Attributed Multi-order Graph Convolutional Network for Heterogeneous Graphs

Heterogeneous graph neural networks aim to discover discriminative node embeddings and relations from multi-relational networks.One challenge of heterogeneous graph learning is the design of learnable meta-paths, which significantly influences the quality of learned embeddings.Thus, in this paper, we propose an Attributed Multi-Order Graph Convolutional Network (AMOGCN), which automatically studies meta-paths containing multi-hop neighbors from an adaptive aggregation of multi-order adjacency matrices. The proposed model first builds different orders of adjacency matrices from manually designed node connections. After that, an intact multi-order adjacency matrix is attached from the automatic fusion of various orders of adjacency matrices. This process is supervised by the node semantic information, which is extracted from the node homophily evaluated by attributes. Eventually, we utilize a one-layer simplifying graph convolutional network with the learned multi-order adjacency matrix, which is equivalent to the cross-hop node information propagation with multi-layer graph neural networks. Substantial experiments reveal that AMOGCN gains superior semi-supervised classification performance compared with state-of-the-art competitors

The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer

Matrix metalloproteinases (MMPs) are an important class of enzymes in the body that function through the extracellular matrix (ECM). They are involved in diverse pathophysiological processes, such as tumor invasion and metastasis, cardiovascular diseases, arthritis, periodontal disease, osteogenesis imperfecta, and diseases of the central nervous system. MMPs participate in the occurrence and development of numerous cancers and are closely related to immunity. In the present study, we review the immunomodulatory role of MMPs in colitis-associated cancer (CAC) and discuss relevant clinical applications. We analyze more than 300 pharmacological studies retrieved from PubMed and the Web of Science, related to MMPs, cancer, colitis, CAC, and immunomodulation. Key MMPs that interfere with pathological processes in CAC such as MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13, as well as their corresponding mechanisms are elaborated. MMPs are involved in cell proliferation, cell differentiation, angiogenesis, ECM remodeling, and the inflammatory response in CAC. They also affect the immune system by modulating differentiation and immune activity of immune cells, recruitment of macrophages, and recruitment of neutrophils. Herein we describe the immunomodulatory role of MMPs in CAC to facilitate treatment of this special type of colon cancer, which is preceded by detectable inflammatory bowel disease in clinical populations

Chemoenzymatic synthesis of fucosylated oligosaccharides using Thermosynechococcus α1–2-fucosyltransferase and their application in the regulation of intestinal microbiota

A novel bacterial α 1-2-fucosyltransferase (α 2FT) from Thermosynechococcus sp. NK55a (Ts2FT) has been discovered and characterized. It shares 28-62% protein sequence homology to α 2FTs reported previously. The Ts2FT was cloned as an N-terminal His6-tagged recombinant protein (His6-Ts2FT) and expressed in E. coli BL21 (DE3). It was expressed at a level of 6.2 mg/L culture after induction with 0.05 mM of isopropylβ-d-1-thiogalactoside (IPTG) at 16 °C for 20 h. It showed the optimal activity at a reaction temperature of 40 °C and pH of 7.0. The presence of a Mg2+ improved its catalytic efficiency. Ts2FT displayed a strict acceptor specificity and could recognize only β1-3-galatoside acceptors. It was used efficiently for one-pot multienzyme synthesis of fucosylated oligosaccharides. One of the products, lacto-N-fucopentaose I was shown to promote the growth of intestinal probiotics including those belonging to Acidobacteria, Actinobacteria, Proteobacteria, Planctomycetes, and Chloroflexi

Chemoenzymatic synthesis of fucosylated oligosaccharides using Thermosynechococcus alpha 1-2-fucosyltransferase and their application in the regulation of intestinal microbiota

A novel bacterial alpha 1-2-fucosyltransferase (alpha 2FT) from Thermosynechococcus sp. NK55a (Ts2FT) has been discovered and characterized. It shares 28-62% protein sequence homology to alpha 2FTs reported previously. The Ts2FT was cloned as an N-terminal His(6)-tagged recombinant protein (His(6)-Ts2FT) and expressed in E. coli BL21 (DE3). It was expressed at a level of 6.2 mg/L culture after induction with 0.05 mM of isopropyl beta-D-1-thio-galactoside (IPTG) at 16 degrees C for 20 h. It showed the optimal activity at a reaction temperature of 40. C and pH of 7.0. The presence of a Mg2+ improved its catalytic efficiency. Ts2FT displayed a strict acceptor specificity and could recognize only beta 1-3-galatoside acceptors. It was used efficiently for one-pot multienzyme synthesis of fucosylated oligosaccharides. One of the products, lacto-N-fucopentaose I was shown to promote the growth of intestinal probiotics including those belonging to Acidobacteria, Actinobacteria, Proteobacteria, Planctomycetes, and Chloroflexi

MOTS-c Functionally Prevents Metabolic Disorders

Mitochondrial-derived peptides are a family of peptides encoded by short open reading frames in the mitochondrial genome, which have regulatory effects on mitochondrial functions, gene expression, and metabolic homeostasis of the body. As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10. However, there is a lack of articles summarizing the genes and pathways involved in the physiological activity of MOTS-c. This article aims to summarize and interpret the interesting and updated findings of MOTS-c-associated genes and pathways involved in pathological metabolic processes. Finally, it is expected to develop novel diagnostic markers and treatment approaches with MOTS-c to prevent and treat metabolic disorders in the future

ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model

Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the poultry industry and may threaten human health due to its potential zoonosis. In this study, we confirmed that clbG was necessary for the APEC XM strain to produce colibactin. The deletion of clbG on APEC XM contributed to lowered γH2AX expression, no megalocytosis, and no cell cycle arrest in vitro. None of the 4-week Institute of Cancer Research mice infected with the APEC XM ΔclbG contracted meningitis or displayed weakened clinical symptoms. Fewer histopathological lesions were observed in the APEC XM ΔclbG group. The bacterial colonization of tissues and the relative expression of cytokines (IL-1β, IL-6, and TNF-α) in the brains decreased significantly in the APEC XM ΔclbG group compared to those in the APEC XM group. The tight junction proteins (claudin-5, occludin, and ZO-1) were not significantly destroyed in APEC XM ΔclbG group in vivo and in vitro. In conclusion, clbG is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice

<i>In vivo</i> imaging of mice infected intragastrically or intrarectally with luciferase-expressing <i>C</i>. <i>muridarum</i>.

<p>CBA/J mice were intragastrically (i.g., n = 5, panels a-i) or intrarectally (i.r., n = 5, j-r) inoculated with 5 x 10⁴ IFUs of luciferase-expressing <i>C</i>. <i>muridarum</i>. On different days after the inoculations as indicated on top of the figure, a whole body <i>in vivo</i> imaging was used to detect the luciferase-generated bioluminescence signals as displayed in red/green/blue colors (in the order of decreasing intensity). Images taken from one of the mice in each group were shown. It is worth noting that the bioluminescence signals were detectable as early as day 3 after inoculation at the initial inoculation sites either stomach (panel a) or anorectum (j). Starting on day 7, the signals persisted in the mouse abdominal area throughout the experiments with similar distribution patterns regardless of the initial inoculation routes.</p

Evaluating the gross pathology in the genital tracts of CBA/j mice infected with <i>C</i>. <i>muridarum</i>.

<p>The three parallel groups of CBA/J mice infected with luciferase-expressing <i>C</i>. <i>muridarum</i> intragastrically (i.g., panel a, n = 5), intrarectally (i.r., b, n = 5) or intravaginally (i.vag., panels c, n = 5) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155880#pone.0155880.g003" target="_blank">Fig 3</a> legend were sacrificed on day 70 after infection for visually identifying (arrow) and scoring (white numbers) hydrosalpinx. Mice with hydrosalpinx on either side of the genital tract were defined positive for hydrosalpinx. The severity of hydrosalpinx was scored from each oviduct independently and the scores from both sides of the same mouse were added together as the score for that mouse. Both incidence rates and severity scores of hydrosalpinx from each group were listed beside the corresponding images. Note that significant hydrosalpinx was detected only in mice infected intravaginally but intragastrically or intrarectally.</p

Monitoring <i>C</i>. <i>muridarum</i> infection in the GI and genital tracts of C57BL/6J and C3H/HeJ mice following an intrarectal inoculation.

<p>C57BL/6J (panels a1-a3, n = 4) and C3H/HeJ (b1-3, n = 3) mice were intrarectally infected with <i>C</i>. <i>muridarum</i> and both anorectal and cervico-vaginal swabs were taken on different days after infection as listed along the X-axis in the bottom of the figure. The number of live organisms recovered from the swabs was expressed as Log10 IFUs. "ND” denotes not detected. On day 70 after infection, mice were sacrificed for harvesting the genital tracts for visually identifying and scoring hydrosalpinx (a3 & b3) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155880#pone.0155880.g003" target="_blank">Fig 3</a> legend. Note that although significant levels of live organisms were continuously detectable in the mouse GI tract throughout the experiment, no significant level of live organisms was detected in the mouse vaginal swabs and there was no significant hydrosalpinx in any of the mice.</p

Evaluating the microscopic pathology in the mouse genital tracts.

<p>The same mouse genital tissues harvested on day 70 after infection as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155880#pone.0155880.g005" target="_blank">Fig 5</a> legend were examined for inflammatory infiltration in the genital tract tissues. (A) Representative images of H&E-stained sections of vagina (panels a, d & g under 10x objective lens while a1, d1 & g1 under 100x), uterine/uterine horn (b, e & h, 10x; b1, e1 & h1, 100x) and oviduct (c, f & i, 10x; c1, f1 & i1, 100x) from mice infected intragastrically (i.g., a-c), intrarectally (i.r., d-f) and intravaginally (i.vag., g-i) were shown. (B) The Inflammatory infiltration from the vagina (a), uterine/uterine horn (b) and oviduct (c) tissues were semi-quantitatively scored (shown along the Y-axis) as described in the Materials and Method section. Kruskal-Wallis Test was used to calculate the p values listed in the figure. Note that only the tissues from the intravaginally infected mice displayed significant levels of inflammatory infiltration.</p