Search Results (2,252)

A series of novel substituted derivatives of the closo-decaborate anion [B₁₀H₁₀]²⁻ bearing alkoxy spacer chains of varying length derived from ring-opened crown ethers (12-crown-4, 15-crown-5, and 18-crown-6) with pendant L-amino acid methyl ester residues (L-tryptophan and L-histidine) have been synthesized. The synthetic approach involved the nucleophilic ring-opening of oxonium crown ether derivatives of the closo-decaborate anion followed by coupling with amino acid methyl esters via mixed anhydride activation. The obtained compounds were characterized by multinuclear NMR spectroscopy (¹H, ¹¹B, ¹³C), IR spectroscopy, elemental analysis, and electrospray ionization mass spectrometry (ESI-MS). The compounds were obtained as sodium salts and evaluated for their in vitro cytotoxic and antiviral properties against the influenza A virus strain A/Moscow/78/2020 (H1N1)pdm09, which contains the S31N mutation conferring resistance to adamantane-class drugs. Cytotoxicity was assessed on MDCK cells, and antiviral activity was determined by cell ELISA. The results revealed a clear structure–activity relationship: the length of the alkoxy spacer chain significantly influenced both antiviral activity and selectivity. The shortest spacer (derived from 12-crown-4) proved to be optimal, while elongation of the chain led to a decrease in antiviral potency. The compound containing a 12-crown-4-derived spacer and a tryptophan methyl ester residue exhibited the highest selectivity index (SI = 155) with low cytotoxicity (CC₅₀ = 155 µg/mL) and high antiviral activity (IC₅₀ = 1.0 µg/mL). Tryptophan-containing derivatives consistently outperformed their histidine analogues, confirming the key role of the indole side chain in antiviral activity. Overall, the closo-decaborate platform with crown ether-derived spacers and amino acid ester pendant groups represents a promising scaffold for the development of low-toxicity, highly selective inhibitors of influenza A virus replication. The compound with the 12-crown-4-derived spacer and a tryptophan methyl ester residue merits further investigation as the most promising among the synthesized samples. Full article

Spanning structures that must be maintained, not merely rebuilt, underlie sensor fabrics, peer-to-peer overlays, and software-defined networks. We give a complete treatment of distributed minimum-spanning-tree (MST) construction and maintenance built on non-tree-edge (NTE) tracking, which certifies the edges excluded from the tree rather than growing tree fragments. First, we provide the full specification and correctness proofs of the static NTE algorithm—previously available only in outline—achieving $O\left(m\right)$ messages of $O\left(\log n\right)$ bits in $O\left(d\right)$ rounds with only three message types. Second, we prove an exact maintenance algorithm for edge-weight updates: three of four update cases resolve in $O\left(1\right)$, and the fourth is resolved by ExactSwap within a message bound that experiments show to be tight (median ratio 1.00); across 221,874 update records, the median affected set is 2, independent of scale ($n=500$–$\mathrm{20,000}$). Third, we establish a separation result: verifying a replacement edge distributively provably requires examining the entire search region, an obstruction with no centralized analogue. Fourth, we show that prediction is best used for scheduling: under contention, prioritizing predicted-cheap updates improves mean time-to-resolution by 2.1–3.8× over FIFO, matching an oracle, with a linear model sufficing. Full article

We study the notion of semicomplete Leibniz algebras and investigate their fundamental properties. In particular, we classify all non-Lie Leibniz algebras of dimension at most three according to their semicompleteness and establish structural results concerning direct sums, extensions, and holomorphs, obtaining Leibniz algebra analogues of key results from the theory of complete and semicomplete Lie algebras. As an application, we explicitly determine the algebras of derivations and inner derivations of all complex perfect non-semisimple Lie algebras of dimension at most nine and show that no such Lie algebra is semicomplete. Full article

Gymnodinium catenatum is a paralytic shellfish toxin (PST)-producing dinoflagellate that produces classical PSTs and hydroxybenzoate analogues known as GC toxins. Toxicological evaluation of GC toxins remains limited because certified reference materials (CRMs) and toxicity data are unavailable. This study applied the Neuro-2a (N2a) cell-based assay to evaluate PST functional toxicity in a Korean G. catenatum strain. The algal extract was analyzed by dose–response curve fitting to estimate total saxitoxin (STX)-equivalent toxicity, while GC1 & 2, GC3, and GC4 & 5, isolated from large-scale culture and structurally confirmed by NMR and LC-MRM-MS/MS, were evaluated to determine toxicity equivalence factors (TEFs). A clear sigmoidal curve yielded a functional toxicity of 3.7275 pg STX eq cell⁻¹, and TEFs followed the order GC3 > GC4 & 5 > GC1 & 2, with potency gaps considerably larger than previously reported receptor-binding differences. These findings support the N2a assay as a complementary approach for PST analogues lacking CRMs and suggest that receptor-binding affinity alone does not fully predict cellular functional potency. Although the proposed TEFs, obtained from single assays per preparation, are preliminary and assay-specific, this study provides the first functional toxicity estimates for GC toxins, contributing to the toxicological characterization of novel PST analogues. Full article

California’s Proposition 65 requires warning labels for chemicals associated with carcinogenicity or reproductive toxicity, affecting global cosmetic and fragrance formulations. While safrole has an established safe harbor level (No Significant Risk Level, NSRL) of 3 µg/day, its structural analogues, estragole and methyleugenol, lack specific safe harbor thresholds. To address this data gap using non-animal methodologies, this study evaluated a Next-Generation Risk Assessment (NGRA) workflow combining read-across and in silico modeling. Structural, physicochemical, and skin-permeation profiling supported category homogeneity (Tanimoto Tc ≥ 0.82 and comparable log Kp values) in accordance with OECD and ECHA guidelines. Multi-platform QSAR consensus (ToxTree, Danish QSAR, and VEGA QSAR) indicated that while parent phenylpropenes lack direct bacterial mutagenicity, they share a hepatic bioactivation pathway leading to mammalian clastogenicity and carcinogenicity predictions. Molecular docking with human Cytochrome P450 1A2 (CYP1A2; PDB: 2H14) identified safrole as the category’s conservative toxicological benchmark, exhibiting the highest binding affinity (−8.026 kcal/mol) and closest proximity to the catalytic HEME iron. Consequently, applying safrole’s 3 µg/day NSRL to estragole and methyleugenol provides a quantitative threshold to evaluate consumer exposure in cosmetic products, ensuring public health protection and regulatory compliance. Full article

Canavanine (CAN) is a nonproteinogenic amino acid, synthesised by many legumes (e.g., alfalfa, hairy vetch) and acts as a strong inhibitor of root growth. Thus, CAN may be considered as an allelopathic compound, influencing natural and agroecosystems. CAN is a structural analogue of arginine (Arg), so its toxicity results from its primary mode of action due to interference with Arg-dependent processes, especially incorporation into proteins instead of Arg. The aim of the work was to investigate the impact of CAN (10, 50 µM) treatment (24 or 72 h) on Arg catabolism and content of polyamines (PAs) in the roots of tomato (Solanum lycopersicum L.) seedlings. In the roots of plants cultured in the presence of CAN for 72 h, whosegrowth was completely inhibited, arginase activity and transcript levels of ARG1 and ARG2 were elevated, while ornithine (the product of Arg catabolism by arginase) content was low. CAN application resulted also in decreased total PAs level and increased relative contribution of spermine in the roots of tomato seedlings. CAN-induced alterations in PAs content in the roots were accompanied by changes in transcript levels of genes related to PAs synthesis (SPMS, SPDS) and PAs catabolism (PAO1). Full article

A fraction from an extract of the marine sponge Geodia microspinosa was identified as active in a high-throughput screen for molecules that impair the viability of diffuse pleural mesothelioma (DPM) cell lines. Bioassay-guided isolation led to the identification of microspinosamides B and D, and a new artifact, microspinosamide C, together with two previously reported analogues, microspinosamide and polydiscamide B, as the active principles. Their planar structures were solved by NMR and HRESIMS analyses, while advanced Marfey’s reaction, ROESY, and ECD were used for the establishment of their absolute configurations. All pure metabolites demonstrated low micromolar potency for the reduction in viability of the DPM cell lines. Full article

In this paper, we introduce and systematically study a new two-parameter family of affine $(q,\eta )$-Gould–Hopper-based Appell polynomials. These polynomials arise by fusing the affine $(q,\eta )$-exponential Gould–Hopper kernel with an invertible Appell multiplier. A central contribution is the affine quasi-monomial construction: an explicit raising operator obtained from a logarithmic-difference quotient of the combined kernel, together with the lowering operator and the resulting q-commutation structure. An explicit double-sum series representation and an affine diffusion equation of order j connecting differences in the two variables, and the full quasi-monomial framework identifying the operator pair $(P_{q,\eta }^{+},P_{q,\eta }^{-})$ are developed. Additional results include a governing difference equation, a converse characterisation, a determinantal representation, an affine addition formula, and an order recursion. Further, the Bernoulli and Euler sub-families are obtained as invertible specialisations, while the Genocchi family is treated separately as a derived noninvertible family through its exact relation with the Euler family. The corresponding structural results are stated with these hypotheses made explicit. Surface plots, numerical value tables, and a numerical illustration of real zeros accompany the theoretical development. The diffusion relation provides a discrete affine analogue of a higher-order evolution equation; no claim of a fully developed physical model is made in the present work. Full article

The Upper Rhine Graben (URG) has been a key area for subsurface energy activities for decades, with a focus on hydrocarbons during the mid- to late 1900s and a gradual shift toward energy transition applications such as geothermal energy and, potentially in the future, underground hydrogen storage (UHS). This study focuses on the northern URG, where legacy hydrocarbon fields and saline aquifers provide suitable subsurface structures and infrastructure for assessing the feasibility of UHS, although data coverage varies and remains limited in some areas. Some of these were converted into underground gas storage (UGS) in the past and are still in use, providing operational experience. The aim is to use data from well-understood sites to forecast UHS scenarios and assess the suitability for locations with similar geological settings. Two UGS sites, Stockstadt and Hähnlein, were used as analogue fields due to their comprehensive production and storage datasets to investigate their potential for future UHS. A structural model was developed using well and seismic data, followed by dynamic simulation to investigate flow behaviour under shallow reservoir conditions (depth of 300–500 m and temperature of ~29 °C) in a porous reservoir. The model was calibrated through history matching of both earlier production and UGS phases to capture aquifer dimensions and their role in pressure support and recovery, which is particularly important in this region due to the presence of an active aquifer. Based on this validated model, two hypothetical UHS scenarios were simulated using different working gas (WG) compositions: a low-H₂ case (5% H₂ and 95% CH₄) and a pure-H₂ case, while the remaining natural gas in the reservoir was considered as cushion gas (CG). The simulation results highlight the high mobility and low viscosity of hydrogen, as the pure-H₂ case shows sharper production peaks, faster decline, and increased water production compared to the low-H₂ case. In contrast, the CH₄-rich WG provides a more stable flow behaviour and smoother production response. Over successive cycles, the hydrogen fraction in the produced gas increases, indicating the gradual establishment of the WG zone. Based on the analogue, the potential of the nearby old gas fields was assessed using map-based estimation with Monte Carlo simulation, which indicated promising conditions for UHS development. Full article

A series of gallium and indium complexes bearing pyridine-2,6-bis(phenolate) ligands with ortho-substituents of increasing steric bulk (^tBu, SiMe₃, SiPh₃) was synthesized via SiMe₄ elimination from M(CH₂SiMe₃)₃ (M = Ga, In). The gallium complexes 2a–c were structurally characterized by X-ray diffraction, revealing monomeric four-coordinate distorted trigonal pyramidal geometries. DOSY NMR studies revealed that the indium complexes 3a (^tBu) and 3b (SiMe₃) are dimeric in solution, whereas the bulkier 3c (SiPh₃) is monomeric. All complexes were tested as initiators for ring-opening polymerization (ROP) of ε-caprolactone, L-lactide, and rac-lactide in the presence of benzyl alcohol. The M-CH₂SiMe₃ bond is inert toward alcohols, pointing to an activated monomer mechanism. Indium complexes exhibited higher activity than their gallium analogues, and the activity strongly depends on the ligand steric bulk: the most hindered SiPh₃ derivative 3c showed the highest activity, reaching full ε-CL conversion in 24 h at 80 °C, whereas the analogous gallium complex 2c was almost inactive. Full article

Telomerase is an interesting biological target for cancer treatment. Despite recent advances in telomerase research and the rapid development of new methodologies, significant challenges remain in identifying effective telomerase inhibitors with anticancer activity. In this manuscript, we provide computational studies to analyse how structural modification of BIBR1532, a selective and non-competitive telomerase inhibitor, may affect binding by a newly reported human telomerase model. BIBR1532 has been extensively studied in various cancer types, but analyses have shown its low anticancer activity. Further modification of BIBR1532 yielded compound BIBR1591 through a lipophilic morpholine ring extension of the benzoic acid. Interestingly, BIBR1591 showed approximately five-fold weaker inhibitory activity toward human telomerase relative to BIBR1532, but its in vivo preclinical studies have demonstrated significant anti-tumour and pro-apoptotic efficacy. Despite promising preclinical activities, neither compound has advanced to clinical trials, reportedly due to challenges with its pharmacokinetic properties. BIBR1532 suffers from poor solubility and low cellular uptake. This manuscript aims to provide an updated overview of human telomerase inhibition by BIBR1532 analogues and emphasise the importance of understanding its molecular mode of action based on the most updated literature. Using an in silico approach, we analysed how the structural modification of the BIBR scaffold influences the binding mode at the BIBR binding site recently discovered in the structure of human telomerase. We have also assessed whether reported analogues offer a measurable advantage over the parent compound. Full article

Background/Objectives: The rapid emergence of antimicrobial resistance has created an urgent need for new chemotypes with activity against bacterial, fungal, and mycobacterial pathogens. Rhodanine-based compounds are recognized as privileged scaffolds in medicinal chemistry because of their broad spectrum of biological activities, making them attractive candidates for the development of novel antimicrobial agents. Methods: A library of thirty-two novel rhodanine-based hydrazide derivatives (21–52) was synthesized by condensation of 5-ethoxymethylidenerhodanine derivatives with aromatic acid hydrazides and characterized by IR, ¹H NMR, and ¹³C NMR spectroscopy. Their drug-likeness and pharmacokinetics properties were evaluated using SwissADME, while antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria, Candida spp., and both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains using minimum inhibitory concentration (MIC) assays. Results: The synthesized compounds demonstrated selective activity against Gram-positive bacteria, whereas only limited activity was observed against Gram-negative species. The most potent derivatives (36, 40, 46, and 50) inhibited Micrococcus luteus with MIC values as low as 31.3 mg/L. Several compounds also demonstrated noteworthy antifungal activity, particularly against Candida parapsilosis (MIC = 15.6–31.3 µg/mL). Pyridyl-containing analogues displayed moderate antitubercular activity and, importantly, compounds 49 and 52 retaining activity against both drug-susceptible and drug-resistant M. tuberculosis strains. In silico analysis indicated favorable drug-like properties for most compounds, with good compliance with Lipinski’s rule of five and predicted oral bioavailability. Preliminary structure–activity relationship analysis revealed that a 3-phenylrhodanine core combined with para-halogen or para-nitro substituents significantly enhanced antimicrobial potency. Conclusions: The present study identifies rhodanine-based hydrazide derivatives as promising multifunctional antimicrobial scaffolds with activity against Gram-positive bacteria, pathogenic yeasts, and M. tuberculosis. The identified structure–activity relationships provide a rational basis for further lead optimization and support continued development of this chemotype as a potential source of new antimicrobial agents. Full article

Dysregulation of the autophagy–lysosome pathway is implicated in neurodegenerative disorders. To extend the chemical diversity of jatrophane diterpenoids from Euphorbia peplus and evaluate lysosome-associated phenotypes, phytochemical isolation and a LysoTracker Green assay in HeLa cells were performed. Five previously undescribed jatrophane diterpenoids, Euphjatrophanes M–Q (1–5), together with three known analogues (6–8), were isolated. The structures of 1–5 were assigned from one- and two-dimensional NMR, IR, and UV and the available HR-ESI-MS data, together with a comparison with reported compounds. At 10 and 40 μM, compounds 1, 2, and 4–8 produced higher LysoTracker-associated fluorescence than the DMSO vehicle control, whereas compound 3 showed a small numerical increase at 10 μM and a decrease at 40 μM. Compound 1 gave the largest numerical response (1.76-fold and 3.01-fold at 10 and 40 μM, respectively). These findings provide preliminary cell-based phenotypic evidence of lysosome-modulating activity and require orthogonal validation. Full article

Continuous Integration (CI) pipelines for multi-layer software systems face a tension between validation completeness and execution efficiency. Regression test selection and learned prioritization address this tension but typically operate as black boxes, offering no interpretable justification for their decisions. This paper introduces MOX, a preliminary decision-support framework for risk-aware test selection that jointly optimizes four objectives: execution cost, fault-detection impact, affected-test coverage, and a proposed explainability score, formalized as a first-class, numerically optimizable objective (a structural traceability proxy, not a validated measure of human interpretability) and traded off within a Pareto-based selection mechanism governed by a configurable impact budget. We evaluate MOX retrospectively on two public industrial CI datasets from ABB, iofrol (1941 tests, 320 cycles) and paintcontrol (89 tests, 352 cycles), containing execution logs of integration-level regression tests for industrial robot software. No new tests are developed or executed: selections are replayed per historical cycle against the recorded pass/fail verdicts. Because the logs contain no code changes, each cycle’s change event is inferred from its failing tests, so detection figures must be read as retrospective retention of failed tests under a selection budget, not prospective fault detection. Under this protocol MOX retains 96.7% (iofrol) and 98.2% (paintcontrol) of recorded failures at 53.9–57.5% of full-suite cost over the evaluated failure-containing cycles and raises the Average Percentage of Faults Detected (APFD) from 0.507 to 0.626 and from 0.596 to 0.815; paired Wilcoxon tests are highly significant ($p<{10}^{-13}$), with MOX ordering the recorded failures earlier than the informative prioritizing baselines, including the input-matched single-objective analogue, in roughly 70–80% of cycles. Within the protocol, an objective-removal ablation associates the ordering gains with the explainability objective, and the cheapest configurations also score highest on the proposed traceability measure. Full article

Mudstone caprocks are important sealing formations for geological CO₂ storage, but the extent and mineralogical response of CO₂-induced alteration within mudstone caprocks remain poorly constrained. This study examines a Paleocene mudstone caprock from the Mingyuefeng Formation in the Lishui Sag, East China Sea Basin, where natural CO₂ charging has occurred. Mineralogical and geochemical analyses, including X-ray diffraction (XRD), rare earth elements (REE), and carbon–oxygen isotopes, were used to characterize CO₂–water–rock interaction at the reservoir–caprock transition. The studied caprock is dominated by quartz and clay minerals, with mineralogical characteristics favorable for caprock sealing. REE signatures indicate a felsic source and limited vertical REE redistribution within the studied interval. Carbonate minerals display distinct vertical variations across the sandstone–mudstone interface, with localized carbonate redistribution near the transition and carbonate depletion accompanied by clay-mineral alteration above it. Most samples retain δ¹³C values close to background levels, whereas a decimeter-scale interval adjacent to the interface exhibits depleted δ¹³C values accompanied by localized δ¹⁸O variations, consistent with the localized influence of CO₂-bearing fluids. The altered zone is restricted to a decimeter-scale interval above the reservoir–caprock transition, suggesting that CO₂-related alteration was spatially restricted within the studied interval. Carbonate redistribution and clay-mineral transformation may have contributed to geochemical buffering during CO₂–water–rock interaction, although their quantitative effects on pore structure and sealing performance require further petrophysical investigation. These results provide a natural analogue for understanding localized CO₂-induced alteration and potential geochemical self-sealing processes at reservoir–caprock interfaces. Full article