Integrative Analysis of Metabolome and Transcriptome Reveals the Mechanism of Color Formation in Yellow-Fleshed Kiwifruit.

During the development of yellow-fleshed kiwifruit (Actinidia chinensis), the flesh appeared light pink at the initial stage, the pink faded at the fastest growth stage, and gradually changed into green. At the maturity stage, it showed bright yellow. In order to analyze the mechanism of flesh color change at the metabolic and gene transcription level, the relationship between color and changes of metabolites and key enzyme genes was studied. In this study, five time points (20 d, 58 d, 97 d, 136 d, and 175 d) of yellow-fleshed kiwifruit were used for flavonoid metabolites detection and transcriptome, and four time points (20 d, 97 d, 136 d, and 175 d) were used for targeted detection of carotenoids. Through the analysis of the content changes of flavonoid metabolites, it was found that the accumulation of pelargonidin and cyanidin and their respective anthocyanin derivatives was related to the pink flesh of young fruit, but not to delphinidin and its derivative anthocyanins. A total of 140 flavonoid compounds were detected in the flesh, among which anthocyanin and 76% of the flavonoid compounds had the highest content at 20 d, and began to decrease significantly at 58 d until 175 d, resulting in the pale-pink fading of the flesh. At the mature stage of fruit development (175 d), the degradation of chlorophyll and the increase of carotenoids jointly led to the change of flesh color from green to yellow, in addition to chlorophyll degradation. In kiwifruit flesh, 10 carotenoids were detected, with none of them being linear carotenoids. During the whole development process of kiwifruit, the content of ß-carotene was always higher than that of α-carotene. In addition, ß-cryptoxanthin was the most-accumulated pigment in the kiwifruit at 175 d. Through transcriptome analysis of kiwifruit flesh, seven key transcription factors for flavonoid biosynthesis and ten key transcription factors for carotenoid synthesis were screened. This study was the first to analyze the effect of flavonoid accumulation on the pink color of yellow-fleshed kiwifruit. The high proportion of ß-cryptoxanthin in yellow-fleshed kiwifruit was preliminarily found. This provides information on metabolite accumulation for further revealing the pink color of yellow-fleshed kiwifruit, and also provides a new direction for the study of carotenoid biosynthesis and regulation in yellow-fleshed kiwifruit.

Improved Regional Homogeneity in Chronic Insomnia Disorder After Amygdala-Based Real-Time fMRI Neurofeedback Training.

Background: Chronic insomnia disorder (CID) is a highly prevalent sleep disorder, which influences people's daily life and is even life threatening. However, whether the resting-state regional homogeneity (ReHo) of disrupted brain regions in CID can be reshaped to normal after treatment remains unclear. Methods: A novel intervention real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) was used to train 28 CID patients to regulate the activity of the left amygdala for three sessions in 6 weeks. The ReHo methodology was adopted to explore its role on resting-state fMRI data, which were collected before and after training. Moreover, the relationships between changes of clinical variables and ReHo value of altered regions were determined. Results: Results showed that the bilateral dorsal medial pre-frontal cortex, supplementary motor area (SMA), and left dorsal lateral pre-frontal cortex had decreased ReHo values, whereas the bilateral cerebellum anterior lobe (CAL) had increased ReHo values after training. Some clinical scores markedly decreased, including Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck Depression Inventory, and Hamilton Anxiety Scale (HAMA). Additionally, the ReHo values of the left CAL were positively correlated with the change in the Hamilton depression scale score, and a remarkable positive correlation was found between the ReHo values of the right SMA and the HAMA score. Conclusion: Our study provided an objective evidence that amygdala-based rtfMRI-NF training could reshape abnormal ReHo and improve sleep in patients with CID. The improved ReHo in CID provides insights into the neurobiological mechanism for the effectiveness of this intervention. However, larger double-blinded sham-controlled trials are needed to confirm our results from this initial study.

Real-Time fMRI Neurofeedback Training Changes Brain Degree Centrality and Improves Sleep in Chronic Insomnia Disorder: A Resting-State fMRI Study.

Background: Chronic insomnia disorder (CID) is considered a major public health problem worldwide. Therefore, innovative and effective technical methods for studying the pathogenesis and clinical comprehensive treatment of CID are urgently needed. Methods: Real-time fMRI neurofeedback (rtfMRI-NF), a new intervention, was used to train 28 patients with CID to regulate their amygdala activity for three sessions in 6 weeks. Resting-state fMRI data were collected before and after training. Then, voxel-based degree centrality (DC) method was used to explore the effect of rtfMRI-NF training. For regions with altered DC, we determined the specific connections to other regions that most strongly contributed to altered functional networks based on DC. Furthermore, the relationships between the DC value of the altered regions and changes in clinical variables were determined. Results: Patients with CID showed increased DC in the right postcentral gyrus, Rolandic operculum, insula, and superior parietal gyrus and decreased DC in the right supramarginal gyrus, inferior parietal gyrus, angular gyrus, middle occipital gyrus, and middle temporal gyrus. Seed-based functional connectivity analyses based on the altered DC regions showed more details about the altered functional networks. Clinical scores in Pittsburgh sleep quality index, insomnia severity index (ISI), Beck depression inventory, and Hamilton anxiety scale decreased. Furthermore, a remarkable positive correlation was found between the changed ISI score and DC values of the right insula. Conclusions: This study confirmed that amygdala-based rtfMRI-NF training altered the intrinsic functional hubs, which reshaped the abnormal functional connections caused by insomnia and improved the sleep of patients with CID. These findings contribute to our understanding of the neurobiological mechanism of rtfMRI-NF in insomnia treatment. However, additional double-blinded controlled clinical trials with larger sample sizes need to be conducted to confirm the effect of rtfMRI-NF from this initial study.