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MiRNAs are small, non-coding RNAs that can silence the expression of various target genes by binding their mRNAs and thus regulate a wide range of crucial bodily functions. However, the miRNA expression profile of schizophrenia after antipsychotic mediation is largely unknown. Non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonists such as MK-801 have provided useful animal models to investigate the effects of schizophrenia-like symptoms in rodent animals. Herein, the hippocampal miRNA expression profiles of Sprague-Dawley rats pretreated with MK-801 were examined after antipsychotic clozapine (CLO) treatment. Total hippocampal RNAs from three groups were subjected to next-generation sequencing (NGS), and bioinformatics analyses, including differential expression and enrichment analyses, were performed. Eight miRNAs were differentially expressed between the MK-801 and vehicle (VEH) control groups. Interestingly, 14 miRNAs were significantly differentially expressed between the CLO + MK-801 and MK-801 groups, among which rno-miR-184 was the most upregulated. Further analyses suggested that these miRNAs modulate target genes that are involved in endocytosis regulation, ubiquitin-mediated proteolysis, and actin cytoskeleton regulation and thus might play important roles in the pathogenesis of schizophrenia. Our results suggest that differentially expressed miRNAs play important roles in the complex pathophysiology of schizophrenia and subsequently impact brain functions.

The integrin α4β7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissue (GALT). Here, we describe unexpected involvement of the tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec-2) in the regulation of α4β7 surface expression and gut immunity. Shp1 selectively inhibited β7 endocytosis, enhancing surface α4β7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β7 on the cell surface to target intracellular Shp1 to β7. Shp1 restrained plasma membrane β7 phosphorylation and inhibited β7 endocytosis without affecting β1 integrin. B cells with reduced Shp1 activity, lacking CD22 or expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α4β7 and in homing to GALT. Consistent with the specialized role of α4β7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses.

SUMMARYImmunoglobulin family and carbohydrate vascular addressins encoded byMadcam1andSt6gal1control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules, providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions ofMadcam1andSt6gal1that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. TheMadcam1element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define a genomic address code for targeted expression of mucosal vascular addressins and implicate NCCE in fundamental processes in cell specification and development.

The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4α) plays a critical role in the regulation of metabolic homeostasis, including glucose homeostasis. Sulfotransferases (SULTs) catalyze the transfer of a sulfate group from 3-phosphoadenosine 5-phosphosulfate (PAPS) to an acceptor molecule. Sulfonation plays an essential role in regulating the chemical and functional homeostasis of endogenous and exogenous molecules. Among SULTs, the cholesterol sulfotransferase 2B1b (SULT2B1b) preferentially catalyzes the sulfoconjugation of cholesterol and oxysterols to form cholesterol sulfate and oxysterol sulfates. Hepatic gluconeogenesis represents a critical component of energy metabolism. Although there have been reviews on the regulation of glucose homeostasis by HNF4α, the interplay between HNF4α and SULT2B1b in hepatic glucose homeostasis remains scattered. In this review, we intend to provide an overview on how HNF4α functionally cross-talks with SULT2B1b to regulate hepatic glucose homeostasis and whether the HNF4α-SULT2B1b axis represents a novel therapeutic target for the management of metabolic liver disease and metabolic syndrome. Keywords: Nuclear receptor, Hepatocyte nuclear factor 4alpha (HNF4α), Sulfotransferase (SULT), Cholesterol sulfotransferase 2B1b (SULT2B1b), Energy homeostasis

The integrin α4β7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissue (GALT). Here, we describe unexpected involvement of the tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec-2) in the regulation of α4β7 surface expression and gut immunity. Shp1 selectively inhibited β7 endocytosis, enhancing surface α4β7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β7 on the cell surface to target intracellular Shp1 to β7. Shp1 restrained plasma membrane β7 phosphorylation and inhibited β7 endocytosis without affecting β1 integrin. B cells with reduced Shp1 activity, lacking CD22 or expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α4β7 and in homing to GALT. Consistent with the specialized role of α4β7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses.

Steroid sulfatase (STS), a desulfating enzyme that converts steroid sulfates to hormonally active steroids, plays an important role in the homeostasis of sex hormones. STS is expressed in the adipose tissue of both male and female mice, but the role of STS in the development and function of adipose tissue remains largely unknown. In this report, we show that the adipose expression of Sts was induced in the high-fat diet (HFD) and ob/ob models of obesity and type 2 diabetes. Transgenic overexpression of the human STS in the adipose tissue of male mice exacerbated the HFD-induced metabolic phenotypes, including increased body weight gain and fat mass, and worsened insulin sensitivity, glucose tolerance, and energy expenditure, which were accounted for by adipocyte hypertrophy, increased adipose inflammation, and dysregulation of adipogenesis. The metabolic harm of the STS transgene appeared to have resulted from increased androgen activity in the adipose tissue, and castration abolished most of the phenotypes. Interestingly, the transgenic effects were sex specific, because the HFD-fed female STS transgenic mice exhibited improved metabolic functions, which were associated with attenuated adipose inflammation. The metabolic benefit of the STS transgene in female mice was accounted for by increased estrogenic activity in the adipose tissue, whereas such benefit was abolished upon ovariectomy. Our results revealed an essential role of the adipose STS in energy homeostasis in sex- and sex hormone-dependent manner. The adipose STS may represent a therapeutic target for the management of obesity and type 2 diabetes.

The integrin α4β7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissues (GALT). Here we describe unexpected involvement of tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec 2) in regulation of α4β7 surface expression and gut immunity. Shp1 selectively inhibited β7 endocytosis, enhancing surface α4β7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β7 on the cell surface to target intracellular Shp1 to β7. Shp1 restrained plasma membrane β7 phosphorylation and inhibited β7 endocytosis without affecting β1 integrin. B cells with reduced Shp1 activity, B cells lacking CD22, or B cells expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α4β7 and in homing to GALT. Consistent with the specialized role of α4β7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses.

Background & Aims The role of aryl hydrocarbon receptor (AhR) in liver fibrosis is controversial because loss and gain of AhR activity both lead to liver fibrosis. The goal of this study was to investigate how the expression of AhR by different liver cell types, hepatic stellate cells (HSCs) in particular, affects liver fibrosis in mice. Methods We studied the effects of AhR on primary mouse and human HSCs, measuring their activation and stimulation of fibrogenesis using RNA-sequencing analysis. C57BL/6J mice were given the AhR agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE); were given carbon tetrachloride (CCl4); or underwent bile duct ligation. We also performed studies in mice with disruption of Ahr specifically in HSCs, hepatocytes, or Kupffer cells. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, and immunoblotting. Results AhR was expressed at high levels in quiescent HSCs, but the expression decreased with HSC activation. Activation of HSCs from AhR-knockout mice was accelerated compared with HSCs from wild-type mice. In contrast, TCDD or ITE inhibited spontaneous and transforming growth factor β–induced activation of HSCs. Mice with disruption of Ahr in HSCs, but not hepatocytes or Kupffer cells, developed more severe fibrosis after administration of CCl4 or bile duct ligation. C57BL/6J mice given ITE did not develop CCl4-induced liver fibrosis, whereas mice without HSC AhR given ITE did develop CCl4-induced liver fibrosis. In studies of mouse and human HSCs, we found that AhR prevents transforming growth factor β–induced fibrogenesis by disrupting the interaction of Smad3 with β-catenin, which prevents the expression of genes that mediate fibrogenesis. Conclusions In studies of human and mouse HSCs, we found that AhR prevents HSC activation and expression of genes required for liver fibrogenesis. Development of nontoxic AhR agonists or strategies to activate AhR signaling in HSCs might be developed to prevent or treat liver fibrosis.

To assess the risk of foodborne disease caused by Salmonella in broiler chickens from retail to table, and to find effective preventive measures according to the risk assessment results.Using dose-response model and Combase database, to evaluate the chicken-Salmonella poisoning risk through the crosscontamination in the kitchen with @ RISK by combining monitoring data of broiler chickens in Heilongjiang Province and related data.According to the results of the quantitative risk assessment, there was a high risk of chicken-Salmonella poisoning because of cross-contamination in the kitchen. Scenario analysis suggested that, if the raw chicken was frozen or refrigerated storage in retail, the average risk of chicken-Salmonella poisoning can be reduced 1/5.The risk of Chinese residents suffering from chicken-Salmonella poisoning will be reduced effectively by using cold chain management of raw chicken in retail.

The microstructure, wettability and chemical composition of the butterfly wing surfaces were investigated by a scanning electron microscope, a contact angle meter and a Fourier transform infrared spectrometer. The micro/nano structural models for hydrophobicity of the butterfly wing surfaces were established on the basis of the Cassie equation. The hydrophobicity mechanisms were discussed from the perspective of biological coupling. The butterfly wing surfaces are composed of naturally hydrophobic material and possess micro/nano hierarchical structures, including primary structure (micrometric scales), secondary structure (nano longitudinal ridges and lateral bridges) and tertiary structure (nano stripes). The wing surfaces exhibit high hydrophobicity (contact angle 138°–157°) and low adhesion (sliding angle 1°–3°). The micromorphology and self-cleaning performance of the wing surfaces demonstrate remarkable anisotropism. The special complex wettability ascribes to a coupling effect of the material element and the structure element. In micro-dimension, the smaller the width and the bigger the spacing of the scale, the stronger the hydrophobicity of the wing surfaces. In nano-dimension, the smaller the height and the smaller the width and the bigger the spacing of the longitudinal ridge, the stronger the hydrophobicity of the wing surfaces. This work promotes our understanding of the hydrophobicity mechanism of bio-surfaces and may bring inspiration for biomimetic design and preparation of smart interfacial materials.

The cholesterol sulfotransferase SULT2B1b converts cholesterol to cholesterol sulfate (CS). We previously reported that SULT2B1b inhibits hepatic gluconeogenesis by antagonizing the gluconeogenic activity of hepatocyte nuclear factor 4α (HNF4α). In this study, we showed that the SULT2B1b gene is a transcriptional target of HNF4α, which led to our hypothesis that the induction of SULT2B1b by HNF4α represents a negative feedback to limit the gluconeogenic activity of HNF4α. Indeed, downregulation of Sult2B1b enhanced the gluconeogenic activity of HNF4α, which may have been accounted for by the increased acetylation of HNF4α as a result of decreased expression of the HNF4α deacetylase sirtuin 1 (Sirt1). The expression of Sult2B1b was also induced by HNF4α upon fasting, and the Sult2B1b null (Sult2B1b-/-) mice showed increased gluconeogenic gene expression and an elevated fasting glucose level, suggesting that SULT2B1b also plays a restrictive role in HNF4α-mediated fasting-responsive gluconeogenesis. We also developed thiocholesterol, a hydrolysis-resistant derivative of CS, which showed superior activity to that of the native CS in inhibiting gluconeogenesis and improving insulin sensitivity in high-fat-diet-induced diabetic mice. We conclude that the HNF4α-SULT2B1b-CS axis represents a key endogenous mechanism to prevent uncontrolled gluconeogenesis. Thiocholesterol may be used as a therapeutic agent to manage hyperglycemia.

Hydrophobic nano silver films were fabricated on butterfly wings as bio-template. The micrometric/nano structures and hydrophobicity of the surfaces were investigated with the help of scanning electron microscope(SEM) and video-based contact angle meter. The hydrophobic mechanism of silver film was analyzed with the aid of Cassie’s formula. On the nano silver films of various thicknesses(5, 10, 20, 40, 60, 80, 100 nm), all the contact angles( CAs) of water were bigger than 120°. When the silver film was 5 nm, the CAs of water on it on the wing surfaces of Mimathyma nycteis and Speyeria aglaja were 143.2° and 139.2°, respectively. Coated with the sliver film of the same thickness, butterfly wing surface exhibited the CA remarkably bigger than glass slide surface, exhibiting its high hydrophobicity. With the increase of silver film thickness on butterfly wing surface, the hydrophobicity kept decreasing. The micrometric/nano hierarchical structures on butterfly wing surface result in the transition of metal silver from hydrophilicity to hydrophobicity.

Conventional methods of detecting food-borne pathogens in food are cumbersome and time-consuming. To study a rapid detecting method, investigate the usefulness of a filtration for the concentrate bacteria from raw milk and to establish an accuracy and sensitive multiplex PCR for simultaneous detection of five food-borne pathogens in raw milk. The assay can be completed in about 7 h and the limit of detection of all five food-borne pathogens for multiplex PCR was as low as 102 CFU/ml of raw-milk. This study, which increases the accuracy and sensitivity, improves traditional methods and can be applied to the food microorganism detection.

Listeria monocytogenes is a food-borne pathogen which can cause zoonosis. A detection method based on real time reverse-transcription PCR amplification of mRNA was established in the study. This method can overcome false-positive result caused by amplification of nonviable L.monocytogenes. Sensitivity and specificity of the method were studied, as well as artificially contaminated dairy products by L.monocytogenes, dairy products from market and L.monocytogenes biofilm. For contaminated milk, detection sensitivity was 17CFU/ml after 6h enrichment. Detection limit in biofilm was 2×10 2 CFU/cm 2 after 7h enrichment. The results indicate that the method can satisfy detection of L.monocytogenes in dairy products and biofilm. Key words-real time RT-PCR; Listeria monocytogenes; biofilm

We evaluated relative quantification by real-time RT PCR of a target gene transcription.On the basis of (1+E)(-deltadeltaCt) mathematical model and the E=10[-1/slope]-1 equation, the detected Ct data of the real-time RT PCR was analyzed by the new DNA subtraction assay. DNA was used as standard for the initial amount of bacteria. RT and RT- samples for real-time PCR detection were prepared to quantify the DNA that simultaneously existed with RNA isolated from the bacteria samples. The detected quantitative data were subtracted from total nucleic acid simultaneously contained RNA and DNA. Enzymatic digestion with DNase I was not included in this protocol.The gene expression of staphylococcal enterotoxin A (sea), 16S rRNA and RNA III of Staphylococcus aureus were detected. These two different analysis methods, DNA subtraction method and absolute quantitative method, led to similar results (p0.05).This is a time-saving and efficient method. Additionally, for further studies it would be conceivable to extend the detection of genes expression from S. aureus to other prokaryote.