Physiological, Metabolome and Gene Expression Analyses Reveal the Accumulation and Biosynthesis Pathways of Soluble Sugars and Amino Acids in Sweet Sorghum under Osmotic Stresses.

Water scarcity is a major environmental constraint on plant growth in arid regions. Soluble sugars and amino acids are essential osmolytes for plants to cope with osmotic stresses. Sweet sorghum is an important bioenergy crop and forage with strong adaptabilities to adverse environments; however, the accumulation pattern and biosynthesis basis of soluble sugars and amino acids in this species under osmotic stresses remain elusive. Here, we investigated the physiological responses of a sweet sorghum cultivar to PEG-induced osmotic stresses, analyzed differentially accumulated soluble sugars and amino acids after 20% PEG treatment using metabolome profiling, and identified key genes involved in the biosynthesis pathways of soluble sugars and amino acids using transcriptome sequencing. The results showed that the growth and photosynthesis of sweet sorghum seedlings were significantly inhibited by more than 20% PEG. After PEG treatments, the leaf osmotic adjustment ability was strengthened, while the contents of major inorganic osmolytes, including K+ and NO3-, remained stable. After 20% PEG treatment, a total of 119 and 188 differentially accumulated metabolites were identified in the stems and leaves, respectively, and the accumulations of soluble sugars such as raffinose, trehalose, glucose, sucrose, and melibiose, as well as amino acids such as proline, leucine, valine, serine, and arginine were significantly increased, suggesting that these metabolites should play key roles in osmotic adjustment of sweet sorghum. The transcriptome sequencing identified 1711 and 4978 DEGs in the stems, as well as 2061 and 6596 DEGs in the leaves after 20% PEG treatment for 6 and 48 h, respectively, among which the expressions of genes involved in biosynthesis pathways of sucrose (such as SUS1, SUS2, etc.), trehalose (including TPS6), raffinose (such as RAFS2 and GOLS2, etc.), proline (such as P5CS2 and P5CR), leucine and valine (including BCAT2), and arginine (such as ASS and ASL) were significantly upregulated. These genes should be responsible for the large accumulation of soluble sugars and amino acids under osmotic stresses. This study deepens our understanding of the important roles of individual soluble sugars and amino acids in the adaptation of sweet sorghum to water scarcity.

Comparative Physiological and Gene Expression Analyses Reveal Mechanisms Involved in Maintaining Photosynthesis Capacity, Alleviating Ion Toxicity and Oxidative Stress of Kentucky Bluegrass under NaCl Treatment.

Kentucky bluegrass (Poa pratensis L.), a widely used cool-season turfgrass, shows a high sensitivity to soil salinity. Clarifying the adaptative mechanisms of Kentucky bluegrass that serve to improve its salt tolerance in saline environments is urgent for the application of this turfgrass in salt-affected regions. In this study, physiological responses of the Kentucky bluegrass cultivars "Explorer" and "Blue Best" to NaCl treatment, as well as gene expressions related to photosynthesis, ion transport, and ROS degradation, were analyzed. The results showed that the growth of "Explorer" was obviously better compared to "Blue Best" under 400 mM NaCl treatment. "Explorer" exhibited a much stronger photosynthetic capacity than "Blue Best" under NaCl treatment, and the expression of key genes involved in chlorophyll biosynthesis, photosystem II, and the Calvin cycle in "Explorer" was greatly induced by salt treatment. Compared with "Blue Best", "Explorer" could effectively maintain Na+/K+ homeostasis in its leaves under NaCl treatment, which can be attributed to upregulated expression of genes, such as HKT1;5, HAK5, and SKOR. The relative membrane permeability and contents of O2- and H2O2 in "Explorer" were significantly lower than those in "Blue Best" under NaCl treatment, and, correspondingly, the activities of SOD and POD in the former were significantly higher than in the latter. Moreover, the expression of genes involved in the biosynthesis of enzymes in the ROS-scavenging system of "Explorer" was immediately upregulated after NaCl treatment. Additionally, free proline and betaine are important organic osmolytes for maintaining hydration status in Kentucky bluegrass under NaCl treatment, as the contents of these metabolites in "Explorer" were significantly higher than in "Blue Best". This work lays a theoretical basis for the improvement of salt tolerance in Kentucky bluegrass.

Downregulation of LINC01508 contributes to cisplatin resistance in ovarian cancer via the regulation of the Hippo-YAP pathway.

BACKGROUND: Some long non-coding RNAs (lncRNAs) have been found to contribute to cisplatin resistance. Here, we identified a novel lncRNA that was downregulated in cisplatin-resistant to ovarian cancer (OC) cells and aimed to examine the contribution of LINC01508 to cisplatin resistance in OC cells. METHODS: Differences in the lncRNA expression profile between OV2008 and C13K cells were assessed by lncRNA expression microarray. The expression of LINC01508 in ovarian epithelial cells, four OC cells, and OC, benign ovary tumor and normal ovary, cisplatin-resistant and non-resistant OC specimens were evaluated by quantitative real-time polymerase chain reaction (qPCR). The role of LINC01508 in OC cisplatin-resistant was evaluated by cell counting kit-8 (CCK-8), flow cytometry, colony formation, wound healing, Transwell, and tumor growth inhibition study in vivo. The clinical associations of LINC01508 in OC were evaluated using correlation analysis. The effects of verteporfin (VP) on cisplatin were explored to reveal the function of the hippo-YAP pathway on the cisplatin tolerance of C13K. RESULTS: LINC01508 was downregulated in cisplatin-resistant OC cells and platinum-resistant OC tissue (p<0.01). LINC01508 downregulation was correlated with tumor size, residual tumor, and platinum resistance. The overexpression of LINC01508 improves in vitro and in vivo sensitivity to cisplatin while predicts the poor overall survival which need further follow-up research. The increased level of LINC01508 could suppress the cisplatin resistance of OC cells through the inhibition of the hippo-YAP pathway. CONCLUSIONS: The study proposes that dysregulation of LINC01508 expression results in resistance of OC to cisplatin through the inhibition of the hippo-YAP pathway.

A case report for severe hand-foot skin reaction caused by chemotherapy with actinomycin D in a patient with oculocutaneous albinism.

Gestational trophoblastic neoplasms (GTN) are highly curable tumors, with an overall patient survival of 90%, due to the individualized chemotherapy. However, chemotherapy regimens vary between different treatment centers and the comparable benefits and risks of these different regimens are unclear. Here, we reported a case of GTN with oculocutaneous albinism (OCA) is resistant to fluorouracil (5-FU), extremely sensitive to actinomycin D (Act-D) with severe hand-foot skin reaction (HFSR). We hypothesized that the known, or unknown, gene mutations might be correlated with drug resistance, supersensitivity and severe drug side effects in OCA patients. Thus, we considered that OCA related genes influence some drug sensitivity and that the absence of melanin likely contributes to some drug resistance. It is important to assess the OCA related gene mutations locus of drug sensitivity, and resistance in OCA patients in future research.

Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer.

BACKGROUND: Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. . RESULTS: We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells. CONCLUSIONS: These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.