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关键词： Antibacterial efficacy   Anticancer studies   Isoxazole-triazole hybrids   Sulphonamide-isoxazole conjugates  

摘要： This study addresses the design and development of novel isoxazole molecules tethered with triazole and sulphonamide derivatives to elucidate their pharmacological response for antibacterial and anticancer activities. The ionic liquid mediated protocol garners the respective derivatives tolerating an array of functionalised and substituted molecular hybrids. Antimicrobial exploration performed against six bacterial strains with antibiotic associated resistance mechanisms, identified five scaffold that exhibited significant inhibitory activity. The sulphonamide-isoxazole moiety demonstrated cross-species effectiveness encompassing both the resistant and non-resistant bacterial strains. ScXRD provides the exact molecular conformation and regioselective formation of 3,5-disubstituted isoxazole-sulphonamide hybrid. The heterocyclic conjugates also elicit a concentration- and time-dependent reduction in hepatocellular carcinoma cell (HepG2) with pronounced cell death observed for triazole hybrids bearing chloro substituents. The binding affinities of these compounds with the microbial protein targets and their interactions with Heat Shock Protein 90 (Hsp90) for the cancer cell line probed by the docking studies corroborates with the experimental findings.

关键词： Macrobrachium rosenbergii   Decapod iridescent virus 1   Genome sequencing   Susceptible cell model   In vitro infection  

摘要：

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  An in vitro infection model for DIV1 was established using mosquito cells.
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  DIV1 propagated in the established cell model reached a titer of 10^-2.67 TCID₅₀ per 0.1 mL and induced characteristic cytopathic effects.
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  Cell-cultured DIV1 retained high pathogenicity in Macrobrachium rosenbergii, causing dose-dependent mortality.
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  Complete genome of a DIV1 strain was sequenced (165,567 bp, 176 ORFs), confirming its classification within the genus Decapodiridovirus.

摘要： Glycidyl methacrylate (GMA), a widely used industrial epoxy monomer, is classified as a Group 2A carcinogen by the International Agency for Research on Cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a critical phase II detoxifying enzyme that maintains cellular redox homeostasis and is frequently upregulated in lung cancer. However, the molecular mechanism of GMA-induced lung adenocarcinoma remains unclear, particularly the regulatory role of NQO1 in this malignant process. This study aimed to investigate NQO1 expression and function during GMA-induced malignant transformation of lung epithelial cells and its correlation with oxidative stress signaling. A malignant cell model was established by chronic GMA exposure. Functional assays and xenograft tumor experiments were performed to evaluate malignant phenotypes, while transcriptomic sequencing and molecular verification were applied to screen and validate key molecules. Long-term GMA exposure significantly promoted the malignant transformation of lung epithelial cells. NQO1 was markedly upregulated in transformed cells, and NQO1 knockdown suppressed malignant behaviors and induced apoptosis. GMA increased intracellular reactive oxygen species and activated Nrf2/HO-1 signaling, which was reversed by antioxidant treatment. NQO1 was also highly expressed in clinical lung adenocarcinoma tissues. Collectively, NQO1 facilitates GMA-induced malignant transformation via the reactive oxygen species-Nrf2/HO-1 signaling pathway.

关键词： Diels-Alder cycloaddition   1,3-Butadiene   Ethylene   RRKM   Kinetic modeling  

摘要：

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  Reveal the concerted and stepwise diradical pathways for C₄H₆ + C₂H₄ cycloaddition.
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  Develop a kinetic model based on the canonical TST and RRKM theories.
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  Include correction for tunneling and anharmonic torsion in the kinetic evaluation.
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  Rate constants exhibit the pronounced temperature and pressure dependence.

关键词： Alternating polarity   Cross-coupling   Redox catalysis   Metal free   Electrosynthesis  

摘要： In this work, an electrosynthetic cross-coupling reaction is presented between the carbonyl group of N-(aryl)phthalimides and benzyl/allyl bromides that produces 3-alkyl, 3‑hydroxy isoindolin-1-ones. The reaction proceeds via homogeneous reductive catalytic activation of the bromo‑compound using N-(aryl)phthalimides as mediators and rapid alternating polarity (rAP) electrolysis; the latter technique permits a more efficient use of the alkyl halide. It is detailed how the reaction was optimized, while citing general trends observed when working with rAP. Voltammetric exploration shows that bromide ion release from the catalytic coupling feeds the counter-electrode reaction, protecting the product from decomposition. These conditions may be extrapolated to carbonyls in general to produce tertiary alcohols as well. Finally, exploration of the reaction scope enabled us to apply the developed reaction to the synthesis of 18 examples of 3-alkyl, 3‑hydroxy isoindolin-1-one derivatives and other tertiary alcohols in moderate to good yields at room temperature using carbon-based electrodes, without sub-zero temperatures, metals or unstable reagents.

关键词： High-pressure Phase Equilibrium   Thermodynamic modelling   Principle of Congruence   RK-Aspen   Supercritical carbon dioxide   Solute-solute interactions   Hydrogen bonding  

摘要： The application of the principle of congruence to mixtures of n-alkanes, 1-alcohols, carboxylic acid and methyl ester in carbon dioxide was investigated. Four ternary CO₂ + (50 mol% solute + 50 mol% solute) mixtures were measured, where the solutes are from the same homologous series. Data were measured between 308.15 K and 358.15 K and for total solute fractions between 0.019 and 0.610 g·g⁻¹ thus ensuring the dew-point, mixture critical and bubble-point regions have been characterised. The mixture data were compared to the corresponding mole-fraction-averaged binary systems, and good agreement between the ternary and binary data were evident. Slight deviations were evident for the 1-alcohol and carboxylic acid mixtures, indicating deviation from the principle of congruence, presumably due to hydrogen bonding effects that are present in these systems. The RK-Aspen model provided adequate description of all the mixtures, without the inclusion of solute + solute binary interaction parameters. Slight deviations are again evident for the 1-alcohol and carboxylic acid mixtures, further reinforcing the idea that solute + solute interactions are prevalent, leading to the deviation from the principle of congruence that was observed experimentally. Despite these deviations, the RK-Aspen model is still able to provide good quantitative description of each of the mixtures.

摘要： This research aims to identify novel and promising signatures for the diagnosis and monitoring of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections, severe global health challenges affecting millions. Our study focused on evaluating the serum levels of Interleukin-1 beta (IL-1β), the mRNA expression level of the PTX3 gene, and the miR-21-3p/5p in patients diagnosed with HBV and HCV compared to controls. Enzyme-linked immunosorbent assay (ELISA) is used to quantify IL-1β level. RNA and miRNA were extracted using a specialized kit, followed by reverse transcription to cDNA, and quantitative real-time PCR (qRT-PCR) was evaluated for PTX3 and miR-21-3p/5p. The findings of the current study revealed a significant elevation in serum IL-1β levels in both HBV and HCV patient groups compared to healthy individuals. Furthermore, our results demonstrated a significant increase in both PTX3 and miR-21-3p fold expression in both patient subgroups. Furthermore, current findings suggest that miR-21-5p may target PTX3, proposing a potential regulatory association between them within the context of the disease. Conversely, a noticeable decrease in miR-21-5p levels was observed in both patient groups. Moreover, ROC curve analysis indicated that IL-1β, PTX3, and miR-21-3p exhibit good characteristics as potential diagnostic biomarkers for viral hepatitis. While miR-21-5p showed lower sensitivity and specificity compared to miR-21-3p, suggesting the need for future studies with larger sample sizes to fully elucidate its role. In conclusion, these findings underscore the pivotal role of IL-1β, PTX3, and miR-21-3p as promising indicators that can contribute to improving prognosis and enhancing our understanding of the pathogenic mechanisms of HBV and HCV infections.

关键词： Aspirin   Blood-brain barrier   ICAM-1   MMP-9   Sepsis-associated encephalopathy  

摘要： Sepsis-associated encephalopathy (SAE) is a devastating complication contributing substantially to intensive care unit mortality and long-term cognitive impairment. Although observational studies suggest that aspirin use was associated with reduced sepsis-related mortality, its neuroprotective potential against SAE and underlying molecular mechanisms remain unclear. Using data from the Medical Information Mart for Intensive Care IV and eICU Collaborative Research Database, we demonstrated through propensity score matching and inverse probability of treatment weighting that aspirin use was significantly associated with reduced SAE incidence without increased gastrointestinal bleeding risk. Meta-analysis yielded a pooled protective association (OR 0.69, 95% CI 0.57–0.83) with moderate heterogeneity (I² = 63.6%). Transcriptomic profiling of hippocampal tissues from lipopolysaccharide (LPS)-induced SAE mice revealed intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) as aspirin-responsive hub genes enriched in leukocyte adhesion and extracellular matrix remodeling pathways. In murine models, aspirin significantly improved cognitive performance in novel object recognition and Y-maze tests, while reducing anxiety-like behavior. Mechanistically, aspirin suppressed LPS-induced upregulation of ICAM-1 and MMP-9 expression in hippocampus and prefrontal cortex, preserved blood-brain barrier integrity by restoring tight junction-related and adherens junction-related proteins reducing Evans blue extravasation, attenuated neuroinflammatory signaling through decreased cyclooxygenase-2, nuclear factor-κB, tumor necrosis factor-α, interleukin-6, and prostaglandin E2 expression, and reduced cleaved caspase-3–mediated neuronal apoptosis. These findings provide convergent evidence that aspirin mitigates SAE through suppression of ICAM-1 and MMP-9–associated inflammatory and endothelial dysfunction, supporting its potential as a neuroprotective ad

关键词： 1,3-Aminofluorination   Copper(II)-Catalyzed   High diastereoselectivity   γ-Fluoramine  

摘要： 1,3-aminofluorinations as a powerful strategy to synthesize γ-fluoroamines are in urgent need of development. Herein, a copper(II)-catalyzed 1,3-aminofluorination of spirovinylcyclopropyl oxindoles and N-fluorobenzenesulfonimide (NFSI) was realized. The protocol enables access to γ-fluoroamines containing oxindole in moderate to good yields (up to 75%) with high diastereoselectivity (all >20:1 dr). Notably, TMSCN as an additive enhances the reaction effect rather than the traditional cyanation reagent. Based on experimental results and the free radical capture experiments, a plausible reaction mechanism has been proposed, revealing the reason why TMSCN promotes the reaction.

关键词： CTAO   LST-1   MAGIC   Trigger   Stereoscopy   Cherenkov   Gamma-ray  

摘要： We present the implementation and validation of a hardware stereoscopic trigger (HaST) linking the Large-Sized Telescope prototype (LST-1) of the Cherenkov Telescope Array Observatory (CTAO) with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov Telescope) telescopes at the Roque de los Muchachos Observatory. This setup enables real-time exchange of camera-level trigger signals, allowing joint data acquisition and providing a commissioning platform for the future 4-LST HaST system.