Can gaze-cueing be helpful for detecting sound in autism spectrum disorder?

Autism spectrum disorder (ASD) is a developmental disorder characterized by impaired social interaction, including joint attention, but psychological studies generally have reported intact gaze-triggered joint attention in ASD. These studies used a uni-modal paradigm (i.e. visual cue–target pairs) with eyes or faces as cues and letters or dots as targets. However, it has not been determined whether joint attention is impaired under cross-modal conditions in ASD, although cross-modal impairment has been reported. This study investigated joint attention in ASD under cross-modal conditions with gaze stimuli as visual cues and two kinds of sound (social voice or non-social tone) stimuli as targets. The task for the subject was to locate the target sound and click as soon and as accurately as possible. The ASD group was impaired in joint attention when a tone was used as the target, while both groups showed joint attention to a voice. The results suggest that cross-modal joint attention is impaired in the ASD group when the cue–target relationship is weak (i.e. social cue and non-social target) while it is unimpaired when there is a strong cue–target relationship (i.e. social cue and social target).     

Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization

The mucosal immune system produces secretory IgA (sIgA) as the first line of defense against invasion by foreign pathogens. Our aim was to develop a galactose-modified liposome as a targeted carrier which can be specifically recognized by macrophage, one of the most important antigen presenting cells. First, galactose was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was then incorporated into a liposomal bilayer to form a galactosylated liposome carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated liposome carriers and mice were intranasally immunized. Confocal laser scanning microscopy and flow cytometry analysis showed that the targeted galactosylated liposome carrier had a higher uptake rate than unmodified liposomes. The targeted galactosylated liposome induced higher levels of tumor necrosis factor-α and interleukin-6 production than unmodified liposomes (P < 0.05). Furthermore, 6-week-old BALB/c female mice immunized with the OVA-encapsulated targeted galactosylated liposome had significantly higher OVA-specific s-IgA levels in the nasal and lung wash fluid (P < 0.05). In addition, the targeted galactosylated liposome simultaneously augmented the serum IgG antibody response. In summary, the OVA-encapsulated targeted galactosylated liposome induced significantly higher mucosal IgA and systemic IgG antibody titers and is a potential antigen delivery carrier for further clinical applications.     

Mycoplasma fermentans MALP-2 Induces Heme Oxygenase-1 Expression via Mitogen-Activated Protein Kinases and Nrf2 Pathways To Modulate Cyclooxygenase 2 Expression in Human Monocytes

Heme oxygenase-1 (HO-1) is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury and performs a vital function in the maintenance of cell hemostasis. Increasing numbers of reports have indicated that mycoplasma-derived membrane lipoproteins/lipopeptides, such as macrophage-activating lipopeptide-2 (MALP-2), function as agents that stimulate the immune system by producing various inflammatory mediators, such as cytokines and cyclooxygenase 2 (COX-2), which play roles in the pathogenesis of inflammatory responses during mycoplasma infection. Here, we report that MALP-2 induced HO-1 mRNA and protein expression and upregulated HO-1 enzyme activity in THP-1 cells. Specific inhibitors of mitogen-activated protein kinases (MAPKs), SB203580, PD98059, and SP600125, significantly abolished HO-1 expression. In addition, MALP-2 also induced NF-E2-related factor 2 (Nrf2) translocation, and the silencing of Nrf2 expression in THP-1 cells decreased the levels of MALP-2-mediated HO-1 expression. Furthermore, COX-2 protein expression levels were upregulated in THP-1 cells in response to MALP-2, and transfection with small interfering RNAs of HO-1 significantly increased COX-2 accumulation. These results demonstrate that MALP-2 induces HO-1 expression via MAPKs and Nrf2 pathways and, furthermore, that MALP-2-induced COX-2 expression was modulated by HO-1 in THP-1 cells.     

Serologic Evidence of Pandemic Influenza Virus H1N1 2009 Infection in Cats in China

Infection of domestic cats with (H1N1) pandemic 2009 (pdm09) influenza A virus has recently been documented. In this paper, we report for the first time the sporadically current seroprevalence of (H1N1) pdm09 influenza A virus infection in cats in China. Thirteen of 1,080 sera were found positive by nucleoprotein (NP)-specific enzyme-linked immunosorbent assays (ELISAs) in different cat populations in southern China. It is very important to stress further surveillance of pandemic (H1N1) 2009 influenza A virus in cats in southern China.     

Clinical significance and prevalence of anti-Saccharomyces cerevisiae antibody in Chinese patients with primary biliary cirrhosis

Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) and its prevalence in Chinese primary biliary cirrhosis (PBC) patients have not been characterized and therefore needs to be defined. Enzyme-linked immunosorbent assay was used to test ASCA in sera from 198 PBC patients, 85 patients with other liver diseases (OLD) and 35 health controls (HC). Indirect immunofluorescence was used to detect anti-mitochondrial antibodies (AMA) in PBC. Results showed that the frequency of ASCA in PBC, 29.8 %, was higher than other disease groups. And ASCA occurred more frequently in PBC patients with positive anti-gp210 than the negative ones. Also, ASCA was detected in 7 out of 15 PBC negative for AMA. Some liver-related biochemical indices and inflammatory indices were significantly higher in PBC patients with positive ASCA (p < 0.05). In conclusion, the prevalence of ASCA in Chinese PBC patients is 29.8 %. PBC patients with positive ASCA are associated with more severe liver injury, and ASCA-IgA might be related to disease activity of PBC.     

人皮肤成纤维细胞的分离培养及鉴定

目的：建立人皮肤成纤维细胞的体外原代及传代培养并鉴定的技术方法.方法：取临床无菌切除的幼儿包皮,利用胶原酶分离表皮和真皮,将真皮剪成肉糜状,再用胰蛋白酶消化,接种于培养皿,加少许含10％小牛血清的DMEM-高糖培养液进行培养,次日补加培养液.原代长满后,进行传代,并对所培养的细胞进行形态学观察及组化鉴定.结果：接种次日倒置镜下可见有长梭形细胞迁出、生长,5-6d进行传代,传代后约5d长满,可长期传代.免疫组化Vimentin表达阳性.结论：该方法可快速高效获得构建组织皮肤真皮所需的成纤维细胞.     

A micro-computed tomography study of the root canal morphology of the mandibular first premolar in a population from southwestern China

Objectives

This study aimed to investigate the root canal morphology of mandibular first premolar teeth in a population from southwestern China by micro-computed tomography (micro-CT).

Materials and methods

Human mandibular first premolars (115) were selected and prepared for micro-CT analysis with a slice thickness of 30 μm. Details of root canal orifices, canals, accessory canals, apical foramina–apical delta intercanal communication, loops and isthmuses, and mesial invagination were analyzed from reconstructed three-dimensional (3D) images.

Results

Canal patterns categorized according to the classification defined by Vertucci (Endod Top 10:3–29, 2005) as types I (65.2 %), III (2.6 %), V (22.6 %), and VII were identified (0.9 %). Accessory canals were present in 35.7 % of the samples and were predominantly located in the apical third of the root. A single apical foramen was observed in 50.4 % of the samples and two or three foramina in 28.7 % and 14.8 %, respectively. Apical delta was identified in 6.1 % of the samples and the prevalence of intercanal communication and loops was 3.5 % and 7 %, respectively. Mesial invagination of the root was identified in 27.8 % of the samples, the majority of which contained multiple canals.

Conclusions

The data obtained in this study revealed complex root morphology with high prevalence of multiple canals, more than half of which exhibited type I canal patterns.

Clinical relevance

Micro-CT was used as a noninvasive technique for 3D investigation of root canal morphology in the mandibular first premolars of a population from southwestern China. Furthermore, data obtained revealed complex anatomy of various types.     

不同类型附着体种植覆盖义齿的临床疗效评价

目的总结与评价应用不同类型附着体的种植覆盖义齿的临床效果。方法对28例无牙颌患者分别采用种植体支持的磁附着体、杆卡式、套筒冠、球帽式覆盖义齿随访及效果进行对比评价。观察随访,定期拍摄X线片及口腔检查,观察种植体骨吸收和软组织状况,并对使用4种类型覆盖义齿的患者进行满意度调查和并发症分析。结果除1例磁附着体覆盖义齿患者发生3枚种植体脱落现象外,其余种植体均稳定。不同类型附着体种植覆盖义齿的骨吸收量、牙龈指数和满意度评价的差异均无统计学意义﹙P>0.05﹚;患者戴牙前后的义齿总体满意度、义齿固位及稳定情况、咀嚼效率、舒适度方面有明显的改善(P<0.05﹚。结论各类种植体支持的覆盖义齿稳定舒适,咀嚼功能增强,患者对满意度有较高的评价,提高了无牙颌患者的生存质量。     

Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2

Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. However, whether Aβ induces hepatic insulin resistance in vivo is still unclear. Here we show C57BL/6J mice intraperitoneally injected with Aβ42 exhibit increased fasting blood glucose level, impaired insulin tolerance, and hepatic insulin signaling. Moreover, the APPswe/PSEN1dE9 AD model mice intraperitoneally injected with anti-Aβ neutralizing antibodies show decreased fasting blood glucose level and improved insulin sensitivity. Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM.More than 250 million people worldwide were diagnosed with type 2 diabetes mellitus (T2DM) in 2011, and this number is expected to double within the next 20 years (1). Insulin resistance is a key element in the pathogenesis of T2DM, defined as a state of reduced responsiveness to normal circulating levels of insulin in insulin-target liver, skeletal muscle, and adipose tissues (2). Many states give rise to insulin resistance, and all are explained by numerous mechanisms in which insulin signaling is decreased (3). Interestingly, it has been reported that brains from Alzheimer’s disease (AD) patients display impaired insulin signaling (4,5), and some AD patients exhibit impaired glucose metabolism and hyperinsulinemia (6,7). Furthermore, an epidemiological study indicates patients with AD have an increased risk of developing T2DM (8), and experimental studies demonstrate AD model mice also exhibit diabetic phenotype (9,10). These studies together reveal a strong correlation between AD and insulin resistance/T2DM.Amyloid-β (Aβ) is a natural product during cell metabolism and originates from proteolysis of the amyloid precursor protein (APP) by the sequential enzymatic actions of β-site amyloid precursor protein–cleaving enzyme 1 (BACE-1) and γ-secretase (11). According to the amyloid cascade hypothesis, Aβ has an early and vital role in the pathogenesis of AD (11,12). In the central nervous system, Aβ has been reported to impair neuronal synaptic function in early AD by compromising insulin signaling (13–16). Interestingly, Aβ can be detected in the peripheral circulation and tissues (17–19).We have previously reported that Aβ induces insulin resistance in cultured hepatocytes mainly through the JAK2/STAT3/SOCS-1 signaling pathway (10), indicating that Aβ is an inducer of insulin resistance in vitro. On the other hand, animal studies demonstrate that the crossbred mice of APP23 transgenic AD model mice and ob/ob mice showed an accelerated diabetic phenotype (20). Moreover, APPswe/PS1^(A246E) transgenic AD model mice with increased plasma Aβ42 level exhibit impaired glucose tolerance when fed a chow diet (9,21). Consistently, we have recently reported that APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice with increased plasma Aβ40/42 levels show impaired glucose/insulin tolerance and hepatic insulin signaling, hyperinsulinemia, and upregulation of SOCS-1 and phosphorylated JAK2 and STAT3 in the liver (10). However, it is still possible that the insulin resistance in AD model mice might be due to the overexpression of presenilin 1, APP, and/or APP cleavage products except Aβ. Thus, whether Aβ itself can induce insulin resistance in vivo is yet to be elucidated. In addition, we previously showed that Aβ induces insulin resistance by activating the JAK2/STAT3/SOCS-1 signaling pathway in cultured hepatocytes (10). Whether Aβ also induces hepatic insulin resistance in vivo by activating the JAK2/STAT3/SOCS-1 signaling pathway is still unclear.In this study, we investigated the effect of Aβ on insulin sensitivity in vivo by injection of Aβ42 into wild-type mice and injection of Aβ-neutralizing antibodies or adenovirus expressing JAK2 small interfering (si)RNA into APP/PS1 AD model mice. We found that injection of Aβ42 into C57BL/6J mice induces insulin resistance and activates hepatic JAK2/STAT3/SOCS-1 signaling. Moreover, APP/PS1 mice treated with anti–Aβ-neutralizing antibodies show improved insulin sensitivity and attenuated hepatic JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by adenovirus inhibited JAK2/STAT3/SOCS-1 signaling and improved insulin sensitivity in APP/PS1 mice.