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Atherosclerosis is a chronic inflammatory disease that has its origins in early life. Postnatal inflammation exacerbates atherosclerosis, but the possible effect of intrauterine inflammation is largely unexplored. Exposure to inflammation in utero is common, especially in infants born preterm, who have increased cardiovascular risk in adulthood. We hypothesised that exposure to inflammation before birth would accelerate the development of atherosclerosis, with the most severe atherosclerosis following exposure to both pre- and postnatal inflammation. Here we studied the effect of prenatal and postnatal inflammation on the development of atherosclerosis by combining established techniques for modelling histological chorioamnionitis and atherosclerosis using apolipoprotein E (ApoE) knockout mice. A single intra-amniotic (IA) injection of lipopolysaccharide (LPS) caused intrauterine inflammation, and increased atherosclerosis at 13 weeks of postnatal age. In mice exposed to postnatal LPS, chorioamnionitis modulated subsequent responses; atherosclerotic lesion size, number and severity were greatest for mice exposed to both intrauterine and postnatal inflammation, with a concomitant decrease in collagen content and increased inflammation of the atherosclerotic plaque. In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies.

Key points Experimental maternal allergic asthma in sheep provides an experimental model in which to test impacts on progeny. Fetuses from allergic asthmatic ewes had fewer surfactant‐producing cells in lungs. A greater proportion of lymphocytes from thymus were CD44 positive in fetuses from allergic asthmatic ewes than in controls. These changes to fetal development might contribute to poor neonatal lung function and increased risk of allergy seen in offspring of pregnancies complicated by asthma. Abstract Asthma is prevalent in pregnancy and increases the risk of disease in offspring, including neonatal respiratory distress and childhood asthma and allergy, but the mechanisms are not understood. We hypothesized that fetal lung structure and immune phenotype in late gestation fetal sheep would be impaired in our sheep model of maternal allergic asthma during pregnancy. Singleton‐bearing ewes were either sensitized before pregnancy to house dust mite (HDM, allergic, n = 7) or were non‐allergic (control, n = 5). The ewes were subsequently subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Tissues were collected at 140 ± 1 days gestational age (term, ∼147 days). The density of type II alveolar epithelial cells (surfactant protein C‐immunostained) in the lungs was 30% lower in fetuses from allergic ewes than in controls (P < 0.001), but tissue‐to‐air space ratio and numbers of leucocytes and macrophages were not different between groups. The proportion of CD44+ lymphocytes in the fetal thymus was 3.5‐fold higher in fetuses from allergic ewes than in control ewes (P = 0.043). Fewer surfactant‐producing type II alveolar epithelial cells may contribute to the increased risk of neonatal respiratory distress in infants of asthmatic mothers, suggesting that interventions to promote lung maturation could improve their neonatal outcomes. If the elevated lymphocyte expression of CD44 persists postnatally, this would confer greater susceptibility to allergic diseases in progeny of asthmatic mothers, consistent with observations in humans. Further experiments are needed to evaluate postnatal phenotypes of progeny and investigate potential interventions.

BackgroundAmmonia and tumor necrosis factor-alpha (TNF-α) play important roles in the mechanisms of hepatic encephalopathy (HE). Rhesus glycoprotein C (Rhcg) is important for ammonia transport especially in the kidney. The aim of the present study was to investigate the role of Rhcg in the brain in acute liver failure (ALF) and the effect of TNF-α on Rhcg expression.MethodsALF mouse models were generated by treatment with d-galactosamine (D-GalN) and lipopolysaccharide (LPS), or D-GalN and TNF-α. ALF induction was blocked by pretreatment with anti-TNF-α IgG. The levels of serum TNF-α were determined by ELISA. Blood ammonia and brain ammonia concentrations were detected using an ammonia assay kit. The expression and distribution of Rhcg in the brain tissues of ALF mice were examined by western blotting, real-time PCR, immunohistochemical, and immunofluorescence analyses.ResultsSerum TNF-α levels were increased in the LPS/D-GalN group. Blood and brain ammonia were increased in the LPS/D-GalN- and TNF-α/D-GalN-induced ALF groups. Rhcg mRNA and protein levels were elevated in both ALF groups, consistent with the increase in blood and brain ammonia. Rhcg was mainly expressed in vascular endothelial cells and astrocytes. Pretreatment with anti-TNF-α IgG antibody downregulated Rhcg in brain tissues in the LPS/D-GalN group, prevented the occurrence of ALF, and reduced blood and brain ammonia levels in the LPS/D-GalN group.ConclusionTNF-α promoted the transport of ammonia from the blood to brain tissues and exacerbated the toxic effects of ammonia by upregulating Rhcg.

Previous studies on reducing employees’ cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one’s current behavior. To explore further whether and how employees’ future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees’ future orientation and cyberloafing behaviors. The mediation effect of employees’ objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees’ future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2) to examine the causal relationship and psychological mechanism between employees’ future orientation and cyberloafing behaviors. The results demonstrated that employees’ future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed.

Apolipoprotein A-I (apoA-I) is the major functional protein fraction of high-density lipoprotein. The prophylactic effect and mechanism of human apoA-I on atherosclerosis (AS) were investigated in a high-fat diet-induced AS rabbit model. The rabbits were injected with apoA-I once a week while fed high-fat diet for 20 weeks. Our results showed that apoA-I could raise the serum level of high-density lipoprotein-cholesterol and reduce those of lipid total cholesterol, triglyceride, and low-density lipoprotein-cholesterol in AS rabbits. Decreased aortic plaque area and aortic injury degree were also observed by Oil Red O staining and HE staining in apoA-I-treated high-fat diet-induced AS rabbits. Further study elucidated that apoA-I could down-regulate the expression of some inflammatory mediators including intercellular adhesion molecule type 1, vascular adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-6 (IL-6), and C-reactive protein in serum and aorta of AS rabbits. In addition, real-time quantitative RT-PCR analyses showed that the apoA-I infusions decreased the mRNA levels of two pro-inflammatory molecules, i.e. nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), in aorta of AS rabbits, which was associated with a concomitant reduction in endothelial VCAM-1 and IL-6 mRNA transcription. Together, our results support the atheroprotective and prophylactic role of apoA-I in vivo, and this activity may be correlated with its anti-inflammatory effect.

Otitis media (OM) is a common inflammatory disease of the middle ear cavity and mainly occurs in children. As a critical regulator of inflammation response, the nuclear factor kappa B (NF-κB) pathway has been found to play an essential role in the pathogenesis of various human diseases. The aim of this study was to explore the potential mechanism under the inflammatory response of human middle ear epithelial cells (HMEECs). We established in vitro models of OM by treating HMEECs with lipopolysaccharide (LPS) or interleukin 17A (IL-17A). Enzyme-linked immunosorbent assay and western blot analysis were used to measure the inflammatory response of HMEECs under LPS or IL-17A stimulation. The results revealed that the concentrations of proinflammatory cytokines ( p < 0.001 ) and protein levels of mucin (MUC) (for MUC5AC, p = 0.002 , p = 0.004 ; for MUC8, p = 0.004 , p < 0.001 ) were significantly elevated by LPS or IL-17A stimulation in HMEECs. Moreover, we found that LPS or IL-17A treatment promoted the phosphorylation of IκBα (for p-IκBα, p = 0.018 , p = 0.002 ; for IκBα, p = 0.238 , p = 0.057 ) and the translocation of p65 from cytoplasm to nucleus in HMEECs (for nucleus p65, p = 0.01 ; for cytoplasm p65, p < 0.001 ). In addition, RT-qPCR analysis revealed that long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was verified to be upregulated in LPS- or IL-17A-stimulated HMEECs ( p < 0.001 ). Western blot analysis and immunofluorescence staining assay revealed that that MALAT1 knockdown significantly suppressed the activation of the NF-κB pathway by reducing phosphorylated IκBα levels and inhibiting the nuclear translocation of p65 ( p < 0.001 ) in LPS- or IL-17A-stimulated HMEECs (for p-IκBα, p < 0.001 ; for IκBα, p = 0.242 , p = 0.647 ). Silence of MALAT1 decreased the proinflammatory cytokine production and MUC protein levels ( p < 0.001 ). Furthermore, rescue assays revealed that the increase of proinflammatory cytokine production (for TNF-α, p = 0.002 , p = 0.015 ; for IL-1β, p < 0.001 , p = 0.006 ; for IL-6, p = 0.002 , p < 0.001 ) and MUC protein levels (for MUC5AC, p = 0.001 , p < 0.001 ; for MUC8, p < 0.001 , p = 0.001 ) induced by MALAT1 overexpression was neutralized by 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4, 6-diamine (QNZ) treatment in LPS- or IL-17A-stimulated HMEECs. In conclusion, MALAT1 promotes inflammatory response in LPS- or IL-17A- stimulated HMEECs via the NF-κB signaling pathway, which may provide a potential novel insight for the treatment of OM.

Based on the fluctuations ensembled over neighbouring neurons, blood oxygen level‐dependent (BOLD) signal is a mesoscale measurement of brain signals. Intraregional temporal features (IRTFs) of BOLD signal, extracted from regional neural activities, are utilized to investigate how the brain functions in local brain areas. This literature highlights four types of IRTFs and their representative calculations including variability in the temporal domain, variability in the frequency domain, entropy, and intrinsic neural timescales, which are tightly related to cognitions. In the brain‐wide spatial organization, these brain features generally organized into two spatial hierarchies, reflecting structural constraints of regional dynamics and hierarchical functional processing workflow in brain. Meanwhile, the spatial organization gives rise to the link between neuronal properties and cognitive performance. Disrupted or unbalanced spatial conditions of IRTFs emerge with suboptimal cognitive states, which improved our understanding of the aging process and/or neuropathology of brain disease. This review concludes that IRTFs are important properties of the brain functional system and IRTFs should be considered in a brain‐wide manner.