The Royal Society of Chemistry最新文献

Spectrin αII and βII, the predominant non-erythroid isoforms, assemble into cytoskeletal networks that shape the plasma membrane. However, how these networks interact with membranes of different curvatures remains unclear. Using microfluidic deformation cytometry, we show that spectrin βII overexpression increases the apparent stiffness of MDA-MB-231 breast cancer cells. Fluorescence microscopy further demonstrates that spectrin is excluded from highly curved regions and enriched on flatter membranes in vivo, specifically those with an absolute curvature |κ| < 0.2 µm⁻¹. Consistently, in vitro reconstitution with spherical supported lipid bilayers (SSLBs) shows that purified spectrin heterodimers preferentially bind low-curvature membranes, exhibiting ∼15-fold higher association with 1000 nm SSLBs (|κ| ≈ 0.5 µm⁻¹) than with 30 nm SSLBs (|κ| ≈ 66.7 µm⁻¹). This common curvature-dependent preference is promoted by spectrin oligomerization. Together, these results establish spectrin as a curvature-responsive cortical scaffold that selectively stabilizes flat membrane domains, thereby maintaining cellular stiffness.

Lithocarpus litseifolius [Hance] Chun (L. litseifolius), a herbal tea rich in bioactive polysaccharides, has garnered attention for its health-promoting potential. Polysaccharides represent its principal bioactive component and play a significant role in regulating the gut microbiota. This study investigated the physicochemical characteristics and in vitro digestion bioactivities of special-grade polysaccharides (STPs) and first-grade polysaccharides (FTPs) from L. litseifolius green tea, alongside their modulatory effects on the gut microbiota following in vitro fermentation. The results demonstrated that STPs exhibited higher total carbohydrate and uronic acid content, higher molecular weight, and greater in vitro bioactivity compared to FTPs, despite structural similarities. During in vitro simulated digestion, polysaccharides underwent moderate physicochemical modifications accompanied by partial loss of bioactivity. Notably, STPs exhibited a greater extent of degradation compared to FTPs. Despite differential digestion-induced degradation, most STPs and FTPs remained largely intact upon reaching the colon and were thus accessible to the gut microbiota for fermentation. Fecal fermentation demonstrated efficient microbial utilization of STPs and FTPs, each modulating the architecture of the human gut microbiota, characterized by carbohydrate consumption, a decrease in pH, and an elevated relative abundance of beneficial bacterial phyla, including Firmicutes and Bacteroidota. Concurrently, a marked increase in short-chain fatty acid (SCFA) output-particularly acetate and propionate-was observed. STPs primarily enriched Actinobacteria, whereas FTPs favored Bacteroidota, both contributing to elevated acetate and propionate levels while suppressing potential pathogens such as Proteobacteria and Escherichia-Shigella. These findings underscore the potential of L. litseifolius green tea polysaccharides to serve as effective prebiotics for gut microbiota modulation.

Quasi-elastic neutron scattering was applied to the study of human serum albumin metalation by anticancer drugs, with a specific focus on understanding the effects on the protein dynamics at the atomic scale. Two drugs were studied, a dinuclear Pd-complex and the clinical agent cisplatin. Both drugs prompted a decrease in the overall mobility of the protein, and this perturbation is closely associated with the protein's hydration layer. Opposite effects were detected for the Pt- and Pd-agents regarding the protein's local and internal dynamics. The influence of the Pd-compound at the nanosecond scale is particularly intriguing, as it reduced the observed backbone dynamics below 290 K. This enhanced knowledge on the drug's pharmacokinetics is expected to contribute to the design of improved anticancer agents (with lower toxicity and increased bioavailability at the target).

Continuous selective hydrogenation of aromatic compounds exhibits broad application prospects, serving as a key process for the synthesis of high-value-added polymer monomers and pharmaceutical intermediates. The fabrication of heterogeneous catalysts being even more critical to enabling this continuous process. Herein, the traditional preparation protocol of supported Ru-based catalysts was systematically optimized, resulting in a novel Ru/MgO–Al₂O₃ catalyst with highly dispersed, ultra-small Ru nanoparticles. This innovative catalyst demonstrated exceptional catalytic activity and selectivity for the hydrogenation of phenolic compounds to alicyclic alcohols, with preferential aromatic ring hydrogenation and suppressed C–O/C–C bond hydrogenolysis. Leveraging this insight, additional studies revealed its comparable outstanding activity and selectivity in the hydrogenation of aromatic esters and ethers to corresponding alicyclic derivatives. This discovery is critical for realizing aromatic hydrocarbon saturation and non-aromatic residue in chemical processes, thereby endowing it with profound significance in the field of chemical manufacturing.

This study aimed to evaluate the potential hypoglycemic properties of brewer's spent yeast β-glucan concentrate (β-GC) through the study of its inhibitory effect on dipeptidyl peptidase IV (DPP-IV), α-amylase, and α-glucosidase enzymes either alone or incorporated into an extruded rice product subjected to simulated gastrointestinal digestion. Moreover, the hypoglycemic effect on 2D mouse jejunal organoids of bioaccessible compounds from extruded rice products to which are added β-glucans was studied. The β-GC showed DPP-IV, α-amylase, and α-glucosidase inhibitory activities increased by the presence of peptides and phenolic acids. The kinetic analysis of α-amylase and DPP-IV inhibition showed that β-GC inhibited these enzymes in a non-competitive mode, while for α-glucosidase, it was competitive. Extruded product with β-GC (ERB) showed a lower degree of starch hydrolysis than that observed for extruded rice (ER). The estimated glycemic index value for ERB was 12% lower than that found for ER (61.2 ± 0.2 vs. 69.5 ± 0.1%, respectively). The ERB-digested products had lower IC₅₀ values for α-amylase, α-glucosidase, and DPP-IV enzymes than those of β-GC, indicating a hypoglycemic-promoting effect on the food matrix, which was associated with the release of phenolic acids and bioactive peptides during in vitro digestion. Moreover, phenolic acids and mannose-linked peptides dialyzed from ERB enhanced the hypoglycemic properties of β-glucan through the inhibition of α-glucosidase and DPP-IV enzymes and the reduction of lactase, sucrose-isomaltase, and glucose transporter 2-gene expression in organoids, which confirmed their hypoglycemic properties.

β-Caryolane derivatives possess a unique skeletal structure and a wide range of practical applications. Recent studies suggest that certain β-caryolane derivatives may exhibit enhanced anti-colorectal cancer activity compared to their natural parent compounds, β-caryolanol and β-caryophyllene (β-CP). However, the structural diversity of known β-caryolane derivatives remains limited, likely due to challenges in their synthesis. In this study, we systematically investigated, for the first time, the reactivity of three nucleophiles (sulfonamides, amides, and azide) with β-CP under acid catalysis. The corresponding β-caryolane-type products were successfully obtained in a single step. The azide-addition product further underwent click reactions with various alkynes to yield triazole derivatives. Compared to β-CP or β-caryolanol, most amino-substituted β-caryolane derivatives demonstrated significantly improved anti-proliferative activity against several colorectal cancer cell lines, especially HT-29 cells. Among them, compound NC-19 showed the most potent antiproliferative effect against HT-29 cells with an IC₅₀ of 2.496 ± 0.255 µM. Preliminary pharmacological mechanism studies indicated that NC-19 induces apoptosis, arrests the cell cycle at the G0/G1 phase, significantly increases intracellular ROS levels and suppresses cell migration in HT-29 cells. These results expanded the chemical diversity of bioactive β-caryolane derivatives and offered new options for the development of anti-colorectal cancer agents.

A new class of compounds was designed and synthesised using a molecular hybridisation technique based on the dihydropyridine, isatin, triazole, thiazole, benzothiazole, and glucose scaffolds. The alkyne derivatives of dihydropyridine were synthesised by using reusable Fe-doped Ce-oxide nanoparticles via a three-component Biginelli reaction. The substances were then tested for their cytotoxic effects on two human breast tumour cell lines, MCF-7 and MDA-MB-231, as well as non-cancerous breast epithelial cell lines (i.e., HEK293). The primary objective was to synthesise the more efficient breast cancer cell inhibitory molecules, which contain multiple scaffolds, and to investigate their potential as anti-breast cancer cell inhibitory therapeutic agents. Notably, compound-6, 7 and 14a exhibited remarkable anti-cancer activity against two prominent breast-cancer cell-lines, MCF-7 and MDA-MB-231. The IC₅₀ values of the compounds 6, 7, and 14a against MCF-7 and MDA-MB-231breast cancer cell lines were found to be the lowest. The successful synthesis of these dihyropyrimidines using an environmentally friendly approach emphasises the significance of sustainable and eco-friendly methodologies in pharmaceutical research.

We carried out theoretical analysis and experimental investigations to update our understanding concerning rupture and fracture transitions in continuous stretching of vulcanized natural rubber (NR). Besides a previously reported rupture transition in notch-free NR as a function of test temperature, we predict and confirm at elevated temperatures the existence of a rupture transition with respect to the applied stretch rate. In addition to the previously observed fracture transition in prenotched NR with respect to notch size, we also predict and observe two other transitions when either stretch rate or temperature is varied. For the first time we explain, based on our recently proposed kinetic theory of bond dissociation (KTBD) for elastomeric rupture and fracture, why these five transitions are abrupt with respect to the three variables of notch size, stretch rate and temperature for both unnotched and prenotched NR. Since the transition is determined by whether strain induced crystallization (SIC) in NR occurs - SIC reinforces NR by prolonging its lifetime, the essential physics behind these transitions can be understood by answering whether the polymer network could undergo sufficient stretching to produce SIC before the network breakdown through chain scission. The lifetime of the network competes with the timescale required for strain-induced crystallization, and the experimental timescale prescribed by the stretch rate is the third timescale. The competition among these timescales exhibits itself in the form of these abrupt transitions.

Trauma and diseases such as gangrene, diabetes mellitus, leprosy, or advanced-stage cancer requiring resections may lead to digit loss due to the limited capacity of tissue regeneration. The increasing global incidence of phalanx fractures necessitates surgical intervention for restoring organ function. Early mobilization post-surgery significantly improves the range of motion and overall functional outcomes, emphasizing the need for mechanically stable and biologically responsive solutions. In this study, a CT-derived, site-specific "personalized" phalanx reconstruction was fabricated using bioresorbable fibres by melt-extrusion printing. Scaffold architecture was optimized to provide partial mechanical stability, thus promoting early-stage soft-tissue integration and joint articulation. The composition of PCL-bioglass material was optimized as a bioactive template with biodegradability in vivo. Finite-element analysis (FEA) was employed to ensure efficient stress distribution, optimum deformation, and site-specific modulus matching. Physicochemical characterization, in vitro and in vivo biological assessment, especially site-specific implantation in a rabbit model, revealed the ability of the scaffold to accelerate bone remodelling. An AI-assisted mathematical model trained on micro-CT-derived experimental data was developed to predict the intermediate period of bone regeneration over three years, providing a next-generation solution for personalized implant-based treatment to restore skeletal tissue function.