ß-Indole-3-acetic acid attenuated collagen-induced arthritis through reducing the ubiquitination of Foxp3 via the AhR-TAZ-Tip60 pathway.

Massive evidence shows that intestinal tryptophan metabolites affected by intestinal flora can modulate the progression of rheumatoid arthritis (RA). However, the effects and mechanisms of intestinal tryptophan metabolites on RA are not yet detailed. Herein, we investigated the protective effects of intestinal tryptophan metabolites on RA and its detailed mechanisms. In this study, the collagen-induced arthritis (CIA) rat model was established. Based on metabolomics analysis, the contents of ß-indole-3-acetic acid (IAA), indolylpropionic acid, and indole-3-ß-acrylic acid in the sera of CIA rats were significantly less compared with those of the normal rats. Under the condition of Treg or Th17 cell differentiation, IAA significantly promoted the differentiation and activation of Treg cells instead of Th17 cells. Intestinal tryptophan metabolites are well-known endogenic ligands of aryl hydrocarbon receptor (AhR). Not surprisingly, IAA increased the level of Foxp3 through activating the AhR pathway. Interestingly, IAA had little impact on the level of Foxp3 mRNA, but reducing the ubiquitination and degradation of Foxp3. Mechanically, IAA reduced the expression of the transcriptional coactivator TAZ, which was almost completely reversed by either AhR antagonist CH223191 or siRNA. In vitro, IAA decreased the combination of TAZ and the histone acetyltransferase Tip60, while it increased the combination of Tip60 and Foxp3. In CIA rats, oral administration of IAA increased the number of Treg cells and relieved the inflammation. A combined use with CH223191 almost abolished the effect of IAA. Taken together, IAA attenuated CIA by promoting the differentiation of Treg cells through reducing the ubiquitination of Foxp3 via the AhR-TAZ-Tip60 pathway.

Modulating the Asymmetric Atomic Interface of Copper Single Atoms for Efficient CO2 Electroreduction.

Cu single-atom catalysts (Cu SACs) have been considered as promising catalysts for efficient electrocatalytic CO2 reduction reactions (ECRRs). However, the reports on Cu SACs with an asymmetric atomic interface to obtain CO are few. Herein, we rationally designed two Cu SACs with different asymmetric atomic interfaces to explore their catalytic performance. The catalyst of CuN3O/C delivers high ECRR selectivity with an FECO value of above 90% in a wide potential window from -0.5 to -0.9 V vs RHE (in particular, 96% at -0.8 V), while CuCO3/C delivers poor selectivity for CO production with a maximum FECO value of only 20.0% at -0.5 V vs RHE. Besides, CuN3O/C exhibited a large turnover frequency (TOF) up to 2782.6 h-1 at -0.9 V vs RHE, which is much better than the maximum 4.8 h-1 of CuCO3/C. Density functional theory (DFT) results demonstrate that the CuN3O site needs a lower Gibbs free energy than CuCO3 in the rate-determining step of CO desorption, leading to the outstanding performance of CuN3O/C on the process of ECRR-to-CO. This work provides an efficient strategy to improve the selectivity and activity of the ECRR via regulating asymmetric atomic interfaces of SACs by adjusting the coordination atoms.

Microenvironment Modulation in Carbon-Supported Single-Atom Catalysts for Efficient Electrocatalytic CO2 Reduction.

The electrocatalytic CO2 reduction reaction (ECRR) becomes an effective way to reduce excess CO2 in the air and a promising strategy to maintain carbon balance. Carbon-supported single-atom catalysts (C-SACs) is a kind of cost savings and most promising catalysts for ECRR. For C-SACs, the key to achieving efficient ECRR performance is to adjusting the electronic structure of the central metal atoms by modulating their microenvironment of the catalysts. Not only the coordination numbers and hetero-atom coordination, but also the regulation of diatomic sites have a great influence on the performance of C-SACs. This review mainly focuses on recent studies for the microenvironment modulation in C-SACs for efficient ECRR. We hope that this review can contribute readers a comprehensive insight in the current research status of C-SACs for ECRR, as well as provide help for the rational design of C-SACs with better ECRR performance.

Cofluctuation analysis reveals aberrant default mode network patterns in adolescents and youths with autism spectrum disorder.

Resting-state functional connectivity (rsFC) approaches provide informative estimates of the functional architecture of the brain, and recently-proposed cofluctuation analysis temporally unwraps FC at every moment in time, providing refined information for quantifying brain dynamics. As a brain network disorder, autism spectrum disorder (ASD) was characterized by substantial alteration in FC, but the contribution of moment-to-moment-activity cofluctuations to the overall dysfunctional connectivity pattern in ASD remains poorly understood. Here, we used the cofluctuation approach to explore the underlying dynamic properties of FC in ASD, using a large multisite resting-state functional magnetic resonance imaging (rs-fMRI) dataset (ASD = 354, typically developing controls [TD] = 446). Our results verified that the networks estimated using high-amplitude frames were highly correlated with the traditional rsFC. Moreover, these frames showed higher average amplitudes in participants with ASD than those in the TD group. Principal component analysis was performed on the activity patterns in these frames and aggregated over all subjects. The first principal component (PC1) corresponds to the default mode network (DMN), and the PC1 coefficients were greater in participants with ASD than those in the TD group. Additionally, increased ASD symptom severity was associated with the increased coefficients, which may result in excessive internally oriented cognition and social cognition deficits in individuals with ASD. Our finding highlights the utility of cofluctuation approaches in prevalent neurodevelopmental disorders and verifies that the aberrant contribution of DMN to rsFC may underline the symptomatology in adolescents and youths with ASD.