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Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
A liquid–gas interface (LGI) on submerged microstructure surfaces has the potential to achieve large slip velocities, which is significant for underwater applications such as drag reduction. However, surfactants adsorbing on the LGI can cause surface tension gradient against the mainstream, which weakens the flow near the LGI and severely limits drag reduction. The mechanism of the effect of surfactants on two-dimensional flows has already been proposed, while the effect of surfactants on the three-dimensional flow near the LGI is still not clear. In our study, we specifically design an experimental system to directly observe a three-dimensional backflow at the LGI. The formation as well as the behaviour of the backflow are demonstrated to be significantly influenced by the surfactant. Combining experimental measurements, theoretical analyses and numerical simulations, we reveal the underlying mechanism of the backflow, which is a competition between the mainstream and the Marangoni flows generated by the interfacial concentration gradients of surfactant simultaneously in streamwise and spanwise directions, reflecting the three-dimensional feature of the backflow. In addition, a kinematic similarity is obtained to characterize the backflow. The current work provides a model system for investigating the three-dimensional backflow at the LGI with surfactants, which is significant for practical applications such as drag reduction and superhydrophobicity.
Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
(1 − x)Ba(Mg1/3Ta2/3)O3–xBa(Co1/3Nb2/3)O3 (BMT–BCN, x = 0.0, 0.20, 0.25, 0.30, 0.40) ceramics were prepared using the traditional solid-state reaction method. X-ray diffraction patterns have shown that the intensities of (001) and (100) super-lattices decrease with the increase in the BCN content. Seven main Raman vibrational modes are observed, assigned, and illustrated, in particular. Raman shifts of Eg(O) modes and the FWHM values of F2g(O)/A1g(O) modes have close relationship with the dielectric properties. The calculated values by the four-parameter semiquantum model based on IR reflectivity match well with the measured data (@3.8 GHz), which means that most of dielectric contribution to the system may be ascribed to the absorption of structural phononic oscillations at the infrared region, and the contribution from the scattering of the defective phonons is small. The contributions of each vibrational mode on the dielectric responses were investigated in detail, indicating that the low-frequency modes (A2u(1) and Eu(1)) have a decisive role to the dielectric properties.
This study was conducted to evaluate whether medium-chain TAG (MCT) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial inflammatory response, as well as necroptosis. A total of twenty-four weanling piglets were randomly allotted to one of four treatments in a 2×2 factorial arrangement including diet type (5 % maize oil v. 4 % MCT+1 % maize oil) and immune stress (saline v. E. coli LPS). The piglets were fed diets containing maize oil or MCT for 21 d. On 21 d, piglets were injected intraperitoneally with saline or LPS. The blood and intestinal samples were collected at 4 h post injection. Supplementation with MCT improved intestinal morphology, digestive and barrier function, indicated by increased jejunal villus height, increased jejunal and ileal disaccharidases (sucrase and maltase) activities, as well as enhanced protein expression of claudin-1. Furthermore, the protein expression of heat-shock protein 70 in jejunum and the concentration of TNF-α in plasma were reduced in the piglets fed diets supplemented with MCT. In addition, MCT down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerisation domain proteins (NOD) signalling-related genes in jejunum and ileum. Finally, MCT inhibited jejunal and ileal enterocyte necroptosis indicated by suppressed mRNA expression of the receptor-interacting protein 3 and mixed-lineage kinase domain-like protein. These results indicate that MCT supplementation may be closely related to inhibition of TLR4, NOD and necroptosis signalling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.
In this paper we use the method of conjugate duality to investigate a class of stochastic optimal control problems where state systems are described by stochastic differential equations with delay. For this, we first analyse a stochastic convex problem with delay and derive the expression for the corresponding dual problem. This enables us to obtain the relationship between the optimalities for the two problems. Then, by linking stochastic optimal control problems with delay with a particular type of stochastic convex problem, the result for the latter leads to sufficient maximum principles for the former.
Pro-inflammatory cytokines are critical in mechanisms of muscle atrophy. In addition, asparagine (Asn) is necessary for protein synthesis in mammalian cells. We hypothesised that Asn could attenuate lipopolysaccharide (LPS)-induced muscle atrophy in a piglet model. Piglets were allotted to four treatments (non-challenged control, LPS-challenged control, LPS+0·5 % Asn and LPS+1·0 % Asn). On day 21, the piglets were injected with LPS or saline. At 4 h post injection, piglet blood and muscle samples were collected. Asn increased protein and RNA content in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). However, Asn had no effect on the protein abundance of MAFbx and MuRF1. In addition, Asn decreased muscle AMP-activated protein kinase (AMPK) α phosphorylation, but increased muscle protein kinase B (Akt) and Forkhead Box O (FOXO) 1 phosphorylation. Moreover, Asn decreased the concentrations of TNF-α, cortisol and glucagon in plasma, and TNF-α mRNA expression in muscles. Finally, Asn decreased mRNA abundance of muscle toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) signalling-related genes, and regulated their negative regulators. The beneficial effects of Asn on muscle atrophy may be associated with the following: (1) inhibiting muscle protein degradation via activating Akt and inactivating AMPKα and FOXO1; and (2) decreasing the expression of muscle pro-inflammatory cytokines via inhibiting TLR4 and NOD signalling pathways by modulation of their negative regulators.
Stress induces injury in intestinal barrier function in piglets. Long-chain n-3 PUFA have been shown to exhibit potential immunomodulatory and barrier protective effects in animal models and clinical trials. In addition, corticotropin-releasing hormone (CRH)/CRH receptor (CRHR) signalling pathways play an important role in stress-induced alterations of intestinal barrier function. We hypothesised that fish oil could affect intestinal barrier function and CRH/CRHR signalling pathways. In total, thirty-two weaned pigs were allocated to one of four treatments. The experiment consisted of a 2×2 factorial design, and the main factors included immunological challenge (saline or lipopolysaccharide (LPS)) and diet (5 % maize oil or 5 % fish oil). On d 19 of the trial, piglets were treated with saline or LPS. At 4 h after injection, all pigs were killed, and the mesenteric lymph nodes (MLN), liver, spleen and intestinal samples were collected. Fish oil decreased bacterial translocation incidence and the number of translocated micro-organisms in the MLN. Fish oil increased intestinal claudin-1 protein relative concentration and villus height, as well as improved the intestinal morphology. In addition, fish oil supplementation increased intestinal intraepithelial lymphocyte number and prevented elevations in intestinal mast cell and neutrophil numbers induced by LPS challenge. Moreover, fish oil tended to decrease the mRNA expression of intestinal CRHR1, CRH and glucocorticoid receptors. These results suggest that fish oil supplementation improves intestinal barrier function and inhibits CRH/CRHR1 signalling pathway and mast cell tissue density.
The intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa may lead to intestinal damage. Asparagine (Asn) is a precursor for many other amino acids such as aspartate, glutamine and glutamate, which can be used to supply energy to enterocytes. In the present study, we hypothesise that dietary supplementation of Asn could alleviate bacterial lipopolysaccharide (LPS)-induced intestinal injury via improvement of intestinal energy status. A total of twenty-four weaned piglets were assigned to one of four treatments: (1) non-challenged control; (2) LPS+0 % Asn; (3) LPS+0·5 % Asn; (4) LPS+1·0 % Asn. On day 19, piglets were injected with LPS or saline. At 24 h post-injection, piglets were slaughtered and intestinal samples were collected. Asn supplementation improved intestinal morphology, indicated by higher villus height and villus height:crypt depth ratio, and lower crypt depth. Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. In addition, Asn supplementation attenuated bacterial LPS-induced intestinal energy deficits, indicated by increased ATP and adenylate energy charge levels, and decreased AMP:ATP ratio. Moreover, Asn administration increased the activities of key enzymes involved in the tricarboxylic acid cycle, including citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-α1 (AMPKα1), AMPKα2, silent information regulator 1 (SIRT1) and PPARγ coactivator-1α (PGC1α), and reduced intestinal AMPKα phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status.
Pro-inflammatory cytokines play a key role in many models of hepatic damage. In addition, asparagine (Asn) plays an important role in immune function. We aimed to investigate whether Asn could attenuate lipopolysaccharide (LPS)-induced liver damage. Forty-eight castrated barrows were allotted to four groups including: (1) non-challenged control; (2) LPS-challenged control; (3) LPS+0·5 % Asn; and (4) LPS+1·0 % Asn. After 19 d feeding with control, 0·5 or 1·0 % Asn diets, pigs were injected with LPS or saline. Blood and liver samples were obtained at 4 h (early stage) and 24 h (late stage) post-injection. Asn alleviated liver injury, indicated by reduced serum aspartate aminotransferase and alkaline phosphatase activities linearly and quadratically; it increased claudin-1 protein expression linearly and quadratically at 24 h, and less severe liver morphological impairment at 4 or 24 h. In addition, Asn decreased mRNA expression of TNF-α and heat shock protein 70 (HSP70) linearly and quadratically at 4 h; it increased TNF-α mRNA expression, and HSP70 protein expression linearly and quadratically at 24 h. Moreover, Asn increased inducible NO synthase activity linearly and quadratically. Finally, Asn down-regulated the mRNA expression of Toll-like receptor 4 (TLR4) signalling molecules (TLR4, IL-1 receptor-associated kinase 1 (IRAK1), TNF-α receptor-associated factor 6), nucleotide-binding oligomerisation domain protein (NOD) signalling molecules (NOD1, NOD2 and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2 (RIPK2)), and NF-κB p65 linearly or quadratically at 4 h. Oppositely, Asn up-regulated mRNA expressions of TLR4 and NOD signalling molecules (TLR4, myeloid differentiation factor 88, IRAK1, NOD2 and RIPK2), and their negative regulators (radioprotective 105, single Ig IL-1R-related molecule, Erbb2 interacting protein and centaurin β1) linearly or quadratically at 24 h. These results indicate that, in early and late stages of LPS challenge, Asn improves liver integrity and exerts different regulatory effects on mRNA expression of TLR4 and NOD signalling molecules.
Tributyrin (TBU) is a good dietary source of butyrate and has beneficial effects on the maintenance of normal intestinal morphology. The present study tested the hypothesis that dietary TBU supplementation could alleviate intestinal injury in the acetic acid (ACA)-induced porcine model of colitis. A total of eighteen piglets (25 d old) were randomly allocated to one of three treatment groups (control, ACA and TBU). The control and ACA groups were fed a basal diet and the TBU group was fed the basal diet supplemented with 0·1 % TBU. On day 15 of the trial, under anaesthesia, a soft catheter was inserted into the rectum of piglets (20–25 cm from the anus), followed by administration of either saline (control group) or ACA (10 ml of 10 % ACA solution for ACA and TBU groups). On day 22 of the trial, after venous blood samples were collected, piglets were killed to obtain mid-ileum and mid-colon mucosae. Compared with the control group, the ACA group exhibited an increase (P< 0·05) in lymphocyte counts, creatinine, PGE2, and malondialdehyde concentrations and diamine oxidase and inducible NO synthase activities in the plasma and lymphocyte density in the colon and a decrease in insulin concentrations and glutathione peroxidase activity, ileal villus height:crypt depth ratios and goblet cell numbers in the colon. These adverse effects of ACA were attenuated by TBU supplementation. Moreover, TBU prevented the ACA-induced increase in caspase-3 levels while enhancing claudin-1 protein and epidermal growth factor receptor (EGFR) mRNA expression in the colonic mucosa. Collectively, these results indicate that dietary supplementation with 0·1 % TBU alleviates ACA-induced intestinal injury possibly by inhibiting apoptosis, promoting tight-junction formation and activating EGFR signalling.
The present study determined whether α-ketoglutarate (AKG) might affect the expression of AMP-activated protein kinase (AMPK) and energy status in the intestinal mucosa of piglets challenged with Escherichia coli lipopolysaccharide (LPS). A total of eighteen piglets (weaned at 21 d of age) were allocated to one of three treatments: (1) non-challenged (control); (2) LPS-challenged (LPS); (3) LPS+1 % AKG (LPS+AKG). Piglets in the control and LPS groups were fed a maize- and soyabean meal-based diet, and the LPS+AKG group was fed the basal diet supplemented with 1 % AKG. On days 10, 12, 14 and 16 of the trial, piglets in the LPS and LPS+AKG groups were challenged with LPS (80 μg/kg body weight), whereas piglets in the control group received the same volume of sterile saline. Pigs were euthanised 24 h after the last administration of LPS or saline to obtain intestinal mucosae for biochemical analysis. Compared with the control group, LPS administration decreased (P < 0·05) the oxidation of AKG, oleic acid, glutamine and glucose in enterocytes, decreased concentrations of ATP in the duodenal and jejunal mucosae and decreased adenylate energy charge (AMP:ATP ratio) in the jejunal and ileal mucosae. Additionally, LPS treatment reduced (P < 0·05) mucosal concentrations of phosphorylated AMPK in the jejunum and ileum as well as acetyl-CoA carboxylase in all segments of the small intestine. The adverse effects of LPS were reversed by AKG. Collectively, these results indicate that dietary supplementation with 1 % AKG beneficially modulates the AMPK signalling pathway to improve energy status in the small intestine of LPS-challenged piglets.
We study positive solutions to the porous media equation of degenerate logistic type −Δu = a(x)u1/m – b(x)f(u), m > 1, which blow up at the inner boundary and satisfy a homogeneous boundary condition at the outer boundary of a multiply connected domain. In particular, we investigate uniqueness and blow-up rate near the inner boundary for such solutions. We also look at the limiting behaviour as m ↘ 1 for the special case where b(x) > 0 and f(u) = up/m with p > m.
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