Significance: Inflammatory bowel diseases (IBDs) have been characterized by immune-mediated destruction of intestinal homeostasis. Until now, there have been no optimal therapies due to lack of a comprehensive understanding on pathophysiology during IBDs. The enteric nervous system (ENS) is emerging as a critical participant in intestinal immunomodulation, but the interaction between the ENS and intestinal immunity in IBDs remains unclear. Here, we discover the alteration of the ENS featured with reduced neurons and decreased acetylcholine (ACh) in IBDs. Moreover, ACh directly enhances the antiinflammatory activity of monocytic myeloid-derived suppressor cells by promoting interleukin-10 production through nicotinic ACh receptors, and thus ameliorates colitis. Our data highlight a neuroimmunomodulatory pathway and provide an alternative avenue by locally increasing ACh level for IBD therapy.

Dynamic regulation of wound physiological signals is the basis of wound healing. Conventional biomaterials delivering growth factors to drive wound healing leads to the passive repair of soft tissues because of the mismatch of wound healing stages. Meanwhile, the bioactivity of wound exudate is often restricted by oxidation and bacterial contamination. Herein, an extracellular matrix mimicked nanofiber/hydrogel interpenetrated network (NFHIN) was constructed with a 3D nanofibrous framework for cell immigration, and interfiled aerogel containing cross-linked hyaluronic acid and hyperbranched polyamidoamine to balance the wound microenvironment. The aerogel can collect wound exudate and transform into a polycationic hydrogel with contact-killing effects even against intracellular pathogens (bactericidal rate > 99.9% in 30 min) and real-time scavenging property of reactive oxygen species. After co-culturing with the NFHIN, the bioactivity of fibroblast in the ex vivo blister fluid was improved by 389.69%. The NFHIN showed sustainable exudate management with moisture–vapor transferring rate (6000 g m⁻² ×24 h), equilibrium liquid content (75.3%), Young’s modulus (115.1 ± 7 kPa), and anti-tearing behavior similar to human skin. The NFHIN can collect and activate wound exudate, turning it from a clinical problem to an autoimmune-derived wound regulation system, showing potential for wound care in critical skin diseases.

Accurate evaluation of HIF-1α levels can facilitate the detection of hypoxia niches in glioma and treatment decisions. To investigate the feasibility of intravoxel incoherent motion (IVIM) and R2* Mapping for detecting HIF-1α expression levels, sixteen rats with intracranial C6 gliomas were subjected to IVIM and R2* Mapping using a 7 Tesla MRI scanner. For each model, the brain tissue on the HIF-1α-stained slices was subdivided into multiple square regions of interest (ROIs) with areas of 1 mm², for which HIF-1α expression was assessed by HALO software to form a maps of HIF scores with a 0–300 range. The IVIM and R2* Mapping images were processed to create maps of the D, D*, f and R2* that were then paired with the corresponding HIF score maps. The average D, D*, f, perfusion (f × D*) and R2* values were calculated for the ROIs in the tumor and normal brain regions with different HIF-1α levels and used in further analysis. In this study, the average tumor size of sixteen C6 model rats was 458 ± 46.52 mm³, and the 482 included ROIs consisted of 280 tumoral and 202 normal ROIs. The average HIF score for the tumor regions was significantly higher than normal brain tissue (p < 0.001), and higher HIF scores were obtained for the central part of tumors than peripheral parts (p=0.03). Compared with normal brain tissues, elevated perfusion and f values were observed in tumor regions (p = 0.021, 0.004). In tumoral ROIs, the R2* values were higher in the group with high HIF-1α expression than in the group with low HIF-1α expression (p = 0.003). A correlation analysis revealed a positive correlation between the R2* value and HIF scores (r = 0.43, p < 0.001) and a negative correlation between D* and the HIF scores (r = -0.30, p = 0.001). Discrepancies in HIF-1α expression were found among different intratumoral areas, and IVIM and R2* Mapping were found to be promising means of noninvasive detection of the distribution and expression level of HIF-1α.

To explore the alterations of spontaneous neuronal activity using amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) in non-NPSLE patients and their relationship with the anxiety and depression statuses. Twenty-three non-NPSLE patients and 28 healthy controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by ALFF, fALFF, and ReHo. The relationships between ALFF/fALFF/ReHo values of abnormal regions and anxiety/depression rating scales, including Self-Rating Anxiety (SAS) and Self-Rating Depression (SDS), were also analyzed. Compared with HC, non-NPSLE had decreased ALFF values in the bilateral postcentral gyrus, while increased ALFF values in the bilateral inferior temporal gyrus, left putamen, and bilateral precuneus. Non-NPSLE showed reduced fALFF values in the left lingual gyrus, left middle occipital gyrus, right postcentral gyrus, and left superior parietal gyrus, while increased fALFF values were in the left inferior temporal gyrus, right hippocampus, bilateral precuneus, and bilateral superior frontal gyrus. Reduced ReHo values were in the bilateral postcentral gyrus and higher ReHo values were in the left inferior temporal gyrus, left putamen, and bilateral superior frontal gyrus. In the non-NPSLE group, the mean ALFF values of bilateral precuneus were positively correlated with the SAS rating scales (R = 0.5519, p = 0.0176); either were the mean ALFF values of right inferior temporal gyrus and SAS rating scales (R = 0.5380, p = 0.0213). The mean fALFF values of left inferior temporal gyrus were positively correlated with SAS rating scales (R = 0.5700, p = 0.0135). And the mean ReHo values of left putamen were positively correlated with SDS (R = 0.5477, p = 0.0186). Non-NPSLE exhibited abnormal spontaneous neural activity and coherence in several brain regions mainly associated with cognitive and emotional functions. The ALFF values of bilateral PCUN, the right ITG, the fALFF values of left ITG, and the ReHo values of left PUT may be complementary biomarkers for assessing the psychiatric symptoms.

Introduction: Systemic lupus erythematosus is a heterogeneous autoimmune disease. A burst of autoimmune reactions in various systems can lead to severe clinical conditions closely associated with mortality. T cells serve as mediators that drive the occurrence and maintenance of inflammatory processes. Methods: In this work, we employed single-cell transcriptome sequencing (scRNA-seq) involving 27704 cells from the brain and spleen tissues of MRL/lpr mice and 25355 healthy controls from BALB/c mice to explore the heterogeneity of T cells and their migration from the spleen to the brain. Results: We identified a distinct group of double-negative T cells in systemic lupus erythematosus (SLE) mice that significantly expressed Eomes and other specific markers. We used the analysis of pseudotime trajectory and enrichment to show that double-negative T cells in SLE mice are strongly associated with cellular senescence and exhaustion. Additionally, we focused on the interactions among DNT, astrocytes, and microglia in the mice brain. We observed greater expression of MDK-related ligand‒receptor pairs between astrocytes and double-negative T cells, indicating that MDK may be a therapeutic target for treating neuroinflammation in SLE. Discussion: This research sheds light on the intricate dynamics of immune responses in mice with SLE, specifically highlighting the role of double-negative T cells and their connection to cellular senescence. The exploration of interactions between T cells, astrocytes, and microglia in the mice brain unveils potential avenues for therapeutic intervention, particularly in addressing neuronal inflammation in SLE.