Aggregate (Hoboken, N.J.)最新文献

Accumulating evidence indicates that G-quadruplexes (G4s) are involved in transcriptional regulation. Previous studies have demonstrated that DHX36 preferentially resolves G4s, suggesting its potential impact on gene transcription mediated by these structures. However, systematic validation is required to establish a link between DHX36 activity and its roles in transcriptional regulation. In this study, we investigate the role of DHX36 in transcription. First, we employ the cleavage under targets and tagmentation (CUT&Tag), an efficient method for mapping protein–DNA interactions, to identify the binding sites in the chromatin of MCF-7 cells. Subsequently, we use the auxin-inducible degron (AID) protein degradation system and improved nascent RNA sequencing method acrylonitrile-mediated uridine-to-cytidine conversion sequencing (AMUC-seq) to pinpoint genes directly regulated by DHX36. Our results reveal a significant enrichment of G4 structures at DHX36 target sites, predominantly located in active genomic regions. In vitro assays further demonstrate DHX36's interaction with G4 sequences from three specific oncogenes. These findings underscore the potential role of DHX36 in modulating gene transcription through G4 structures.

Recent experiments have shown that hole traps could be suppressed in polymer light-emitting diodes under current stress by diluting the light-emitting conjugated polymers within an “inert” large-bandgap host material. However, it is unclear why there is an enhanced dilution effect in partially miscible blends rather than fully miscible blends, as intuition would suggest that better miscibility leads to better dilution. In this work, we propose a cascade analysis by combining multiple fluorescence microscopic techniques and all-atom molecular dynamics simulations to study the solid-to-solid dilution of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) in MEH-PPV/polystyrene (PS) blends and MEH-PPV/poly(vinylcarbazole) (PVK) blends. By varying the molecular weights of PS and PVK, we can regulate their miscibility with MEH-PPV. The results corroborate that the dilution effect is enhanced in partially miscible blends rather than fully miscible ones. This is because, in partially miscible blends undergoing phase separation, the concentration of MEH-PPV is notably decreased in the phase occupying the majority of the volume, leading to an overall greater dilution effect than in fully miscible blends. Moreover, MEH-PPV could adopt the more extended conformation in the fully miscible blend, causing a shorter intermolecular distance to further undermine the dilution effect. These findings explain the seemingly counterintuitive more effective dilution effect observed in the recently reported partially miscible blends and provide guidance for further enhancing the performance of future generations of polymer light-emitting diodes.

Poly(vinyl alcohol) (PVA) is biodegradable, recyclable, and has high tensile strength. Therefore, it is ideal for the development of environment-friendly sustainable bioplastics. However, at elevated humidity, the mechanical properties of PVA bioplastic films undergo degradation owing to their intrinsic hydrophilic and hygroscopic nature, hindering their applications. This study proposes a nanoconfined assembly strategy to produce humidity-adaptive, mechanically robust, and recyclable bioplastic film. The strong hydrogen bonds between PVA and cellulose nanofibrils inhibit the penetration of water molecules into the film to promote humidity resistance. Further, the robust coordination interactions between bentonite nanoplates, PVA, and cellulose nanofibrils restrict the slip of polymer chains during deformation, leading to enhanced mechanical properties. Benefiting from the nanoconfined assembly architecture in aggregated composites, the resulting reinforced PVA film simultaneously exhibits strength, stiffness, toughness, fracture energy, and tearing energy of 55.9 MPa, 1,275.6 MPa, 162.9 MJ m⁻³, 630.9 kJ m⁻², and 465.0 kJ m⁻², respectively. Moreover, the film maintains a strength of approximately 48.7 MPa even at 80% relative humidity for 180 days. This efficient design strategy applies to diverse scales and structured cellulose biomacromolecules. Moreover, it facilitates the application of recyclable high-performance bioplastic films to settings that require high humidity tolerance.

Curved π-electron systems show unique properties and assembly feature that enable the specific applications in materials science and supramolecular chemistry. Herein, fullerene, carbon nanohoop and π-bowl are integrated by the coupling of covalent and supramolecular tactics. Firstly, π-bowl trichalcogenasumanenes (TCSs) are fused with a carbon nanohoop [10]CPP via covalent joint to form molecular crowns 4a/4b, which show structural and electronic complementarity and accordingly strong binding affinity to C₆₀/C₇₀. Secondly, the supramolecular assemblies of 4a/4b with fullerenes afford the host-guest complexes 4a/4b⊃C₆₀/C₇₀ in solution (molar ratio, 2:1) and solid state (molar ratio, 1:1). In the crystals of host–guest complexes, the intra-cluster and inter-cluster interactions are respectively dominated by the [10]CPP and TCSs moieties of 4a/4b. Additionally, it is found that 4a/4b are good photosensitizers for generating ¹O₂ and show structural adaptability in accordance to assembly conditions. 4a/4b take an endo-conformation in their own crystals with TCSs and [10]CPP moieties being bowl-shaped and elliptical, respectively. In contrast, the [10]CPP on 4a/4b changes into circular and the TCSs moiety becomes flat (for 4b) or shows bowl inversion to be exo-conformation (for 4a) in 4a/4b⊃C₆₀/C₇₀.

Macrocycles are key tools for molecular recognition and self-assembly. However, traditionally prevalent macrocyclic compounds exhibit specific cavities with diameters usually less than 1 nm, limiting their range of applications in supramolecular chemistry. The efficient synthesis of giant macrocycles remains a significant challenge because an increase in the monomer number results in cyclization-entropy loss. In this study, we developed a low-entropy-penalty synthesis strategy for producing giant macrocycles in high yields. In this process, long and rigid monomers possessing two reaction modules were condensed with paraformaldehyde via Friedel–Crafts reaction. A series of giant macrocycles with cavities of sizes ranging from 2.0 to 4.7 nm were successfully synthesized with cyclization yields of up to 72%. Experimental results and theoretical calculations revealed that extending the monomer length rather than increasing the monomer numbers could notably reduce the cyclization-entropy penalty and avoid configuration twists, thereby favoring the formation of giant macrocycles with large cavities. Significantly, the excellent self-assembly capacity of these giant macrocycles promoted their assembly into organogels. The xerogels exhibited enhanced photoluminescence quantum efficiencies of up to 83.1%. Mechanism investigation revealed the excellent assembly capacity originated from the abundant π–π interactions sites of the giant macrocycles. The outstanding emission enhancement resulted from the restricted nonradiative decay processes of rotation/vibration and improved radiative decay process of fluorescence. This study provides an effective and general method for achieving giant macrocycles, thereby expanding the supramolecular toolbox for host–guest chemistry and assembly applications. Moreover, the intriguing assembly and photophysical properties demonstrate the feasibility of developing novel and unique properties by expanding the macrocycle size.

The presence of bacterial biofilms and the occurrence of excessive inflammatory response greatly imped the healing process of chronic wounds in diabetic patients. However, effective strategies to simultaneously address these issues are still lacking. Here, a microenvironment-adaptive nanodecoy (GC@Pd) is constructed via the coordination and in situ reduction of palladium ions on gallic acid-modified chitosan (GC) to promote wound healing by synergistic biofilm eradication, inflammation alleviation, and immunoregulation. During the weakly acidic conditions of the biofilm infection stage, GC@Pd serves as a nanodecoy to induce bacterial aggregation. Subsequently, through its oxidase-like activity generating reactive oxygen species and the hyperthermia from photothermal effects, it effectively eliminates the biofilm. As the local microenvironment of diabetic wounds transitions to an alkaline inflammatory state, the enzyme-like activity of GC@Pd adapts to catalase-like activity, effectively eliminating reactive oxygen species at the site of inflammation. Additionally, GC@Pd could selectively capture pro-inflammatory cytokines through Michael addition reactions. In vivo experiments and transcriptomic analysis confirmed that GC@Pd could accelerate the wound transition from inflammatory to proliferative phase by eliminating biofilm infection and reducing the inflammatory response, thus promoting diabetic chronic wound healing. The nanodecoy provides a potential therapeutic strategy for treating biofilm-infected diabetic chronic wounds.

Solid bubbles have expanded the SERS assay toolbox, but their detection performance in biofluids is still hampered by the irrational design of the plasmonic sensing interface. A plasmonic bubble aggregate-driven DNA-encoded SERS assay is reported here that enables simultaneous, ultrasensitive, and specific detection of multiple miRNAs in blood samples for accurate cancer diagnosis. In this assay, the buoyancy of plasmonic bubbles allows them to self-aggregate at a droplet apex for SERS reconfiguration, form single-layer bubble aggregates with plasmonic nanogaps, and prevent the coffee ring effect during evaporation assembly. Furthermore, DNA-encoded plasmonic bubbles seamlessly couple with dual-color catalytic hybridization assembly to amplify the specific miRNA-responsive Raman signal, and function as both an analyte concentrator and a Raman signal aggregator without external forces. Using these merits, this magnet-free, portable assay achieves femtomolar dual-miRNA quantitation with single-base resolution, simultaneous miRNA detection across four cell lines, and accurate cancer diagnosis (AUC = 1) via analyzing 40 blood samples with machine learning, thus providing a promising tool for clinical diagnosis.

To address the unique challenges of diabetic wound healing, wound dressings, particularly multifunctional hydrogels have garnered considerable interest. For the first time, a novel environmentally friendly soy protein-based hydrogel is developed to accelerate the healing of diabetic chronic wounds. Specifically, this hydrogel framework is in direct formation through the dynamic Schiff base between oxidized guar gum and epigallocatechin-3-gallate (EGCG)-modified soy protein isolate. Meantime, the addition of Ag⁺ enhances the cross-linking of the hydrogel network by forming metal-ligand bonds with the catechol groups in EGCG. Interestingly, the stretchability (up to 380%), swelling, and rheology properties of the hydrogel can be controlled by fine-tuning the density of metal-ligand bonds, endowing them with a high potential for precise matching. Additionally, various dynamic bonds endow hydrogel with excellent self-healing ability, adhesiveness, and injectability. This hydrogel also exhibits good antibacterial properties, biocompatibility, and cell migration capabilities. Both in vivo and in vitro experiments demonstrated the outstanding anti-inflammatory capacity of the hydrogel and its ability to modulate macrophage polarization. Consequently, the hydrogel has proven effective in promoting wound healing in a diabetic full-thickness wound model through enhanced angiogenesis and collagen deposition. This eco-friendly plant protein hydrogel offers a sustainable solution for wound care and environmental protection.

Ultralong thermally activated delayed fluorescence (UTADF) materials play an important role in realizing time-dependent color-tunable afterglow. Some typical carbazole (Cz) derivatives have been reported to exhibit UTADF properties. However, a 10-fold difference in TADF lifetime was found between commercial Cz derivatives and the corresponding lab-synthesized ones, which indicated that UTADF may not be derived from the single Cz derivatives as reported. To reveal the real mechanism, we synthesized three Cz derivatives and one isomer to form three host-guest pairs for optical studies. The photophysical properties revealed that UTADF originated from the intermolecular charge transfer between host and guest, while the ultralong organic phosphorescence was from the guest. Thanks to the rich color variations in luminescence displayed by 4-(1H-benzo[f]indol-1-yl)−4′-(9H-carbazol-9-yl)-[1,1′-biphenyl]−3,3′-dicarbonitrile/4,4′-di(9H-carbazol-9-yl)-[1,1′-biphenyl]−3,3′-dicarbonitrile (CBP-2CN) at different delay times, it can be applied to realize multi-dimensional encryption in both delay time and luminescent color.

Photodynamic therapy is a highly recommended alternative treatment for solid tumors, such as cutaneous or luminal tumors, in clinical practice. However, conventional photosensitizers (PSs) often induce undesirable phototoxic effects because of their normal tissue distribution and a reduction in antitumor effects resulting from aggregation-caused quenching effects. The present study developed a novel nano-formulated aggregation-induced emission (AIE)-characteristic PS, nab-TTVPHE, which is composed of human serum albumin as a carrier and TTVPHE as a therapeutic agent, as a more effective cancer treatment with lower phototoxic effects. Notably, the reactive oxygen species generated by TTVPHE were shielded by the nanoaggregate structure, and the photodynamic activity was after nanostructure dissociation. Nab-TTVPHE was actively internalized in tumor cells via secreted protein, acidic and rich in cysteine and released to form nanoaggregates. TTVPHE accumulated in mitochondria, where it triggered mitochondrial damage under light irradiation via its photodynamic activity and induced pyroptosis via the caspase-3/gasdermin E (GSDME) signaling pathway to kill tumor cells. Therefore, this nano-formulated AIE-characteristic PS provides an innovative strategy for cancer treatment with lower phototoxic effect and the ability to boost potential antitumor immunity via GSDME-mediated pyroptosis.