A TCR mechanotransduction signaling loop induces negative selection in the thymus.

The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR-pMHC-CD8 trimolecular 'catch bonds', whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR-pMHC and pMHC-CD8 bimolecular 'slip bonds'. Catch bonds were not intrinsic to either the TCR-pMHC or the pMHC-CD8 arm of the trans (cross-junctional) heterodimer but resulted from coupling of the extracellular pMHC-CD8 interaction to the intracellular interaction of CD8 with TCR-CD3 via associated kinases to form a cis (lateral) heterodimer capable of inside-out signaling. We suggest that the coupled trans-cis heterodimeric interactions form a mechanotransduction loop that reinforces negative-selection signaling that is distinct from positive-selection signaling in the thymus.

Polyoxometalate Functionalized Cyclic Trinuclear Copper Compounds for Bifunctional Electrochemical Detection and Photocatalytic Reduction of Cr(VI).

The design and intentional construction of crystalline materials containing two clusters with redox properties in one framework still remains challenging. Linking oxidative polyoxometalate (POM) clusters and a reductive cyclic trinuclear copper complex (Cu-CTC) to prepare stable catalysts is rarely reported. Herein, we successfully obtained two new polyoxometalate-based metal-organic compounds (POMOCs) [CuII3(PyCA)3(µ3-OH)(ß-Mo8O26)0.5(H2O)2]·5H2O (1), [CuII3(PyCA)3(µ3-OH)]2(CuIIW12O40)[CuII(H2O)6] (2) (PyCA = 1H-pyrazole-4-carbaldehyde) by enabling precursors of Cu-CTC and POM cocrystallization in one pot via hydrothermal method. The [ß-Mo8O26]4- cluster in compound 1 combined with Cu-CTC units to form a 1D structure, and the [CuW12O40]6- unit in compound 2 linked two Cu-CTC units to form a sandwich-like 0D structure. Also, Cu-CTC CuI3(PyCA)3·H2O (Cu3) was synthesized for performance comparison. A series of characterizations indicate that compound 1 is more conducive to electron transfer than compound 2. In addition, compounds 1 and 2 can act as bifunctional catalysts for the electrochemical detection and photocatalytic reduction of Cr(VI). Particularly, the photoreduction rates of Cr(VI) by compounds 1 and 2 are 96.7% and 96.3% for only 10 and 14 min under visible light, respectively, and it is better than that of Cu3 and most other reported photocatalysts. Furthermore, the active sites and mechanisms for electrochemical detection and photocatalytic reduction of Cr(VI) were discussed.

Comparison of linear energy transfer measurement for therapeutic carbon beam using CR-39 and TLD.

The measurement of linear energy transfer (LET) is crucial for the evaluation of the radiation effect in heavy ion therapy. As two detectors which are convenient to implant into the phantom, the performance of CR-39 and thermoluminescence detector (TLD) for LET measurement was compared by experiment and simulation in this study. The results confirmed the applicability of both detectors for LET measurements, but also revealed that the CR-39 detector would lead to potential overestimation of dose-averaged LET compared with the simulation by PHITS, while the TLD would have a large uncertainty measuring ions with LET larger than 20 keVµm-1. The results of this study were expected to improve the detection method of LET for therapeutic carbon beam and would finally be benefit to the quality assurance of heavy ion radiotherapy.

The kinetics of E-selectin- and P-selectin-induced intermediate activation of integrin αLß2 on neutrophils.

Selectins and integrins are key players in the adhesion and signaling cascade that recruits leukocytes to inflamed tissues. Selectin binding induces ß2 integrin binding to slow leukocyte rolling. Here, a micropipette was used to characterize neutrophil adhesion to E-selectin and intercellular adhesion molecule-1 (ICAM-1) at room temperature. The time-dependent adhesion frequency displayed two-stage kinetics, with an E-selectin-mediated fast increase to a low plateau followed by a slow increase to a high plateau mediated by intermediate-affinity binding of integrin αLß2 to ICAM-1. The αLß2 activation required more than 5 s contact to E-selectin and spleen tyrosine kinase (Syk) activity. A multi-zone channel was used to analyze αLß2 activation by P-selectin in separate zones of receptors or antibodies, finding an inverse relationship between the rolling velocity on ICAM-1 and P-selectin dose, and a P-selectin dose-dependent change from bent to extended conformations with a closed headpiece that was faster at 37°C than at room temperature. Activation of αLß2 exhibited different levels of cooperativity and persistent times depending on the strength and duration of selectin stimulation. These results define the precise timing and kinetics of intermediate activation of αLß2 by E- and P-selectins.

The role of main pancreatic duct stent in the enucleation of benign/borderline pancreatic head tumors: a cohort study.

PURPOSE: This study aimed to reveal the role of preoperative main pancreatic duct (MPD) stent placement in reducing the intraoperative main pancreatic duct injury rate and the incidence of postoperative pancreatic leakage following pancreatic tumor enucleation. METHODS: A retrospective cohort analysis was performed for all patients with benign/borderline pancreatic head tumors who were treated with enucleation. The patients were divided into two groups (standard vs. stent) depending on whether they underwent main pancreatic duct stent placement prior to surgery. RESULTS: Thirty-three patients were finally included in the analytical cohort. Compared with the standard group, patients in the stent group had a shorter distance between tumors and main pancreatic duct (p=0.01) and presented with larger tumors (p<0.01). The rates of POPF (grade B&C) were 39.1% (9/23) and 20% (2/10) in the standard and stent groups, respectively (p<0.01). Major postoperative complications occurred more frequently in the standard group than in the stent group (14 versus 2; p<0.01). No significant differences in mortality, in-hospital stay or medical cost were observed between the two groups (p>0.05). CONCLUSIONS: MPD stent placement prior to surgery may facilitate pancreatic tumor enucleation, minimize MPD injury and decrease the occurrence of postoperative fistula.

Clinical significance of hemoglobin level and blood transfusion therapy in elderly sepsis patients: A retrospective analysis.

INTRODUCTION: The clinical significance of hemoglobin level and blood transfusion therapy in elderly sepsis patients remains controversial. The study investigated the relationship between mortality, hemoglobin levels, and blood transfusion in elderly sepsis patients. METHODS: Elderly sepsis patients were included in the Marketplace for Medical Information in Intensive Care (MIMIC-IV) database. A multivariate regression model analyzed the relationship between the Hb level and the 28-day mortality risk. Logistic Multivariate analysis, Propensity Matching (PSM) analysis, an Inverse Probabilities Weighting (IPW) model and doubly robust estimation were applied to analyze the 28-day mortality risk between transfused and non-transfused patients in Hb at 7-8 g/dL, 8-9 g/dL, 9-10 g/dL, and 10-11 g/dL groups. RESULTS: 7473 elderly sepsis patients were enrolled in the study. The Hb level in the ICU and the 28-day mortality risk of patients with sepsis shared a non-linear relationship. The patients with Hb levels of <10 g/dL(p < 0.05) and > 15 g/dL(p < 0.05) within 24 h had a high mortality risk in multivariate analysis. In the Hb level 7-8 g/dL and 8-9 g/dL subgroup, the Multivariate analysis (p < 0.05), PSM (p < 0.05), IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could reduce the mortality risk. In the subgroup with a Hb level of 10-11 g/dL, IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could increase the mortality risk of elderly sepsis patients. CONCLUSION: A non-linear relationship between the Hb level and the 28-day mortality risk and Hb levels of <10 g/dL and > 15 g/dL may increase the mortality risk, and blood transfusion with a Hb level of <9 g/dL may minimize mortality risk in elderly sepsis patients.

Luminescence intensity ratio thermometry based on combined ground and excited states absorptions of Tb3+ doped CaWO4.

Luminescence intensity ratio (LIR) thermometry is of great interest, because of its wide applications of noninvasive temperature sensing. Here, a LIR thermometry based on combined ground and excited states absorptions is developed using CaWO4:Tb3+. The ratio of single luminescence (5D4-7F5) intensities under 379 and 413 nm excitations with opposite temperature dependences, attributed to the thermal coupling of ground state 7F6 and excited state 7F5, is used to measure temperature. This LIR method achieves a high relative sensitivity of 2.8% K-1, and can avoid complex spectral splitting by collecting all down-shifting luminescence bands, being a promising accurate luminescence thermometry.

Spatial Heterojunction in Nanostructured TiO2 and Its Cascade Effect for Efficient Photocatalysis.

A highly efficient photoenergy conversion is strongly dependent on the cumulative cascade efficiency of the photogenerated carriers. Spatial heterojunctions are critical to directed charge transfer and, thus, attractive but still a challenge. Here, a spatially ternary titanium-defected TiO2@carbon quantum dots@reduced graphene oxide (denoted as VTi@CQDs@rGO) in one system is shown to demonstrate a cascade effect of charges and significant performances regarding the photocurrent, the apparent quantum yield, and photocatalysis such as H2 production from water splitting and CO2 reduction. A key aspect in the construction is the technologically irrational junction of Ti-vacancies and nanocarbons for the spatially inside-out heterojunction. The new "spatial heterojunctions" concept, characteristics, mechanism, and extension are proposed at an atomic-/nanoscale to clarify the generation of rational heterojunctions as well as the cascade electron transfer.

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.

Analysis of nifH DNA and RNA reveals a disproportionate contribution to nitrogenase activities by rare plankton-associated diazotrophs.

BACKGROUND: Holobionts comprising nitrogen-fixing diazotrophs and phytoplankton or zooplankton are ubiquitous in the pelagic sea. However, neither the community structure of plankton-associated diazotrophs (PADs) nor their nitrogenase transcriptional activity are well-understood. In this study, we used nifH gene Illumina sequencing and quantitative PCR to characterize the community composition and nifH expression profile of PADs with > 100 µm size fraction in the euphotic zone of the northern South China Sea. RESULTS: The results of DNA- and RNA-derived nifH gene revealed a higher alpha-diversity in the active than in the total community. Moreover, the compositional resemblance among different sites was less for active than for total communities of PADs. We characterized the 20 most abundant OTUs by ranking the sum of sequence reads across 9 sampling stations for individual OTUs in both nifH DNA and RNA libraries, and then assessed their phylogenetic relatedness. Eight of the 20 abundant OTUs were phylogenetically affiliated with Trichodesmium and occurred in approximately equal proportion in both the DNA and RNA libraries. The analysis of nifH gene expression level showed uneven attribute of the abundance and nitrogenase activities by the remaining 12 OTUs. Taxa belonging to cluster III and Betaproteobacteria were present at moderate abundance but exhibited negligible nitrogenase transcription activity. Whereas, the abundances of Richelia, Deltaproteobacteria and Gammaproteobacteria were low but the contribution of these groups to nitrogenase transcription was disproportionately high. CONCLUSIONS: The substantial variation in community structure among active dizatrophic fractions compared to the total communities suggests that the former are better indicators of biological response to environmental changes. Altogether, our study highlights the importance of rare PADs groups in nitrogen fixation in plankton holobionts, evidenced by their high level of nitrogenase transcription.

A systematic review and meta-analysis of the overall effects of school-based obesity prevention interventions and effect differences by intervention components.

BACKGROUND: Childhood obesity is a serious public health concern. School-based interventions hold great promise to combat the rising trend of childhood obesity. This systematic review aimed to assess the overall effects of school-based obesity prevention interventions, and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity. METHODS: We systematically searched MEDLINE, CENTRAL and Embase databases to identify randomized- or cluster randomized- controlled trials of school-based obesity interventions published between 1990 and 2019. We conducted meta-analyses and subgroup analyses to determine the overall effects of obesity prevention programs and effect differences by various characteristics of intervention components on body mass index (BMI) or BMI Z-score of children. RESULTS: This systematic review included a total of 50 trials (reported by 56 publications). Significant differences were found between groups on BMI (- 0.14 kg/m2 (95% confidence interval: - 0.21, - 0.06)) and BMI Z-score (- 0.05 (- 0.10, - 0.01)) for single-component interventions; significant differences were also found between groups on BMI (- 0.32 (- 0.54, - 0.09) kg/m2) and BMI Z-score (- 0.07 (- 0.14, - 0.001)) for multi-component interventions. Subgroup analyses consistently demonstrated that effects of single-component (physical activity) interventions including curricular sessions (- 0.30 (- 0.51, - 0.10) kg/m2 in BMI) were stronger than those without curricular sessions (- 0.04 (- 0.17, 0.09) kg/m2 in BMI); effects of single-component (physical activity) interventions were also strengthened if physical activity sessions emphasized participants' enjoyment (- 0.19 (- 0.33, - 0.05) kg/m2 in BMI for those emphasizing participants' enjoyment; - 0.004 (- 0.10, 0.09) kg/m2 in BMI for those not emphasizing participants' enjoyment). The current body of evidence did not find specific characteristics of intervention components that were consistently associated with improved efficacy for multi-component interventions (P > 0.05). CONCLUSIONS: School-based interventions are generally effective in reducing excessive weight gain of children. Our findings contribute to increased understandings of potentially effective intervention characteristics for single-component (physical activity) interventions. The impact of combined components on effectiveness of multi-component interventions should be the topic of further research. More high-quality studies are also needed to confirm findings of this review.

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species.

The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.

The pro-fibrotic role of dipeptidyl peptidase 4 in carbon tetrachloride-induced experimental liver injury.

Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice. DPP4 gko had less liver fibrosis and inflammation and fewer B cell clusters than wild type mice in the fibrosis model. DPP4 inhibitor-treated mice also developed less liver fibrosis. DNA microarray and PCR showed that many immunoglobulin (Ig) genes and some metabolism-associated transcripts were differentially expressed in the gko strain compared with wild type. CCl4-treated DPP4 gko livers had more IgM+ and IgG+ intrahepatic lymphocytes, and fewer CD4+, IgD+ and CD21+ intrahepatic lymphocytes. These data suggest that DPP4 is pro-fibrotic in CCl4-induced liver fibrosis and that the mechanisms of DPP4 pro-fibrotic action include energy metabolism, B cells, NK cells and CD4+ cells.

Circulating Tumor Cells and Circulating Tumor DNA Provide New Insights into Pancreatic Cancer.

Pancreatic cancer has a rather dismal prognosis mainly due to high malignance of tumor biology. Up to now, the relevant researches on pancreatic cancer lag behind seriously partly due to the obstacles for tissue biopsy, which handicaps the understanding of molecular and genetic features of pancreatic cancer. In the last two decades, liquid biopsy, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), is promising to provide new insights into the biological and clinical characteristics of malignant tumors. Both CTCs and ctDNA provide an opportunity for studying tumor heterogeneity, drug resistance, and metastatic mechanism for pancreatic cancer. Furthermore, they can also play important roles in detecting early-stage tumors, providing prognostic information, monitoring tumor progression and guiding treatment regimens. In this review, we will introduce the latest findings on biological features and clinical applications of both CTCs and ctDNA in pancreatic cancer. In a word, CTCs and ctDNA are promising to promote precision medicine in pancreatic cancer.

Transduodenal ampullectomy provides a less invasive technique to cure early ampullary cancer.

BACKGROUND: The aim of this study was to evaluate the clinical efficiency of transduodenal ampullectomy (TDA) compared to conventional pancreatoduodenectomy (PD) in patients with early ampullary cancers. METHODS: We carried out a retrospective study by reviewing the medical records of 43 patients with early ampullary cancer who underwent either TDA or PD from January 2001 to December 2014. TDA and PD were performed on 22 patients and 21 patients, respectively. Clinical data, perioperative clinical outcomes and prognosis were evaluated. The median follow-up was 75 (range, 38-143) months. RESULTS: The sensitivity of intraoperative frozen resection was 100 % (4/4) and 94.9 % (37/39) in patients with pTis and pT1 tumors compared to final histologic diagnoses. The 5-year survival rate of patients with early ampullary cancer was 77.3 % in TDA group and 75.9 % in PD group (P = 0.927). Patients with lymph node metastasis presented a shorter 5-year survival rate (P = 0.014). TDA was associated with lower surgical morbidity (P = 0.033), estimated blood loss (P = 0.002), medical cost (P = 0.028) compared to PD. No pancreatic fistula and surgical mortality occurred in TDA group. CONCLUSIONS: TDA could produce satisfactory clinical efficiency in patients fulfilled the following criteria simultaneously: pTis or pT1 stage, tumor size ≤ 2 cm, without lymph node metastasis. To achieve favorable outcomes, intraoperative frozen section examinations should be reliable and resection margins should be negative.

Responses of bacterial communities in seagrass sediments to polycyclic aromatic hydrocarbon-induced stress.

The seagrass meadows represent one of the highest productive marine ecosystems, and have the great ecological and economic values. Bacteria play important roles in energy flow, nutrient biogeochemical cycle and organic matter turnover in marine ecosystems. The seagrass meadows are experiencing a world-wide decline, and the pollution is one of the main reasons. Polycyclic aromatic hydrocarbons (PAHs) are thought be the most common. Bacterial communities in the seagrass Enhalus acoroides sediments were analyzed for their responses to PAHs induced stress. Dynamics of the composition and abundance of bacterial communities during the incubation period were explored by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and quantitative PCR assay, respectively. Both the incubation time and the PAHs concentration played significant roles in determining the microbial diversity, as reflected by the detected DGGE bands. Analysis of sequencing results showed that the Gammaproteobacteria were dominant in the seagrass sediments, accounting for 61.29 % of all sequenced bands. As PAHs could be used as carbon source for microbes, the species and diversity of the PAH-added groups (group 1 and 2) presented higher Shannon Wiener index than the group CK, with the group 1 showing the highest values almost through the same incubation stage. Patterns of changes in abundance of the three groups over the experiment time were quite different. The bacterial abundance of the group CK and group 2 decreased sharply from 4.15 × 10(11) and 6.37 × 10(11) to 1.17 × 10(10) and 1.07 × 10(10) copies/g from day 2 to 35, respectively while bacterial abundance of group 1 increased significantly from 1.59 × 10(11) copies/g at day 2 to 8.80 × 10(11) copies/g at day 7, and then dropped from day 14 till the end of the incubation. Statistical analysis (UMPGA and PCA) results suggested that the bacterial community were more likely to be affected by the incubation time than the concentration of the PAHs. This study provided the important information about dynamics of bacterial community under the PAHs stress and revealed the high bacterial diversity in sediments of E. acoroides. Investigation results also indicated that microbial community structure in the seagrass sediment were sensible to the PAHs induced stress, and may be used as potential indicators for the PAHs contamination.

Illumina-based analysis the microbial diversity associated with Thalassia hemprichii in Xincun Bay, South China Sea.

In order to increase our understanding of the microbial diversity associated with seagrass Thalassia hemprichii in Xincun Bay, South China Sea, 16S rRNA gene was identified by highthrough sequencing method. Bacteria associated with seagrass T. hemprichii belonged to 37 phyla, 99 classes. The diversity of bacteria associated with seagrass was similar among the geographically linked coastal locations of Xincun Bay. Proteobacteria was the dominant bacteria and the α-proteobacteria had adapted to the seagrass ecological niche. As well, α-proteobacteria and Pseudomonadales were associated microflora in seagrass meadows, but the interaction between the bacteria and plant is needed to further research. Burkholderiales and Verrucomicrobiae indicated the influence of the bay from anthropogenic activities. Further, Cyanobacteria could imply the difference of the nutrient conditions in the sites. γ-proteobacteria, Desulfobacterales and Pirellulales played a role in the cycle of sulfur, organic mineralization and meadow ecosystem, respectively. In addition, the less abundance bacteria species have key functions in the seagrass meadows, but there is lack knowledge of the interaction of the seagrass and less abundance bacteria species. Microbial communities can response to surroundings and play key functions in the biochemical cycle.

The diversity of coral associated bacteria and the environmental factors affect their community variation.

Coral associated bacterial community potentially has functions relating to coral health, nutrition and disease. Culture-free, 16S rRNA based techniques were used to compare the bacterial community of coral tissue, mucus and seawater around coral, and to investigate the relationship between the coral-associated bacterial communities and environmental variables. The diversity of coral associated bacterial communities was very high, and their composition different from seawater. Coral tissue and mucus had a coral associated bacterial community with higher abundances of Gammaproteobacteria. However, bacterial community in seawater had a higher abundance of Cyanobacteria. Different populations were also found in mucus and tissue from the same coral fragment, and the abundant bacterial species associated with coral tissue was very different from those found in coral mucus. The microbial diversity and OTUs of coral tissue were much higher than those of coral mucus. Bacterial communities of corals from more human activities site have higher diversity and evenness; and the structure of bacterial communities were significantly different from the corals collected from other sites. The composition of bacterial communities associated with same coral species varied with season's changes, geographic differences, and coastal pollution. Unique bacterial groups found in the coral samples from more human activities location were significant positively correlated to chemical oxygen demand. These coral specific bacteria lead to coral disease or adjust to form new function structure for the adaption of different surrounding needs further research.

H19 promotes pancreatic cancer metastasis by derepressing let-7's suppression on its target HMGA2-mediated EMT.

The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.

SUMO-specific protease 1 regulates pancreatic cancer cell proliferation and invasion by targeting MMP-9.

SUMOylation is a dynamic process which can be reversed by a family of sentrin/SUMO-specific protease (SENPs). Recently, SENP1, a member of SENPs family was shown to have a pro-oncogenic role in many types of cancer. Here, we showed that SENP1 was upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues. Moreover, clinical data showed that SENP1 was positively associated with lymph node metastasis and TNM stage. Furthermore, knockdown of SENP1 by SENP1-siRNA inhibited pancreatic cancer cell proliferation, migration, and invasion, suggesting that SENP1 played an important role in PDAC progression and metastasis. Mechanistically, silencing of SENP1 results in downregulation of MMP-9, which is pivotal for PDAC cell growth and migration. Taken together, these results suggest that SENP1 may serve as a potential novel diagnostic and therapeutic target of PDAC.