Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis.

The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases.

A dRASSF-STRIPAK-Imd-JAK/STAT axis controls antiviral immune response in Drosophila.

Host antiviral immunity suffers strong pressure from rapidly evolving viruses. Identifying host antiviral immune mechanisms has profound implications for developing antiviral strategies. Here, we uncover an essential role for the tumor suppressor Ras-association domain family (RASSF) in Drosophila antiviral response. Loss of dRassf in fat body leads to increased vulnerability to viral infection and impaired Imd pathway activation accompanied by detrimental JAK/STAT signaling overactivation. Mechanistically, dRASSF protects TAK1, a key kinase of Imd pathway, from inhibition by the STRIPAK PP2A phosphatase complex. Activated Imd signaling then employs the effector Relish to interfere with the dimerization of JAK/STAT transmembrane receptor Domeless, therefore preventing excessive JAK/STAT signaling. Moreover, we find that RASSF and STRIPAK PP2A complex are also involved in antiviral response in human cell lines. Our study identifies an important role for RASSF in antiviral immunity and elucidates a dRASSF-STRIPAK-Imd-JAK/STAT signaling axis that ensures proper antiviral responses in Drosophila.

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma.

Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature on the basis of long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of patients with LUAD. We selected ARlncRNAs associated with prognosis to construct a model and divided each sample into different groups on the basis of risk score. The ARlncRNA signature could be recognized as an independent prognostic factor for patients with LUAD, and patients in the low-risk group had a greater survival advantage. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden. Low-risk patients had a higher PD-1, CTLA-4, and HAVCR2 expression and had a better efficacy of immune checkpoint inhibitors, including PD-1/CTLA-4 inhibitor. A reliable signature on the basis of ARlncRNAs was constructed to explore the TIME and prognosis of patients with LUAD, which could provide valuable information for individualized LUAD treatment.

Evaluation use of bioaugmentation and biostimulation to improve degradation of sulfolane in artificial groundwater.

Column systems were used to evaluate the effectiveness of different bioremediation methods (biostimulation (BS) and bioaugmentation (BA)) in treating sulfolane-contaminated groundwater. Batch test results confirmed that Cupriavidus sp. Y9 (Y9) was the most effective strain for BA. The optimal ratio of added native bacteria to Y9 was 10:3. The BA column adapted to a high sulfolane concentration (150 mg L-1) more rapidly and had higher sulfolane removal efficiency (90%) than did the BS column. The change in the biotoxicity of sulfolane-contaminated groundwater upon bioremediation, according to a Microtox test, revealed decreases in the inhibition of the passing of light by the BS column and BS + BA column of 38% and 63%, respectively. These results reveal that combining BS with BA can reduce the biotoxicity of sulfolane. The column tests confirmed the most effective added bacterium in BA, the operating conditions for high-efficiency bioremediation, and possible problems in its future application. The results provide an important reference for the design of methods for the remediation of contaminated sites.

Critical factors for enhancing the bioremediation of a toxic pollutant at high concentrations in groundwater: Toxicity evaluation, degrader tolerance, and microbial community.

Groundwater near refinery and natural gas plants often contain elevated concentrations of toxic sulfolane. Studies on any concentration of sulfolane are limited. Column experiment was conducted to investigate the effects of adding a low dose of H2O2 and nutrient on bioremediation. Vibrio fischeri light inhibition test was used evaluate the toxicity of effluents. The continuous column experiment conditions were sulfolane at 100 mg L-1, dissolved oxygen at 7 mg L-1, absence of phosphorus, and very short hydraulic retention time (7.9 h). A low dose of H2O2 (5.88 mM) enhanced the sulfolane (27.1%) and COD removal (11.8%) in comparison with the control set. Adding nutrient increased bicinchoninic acid protein assay levels, sulfolane removal (99.6%) and COD removal (80.3%). Addition of both H2O2 and nutrient further improved COD removal (90.3%) and COD/sulfolane ratio (0.90) and toxicity removal (Vibrio fischeri light inhibition ratio < 1%). Batch experiment indicated the degraders tolerated sulfolane up to 400 mg L-1. The DGGE method and dendrogram analysis were utilized to investigate the changes of degrader community structure.

Mono-ADP-ribosylation of histone 3 at arginine-117 promotes proliferation through its interaction with P300.

Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research, arginine-117 (Arg-117; R-117) of hsitone3(H3) is identified as the a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated ß-catenin, which could increase the expression of c-myc and cyclin D1.

[Epidemiology characteristics of crawfish related rhabdomyolysis in Nanjing, 2016: a multicenter retrospective investigation].

OBJECTIVE: To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016. METHODS: Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation. RESULTS: A total of 1 183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1 124 patients were enrolled. The proportion of men was 36.48% (410/1 124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1 124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: Moran I = 0.427, Z = 2.646, P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the "high-high" concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing. CONCLUSIONS: The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.