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Background: The prognostic roles of three lymph node classifications, number of positive lymph nodes (NPLN), log odds of positive lymph nodes (LODDS), and lymph node ratio (LNR) in lung adenocarcinoma are unclear. We aim to find the classification with the strongest predictive power and combine it with the American Joint Committee on Cancer (AJCC) 8th TNM stage to establish an optimal prognostic nomogram.Methods: 25,005 patients with T1-4N0-2M0 lung adenocarcinoma after surgery between 2004 to 2016 from the Surveillance, Epidemiology, and End Results database were included. The study cohort was divided into training cohort (13,551 patients) and external validation cohort (11,454 patients) according to different geographic region. Univariate and multivariate Cox regression analyses were performed on the training cohort to evaluate the predictive performance of NPLN (Model 1), LODDS (Model 2), LNR (Model 3) or LODDS+LNR (Model 4) respectively for cancer-specific survival and overall survival. Likelihood-ratio χ2 test, Akaike Information Criterion, Harrell concordance index, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to evaluate the predictive performance of the models. Nomograms were established according to the optimal models. They're put into internal validation using bootstrapping technique and external validation using calibration curves. Nomograms were compared with AJCC 8th TNM stage using decision curve analysis.Results: NPLN, LODDS and LNR were independent prognostic factors for cancer-specific survival and overall survival. LODDS+LNR (Model 4) demonstrated the highest Likelihood-ratio χ2 test, highest Harrell concordance index, and lowest Akaike Information Criterion, and IDI and NRI values suggested Model 4 had better prediction accuracy than other models. Internal and external validations showed that the nomograms combining TNM stage with LODDS+LNR were convincingly precise. Decision curve analysis suggested the nomograms performed better than AJCC 8th TNM stage in clinical practicability.Conclusions: We constructed online nomograms for cancer-specific survival and overall survival of lung adenocarcinoma patients after surgery, which may facilitate doctors to provide highly individualized therapy. [ABSTRACT FROM AUTHOR]

Background: Crucian carp is a popular ornamental strain in Asia with variants in body color. To further explore the genetic mechanisms underlying gray and red body color formation in crucian carp, the skin transcriptomes and partial DNA methylation sites were obtained from red crucian carp (RCC) and white crucian carp (WCC). Here, we show significant differences in mRNA expression and DNA methylation sites between skin tissues of RCC and WCC. Results: Totals of 3434 and 3683 unigenes had significantly lower and higher expression in WCC, respectively, compared with unigenes expressed in RCC. Some potential genes for body color development were further identified by quantitative polymerase chain reaction, such as mitfa, tyr, tyrp1, and dct, which were down-regulated, and foxd3, hpda, ptps, and gch1, which were up-regulated. A KEGG pathway analysis indicated that the differentially expressed genes were mainly related to mitogen activated protein kinase (MAPK), Wnt, cell cycle, and endocytosis signaling pathways, as well as variations in melanogenesis in crucian carp. In addition, some differentially expressed DNA methylation site genes were related to pigmentation, including mitfa, tyr, dct, foxd3, and hpda. The differentially expressed DNA methylation sites were mainly involved in signaling pathways, including MAPK, cAMP, endocytosis, melanogenesis, and Hippo. Conclusions: Our study provides the results of comparative transcriptome and DNA methylation analyses between RCC and WCC skin tissues and reveals that the molecular mechanism of body color variation in crucian carp is strongly related to disruptions in gene expression and DNA methylation during pigmentation. [ABSTRACT FROM AUTHOR]

Exosomes are nanoscale extracellular membrane vesicles that are created by the fusion of an intracellular multivesicular body with the cell membrane. They are widely distributed in serum, urine, saliva and other biological fluids. As important transfer vectors for intercellular communication and genetic material, exosomes can stimulate target cells directly via receptor-mediated interactions or via the transfer of various bioactive molecules, such as cell membrane receptors, proteins, mRNAs and microRNAs, thus exerting their biological functions. This review focuses on the biological characteristics of exosomes, as well as their role and underlying mechanisms of action in the evolution of tumor formation, metastasis, drug resistance and other malignant behaviors. Additionally, this review emphasizes the potential applications of exosomes in the treatment of tumors. Further research may provide new ideas and methods to establish effective, exosome-based strategies for the early diagnosis and treatment of tumors. [ABSTRACT FROM AUTHOR]

Background: New Delhi metallo-β-lactamase (blaNDM), a plasmid-borne carbapenemase gene associated with significant mortality and severely limited treatment options, is of global public health concern as it is found in extremely diverse Gram-negative bacterial strains. This study thus aims to genetically characterize local and global spread of blaNDM. Methods: To investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 blaNDM-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare blaNDM-positive plasmids; and (2) study the phylogenetic relationship of the bacteria chromosomes. The global analysis was conducted by analyzing 2749 complete plasmid sequences (including 39 blaNDM-positive plasmids) in the NCBI database, where: (1) the plasmids were clustered based on their gene composition similarity; (2) phylogenetic study was conducted for each blaNDM-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing blaNDM into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids' incompatibility group and geographical distribution. Results: Analysis of the first 11 blaNDM-positive isolates from a single hospital revealed very low blaNDM-positive plasmid diversity. Local transmission was characterized by clonal spread of a predominant plasmid with 2 sporadic instances of plasmid introduction. In contrast to the low diversity locally, global blaNDM spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were blaNDM-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The blaNDM gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions. Conclusions: Our analysis revealed the complex genetic pathways of blaNDM spread, with global dissemination characterized mainly by transposition of the blaNDM gene cassette into varied plasmids. Early local transmission following plasmid introduction is characterized by plasmid conjugation and bacterial spread. Our findings emphasize the importance of plasmid molecular epidemiology in understanding blaNDM spread. [ABSTRACT FROM AUTHOR]

Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment. [ABSTRACT FROM AUTHOR]