Abnormal functional connectivity (FC) at rest has been identified in clinical depressive disorder. However, very few studies have been conducted to understand the underlying neural substrates of subclinical depression. The newly proposed centrality analysis approach has been increasingly used to explore the large-scale brain network of mental diseases. This study aimed to identify the degree centrality (DC) alteration of the brain network in subclinical depressive subjects. Thirty-seven candidates with subclinical depression and 34 well-matched healthy controls (HCs) were recruited from the same sample of college students. All subjects underwent a resting-state fMRI (rs-fMRI) scan to assess the DC of the whole brain. Compared with controls, subclinical depressive subjects displayed decreased DC in the right parahippocampal gyrus (PHG), left PHG/amygdala, and left caudate and elevated DC in the right posterior parietal lobule (PPL), left inferior frontal gyrus (IFG) and left middle frontal gyrus (MFG). In addition, by using receiver operating characteristic (ROC) analysis, we determined that the DC values in the regions with altered FC between the two groups can be used to differentiate subclinical depressive subjects from HCs. We suggest that decreased DC in subcortical and increased DC in cortical regions might be the neural substrates of subclinical depression.

Methylation of the O⁶‐methylguanine methyltransferase (MGMT) gene promoter is correlated with the effectiveness of the current standard of care in glioblastoma patients. In this study, a deep learning pipeline is designed for automatic prediction of MGMT status in 87 glioblastoma patients with contrast‐enhanced T1W images and 66 with fluid‐attenuated inversion recovery(FLAIR) images. The end‐to‐end pipeline completes both tumor segmentation and status classification. The better tumor segmentation performance comes from FLAIR images (Dice score, 0.897 ± 0.007) compared to contrast‐enhanced T1WI (Dice score, 0.828 ± 0.108), and the better status prediction is also from the FLAIR images (accuracy, 0.827 ± 0.056; recall, 0.852 ± 0.080; precision, 0.821 ± 0.022; and F₁ score, 0.836 ± 0.072). This proposed pipeline not only saves the time in tumor annotation and avoids interrater variability in glioma segmentation but also achieves good prediction of MGMT methylation status. It would help find molecular biomarkers from routine medical images and further facilitate treatment planning.

Amphiphilic diblock poly(ε-caprolactone)-b-glycopolypeptides (PCL–SS–GPPs) bearing disulfide bonds were synthesized from a clickable poly(ε-caprolactone)–SS–poly(2-azidoethyl-L-glutamate) diblock copolymer. Galactosyl and lactosyl sugar units as targeting ligands were conjugated to the polypeptide blocks via an efficient click reaction. The chemical structures of PCL–SS–GPPs were characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis. Owing to their amphiphilic nature, these copolymers could self-assemble into spherical nano-sized micelles in an aqueous medium, as confirmed by fluorometry, transmission electron microscopy, and dynamic light scattering. The hydrophobic anticancer drug doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as the magnetic resonance imaging (MRI) contrast agent, were simultaneously encapsulated in the hydrophobic core of the micelles via dialysis. The release profiles of encapsulated DOX from the SPIO/DOX-loaded PCL–SS–GPPs micelles were shown to be rapid in the presence of 10 mM glutathione (GSH) within 24 h, whereas in the absence of GSH, there was less than 35% DOX released from the PCL–SS–GPPs micelles in 24 h. Inverted fluorescence microscopy revealed the specific interaction between the sugars units on the PCL–SS–GPPs surface with the FITC-lectin. MTT assay demonstrated that the blank PCL–SS–GPPs micelles were nontoxic to the HepG2 cells, even for concentrations up to 500 μg mL⁻¹, whereas the free DOX and DOX-loaded PCL–SS–GPPs micelles showed significant cytotoxicity against the HepG2 cells. The fluorescence images and flow cytometry tests revealed that DOX could be efficiently transported into HepG2 tumor cells by PCL–SS–GPPs micelles. The PCL–SS–GPPs micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles enabled excellent MRI contrast enhancement, thus confirming their effectiveness for MR imaging.

Accurate detection and characterization of focal liver lesions, including differentiation between malignant and benign lesions, are particularly important. The objective of this meta-analysis was to evaluate the parameters of intravoxel incoherent motion (IVIM), including apparent diffusion coefficient (ADC), pure molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*), and perfusion fraction (f) in differentiating focal liver lesions. IVIM method employed for focal liver lesion and the quality assessment of diagnostic studies were evaluated. Standardized mean differences and 95% confidence intervals were calculated. The heterogeneity was quantified with the I2 statistic. The difference between groups was analyzed according to the I2 values from 6 different studies using fixed effects or random effects models. Significant differences in ADC (P < .001) and D (P < .001) were observed between benign and malignant lesions. Moreover, significant differences in ADC (P < .001), D (P < .001), and f (P = .01) were found between hemangioma and hepatocellular carcinoma (HCC). In addition, no significant difference was observed between the metastases and HCC. D and ADC values were useful for the differentiation between benignity and malignancy; higher values of ADC, D, and f were observed in hemangioma compared to HCC. Nevertheless, IVIM did not result as the optimal approach for differentiation between the metastases and HCC.

Reduction-sensitive, amphiphilic dextran derivatives were developed from disulfide-linked dextran-g-poly-(N-ε-carbobenzyloxy-L-lysine) graft polymer (Dex-g-SS-PZLL), and used as theranostic nanocarriers for chemotherapy and MR imaging. Dex-g-SS-PZLLs were synthesized by click conjugation between azidized dextran (Dex-N₃, 40 kD) and α-alkyne-SS-PZLL (degree of polymerization = 10, 15 and 25). The chemical structures of dextran derivatives were characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to their amphiphilic nature, these copolymers can self-assemble into spherical nanosized micelles in an aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. Interestingly, the hydrodynamic radii of the micelles (65–100 nm in diameter) were dependent on the block length of PZLL, and their critical micelle concentrations were in the range of 0.020–0.007 mg mL⁻¹, which decreased as the length of PZLL increased. The anticancer drug doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as the magnetic resonance imaging (MRI) contrast agent, were simultaneously encapsulated in the hydrophobic core of the micelles by the dialysis method. The release profiles of encapsulated DOX from SPIO/DOX-loaded micelles were shown to be rapid in the presence of 10 mM glutathione (GSH) within 24 h, whereas less than 30% DOX was released from reduction insensitive Dex-g-PZLL micelles in 48 h. Only about 35% DOX was released from Dex-g-SS-PZLL micelles in the same timeframe. According to the in vitro cytotoxicity test, it was found that reduction-sensitive micelles showed higher toxicity to HepG2 cancer cells than the reduction-insensitive micelles incubated with equivalent DOX concentration. Flow cytometry and fluorescence microscopy analyses further demonstrated that the reduction-sensitive micelles exhibited faster drug release behavior than reduction-insensitive micelles, which also led to higher cytotoxicity. The SPIO/DOX-loaded micelles demonstrated excellent MRI contrast enhancement, and the r₂ relaxivity values of the SPIO/DOX-loaded micelles were up to 261.3 Fe mM⁻¹ s⁻¹. Consequently, these reduction-sensitive amphiphilic dextran derivatives are promising theranostic nanocarriers for MR imaging and chemotherapy.