The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Neural network of metaphor comprehension: an ALE meta-analysis and MACM analysis.

The comprehension of metaphor, a vivid and figurative language, is a complex endeavor requiring cooperation among multiple cognitive systems. There are still many important questions regarding neural mechanisms implicated in specific types of metaphor. To address these questions, we conducted activation likelihood estimation meta-analyses on 30 studies (containing data of 480 participants) and meta-analytic connectivity modeling analyses. First, the results showed that metaphor comprehension engaged the inferior frontal gyrus, middle temporal gyrus, fusiform gyrus, lingual gyrus, and middle occipital gyrus-all in the left hemisphere. In addition to the commonly reported networks of language and attention, metaphor comprehension engaged networks of visual. Second, sub-analysis showed that the contextual complexity can modulate figurativeness, with the convergence on the left fusiform gyrus during metaphor comprehension at discourse-level. Especially, right hemisphere only showed convergence in studies of novel metaphors, suggesting that the right hemisphere is more associated with difficulty than metaphorical. The work here extends knowledge of the neural mechanisms underlying metaphor comprehension in individual brain regions and neural networks.

Polymorphisms of the Matrix Metalloproteinase Genes are Associated with Acute Ischemic Stroke in Chinese Han Population.

Background and Purpose: Studies have shown that matrix metalloproteinase (MMP-2,3,9) plays an important role in the pathologic process of ischemic stroke (IS). The aim of this study was to investigate the relationship between C1306T, 1612-5A/6A, C-1562T polymorphisms of MMP-2,3,9 genes and IS in Chinese Han population. Methods: The polymorphisms of MMP-2(C1306T), -3(1612-5A/6A), -9(C-1562T) gene were detected by PCR-RFLP and SNaPshot sequencing. Then, stratified analysis was used to study the relationship between IS subtypes and MMP-2,3,9 polymorphisms. Results: For the MMP-2 gene C1306T polymorphism, TT genotype and T allele were significantly associated with a reduced risk of IS (P = 0.015, P = 0.003, respectively). T allele was significantly associated with a reduced risk of small artery occlusion (SAO) subtype compared with the control group (P = 0.012, OR = 0.550, 95% CI = 0.065-1.291). For the MMP-3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the IS group (P = 0.011, OR = 0.370, 95% CI = 0.168-0.814), especially in the large-artery atherosclerosis (LAA) subtype (P = 0.001, OR = 2.345) as compared to the control group. Conclusion: Our study suggested that the T allele of MMP-2 may be a protective factor of IS, especially in SAO subtype, while the 5A/5A gene of MMP-3 may increase the risk of IS, especially in LAA subtype in Chinese Han population.

CAMTA1 gene affects the ischemia-reperfusion injury by regulating CCND1.

Epigenetic modulations lead to changes in gene expression, including DNA methylation, histone modifications, and noncoding RNAs. In recent years, epigenetic modifications have been related to the pathogenesis of different types of cancer, cardiovascular disease, and other diseases. Emerging evidence indicates that DNA methylation could be associated with ischemic stroke (IS) and plays a role in pathological progression, but the underlying mechanism has not yet been fully understood. In this study, we used human methylation 850K BeadChip to analyze the differences in gene methylation status in the peripheral blood samples from two groups (3 IS patients vs. 3 healthy controls). According to their bioinformatics profiling, we found 278 genes with significantly different methylation levels. Seven genes with the most significant methylation modifications were validated in two expanded groups (100 IS patients vs. 100 healthy controls). The CAMTA1 gene had significantly different methylation changes in patients compared to the controls. To understand the CAMTA1 function in stroke, we generated CAMTA1 knockout in SH-SY5Y cells. RNA seq results in CAMTA1 knockout cells revealed the pathways and gene set enrichments involved in cellular proliferation and cell cycle. Furthermore, a series of experiments demonstrated that in the oxygen-glucose deprivation/re-oxygenation (OGD/R) model system, the expression of cyclin D1, an essential regulator of cell cycle progression, was increased in SH-SY5Y CAMTA1 KO cells. Increasing evidence demonstrated that ischemic stress could inappropriately raise cyclin D1 levels in mature neurons. However, the molecular signals leading to an increased cyclin D1 level are unclear. Our findings demonstrate for the first time that the CAMTA1 gene could regulate cyclin D1 expression and implicate their role in strokes.

Genetic variations in ABCA1/G1 associated with plasma lipid levels and risk of ischemic stroke.

BACKGROUND: ATP binding cassette transporters ABCA1 and ABCG1 play a crucial role in cholesterol efflux and reverse cholesterol transport (RCT), thereby rendering ischemic stroke (IS) susceptibility. Variants of ABCA1/G1 have been implicated in etiology of IS. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of ABCA1/G1 with plasma lipid variability and the risk of IS in Chinese Han Population. METHODS: Totally 249 IS patients and 226 healthy controls were enrolled and 10 SNPs of ABCA1/G1 were screened for genotyping by kompetitive allele-specific polymerase chain reaction (KASP) and validated by sanger sequencing. The logistic regression analysis was performed to identify risk alleles of IS and appropriate genetic model. The genetic risk scores (GRS) and predicted risks for all individuals was computed. Based on different plasma lipid levels, we applied stratified analyses for subgroups. Linkage disequilibrium (LD) test was used to explore different functional haplotype combinations. Association between specific allele or genotype of the SNPs of ABCA1/G1 and plasma lipid or lipoproteins levels were also investigated. RESULTS: Besides total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), significant differences of clinical data were observed between IS and control group. The rare GG genotype frequencies of rs4149338 on ABCA1 was higher in IS patients than those in controls (11.4%, 4.6%, respectively, P = 0.037). Frequencies of rs57137919 on ABCG1 for rare AA genotype was lower in IS group than those in control group (4.6%, 13.3%, respectively, P = 0.030). GRS showed ability to discriminate IS patients and controls (AUC = 0.633, P < 0.001). Haplotype A-A (rs4149339-rs4149338) was correlated with reduced risk of IS (P = 0.023). Association analysis showed that subjects with rare AA genotype of rs57137919 had the lowest LDL-C levels while rare GG genotype of rs4149338 had lower TC level than those with AA genotype. The mRNA expression of ABCG1 was higher in IS patients, especially in the patients with frequent GG genotype of rs57137919, and was positively correlated with higher ABCG1 expression level and plasma LDL-C level. CONCLUSIONS: Polymorphisms of ABCA1/G1 associated with varieties of plasma lipid levels and risk of IS.

Influence of oral administration of Akkermansia muciniphila on the tissue distribution and gut microbiota composition of acute and chronic cadmium exposure mice.

Cadmium (Cd) contamination is a serious food safety problem. Acute and chronic Cd exposure changes the gut microbiota composition and damages the gut barrier function. Akkermansia muciniphila (AKK), a promising candidate for the next-generation probiotics, has been reported to protect the mucus layer in the colon and significantly decrease the effects of Cd exposure in mice. Thus, the mice model was adopted to investigate the influence of oral administration of AKK on the toxic distribution and changes of gut microbiota composition caused by acute and chronic Cd exposure. In both acute and chronic Cd exposure experiments, 40 mice were divided into four groups (normal group, AKK group, Cd group and Cd plus AKK group). The Cd contents in feces and tissues were measured by a flame or graphite furnace atomic absorption spectrophotometer and gut microbiota composition was determined through 16S rRNA gene sequencing. The results showed that the gavage of AKK could not reduce the accumulation of Cd in the liver and kidney. The oral administration of AKK showed a certain influence on the gut microbiota composition of acute Cd exposure mice and limited influence on that of chronic Cd exposure mice. These results indicate the failure of AKK, as a potential protective probiotic, to reduce Cd toxicity. However, the gavage of AKK did have an influence on the gut microbiota composition of normal mice, especially on some genera in the Clostridiales order. Besides, when considering AKK's probiotic potential and its effects on host health and disease, we should take into consideration its influence on the gut microbiota composition and micro-environment.

[Mucoepidermoid Carcinoma of the Lung: Report of 29 Cases].

BACKGROUND: Pulmonary mucoepidermoid carcinoma (MEC) is an extremely rare pulmonary malignant tumor, its clinical features and conditions of prognosis is not entirely clear. The aim of this study is to discuss clinical features, diagnostic and therapeutic methods, and prognosis of pulmonary MEC. METHODS: We retrospectively studied 29 pulmonary MEC patients who diagnosed from January 2006 to December 2015 in Affiliated Hospital of Zhengzhou University. The clinical features, prognosis, diagnostic and therapeutic methods were analyzed. RESULTS: There were 20 patients identified as pulmonary MEC, which constitutes 0.18% of all the lung tumor patients. There were 18 males and 11 females, the median age of the patients was 45 years (range 10-79). There were 17 patients identified as high-grade pulmonary MEC and 12 low-grade. Epidermal growth factor receptor (EGFR) mutation detection was performed in six patients, none was positive. 17 cases was underwent surgery based comprehensive treatment, 12 cases non-operatived treatment. The median follow-up time was 35 (5-114) months in this cohort of 29 patients. During the follow up, incidence of death was found in 17 cases. The overall 1-, 3-, 5-year survival rates were 65.5%, 51.2%, 39.4%, respectively. The median survival time was 37 months. CONCLUSIONS: The incidence of pulmonary MEC is low, lacking specific clinical characterization. The diagnosis mainly depends on postoperative pathology, aided by immunohistochemical. Surgery is the main treatment method. The majority of pathology was high-grade type. The prognosis of pulmonary MEC closely relates to the pathological types and clinical stage. EGFR-tyrosine kinase inhibitor (EGFR-TKI) is expected to improve the prognosis of pulmonary MEC.