The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters.

Campylobacter is a well-known food-borne pathogen that causes human gastroenteritis. Food products that contain Campylobacter may also be contaminated by other pathogens, however, whether this multiple contamination leads to more severe infection remains unclear. In this study, mice were gavaged with Campylobacter jejuni and other food-borne pathogenic bacteria to mimic a multiple infection. It was demonstrated that the C. jejuni load was elevated when the mice were co-infected with C. jejuni and Salmonella typhimurium, and the campylobacteriosis that followed was also enhanced, with features of decreased body weight, heavier bloody stools and more pronounced inflammatory changes to the colon. In addition, infection with C. jejuni was also promoted by co-infection with entero-invasive Escherichia coli but unaffected over time. In contrast to S. typhimurium and entero-invasive E. coli, co-infection by Listeria monocytogenes showed little effect on C. jejuni infection and even hindered its progress. In addition, the intestinal microecology was also affected by co-infection of C. jejuni with other pathogens, with an increased relative abundance of unclassified Enterobacteriaceae, decreased levels of butyric acid and changes in the abundance of several genera of gut microbe, which suggests that some food-borne pathogenic bacteria might affect the progression of C. jejuni infection in mice by influencing the composition of the gut microbiota and the resulting changes in SCFA levels. Collectively, our findings suggest that co-infection of Campylobacter with other pathogenic bacteria can impact on the progression of infection by C. jejuni in mice, which may also have implication for the etiology of Campylobacter on human health.

Microrchidia (MORC) family CW-type zinc-finger 2 (MORC2) regulates chromatin remodeling during the DNA-damage response, represses gene transcription, promotes lipogenesis. Here, we found that MORC2 down-regulated p21 by recruiting HDAC1 to the p21 promoter, in a p53-independent manner. MORC2-mediated down-regulation of p21 in turn promoted cell cycle progression in gastric cancer cells. Furthermore, MORC2 expression correlated negatively with p21 expression in gastric tumors in patients. We suggest that MORC2 may be a potential therapeutic target in cancer.

The expression and activity of CCAAT/enhancer-binding protein α (C/EBPα) are involved in sumoylation modification, which is critical to divert normal cells from differentiation to proliferation. However, the role and underlying mechanism of C/EBPα in cancer is poorly understood. Human MORC2 (microrchidia family CW-type zinc-finger 2), is a member of the MORC proteins family containing a CW-type zinc-finger domain. Here, we found that MORC2 interacted with TE-III domain of C/EBPα, and the overexpression of MORC2 promoted wild-type C/EBPα sumoylation and its subsequent degradation, which didn't significantly observe in mutant C/EBPα-K161R. Furthermore, the overexpression of MORC2 inhibited C/EBPα-mediated C2C12 cell differentiation to maintain cell cycle progression. Moreover, the striking correlation between the decreased C/EBPα expression and the increased MORC2 expression was also observed in the poor differentiation status of gastric cancer tissues. Most notably, the high expression of MORC2 is correlated  with an aggressive phenotype of clinical gastric cancer and shorter overall survival of patients. Taken together, our findings demonstrated that MORC2 expression regulated C/EBPα-mediated the axis of differentiation/proliferation via sumoylation modification, and affected its protein stability, causing cell proliferation and tumorigenesis.

Lactobacillus acidophilus is a common kind of lactic acid bacteria usually found in the human gastrointestinal tract, oral cavity, vagina, and various fermented foods. At present, many studies have focused on the probiotic function and industrial application of L. acidophilus. Additionally, dozens of L. acidophilus strains have been genome sequenced, but there has been no research to compare them at the genomic level. In this study, 46 strains of L. acidophilus were performed comparative analyses to explore their genetic diversity. The results showed that all the L. acidophilus strains were divided into two clusters based on ANI values, phylogenetic analysis and whole genome comparison, due to the difference of their predicted gene composition of bacteriocin operon, CRISPR-Cas systems and prophages mainly. Additionally, L. acidophilus was a pan-genome open species with a difference in carbohydrates utilization, antibiotic resistance, EPS operon, surface layer protein operon and other functional gene composition. This work provides a better understanding of L. acidophilus from a genetic perspective, and offers a frame for the biotechnological potentiality of this species.

The optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to accurately assess the effect of anticoagulant therapy in reducing recurrent VTE against the risk of inducing major bleeding.

The proteinase with milk-clotting activity (MCA) from Paenibacillus spp. BD3526 is characterized as a neutral metalloproteinase of 35kDa. However, the rapid reduction of its MCA during separation and purification leads to low enzyme recovery. The effects of metal ions, inactivation kinetics, and concentration of calcium on the enzymatic activities and thermal stability of the BD3526 metalloproteinase were investigated. In the absence of calcium, the residual activities of the BD3526 metalloproteinase sharply declined during the first three hours, and continued to slowly decrease thereafter. The activities were well fitted by a double-exponential decay model. The inactivation rates were significantly inhibited by calcium and the residual enzyme activities were maintained at more than 80% for 30d at room temperature with 50-100mM calcium. An intermolecular autoproteolytic mechanism was responsible for BD3526 metalloproteinase inactivation. The target protein band with MCA remained largely undegraded in the enzyme solution that was supplemented with 100mM of calcium, but gradually diminished over time in the absence of calcium. N-terminal amino acid sequencing showed that cleavage at the His252-Ala253 peptide bond facilitated the conversion of the zymogen into the active enzyme. Sequence alignment revealed the presence of two highly conserved motifs, HEXXH and GXXNEXXSD, indicating that the enzyme belonged to the metalloproteinase family M4, also known as thermolysin-like proteinases (TLPs). Further structural analysis showed that the observed calcium-dependent stability of the BD3526 TLP may be attributable to a partly degenerated calcium-binding site, Ca1-2, and a mutant calcium-binding site, Ca3.

Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).

EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play?

Constipation is a prevalent gastrointestinal disorder that seriously reduces the quality of life. Clinical studies have shown that a great change or severe imbalance occurs in the intestinal microbiota of people with constipation. This study explored whether bacteriocin-producing and non-bacteriocin-producing Pediococcus acidilactici strains resulted in differences in the alleviation of constipation and changes in the fecal flora in BALB/c mice. The constipation-related indicators, gastrointestinal regulatory peptides and gut microbiota were identified to evaluate their alleviating effects and underlying mechanisms. The time to the first black-stool defecation and the gastrointestinal transit rate in constipated mice were found to be somewhat improved by four P. acidilactici strains (P > 0.05). Moreover, there were significant differences in the level of most gastrointestinal regulatory peptides in the serum, as well as in the composition and abundance of intestinal microbiota in different groups (P < 0.05). At the phylum level, the relative abundance of Firmicutes was significantly increased, but those of Bacteroidetes and Proteobacteria were significantly reduced after the administration of four P. acidilactici strains for 14 d (P < 0.05). The levels of Bacteroides and genera from Enterobacteriaceae were significantly decreased, whereas Bifidobacterium and Lactobacillus were upregulated when bacteriocin-producing P. acidilactici CCFM18 and CCFM28 strains were provided in the diet (P < 0.05). The results indicated that although constipation-related symptoms were alleviated to only a limited degree, the administration of four P. acidilactici strains effectively regulated the gut flora and provided a potential health benefit to the host, especially the bacteriocin-producing P. acidilactici strains.

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Our previous studies demonstrated that eyes absent homolog 4 (EYA4), a member of the eye development-related EYA family in Drosophila, is frequently methylated and silenced in hepatocellular carcinoma (HCC) specimens and associated with shorter survival. The current work aimed to explore the mechanisms through which EYA4 functions as a tumor suppressor in HCC.

Ebola virus (EBOV) can cause severe hemorrhagic fever in humans, and no approved treatment is currently available. Although several antibodies have achieved good protection in animal models, the potential emerging isolates of ebolavirus and the unknown effects of experimental antibodies in humans underscore the need to develop additional antibodies to address the threat of Ebola. Here, we isolated a series of memory B cell-derived monoclonal antibodies from healthy Chinese adults vaccinated with Ad5-EBOV. These antibodies were encoded by diverse germline genes and had high levels of somatic hypermutation. Most antibodies were cross-reactive and could bind at least two ebolavirus glycoproteins (GPs). Seven neutralizing antibodies were identified using HIV-EBOV GP-Luc pseudovirus, and they effectively neutralized authentic EBOV. In particular, monoclonal antibody 2G1 exhibited potent cross-neutralization against HIV-EBOV/SUDV/BDBV GP-Luc bearing different ebolavirus GPs. We used truncated GPs, competition assays, and software prediction to analyze seven neutralizing antibodies, which bound four different epitopes on GP. Importantly, three of these antibodies provided complete protection in mice when administered one day post-infection. Our study expands the list of candidate antibodies and the options for successfully treating ebolavirus infection.

Pediococcus pentosaceus isolated from fermented food and the gastrointestinal tracts of humans and animals have been widely identified, and some strains have been reported to reduce inflammation, encephalopathy, obesity and fatty liver in animals. In this study, the genomes of 65 P. pentosaceus strains isolated from human and animal feces and different fermented food were sequenced and comparative genomics analysis was performed on all strains along with nine sequenced representative strains to preliminarily reveal the lifestyle of P. pentosaceus, and investigate the genomic diversity within this species. The results reveal that P. pentosaceus is not host-specific, and shares core genes encoding proteins related to translation, ribosomal structure and biogenesis and signal transduction mechanisms, while its genetic diversity relates mainly to carbohydrate metabolism, and horizontally transferred DNA, especially prophages and bacteriocins encoded on plasmids. Additionally, this is the first report of a type IIA CRISPR/Cas system in P. pentosaceus. This work provides expanded resources of P. pentosaceus genomes, and offers a framework for understanding the biotechnological potential of this species.

Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved intracellular protein that is involved in the maturation of the Fe/S protein, iron regulatory protein 1 (IRP1), and the mitochondria-related apoptosis of gastrointestinal stromal tumor cells. In this study, we used a mouse model of chemically induced colitis to investigate the physiological role of FAM96A in intestinal homeostasis and inflammation. At baseline, colons from Fam96a-/- mice exhibited microbial dysbiosis, dysregulated epithelial cell turnover, an increased number of goblet cells, and disordered tight junctions with functional deficits affecting intestinal permeability. After cohousing, the differences between wild-type and Fam96a-/- colons were abrogated, suggesting that FAM96A affects colonic epithelial cells in a microbiota-dependent manner. Fam96a deficiency in mice resulted in increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Importantly, the colitogenic activity of Fam96a-/- intestinal microbiota was transferable to wild-type littermate mice via fecal microbial transplantation (FMT), leading to exacerbation of DSS-induced colitis. Taken together, our data indicate that FAM96A helps to maintain colonic homeostasis and protect against DSS-induced colitis by preventing gut microbial dysbiosis. This study used gene knockout animals to help to understand the in vivo effects of the Fam96a gene for the first time and provides new evidence regarding host-microbiota interactions.

Lysogenic bacterial strains abound in the Lactobacillus genus and contain dormant prophages inserted within their genomes. To evaluate the prophage-induction potential of the Lactobacillus strains of six species, 142 randomly selected strains from these species were induced with Mitomycin C. Eight newly-induced phages were identified and found to be diverse in morphology. Among the six species assessed, Lactobacillus plantarum and Lactobacillus rhamnosus strains were generally insensitive to induction. The genomic characterizations of eight phages were performed via whole genome sequencing and protein prediction. Meanwhile, genome comparison of the induced phages and predicted prophages demonstrated that the prediction software PHASTER can accurately locate major prophage regions in Lactobacillus. A phylogenetic tree of the Lactobacillus phage population was constructed to obtain further insights into the clustering of individuals, two major groups were found, one of which consisted mostly of L. plantarum virulent phages, the other was represented by Lactobacillus casei/paracasei temperate phages. Finally, it was confirmed via genomic collinear analysis, which seven of the eight Lactobacillus temperate phages were newly discovered, and two Lactobacillus brevis temperate phages belonged to a novel lineage.

Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results.

gastritis is a common stomach disease with a high global incidence and can potentially develop into gastric cancer. The treatment of gastritis focuses on medication or diets based on national guidelines. However, the specific diet that can alleviate gastritis remains largely unknown.

Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.

Campylobacter jejuni is the major micro-bacillary pathogen responsible for human coloenteritis. Lactic acid bacteria (LAB) have been shown to protect against Campylobacter infection. However, LAB with a good ability to inhibit the growth of C. jejuni in vitro are less effective in animals and animal models, and have the disadvantages of high cost, a long cycle, cumbersome operation and insignificant immune response indicators. Caenorhabditis elegans is increasingly used to screen probiotics for their anti-pathogenic properties. However, no research on the use of C. elegans to screen for probiotic candidates antagonistic to C. jejuni has been conducted to date.