Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic–basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

These findings provide novel evidence regarding the trait and state markers of depression on neural responses to psychosocial stress. Regional activation changes in the ventromedial prefrontal cortex and precuneus may reflect the trait markers of depression. Hyperactivation in the dorsolateral prefrontal cortex and striatum may represent a state-dependent compensatory mechanism during depression remission.