There is heterogeneity in metabolic topography of AIE which is characterized by hypometabolism most commonly involving the parietal and occipital cortices and hypermetabolism most commonly involving the basal ganglia. Scenium analysis using regional Z-scores can complement visual evaluation for demonstration of these metabolic patterns on FDG PET.

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has received increasing attention for its involvement in severe human infections worldwide as well as in multidrug resistance. Two-component signaling systems (TCSSs) play important roles in bacterial adaptation to various environmental stimuli. In this study, we identified a novel TCSS located in serotype 2 (SS2), designated VraSR, which is involved in bacterial pathogenicity and susceptibility to antimicrobials. Our data demonstrated that the gene, located upstream of , shared the same promoter with the TCSS genes, which was directly regulated by VraSR, as shown in electrophoretic mobility shift assays. Notably, YvqF and VraSR constitute a novel multidrug resistance module of SS2 that participates in resistance to certain groups of antimicrobials. Further analyses showed that VraSR inactivation significantly attenuated bacterial virulence in animal models, which, coupled with the significant activation of VraSR expression observed in host blood, strongly suggested that VraSR is an important regulator of SS2 pathogenicity. Indeed, RNA-sequencing analyses identified 106 genes that were differentially expressed between the wild-type and Δ strains, including genes involved in capsular polysaccharide (CPS) biosynthesis. Subsequent studies confirmed that VraSR indirectly regulated the transcription of CPS gene clusters and, thus, controlled the CPS thickness shown by transmission electron microscopy. Decreased CPS biosynthesis caused by deletion subsequently increased bacterial adhesion to epithelial cells and attenuated antiphagocytosis against macrophages, which partially clarified the pathogenic mechanism mediated by VraSR Taken together, our data suggest that the novel TCSS, VraSR, plays critical roles for multidrug resistance and full virulence in SS2.

The aim of this study is to explore the impact of sodium butyrate on d-glutamyl- meso-diaminopimelic acid (iE-DAP)-induced liver inflammation in dairy goats during subacute ruminal acidosis (SARA) caused by high-concentrate feed. To achieve this aim, 12 lactating dairy goats were randomly divided into two groups: a high-concentrate feed group ( n = 6, concentrate/forage = 6:4) as the control group and a sodium butyrate (SB) with high-concentrate feed group ( n = 6, concentrate/forage = 6:4, with 1% SB by wt.) as the treatment group. A rumen pH below 5.6 lasted for at least 4 h/d due to long-term HC feeding. The concentration of iE-DAP was significantly lower (11.67 ± 3.85 μg/mL, and 7.74 ± 1.46 μg/mL, at the fourth h and sixth h of feeding, respectively) in the SB-treated group than that in the HC group (51.45 ± 5.71 μg/mL, and 18.31 ± 3.83 μg/mL, at the fourth h and sixth h of feeding, respectively). Meanwhile, SB significantly suppressed the mRNA expression of inflammatory genes (NOD1, RIPK2, TAK1, NF-κB/p65, ERK, JNK2, p38, IL-1β, TNF-α, CCL5, CCL20, CXCL12, FOS, β-defensin/LAP). Moreover, the protein expression of NOD1, p-IκBα, p-NF-κB/p-p65, p-ERK1/2, p-JNK, p-p38, and HDAC3 was significantly downregulated in the HC+SB group. In conclusion, iE-DAP-induced inflammation and liver disruption generated by the HC diet was mitigated by SB treatment.

Nucleotide oligomerization domain protein-1 (NOD1), a cytosolic pattern recognition receptor for the γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) is associated with the inflammatory diseases. Very little is known how bovine hepatocytes respond to specific ligands of NOD1 and sodium butyrate (SB). Therefore, the aim of our study was to investigate the role of bovine hepatocytes in NOD1-mediated inflammation during iE-DAP or LPS treatment or SB pretreatment. To achieve this aim, hepatocytes separated from cows at ∼160 days in milk (DIM) were divided into six groups: The nontreated control group (CON), the iE-DAP-treated group (DAP), the lipopolysaccharide-treated group (LPS), iE-DAP with SB group (DSB), LPS with SB group (LSB), and the SB group. Both iE-DAP and LPS highly increased the expression of both NOD1 and RIPK2, the two key factors for the immune response in hepatocytes. IκBα, NF-κB/p65, and MAP kinases (ERK, JNK, and p38) were activated through phosphorylation. The activation of NF-κB and MAPK pathway consequently increased the proinflammatory cytokines, IL-6, TNF-α, IL-8, and IFN-γ and the chemokines CCL5, CCL20, and CXCL-10.Both treatments improved iNOS/NOS2 expression. However, iE-DAP was failed to express acute phase protein SAA3, but HP and LPS HP but SAA3. These ligands also increased LRRK2, TAK1, TAB1, and β-defensins expression. The SB pretreatment at lower dose restored the function of hepatocytes by suppressing these increased molecules, as HDAC3 was inhibited. The activated NOD1 negatively regulated the expression of FOXA2. Altogether these data suggest an important role of bovine hepatocytes to promote immune responses via NOD1 expression during infection in the liver and a key role of SB to attenuate inflammation.