Science Bulletin最新文献

Combination therapy is a widely used clinical strategy to enhance treatment efficacy against solid tumors. However, the diversity of medicinal drugs and the complexity of in vivo delivery processes present significant challenges for the rational selection and efficient delivery of drug combinations. As a proof of concept, we herein developed an omics-based high-throughput drug screening platform, pharmacotranscriptomic signature enrichment analysis (PSEA), for the prediction of drug combinations of resiquimod (R848) to improve macrophage-mediated cancer immunotherapy. By comparing the critical transcriptional signatures of R848 with chemical perturbation signatures from the LINCS database, PSEA identified mitoxantrone (MIT) as a promising candidate. We then engineered an MIT/R848 co-loaded hydrogel (MIT/R848@Gel) and tested its therapeutic effect in multiple tumor models including the MMTV-PyMT transgenic mouse tumor and VX2 rabbit tumor. Local injection of MIT/R848@Gel not only suppressed the growth of primary tumors but also potently inhibited tumor recurrence and metastasis by eliciting durable and robust systemic antitumor immune responses, resulting in long-term remission in a high percentage of animals. Transcriptional and flow cytometry results indicated that MIT/R848@Gel remarkably reprogrammed immunosuppressive macrophages toward an antitumor phenotype and effectively activated the antitumor effect of cytotoxic T cells. This study establishes a novel framework integrating omics-driven drug discovery with localized combination therapy for enhanced cancer immunotherapy.

Recent experimental advances have uncovered fractional Chern insulator (FCI) states in twisted MoTe₂ (tMoTe₂) systems under zero magnetic field. Understanding the interaction effects on topological phases within realistic model presents a significant theoretical challenge. Here, we construct a moiré superlattice model tailored for tMoTe₂ and conduct investigations using state-of-the-art tensor-network methods. Our ground-state calculations reveal a rich variety of interaction-driven and filling-dependent topological phases, including FCIs, Chern insulators, and generalized Wigner crystals, which are revealed in recent experiments. For FCI state, dynamical simulations uncover a single-particle excitation continuum with a finite charge gap, reflecting the fractionalized charge excitations. Finite-temperature calculations further determine characteristic charge activation and ferromagnetic transition temperatures, reconciling existing experimental discrepancies. Furthermore, using this realistic lattice model, we predict the presence of quantum anomalous Hall crystals exhibiting integer Hall conductivity at fractional fillings in tMoTe₂. By integrating ground-state, finite-temperature, and dynamical analyses, our work establishes a comprehensive framework for understanding correlated topological phases in tMoTe₂ and related moiré systems.

While intramolecular cyclization effectively modulates photoelectronic properties of multi-resonance (MR)-thermally activated delayed fluorescence (TADF) emitters, simultaneous narrowing full width at half maxima (FWHM) of spectra and accelerating reverse intersystem crossing (RISC) remain a formidable challenge. Here, we introduce a phosphorus-carbon-bridged cyclization in MR skeletons to synergistically suppress high-frequency molecular vibrations via skeleton rigidification and enhance spin-orbital coupling through introducing heavy-atom effects. Implementing this approach, two blue emitters, phenylphosphine oxide-bridged (BCzBN-PO) and phenylphosphine sulfide-bridged (BCzBN-PS), are developed and exhibit emission peaks at 467 and 474 nm with FWHMs of 19 and 18 nm, respectively. Moreover, benefiting from the additional heavy atom effect of sulfur complementing that of phosphorus, BCzBN-PS achieved a kRISC of 8.5 × 10⁵ s^-1, nearly 8-fold higher than that of BCzBN-PO (1.1 × 10⁵ s^-1). In the non-sensitized device architecture, both emitters exhibited narrowband emission with a FWHM < 30 nm and a maximum external quantum efficiency (EQE) > 20%. Notably, BCzBN-PS, leveraging its higher upconversion rate, demonstrated a superior maximum EQE and lower efficiency roll-off. Furthermore, in the TADF-sensitized device configuration, the organic light-emitting diodes further validated the enhanced upconversion efficiency-evidenced by BCzBN-PS delivering a higher maximum EQE than BCzBN-PO (43.0% vs. 41.2%) and a reduced efficiency roll-off (30.1% vs. 25.9% at 1000 cd m^-2). This work establishes a molecular engineering paradigm that balances color purity and exciton utilization efficiency, paving new avenues for high-performance narrowband electroluminescence.