Search Results (782)

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

Silica aerogels are ideal candidates for gas adsorption due to their exceptional porosity and high specific surface area; however, the inherent mechanical fragility of their skeletal framework significantly compromises their operational stability in engineering applications. While the incorporation of carbon nanomaterials effectively enhances the mechanical robustness of aerogels, the specific microscopic mechanisms by which filler microstructure and surface chemistry dictate gas adsorption behavior remain insufficiently understood. In this study, we employed all-atom molecular dynamics (MD) simulations to develop a model of silicon-based porous composites synergistically doped with carbon nanotubes (CNTs) and graphene. The adsorption and diffusion characteristics of nitrogen (N₂) were systematically investigated across a CNT doping concentration range of 5% to 20%, and the influence of surface hydrophilicity/hydrophobicity on adsorption performance was quantitatively analyzed by modulating potential energy parameters. Our results demonstrate that the introduction of CNTs reconfigures the porous architecture, leading to an approximately 18.25% increase in the normalized specific surface area, which subsequently drives a 15% enhancement in the overall adsorption capacity of the composite. Nevertheless, analysis reveals that the weight-specific adsorption efficiency of the CNT component itself exhibits a declining trend as the doping concentration increases. This phenomenon is primarily attributed to the convex curvature of the CNTs, which restricts the effective contact area and weakens the adsorption potential, alongside the steric hindrance effects arising from local filler agglomeration at higher concentrations. Furthermore, surface chemical properties exert a significant regulatory influence on adsorption; a strongly hydrophilic modified surface (λ = 1.5) achieved an adsorption capacity approximately 98% higher than the baseline condition—an improvement that exceeds the gains provided by purely physical volume expansion. This research elucidates the synergistic mechanism between physical architecture and surface chemical modification in the adsorption process, suggesting that while the physical architecture determines the abundance of potential adsorption sites, the surface chemistry governs the actual efficiency of site utilization. These findings provide critical theoretical insights for the future design of composite aerogel materials that balance structural stability with superior adsorption performance. Full article

Driven by the demand for miniaturization, high capacitance, and enhanced reliability in high-performance multilayer ceramic capacitors (MLCCs), the continuous thinning of inner electrode layers imposes increasingly stringent requirements on the size, distribution, morphology, and dispersion of nano-nickel powders. We systematically investigate how functional additives regulate the nucleation, growth, and microstructural evolution of nano-nickel synthesized via hydrazine-driven liquid-phase reduction of nickel sulfate. The results demonstrate that the alkanolamine complexing agent (TAC) significantly refines the average particle size and morphology of the nano-nickel through coordination effects. Furthermore, inorganic sulfur salts (ISP), acting via surface adsorption to passivate growth sites and provide catalytic effects, enable a precise and continuous reduction in the average particle diameter from 330 nm down to 60 nm at a mere trace dosage of ~10⁻⁷ mol/L. Regarding dispersion optimization, highly dispersed face-centered cubic (FCC) nano-nickel was successfully prepared by introducing multidentate carboxylate (NNA). High-resolution transmission electron microscopy (HRTEM) was employed to unveil, for the first time, the crystallographic origin of the anomalous surface protrusions typically observed in conventional reaction systems. We confirmed that the family of $\left\{10\overline{1}0\right\}$ crystal planes within these regions, which exhibits interfacial angles of 58.7° and 58.3°, corresponds to a thermodynamically metastable hexagonal close-packed (HCP) nickel phase originating from atomic stacking faults induced by rapid growth kinetics. To address this microstructural defect, a thioether-based amino acid (TAA) was introduced. TAA effectively suppresses the anisotropic growth of the metastable HCP phase through the strong steric hindrance of its long side chains and its selective adsorption onto high-energy facets. Full article

Poly(9,9-di-n-octylfluorene) (PFO) suffers from interchain aggregation, which degrades its blue spectral stability and charge transport. To address this, a series of rod-coil diblock copolymers (PFO-b-PMMAs) with varying poly(methyl methacrylate) (PMMA) chain lengths were synthesized via Steglich coupling. The non-conjugated PMMA blocks act as bulky steric spacers in the solid state, effectively suppressing detrimental PFO aggregation and enhancing pure blue emission stability. Furthermore, moderate PMMA blocks (PFO-b-PMMA1 and PFO-b-PMMA2) promote favorable β-phase formation and ordered crystalline packing. This microstructural optimization yields a maximum electron mobility of 1.98 × 10⁻⁶ cm²/(V·s) for PFO-b-PMMA2, markedly higher than the PFO-2 homopolymer (4.13 × 10⁻⁷ cm²/(V·s)). However, an overlong PMMA block (PFO-b-PMMA3) introduces excessive steric hindrance (T_g = 66 °C) that disrupts crystallization, acting as an insulating barrier that reduces mobility. Thus, precisely tuning the non-conjugated block length effectively maximizes both the blue spectral stability and electron transport capabilities of PFO-based materials. Full article

Currently, poly- and monophenol antioxidants should be considered not only as inhibitors that interact with free radicals, but also take into account that they are biologically active substances that affect specific targets in cells and can induce the activity of certain genes or stimulate various signaling pathways. The phenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. In our present study the effect of two antioxidants, sterically hindered monophenols sodium anphene (ANa) and potassium phenosan (PhK), on cell apoptosis of splenocytes was studied by fluorescence and confocal microscopy. PhK has already been introduced into medical practice in the Russian Federation because it proved effective as an anticonvulsant and was useful in treating neonatal hypoxia. The study of ANa continues; it may be a promising anticancer drug for some types of tumors. The fluorescent and confocal microscopy methods demonstrate that ANa in combination with H₂O₂ enhances apoptosis in suspension of Lewis carcinoma cells and to a lesser extent in splenocyte culture. We also discovered that autofluorescence of FAD and immunofluorescence of NADPH enzymatic complexes (with the AV-FITC fluorophore) in splenocytes of normal cells increases symbatically. The autofluorescence of FAD in splenocytes of Lewis carcinoma cells significantly exceeded that of splenocytes of healthy animals. The exact distinctive result was obtained when using potassium phenozan. It turned out that PhK prevents the development of apoptosis in mouse splenocyte cell culture (F1(CBA×C57B)). The combined use of ANa and PhK had no effect on splenocyte apoptosis. We show that fluorescence and confocal microscopy allow observing and quantifying the apoptotic effect of ANa and hydrogen peroxide, and make it possible to visualize metabolic changes in the cell, increased FAD fluorescence in tumor cells and NADPH -oxidase complexes in splenocytes. The data obtained indicate the possibility of using ANa in combination with hydrogen peroxide as an antitumor drug acting on certain types of cells. The different effects of sterically hindered monophenols ANa and PhK on the level of the anti-apoptotic protein Bcl-2 in the cell were established. ANa acts to lower Bcl-2 levels, signaling apoptosis, while PhK prevents the development of apoptosis and induces repair processes. Full article

This study employs molecular dynamics simulations to investigate the influence of functionalized UiO-66 materials (with -H, -NH₂, -NO₂, and -(OH)₂ groups) on the adsorption and diffusion behaviors of ethanol and waste oil before transesterification reactions. A multi-scale modeling approach, including a three-layer interfacial model, surface adsorption, and intra-framework adsorption, was utilized to systematically evaluate the effects of functionalization on structural properties, molecular diffusion, adsorption performance, and interfacial interactions. The simulation results reveal that functionalization enhances the intrinsic diffusivity of the metal–organic framework but generally suppresses the diffusion of ethanol and waste oil. The -(OH)₂ group exhibits the most significant diffusion hindrance due to steric effects and strong hydrogen bonding. Adsorption of waste oil is dominated by coordination and hydrophobic interactions, while ethanol adsorption relies on hydrogen bonding. Within the framework, functionalization does not improve ethanol adsorption capacity; instead, pristine UiO-66 shows the highest uptake due to its optimal pore size. Adsorption energy calculations on the (002) surface indicate that the -NO₂ group exhibits the strongest affinity for oleic acid, owing to its strong electronegativity and synergistic effects with metal sites. For polyunsaturated fatty acids, adsorption performance depends critically on the compatibility between the hydrophobic pore environment and molecular conformation. Ethanol adsorption is governed primarily by hydrogen bonding and metal coordination. This study provides molecular-level insights into the structure–function relationships governing pre-reaction adsorption and mass transport mechanisms of functionalized UiO-66 in transesterification reactions, providing a theoretical foundation for the rational design of efficient pre-reaction microenvironments in biodiesel catalysts. Full article

Traditional chemical hair dyes are associated with potential health risks, while botanical alternatives are often hampered by poor stability and limited color longevity. In this study, discarded squid ink was used to prepare bionic hair colorants of high performance. By synergizing ultrasound disruption with enzymatic hydrolysis, the crude ink aggregates were transformed into highly uniform squid ink melanin nanoparticles (SIMNPs) with size and zeta potential of ~174 nm and −37.5 mV, respectively. This effectively improved the solubility but reduced the steric limitation of natural melanin. To overcome the weak affinity between melanin and human hair, a biomimetic interface where Fe(III) ions act as supramolecular bridges was further engineered to stably bind the SIMNPs to hair keratin. Under optimized conditions (pH 8.0, 45 °C, and 80 min), the dyed hair achieved a natural deep black with a total color difference (ΔE*) of 68.79 ± 0.29, which was maintained at 63.19 ± 0.27 even after 13 consecutive water washing cycles. Unlike destructive oxidative dyes, this SIMNP dyeing system assisted by coordination-driven assembly preserved the native α-helical architecture and disulfide bond networks of hair keratin. Furthermore, the deposited SIMNP layer effectively protected hair fibers from ultraviolet (UV) damage due to its powerful UV-shielding capacity. Crucially, in vitro and in vivo evaluations confirmed the exceptional biosafety of this formulation, demonstrating robust cellular tolerance and absence of murine skin irritation. The work demonstrates a green, low-damage paradigm for the development of bio-based hair colorants of high performance and presents a promising pathway for the high-value utilization of marine by-products. Full article

To achieve stable dispersion of ZnO nanoparticles in the base fluid and enhance thermal conductivity (λ), a PGPR@ZnO nano-hyperdispersant was synthesized using polyglycerol polyricinoleate (PGPR) and ZnO. FT-IR and DSC confirmed the bonding interaction between PGPR and ZnO, and zeta potential analysis verified the steric hindrance effect that effectively inhibits particle agglomeration. The PGPR@ZnO was dispersed into di(2-ethylhexyl) carbonate (DEHC) by ultrasonication and stirring, yielding a stable DEHC-PGPR@ZnO nanofluid. This nanofluid achieved a 16.2% increase in λ while retaining the low viscosity and low pour point of the base fluid. Stability assessments showed consistent particle size main peaks before and after static and dynamic tests, with no obvious agglomeration peaks, average particle size variation below 6%, PDI below 0.3, and negligible zeta potential fluctuation. Following static and dynamic stability tests, the thermal conductivity decreased by 0.85% and 7.98%, respectively. These results indicate excellent dispersion stability and provide a valuable reference for evaluating the operational adaptability of the coolant. The nanofluid meets the basic standards for immersion coolants and exhibits a figure of merit (FOM) superior to most oil-based coolants. Compared with PAO2, it offers advantages in raw material availability and resistance to hydrolysis and acidification, providing research and practical foundation for the development of high-performance immersion coolants. Full article

Against the backdrop of the global trends toward lightweighting, multi-functionalization, and greening of materials, polypropylene (PP) has been extensively applied owing to its advantages of low density and low cost. However, its inferior foaming performance fails to meet high-end application requirements, which is primarily attributed to its low melt strength and restricted crystallization behavior. In this paper, the five-dimensional selection mechanism and classification of components for PP micro/nanocomposites fabricated via supercritical foaming are systematically summarized. The regulatory effects of micro/nano additives on the crystallization, rheological properties, and foaming behavior of PP are quantitatively analyzed. The parameter optimization windows of three foaming processes, namely batch foaming, extrusion foaming, and injection foaming, are integrated (e.g., a foaming temperature of 150–170 °C and a saturation pressure of 8–20 MPa). Additionally, the application progress of PP micro/nanocomposite foams in fields such as automotive lightweighting (with a weight reduction rate of 64.29%) and building thermal insulation (with a thermal conductivity as low as 29 mW/(m·K)) is outlined. The core novel insight of this work lies in clarifying the unified mechanism of crystal refinement induced by reinforcing agents with different geometric morphologies, which is dominated by the synergy between heterogeneous nucleation and steric hindrance. This finding provides theoretical and technical guidelines for the industrial-scale preparation of high-performance PP foams. Full article

This study investigates the influence of the physical and chemical characteristics of three polycarboxylate ether (PCE) superplasticizers—differing in main-chain length, side-chain density, and dispersing-to-stabilizing polymer ratio (75:25, 50:50, and 25:75)—on the dispersion of calcined clays with varying metakaolinite contents (30.04–74.91 wt%) in synthetic cement pore solution (SCPS). Clays were characterized by XRF, XRD, TGA, FTIR, BET, Blaine fineness, and particle size distribution; PCEs were characterized by FTIR, ¹H NMR, GPC, and zeta potential. Dispersion was assessed via mini-slump tests for water demand, PCE dosage to achieve 260 ± 5 mm spread, and slump retention over 120 min, quantified by a normalized spread retention index (SR₁₂₀). Results revealed that clays with a higher metakaolinite content (58.45–74.91 wt%) and Blaine fineness (up to 13.116 m²/g) required two times higher PCE dosages and exhibited greater water demand due to enhanced surface reactivity and Ca²⁺/carboxylate affinity. Slump retention depended on PCE–clay compatibility: at a low metakaolinite content (30.04 wt%), all PCEs yielded SR₁₂₀ ≈ 1; at higher contents, dispersing-rich PCEs (e.g., 75:25 ratio) sustained superior retention (SR₁₂₀ > 1 in intermediate cases), while stabilizing-rich variants showed rapid loss. Zeta potential values remained close to zero due to the high ionic strength of the SCPS, indicating that electrostatic interactions play only a secondary role in the dispersion process, while steric effects govern the performance of the investigated PCEs. Overall, optimal PCE selection requires matching polymer architecture to clay reactivity for effective dispersion and fluidity retention in sustainable calcined clay systems. Full article

To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of halogens on the binding properties of compounds bearing benzamidomethyl units was investigated, whereby the type of halogen and its ring position were varied. The question was whether the presence of halogens could lead to an increase in binding effectivity and whether this increase can be attributed to the formation of halogen bonds (especially for X = Br and I in ortho position) with the sugar substrate or to other effects. The binding studies revealed some interesting relationships between structure and binding affinity for the tested compounds 1–9. For those bearing the halogen substituent in the ortho position to the amide functionality, the binding affinity increases in the expected order 4 (o-F) < 3 (o-Cl) < 2 (o-Br) < 1 (o-I). In the presence of small amounts of water in CDCl₃, an increase in binding strength was observed in comparison to experiments conducted in dry CDCl₃. The present studies aim to provide impulses for the use of halogenated building blocks in the design of artificial carbohydrate receptors. Optimizing the type of halogenated units and the receptor architecture should result in more effective carbohydrate receptors capable of functioning effectively in aqueous media through a combination of different noncovalent interactions. Full article

Sodium alginate (SA)-modified shellac nanoparticles were developed as pH-responsive carriers for cinnamon essential oil (CEO) encapsulation in aquatic product preservation. Three polyelectrolytes (SA, chitosan (CS), gelatin (Gel)) were evaluated at concentrations of 0.025–0.3% (w/v). Under pH conditions simulating spoilage (6.0–7.5), SA-SNPs exhibited superior stability with minimal changes in particle size, PDI, and zeta potential, while CS and Gel systems aggregated near their pKa values. At 0.1% SA, CEO-loaded nanoparticles (SA-SCNPs) showed excellent properties: small size (160 nm), high encapsulation efficiency (90%), and pH-triggered release (77.76% at pH 7.0 via Ritger–Peppas kinetics, n = 0.58). FT-IR confirmed ionic and hydrogen bonding between the SA and shellac. SA-SCNPs enhanced antibacterial efficacy against Shewanella putrefaciens and Pseudomonas fluorescens and maintained stability under ionic strength (300 mmol/L NaCl) and temperature variations (−18 °C to 25 °C), attributed to SA’s cryo-resistance and steric effects. This system offers a smart delivery platform for aquatic preservation. Full article

Improving the interfacial compatibility between cellulose and poly(butylene adipate-co-terephthalate) (PBAT) is critical for enhancing the performance of PBAT-based composites. Here, microcrystalline cellulose (MCC) was homogeneously silanized at the molecular chain level using t-hexyldimethylchlorosilane (TDMS-Cl) as the modifier, yielding t-hexyldimethylsilylated cellulose (TDMS-Cell). TDMS-Cell/PBAT composite films were then prepared by solution blending and casting in tetrahydrofuran (THF). Structural characterizations confirmed the successful grafting of TDMS-Cl onto cellulose chains, resulting in TDMS-Cell with a degree of substitution of approximately 2. Microstructural observations combined with thermal analysis revealed that TDMS-Cell exerted a dual effect on the crystallization behavior of PBAT: it acted as a heterogeneous nucleating agent that increased the crystallization temperature, while the pronounced steric hindrance simultaneously suppressed crystal growth. Mechanical testing showed that simultaneous strengthening and toughening were achieved at an optimal TDMS-Cell loading of 3–5 wt%. Specifically, the tensile strength increased from ~16 MPa for neat PBAT to 21 MPa (31.25% improvement), and the elongation at break increased from ~700% to 964% (37.7% improvement). In addition, the incorporation of an appropriate amount of TDMS-Cell effectively enhanced the surface hydrophobicity of the composite films. At higher filler loading, however, solvent evaporation-induced phase separation led to self-aggregation of TDMS-Cell, which in turn deteriorated both the mechanical properties and surface hydrophobicity of the composites. Overall, this work systematically elucidates the structure–property relationships of silanized cellulose/PBAT composites in a homogeneous solution system, providing a rational basis for interfacial design and property optimization of PBAT/biomass-based composite materials. The prepared TDMS-Cell/PBAT composite films with balanced mechanical strength, tunable crystallization behavior, and improved surface hydrophobicity exhibit great potential for practical applications in high-performance flexible packaging materials, functional film substrates, lightweight composite structural components, and tunable hydrophobicity coating substrates. Full article

This study aims to systematically investigate the influence of substituent effects on the strength of Lewis acid–base interactions in frustrated Lewis pairs (FLPs). Specifically, -C₆F₅ groups of the classical Lewis acid B(C₆F₅)₃ are sequentially replaced with -C₆Cl₅, -C₆Br₅, and -C₆I₅ groups, and the Lewis acids are paired with the Lewis base 1,3-disubstituted imidazol-2-ylidene (ItBu) to form FLPs. Further energy decomposition analysis (sobEDA), orbital analysis, and molecular fragment density difference (MFDD) analysis reveal the nature of the substituent effect on the interaction energy (∆Eint) of the FLPs. The research findings indicate that the ∆Eint of B(C₆F₅)3-ItBu, B(C₆F₅)_x(C₆Y₅)_3−x-ItBu (x = 0, 1, 2; Y = Cl, Br, I) originates mainly from the interaction between the outermost halogen atom of the Lewis acid and the central carbon (C) atom of the Lewis base, rather than from the interaction between the central atoms boron (B) and carbon (C). This mechanism ultimately leads to a ∆Eint for B(C₆F₅)₂(C₆Y₅)-ItBu (Y = Cl, Br, I) that is comparable to that of B(C₆F₅)₃-ItBu. This indicates that modified B(C₆F₅)₂(C₆Y₅) (Y = Cl, Br, I) exhibits greater potential for the construction of novel FLPs. Full article

Non-metallic hydride donors have emerged as an interesting, highly tunable class of compounds capable of CO₂ reduction, with benzimidazoles being simple, yet efficient and regenerable, representatives. In this work, the role of superbases as auxiliary groups attached to the benzimidazole framework was investigated using the CPCM(CH₃CN)/ωB97xD/aug-cc-pVTZ//CPCM(CH₃CN)/ωB97xD/6-31+G(d,p) approach. Three modes of operation were assessed through hydricity calculations and the modeling of two different CO₂ reduction mechanisms. Among the superbases considered, phosphazene substituents yielded the largest increase in the hydride donation ability, lowering hydricity by 6 kcal mol⁻¹ relative to 2-methylbenzimidazole, with the α-substitution exerting a stronger effect than β-substitution. For most systems, changes in hydricity correlate with changes in aromaticity, except in systems where steric congestion limits optimal substituent alignment. CO₂ activation pathways encompassing guanidine/CO₂ hydrogen bonding and guanidinium carboxamidine formation were modeled. In the former, transition state structures were significantly stabilized, and the overall exergonicity of the reduction is enhanced. Also, utilizing the longer and more flexible linker additionally decreases the barrier for the reaction. The carboxamidine pathway is disfavored because of the high stability of the carboxamidine intermediate and low barrier for the C–N bond cleavage, which reverses the mechanism to the reduction of isolated CO₂. Full article