Tumor microenvironment-activated theranostic nanozymes for trimodal imaging-guided combined therapy.

Synergistic therapy is expected to be a promising strategy for highly effective cancer treatment. However, the rational design of a simple and multifunctional nanoplatform still remains a grand challenge. Considering the nature of weak acidic, hypoxic, and H2O2 abundant tumor microenvironment, we constructed an indocyanine green (ICG) modified platinum nanoclusters (Pt NCs) decorated gold nanobipyramids (Au NBPs) to form the multifunctional nanocomposites (Au NBPs@Pt NCs-ICG) for multimodal imaging mediated phototherapy and chemodynamic cancer therapy. The photosensitizer ICG was covalently linked to Au NBPs@Pt NCs by bridging molecules of SH-PEG-NH2 for both photodynamic therapy (PDT) and fluorescence imaging. Besides, Au NBPs@Pt NCs-ICG nanocomposites exhibited catalase- and peroxidase-like activities to generate O2 and ·OH, which relieved the tumor hypoxia and upregulated antitumoral ROS level. Moreover, the combination of Au NBPs and ICG endowed the Au NBPs@Pt NCs-ICG with super photothermal conversion for effective photothermal imaging and therapy. In addition, the Au NBPs@Pt NCs-ICG nanoplatform displayed excellent X-ray computed tomography (CT) imaging ability due to the presence of high-Z elements (Au and Pt). Overall, our results demonstrated that Au NBPs@Pt NCs-ICG nanoplatform exhibited a multimodal imaging guided synergistic PTT/PDT/CDT therapeutic manners and held great potential as an efficient treatment for breast cancer.

Recovery of glymphatic system function in patients with temporal lobe epilepsy after surgery.

OBJECTIVES: To investigate the recovery of human glymphatic system (GS) function in patients with temporal lobe epilepsy (TLE) after successful anterior temporal lobectomy (ATL) using diffusion tensor image analysis along the perivascular space (DTI-ALPS). METHODS: We retrospectively analysed DTI-ALPS index in 13 patients with unilateral TLE before and after ATL, and compared the index with 20 healthy controls (HCs). Two-sample t tests and paired t tests were performed to analyse differences in the DTI-ALPS index between patients and HCs. The Pearson correlation analysis was used to observe the relationship between the disease duration and GS function. RESULTS: The DTI-ALPS index before ATL was significantly lower in the hemisphere ipsilateral to the epileptogenic foci than in the contralateral hemisphere of the patients (p < 0.001, t = - 4.81) and in the ipsilateral hemisphere of the HCs (p = 0.007, t = - 2.90). A significant increase in the DTI-ALPS index was found in the hemisphere ipsilateral to the epileptogenic foci after successful ATL (p = 0.01, t = - 3.01). In addition, the DTI-ALPS index of the lesion side before ATL was significantly correlated with disease duration (p = 0.04, r = - 0.59). CONCLUSIONS: DTI-ALPS may be used as a quantitative biomarker evaluating surgical outcomes and TLE disease duration. DTI-ALPS index may also help localise epileptogenic foci in unilateral TLE. Overall, our study suggests that GS may potentially serve as a new method for the management of TLE and a new direction for investigating the mechanism of epilepsy. KEY POINTS: • DTI-ALPS index may contribute to epileptogenic foci lateralisation in TLE. • DTI-ALPS index is a potential quantitative feature evaluating surgical outcomes and TLE disease duration. • The GS provides a new perspective for the study of TLE.

Topological patterns of motor networks in Parkinson's disease with different sides of onset: A resting-state-informed structural connectome study.

Parkinson's disease (PD) has a characteristically unilateral pattern of symptoms at onset and in the early stages; this lateralization is considered a diagnostically important diagnosis feature. We aimed to compare the graph-theoretical properties of whole-brain networks generated by using resting-state functional MRI (rs-fMRI), diffusion tensor imaging (DTI), and the resting-state-informed structural connectome (rsSC) in patients with left-onset PD (LPD), right-onset PD (RPD), and healthy controls (HCs). We recruited 26 patients with PD (13 with LPD and 13 with RPD) as well as 13 age- and sex-matched HCs. Rs-fMRI and DTI were performed in all subjects. Graph-theoretical analysis was used to calculate the local and global efficiency of a whole-brain network generated by rs-fMRI, DTI, and rsSC. Two-sample t-tests and Pearson correlation analysis were conducted. Significantly decreased global and local efficiency were revealed specifically in LPD patients compared with HCs when the rsSC network was used; no significant intergroup difference was found by using rs-fMRI or DTI alone. For rsSC network analysis, multiple network metrics were found to be abnormal in LPD. The degree centrality of the left precuneus was significantly correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) score and disease duration (p = 0.030, r = 0.599; p = 0.037, r = 0.582). The topological properties of motor-related brain networks can differentiate LPD and RPD. Nodal metrics may serve as important structural features for PD diagnosis and monitoring of disease progression. Collectively, these findings may provide neurobiological insights into the lateralization of PD onset.

Evaluation of the Glymphatic System Using the DTI-ALPS Index in Patients with Spontaneous Intracerebral Haemorrhage.

Objective: To investigate the function of the human glymphatic system (GS) in patients with spontaneous intracerebral haemorrhage (sICH) using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS). Methods: Twenty patients with sICH and 31 healthy controls (HCs) were recruited for DTI and susceptibility-weighted imaging scanning. The diffusivity along the perivascular spaces, as well as the projection fibres and association fibres, was evaluated separately. The DTI-ALPS index of each subject was also calculated. Two-sample t-tests and paired t-tests were performed to analyse the difference in ALPS scores between patients and HCs, as well as that between the lesion side and contralateral side. Pearson correlation analysis was used to observe the relationship between disease duration and GS function. Results: The DTI-ALPS index on the lesion side was significantly lower than that of the contralateral side in patients with sICH (p < 0.01, t = -5.77), and it was also significantly lower than that of the ipsilateral side of HCs (p < 0.01, t = -9.50). No significant differences were found in the DTI-ALPS index on the nonlesion side between patients and HCs (p = 0.96, t = 0.05) or between the left and right cerebral hemispheres of HCs (p = 0.41, t = -0.83). The DTI-ALPS index of the lesion side in patients with sICH was significantly correlated with disease duration (p = 0.018, r = 0.537). Conclusions: The present study confirmed that GS dysfunction on the ipsilateral side of the lesion is impaired in patients with haemorrhagic stroke, indicating that the GS may be a separate system in the left and right cerebral hemispheres. The DTI-ALPS index can reflect disease duration. These findings have significant implications for understanding sICH from a new perspective.