Nuclear Nicotinamide Adenine Dinucleotide Deficiency by Nmnat1 Deletion Impaired Hepatic Insulin Signaling, Mitochondrial Function, and Hepatokine Expression in Mice Fed a High-Fat Diet.

Metabolic syndrome (MetS) is a worldwide challenge that is closely associated with obesity, nonalcoholic liver disease, insulin resistance, and type 2 diabetes. Boosting nicotinamide adenine dinucleotide (NAD+) presents great potential in preventing MetS. However, the function of nuclear NAD+ in the development of MetS remains poorly understood. In this study, hepatocyte-specific Nmnat1 knockout mice were used to determine a possible link between nuclear NAD+ and high-fat diet (HFD)-induced MetS. We found that Nmnat1 knockout significantly reduced hepatic nuclear NAD+ levels but did not exacerbate HFD-induced obesity and hepatic triglycerides accumulation. Interestingly, loss of Nmnat1 caused insulin resistance. Further analysis revealed that Nmnat1 deletion promoted gluconeogenesis but inhibited glycogen synthesis in the liver. Moreover, Nmnat1 deficiency induced mitochondrial dysfunction by decreasing mitochondrial DNA (mtDNA)-encoded complexes Ⅰ and Ⅳ, suppressing mtDNA replication and mtRNA transcription and reducing mtDNA copy number. In addition, Nmnat1 depletion affected the expression of hepatokines in the liver, particularly downregulating the expression of follistatin. These findings highlight the importance of nuclear NAD+ in maintaining insulin sensitivity and provide insights into the mechanisms underlying HFD-induced insulin resistance.

Conventional type 1 dendritic cells protect against gut barrier disruption via maintaining Akkermansia muciniphila in alcoholic steatohepatitis.

BACKGROUND AND AIMS: Alcohol-perturbed gut immune homeostasis is associated with the development of alcoholic liver disease (ALD). However, the role of intestinal dendritic cells (DCs) in ALD progression is still unknown. This study aimed to investigate the cellular and molecular mechanisms through which intestinal DCs respond to alcohol exposure and contribute to the pathogenesis of ALD. APPROACH AND RESULTS: After 8 weeks of alcohol consumption, the number of basic leucine zipper transcription factor ATF-like 3 ( Batf3 )-dependent conventional type 1 DCs (cDC1s) was dramatically decreased in the intestine but not the liver. cDC1 deficient Batf3 knockout mice along with wild-type mice were subjected to chronic-binge ethanol feeding to determine the role of intestinal cDC1s reduction in ALD. cDC1s deficiency exacerbated alcohol-induced gut barrier disruption, bacterial endotoxin translocation into the circulation, and liver injury. Adoptive transfer of cDC1s to alcohol-fed mice ameliorated alcohol-mediated gut barrier dysfunction and liver injury. Further studies revealed that intestinal cDC1s serve as a positive regulator of Akkermansia muciniphila ( A. muciniphila ). Oral administration of A. muciniphila markedly reversed alcoholic steatohepatitis in mice. Mechanistic studies revealed that cDC1s depletion exacerbated alcohol-downregulated intestinal antimicrobial peptides which play a crucial role in maintaining A. muciniphila abundance, by disrupting the IL-12-interferon gamma signaling pathway. Lastly, we identified that intestinal cDC1s were required for the protective role of Lactobacillus reuteri in alcoholic steatohepatitis. CONCLUSIONS: This study demonstrated that cDC1s protect alcohol-induced liver injury by maintaining A. muciniphila abundance in mice. Targeting cDC1s may serve as a promising therapeutic approach for treating ALD.

Gastric cancer cell-originated small extracellular vesicle induces metabolic reprogramming of BM-MSCs through ERK-PPARγ-CPT1A signaling to potentiate lymphatic metastasis.

Tumor microenvironment and metabolic reprogramming are critical for tumor metastasis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely involved in the formation of tumor microenvironment and present oncogenic phenotypes to facilitate lymph node metastasis (LNM) in response to small extracellular vesicles (sEV) released by gastric cancer (GC) cells. However, whether metabolic reprograming mediates transformation of BM-MSCs remains elusive. Herein, we revealed that the capacity of LNM-GC-sEV educating BM-MSCs was positively correlated with the LNM capacity of GC cells themselves. Fatty acid oxidation (FAO) metabolic reprogramming was indispensable for this process. Mechanistically, CD44 was identified as a critical cargo for LNM-GC-sEV enhancing FAO via ERK/PPARγ/CPT1A signaling. ATP was shown to activate STAT3 and NF-κB signaling to induce IL-8 and STC1 secretion by BM-MSCs, thereby in turn facilitating GC cells metastasis and increasing CD44 levels in GC cells and sEV to form a persistent positive feedback loop between GC cells and BM-MSCs. The critical molecules were abnormally expressed in GC tissues, sera and stroma, and correlated with the prognosis and LNM of GC patients. Together, our findings uncover the role of metabolic reprogramming mediated BM-MSCs education by LNM-GC-sEV, which presents a novel insight into the mechanism underlying LNM and provides candidate targets for GC detection and therapy.

Treatment of cytokine release syndrome-induced vascular endothelial injury using mesenchymal stem cells.

Cytokine release syndrome (CRS) is an acute systemic inflammatory reaction in which hyperactivated immune cells suddenly release a large amount of cytokines, leading to exaggerated inflammatory responses, multiple organ dysfunction, and even death. Although palliative treatment strategies have significantly reduced the overall mortality, novel targeted treatment regimens with superior therapy efficacy are urgently needed. Vascular endothelial cells (ECs) are important target cells of systemic inflammation, and their destruction is considered to be the initiating event underlying many serious complications of CRS. Mesenchymal stem/stromal cells (MSCs) are multipotent cells with self-renewing differentiation capacity and immunomodulatory properties. MSC transplantation can effectively suppress the activation of immune cells, reduce the bulk release of cytokines, and repair damaged tissues and organs. Here, we review the molecular mechanisms underlying CRS-induced vascular endothelial injury and discuss potential treatments using MSCs. Preclinical studies demonstrate that MSC therapy can effectively repair endothelium damage and thus reduce the incidence and severity of ensuing CRS-induced complications. This review highlights the therapeutic role of MSCs in fighting against CRS-induced EC damage, and summarizes the possible therapeutic formulations of MSCs for improved efficacy in future clinical trials.

Immune and cytokine alterations and RNA-sequencing analysis in gestational tissues from pregnant women after recovery from COVID-19.

BACKGROUND: COVID-19 is a global pandemic. Understanding the immune responses in pregnant women recovering from COVID-19 may suggest new therapeutic approaches. METHODS: We performed a cross-sectional study between March 1, 2020, and September 1, 2020. Participants were assigned into the convalescent COVID-19 group if they had a previous COVID-19 infection during pregnancy or the healthy control group. RNA-Seq was performed on human umbilical cord mesenchymal stem cells (hUMSCs) and human amniotic mesenchymal stem cells (hAMSCs). Immunohistochemical staining, cytokine testing, lymphocyte subset analysis, RNA-Seq, and functional analyses were performed on the placental and umbilical cord blood (UCB) and compared between the two groups. RESULTS: A total of 40 pregnant women were enrolled, with 13 in the convalescent group and 27 in the control group. There were 1024, 46, and 32 differentially expressed genes (DEGs) identified in the placental tissue, hUMSCs, and hAMSCs between the convalescent and control groups, respectively. Enrichment analysis showed those DEGs were associated with immune homeostasis, antiviral activity, cell proliferation, and tissue repair. Levels of IL-6, TNF-α, total lymphocyte counts, B lymphocytes, Tregs percentages, and IFN-γ expressing CD4+ and CD8+ T cells were statistically different between two groups (p ≤ 0.05). ACE2 and TMPRSS2 expressed on the placenta were not different between the two groups (p > 0.05). CONCLUSION: Multiple changes in immune responses occurred in the placental tissue, hUMSCs, and hAMSCs after maternal recovery from COVID-19, which might imply their protective roles against COVID-19 infection.

Sow-Offspring Diets Supplemented with Probiotics and Synbiotics Are Associated with Offspring's Growth Performance and Meat Quality.

Probiotics and synbiotics supplementation have been shown to play potential roles in animal production. The present study aimed to evaluate the effects of dietary probiotics and synbiotics supplementation to sows during gestation and lactation and to offspring pigs (sow-offspring) on offspring pigs' growth performance and meat quality. Sixty-four healthy Bama mini-pigs were selected and randomly allocated into four groups after mating: the control, antibiotics, probiotics, and synbiotics groups. After weaning, two offspring pigs per litter were selected, and four offspring pigs from two litters were merged into one pen. The offspring pigs were fed a basal diet and the same feed additive according to their corresponding sows, representing the control group (Con group), sow-offspring antibiotics group (S-OA group), sow-offspring probiotics group (S-OP group), and sow-offspring synbiotics group (S-OS group). Eight pigs per group were euthanized and sampled at 65, 95, and 125 d old for further analyses. Our findings showed that probiotics supplementation in sow-offspring diets promoted growth and feed intake of offspring pigs during 95-125 d old. Moreover, sow-offspring diets supplemented with probiotics and synbiotics altered meat quality (meat color, pH45min, pH24h, drip loss, cooking yield, and shear force), plasma UN and AMM levels, and gene expressions associated with muscle-fiber types (MyHCI, MyHCIIa, MyHCIIx, and MyHCIIb) and muscle growth and development (Myf5, Myf6, MyoD, and MyoG). This study provides a theoretical basis for the maternal-offspring integration regulation of meat quality by dietary probiotics and synbiotics supplementation.

ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis.

OBJECTIVE: Mitochondrial dysfunction plays a dominant role in the pathogenesis of alcoholic liver disease (ALD); however, the underlying mechanisms remain to be fully understood. We previously found that hepatic activating transcription factor 4 (ATF4) activation was associated with mitochondrial dysfunction in ALD. This study aimed to investigate the function and mechanism of ATF4 in alcohol-induced hepatic mitochondrial dysfunction. DESIGN: ATF4 activation was detected in the livers of patients with severe alcoholic hepatitis (AH). The role of ATF4 and mitochondrial transcription factor A (TFAM) in alcohol-induced liver damage was determined in hepatocyte-specific ATF4 knockout mice and liver-specific TFAM overexpression mice, respectively. RESULTS: Hepatic PERK-eIF2α-ATF4 ER stress signalling was upregulated in patients with AH. Hepatocyte-specific ablation of ATF4 in mice ameliorated alcohol-induced steatohepatitis. ATF4 ablation also attenuated alcohol-impaired mitochondrial biogenesis and respiratory function along with the restoration of TFAM. Cell studies confirmed that TFAM expression was negatively regulated by ATF4. TFAM silencing in hepatoma cells abrogated the protective effects of ATF4 knockdown on ethanol-mediated mitochondrial dysfunction and cell death. Moreover, hepatocyte-specific TFAM overexpression in mice attenuated alcohol-induced mitochondrial dysfunction and liver damage. Mechanistic studies revealed that ATF4 repressed the transcription activity of nuclear respiratory factor 1 (NRF1), a key regulator of TFAM, through binding to its promoter region. Clinical relevance among ATF4 activation, NRF1-TFAM pathway disruption and mitochondrial dysfunction was validated in the livers of patients with AH. CONCLUSION: This study demonstrates that hepatic ATF4 plays a pathological role in alcohol-induced mitochondrial dysfunction and liver injury by disrupting the NRF1-TFAM pathway.

Paneth Cell Dysfunction Mediates Alcohol-related Steatohepatitis Through Promoting Bacterial Translocation in Mice: Role of Zinc Deficiency.

BACKGROUND AND AIMS: Microbial dysbiosis is associated with alcohol-related hepatitis (AH), with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides, α-defensins, and to define the link between PC dysfunction and AH. APPROACH AND RESULTS: Translocation of pathogen-associated molecular patterns (PAMPs) was determined in patients with severe AH and in a mouse model of alcoholic steatohepatitis. Microbial composition and PC function were examined in mice. The link between α-defensin dysfunction and AH was investigated in α-defensin-deficient mice. Synthetic human α-defensin 5 (HD5) was orally given to alcohol-fed mice to test the therapeutic potential. The role of zinc deficiency in α-defensin was evaluated in acute and chronic mouse models of zinc deprivation. Hepatic inflammation was associated with PAMP translocation and lipocalin-2 (LCN2) and chemokine (C-X-C motif) ligand 1 (CXCL1) elevation in patients with AH. Antibiotic treatment, lipopolysaccharide injection to mice, and in vitro experiments showed that PAMPs, but not alcohol, directly induced LCN2 and CXCL1. Chronic alcohol feeding caused systemic dysbiosis and PC α-defensin reduction in mice. Knockout of functional α-defensins synergistically affected alcohol-perturbed bacterial composition and the gut barrier and exaggerated PAMP translocation and liver damage. Administration of HD5 effectively altered cecal microbial composition, especially increased Akkermansia muciniphila, and reversed the alcohol-induced deleterious effects. Zinc-regulated PC homeostasis and α-defensins function at multiple levels, and dietary zinc deficiency exaggerated the deleterious effect of alcohol on PC bactericidal activity. CONCLUSIONS: Taken together, the study suggests that alcohol-induced PC α-defensin dysfunction is mediated by zinc deficiency and involved in the pathogenesis of AH. HD5 administration may represent a promising therapeutic approach for treating AH.

Elevated atmospheric CO2 reduces yield-scaled N2 O fluxes from subtropical rice systems: Six site-years field experiments.

Increasing levels of atmospheric CO2 are expected to enhance crop yields and alter soil greenhouse gas fluxes from rice paddies. While elevated CO2 ( E CO 2 ) effects on CH4 emissions from rice paddies have been studied in some detail, little is known how E CO 2 might affect N2 O fluxes or yield-scaled emissions. Here, we report on a multi-site, multi-year in-situ FACE (free-air CO2 enrichment) study, aiming to determine N2 O fluxes and crop yields from Chinese subtropical rice systems as affected by E CO 2 . In this study, we tested various N fertilization and residue addition treatments, with rice being grown under either E CO 2 (+200 µmol/mol) or ambient control. Across the six site-years, rice straw and grain yields under E CO 2 were increased by 9%-40% for treatments fertilized with ≥150 kg N/ha, while seasonal N2 O emissions were decreased by 23%-73%. Consequently, yield-scaled N2 O emissions were significantly lower under E CO 2 . For treatments receiving insufficient fertilization (≤125 kg N/ha), however, no significant E CO 2 effects on N2 O emissions were observed. The mitigating effect of E CO 2 upon N2 O emissions is closely associated with plant N uptake and a reduction of soil N availability. Nevertheless, increases in yield-scaled N2 O emissions with increasing N surplus suggests that N surplus is a useful indicator for assessing N2 O emissions from rice paddies. Our findings indicate that with rising atmospheric CO2 soil N2 O emissions from rice paddies will decrease, given that the farmers' N fertilization is usually sufficient for crop growth. The expected decrease in N2 O emissions was calculated to compensate 24% of the simultaneously observed increase in CH4 emissions under E CO 2 . This shows that for an agronomic and environmental assessment of E CO 2 effects on rice systems, not only CH4 emissions, but also N2 O fluxes and yield-scaled emissions need to be considered for identifying most climate-friendly and economically viable options for future rice production.

Intravoxel incoherent motion magnetic resonance imaging in predicting IDH1 gene mutations in high-grade gliomas.

BACKGROUND: Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) has been applied to gliomas; however, the relationships between its parameters and isocitrate dehydrogenase 1 (IDH1) mutations in gliomas remain to be investigated. PURPOSE: To investigate the value of IVIM in predicting IDH1 mutations in high-grade gliomas before surgery. MATERIAL AND METHODS: A total of 72 patients with pathologically confirmed high-grade gliomas underwent conventional brain MRI and IVIM from September 2016 to May 2020. Among them, 22 cases were IDH1 mutant and 50 cases were IDH1 wild type. The independent samples t test (normal distribution and homogeneity of variance) or Mann-Whitney rank-sum test (non-normal distribution or heterogeneity of variance) was conducted, and receiver operating characteristic curves were generated to determine parameters for distinguishing IDH1-mutated from IDH1 wild-type high-grade gliomas. These parameters included apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). RESULTS: ADC, D, and f were significantly higher in IDH1-mutated gliomas than in IDH1 wild-type gliomas (P < 0.05 for all). There was no significant difference in the D* value between the two groups (P = 0.053). The areas under the curve of ADC, D, and f in predicting IDH1 mutations in gliomas were 0.798, 0.810, and 0.823, respectively. The specificity of ADC was highest (80.0%), and the sensitivity of the f value was the highest (100.0%). CONCLUSION: IVIM can be used for the quantitative prediction of IDH1 mutations in high-grade gliomas before surgery, and the f value is the most effective.

Ki-67 labeling index and the grading of cerebral gliomas by using intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling magnetic resonance imaging.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) have been applied to brain tumors; however, the relationship between their parameters and the Ki-67 labeling index (Ki-67 LI) for the grading of gliomas have yet to be investigated. PURPOSE: The aim of this study is to compare multiple parameters obtained from IVIM-DWI and 3D-ASL with the Ki-67 LI when grading gliomas. MATERIAL AND METHODS: Fifty-two patients with pathologically confirmed gliomas had undergone magnetic resonance imaging (MRI), including IVIM-DWI and 3D-ASL imaging. Mann-Whitney U tests were conducted and receiver operating characteristic (ROC) curves were generated to determine parameters for distinguishing high-grade gliomas (HGGs) from low-grade gliomas (LGGs). These parameters included the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo diffusivity (D*), perfusion fraction (f), cerebral blood flow (CBF), and their relative values (rADC, rD, rD*, rf, and rCBF). Spearman correlation analysis was used to assess the correlations of the parameters of MRI with the Ki-67 LI. RESULTS: The rADC, rD, and rf were significantly lower in HGGs than in LGGs (P < 0.005 for all). The rD had a significantly greater area under the ROC curve than that of the other parameters in the differentiation of HGGs from LGGs (P < 0.05). Both the rD and rf were moderately negatively correlated with the Ki-67 LI. CONCLUSION: Both the rD and rf can be used for the quantitative prediction of the Ki-67 LI. Among the extracted parameters, the rD had the significantly greatest diagnostic efficacy.

Dual functions of insect wings in an odor-guided aeronautic navigation.

Insects can detect and locate distant odor sources (food, mate, etc.) by tracking odor plumes, which is key to their survival. During an odor-guided navigation, flapping wings have been speculated to actively draw odorants to the antennae and enhance olfactory sensitivity. Utilizing an in-house computational fluid dynamics solver, we have quantified the odor plume structures of a fruit fly in a forward flight motion and have confirmed that the flapping wings induce a strong vortex flow over the insect's head, thereby enhancing the odor mass flux around the antennae (by ~1.8 times). To further understand the function of different wing area in terms of aerodynamics and olfaction, we designed an altered fruit fly wing by removing its trailing-edge portion; subsequent simulations showed that this altered wing has an improved lift production but with significantly reduction of the induced odor mass flux. Contrary to the common belief that the wing shapes of an insect are optimized only for aerodynamic performance, our results suggest that, because both aerodynamic and olfactory functions are indispensable during the odor-guided navigation, insects may sacrifice some aerodynamic potential to enhance olfactory detection; and the shape and size of the wing may be a balance between the two functions. Furthermore, we found that higher wing beat frequency and wing reversal phase induce higher odor mass flux, while lower beat frequency and downstroke phase produce better lift coefficient, which indicates another balance between the two functions.

Support vector machine-based multivariate pattern classification of methamphetamine dependence using arterial spin labeling.

Arterial spin labeling (ASL) magnetic resonance imaging has been widely applied to identify cerebral blood flow (CBF) abnormalities in a number of brain disorders. To evaluate its significance in detecting methamphetamine (MA) dependence, this study used a multivariate pattern classification algorithm, ie, a support vector machine (SVM), to construct classifiers for discriminating MA-dependent subjects from normal controls. Forty-five MA-dependent subjects, 45 normal controls, and 36 heroin-dependent subjects were enrolled. Classifiers trained with ASL-CBF data from the left or right cerebrum showed significant hemispheric asymmetry in their cross-validated prediction performance (P < 0.001 for accuracy, sensitivity, specificity, kappa, and area under the curve [AUC] of the receiver operating characteristics [ROC] curve). A classifier trained with ASL-CBF data from all cerebral regions (bilateral hemispheres and corpus callosum) was able to differentiate MA-dependent subjects from normal controls with a cross-validated prediction accuracy, sensitivity, specificity, kappa, and AUC of 89%, 94%, 84%, 0.78, and 0.95, respectively. The discrimination map extracted from this classifier covered multiple brain circuits that either constitute a network related to drug abuse and addiction or could be impaired in MA-dependence. The cerebral regions contribute most to classification include occipital lobe, insular cortex, postcentral gyrus, corpus callosum, and inferior frontal cortex. This classifier was also specific to MA-dependence rather than substance use disorders in general (ie, 55.56% accuracy for heroin dependence). These results support the future utilization of ASL with an SVM-based classifier for the diagnosis of MA-dependence and could help improve the understanding of MA-related neuropathology.

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model.

BACKGROUND: Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation. METHODS: Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose. RESULTS: Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20-2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100-500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz. CONCLUSION: Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the downstream trachea, can generate audible sound levels.

Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms.

Methyl donors play critical roles in nutritional programming through epigenetic regulation of gene expression. Here we fed gestational sows with control or betaine-supplemented diets (3g/kg) throughout the pregnancy to explore the effects of maternal methyl-donor nutrient on neonatal expression of hepatic lipogenic genes. Betaine-exposed piglets demonstrated significantly lower liver triglyceride content associated with down-regulated hepatic expression of lipogenic genes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD) and sterol regulatory element-binding protein-1c. Moreover, s-adenosyl methionine to s-adenosyl homocysteine ratio was elevated in the liver of betaine-exposed piglets, which was accompanied by DNA hypermethylation on FAS and SCD gene promoters and more enriched repression histone mark H3K27me3 on SCD gene promoter. Furthermore, glucocorticoid receptor (GR) binding to SCD gene promoter was diminished along with reduced serum cortisol and liver GR protein content in betaine-exposed piglets. GR-mediated SCD gene regulation was confirmed in HepG2 cells in vitro. Dexamethasone (Dex) drastically increased the luciferase activity of porcine SCD promoter, while the deletion of GR response element on SCD promoter significantly attenuated Dex-mediated SCD transactivation. In addition, miR-let-7e, miR-1285 and miR-124a, which respectively target porcine SCD, ACC and GR, were significantly up-regulated in the liver of betaine-exposed piglets, being in accordance with decreased protein content of these three genes. Taken together, our results suggest that maternal dietary betaine supplementation during gestation attenuates hepatic lipogenesis in neonatal piglets via epigenetic and GR-mediated mechanisms.

Microstructures in striato-thalamo-orbitofrontal circuit in methamphetamine users.

Background Striato-thalamo-orbitofrontal (STO) circuit plays a key role in the development of drug addiction. Few studies have investigated its microstructural abnormalities in methamphetamine (MA) users. Purpose To evaluate the microstructural changes and relevant clinical relevance of the STO circuit in MA users using diffusion tensor imaging (DTI). Material and Methods Twenty-eight MA users and 28 age-matched normal volunteers were enrolled. 3T magnetic resonance imaging (MRI) was employed to obtain structural T1-weighted (T1W) imaging and diffusion-tensor imaging (DTI) data. Freesurfer software was used for automated segmentation of the bilateral nucleus accumbens (NAc), thalami, and orbitofrontal cortex (OFC). Four DTI measures maps, fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) were generated and non-linearly co-registered to structural space. Comparisons of DTI measures of the STO circuit were carried out between MA and controls using repeated measures analysis of variance. Correlation analyses were performed between STO circuit DTI measures and clinical characteristics. Results The MA group had significant FA reduction in the bilateral NAc, OFC, and right thalamus ( P < 0.05). Lower left OFC FA and right NAc FA/AD were associated with longer duration of MA use. Lower right OFC FA was associated with younger age at first MA use. Higher FA and lower MD/RD in the thalamus, as well as higher left OFC RD, were associated with increased psychiatric symptoms. Conclusion The STO circuit has reduced microstructural integrity in MA users. Microstructural changes in the thalamus may compensate for dysfunction in functionally connected cortices, which needs further investigation.

Downregulation of prostaglandin E2 is involved in hindgut mucosal damage in lactating goats fed a high-concentrate diet.

NEW FINDINGS: What is the central question of this study? A high-concentrate (HC) diet results in damage to the hindgut mucosa. The aim of the study was to investigate the status of epithelial proliferation in the hindgut mucosa of goats with subacute ruminal acidosis and, simultaneously, to evaluate prostaglandin E2 synthesis and the downstream signalling pathways. What is the main finding and its importance? The downregulation of local prostaglandin E2 synthesis and its downstream signalling pathway are involved in the process of inhibiting epithelial proliferation in the hindgut epithelium of HC-fed goats. Our results provide new insight into the relationship between abnormal fermentation in the hindgut and damage to the intestinal mucosal barrier. Our previous data demonstrated that feeding a high-concentrate (HC) diet to lactating goats for a long time causes severe damage to the hindgut mucosa and parallels the activation of cell apoptosis and local oxidative stress. In the present study, changes in production of prostaglandin E2 (PGE2 ) and its signalling pathway were evaluated in the process of epithelial barrier disruption in the hindgut. Twelve goats in mid-lactation were randomly assigned to either a HC diet group or a low-concentrate (LC) diet group for 10 weeks. Cell proliferation markers, cyclooxygenase-2 activity, PGE2 content and the relative signalling pathway, including CREB and AKT, were analysed by enzyme-linked immunosorbent assay and Western blot, respectively. The mRNA and protein expressions of MKI67 and CCND2 (two proliferation markers) were significantly decreased in the caecal mucosa of HC- compared with LC-fed goats (P < 0.05). The protein content of interleukin-10 and ß-defensin in the caecal mucosa was also downregulated in HC-fed goats (P < 0.05). The HC-fed goats showed a tendency to a decrease in cyclooxygenase-2 enzyme activity (P = 0.081) and a significant decrease of local PGE2 content and EP4 (PGE2 receptor) protein expression in caecal mucosa (P < 0.05). Moreover, the protein abundance of p-CREB (P = 0.069) and p-AKT (P < 0.05) and the mRNA expression of epidermal growth factor receptor (P < 0.05) were downregulated in caecal mucosa of HC- compared with LC-fed goats. These results indicate that a reduction in epithelial cell proliferation was partly responsible for the damage to the epithelial barrier, which might be associated with the downregulation of PGE2 synthesis and its downstream signalling pathway.

Edge detection based on Retinex theory and wavelet multiscale product for mine images.

The application of visual technology to mine robots has become a hot topic in the development of coal mine automatic production. Key techniques of robot control are the feature recognition of sampled videos and the perception of complex surroundings. However, it is difficult for features in underground images with dark hue and low target discrimination to be recognized and extracted, especially for reasons of the nonuniform illumination and heavy dust concentration in mines. Hence, an edge detection algorithm based on the Retinex theory and wavelet multiscale product is proposed in this paper for low-light-level mine image feature extraction, which employs a modified multiscale Retinex method to deal with the low frequency subplot after the wavelet decomposition, an improved fuzzy enhancement approach to handle high frequency components, and finally a revised multiscale product edge detection algorithm to obtain the ultima edge image. Compared with a variety of algorithms by detecting edges of both normal illuminated and underground images, experimental results show that with characteristics of high real-time performance and detection accuracy, the proposed algorithm can exactly meet the needs of surrounding environment perception for mine robots, which applies well to image edge detection in low illumination mines.

Comparison of image quality and application values on different field-of-view diffusion-weighted imaging of breast cancer.

BACKGROUND: Single-shot echo planar imaging (SS-EPI) diffusion-weighted magnetic resonance imaging (DW-MRI) is the most-widely sequence in breast MRI. MRI artifacts and magnetic susceptibility are sometimes severe when this sequence is utilized at 3T. PURPOSE: To compare the imaging quality, ADC values between SS-EPI DWI sequence and two reduced field-of-view (rFOV) DWI sequences of breast cancer. MATERIAL AND METHODS: Twelve cases with breast cancer were scanned using SS-EPI DWI (FOV, 360 × 360 mm), rFOV DWI1 (FOV, 360 × 180 mm), and rFOV DWI2 (FOV, 280 × 140 mm), respectively. Image quality (scores 1 to 5) and ADC values of breast imaging were compared among three groups by different DWI sequences. SNR were compared between rFOV DWI1 and rFOV DWI2. RESULTS: The imaging quality score of 12 cases was 5.00 in rFOV DWI1, 3.60 in SS-EPI DWI, and 3.75 in rFOV DWI2. The mean ADC value of 12 cases was 1.211 × 10(-3 )mm(2)/s in SS-EPI DWI, 1.107 × 10(-3 )mm(2)/s in rFOV DWI1, and 1.038 × 10(-3 )mm(2)/s in rFOV DWI2. SNR of rFOV DWI1 images was much higher than that of rFOV DWI2. CONCLUSION: rFOV DWI1 is the optimal DWI sequence in our study. Comparing with SS EPI DWI, suitable rFOV DWI has an obvious advantage, which can present higher image resolution and less distortion. It may be helpful in the diagnosis of breast cancer.

To assess the association between vertebral marrow fat content and colorectal adenoma in postmenopausal women using magnetic resonance spectroscopy.

BACKGROUND: Although lower bone mineral density (BMD) is considered to have an increased risk for colorectal adenoma, no association between marrow fat content and colorectal adenoma has been elucidated yet. PURPOSE: To evaluate the relationship between marrow fat fraction (MFF) and the presence of colorectal adenoma in postmenopausal women using magnetic resonance spectroscopy (MRS). MATERIAL AND METHODS: We performed a cross-sectional observational study on 152 postmenopausal patients with colorectal adenoma and 100 matched control subjects who underwent screening colonoscopy, biochemical measurements, dual-energy X-ray absorptiometry, and MRS. Logistic regression models were performed to assess the relationships among BMD, MFF, and colorectal adenoma. RESULTS: With univariate analysis, marrow fat accumulation was higher and BMD values were lower in patients with colorectal adenoma compared with those in controls. After adjustment for potential confounders including demographics, health history, blood lipid levels, indexes of glucose metabolism, and validated measures of diet and physical activity, MFF was significantly positively associated with colorectal adenoma (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.10-2.46; P = 0.008). Vertebral BMD, but not total hip and femoral neck BMD, was inversely related with colorectal adenoma (OR, 0.62; 95% CI, 0.14-0.89; P = 0.027). Additionally, MFF was associated with adenoma number, size, and high-risk adenoma (all P < 0.01). MFF was found to be an independent risk factor of a high-risk colorectal adenoma (OR, 2.08; 95% CI, 1.24-3.60; P = 0.019). CONCLUSION: Marrow fat accumulation is highly associated with colorectal adenoma, particularly high-risk adenoma, in postmenopausal women.