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Chronic insomnia disorder (CID) is a multidimensional disease that may influence various levels of brain organization, spanning the macroscopic structural connectome to microscopic gene expression. However, the connection between genomic variations and morphological alterations in CID remains unclear. Here, we investigated brain structural changes in CID patients at the whole-brain level and whether these link to transcriptional characteristics. Brain structural data from 104 CID patients and 102 matched healthy controls (HC) were acquired to examine cortical structural alterations using morphometric similarity (MS) analysis. Partial least squares (PLS) regression and transcriptome data from the Allen Human Brain Atlas were used to extract genomes related to MS changes. Gene-category enrichment analysis (GCEA) was used to identify potential molecular mechanisms behind the observed structural changes. We found that CID patients exhibited MS reductions in the parietal and limbic regions, along with enhancements in the temporal and frontal regions compared to HCs (pFDR < .05). Subsequently, PLS and GCEA revealed that these MS alterations were spatially correlated with a set of genes, especially those significantly correlated with excitatory and inhibitory neurons and chronic neuroinflammation. This neuroimaging-transcriptomic study bridges the gap between cortical structural changes and the molecular mechanisms in CID patients, providing novel insight into the pathophysiology of insomnia and targeted treatments.
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BACKGROUND: Despite numerous studies on auditory event-related potentials (ERPs) in insomnia disorder (ID), the results are inconsistent across different ERP components (e.g. N1, P2, P3, and N350), types of auditory stimuli (e.g. standard and deviant), and stages of sleep (e.g. wakefulness, NREM sleep, and REM sleep). In light of this variability, we conducted a systematic meta-analysis of previous auditory ERP studies in ID to provide a quantitative review of the existing literature. METHODS: Relevant literatures were searched on the Embase, PubMed/MEDLINE, PsycINFO and Cochrane Library. A total of 12 studies comprising 497 participants were finally included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42022308348. RESULTS: We found that patients with ID have significantly decreased N1 (Hedges' g = 0.34, 95%CI [0.04, 0.65]) and P3 (Hedges'g = -1.21, 95%CI [-2.37, -0.06]) amplitudes during wakefulness. In addition, decreases in P2 (Hedges'g = -0.57, 95%CI [-0.96, -0.17]) amplitude during wakefulness and N350 (Hedges' g = 0.73, 95%CI [0.36, 1.09]) amplitude during NREM. CONCLUSIONS: This meta-analysis represents the first systematic investigation of ERP features across different stages of sleep in individuals with ID. Our results suggest that in patients with insomnia, the absence or deficiency of arousal inhibition during the nighttime sleep initiation or maintenance process may interfere with the normal process of sleep.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica/métodos , Eletroencefalografia , Potenciais Evocados/fisiologiaRESUMO
Four new cyclic diarylheptanoids, casuarinols A-C (1-3) and casuarinolide A (4), together with six known ones (5-10), were isolated from the roots of Casuarina equisetifolia. Structures were elucidated by extensive spectroscopic analysis, theoretical conformational, and electronic circular dichroism analyses. Casuarinol C (3) is a novel cyclic diarylheptanoid-aldehyde adduct. Casuarinolide A (4) represents the first structure of a seco-cyclic diarylheptanoid. Compounds 1-9 were evaluated for their anti-influenza A virus (IAV) activity against A/WSN/33 (H1N1). (-)-(M)-11-Oxo-3,12R,17-trihydroxy-9-ene-[7,0]-metacyclophane (5) displayed significant anti-IAV activity with an IC50 value of 8.64 ± 2.49 µM and a CC50 higher than 100 µM.
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Diarileptanoides , Vírus da Influenza A Subtipo H1N1 , Raízes de Plantas , Aldeídos/química , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Diarileptanoides/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Estrutura Molecular , Raízes de Plantas/químicaRESUMO
Polygonatum odoratum is a historically traditional Chinese medicine plant. However, the consecutive monoculture problem (CMP) widespread in other Chinese medicine limiting their cultivation on a large scale. In this study, the physiological data showed the adverse effect of CMP on the growth of P. odoratum under the consecutive cropping (CC) compared with the first cropping (FC). Then the high-throughput sequencing of miRNA and mRNA libraries of leaves and roots from FC and CC P. odoratum plants identified 671 differentially expressed genes (DEGs) and 184 differentially expressed miRNAs and revealed that the DEGs and target genes of the miRNAs were mainly involved in starch and sucrose metabolism, phenylpropanoid and brassinosteroid biosynthesis. The KEGG analysis revealed that the DEGs between CC and FC roots were enriched in the plant-pathogen interaction pathway. This study provided the expression regulation of genes related to CMP of P. odoratum but also suggested that CMP may result in the serious damage of pathogens to roots and cause the slow growth in the consecutive cropping plants.
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MicroRNAs/metabolismo , Polygonatum/genética , Transcriptoma , Regulação da Expressão Gênica de Plantas , Medicina Tradicional Chinesa , Células Vegetais/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Polygonatum/citologia , Polygonatum/metabolismo , RNA de Plantas/metabolismoRESUMO
STUDY OBJECTIVES: Chronic insomnia disorder (CID) is a prevalent sleep disorder that frequently cooccurs with anxiety. The association between insomnia and anxiety has been established; however, the neurobiological basis of this relationship remains unclear. This study aimed to investigate the neural markers of CID patients with and without anxiety and to determine whether specific neural connectivity mediates the relationship between insomnia and anxiety. METHODS: This study included 180 participants, comprising CID patients with anxiety (CID-A), CID patients without anxiety (CID-NA), and good sleep controls. All participants completed self-reported measures of sleep quality and anxiety severity and underwent functional magnetic resonance imaging. Brain functional integration was measured using functional connectivity density (FCD) and resting-state functional connectivity (rsFC). Correlation and mediation analyses were used to examine the relationships among brain connectivity, sleep quality, and anxiety severity. RESULTS: The CID-NA and CID-A groups showed decreased local FCD in the medial prefrontal cortex (mPFC) and disrupted rsFC between the precuneus and other brain regions. Only the CID-A group exhibited altered long-range FCD in the precuneus and the rsFC between the anterior default mode network (DMN, e.g. mPFC) and posterior DMN (e.g. precuneus). Mediation analysis revealed DMN dysconnectivity underlying the association between poor sleep quality and anxiety symptoms. CONCLUSIONS: This study identified shared and distinct brain circuit disruptions in the CID-NA and CID-A groups, with deficits in DMN connectivity as a potential neural mechanism through which disrupted sleep augments anxiety. These findings may facilitate the development of personalized therapies for insomnia and associated anxiety problems.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Qualidade do Sono , Rede de Modo Padrão , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ansiedade/complicações , Ansiedade/diagnóstico por imagem , Mapeamento EncefálicoRESUMO
OBJECTIVE: This study used event-related potential (ERP) and resting-state functional connectivity (rs-FC) approaches to investigate the neural mechanisms underlying the emotional attention bias in patients with chronic insomnia disorder (CID). METHODS: Twenty-five patients with CID and thirty-three demographically matched healthy controls (HCs) completed clinical questionnaires and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) scans. EEG analysis examined the group differences in terms of reaction times, P3 amplitudes, event-related spectral perturbations, and inter-trial phase synchrony. Subsequently, seed-based rs-FC analysis of the amygdala nuclei (including the central-medial amygdala [CMA] and basolateral amygdala [BLA]) was performed. The relationship between P3 amplitude, rs-FC and clinical symptom severity in patients with CID was further investigated by correlation analysis. RESULTS: CID patients exhibited shorter reaction times than HCs in both standard and deviant stimuli, with the abnormalities becoming more pronounced as attention allocation increased. Compared to HCs, ERP analysis revealed increased P3 amplitude, theta wave power, and inter-trial synchrony in CID patients. The rs-FC analysis showed increased connectivity of the BLA-occipital pole, CMA-precuneus, and CMA-angular gyrus and decreased connectivity of the CMA-thalamus in CID patients. Notably, correlation analysis of the EEG and fMRI measurements showed a significant positive correlation between the P3 amplitude and the rs-FC of the CMA-PCU. CONCLUSION: This study confirms an emotional attention bias in CID, specifically in the neural mechanisms of attention processing that vary depending on the allocation of attentional resources. Abnormal connectivity in the emotion-cognition networks may constitute the neural basis of the abnormal scalp activation pattern.
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Viés de Atenção , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Emoções , Lobo Parietal , Tonsila do Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
The hypothalamus is a well-established core structure in the sleep-wake cycle. While previous studies have not consistently found whole hypothalamus volume changes in chronic insomnia disorder (CID), differences may exist at the smaller substructural level of the hypothalamic nuclei. The study aimed to investigate the differences in total and subfield hypothalamic volumes, between CID patients and healthy controls (HCs) in vivo, through an advanced deep learning-based automated segmentation tool. A total of 150 patients with CID and 155 demographically matched HCs underwent T1-weighted structural magnetic resonance scanning. We utilized FreeSurfer v7.2 for automated segmentation of the hypothalamus and its five nuclei. Additionally, correlation and causal mediation analyses were performed to investigate the association between hypothalamic volume changes, insomnia symptom severity, and hypothalamus-pituitary-adrenal (HPA) axis-related blood biomarkers. CID patients exhibited larger volumes in the right anterior inferior, left anterior superior, and left posterior subunits of the hypothalamus compared to HCs. Moreover, we observed a positive association between blood corticotropin-releasing hormone (CRH) levels and insomnia severity, with anterior inferior hypothalamus (a-iHyp) hypertrophy mediating this relationship. In conclusion, we found significant volume increases in several hypothalamic subfield regions in CID patients, highlighting the central role of the HPA axis in the pathophysiology of insomnia.
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Hormônio Liberador da Corticotropina , Distúrbios do Início e da Manutenção do Sono , Humanos , Hormônio Liberador da Corticotropina/metabolismo , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Hipotálamo/diagnóstico por imagemRESUMO
STUDY OBJECTIVES: Perimenopausal insomnia (PMI) is associated with observable performance impairments in visual search tasks. This study examines how various cognitive processing stages contribute to search performance delays in PMI compared to healthy controls (HCs). METHODS: We recruited 76 participants diagnosed with PMI and 63 HCs. Event-related potentials (ERPs) were recorded as participants engaged in a visual search task, reporting the orientation of a color popout target within an array of ellipses. We analyzed group differences in behavioral performance and ERP components across cognitive processing stages. RESULTS: Compared to HCs, PMI patients exhibited behavioral response delays, although accuracy was not different between groups. Electrophysiological analyses revealed group differences across several ERP components. Firstly, the N1 component's amplitude increased bilaterally, suggesting enhanced visual sensory processing. Secondly, a slower and smaller N2pc indicated reduced attentional orienting. Thirdly, a decreased SPCN amplitude pointed to deficits in target discrimination. Fourthly, an increased amplitude of the stimulus-locked LRP, with unchanged latency, suggested heightened neural inputs for maintaining motor initiation speed. Fifthly, prolonged response-locked LRP latency indicated slower motor execution. Finally, these changes in ERP components, along with significant correlations between LRP components and insomnia symptoms, suggest potential neural biomarkers for PMI. CONCLUSIONS: Our findings provide high-temporal-resolution insights into the neurocognitive disruptions associated with PMI, highlighting how sleep disturbances affect cognitive processing in visual tasks. These insights enhance our understanding of PMI and contribute to discussions on neural mechanisms driving behavioral performance in various conditions.
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STUDY OBJECTIVES: This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions. METHODS: We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively. RESULTS: CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDRâ <â .05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like "cognitive control" and "emotion regulation." Notably, GBC patterns were associated with neurotransmitter profiles (pspinâ <â .05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions. CONCLUSIONS: This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID.
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Conectoma , Eletroencefalografia , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Conectoma/métodos , Eletroencefalografia/métodos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Máquina de Vetores de Suporte , NeurotransmissoresRESUMO
Alnus cremastogyne Burkill (Betulaceae), an actinorhizal plant, can enter a mutualistic symbiosis with Frankia species that leads to the formation of nitrogen fixing root nodules. Some primary metabolites (carbohydrates, dicarboxylic acids, amino acids, citrulline and amides) involved in carbon and nitrogen metabolism in actinorhizal nodules have been identified, while specialized metabolites in A. cremastogyne root nodules are yet to be characterized. In this study, we isolated and identified three undescribed 3-pentanol glycosides, i.e., 3-pentyl α-l-arabinofuranosyl-(1''â6')-ß-d-glucopyranoside, 3-pentyl α-l-rhamnopyranosyl-(1''â6')-ß-d-glucopyranoside, and 3-pentyl 6'-(3-hydroxy3-methylglutaryl)-ß-d-glucopyranoside, as well as seventeen known compounds from A. cremastogyne root nodules. 3-Pentanol glycosides are abundantly distributed in root nodules, while they are distributed in stems, roots, leaves and fruits at low/zero levels. A. cremastogyne plants treated by root nodule suspension emit 3-pentanol. This study enriches the knowledge about specialized metabolites in the actinorhizal host, and provides preliminarily information on the signal exchange in the actinorhizal symbiosis between A. cremastogyne and Frankia.
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Alnus , Frankia , Pentanóis/metabolismo , Glicosídeos/metabolismo , Raízes de Plantas , Frankia/metabolismo , Simbiose , Plantas , Nitrogênio/metabolismo , Fixação de Nitrogênio , Nódulos Radiculares de PlantasRESUMO
OBJECTIVE: This study aimed to investigate the neural mechanisms underlying working memory impairment in patients with chronic insomnia disorder (CID) using event-related potentials (ERP) and resting-state functional connectivity (rsFC) approaches. METHODS: Participants, including CID patients and healthy controls (HCs), completed clinical scales and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). EEG analysis compared reaction times, P3 amplitudes, event-related spectral perturbations (ERSP), and inter-trial phase synchronisation (ITPS) between CID patients and HCs. Subsequently, frontal regions (i.e., the Superior Frontal Gyrus [SFG] and Middle Frontal Gyrus [MFG]) corresponding to the EEG were selected as seeds for rsFC analysis. Correlation analyses were conducted to further investigate the relationship between functional connectivity abnormalities in brain regions and clinical symptom severity and P3 amplitude in CID patients. RESULTS: Compared to HCs, CID patients exhibited slower reaction times across all working memory conditions, with the deficits becoming more pronounced as memory load increased. ERP analysis revealed increased P3 amplitude, theta wave power, and reduced inter-trial synchrony in CID patients. rsFC analysis showed decreased connectivity of SFG-posterior cingulated cortex (PCC), SFG-MFG, and MFG-frontal pole (FP), and increased connectivity of MFG- Middle Temporal Gyrus (MTG)in CID patients. Importantly, a significant correlation was found between the rsFC of SFG-MTG and P3 amplitude during 1-back. CONCLUSION: This study confirms deficits in working memory capacity in patients with CID, specifically in the neural mechanisms of cognitive processing that vary depending on the level of cognitive load. Alterations in connectivity patterns within and between the frontal and temporal regions may be the neural basis of the cognitive impairment.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Memória de Curto Prazo , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodosRESUMO
Two new α-pyrones, micropyrones A (1) and B (2), along with four known γ-pyrones, nocapyrone D (3), nocapyrone A (4), marinactinone A (5), and nocapyrone H (6), were isolated from the culture extract of actinomycete Microbacterium sp. GJ312, which was isolated from Glycyrrhiza uralensis. The structures of these compounds were identified by analysis of spectral data. They are the first α- and γ-pyrones reported from the genus Microbacterium. The antibacterial activity of all compounds against Staphylococcus aureus and methicillin resistant S. aureus was evaluated. However, none of them showed significant activity. This study represents the first phytochemical example of a Glycyrrhiza-derived actinomycete.
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Actinobacteria , Glycyrrhiza uralensis , Glycyrrhiza , Staphylococcus aureus Resistente à Meticilina , Glycyrrhiza uralensis/química , Pironas , MicrobacteriumRESUMO
BACKGROUND: Sleep is instrumental in safeguarding emotional well-being. While the susceptibility to both insomnia and anxiety has been demonstrated to involve intricate brain systems, the neuroimaging profile of chronic insomnia disorder with comorbid anxiety symptoms (CID-A) remains unexplored. Employing machine learning methodologies, this study aims to elucidate the distinct neural substrates underlying CID-A and to investigate whether these cerebral markers can prognosticate anxiety symptoms in patients with insomnia. METHODS: Functional magnetic resonance imaging (fMRI) data were procured from a relatively large cohort (dataset 1) comprised of 47 CID-A patients, 49 CID patients without anxiety (CID-NA), and 48 good sleeper controls (GSC). Aberrant cerebral functional alterations were assessed through functional connectivity strength (FCS) and resting-state functional connectivity (rsFC). Subsequently, Support Vector Regression (SVR) models were constructed to predict anxiety symptoms in CID patients based on neuroimaging features, which were validated utilizing an external cohort (dataset 2). RESULTS: In comparison to CID-NA and GSC subjects, CID-A patients exhibited heightened FCS in the right dorsomedial prefrontal cortex (DMPFC), a central hub within the negative affective network. Moreover, the SVR models revealed that DMPFC-related rsFC/FCS features could be employed to predict anxiety symptoms in two independent cohorts of CID patients. LIMITATION: Modifications in brain functionality might vary across insomnia subtypes. CONCLUSION: The present findings suggest a potential negative affective network model for the neuropathophysiology of CID accompanied by anxiety. Importantly, the negative affective network pattern may serve as a predictor for anxiety symptoms in CID patients.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Neuroimagem , Ansiedade/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodosRESUMO
Background and aims: Land abandonment and selective farming are two common management methods to restore the soil conditions of low-pollution farmland in mining areas. The soil bacterial community plays an important role in farmland soil restoration; however, few studies have compared the composition and diversity of soil bacteria between the abandoned farmlands (AFS) and selective-farming farmlands (FFS). Here, the effects of AFS and FFS on soil properties and bacterial diversity were evaluated in an antimony (Sb) mining area in southern China. This study aimed to identify effective land management methods in terms of positive or negative changes in soil environment and bacterial diversity. Methods: 16S rRNA high-throughput sequencing was used to compare the diversity and composition of soil bacteria between AFS and FFS in the Xikuangshan (the largest Sb mine in the world). Results: Compared to AFS, FFS had higher Sb concentration and nutritional properties (e.g., available N, P, and K) and lower Zn concentration (p < 0.05). The bacterial alpha diversity including Chao1 index, Simpson index, Shannon index and Pielou-e index in FFS was higher than AFS (p < 0.05). At the phylum level, FFS had higher relative abundances of Chloroflexi, Acidobacteria, Gemmatimonadetes, and Rokubacteria, and lower relative abundances of Firmicutes, Actinobacteria, and Bacteroidetes. At the genus level, FFS had higher relative abundances of Acidothermus, Haliangium, and Rokubacteriales, and lower relative abundances of Bacillus, Rhodococcus, Sphingomonas, and 67-14. Redundancy analysis indicated that soil heavy metal content and soil fertility were closely correlated with the soil bacterial community. Altogether, selective farming of low-pollution farmland in the mining area can improve soil properties and soil bacterial diversity.
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The pesticide atrazine poses a potential threat to the health of frogs living in farmland areas. The exposure concentration in traditional pesticide experiments is usually constant, while pesticide pollution in actual water may fluctuate due to periodic or seasonal application. We examined the effects of different concentrations of atrazine (50, 100 and 500 µg/L) over a 14-day exposure and a 7-day recovery on intestinal histology, bacterial composition and intestinal metabolites of male Pelophylax nigromaculatus. HE staining revealed that after a 14-day atrazine exposure, the 100 µg/L and 500 µg/L groups showed obvious cysts and significantly decreased intestinal crypt depth and villus height. After a 7-day recovery, the damaged intestine in the 100 µg/L group was partially recovered, while in the 500 µg/L exposure group there was no improvement. 16S rRNA gene analysis of intestinal bacteria showed that 500 µg/L atrazine exposure significantly caused a persistent decrease in bacterial α diversity. Compared to the control and other atrazine exposure groups, the 500 µg/L group showed significant changes in the relative abundance of predominant bacteria. In addition, most dominant bacteria in the 500 µg/L recovery group showed significant differences with the 50 µg/L and 100 µg/L recovery groups. Nontargeted metabolomics profiling based on UPLC/MS analysis showed that atrazine exposure and recovery induced changes in the intestinal metabolic profile. The changes in metabolites were mainly related to purine/pyrimidine metabolism, glycine, serine and threonine metabolism, and arginine and proline metabolism. In general, these pathways were closely related to energy metabolism and amino acid metabolism. These results suggest that the short-term exposure to 500 µg/L atrazine causes persistent harm to intestinal health. This study is an important step toward a better understanding of the toxic effects of atrazine exposure and recovery in frog intestines.