Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA ...virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115
organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115
cells compared to the wild-type counterparts. Consequently, the Rnf115
mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling.
We compared the proportions and differences in the polysaccharides of
(Berkeley) after drying them by various processes, such as 18 °C cold air, 50 °C hot air, and freeze-drying. We also focused on ...the moisture capacity kinetic parameters of
polysaccharides using various thermal analyses, including differential scanning calorimetry and thermogravimetric techniques. Erofeev's kinetic and proto-kinetic equations, utilized for kinetic model simulation, can predict the moisture capacity due to the thermal effect. Among the various drying processes, cold air-drying had the highest molecular weight of 2.41 × 10
Da and a moisture content of 13.05% for
polysaccharides. Overall, the freeze-dried products had the best thermal decomposition properties under the conditions of a closed system, with an air or nitrogen atmosphere, and had an excellent moisture capacity of around 35 kJ/kg under a closed system for all samples.
The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted ...significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated.
CAPE and CAPPE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of CRC cells both in vitro and in vivo. Anti-cancer effects of these CA derivatives were measured by using proliferation assays, cell cycle analysis, western blotting assay, reporter gene assay and immunohistochemical (IHC) staining assays both in vitro and in vivo. This study demonstrates that CAPE and CAPPE exhibit a dose-dependent inhibition of proliferation and survival of CRC cells through the induction of G0/G1 cell cycle arrest and augmentation of apoptotic pathways. Consumption of CAPE and CAPPE significantly inhibited the growth of colorectal tumors in a mouse xenograft model. The mechanisms of action included a modulation of PI3-K/Akt, AMPK and m-TOR signaling cascades both in vitro and in vivo. In conclusion, the results demonstrate novel anti-cancer mechanisms of CA derivatives against the growth of human CRC cells.
CA derivatives are potent anti-cancer agents that augment AMPK activation and promote apoptosis in human CRC cells. The structure of CA derivatives can be used for the rational design of novel inhibitors that target human CRC cells.
Abstract
As a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have ...been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal β-WP
2
crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the “spike-like” Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of β-WP
2
. These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials.
Abstract
Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived ...metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.
In this paper, we propose a binaural system for virtual auditory space synthesis and reproduction. We introduce a subjective listening test for head-related transfer function (HRTF) customization and ...real-time implementation of ambisonic surround sound over headphones. In this test, a listener first selects the closest-matching HRTF dataset from an existing database. The selected HRTF dataset must fulfill the criteria of front-back discrimination and up-down discrimination. Secondly, the selected HRTF dataset is utilized to build a binaural ambisonic system composed of an encoder for synthesizing multiple sound sources, an image-source model for listening-room simulation, an ambisonic rotator responding to head motion in three axes, and a binaural ambisonic decoder. Additionally, we propose a system optimization technique that minimizes computational cost and enhances audio quality. Finally, we present both subjective and objective measurements of the perceived audio quality that were conducted to validate this approach. The audio quality assessment examined the frequency hearing impairment, localization error, and localization blur. The proposed system is especially suitable for mixing and rendering immersive sound in virtual reality.
Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent ...over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.
•A novel prediction method that utilizes the gradient boosting machine (GBM) method to analyze slope stability.•221 different actual slope cases between 1994 and 2011 with circular mode failure are ...examined using GBM method.•Three performance metrics, the AUC, classification accuracy rate and Cohen’s Kappa coefficient are employed.•The GBM model has high credibility for the prediction of slope stability.•Geometrical slope design parameters (γ, C and H) are the most influential on the stability of slope.
Prediction of slope stability is one of the most crucial tasks in mining and geotechnical engineering projects. The accuracy of the prediction is very important for mitigating the risk of slope instability and enhancing mine safety in preliminary design. However, existing methods such as traditional statistical learning models are unable to provide accurate results for slope instability due to the complexity and uncertainties of multiple related factors with small unbalanced data samples thus requiring complex data processing algorithms. To address this limitation, this paper presents a novel prediction method that utilizes the gradient boosting machine (GBM) method to analyze slope stability. The GBM-based model is developed by the freely available R Environment software, trained and tested with the parameters obtained from the detailed investigation of 221 different actual slope cases between 1994 and 2011 with circular mode failure available in the literature. The stability of the circular slope accounts for the unit weight (γ), cohesion (c), angle of internal friction (φ), slope angle (β), slope height (H) and pore water pressure coefficient (ru). A fivefold cross-validation procedure is implemented to determine the optimal parameter values during the GBM modeling and an external testing set is employed to validate the prediction performance of models. Area under the curve (AUC), classification accuracy rate and Cohen’s Kappa coefficient have been employed for measuring the performance of the proposed model. The analysis of AUC, accuracy together with kappa for the dataset demonstrate that the GBM model has high credibility as it achieves a comparable AUC, classification accuracy rate and Cohen’s kappa values of 0.900, 0.8654 and 0.7324, respectively for the prediction of slope stability. Also, variable importance and partial dependence plots are used to interpret the complex relationships between the GBM predictive results and predictor variables.
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