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In vivo toxicity of aromatic ring (BODIPY, 1,3,5,7,8-pentamethyl dipyrrin borondifluoride) attached monofunctional Pt(II) complexes mCBP {[cis-Pt(NH3)2Cl] 8-(para-pyridine-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}+ Nitrate- and dCBP {[cis-Pt(NH3)2Cl]28-(1,3-pyrimidine-5-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}2+ diNitrate2- were tested in Caenorhabditis elegans (C. elegans). dCBP showed promising reactive oxygen ROS (reactive oxygen species) generating capability. This complex resulted reduction of lifespan, body length and egg laying rate under dark and light irradiation in both N2 (wild-type, cisplatin resistant) and ok938 (asna-1, cisplatin sensitive) C. elegans. Expressional change of several key cancer related pathway (JNK (c-Jun N-terminal kinase) and Wnt/β-catenin (Wingless/Integrated/β-catenin)) related genes (for instance, jnk-1, wrm-1 and gst-4) were confirmed by RNA sequencing experiments. These transcriptional alternations could explain physiological parameters change in nematode and partially revealed how both Pt(II) based complexes influence cancer related pathways. Furthermore, these associated genes exhibited the function of apoptosis, reduced chemoresistance of cancer cells and most of those expressional changes were linked to extended survival of cancer patients.

Chronic lead exposure can result in cognitive dysfunction and behavioral disorders. However, the current treatments for alleviating lead poisoning have many side effects. Previous studies have suggested that probiotics may have the potential to ameliorate neurotoxicity caused by lead exposure. This study determines the alleviating effects of Lactobacillus plantarum WSJ-06 on neurological disorders induced by chronic lead exposure from the perspective of the gut microbiota and serum metabolites. The results showed that treatment with Lactobacillus plantarum WSJ-06 alleviated memory dysfunction and reduced the levels of inflammatory cytokines in the serum and hippocampus induced by lead exposure. In addition, Lactobacillus plantarum WSJ-06 partially restored the lead-induced gut microbiota dysbiosis. It also increased the proportion of some beneficial metabolites in the serum, such as arachidonic acid, tryptophan hydroxylase, serotonin, vitamin B12, trehalose, and kynurenic acid, and decreased some metabolites in the serum, such as LPS 20:5 and L-kynurenine. A correlation analysis further indicated that lead-induced neurobehavioral disorders were related to intestinal microbiota (the [Eubacterium]_siraeum_group, Roseburia, Lactobacillus, etc) and serum metabolites (LPS 20:5, serotonin, vitamin B12, etc). In conclusion, Lactobacillus plantarum WSJ-06 alleviated neuroinflammation and memory impairment caused by lead exposure by modulating the gut microbiota and metabolites in the serum.

Two novel fluorophore (BODIPY)-bearing complexes, pyriplatin (

Toll-like receptor (TLR) genes are the earliest reported pathogen recognition receptors (PRRs) and have been extensively studied. These genes play pivotal roles in the innate immune defense against pathogen invasion. In this study, a total of 16 tlr genes were identified and characterized in spotted sea bass (Lateolabrax maculatus). The tlr genes of spotted sea bass were classified into five subfamilies (tlr1-subfamily, tlr3-subfamily, tlr5-subfamily, tlr7-subfamily, and tlr11-subfamily) according to the phylogenetic analysis, and their annotations were confirmed by a syntenic analysis. The protein domain analysis indicated that most tlr genes had the following three major TLR protein domains: a leucine-rich repeat (LRR) domain, a transmembrane region (TM) and a Toll/interleukin-1 receptor (TIR) domain. The tlr genes in spotted sea bass were distributed in 11 of 24 chromosomes. The mRNA expression levels of 16 tlr genes in response to Vibrio harveyi infection were quantified in the head kidney. Most genes were downregulated following V. harveyi infection, while only 5 tlr genes, including tlr1-1, tlr1-2, tlr2-2, tlr5, and tlr7, were significantly upregulated. Collectively, these results help elucidate the crucial roles of tlr genes in the immune response of spotted sea bass and may supply valuable genomic resources for future studies investigating fish disease management.

The glucose transporters (GLUTs) are well known for their essential roles in moving the key metabolites, glucose, galactose, fructose and a number of other important substrates in and out of cells. In this study, we identified a total of 21 glut genes in spotted sea bass (Lateolabrax maculatus) through extensive data mining of existing genomic and transcriptomic databases. Glut genes of spotted sea bass were classified into three subfamilies (Class I, Class II and Class III) according to the phylogenetic analysis. Glut genes of spotted sea bass were distributed in 15 out of 24 chromosomes. Deduced gene structure analysis including the secondary structure and the three-dimensional structures, as well as the syntenic analysis further supported their annotations and orthologies. Expression profile in healthy tissues indicated that 9 of 21 glut genes were expressed in liver of spotted sea bass. During short-term starvation, the mRNA expression levels of 3 glut genes (glut2, glut5, and glut10) were significantly up-regulated in liver (P 0.05), indicating their potential roles in sugar transport and consumption. These findings in our study will facilitate the further evolutionary characterization of glut genes in fish species and provide a theoretical basis for their functional study.

Fat-tailed sheep have a unique characteristic of depositing fat in their tails. In the present study, we conducted genome-wide association studies (GWAS) on traits related to tail fat deposition and body size in the Hulun Buir sheep. A total number of 300 individuals belonging to two fat-tailed lines of the Hulun Buir sheep breed genotyped with the Ovine Infinium HD SNP BeadChip were included in the current study. Two mixed models, one for continuous and one for binary phenotypic traits, were employed to analyse ten traits, that is, body length (BL), body height (BH), chest girth (CG), tail length (TL), tail width (TW), tail circumference (TC), carcass weight (CW), tail fat weight (TF), ratio of CW to TF (RCT) and tail type (TT). We identified 7, 6, 7, 2, 10 and 1 SNPs significantly associated with traits TF, CW, RCT, TW, TT and CG, respectively. Their associated genomic regions harboured 42 positional candidate genes. Out of them, 13 candidate genes including SMURF2, FBF1, DTNBP1, SETD7 and RBM11 have been associated with fat metabolism in sheep. The RBM11 gene has already been identified in a previous study on signatures of selection in this specific sheep population. Two more genes, that is, SMARCA5 and GAB1 were associated with body size in sheep. The present study has identified candidate genes that might be implicated in tail fat deposition and body size in sheep.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice. Results showed higher levels of specific mucosal and systemic antibody responses induced by intranasal as compared to subcutaneous immunization. Intranasal immunization enhanced the concentration of interleukin-4, interleukin-10, and interferon-γ, while subcutaneous immunization enhanced only the latter two. In addition, intranasal immunization protected against EHEC O157:H7 colonization and infection in mice at a rate of 90%.Histopathological analysis revealed that vaccination reduced colon damage, especially when administered intranasally. In contrast, subcutaneous immunization elicited a weak immune response and exhibited a low protection rate. These findings demonstrate that intranasal immunization with the fusion protein induces both humoral and cellular immune (Th1/Th2) responses in mice. The novel EspA-Tir-M novel fusion protein therefore represents a promising subunit vaccine against EHEC O157:H7 infection.

Euryhaline teleosts can survive in a wide salinity range via alteration of the molecular mechanisms to maintain internal ionic and osmotic balance in osmoregulatory organs such as gill，kidney and intestine. Na

The tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation (14-3-3) proteins are a group of highly conserved homologous and heterologous proteins involved in a wild range of physiological processes, including the regulation of many molecular phenomena under different environmental salinities. In this study, we identified eleven 14-3-3 genes from the spotted sea bass (Lateolabrax maculatus) genome and transcriptomic databases and verified their identities by conducting phylogenetic, syntenic and gene structure analyses. The spotted sea bass 14-3-3 genes are highly conserved based on sequence alignment, conserved domains and motifs, and tertiary structural feature. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 14-3-3 genes in gill of spotted sea bass under normal physiological conditions indicated that the expression level of 14-3-3 zeta was the highest among tested genes, followed by 14-3-3 theta. Furthermore, expression profiles of 14-3-3 genes in gill tissue (in vivo and in vitro) indicated that the 14-3-3 zeta and 14-3-3 theta genes were significantly induced by different environmental salinities in spotted sea bass, suggesting their potential involvement in response to salinity challenge. Our findings may lay the foundation for future functional studies on the 14-3-3 gene family in euryhaline teleosts.

Powdered infant formula is considered as the main transmission vehicle for Cronobacter sakazakii infections including meningitis, septicemia, and necrotizing enterocolitis. The effects of high-pressure processing treatment on inactivation of C. sakazakii ranging from 100 to 400 MPa for 3.0, 5.0, and 7.0 min in whole milk and skim milk were studied. Significant differences in inactivation of C. sakazakii were observed in milk samples under different pressures for 3 to 7 min compared with untreated samples, and C. sakazakii was not detected after 400 MPa for 3 min. The lethality rates of C. sakazakii cells in whole and skim milk with an initial level of 10(4) cfu/mL after 100 and 200 MPa treatments were not significantly different, but relatively higher lethality rates were found in whole milk after 300 MPa treatment than in skim milk. Finally, the scanning electron micrographs indicated that cellular envelope and intracellular damage of C. sakazakii cells were apparent after 300 and 400 MPa for 5.0 min compared with the untreated cells, and a progressive increase of injured cells with increased pressure treatment was found. It was concluded that C. sakazakii was sensitive to high-pressure processing treatment and that high-pressure processing treatment with 400 MPa for 3.0 min can be used to control C. sakazakii contamination in milk samples.

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Motilin (MLN), an interdigestive hormone secreted by endocrine cells of the intestinal mucosa, binds to a G protein-coupled receptor to exert its biological function of regulating gastrointestinal motility. In the present study, we identified the prepromotilin and mln receptor (mlnr) from the spotted sea bass, Lateolabrax maculatus. Mln consisted of an ORF of 336 nucleotides encoding 111 amino acids. The precursor protein contained a 17-amino-acid mature peptide. Mlnr had an ORF of 1089 bp encoding a protein of 362 amino acids. Seven transmembrane domains were predicted with TMHMM analysis. The phylogenetic analysis of mln and mlnr showed that they fell into the same clade with respective counterpart of selected fishes before clustering with other detected vertebrates. Both mln and mlnr genes were highly expressed in intestine of spotted sea bass using quantitative real-time PCR. In situ hybridization indicated that mln and mlnr mRNA were both localized in the lamina propria and the epithelial cell of intestinal villus. The expressions of both genes were regulated under short-term starvation in a time-dependent manner. In vitro experiments indicated that the expressions of ghrelin (ghrl), gastrin (gas) and cholecystokinin (cck) were enhanced by MLN after 3-h treatment, but the effect was absent after 6 or 12-h incubation. Taken together, the MLN and its receptor might play important roles in regulating intestinal motility in spotted sea bass.

Artificial selection has played a critical role in animal breeding. Detection of artificial selection footprints in genomic regions can provide insights for understanding the function of specific phenotypic traits and better guide animal breeding. To more fully understand the relationship between genomic composition and phenotypic diversity arising from breed development, a genome-wide scan was conducted using an OvineSNP50 BeadChip and integrated haplotype score and fixation index analyses to detect selection signatures on the X chromosome in three sheep breeds. We identified 49, 34, and 55 candidate selection regions with lengths of 27.49, 16.47, and 25.42 Mb in German Mutton, Dorper, and Sunit sheep, respectively. Bioinformatics analysis showed that some of the genes in these regions with selection signatures, such as BMP15, were relevant to reproduction. We also identified some selection regions harboring genes that had human orthologs, including BKT, CENPI, GUCY2F, MSN, PCDH11X, PLP1, VSIG4, PAK3, WAS, PCDH19, PDHA1, and SRPX2. The VSIG4 and PCDH11X genes are associated with the immune system and disease, PDHA1 is associated with biosynthetic related pathways, and PCDH19 is expressed in the nervous system and skin. These genes may be useful as candidate genes for molecular breeding.

Chinese indigenous sheep can be classified into three types based on tail morphology: fat-tailed, fat-rumped, and thin-tailed sheep, of which the typical breeds are large-tailed Han sheep, Altay sheep, and Tibetan sheep, respectively. To unravel the genetic mechanisms underlying the phenotypic differences among Chinese indigenous sheep with tails of three different types, we used ovine high-density 600K SNP arrays to detect genome-wide copy number variation (CNV). In large-tailed Han sheep, Altay sheep, and Tibetan sheep, 371, 301, and 66 CNV regions (CNVRs) with lengths of 71.35 Mb, 51.65 Mb, and 10.56 Mb, respectively, were identified on autosomal chromosomes. Ten CNVRs were randomly chosen for confirmation, of which eight were successfully validated. The detected CNVRs harboured 3130 genes, including genes associated with fat deposition, such as PPARA, RXRA, KLF11, ADD1, FASN, PPP1CA, PDGFA, and PEX6. Moreover, multilevel bioinformatics analyses of the detected candidate genes were significantly enriched for involvement in fat deposition, GTPase regulator, and peptide receptor activities. This is the first high-resolution sheep CNV map for Chinese indigenous sheep breeds with three types of tails. Our results provide valuable information that will support investigations of genomic structural variation underlying traits of interest in sheep.

To investigate the inhibitory effect of Lactobacillus rhamnosus GG ( LGG) against Cronobacter-induced meningitis in neonatal rats.The cell adhesion and invasion capacities of Cronobacter were assayed in Caco-2 cells, and the optimal time length and concentration of the bacterium for infection were determined. The suppressive effects of LGG on the adhesion and invasion of Cronobacter in caco-2 cells were tested by competitive and exclusion experiments, and its inhibitory effect against Cronobacter-induced meningitis was evaluated in neonatal rats.Cronobacter showed aggressive adhesion to caco-2 cells with an optimal infection time of 3 h. LGG produced a concentration-dependent inhibition of Cronobacter adhesion and invasion by competing with and excluding the latter for cell adhesion. In neonatal rats, LGG showed an obvious preventive effect and also a moderate therapeutic effect against Cronobacter-induced meningitis.LGG can inhibit Cronobacter entry across the intestinal barrier to achieve preventive and therapeutic effects against Cronobacter-induced meningitis.

The purpose of this study was to determine the efficacy of a nucleic acid sequence-based amplification (NASBA) method of detecting noroviruses in artificially and naturally contaminated shellfish. We used 58 fecal samples that tested positive for noroviruses with electron microscopy (EM) to develop an NASBA assay for these viruses. Oligonucleotide primers targeting the polymerase coding region were used to amplify the viral RNA in an isothermal process that resulted in the accumulation of RNA amplicons. These amplicons were detected by hybridization with digoxigenin-labeled oligonucleotide probes that were highly specific for genogroup I (GI) and genogroup II (GII) of noroviruses. The expected band of 327 bp appeared in denaturing agarose gel without any nonspecific band. The specific signal for each amplicon was obtained through Northern blotting in many repeats. All fecal samples of which 46 (79.3%) belonged to GII and 12 (20.6%) belonged to GI were positive for noroviruses by EM and by NASBA. Target RNA concentrations as low as 5 pg/ml were detected in fecal specimens using NASBA. When the assay was applied to artificially contaminated shellfish, the sensitivity to nucleic acid was 100 pg/1.5 g shellfish tissue. The potential use of this assay was also confirmed in naturally contaminated shellfish collected from different ponds in Guangzhou city of China, of which 24 (18.76%) out of 128 samples were positive for noroviruses; of these, 19 (79.6%) belonged to GII and 5 (20.4%) belonged to GI. The NASBA assay provided a more rapid and efficient way of detecting noroviruses in fecal samples and demonstrated its potential for detecting noroviruses in food and environmental samples with high specificity and sensitivity.