Sex steroid axes in determining male predominance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. The mechanisms for male propensity in HCC incidence, prognosis and treatment responses are complicated and remain inconclusive. Sex-biased molecular signatures in carcinogenesis, viral infections and immune responses have been studied predominantly within the context of sex hormones effects. This review integrates current knowledge on the mechanisms through which the hormones regulate HCC development in sexually dimorphic fashion. Firstly, the androgen/androgen receptor (AR) accelerate cell proliferation and virus infection, especially during the initial stage of HCC, while estrogen/estrogen receptor (ER) function in an opposite way to induce cell apoptosis and immune responses. Interestingly, the controversial effects of AR in late stage of HCC metastasis are summarized and the reasons are attributed to inconsistent cancer grading or experimental models between the studies. In addition, the new insights into these intricate cellular and molecular mechanisms underlying sexual dimorphism are fully discussed. A detailed understanding of sex hormones-associated regulation to male predominance in HCC may help to develop personalized therapeutic strategies in high-risk populations.

Up-regulated SAMD9L modulated by TLR2 and HIF-1α as a promising biomarker in tuberculosis.

The aim of this study was to identify potential biomarkers of TB in blood and determine their function in Mtb-infected macrophages. First of all, WGCNA was used to analyse 9451 genes with significant changes in TB patients' whole blood. The 220 interferon-γ-related genes were identified, and then 30 key genes were screened using Cytoscape. Then, the AUC values of key genes were calculated to further narrow the gene range. Finally, we identified 9 genes from GSE19444. ROC analysis showed that SAMD9L, among 9 genes, had a high diagnostic value (AUC = 0.925) and a differential diagnostic value (AUC>0.865). To further narrow down the range of DEGs, the top 10 hub-connecting genes were screened from monocytes (GSE19443). Finally, we obtained 4 genes (SAMD9L, GBP1, GBP5 and STAT1) by intersections of genes from monocytes and whole blood. Among them, it was found that the function of SAMD9L was unknown after data review, so this paper studied this gene. Our results showed that SAMD9L is up-regulated and suppresses cell necrosis, and might be regulated by TLR2 and HIF-1α during Mtb infection. In addition, miR-181b-5p is significantly up-regulated in the peripheral blood plasma of tuberculosis patients, which has a high diagnostic value (AUC = 0.969).

Alternative electron sinks are crucial for conferring photoprotection in field-grown cotton under water deficit during flowering and boll setting stages.

To clarify the photoprotective mechanisms of cotton leaves under water deficit in the field, leaf gas exchange, chlorophyll a fluorescence as well as the corresponding physiological responses were examined in cotton (Gossypium hirsutum L.) to evaluate electron flux distribution. With increasing water deficit, net photosynthetic rate (Pn) significantly decreased, the total electron flux through PSII [Je(PSII)] gradually decreased and the fraction of electron flux required to sustain CO2 assimilation [Je(PCR)] markedly declined. Simultaneously, the ratio of quantum efficiency of PSII [Φ(PSII)] to the quantum efficiency of CO2 fixation [Φ(CO2)] increased, accompanied by an increase in the alternative electron flux (Ja). The enhanced alternative electron flux of O2-dependent Ja(O2-dependent) indicated that electrons had been transported to O2 in the Mehler-peroxide reaction (MPR) and that the remaining alternative electron flux Ja(O2-independent) had been used for nitrate reduction, as indicated by an increase in nitrate reductase (NR) and glutathinone reductase (GR) activities. In addition, mild water deficit increased the proportion of electron flux for the photorespiratory carbon oxidation [Je(PCO)]. Water deficit significantly increased surperoxide radical production rate (O2-•) and hydrogen peroxide content (H2O2), and the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD) and catalase (CAT) in cotton leaves also increased under water deficit. Therefore, the Mehler-peroxidation reaction, photorespiration and nitrate reduction helped to dissipated excess light energy, being important photoprotective mechanisms for adapting the photosynthetic apparatus to mild and moderate water deficit in cotton.