JACS Au最新文献

Precise control over two-dimensional (2D) polymer nanostructures remains a fundamental challenge, as polymer self-assembly overwhelmingly favors spherical morphologies. Here, we introduce a topology-driven design strategy that overcomes this limitation, enabling the predictable and modular formation of amorphous polymer nanodiscs. Our strategy decouples nanodisc diameter from bottlebrush chemistry. By systematically varying the length of hydrophobic poly-(ethoxyethyl glycidyl ether) (PEE) side chains in the bottlebrush segment, we obtain precise control over nanodisc diameter while maintaining uniform thickness. This tunability allows investigation of size-dependent cellular interactions using MDA-MB-231 cancer cells. Importantly, we show that nanodiscs can serve as pH-responsive carriers that disassemble under acidic conditions and release ICAM-1 inhibitors (A-205804), resulting in effective suppression of cancer cell migration.

The inherently low immunogenicity of tumor-associated carbohydrate antigens poses a significant obstacle to effective cancer immunotherapy. To address this challenge, we here report a biomimetic self-adjuvanting glycoprotein vaccine platform to elicit robust antitumor immunity against disialoganglioside GD2-positive cancers. This platform is constructed through the site-specific conjugation of a TLR4 agonist GAP112 (MPLA adjuvant analogue) to a carrier protein that is loaded with a chemoenzymatically synthesized GD2 glycan antigen. This precisely engineered "adjuvant-protein-antigen" conjugate is further incorporated into a biomimetic liposomal formulation to enhance its delivery and immune response. The resulting vaccine significantly enhanced lymph node migration and promoted both antigen uptake and maturation of antigen-presenting cells (APCs). Crucially, our vaccine elicited a potent GD2-specific IgG antibody response with markedly higher titers than those from an unconjugated mixture. Sera from immunized mice effectively bound to the target tumor cells and mediated potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), demonstrating functional antitumor immunity. This versatile platform presents a powerful strategy for developing robust carbohydrate-based cancer vaccines, holding substantial promise for broad application in cancer immunotherapy.

The water-gas shift (WGS) reaction is pivotal for H₂ production and purification, yet conventional processes rely on coupled middle and high temperature stages (180-300 °C). Development of wide-temperature-window catalysts could avoid temperature switching and reduce the energy demand. However, room-temperature WGS is particularly limited by sluggish water splitting. Here, we report a continuous-flow solution plasma (CSP) strategy to construct an oxygen vacancy-rich Au₁/CeO₂-Fe single-atom catalyst (SAC). Fe is uniformly doped into the CeO₂ lattice to increase the density of oxygen vacancies and Au is stabilized as isolated atomic sites on the CeO₂ surface. By photothermal excitation, the catalyst delivers high WGS activity across 25-300 °C. Notably, at 25 °C, the CO conversion rises from near-zero for conventional catalysts to 35%, overcoming the kinetic barrier of room-temperature WGS for a low CO conversion rate. Mechanistic studies reveal that Fe doping selectively promotes H₂O dissociation, and Au SACs enhance CO adsorption and oxidation. Meanwhile, light activates CeO₂ lattice oxygen and engages a Mars-van Krevelen cycle. The as-developed catalyst maintains significant activity from ambient temperature to 300 °C without temperature switching, providing a process toward energy-efficient H₂ production and purification.

Photoexcitation in scanning ultrafast electron microscopy is a well-known technique to image charge-carrier transfer across numerous semiconductor surfaces. The contrast mechanism generally relies upon the higher-probability emission of secondary electrons from the excited electrons or, in the presence of oxide thin films, band-relaxation which introduces a field that affects secondary electron emission. Here, we present the case where the laser beam induces heterogeneous ultrafast contrast features despite a lack of heterostructures such as junctions. We attribute the heterogeneity of these responses to variations in oxide-bulk interlayer defects that influence the magnitude and direction of band-bending. Furthermore, we hypothesize the high repetition rate used for investigating these phenomena results in the introduction of nonrest equilibrium states at high enough fluences. Rigorous controls and randomized time point scans have demonstrated the ultrafast nature of these contrast features is real and the intensity variation can be directly correlated to either charge carrier concentration (bare semiconductor) or interlayer trap state concentration (oxide thin film).

The instability of metal-halide perovskites intrinsically stems from weak hydrogen bonding in their organic-inorganic hybrid structure. Here, we demonstrate that prolonged pressure treatment at ∼1.8 GPa for 12 h induces a permanent lattice modification in (FAPbI₃)₀._{9 5}(MAPbBr₃)₀._{0 5} polycrystalline films, characterized by strengthened hydrogen bonding between FA cations and iodide. Notably, such pressure-induced H-bond enhancement is preservable after decompression and yields dramatic stability improvements: Light-induced phase segregation is slowed by 12-fold, while resistance to illumination, heat, and moisture improves by four to six times. First-principles calculations reveal that the treatment raises the migration barrier for iodide, explaining the observed suppression of ion migration and phase segregation. These results establish that prolonged pressure treatment can enhance hydrogen bonding and produce substantially more stable perovskite materials and devices without altering their composition.

Photocatalytic chemical conversion shows a bright future in sustainable synthesis but encounters great challenges in scale-up. Photocatalysis in flow is considered as a solution for maximizing light absorption and mass transfer of reactants and thus has attracted fundamental and applied research. This perspective provides an overview of recent progress on photocatalytic chemical conversions in continuous flow from the viewpoint of system design, circulation, immobilization of photocatalysts, and solar-driven photocatalytic systems. An outlook on the future development of photocatalytic chemical conversion in flow is proposed based on a critical analysis of the challenges for applications, revealing the necessity of intensifying potentially profitable reactions using affordable photocatalysts by self-sustained automated flow systems.

Quantum state-resolved studies of molecular photodissociation provide an effective view of how electronic and nuclear motion conspire to break chemical bonds. Here, we use parity-resolved photofragment imaging of trans-HONO photodissociation to show how electronic symmetry actively steers intramolecular vibrational energy redistribution (IVR) at the moment of bond cleavage. By performing Λ-doublet-resolved detection of OH-(X ²Π_3/2, υ = 0, J = 3/2, 5/2, 7/2) with velocity-map ion imaging, we simultaneously determine the vibrational state distributions and angular distributions of the NO-(X ²Π, υ) cofragment. The parity-resolved measurements reveal a striking correlation: one parity class of OH is strongly associated with highly excited NO-(υ = 2), whereas the opposite parity favors NO-(υ = 1). Analysis of the total kinetic energy release, together with ab initio potential energy and spin-orbit coupling calculations, shows that these propensities fingerprint two competing pathways on electronically distinct excited-state surfaces. A prompt, nearly adiabatic dissociation on an A″ surface preserves electronic symmetry and channels energy into a specific NO stretch, whereas nonadiabatic transfer to an A' surface enables electron-mediated IVR via the out-of-plane mode of trans-HONO. The J dependence of the parity-vibrational correlation further reveals near-resonant coupling between the N=O stretch and a combination band. Our results demonstrate that fragment parity can map electronic symmetry onto product energy flow, offering a general strategy for disentangling electronically mediated and near-resonant vibrational dynamics in complex photochemical reactions.

Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene drive aggressive leukemias with a poor prognosis. AF9 (MLLT3), a YEATS family protein, is a core component of transcriptional and epigenetic regulatory complexes essential for hematopoietic stem cell maintenance. In MLL-rearranged leukemia, the MLL-AF9 fusion protein aberrantly recruits transcriptional and epigenetic modifiers, including DOT1L, BCOR, and CBX8, disrupting normal hematopoietic gene regulation. Despite the importance of these interactions, the molecular mechanisms underlying AF9-partner(s) binding and their dissociation remain unclear. Here, we employed Protein-Protein Interaction-Gaussian accelerated Molecular Dynamics (PPI-GaMD) simulations to probe the dissociation pathways of AF9-bound peptides. Free-energy landscapes revealed that the dissociation process proceeds in a stepwise manner through metastable intermediates. Dissociation predominantly occurred through channel 1, a broad electrostatically asymmetric face of AF9. Consistent with the experimental findings, DOT1L formed the most stable complex with AF9, followed by CBX8 and then BCOR. Distinct intermediate conformations and interaction patterns were observed for each partner, reflecting their differential binding stabilities. Partner release was primarily driven by electrostatic interactions, while metastable intermediates were stabilized by hydrophobic contacts. The extended hydrophobic surface of DOT1L accounted for its enhanced binding, evident from its dominant van der Waals contribution. Clustering analysis identified dominant intermediate conformations that highlight critical steps in peptide dissociation and provide structural templates for inhibitor design. These metastable states represent druggable conformations that can be leveraged in structure-based screening, offering a foundation for targeted therapies in MLL-rearranged leukemias.

Despite substantial progress in glycosyl donor design, the development of mild and stereoselective glycosylation methods remains a central challenge in carbohydrate chemistry. Inspired by the native enzymatic ADP-ribosylation process, in which NAD⁺ serves as the glycosyl donor and nicotinamide acts as the leaving group, we developed a pyridinium-based glycosyl donor that chemically mimics this biological transformation. The donor enables the α-selective formation of O-, S-, and N-glycosides under mild activation conditions. Mechanistic studies indicate that the product configuration is independent of that of the donor and is instead governed by thermodynamic control, favoring formation of the α-configured product. Modification of the protecting groups on the donor allows selective access to β-configured products. This pyridinium donor is fully orthogonal to conventional donors, such as glycosyl thioglycosides and o-alkynylbenzoates, enabling iterative assembly of complex oligosaccharides. This bioinspired platform provides a versatile and complementary approach for the stereoselective construction of both α-and β-glycosidic linkages.

Recent progress in DNA nanotechnology has shown the isothermal assembly of several DNA nanostructures. Isothermal assembly allows DNA nanostructure construction in a variety of ions while simplifying DNA nanotechnology by avoiding the need for thermal cyclers and expands utility by enabling attachment of guest biomolecules on DNA nanostructures at ambient or physiological temperatures. The paranemic crossover (PX) DNA motif has been used in the construction of DNA nanostructures, paranemic cohesion has been used to connect DNA structures as an alternate to sticky end cohesion, and PX DNA has also been implied to have a biological role in homology recognition. In that context, here we demonstrate the successful isothermal assembly of the PX DNA motif in magnesium (Mg²⁺), calcium (Ca²⁺), and strontium (Sr²⁺) at 20 and 37 °C. Using isothermal titration calorimetry, we show that interhelix hybridization of half-PX molecules is favored at higher temperatures, with a heat capacity (ΔC_p) of -1.9 kcal/mol·K. To demonstrate a key advantage of isothermal assembly, we show that PX molecules can be designed to contain thrombin-specific aptamers for binding one or two thrombin molecules site specifically in an entirely isothermal procedure. Our work extends isothermal assembly and the use of different counterions for complex DNA motifs while demonstrating the attachment of guest molecules at constant temperatures.