Aggregate (Hoboken, N.J.)最新文献

Biomolecular condensates play crucial roles in cellular physiology and are implicated in neurodegenerative diseases and cancer. However, the mechanisms governing their formation and spatial organization remain poorly understood, largely due to technical challenges. Here, using FUS as a paradigmatic system, we reveal how single-protein sequences determine condensate architecture that is intrinsically linked to biological function. We demonstrate a domain-specific preferential distribution organization: the low-complexity domain (LCD), which drives condensate formation, localizes to the inner layer, while the RNA recognition motif (RRM) preferentially occupies the interfacial layer. This spatial arrangement enhances RNA-binding accessibility, suggesting a direct structure–function relationship. We further propose a sequence–structure–function paradigm for biomolecular condensates: through the cooperation emerging from multiple “stickers,” individual domains function as integrated units in shaping the structure and functionality of biomolecular condensates, which may represent a broader mode of protein–protein interaction (PPI) within condensates. Our findings elucidate the evolutionary logic of protein sequences in driving liquid–liquid phase separation (LLPS) and provide a foundation for designing therapeutics targeting aberrant condensates in disease.

Copper hydride clusters have become especially fascinating in the field of functional cluster-based materials due to the various compositions and architectures as well as intriguing properties especially hydride-related applications. A comprehensive understanding of the synthesis, structure determination, the relationship between structure and properties of copper hydride clusters hold great significance for development of the functional characteristics. In this review, advances in the methodology for the preparation and understanding of atomically precise copper hydride clusters are comprehensively summarized. The functional properties of copper hydride clusters including luminescence behaviors, especially for the tailoring emission features, chirality and catalysis were mainly highlighted. Furthermore, the importance of balancing the stability of copper hydride clusters and the effective development of their functional properties is emphasized. The review discusses the potential of hydride atoms in modulating functionality of copper hydride clusters, which is expected to bring about significant advancements in catalysis and chiral applications. Finally, we provide insights into the prospects for future development on the copper hydride clusters.

Methicillin-resistant Staphylococcus aureus (MRSA), often residing within biofilms and host cells, exhibits heightened resistance to conventional antibiotics and immune clearance, resulting in persistent and recurrent infections. Given the central role of DNA in bacterial proliferation and virulence, it represents an ideal target for the development of next-generation antibacterial agents. In this study, we report the development of a DNA-targeting photosensitizer (PS), TPE-CN, designed for the effective treatment of MRSA-associated infections. TPE-CN demonstrates high specificity for bacterial DNA, along with excellent membrane permeability, enabling disruption of both bacterial DNA and membrane structures. This allows for the efficient eradication of planktonic MRSA. Moreover, TPE-CN can also selectively colocalize with the lysosome of macrophages, facilitating effective eradication of intracellular bacteria while preserving host cell integrity. Furthermore, in vivo studies further validate the potent antimicrobial effects of TPE-CN, resulting in accelerated wound healing in severe MRSA infection models. Collectively, this work presents a novel molecular design strategy for precise bacterial DNA targeting, offering a promising therapeutic avenue for combating drug-resistant pathogens and advancing the development of next-generation antimicrobial therapies.

The interactions that occur in the interface of proteins and ligand-stabilised metal nanoclusters are crucial to understand the adsorption process of biomolecules on the surface of these nanomaterials. Despite the relevance of the adsorption phenomena for biological applications, such as bioimaging, biosensing and targeted drug delivery, efforts to model the interactions observed in the interface of those systems are still scarce in the literature. In this work, a model of the interactions observed in the peptide–Au₃₈(p-MBA)₂₄ interface was developed, employing clustering analysis, an unsupervised machine learning technique. The accuracy of this model was evaluated by simulating the peptide–Au₃₈(p-MBA)₂₄ interaction using molecular dynamics simulations and density functional theory calculations. The insights derived from this model can also be applied to the context of protein–AuNC interactions, given that the model was developed to provide a generalisable approach. The developed model was able to predict the amino acids that could interact well or poorly with the gold nanoclusters (AuNC), defining the specific chemical groups responsible for the effect. The results obtained in this study can lead efforts to accelerate discoveries in the fields that rely on the understanding of the interaction observed in the protein–AuNC interface.

The synthesis of chiral unsubstituted poly(para-phenylene) (PPP) chains has remained elusive for decades, with the production of high-molecular-weight PPP still inaccessible to date. Drawing inspiration from the intrinsic structural chirality of cellulose nanocrystals (CNCs), which plays a crucial role in their self-assembly, we propose a novel strategy to address this synthetic obstacle by effectively immobilizing PPP on individual CNCs. This approach leverages intermolecular forces between CNC and PPP, including the CH–π interaction between the CH group of the pyranose ring and the aromatic ring of the PPP building block, as well as hydrogen bonds formed between the boronic acid groups of the PPP oligomers and the hydroxyl groups of the glucose units within the CNC structure, thereby facilitating the chirality transfer from CNCs to PPP chains. PPP immobilized on the CNC surface exhibits right-handed intrachain helical self-assembly and interchain helical π-stacking, with the degree of polymerization reaching up to 80.2. This helical organization of PPP further laterally demonstrates the right-handedness of individual CNCs in their undried state. Furthermore, suspensions, powders, and films composed of chiral CNC–PPP clusters exhibit pronounced fluorescence, structural coloration, chirality, and circularly polarized luminescence. This work opens novel insights and strategies for inducing chirality into polymer chains via transferring chirality from the nanoobject surface to prepare various chiral assemblies of nanoparticles or conjugated polymers.

Electron transfer is considered to play a critical role in the Type-I photodynamic therapy process, which offers superior performance under hypoxic conditions. However, developing efficient Type-I photosensitizers remains challenging because of the competition between energy and electron transfer processes. Therefore, we designed cyanine dyes (Cy-R) with tunable intersystem crossing (ISC) efficiencies, with the ISC rate reaching 9.29 × 10⁶ s⁻¹. Unlike conventional dimers with short-lived charge-separated states, Cy-R aggregates having sufficiently high ISC efficiency undergo symmetry-breaking charge separation (SBCS) in the triplet state, generating long-lived triplet charge-separated species (Cy-R^•+−Cy-R^•−). This mechanism significantly enhances the production of Type-I reactive oxygen species. Furthermore, Cy-Ac self-aggregation facilitated passive tumor targeting and lysosomal accumulation. Upon photoactivation, Cy-Ac induces lysosomal membrane permeabilization, disrupts autophagy, and triggers lysosome-mediated cell death. This study provides a promising strategy for the development of hypoxia-tolerant Type-I photosensitizers via triplet-state SBCS.

Current phototherapeutic agents based on heptamethine cyanine dyes often rely on symmetric structures, limiting their photodynamic therapy (PDT) efficiency. Herein, we report a novel asymmetric heptamethine cyanine dye (Cyp-TPE) that features a twisted tetraphenylethylene moiety. This design facilitates the formation of stable aggregate nanoparticles (NPs) with a cross-arranged structure, as revealed by molecular dynamics simulations. This specific aggregation mode promotes exciton delocalization and dramatically enhances spin-orbit coupling, leading to an unprecedented ROS quantum yield of 154.54%. Under 808 nm laser irradiation, the Cyp-TPE NPs demonstrate potent synergistic photodynamic and photothermal activity, concurrently triggering ferroptosis and lysosomal dysfunction, thereby achieving multimodal death of cancer cells. Furthermore, the excellent NIR absorption and photothermal conversion of these aggregates enable precise photothermal imaging (PTI) and photoacoustic imaging (PAI). This work highlights the potential of asymmetric molecular design to overcome the limitations of conventional photosensitizers, offering a robust nanoplatform for imaging-guided cancer therapy.

Carbon dots (CDs), as an emerging class of zero-dimensional carbon-based nanomaterials, have attracted widespread attention owing to their remarkable optical properties, solution processability, and environmental friendliness, showing broad application prospects in optoelectronic devices. Nevertheless, although significant research progress has been achieved in recent years, a comprehensive theoretical framework is still absent for clarifying the correlations among the structure, optical properties, and performance of CDs in practical device applications. In this regard, the present review highlights recent developments in utilizing the distinctive optical features of CDs for various optoelectronic systems, including key examples such as photodetectors, optical memristors, lasers, electroluminescent diodes, and photovoltaic cells. Moreover, the current limitations and future research directions for CDs-based optoelectronic technologies are analyzed. The insights provided herein are expected to stimulate further research on enhancing the optical properties of CDs and promoting the rational design of high-performance devices from a new perspective.

The rise in pancreatic diseases, resulting from improved living quality and lifestyle habits changes, has imposed a serious social burden. To better understand the pancreatic functions during disease progression, constructing a bionic pancreas is vital yet challenging in tissue engineering. Herein, inspired by the physiological anatomy of the pancreas, we introduce core-shell microfibers with pancreatic stellate cells (PSCs) in the shell and pancreatic β-cells in the core. Compared to traditional plate culture, the β-cells encapsulated in the microfiber exhibit enhanced glucose-stimulated insulin secretion. Such microfibers also serve as a platform to study the progression of diabetes of the exocrine pancreas, where the PSCs are activated under conditions of pancreatic exocrine diseases such as chronic pancreatitis. The activated PSCs impede insulin synthesis and increase apoptosis in β-cells, resulting in elevated blood glucose. This high-glucose microenvironment further exacerbates the activation of PSCs, causing a vicious cycle of diabetes. Additionally, the bio-inspired pancreas also demonstrates its potential in drug screening, as evidenced by testing the glucagon-like peptide 1 receptor agonist, Exendin-4. Building upon such features, it is convincing that these multi-component microfibers hold promise for exploring the pancreatic exocrine and endocrine interactions, and showing potential in disease modeling, drug screening, and regenerative medicine.

Immunotherapy has emerged as one of the most promising strategies for achieving complete tumor eradication. However, its effectiveness against solid tumors remains limited due to the presence of an immunosuppressive tumor microenvironment. In addition, severe side effects such as cytokine storms further constrain its clinical application. Therefore, there is an urgent need to develop efficient and controllable immunotherapeutic approaches. Herein, we report the development of a novel mitochondrial DNA-releasing photosensitizer, MQ-PPy, which exhibits outstanding mitochondrial localization and robust reactive oxygen species generation. Upon light irradiation, MQ-PPy induces pronounced mitochondrial oxidative damage in tumor cells, triggering the release of immunogenic damage-associated molecular patterns and mitochondrial DNA, which activates the cGAS-STING signaling pathway. Meanwhile, MQ-PPy effectively induces immunogenic cell death, thereby remodeling the tumor immune microenvironment and enhancing antitumor immune responses. In vivo studies confirmed that MQ-PPy-mediated photodynamic therapy significantly inhibits tumor growth and notably increases the infiltration of cytotoxic T cells within the tumor. Moreover, we demonstrated that tumor cells treated with MQ-PPy-mediated PDT can function as a whole-cell vaccine, effectively establishing systemic immune memory and significantly suppressing tumor growth upon rechallenge. This study presents a promising and controllable strategy for advancing tumor immunotherapy through mitochondria-targeted photoactivation.