Platelet to lymphocyte ratio (PLR) was recently reported as a useful index in predicting the prognosis of lung cancer. However, the prognostic role of PLR in lung cancer remains controversial. The aim of this study was to evaluate the association between PLR and clinical outcome of lung cancer patients through a meta-analysis. Relevant literatures were retrieved from PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. A total of 5,314 patients from 13 studies were finally enrolled in the meta-analysis. The summary results showed that elevated PLR predicted poorer overall survival (OS) (HR: 1.526, 95%CI: 1.268-1.836, p < 0.001) in patients with lung cancer and OS (HR: 1.631, 95%CI: 1.447-1.837, p < 0.001) in patients with nonsmall cell lung cancer (NSCLC). Subgroup analysis revealed that increased PLR was also associated with poor OS in NSCLC treated by surgical resection (HR: 1.884, 95%CI: 1.308-2.714, P < 0.001) and non-surgery (HR: 1.570, 95%CI: 1.323-1.863, P < 0.001). In addition, PLR Cut-off value 160 (HR: 1.506, 95%CI: 1.292-1.756, P < 0.001) and PLR Cut-off value>160 (HR: 1.842, 95%CI: 1.523-2.228, P < 0.001). In contrast, elevated PLR was not associated with OS (HR: 1.117, 95%CI: 0.796-1.569, P > 0.05) in patients with small cell lung cancer (SCLC).This meta-analysis result suggested that elevated PLR might be a predicative factor of poor prognosis for NSCLC patients.As the second leading cancer type for the estimated new cancer cases, lung cancer represents the major cause of cancerrelated death worldwide. 1 Despite research on the diagnosis of lung cancer and the use of increasingly advanced technology in its treatment, the prognosis of lung cancer is still poor.

High-osmolarity glycerol (HOG) pathway required for yeast osmoregulation relies upon the mitogen-activated protein kinase (MAPK) Hog1 cascade that comprise the MAPKKKs Ssk2/Ssk22 and Ste11 converging on the MAPKK Pbs2. Here we show a Hog1 cascade with the unique MAPKKK Ssk2 acting in Beauveria bassiana. Hypersensitivity to high osmolarity and high resistance to fludioxonil fungicide appeared in Δssk2, Δpbs2 and Δhog1 mutants whereas the two hallmark phenotypes were reversed in Δste11. Increased sensitivity to heat shock and decreased sensitivity to cell wall perturbation also occurred in the three mutants but not in Δste11 although antioxidant phenotypes were different in all deletion mutants. Intriguingly, signals of Hog1 phosphorylation induced by osmotic, oxidative and thermal cues were present in Δste11 but absent in Δssk2 and Δpbs2. Moreover, vegetative growth on minimal media with different carbon/nitrogen sources was much more suppressed in Δste11 and Δssk2 than in Δpbs2 and Δhog1 although all mutants suffered similar, but severe, conidiation defects on a standard medium. Normal host infection was abolished in Δste11 while virulence was differentially attenuated in other mutants. Our findings exclude Ste11 from the Hog1 cascade that regulates multiple stress responses and environmental adaptation of B. bassiana and perhaps other filamentous fungi.

BackgroundReactive carbonyl species (RCS), such as methylglyoxal (MG) and glyoxal (GO), are synthesized as toxic metabolites in living systems. Mechanisms of RCS detoxification include the glutathione (GSH)-dependent system consisting of glyoxalase I (GLO1) and glyoxalase II (GLO2), and GSH-independent system involving glyoxalase III (GLO3). Hsp31 and DJ-1 proteins are weakly homologous to each other and belong to two different subfamilies of the DJ-1/Hsp31/PfpI superfamily. Recently, the Escherichia coli Hsp31 protein and the DJ-1 proteins from Arabidopsis thaliana and metazoans have been demonstrated to have GLO3 activity.ResultsWe performed a systematic survey of homologs of DJ-1 and Hsp31 in fungi. We found that DJ-1 proteins have a very limited distribution in fungi, whereas Hsp31 proteins are widely distributed among different fungal groups. Phylogenetic analysis revealed that fungal and metazoan DJ-1 proteins and bacterial YajL proteins are most closely related and together form a sister clade to bacterial and fungal Hsp31 proteins. We showed that two Schizosaccharomyces pombe Hsp31 proteins (Hsp3101 and Hsp3102) and one Saccharomyces cerevisiae Hsp31 protein (ScHsp31) displayed significantly higher in vitro GLO3 activity than S. pombe DJ-1 (SpDJ-1). Overexpression of hsp3101, hsp3102 and ScHSP31 could confer MG and GO resistance on either wild-type S. pombe cells or GLO1 deletion of S. pombe. S. pombe DJ-1 and Hsp31 proteins exhibit different patterns of subcellular localization.ConclusionsOur results suggest that fungal Hsp31 proteins are the major GLO3 that may have some role in protecting cells from RCS toxicity in fungi. Our results also support the view that the GLO3 activity of Hsp31 proteins may have evolved independently from that of DJ-1 proteins.

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Rpd3 is a class I histone deacetylase that reverses lysine acetylation thus influencing cellular processes and functions. However, its role in fungal insect pathogens has not been explored yet. Here we show that Rpd3-dependent lysine modification and gene expression orchestrate growth, conidiation and virulence in Beauveria bassiana. Deletion of Rpd3 resulted in severe growth defects on various carbon/nitrogen sources, 97% reduction in conidiation capacity and drastic attenuation in virulence. These phenotypes concurred with differential expression of 1479 proteins and hyperacetylation or hypoacetylation of 2227 lysine residues on 1134 proteins. Many of these proteins fell into carbon/nitrogen metabolism and cell rescue/defence/virulence, indicating vital roles of Rpd3-dependent protein expression and lysine modification in the fungal growth and virulence. Intriguingly, lysine residues of four core histones (H2A, H2B, H3 and H4) and many histone acetyltransferases were also hyper- or hypoacetylated in Δrpd3, suggesting direct and indirect roles for Rpd3 in genome-wide lysine modification. However, crucial development activators were transcriptionally repressed and not found in either proteome or acetylome. Single/double-site-directed H3K9/K14 mutations for hyper/hypoacetylation exerted significant impacts on conidiation and dimorphic transition crucial for fungal virulence. Altogether, Rpd3 mediates growth, asexual development and virulence through transcriptional/translational regulation and posttranslational lysine modification in B. bassiana.