Search Results (41)

Mono- and bis-guanyl hydrazone-functionalized tricyclic compounds were here designed and investigated as putative G-quadruplex ligands in the context of anticancer drug development. The G-quadruplex on Controlled Pore Glass (G4-CPG) assay, a fast and easy screening method based on affinity chromatography for identifying potential G-quadruplex binders, together with biophysical techniques such as circular dichroism and fluorescence spectroscopy, demonstrated a higher selectivity of mono- with respect to disubstituted derivatives in recognizing G-quadruplexes from telomeric and oncogenic DNA regions vs. duplexes. Among the mono-substituted compounds, higher G-quadruplex selectivity was found for those containing the pyrido [3,4-b]indole and dibenzofuran scaffolds compared to the 9H-fluorene, 9H-carbazole, and dibenzothiophene ones. Molecular docking studies suggested that the investigated ligands bound the hybrid telomeric G-quadruplex model by adopting a coplanar arrangement of the core and guanyl hydrazone moieties, both stacked on the 5′-G-quartet, while in the interaction with the parallel oncogenic G-quadruplex model the guanyl hydrazone moieties pointed towards the grooves/loops. Finally, biological assays highlighted the higher potential of mono-guanyl hydrazone-derivatized tricyclic compounds as selective anticancer agents, showing higher anticancer activity and selectivity of action than the bis-guanyl hydrazone derivatives. Full article

G-quadruplexes are guanine-rich DNA or RNA structures comprising two or more stacked guanine tetrads (G-quartet) with nucleobases in the loops linking the G-quartets. The thermal stability of the thrombin-binding aptamer G2 d(G₂T₂G₂TGTG₂T₂G₂) G-quadruplex was quantified using m-values in aqueous glycine betaine (GB), proline, TMAO, and urea solutions using UV-absorbance spectroscopy. The thermal stability of the G2 variants was also explored with nucleobase substitutions in the TGT loop (TAT, TCT, TTT, UGU, and UUU), in the T₂ loops (T₄, U₂), or in both loops (UGU and U₂, UUU and U₂). GB and TMAO strongly stabilized G2 and its variants. Urea weakly destabilized G2 and its variants, while proline acted as a weak stabilizer or destabilizer depending on G2 variant nucleobase sequence. Both the unfolding enthalpy and entropy were positively correlated with cosolute molality for all cosolute and G-quadruplex combinations. Analysis of the change in solvent-accessible surface area (ΔASA) after unfolding G2 suggested the stability of G2 and its variants in aqueous cosolute solutions was driven by favorable interaction of cosolutes with G-quartet ΔASA and net-favorable or unfavorable interactions with the loop ΔASA. Our results reinforce a general mechanism of folded DNA and RNA stability modulation in cosolute solutions. Full article

Small bioactive molecules show significant propensity to form noncovalent addition complexes with guanine quadruplexes, G4. The stabilization energies of these complexes have been computed precisely at the sufficiently high 6-31G** basis set level of density functional quantum chemical theory, DFT. A decisive factor in present model computations is the adopted size of G4 models, whether these consist simply of stacked quanine quartets, or also involve (deoxy)ribose-phosphate fragments of proper nucleic acids. The challenge is in the preservation of physico-chemical accuracy of DFT computations with increasing sizes of models, involving upwards of 120 atoms for the simplest two-layer G4, plus at least 60 pentose-phosphate linker atoms per each pair of guanine quartets. Bioactive ligand sizes add to the requirements for further rigorous analyses of the roles of G4 complexes in biological processes, which thus remain necessarily open-ended. Full article

As pore space serves as the primary migration pathway of radon in rock media, investigating the influences of pore structural characteristics on radon migration is essential. In this study, the rock pore structure was numerically reconstructed via the Quartet Structure Generation Set (QSGS) method, based on the characteristic parameters extracted from real rock pore models obtained from CT scanning. Quantitative comparison results indicate that the permeability and radon diffusion coefficient of the QSGS-reconstructed models are highly consistent with those of the CT-based model, which verifies the reliability and effectiveness of the QSGS method. A series of three-dimensional (3D) rock pore models with different porosities (η), distribution probabilities (Pd), and growth probabilities (G) were constructed using the QSGS method. The radon diffusion coefficient, tortuosity factor and permeability of these models under dry conditions were quantitatively determined. The relationship between the radon diffusion coefficient, water saturation and temperature was obtained using the tortuosity factor of the pore models and the unsaturated non-isothermal radon diffusion coefficient model. Furthermore, the relationship between the relative permeability of the air and water phases and water saturation was obtained by coupling the calculated permeability with the Brooks–Corey model. The results demonstrate that the η was positively correlated with both the radon diffusion coefficient and permeability, with a more pronounced positive correlation observed for permeability. Under low η conditions, Pd was positively correlated with both the radon diffusion coefficient and permeability; under medium-porosity conditions, Pd was positively correlated with the radon diffusion coefficient but negatively correlated with permeability; under high-porosity conditions, Pd exhibited no significant correlation with the radon diffusion coefficient, while it shows a negative correlation with permeability. G in the principal direction was positively correlated with the radon diffusion coefficient and permeability along the same direction, but negatively correlated with those along orthogonal directions. The radon diffusion coefficient was strongly negatively correlated with water saturation, and weakly positively correlated with temperature. With an increase in water saturation, the relative air permeability presented a nonlinear decrease characterized by a fast-then-slow trend, whereas the relative water permeability showed a nonlinear increase with a slow-then-fast pattern. Full article

The prebiological anomeric selectivity of ribonucleosides is a key phenomenon in the understanding of the RNA world hypothesis and the origin of life. While each ribonucleoside can have two anomers (α or β), ribonucleosides naturally occur in the β form, while α anomers are extremely rare. Guanosine, a canonical ribonucleoside, binds to borate and self-assembles into G4-quartets, enabling the formation of borate–guanosine hydrogels. These macrostructures, exhibiting elevated thermal robustness and self-healing properties, have been suggested as plausible frameworks for the syntheses of prebiological molecules. Moreover, their external layers could have prevented degradation of compounds by aggressive primitive radiation and reduced molecular dispersion. Herein it is proposed that anomeric selectivity may have occurred due to the different 3D organization and stereochemical environment formed by each borate–guanosine anomer and subsequent formation of borate–guanosine hydrogels. DFT was applied to the optimization of α and β anomeric structures in four steps, from borate–guanosine diesters to G4 structures. The results obtained suggest that β-syn-guanosine (the most stable structure) is the only anomer that forms a planar G4-quartet with borate, capable of self-assembling into a hydrogel. Given the properties of borate–guanosine hydrogels, this could explain why β-guanosine is currently the sole anomer present in living organisms. Full article

The increasing sophistication of cyberattacks makes Intrusion Detection Systems (IDSs) essential, yet the high dimensionality of modern network traffic hinders accuracy and efficiency. We conduct a comparative study of multi-objective feature selection for IDS using four bio-inspired metaheuristics—Grey Wolf Optimizer (GWO), Genetic Algorithm (GA), Particle Swarm Optimization (PSO), and Ant Colony Optimization (ACO)—on the X-IIoTID dataset. GA achieved the highest accuracy (99.60%) with the lowest FPR (0.39%) using 34 features. GWO offered the best accuracy–subset balance, reaching 99.50% accuracy with 22 features (65.08% reduction) within 0.10 percentage points of GA while using ~35% fewer features. PSO delivered competitive performance with 99.58% accuracy, 32 features (49.21% reduction), FPR 0.40%, and FNR 0.44%. ACO was the fastest (total training time 3001 s) and produced the smallest subset (7 features; 88.89% reduction), at an accuracy of 97.65% (FPR 2.30%, FNR 2.40%). These results delineate clear trade-off regions of high accuracy (GA/PSO/GWO), balanced (GWO), and efficiency-oriented (ACO) and underscore that algorithm choice should align with deployment constraints (e.g., edge vs. enterprise vs. cloud). We selected this quartet because it spans distinct search paradigms (hierarchical hunting, evolutionary recombination, social swarming, pheromone-guided foraging) commonly used in IDS feature selection, aiming for a representative, reproducible comparison rather than exhaustiveness; extending to additional bio-inspired and hybrid methods is left for future work. Full article

Cascading link failures continue to imperil power grids, transport networks, and cyber-physical systems, yet the relationship between a network’s robustness at the moment of attack and its subsequent resiliency remains poorly understood. We introduce a dynamic framework in which connectivity-based cascades and distributed self-healing act concurrently within each time-step. Failure is triggered when a node’s active-neighbor ratio falls below a threshold $\phi$; healing activates once the global fraction of inactive nodes exceeds trigger $T$ and is limited by budget $B$. Two real data sets—a 332-node U.S. airport graph and a 1133-node university e-mail graph—serve as testbeds. For each graph we sweep the parameter quartet ($\phi ,\hspace{0.17em}B,\hspace{0.17em}T,attackmode$) and record (i) immediate robustness $R$, (ii) 90% recovery time T₉₀, and (iii) cumulative average damage. Results show that targeted hub removal is up to three times more damaging than random failure, but that prompt healing with $B\ge 0.12$ can halve T₉₀. Scatter-plot analysis reveals a non-monotonic correlation: high-$R$ states recover quickly only when $B$ and $T$ are favorable, whereas low-$R$ states can rebound rapidly under ample budgets. A multiplicative fit $T_{90}\propto B^{-\beta }g\left(T\right)h\left(R\right)$ (with $\beta \approx 1$) captures these interactions. The findings demonstrate that structural hardening alone cannot guarantee fast recovery; resource-aware, early-triggered self-healing is the decisive factor. The proposed model and data-driven insights provide a quantitative basis for designing infrastructure that is both robust to failure and resilient in restoration. Full article

Layered intercalating V₂O₅ (vanadium pentoxide) is a durable battery-type electrode material exploited in supercapacitors. The advancement of V₂O₅ nanomaterials synthesized from non-aqueous organic solvents holds significant potential for energy storage applications. Liquid-phase synthesis of orthorhombic V₂O₅ cathode material corroborated its compatibility with quartet glycols and allowed examination of their explicit roles in faradic charge storage efficacy. V₂O₅ was found to be an intercalative material in all the quartet glycols. The crystalline, rod-like morphology and monodisperse V₂O₅ electrode were ascribed to the effects of ethylene, diethylene, triethylene, and tetraethylene glycols. Notable differences were observed in the electrochemical analysis of the prepared V₂O₅ (EV, DV, TV, and TTV). In a three-electrode cell setup, the DV electrode demonstrated a superior specific capacity of 460.2 C/g at a current density of 1 A/g. From the Trasatti analysis, the DV electrode exhibited 961.53 C/g of total capacitance, comprising a diffusion-controlled contribution of 898.19 C/g and a surface-controlled contribution of 63.34 C/g. The aqueous asymmetric device DV//AC exhibited a maximum energy density of 65.72 Wh/kg at a power density of 1199.97 W/kg. The glycol-derived electrodes were anticipated to bepromising materials for supercapacitors and have the potential to meet electrochemical energy needs. Full article

G-quadruplex (G4) DNAzymes with peroxidase activities hold potential for applications in biosensing. While these nanozymes are easy to assemble, they are not as efficient as natural peroxidase enzymes. Several approaches are being used to better understand the structural basis of their reaction mechanisms, with a view to designing constructs with improved catalytic activities. Spermine alters the structures and enhances the activities of some G4 DNAzymes. The reported effect of spermine in shifting the conformation of some G4 DNAzymes from antiparallel to parallel has not been tested on multimeric G4 DNAzymes. In this study, we examined the effects of spermine on the catalytic activities of multivalent constructs of Bcl2, c-MYC, PS2.M, and PS5.M. Our findings show that spermine significantly improved the peroxidase activity of PS2.M, an antiparallel G4 DNAzyme, while there was no significant effect on c-MYC, which already exists in a parallel conformation. The addition of spermine led to a substantial increase in the initial velocity of PS2.M and its multimeric form, enhancing it by approximately twofold. Therefore, spermine enhancement offers promise in expanding the range of DNAzymes available for use as biosensing tools. Full article

Dynamic mutations in some human genes containing trinucleotide repeats are associated with severe neurodegenerative and neuromuscular disorders—known as Trinucleotide (or Triplet) Repeat Expansion Diseases (TREDs)—which arise when the repeat number of triplets expands beyond a critical threshold. While the mechanisms causing the DNA triplet expansion are complex and remain largely unknown, it is now recognized that the expandable repeats lead to the formation of nucleotide configurations with atypical structural characteristics that play a crucial role in TREDs. These nonstandard nucleic acid forms include single-stranded hairpins, Z-DNA, triplex structures, G-quartets and slipped-stranded duplexes. Of these, hairpin structures are the most prolific and are associated with the largest number of TREDs and have therefore been the focus of recent single-molecule FRET experiments and molecular dynamics investigations. Here, we review the structural and dynamical properties of nucleic acid hairpins that have emerged from these studies and the implications for repeat expansion mechanisms. The focus will be on CAG, GAC, CTG and GTC hairpins and their stems, their atomistic structures, their stability, and the important role played by structural interrupts. Full article

Let ${\left(k_{\mu }\right)}_{\mu =1}^4$ be a quartet of cyclic cubic number fields sharing a common conductor $c=pqr$ divisible by exactly three prime(power)s, $p,q,r$. For those components of the quartet whose 3-class group ${\mathrm{Cl}}_3\left(k_{\mu }\right)\simeq {(\mathbb{Z}/3\mathbb{Z})}^2$ is elementary bicyclic, the automorphism group $\mathfrak{M}=\mathrm{Gal}({\mathrm{F}}_3^2\left(k_{\mu }\right)/k_{\mu })$ of the maximal metabelian unramified 3-extension of $k_{\mu }$ is determined by conditions for cubic residue symbols between $p,q,r$ and for ambiguous principal ideals in subfields of the common absolute 3-genus field $k^{*}$ of all $k_{\mu }$. With the aid of the relation rank $d_2\left(\mathfrak{M}\right)$, it is decided whether $\mathfrak{M}$ coincides with the Galois group $\mathfrak{G}=\mathrm{Gal}({\mathrm{F}}_3^{\infty }\left(k_{\mu }\right)/k_{\mu })$ of the maximal unramified pro-3-extension of $k_{\mu }$. Full article

Nucleobase-containing molecules are compounds essential in biology due to the fundamental role of nucleic acids and, in particular, G-quadruplex DNA and RNA in life. Moreover, some molecules different from nucleic acids isolated from different vegetal sources or microorganisms show nucleobase moieties in their structure. Nucleoamino acids and peptidyl nucleosides belong to this molecular class. Closely related to the above, nucleopeptides, also known as nucleobase-bearing peptides, are chimeric derivatives of synthetic origin and more rarely isolated from plants. Herein, the self-assembly properties of a vast number of structures, belonging to the nucleic acid and nucleoamino acid/nucleopeptide family, are explored in light of the recent scientific literature. Moreover, several technologically relevant properties, such as the hydrogelation ability of some of the nucleobase-containing derivatives, are reviewed in order to make way for future experimental investigations of newly devised nucleobase-driven hydrogels. Nucleobase-containing molecules, such as mononucleosides, DNA, RNA, quadruplex (G4)-forming oligonucleotides, and nucleopeptides are paramount in gel and hydrogel formation owing to their distinctive molecular attributes and ability to self-assemble in biomolecular nanosystems with the most diverse applications in different fields of biomedicine and nanotechnology. In fact, these molecules and their gels present numerous advantages, underscoring their significance and applicability in both material science and biomedicine. Their versatility, capability for molecular recognition, responsiveness to stimuli, biocompatibility, and biodegradability collectively contribute to their prominence in modern nanotechnology and biomedicine. In this review, we emphasize the critical role of nucleobase-containing molecules of different nature in pioneering novel materials with multifaceted applications, highlighting their potential in therapy, diagnostics, and new nanomaterials fabrication as required for addressing numerous current biomedical and nanotechnological challenges. Full article

The G₄C₂ hexanucleotide repeat expansion in the c9orf72 gene is a major genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), with the formation of G-quadruplexes directly linked to the development of these diseases. Cations play a crucial role in the formation and structure of G-quadruplexes. In this study, we investigated the impact of biologically relevant potassium ions on G-quadruplex structures and utilized ¹⁵N-labeled ammonium cations as a substitute for K⁺ ions to gain further insights into cation binding and exchange dynamics. Through nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we demonstrate that the single d(G₄C₂) repeat, in the presence of ¹⁵NH₄⁺ ions, adopts a tetramolecular G-quadruplex with an all-syn quartet at the 5′-end. The movement of ¹⁵NH₄⁺ ions through the central channel of the G-quadruplex, as well as to the bulk solution, is governed by the vacant cation binding site, in addition to the all-syn quartet at the 5′-end. Furthermore, the addition of K⁺ ions to G-quadruplexes folded in the presence of ¹⁵NH₄⁺ ions induces stacking of G-quadruplexes via their 5′-end G-quartets, leading to the formation of stable higher-ordered species. Full article

Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~10⁵–10⁷ M⁻¹, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20–29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments. Full article

By using quantum chemical calculation data obtained by the DFT method with the B3PW91/TZVP and OPBE/TZVP levels, the possibility of the existence of three Fe(V) complexes, each of which contains in the inner coordination sphere porphyrazine/trans-di[benzo]porphyrazine/tetra[benzo]porphyrazine (phthalocyanine), oxygen (O²⁻) and fluorine (F⁻) ions, was shown. Key geometric parameters of the molecular structure of these heteroligand complexes are given; it is noted that FeN4 chelate nodes, and all metal-chelate and non-chelate cycles in each of these compounds, are practically planar with the deviation from coplanarity, as a rule, by no more than 0.5°. Furthermore, the bond angles between two nitrogen atoms and an Fe atom are equal to 90°, or less than this by no more than 0.1°, while the bond angles between donor atoms N, Fe, and O or F, in most cases, albeit insignificantly, differ from this value. Nevertheless, the bond angles formed by Fe, O and F atoms are exactly 180°. It is shown that good agreement occurs between the structural data obtained using the above two versions of the DFT method. NBO analysis data for these complexes are presented; it is noted that, according to both DFT methods used, the ground state of the each of three complexes under consideration may be a spin quartet or spin doublet. Additionally, standard thermodynamic parameters of formation (standard enthalpy ∆_fH⁰, entropy S⁰ and Gibbs’s energy ∆_fG⁰) for the macrocyclic compounds under consideration are calculated. Full article