Alterations in intra- and inter-network connectivity associated with cognition impairment in insulinoma patients.

Objective: Cognitive dysfunction is common in insulinoma patients, but the underlying neural mechanisms are less well understood. This study aimed to explore the alterations of intra- and inter-network connectivity patterns associated with patients with insulinoma. Methods: Resting-state fMRI were acquired from 13 insulinoma patients and 13 matched healthy controls (HCs). Group Independent component analysis (ICA) was employed to capture the resting-state networks (RSNs), then the intra- and inter-network connectivity patterns, were calculated and compared. Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function. The relationship between connectivity patterns and MoCA scores was also examined. Results: Insulinoma patients performed significantly worse on MoCA compared to HCs. The intra-network connectivity analysis revealed that patients with insulinoma showed decreased connectivity in the left medial superior frontal gyrus within anterior default mode network (aDMN), and decreased connectivity in right lingual gyrus within the visual network (VN). The intra-network connectivity analysis showed that patients with insulinoma had an increased connectivity between the inferior-posterior default mode network (ipDMN) and right frontoparietal network (rFPN) and decreased connectivity between the ipDMN and auditory network (AUN). There was a significant negative correlation between the ipDMN-rFPN connectivity and MoCA score. Conclusion: This study demonstrated significant abnormalities in the intra- and inter-network connectivity in patients with insulinoma, which may represent the neural mechanisms underlying the cognitive impairment in insulinoma patients.

IL-22 promotes occludin expression by activating autophagy and treats ulcerative colitis.

IL-22 serves a protective function in the intestinal barrier. These protective properties of IL-22 may offer a potential treatment for ulcerative colitis (UC). However, the exact mechanisms of action remain unclear. Autophagy plays an important protective role in stabilizing the intestinal barrier. We aimed to explore the role of autophagy in the IL-22-mediated-protective effects in UC. Dextran sulfate sodium (DSS) was administrated via drinking water over 7 days to induce acute UC in BALB/c mice. Treatments with IL-22 (0.25 µg/10 g bodyweight) were started by intraperitoneal injection on days 1, 3, and 5. Weight, disease activity index, histological score, and myeloperoxidase (MPO) activity were used to evaluate the severity of colitis. The expressions of occludin and autophagy-related proteins LC3BII/I were measured by western blot analysis. The lipopolysaccharide-induced HT-29 cell model was used to explore the mechanism. In vivo, IL-22 significantly alleviated DSS-induced clinical manifestations, reduced histological injury, and inhibited MPO activity. IL-22 upregulated the expression of occludin and the LC3B II/I ratio in the colon. In vitro, IL-22 significantly lowered TNF-α levels and enhanced the expression of occludin and the LC3B II/I ratio. Importantly, inhibiting autophagy in vitro by 3-Methyladenine (3-MA) attenuated the occludin protective effects of IL-22. In summary, our findings demonstrate that IL-22 ameliorates DSS-induced ulcerative colitis, which may be attributable to activating autophagy and then promoting occludin expression.

Comparative Transcriptome and iTRAQ Proteome Analyses of Citrus Root Responses to Candidatus Liberibacter asiaticus Infection.

Root samples of 'Sanhu' red tangerine trees infected with and without Candidatus Liberibacter asiaticus (CLas) were collected at 50 days post inoculation and subjected to RNA-sequencing and isobaric tags for relative and absolute quantification (iTRAQ) to profile the differentially expressed genes (DEGs) and proteins (DEPs), respectively. Quantitative real-time PCR was subsequently used to confirm the expression of 16 selected DEGs. Results showed that a total of 3956 genes and 78 proteins were differentially regulated by HLB-infection. Among the most highly up-regulated DEPs were sperm specific protein 411, copper ion binding protein, germin-like proteins, subtilisin-like proteins and serine carboxypeptidase-like 40 proteins whose transcript levels were concomitantly up-regulated as shown by RNA-seq data. Comparison between our results and those of the previously reported showed that known HLB-modulated biological pathways including cell-wall modification, protease-involved protein degradation, carbohydrate metabolism, hormone synthesis and signaling, transcription activities, and stress responses were similarly regulated by HLB infection but different or root-specific changes did exist. The root unique changes included the down-regulation in genes of ubiquitin-dependent protein degradation pathway, secondary metabolism, cytochrome P450s, UDP-glucosyl transferases and pentatricopeptide repeat containing proteins. Notably, nutrient absorption was impaired by HLB-infection as the expression of the genes involved in Fe, Zn, N and P adsorption and transportation were significantly changed. HLB-infection induced some cellular defense responses but simultaneously reduced the biosynthesis of the three major classes of secondary metabolites, many of which are known to have anti-pathogen activities. Genes involved in callose deposition were up-regulated whereas those involved in callose degradation were also up-regulated, indicating that the sieve tube elements in roots were hanging on the balance of life and death at this stage. In addition, signs of carbohydrate starvation were already eminent in roots at this stage. Other interesting genes and pathways that were changed by HLB-infection were also discussed based on our findings.