presented photolysis methodology was found to be most feasible, economical, instantly produce the desired product, and work for a wide range of internal and terminal alkynes; hence, all these features made this method superior to the other reported ones. This report also serves as the first catalytic report of chalcogen-stabilized iron carbonyl clusters for alkyne hydrations. Full article

Ion–molecule reactions between neutral methyl formate (MF) and proton-bound solvent clusters W₂H⁺, W₃H⁺, M₂H⁺, E₂H⁺, and E₃H⁺ (W = water, M = methanol, and E = ethanol) showed that the major reaction product is a solvent molecule loss from the initial encounter complex, followed by the formation of protonated methyl formate (MFH⁺). Collision-induced dissociation breakdown curves of the initially formed solvent-MF proton-bound pairs and trimers were obtained as a function of collision energy and modeled to extract relative activation energies for the observed channels. Density functional theory calculations (B3LYP/6-311+G(d,p)) of the solvent loss reaction were consistent with barrierless reactions in each case. The MF(M)H⁺ ion also exhibited loss of CH₄ at higher collision energies. The reaction was calculated to proceed via the migration of the MF methyl group to form a loosely bound complex between neutral CH₄ and an ion comprising (CH₃OH)(CO₂)H⁺. Overall, the results indicate that the interaction of methyl formate with atmospheric water can form stable encounter complexes that will dissociate to form protonated methyl formate. Full article

Thermo-responsive (TR) gels of the LCST (lower critical solution temperature) type swell in water at temperatures below their volume phase transition temperature $T_{\mathrm{c}}$ and collapse above the critical temperature. When water is partially replaced with an organic liquid, these materials demonstrate three different types of equilibrium solvent uptake diagrams at temperatures below, above, in the close vicinity of $T_{\mathrm{c}}$. A model is developed for equilibrium swelling of TR gels in binary mixtures of solvents. It takes into account three types of phase transitions in TR gels driven by (i) aggregation of hydrophobic side groups into clusters from which solvent molecules are expelled, (ii) replacement of water with cosolvent molecules in cage-like structures surrounding these groups, and (iii) replacement of water with cosolvent as the main element of hydration shells around backbone chains. The model involves a relatively small number of material constants that are found by matching observations on covalently cross-linked poly(N-isopropylacrylamide) macroscopic gels and microgels. Good agreement is demonstrated between the experimental data and results of numerical analysis. Classification is provided of the phase transition points on equilibrium swelling diagrams. Full article