Behçet's disease (BD) is a multi-systemic inflammatory disorder which can affect all types and sizes of blood vessels. This study aims to evaluate the prevalence and characteristics of vascular involvement in BD. Among 796 patients diagnosed with BD, 102 patients (81 male, 21 female) with vascular involvement were included, whose detailed clinical characteristics were recorded. The diagnosis of vascular lesions was made on clinical signs, by Doppler ultrasonography, and/or angiography using computed tomographic or magnetic resonance techniques. Vascular involvement occurred in 12.8 % of BD patients. Male to female ratio was 3.86:1. Mean age at onset of vascular involvement was 29.5 ± 11.3 years. Vascular lesion was the initial sign of BD in 28 patients, accounting for 27.5 %. Of 102 BD patients with vascular involvement, 72 had venous lesions (70.6 %) and 56 had arterial lesions (54.9 %), among which 26 (25.5 %) patients had both venous and arterial involvements. Female BD patients were more often involved with arterial lesions, whereas male BD patients developed venous lesions more often than females, P = 0.000. The most common type of vascular involvement was deep venous thrombosis in lower extremities (n = 49), other affected venous sites including inferior vena cava, superior vena cava, and cerebral venous. The prominent type of arterial lesions was dilatation (n = 25, including 24 cases of aneurysms); other types included eight cases of occlusion and 23 cases of stenosis. The main locations of arterial lesions were the aorta (n = 19), lower extremity arteries (n = 15), pulmonary arteries (n = 13), coronary arteries (n = 5), and subclavian arteries (n = 5). Compared with those without vascular lesions, ocular involvement, genital ulcers, and arthritis were significantly less frequent among patients with vasculo-BD (23.5 vs 35.2 %, P = 0.024; 54.9 vs 76.5 %, P = 0.000; 19.6 vs 30.5 %, P = 0.026), whereas a higher frequency of cardiac involvement was found in vasculo-BD patients (20.6 vs 3.6 %, P = 0.000). Vascular involvement is a complication in BD patients. This study illustrated that venous lesions are more frequently involved than arterial lesions. Vascular lesions correlated with a high frequency of cardiac involvement and a low incidence of ocular lesions, genital ulcers, and arthritis.

Endo-beta-N-acetylglucosaminidase D (Endo D) produced by Streptococcus pneumoniae cleaves the di-N-acetylchitobiose structure in asparagine-linked oligosaccharides. The enzyme generally acts on complex type oligosaccharides after removal of external sugars by neuraminidase, beta-galactosidase, and beta-N-acetylglucosaminidase. We cloned the gene encoding the enzyme and expressed it as a periplasm enzyme in Escherichia coli. The first 37 amino acids in the predicted sequence are removed in the mature enzyme, yielding a protein with a molecular mass of 178 kDa. The substrate specificity of the recombinant enzyme is indistinguishable from the enzyme produced by S. pneumoniae. Endo-beta-N-acetylglucosaminidase A (Endo A) from Arthrobacter protophormiae, the molecular mass of which is 72 kDa, had 32% sequence identity to Endo D, starting from the N-terminal sides of both enzymes, although Endo A hydrolyzes high-mannose-type oligosaccharides and does not hydrolyze complex type ones. Endo D is not related to endo-beta-N-acetylglucosaminidases H, F(1), F(2), or F(3), which share common structural motifs. Therefore, there are two distinct groups of endo-beta-N-acetylglucosaminidases acting on asparagine-linked oligosaccharides. The C-terminal region of Endo D shows homology to beta-galactosidase and beta-N-acetylglucosaminidase from S. pneumoniae and has an LPXTG motif typical of surface-associated proteins of Gram-positive bacteria. It is possible that Endo D is located on the surface of the bacterium and, together with other glycosidases, is involved in virulence.

Clostridioides difficile toxins (TcdA and TcdB) are major exotoxins responsible for C. difficile infection (CDI) associated diseases. The previously reported TcdB variants showed distinct biological features, immunoactivities, and potential pathogenicity in disease progression. Here, we performed global comparisons of amino acid sequences of both TcdA and TcdB from 3,269 C. difficile genomes and clustered them according to the evolutionary relatedness. We found that TcdB was much diverse and could be divided into eight subtypes, of which four were first described. Further analysis indicates that the tcdB gene undergoes accelerated evolution to maximize diversity. By tracing TcdB subtypes back to their original isolates, we found that the distribution of TcdB subtypes was not completely aligned with the phylogeny of C. difficile. These findings suggest that the tcdB genes not only frequently mutate, but also continuously transfer and exchange among C. difficile strains.

IVL should be given more attention by vascular surgeons, although it is extremely rare. Many therapeutic methods are available for uterine leiomyomatosis involving inferior vena cava, among which operation is the best choice.

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The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.

Genes carry out their biological functions through pathways in complex networks consisting of many interacting molecules. Studies on the effect of network architecture on the evolution of individual proteins will provide valuable information for understanding the origin and evolution as well as functional conservation of signaling pathways. However, the relationship between the network architecture and the individual protein sequence evolution is yet little known. In current study, we carried out network-level molecular evolution analysis on TLR (Toll-like receptor ) signaling pathway, which plays an important role in innate immunity in insects and mammals, and we found that: 1) The selection constraint of genes was negatively correlated with its position along TLR signaling pathway; 2) all genes in TLR signaling pathway were highly conserved and underwent strong purifying selection; 3) the distribution of selective pressure along the pathway was driven by differential nonsynonymous substitution levels; 4) The TLR signaling pathway might present in a common ancestor of sponges and eumetazoa, and evolve via the TLR, IKK, IκB and NF-κB genes underwent duplication events as well as adaptor molecular enlargement, and gene structure and conservation motif of NF-κB genes shifted in their evolutionary history. Our results will improve our understanding on the evolutionary history of animal TLR signaling pathway as well as the relationship between the network architecture and the sequences evolution of individual protein.

BackgroundTo survive in a hostile environment, insects have evolved an innate immune system to defend against infection. Studies have shown that natural selection may drive the evolution of immune system-related proteins. Yet, how network architecture influences protein sequence evolution remains unclear. Here, we analyzed the molecular evolutionary patterns of genes in the Toll and Imd innate immune signaling pathways across six Drosophila genomes within the context of a functional network.ResultsBased on published literature, we identified 50 genes that are directly involved in the Drosophila Toll and Imd signaling pathways. Of those genes, only two (Sphinx1 and Dnr1) exhibited signals of positive selection. There existed a negative correlation between the strength of purifying selection and gene position within the pathway; the downstream genes were more conserved, indicating that they were subjected to stronger evolutionary constraints. Interestingly, there was also a significantly negative correlation between the rate of protein evolution and the number of regulatory microRNAs, implying that genes regulated by more miRNAs experience stronger functional constraints and therefore evolve more slowly.ConclusionTaken together, our results suggested that both network architecture and miRNA regulation affect protein sequence evolution. These findings improve our understanding of the evolutionary patterns of genes involved in Drosophila innate immune pathways.