Single-atom-sized catalysts (often called single atom catalysts) are highly desired for maximizing the efficiency of metal atom use. However, their synthesis is a major challenge that largely depends on finding an appropriate supporting substrate to achieve a well-defined and highly dispersed single atom. This work demonstrates, based on density functional theory (DFT) predictions and experimental validations, that graphdiyne is a good substrate for anchoring Fe atoms through the formation of covalent Fe–C bonds to produce graphdiyne-supported single-atom-sized Fe catalysts (Fe–graphdiyne catalysts); moreover, this catalyst shows high catalytic activity to oxygen reduction reactions (ORRs) similar to or even slightly better than the precious metal benchmark (commercial 20 wt % Pt/C catalyst). DFT predicts that the O2 molecule can bind with an Fe atom, and the electron transformation process of ORRs occurs through a 4e– pathway. To validate the theoretical predictions, the Fe–graphdiyne catalyst was then synthesized by a reduction of Fe3+ ions adsorbed on a graphdiyne surface in aqueous solution, and its electrocatalytic activities toward ORR were experimentally evaluated in alkaline electrolytes (0.1 M KOH). The electrochemical measurements indicate that the Fe–graphdiyne catalyst can facilitate the 4e– ORR while limiting the 2e– transfer reaction, showing a high 4e– selectivity for ORRs and a good agreement with DFT predictions. The results presented here demonstrate that graphdiyne can provide a unique platform for synthesizing well-defined and uniform single-atom-sized metal catalysts with high catalytic activity toward ORRs.

No abstract

To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole-body MRI were comparable with those of integrated PET/CT.

No abstract

Tumor ADC, nADC, and nADC are useful markers to predict the aggressiveness of prostate cancer.

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-specific IFN-gamma production, and induced apoptosis of CD4(+) T cells possibly through DC expressing indoleamine 2,3-dioxygenase and/or an IFN-gamma-dependent pathway. As a result, infiltration of macrophages and CD4(+) T cells within the spinal cords was dramatically reduced in animals injected with IFN-gamma-DC as compared to animals injected with PBS or naive DC. This approach may represent a novel possibility of individualized immunotherapy using autologous, in vitro modified DC as a complement to conventional therapy in multiple sclerosis and other diseases with an autoimmune background.

Brucella spp. impedes the production of pro-inflammatory cytokines by its outer membrane protein Omp25 in order to promote survival and immune evasion. However, how Omp25 regulates tumor necrosis factor (TNF-α) expression in different mammalian macrophages remains unclear. In this study, we investigated the potential mechanisms by which Omp25 regulates TNF-α expression and found that Omp25-deficient mutant of B. suis exhibited an enhanced TNF-α expression compared with wild-type (WT) B. suis, whereas ectopic expression of Omp25 suppressed LPS-induced TNF-α production at both protein and mRNA levels in porcine alveolar macrophages (PAMs) and murine macrophage RAW264.7 cells. We observed that Omp25 protein as well as WT B. suis upregulated miR-146a, -181a, -181b, and -301a-3p and downregulated TRAF6 and IRAK1 in both PAMs and RAW264.7 cells, but separately upregulates miR-130a-3p in PAMs and miR-351-5p in RAW264.7. The upregulation of miR-146a or miR-351-5p attenuated TNF-α transcription by targeting TRAF6 and IRAK1 at the 3′ untranslated region (UTR), resulting in inhibition of NF-kB pathway, while upregulation of miR-130a-3p, -181a, or -301a-3p correlated temporally with decreased TNF-α by targeting its 3′UTR in PAMs or RAW264.7 cells. In contrast, inhibition of miR-130a-3p, -146a, -181a, and -301a-3p attenuated the inhibitory effects of Omp25 on LPS-induced TNF-α in PAMs, while inhibition of miR-146a, -181a, -301a-3p, and -351-5p attenuated the inhibitory effects of Omp25 in RAW264.7, resulting in an increased TNF-α production and decreased intracellular bacteria in both cells. Taken together, our results demonstrate that Brucella downregulates TNF-α to promote intracellular survival via Omp25 regulation of different microRNAs in porcine and murine macrophages.

No abstract