Neural mechanisms of working memory dysfunction in patients with chronic insomnia disorder.

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.

Neuroimaging profiles of the negative affective network predict anxiety severity in patients with chronic insomnia disorder: A machine learning study.

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.

Qualitative Classification of Lubricating Oil Wear Particle Morphology Based on Coaxial Capacitive Sensing Network and SVM.

In addition to lubricating and cooling, aero-engine lubricating oil is also a transport medium for wear particles generated by mechanical wear. Online identification of the number and shape of wear particles is an important means to directly determine the wear state of rotating parts, but most of the existing research focuses on the identification and counting of wear particles. In this paper, a qualitative classification method of wear particle morphology based on support vector machine is proposed by using the wear particle capacitance signal obtained by the coaxial capacitive sensing network. Firstly, the coaxial capacitive sensing network simulation model is used to obtain the capacitance signals of different shapes of wear particles entering the detection space of different electrode plates. In addition, a variety of intelligent optimization algorithms are used to optimize the relevant parameters of the support vector machine (SVM) model in order to improve the classification accuracy. By using the processed data and optimized parameters, a SVM-based qualitative classification model for wear particles is established. Finally, the validity of the classification model is verified by real wear particles of different sizes. The simulation and experimental results show that the qualitative classification of different wear particle morphologies can be achieved by using the coaxial capacitive sensing network signal and the SVM model.

A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells.

Dithiocarbamates (DTCs) exhibit a broad spectrum of antitumor activities, however, their molecular mechanisms of antitumor have not yet been elucidated. Previously, we have synthesized a series of novel dithiocarbamate derivatives. These DTCs were examined for cytotoxic activities against five human cancer cell lines. In this study, one of dithiocarbamate (DTC1) with higher potential for HeLa cells was chosen to investigate molecular mechanisms for its anti-tumor activities. DTC1 could inhibit proliferation, and highly induce apoptosis in HeLa cells by activating caspase-3, -6 and -9; moreover, activities of caspase-3, -6 and -9 were inhibited by pan-caspase inhibitor, Z-VAD-FMK. Furthermore, DTC1 decreased the levels of Bcl-2 and Bcl-xL, and increased expression of cytosol cytochrome c, Bak, Bax and p53 in a time-dependent manner but had no effect on the level of Rb. It was shown that DTC1 induced HeLa cells apoptosis through a p53-dependent pathway as tested by the wild type p53 inhibitor, pifithrin-α. Additionally, the relative expression of E6 and E7 were evaluated in HPV18-positive (HeLa cells) by real-time PCR and western blotting. The results firstly demonstrated that DTC1 suppressed both expression of E6 mRNA and E6 oncoprotein, but had no effect on the expression of E7 mRNA and protein in HPV18. Our results suggested that DTC1 may serve as novel chemotherapeutic agents in the treatment of cervical cancer and potential anti-HPV virus candidates that merit further studies.

Molecular cloning and functional analysis of the FLOWERING LOCUS T (FT) homolog GhFT1 from Gossypium hirsutum.

FLOWERING LOCUS T (FT) encodes a member of the phosphatidylethanolamine-binding protein (PEBP) family that functions as the mobile floral signal, playing an important role in regulating the floral transition in angiosperms. We isolated an FT-homolog (GhFT1) from Gossypium hirsutum L. cultivar, Xinluzao 33 GhFT1 was predominantly expressed in stamens and sepals, and had a relatively higher expression level during the initiation stage of fiber development. GhFT1 mRNA displayed diurnal oscillations in both long-day and short-day condition, suggesting that the expression of this gene may be under the control of the circadian clock. Subcellular analysis revealed that GhFT1 protein located in the cytoplasm and nucleus. Ectopic expression of GhFT1 in transgenic arabidopsis plants resulted in early flowering compared with wild-type plants. In addition, ectopic expression of GhFT1 in arabidopsis ft-10 mutants partially rescued the extremely late flowering phenotype. Finally, several flowering related genes functioning downstream of AtFT were highly upregulated in the 35S::GhFT1 transgenic arabidopsis plants. In summary, GhFT1 is an FT-homologous gene in cotton that regulates flower transition similar to its orthologs in other plant species and thus it may be a candidate target for promoting early maturation in cotton breeding.

Genetic mapping of fiber color genes on two brown cotton cultivars in Xinjiang.

In the present study, genetic linkage analysis was carried out to map the fiber color loci Lc 1 and Lc 2 on two brown cotton cultivars with SSR and EST-SSR markers in the reference map by F2 segregation populations. The Lc 1 locus carried by Xincaimian6 (Gossypium hirsutum L.) was flanked by the marker NAU2862 and NAU1043 on the long arm of Chromosome 07, with genetic distance 7.8 cM and 3.8 cM, respectively. The Lc 2 carried by Xincaimian 5 (Gossypium hirsutum L.) was flanked by the marker NAU5433 and NAU2968 on the short arm of Chromosome 06, with genetic distance 4.4 cM and 7.4 cM respectively. Moreover, the marker NAU3735 and marker NAU5434 co-segregated with the Lc 1 and the Lc 2 locus, respectively. The results of marker association studies with these two loci provides the basic information for the final isolation of these important genes in colored cotton, and these linkage markers also could facilitate application of marker assisted selection in the future.

Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and suppression of ERK1/2 MAPK in HeLa cells.

Ursolic acid (UA), a natural pentacyclic triterpenoid compound, has been demonstrated to induce apoptosis in various tumors. The aim of the present study was to elucidate the molecular mechanisms of UA-induced apoptosis in HeLa cells. Here, we reported that UA induced apoptosis through the mitochondrial intrinsic pathway in HeLa cells, as shown by release of cytosol cytochrome c, activation of caspase-9 and -3, reduction of Bcl-2 and Bcl-xL, and increase of Bax and Bak. UA down-regulated the phosphorylation of ERK1/2 and p38, whereas phosphorylation of JNK was unchanged. The roles of ERK1/2 and p38 were further confirmed using the ERK1/2 inhibitor (U0126) and p38 inhibitor (SB203580). U0126 markedly increased UA-induced the Bax/Bcl-2 ratio, the increase of cytosol cytochrome c, and the levels of cleaved caspase-3, but SB203580 had little effects on the above characters, suggesting the ERK1/2 signaling pathway is required for apoptosis. Furthermore, UA up-regulated DUSP 1, 2, 4, 5, 6, 7, 9, and 10 mRNA expressions, which may be a clue for the role of dephosphorylation of ERK1/2 and p38. These data suggested that the apoptotic mechanism of UA treatment in HeLa cells was through the mitochondrial intrinsic pathway and closely associated with the suppression of the ERK1/2 signaling pathway.

[Inhibitory effects of luteolin on human gastric carcinoma xenografts in nude mice and its mechanism].

OBJECTIVE: To explore the in vivo anticancer effects of luteolin with BGC-823 gastric carcinoma xenografts in nude mice and elucidate its mechanism. METHODS: After modeling of gastric carcinoma xenografts in nude mice, 40 BALB/c (nu/nu) nude mice were randomly divided into 5 groups (n = 8 each). And an intraperitoneal injection of luteolin was administered at 10 mg/kg (low-dose), 20 mg/kg (middle-dose) and 40 mg/kg (high-dose) groups. And 5-fluorouracil (30 mg/kg) and control groups were also established. The growth curves of xenografts in nude mice were drawn and weight inhibition rates measured. The morphological features were detected by hematoxylin and eosin staining. And the protein expression levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry. RESULTS: In vivo tumor formation test showed that tumor volume in nude mice treated with luteolin was smaller than that of control group. Tumor weights of high-dose luteolin group were lighter than those of the control ((0.29 ± 0.01) vs (0.38 ± 0.03) g). And the difference was statistically significant (P < 0.01). The rate of tumor inhibition in high-dose luteolin group was up to 24.87%. Lymphocytic invasion of tumor tissue was observed under light microscope in the treatment groups. Results of immunohistochemistry showed the positive cell integral of VEGF in middle and high-dose luteolin groups were 1.25 ± 0.17 and 1.00 ± 0.07 respectively. Both were significantly lower than that of control group (1.50 ± 0.15, both P < 0.05). The positive cell integral of MMP-9 in high-dose luteolin group was markedly lower than that of control group (3.75 ± 1.43 vs 9.00 ± 1.08, P < 0.01). CONCLUSIONS: Luteolin can effectively inhibit the in vivo growth of gastric tumor. The mechanism may be correlated with the stimulation of immune response and the down-regulated expressions of VEGF-A and MMP-9.

Physiological and proteomic responses of two contrasting Populus cathayana populations to drought stress.

The acclimation of plants to water deficit is the result of many different physiological and biochemical mechanisms. To gain a better understanding of drought stress acclimation and tolerance mechanisms in Populus cathayana Rehder, we carried out an integrated physiological and comparative proteomic analysis on the drought stress responses of two contrasting populations originating from wet and dry regions in western China. The plantlets were subjected to continuous drought stress by withholding soil water content at 25% of field capacity (FC) for 45 days, while the control treatments were kept at 100% FC. Drought stress significantly inhibited plant growth, decreased net photosynthetic rate and stomatal conductance of leaves, increased the relative electrolyte leakage and malondialdehyde (MDA) content, and, at the same time, accumulated soluble sugars and free proline in both populations tested. The population from the dry climate region exhibited stronger tolerance to drought stress compared with the wet climate population. The proteomic analyses resulted in the identification of 40 drought-responsive proteins. The functional categories of these proteins include the regulation of transcription and translation, photosynthesis, cytoskeleton, secondary metabolism, HSPs/chaperones, redox homeostasis and defense response. The results suggest that poplars' tolerance to drought stress relates to the control of reactive oxygen species (ROS) and to osmoprotective capacity. The differential regulation of some drought-responsive proteins, such as HSPs and the enzymes related to redox homeostasis and regulation of secondary metabolism, plays an important role in poplars' tolerance and acclimation to drought stress. In conclusion, acclimation to water deficit involves changes in cellular metabolism and the regulation of gene networks. The present study not only provides new insights into the mechanisms of acclimation and tolerance to drought stress in different poplar populations but also provides clues for improving poplars' drought tolerance through breeding or genetic engineering.

Sex-specific responses of Populus cathayana to drought and elevated temperatures.

Dioecious plant species represent an important component of terrestrial ecosystems. Yet, little is known about sex-specific responses to drought and elevated temperatures. Populus cathayana Rehd, which is a dioecious, deciduous tree species, widely distributed in the northern, central and southwestern regions of China, was employed as a model species in our study. In closed-top chamber experiments, sex-specific morphological, physiological and biochemical responses of P. cathayana to drought and different elevated temperatures were investigated. Compared with the controls, drought significantly decreased the growth and the net photosynthesis rate (A), and increased the intrinsic water use efficiency (WUE(i)), carbon isotope composition (delta13C), and the malondialdehyde (MDA) and abscisic acid (ABA) contents in droughted plants. In contrast, elevated temperatures significantly promoted the growth and the A, but decreased the WUE(i), delta13C, MDA and ABA contents in well-watered individuals. When compared with males, elevated temperatures induced well-watered females to express a greater increase in the height growth (HG), basal diameter (BD), leaf area (LA), total number of leaves (TNL), dry matter accumulation (DMA) and specific leaf area (SLA), and a lower decrease in the A value, transpiration (E), stomatal conductance (g(s)), MDA and ABA contents, while elevated temperatures induced drought-stressed females to exhibit lower values of HG, BD, LA, TNL, DMA, A, E, g(s) and the intercellular CO2 concentration (C(i)), and higher levels of SLA, WUE(i), delta13C, MDA and ABA contents. Our results indicated that the female individuals of P. cathayana are more responsive and suffer from greater negative effects than do males when grown under environments with increased drought stress and elevated temperature.