Search Results (818)

The design of ladle furnace (LF) refining pathways for weathering steels requires precise control of multi-component steel/slag reactions governed simultaneously by thermodynamics and interfacial mass transfer kinetics. An EERZ-based kinetic modeling strategy was employed using the Thermo-Calc^® (version 2022a) Process Metallurgy Module and the CALPHAD TCOX11 database to develop LF refining schedules capable of upgrading conventional S355J2R steel to weathering steel grades: S355J2W and S355J2WP. First, the sensitivity of predicted compositions to key kinetic inputs was quantified. The validated model was then used to simulate deoxidation and desulfurization sequences, predicting the evolution of liquid–steel and slag compositions, slag basicity, and FeO activity throughout the LF cycle. Subsequently, Cr- and P-ferroalloys were introduced to design tap-to-tap schedules that meet the EN 10025-5 chemical specifications for S355J2W and S355J2WP. To correlate simulation outcomes with material performance, plates produced following the modeled schedules were evaluated through a 1000 h accelerated salt spray test. Steel density and steel phase mass transfer coefficients were found to produce the highest prediction sensitivity (up to 7.5 wt.% variation in C and S), whereas slag phase parameters exhibited a lower impact. The predicted steel compositions showed strong agreement with industrial values obtained during plant trials. SEM-EDS analyses confirmed the development of a Cr-enriched protective patina and validated model-based alloying strategies. Full article

1,4-Dihydropyridines (1,4-DHPs) are privileged heterocycles with broad relevance in medicinal chemistry and redox-related applications. However, conventional Hantzsch syntheses typically require prolonged thermal heating and often suffer from limited efficiency and regioselectivity. Herein, we report a sustainable and efficient microwave-assisted protocol for the synthesis of 1,4-DHPs, employing phosphotungstic acid (HPW) as a heteropolyacid catalyst in PEG-400 as a green reaction medium. The multicomponent cyclocondensation proceeds rapidly under microwave irradiation, affording the desired 1,4-DHP derivatives in good to excellent yields within short reaction times. Compared with classical acid-catalyzed conditions, the HPW/PEG-400 system markedly enhances regioselectivity toward the 1,4-DHP framework while simultaneously reducing energy input. Moreover, the catalytic system exhibits good recyclability, underscoring its potential as a practical and environmentally responsible platform for the synthesis of bioactive 1,4-dihydropyridine scaffolds. Full article

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents. Full article

Background/Objectives: Recent reports have demonstrated the antiparasitic activity of 1,4-dihydropyridine (1,4-DHPs). This study aimed to assess the in vitro antischistosomal activity of 24 1,4-DHPs against Schistosoma mansoni adult worms. Methods: Sixteen hexahydroquinolines (1–16) and eight Hantzsch esters (17–24) previously obtained through a multicomponent Hantzsch reaction were tested in vitro against Schistosoma mansoni adult worms. In silico studies with the most active compounds were also carried out. Results: Among the tested compounds, the Hantzsch esters 20 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) and 21 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) provided the lowest IC₅₀ (15.2 and 13.1 µM, respectively) and the highest selectivity for this parasite (SI = 2.31 and >4.59, respectively). Conclusions: Docking studies revealed that compound 21 has a high affinity for the S. mansoni target (PDB ID: 6UY4). Furthermore, ADMET predictions indicated that compound 21 meets the drug-likeness criteria without violating any Lipinski, Veber, or Egan’s rules. Full article

Magnesium hydride (MgH₂) is a promising solid-state hydrogen storage material owing to its high hydrogen capacity and low cost, yet its practical application is limited by sluggish kinetics, high operating temperatures, and poor cycling stability. Among various catalytic approaches, Fe-based catalysts have emerged as attractive candidates due to their abundance, compositional tunability, and effective promotion of hydrogen sorption reactions in MgH₂ systems. This review critically summarizes recent progress in Fe-based catalysts for MgH₂ hydrogen storage, encompassing elemental Fe, iron oxides, Fe-based alloys, and advanced composite catalysts with nanostructured and multicomponent architectures. Mechanistic insights into catalytic enhancement are discussed, with particular emphasis on interfacial electron transfer, catalytic phase evolution, hydrogen diffusion pathways, and synergistic effects between Fe-containing species and MgH₂, supported by experimental and theoretical studies. In addition to catalytic activity, key stability challenges—including catalyst agglomeration, phase segregation, interfacial degradation, and performance decay during cycling—are analyzed in relation to structural evolution and kinetic–thermodynamic trade-offs. Finally, a roadmap for the scalable design of Fe-based catalysts is proposed, highlighting rational catalyst selection, interface engineering, and compatibility with large-scale synthesis. This review aims to bridge fundamental mechanisms with practical design considerations for developing durable and high-performance MgH₂-based hydrogen storage materials. Full article

Toughening modification of epoxy resin (EP) matrices is important for advancing high-performance fiber-reinforced composites. A promising strategy involves the use of multi-component additive systems. However, synergistic effects in such additive systems are difficult to achieve for multidimensional performance optimization due to insufficient interfacial interactions and competing toughening mechanisms. Herein, a “hard–soft” biphasic synergistic toughening system was engineered for epoxy resin, composed of furan-ring-grafted polyhedral oligomeric silsesquioxane (FPOSS) and liquid polysulfide rubber. The hybrid toughening agent significantly enhanced the integrated performance of the epoxy system: Young’s modulus, tensile strength, and elongation at break increased by 13%, 56%, and 101%, respectively. These improvements are attributed to the formation of enriched molecular chain entanglement sites and optimized dispersion, facilitated by nucleophilic addition reactions between flexible rubber segments and rigid FPOSS units with the epoxy matrix. The marked enhancement in toughness primarily stems from the synergistic toughening mechanism involving “crazing pinning” and “crazing-shear band”. Concurrently, FPOSS incorporation effectively modulated the curing reaction kinetics, rendering the process more gradual while substantially elevating the glass transition temperature (T_g) of the cured system by 16.82 °C and endowing it with superior thermal degradation stability. This work provides a simple and unique strategy to leverage multi-scale mechanisms for the construction of epoxy-based composites with good toughness and strength, and enhanced heat resistance. Full article

Background/Objectives: Neuropathic pain remains a significant clinical challenge, with current treatments often providing inadequate relief and adverse effects. Sigma receptors (SRs) modulate nociception and have emerged as potential therapeutic targets for neuropathic pain. Although putative sigma-1 receptor (S1R) ligands have demonstrated analgesic efficacy in preclinical models, their in vivo efficacy and safety profiles require further clarification. Methods: Analogs of well-known selective S1R ligand UVM147 were synthesized using 3-component Ugi reactions and examined in vitro for receptor affinity in radioligand competition binding assays and in vivo with mouse models of neuropathic and inflammatory pain and adverse effects. Results: Three novel heterocyclic compounds (RO-4-3, RO-5-3, and RO-7-3) displayed in vitro nanomolar affinity with varying selectivity for both SR subtypes (S1R and S2R). When screened in vivo at a dose of 30 mg/kg s.c. in mice first subjected to chronic constriction injury (CCI), RO-5-3 and RO-7-3 possessed anti-allodynic potential, while UVM147 was inactive. Upon full characterization, RO-5-3 significantly attenuated mechanical allodynia in a dose-dependent manner, while RO-7-3 was ineffective at higher doses. Both compounds dose-dependently attenuated nociceptive behaviors in the mouse formalin assay. RO-5-3 induced mild respiratory depression without impairing locomotor activity, whereas RO-7-3 caused transient respiratory depression and locomotor impairment. Additionally, RO-5-3, but not RO-7-3, induced conditioned place aversion consistent with potential S2R involvement. Conclusions: RO-5-3 exerts antinociceptive and anti-allodynic effects with minimal adverse behavioral effects, supporting the role of SRs in pain modulation. These results add to growing evidence supporting the development of SR ligands as efficacious therapeutics for neuropathic pain with fewer clinical liabilities. Full article

Background/Objectives: Identifying candidate genes underlying quantitative trait loci (QTL) in poultry has traditionally required labor-intensive positional cloning. Previous studies using an F₂ population derived from native Japanese Nagoya (NAG) and White Plymouth Rock (WPR) breeds revealed a major QTL on chromosome 2 affecting 3-week body weight and 4-week pectoralis muscle weight. This study aimed to identify candidate genes for this QTL using a hypothesis-free integrative genetic approach. Methods: We employed a multi-step analytical framework combining QTL remapping, transcriptome analysis, gene enrichment analysis, haplotype frequency comparison, and correlation analysis. QTL remapping was performed using individual traits and their first principal component (PC1) in 239 F₂ chickens. RNA-sequencing (RNA-seq) of liver tissue was conducted for F₂ individuals with extreme PC1 scores, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation. Results: QTL remapping refined the 95% confidence interval to a chromosome 2 region containing 329 genes. RNA-seq analysis identified 23 differentially expressed genes (DEGs) within this interval. Although gene enrichment analysis initially highlighted GATA binding protein 6 (GATA6) as a potential candidate, RT-qPCR in NAG, WPR, and F₁ chickens showed no significant expression differences, excluding GATA6. Haplotype frequency and correlation analyses prioritized cadherin-17 (CDH17) as the strongest candidate gene and ring finger protein 151 (RNF151) as a secondary candidate. Conclusions: Our hypothesis-free integrative approach effectively refined candidate genes for a chromosome 2 QTL influencing early growth and pectoralis muscle weight. CDH17 and RNF151 represent promising targets for functional validation and may support marker-assisted selection to improve muscle-related traits in chickens. Full article

The Kabachnik–Fields (KF) reaction is a versatile three-component method for the condensation of amines, carbonyl compounds, and P–H reagents, enabling efficient synthesis of α-aminophosphonates—key bioactive and functional molecules. This review critically examines the literature from the last 25 years. However, with regard to mechanistic aspects, selected earlier seminal studies are also considered when necessary to provide a coherent and comprehensive mechanistic framework. Advances in catalyst-free methodologies, sustainable synthetic approaches, and Lewis and Brønsted acid catalysis are discussed, alongside developments in enantioselective KF reactions in the presence of chiral metal complexes or organocatalysts. Full article

To explore the aging mechanism of (Styrene Butadiene Styrene) and CR (Crumb Rubber) composite-modified asphalt in a multi-source environment, the characteristics of functional group changes in the infrared spectroscopy of SBS and CR modifiers as well as their single and composite modified asphalts under thermal, UV, and coupled aging were tested using Attenuated Total Reflection–Fourier Transform Infrared Spectroscopy (ATR-FTIR) technology. It was found that SBS and CR modifiers exhibited significant yellowing degradation after aging due to high-energy effects, causing abstraction of α-hydrogen from polybutadiene via oxidation, initiating radical chain reactions. The addition of SBS and CR to asphalt significantly increased the absorption peaks of 966 cm⁻¹ polybutadiene and 699 cm⁻¹ polystyrene. However, certain labile bonds in the modified asphalt, such as the C-H bond, C-C bond, and C=C double bond in polycyclic aromatic hydrocarbons, were easily broken to produce reactive free radicals under aging, which reacted chemically with other components to produce new sulfoxide and carbonyl groups. Overall, the aging reaction of the asphalt was a dual sequential oxidation process. Under normal temperature conditions in the early stage, a large number of sulfoxides were oxidized. In the later stage of the reaction, as the concentration and persistence of active free radicals increased, the oxidation reaction of the asphalt benzyl carbon also enhanced significantly, ultimately generating carbonyls. Full article

The selective catalytic reduction (SCR) system is a key component for addressing NOx emissions from internal combustion engines. To resolve the issues of modeling distortion in SCR systems and the difficulty in characterizing the local reaction mechanism, a multi-dimensional SCR reaction model based on the coupling of Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) dual mechanisms was established and conducted by experiment. The SCR catalytic characteristics and the dual-mechanism reaction process were systematically investigated. Additionally, based on the combined analysis of species concentration distribution coupled with temperature characteristics, a calculation method for the synergy of concentration-temperature fields was developed, and the synergistic characteristics of the concentration-temperature fields were explored. The results showed that high load accelerated the light-off speed, but this effect was counteracted by the negative impact of high flow rate. A strong negative correlation was maintained between temperature and NOx concentration across the full load range, and the axial consistency increased with load increasing. The results provide important theoretical support for the mechanism analysis of diesel engine SCR reactions and the optimization of thermal management. Full article

Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract from Bombyx batryticatus (FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, demanding the continuous search for novel and more selective chemotherapeutic agents. Quinones, particularly naphthoquinones, constitute a privileged class of redox-active compounds with well-documented antitumor activity. Likewise, thiazoles represent a heterocyclic scaffold widely explored in medicinal chemistry due to their broad pharmacophoric adaptability and diverse biological activities. In this context, this review comprehensively explores the chemical synthesis and anticancer potential of hybrid molecules combining the naphthoquinone and thiazole scaffolds. The hybridization of these pharmacophores has emerged as a powerful strategy to design multitarget antitumor agents. The review summarizes key synthetic methodologies, including Hantzsch, hetero Diels–Alder cycloaddition and multicomponent reactions, leading to structurally diverse hybrids. Particular emphasis is placed on derivatives exhibiting strong cytotoxic effects against a broad spectrum of cancer cell lines (e.g., OVCAR3, MCF-7, A549, HCT-116, HeLa, and Jurkat), low toxicity toward normal cells and well-defined mechanisms of action involving topoisomerase IIα, EGFR, STAT3, and CDK1 inhibition, as well as ROS generation and cell cycle arrest. Among these, certain hybrids displayed nanomolar potency and high selectivity indices, reinforcing their potential as promising lead compounds for anticancer drug development. Full article

Pediatric food allergies are an escalating public health concern, with nut allergies representing a primary cause of persistent hypersensitivity and anaphylaxis. New data suggests that pediatric populations with multiple nut allergies (MNA) may be at higher anaphylaxis risk than their counterparts with single nut allergies. Despite this, there is an absence of literature posing multiple nut allergies against singular nut allergy cases. The majority of the research in this topic is directed towards singular nut allergy, without any differentiation between children with one versus multiple sensitivities. Epidemiological evidence indicates that multiple nut allergies are associated with lifelong sensitization, high cross-reactivity potential and increased risk and severity of reactions. Compounding clinical risk factors reinforce the already high risk associated with MNA and indicate that these children require careful monitoring and individual management. Diagnostic tools, including component-resolved diagnostics and oral food challenges, enable differentiation between true multi-nut sensitization and cross-reactivity, guiding targeted interventions. Management strategies must therefore be multifaceted, encompassing selective allergen avoidance, emergency preparedness with epinephrine auto-injectors, asthma control, nutritional support, and psychosocial care. Recognizing MNA as a distinct, high-risk phenotype highlights the necessity of precision-based, biomarker-driven clinical approaches to optimize safety, reduce morbidity, and improve quality of life for affected pediatric populations. Full article

The multicomponent synthesis of a novel and highly symmetric polyheterocycle based on the pyrrolo[3,4-b]pyridin-5-one core incorporating the privileged tetrahydroisoquinoline moiety is described. The target compound was synthesized as an inseparable mixture of stereoisomers through a pseudo-repetitive Ugi–Zhu five-component reaction (PR-UZ-5CR) coupled to a double post-transformation sequence involving an intermolecular aza Diels–Alder cycloaddition, an intramolecular N-acylation, and a final tandem aromatization step. The product was prepared in 63% overall yield, and with an excellent atom economy of 85%, within a total reaction time of 85 min, and a temperature range from 25 to 65 °C. Structural elucidation and molecular mass confirmation were successfully achieved through NMR and FT-IR spectroscopy, and high-resolution mass spectrometry (HRMS), respectively. Full article