University of Beihua

Immune checkpoint inhibitors (ICIs) have emerged as a transformative approach in cancer treatment, yet their efficacy is often limited by low response. Cuproptosis is a novel form of regulated cell death with lipoylated protein aggregation and iron‑sulfur (FeS) cluster protein destabilization. Here, we fabricated a PD-L1 nanobody-engineered bacterial outer membrane vesicles (OMVs) delivering elesclomol (ES) micelles for enhanced immunotherapy in triple-negative breast cancer (TNBC). By decorating OMVs with PD-L1 nanobodies, we enhance the tumor-targeting delivery efficiency of cuproptosis nanoinducers and PD-L1 blockade capability. Simultaneously, the engineered OMVs delivering ES micelles exhibited enhanced cytotoxicity against breast cancer cells via inducing cuproptotic cell death. In mice bearing 4 T1 xenografts, OMV-PD-L1nb@ES demonstrated significant tumor growth suppression. Notably, our nanoparticles elicited a robust antitumor immune response with increased infiltration and activation of CD8⁺ T cells and Treg depletion. By integrating cuproptotic tumor death with immune checkpoint blockade, the dual-functional nanoplatform represents a promising strategy for potentiated immunotherapy.

MicroRNAs (miRNAs) are short strands of RNA, typically 18-24 nucleotides (nt), which have been linked to the development of neurodegenerative diseases, cardiovascular disease and cancer, etc. However, current miRNA detection methods face significant challenges in sensitivity, specificity, and interference resistance. Here, a universal biosensor platform was developed using element tagging and catalytic hairpin assembly (CHA) amplification strategy for triple-signal miRNA detection by inductively coupled plasma mass spectrometry (ICP-MS) and fluorescence spectroscopy. The key element Yttrium (Y) lying in upconversion nanoparticles (UCNPs) serves as a rare earth metal (REM)-tagged signal carrier coupled with cascade CHA reactions for target recycling. Upon miRNA recognition, structural switching of hairpin probes initiates target release for subsequent amplification cycles, enabling single miRNA molecules to drive multiple CHA reactions and generate abundant UCNPs-containing hybrid complexes. Taking advantage of the naturally low background of REMs in biological systems, the routine ICP-MS mode achieved an ultralow detection limit of 0.24 fM, while fluorescence detection reached 3.8 fM. Single-particle ICP-MS (SP-ICP-MS) mode further reduced detection limit to 0.12 fM. The ICP-MS and fluorescence dual-mode design ensured analytical reliability through signal cross-validation. Significantly, this platform demonstrates remarkable versatility-simple modification of DNA sequences enables adaptation to diverse miRNA targets, offering a promising technical solution for clinical miRNA assays.

To evaluate the efficacy of Cognitive Behavioral Therapy (CBT) on improving loneliness among older adults.

A systematic review and meta-analysis.

A systematic search was conducted across 10 electronic databases from their inception to June 21, 2025, to identify eligible randomized controlled trials (RCTs). Studies included older adult participants aged 60 years or above. Two reviewers independently performed the screening process, data extraction, and quality assessment of the selected studies. All statistical analyses were carried out using Stata version 18.0.

Eight RCTs involving 720 participants were included. Pooled analysis revealed a significant and large effect of CBT on improving loneliness among older adults (SMD = -1.00, 95 % CI, -1.59 to -0.42, p < 0.001; low-quality evidence), though substantial heterogeneity was present (I² = 90.5 %). Subgroup analyses indicated that shorter intervention duration (≤12 weeks) (SMD = -1.41, 95 % CI: -2.51 to -0.32, p = 0.011), group-based format (SMD = -1.49, 95 % CI: -2.63 to -0.36, p = 0.010), and online delivery (SMD = -1.51, 95 % CI: -3.93 to 0.92, p = 0.233) may enhance intervention effectiveness. Subgroup analyses also revealed differences across settings. CBT interventions were effective among community-dwelling older adults (SMD = -0.91, 95 % CI: -1.46 to -0.35, p = 0.001), whereas no significant effect was observed among institution-dwelling populations.

CBT was associated with improvements on loneliness among older adults. However, given the substantial heterogeneity observed across studies, these pooled estimates should be interpreted as exploratory rather than definitive. Subgroup findings suggest that intervention format, intervention duration, delivery modality and settings may influence outcomes. Further well-designed rcts are needed to confirm the effectiveness.