R/DWD: distance-weighted discrimination for classification, visualization and batch adjustment

Summary: R/DWD is an extensible package for classification. It is built based on a recently developed powerful classification method called distance weighted discrimination (DWD). DWD is related to, and has been shown to be superior to, the support vector machine in situations that are fundamental to bioinformatics, such as very high dimensional data. DWD has proven to be very useful for several fundamental bioinformatics tasks, including classification, data visualization and removal of biases, such as batch effects. Earlier DWD implementations, however, relied on Matlab, which is not free and requires a license. The major contribution of the R/DWD package is an implementation that is completely in R and thus can be used without any requirements for licensing or software purchase. In addition, R/DWD also provides efficient solvers for second-order-cone-programming and quadratic programming

Regulatory T Cells and Plasmacytoid Dendritic Cells Within the Tumor Microenvironment in Gastric Cancer Are Correlated With Gastric Microbiota Dysbiosis: A Preliminary Study

Substantial evidence indicates that gastric microbiota dysbiosis, immune system dysfunction especially immune escape are critical for gastric cancer (GC) occurrence and progression. As two important elements of tumor microenvironment (TME), the relationship between gastric microbiota and tumor-immune microenvironment is still unclear. Our present study aimed to explore the correlation between gastric mucosal microbiota in different microhabitats and its corresponding gastric immunosuppressive cells such as regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) in the TME. A cohort of 64 GC patients without preoperative chemotherapy was enrolled retrospectively, and 60 normal, 61 peritumoral and 59 tumoral tissues were obtained for gastric mucosal microbiota analysis and immunohistochemistry analysis. From different microhabitats, BDCA2+pDCs and Foxp3+Tregs were observed positively correlated, and increased in tumoral and peritumoral tissues compared to normal ones. The diversity, composition and function of gastric mucosal microbiota also changed more significantly in tumoral tissues than those in normal and peritumoral ones. With pearson's correlation analysis, we found that several non-abundant genera such as Stenotrophomonas and Selenomonas were positively correlated with BDCA2+pDCs and Foxp3+Tregs, respectively, while Comamonas and Gaiella were negatively correlated with BDCA2+pDCs and Foxp3+ Tregs, respectively. The increased BDCA2+pDCs and Foxp3+Tregs might be modulated by gastric mucosal microbiota, both participated in the immunosuppression microenvironment of GC, which might provide evidence to establish new strategies in antitumor therapy targeting on gastric microbiota

Advances in the diagnosis of non-occlusive mesenteric ischemia and challenges in intra-abdominal sepsis patients: a narrative review

Non-occlusive mesenteric ischemia (NOMI) is a type of acute mesenteric ischemia (AMI) with a high mortality rate mainly because of a delayed or misdiagnosis. Intra-abdominal sepsis is one of the risk factors for developing NOMI, and its presence makes early diagnosis much more difficult. An increase in routine abdominal surgeries carries a corresponding risk of abdominal infection, which is a complication that should not be overlooked. It is critical that physicians are aware of the possibility for intestinal necrosis in abdominal sepsis patients due to the poor survival rate of NOMI. This review aims to summarize advances in the diagnosis of NOMI, and focuses on the diagnostic challenges of mesenteric ischemia in patients with intra-abdominal sepsis

Alterations of gastric mucosal microbiota across different stomach microhabitats in a cohort of 276 patients with gastric cancerResearch in context

Background: As part of the tumor microenvironment, the gastric microbiota play vital roles in tumor initiation, progression and metastasis, but stomach microhabitats are not always uniform. We aimed to characterize differences of gastric microbiota in stomach microhabitats associated with gastric cancer (GC) development. Methods: A cohort of 276 GC patients without preoperative chemotherapy was enrolled retrospectively, and 230 normal, 247 peritumoral and 229 tumoral tissues were obtained for gastric microbiota analysis targeting the 16S rRNA gene by MiSeq sequencing. The microbial diversity and composition, bacterial co-occurrence correlations and predictive functional profiles were compared across different microhabitats. Findings: GC-specific stomach microhabitats, not GC stages or types, determine the composition and diversity of the gastric microbiota. Most notably, bacterial richness was decreased in peritumoral and tumoral microhabitats, and the correlation network of abundant gastric bacteria was simplified in tumoral microhabitat. Helicobacter pylori (HP), Prevotella copri and Bacteroides uniformis were significantly decreased, whereas Prevotella melaninogenica, Streptococcus anginosus and Propionibacterium acnes were increased in tumoral microhabitat. Higher HP colonisation influenced the overall structure of the gastric microbiota in normal and peritumoral microhabitats. PiCRUSt analysis revealed that genes associated with nucleotide transport and metabolism and amino acid transport and metabolism were significantly enriched in tumoral microbiota, while gastric acid secretion was significantly higher in HP positive group of the tumoral microbiota. Interpretation: Our present study provided new insights into the roles of gastric microbiota in different stomach microhabitats in gastric carcinogenesis, especially the pathogenesis of HP. Fund: National Natural Science Foundation of China. Keywords: Gastric cancer, Gastric microbiota, Helicobacter pylori, Stomach microhabitat, Tumor microenvironmen

CCR9-CCL25 mediated plasmacytoid dendritic cell homing and contributed the immunosuppressive microenvironment in gastric cancer

Objectives: Plasmacytoid dendritic cells (pDCs) play a crucial role in the microenvironment of tumor. Evidences has been shown that chemokine receptor 9 (CCR9) is an important molecule that attracts pDCs homing to the digestive tract and the latter are involved in the formation of digestive tract immune tolerance. The aim of this study was to explore the role of CCR9-CCL25 interaction in pDC-mediated immunosuppression microenvironment of gastric cancer (GC). Materials and methods: Regulatory T cells (Tregs) and pDCs were detected by immunohistochemistry. CCR9, which expressed on pDC was visualized by immunofluorescence. Western Blot was applied to evaluate the expression of CCL-25. Total pDCs, CCR9+pDCs, CCR9−pDCs, total Tregs, inducible costimulator + (ICOS) Tregs and ICOS−Tregs in peripheral blood and draining lymph nodes were analyzed by flow cytometry. Plasma concentration of the cytokines were measured by enzyme-linked immunosorbent assay Results: Total Tregs, pDCs and CCR9+pDCs were higher in GC tissue. CCL-25 was over-expressed in carcinoma tissue. Peripheral total pDCs, CCR9−pDCs, total Tregs, ICOS+ Tregs, ICOS− Tregs were significantly increased in GC patients. More total pDCs, CCR9+ pDCs, total Tregs, ICOS+ Tregs were found in metastatic lymph nodes. Plasma concentrations of IL-6 and IL-10 were significantly higher in GC patients. More CCR9+ pDCs were found infiltrating carcinoma tissue in patients with later T staging and lymph node metastasis and conferred a poor prognosis. Conclusion: CCR9-CCL25 interaction might play an important role in mediating PDC homing to metastatic lymph nodes and carcinoma tissue, which contributed to the formation of tumor immunosuppressive microenvironment and poor prognosis

Function and expression of cystic fibrosis transmembrane conductance regulator after small intestinal transplantation in mice.

The secretion function of intestinal graft is one of the most important factors for successful intestinal transplantation. Cystic fibrosis transmembrane conductance regulator (CFTR) mediates HCO3(-) and Cl(-) secretions in intestinal epithelial cells. In this study, we made investigation on the expression and function of CFTR in an experimental model of murine small intestinal transplantation. Heterotopic intestinal transplantations were performed in syngeneic mice. The mRNA and protein expressions of CFTR were analyzed by real time PCR and western blot. Murine intestinal mucosal HCO3(-) and Cl(-) secretions were examined in vitro in Ussing chambers by the pH stat and short circuit current (I(sc)) techniques. The results showed that forskolin, an activator of CFTR, stimulated jejunal mucosal epithelial HCO3(-) and Cl(-) secretions in mice, but forskolin-stimulated HCO3(-) and Cl(-) secretions in donor and recipient jejunal mucosae of mice after heterotopic jejunal transplantation were markedly decreased, compared with controls (P<0.001). The mRNA and protein expression levels of CFTR in donor and recipient jejunal mucosae of mice were also markedly lower than those in controls (P<0.001), and the mRNA and protein expression levels of tumor necrosis factor α (TNFα) were markedly increased in donor jejunal mucosae of mice (P<0.001), compared with controls. Further experiments showed that TNFα down-regulated the expression of CFTR mRNA in murine jejunal mucosa. In conclusion, after intestinal transplantation, the function of CFTR was impaired, and its mRNA and protein expressions were down-regulated, which may be induced by TNFα

Continuous biodiesel production under subcritical condition of methanol - Design of pilot plant and packed bed reactor with MnCO3/Na-silicate catalyst

The continuous biodiesel production from soybean oil was carried out under the subcritical condition of methanol with MnCO3/Na-silicate as a heterogeneous catalyst. The transesterification rate was first investigated in a set of experiments performed in a batch autoclave at 448 K using methanol-to-oil molar ratio of 18:1 and various catalyst loadings (5, 10 and 20 wt% based on the oil mass). The results from these experiments, as well as the experimental data and the appropriate kinetic model recently reported in the literature were used for designing a packed bed tubular reactor (PBTR), a main unit of the pilot plant with the capacity of 100 L of biodiesel per day. The pilot plant was constructed and tested under various operating conditions. The first 11 h of the pilot-plant operation was realized in the tubular reactor packed with inert glass beads (i.e. without the catalyst) in order to analyze the effect of the non-catalyzed subcritical biodiesel (fatty acid methyl esters, FAME) production. Then, glass beads were replaced with a mix of MnCO3/Na-silicate catalyst particles and glass beads, and the catalytic biodiesel production was continuously run under the subcritical methanol condition for 85 h. Two mass balance tests during the continuous pilot plant operation were performed

Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients.

Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b(+), CD68(+), and FoxP3(+) cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Furthermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17(+) cells, as well as MCT(+) IL-17(+) cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy