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Background: Although serum cystatin C (sCysC), urinary N-acetyl-β-D-glucosaminidase (uNAG), and urinary albumin/creatinine ratio (uACR) are clinically available, their optimal combination for acute kidney injury (AKI) detection and prognosis prediction remains unclear. We aimed to assess the discriminative abilities of these biomarkers and their possible combinations for AKI detection and intensive care unit (ICU) mortality prediction in critically ill adults.Methods: A multicenter, prospective observational study was conducted in mixed medical-surgical ICUs at three tertiary care hospitals. One thousand eighty-four adult critically ill patients admitted to the ICUs were studied. We assessed the use of individual biomarkers (sCysC, uNAG, and uACR) measured at ICU admission and their combinations with regard to AKI detection and prognosis prediction.Results: AUC-ROCs for sCysC, uNAG, and uACR were calculated for total AKI (0.738, 0.650, and 0.683, respectively), severe AKI (0.839, 0.706, and 0.771, respectively), and ICU mortality (0.727, 0.793, and 0.777, respectively). The panel of sCysC plus uNAG detected total and severe AKI with significantly higher accuracy than either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). For detecting total AKI, severe AKI, and ICU mortality at ICU admission, this panel yielded AUC-ROCs of 0.756, 0.863, and 0.811, respectively; positive predictive values of 0.71, 0.31, and 0.17, respectively; and negative predictive values of 0.81, 0.97, and 0.98, respectively. Moreover, this panel significantly contributed to the accuracy of the clinical models for AKI detection and ICU mortality prediction, as measured by the AUC-ROC, continuous net reclassification index, and incremental discrimination improvement index. The comparable performance of this panel was further confirmed with bootstrap internal validation.Conclusions: The combination of a functional marker (sCysC) and a tubular damage marker (uNAG) revealed significantly superior discriminative performance for AKI detection and yielded additional prognostic information on ICU mortality. [ABSTRACT FROM AUTHOR]

Background: Acetic acid is routinely generated during lignocelluloses degradation, syngas fermentation, dark hydrogen fermentation and other anaerobic bioprocesses. Acetate stream is commonly regarded as a by-product and detrimental to microbial cell growth. Conversion of acetate into lipids by oleaginous yeasts may be a good choice to turn the by-product into treasure. Results: Ten well-known oleaginous yeasts were evaluated for lipid production on acetate under flask culture conditions. It was found that all of those yeasts could use acetate for microbial lipid production. In particular, Cryptococcus curvatus accumulated lipids up to 73.4 % of its dry cell mass weight. When the culture was held in a 3-L stirred-tank bioreactor, cell mass, lipid content, lipid yield and acetate consumption rate were 8.1 g/L, 49.9 %, 0.15 g/g and 0.64 g/L/h, respectively. The fatty acid compositional profiles of the acetate-derived lipids were similar to those of vegetable oil, suggesting their potential for biodiesel production. Continuous cultivation of C. curvatus was conducted under nitrogen-rich condition at a dilution rate of 0.04 h-1, the maximal lipid content and lipid yield were 56.7 % and 0.18 g/g, respectively. The specific lipid formation rate, lipid content and lipid yield were all higher under nitrogen-rich conditions than those obtained under nitrogen-limited conditions at the same dilution rates. Effective lipid production by C. curvatus was observed on corn stover hydrolysates containing 15.9 g/L acetate. Conclusions: Acetate is an effective carbon source for microbial lipid production by oleaginous yeasts. Continuous cultivation of C. curvatus on acetate was promising for lipid production under both nitrogen-rich and nitrogen-limited conditions. These results provide valuable information for developing and designing more efficient acetate-into-lipids bioprocess. [ABSTRACT FROM AUTHOR]

Background: Ursolic acid (UA), a pentacyclic triterpenoid, is known to have anti-tumor activity in various cancers including human non small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the action of UA remain largely unknown. Methods: Cell viability was measured by MTT assays. Apoptosis was analyzed with Annexin V-FITC/PI Apoptosis Detection Kit by Flow cytometry. Western blot analysis was performed to measure the phosphorylation and protein expression of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), DNMT1 [DNA (cytosine-5)-methyltransferase 1], enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and SP1. Exogenous expression of SP1 and DNMT1 was carried out by transient transfection assays. Results: We showed that UA inhibited the growth and induced apoptosis of NSCLC cells in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of SAPK/JNK and suppressed the protein expression of DNMT1 and EZH2. The inhibitor of SAPK/JNK (SP600125) blocked the UA-reduced expression of DNMT1 and EZH2. In addition, UA suppressed the expression of SP1 protein. Conversely, overexpression of SP1 reversed the effect of UA on DNMT1 and EZH2 expression, and feedback attenuated UA-induced phosphorylation of SAPK/JNK. Moreover, exogenous expression of DNMT1 antagonized the effect of UA on SAPK/JNK signaling, EZH2 protein expression, and NSCLC cell growth. Conclusion: Our results show that UA inhibits growth of NSCLC cells through SAPK/JNK-mediated inhibition of SP1; this in turn results in inhibition the expression of DNMT1 and EZH2. Overexpression of DNMT1 diminishes UA-reduced EZH2 protein expression. The negative feedback regulation of SAPK/JNK signaling by SP1 and DNMT1, and the reciprocal interaction of EZH2 and DNMT1 contribute to the overall effects of UA. This study leads to important new insights into the mechanisms by which UA controls growth of NSCLC cells. [ABSTRACT FROM AUTHOR]

Background Microbial lipids produced from lignocellulosic biomass hold great promise for the biodiesel industry. These lipids usually consist of three major processes: pretreatment, enzymatic hydrolysis and lipid production. However, the conventional strategy of using biomass hydrolysates as the feedstock for lipid production suffers from low lipid coefficient and prohibitively high costs. More cost-effective and integrated processes are required to advance lignocellulosic biomass-based microbial lipid technology. Results Three different strategies were tested using the oleaginous yeast Cryptococcus curvatus ATCC 20509 as a lipid producer and alkaline-pretreated corn stover as a model material. It was found that the separate hydrolysis and enhanced lipid production process required more cellulolytic enzymes yet afforded a low lipid coefficient of 115.6 mg/g pretreated corn stover. When biomass hydrolysis and lipid production were integrated, the amounts of cellulase and xylanase were reduced and no β-glucosidase was required. The simultaneous saccharification and lipid production process gave a lipid coefficient of 129.4 mg/g pretreated corn stover. A higher lipid coefficient of 159.4 mg/g pretreated corn stover was obtained using the simultaneous saccharification and enhanced lipid production (SSELP) process. Furthermore, cellulolytic enzymes were found recoverable and reusable upon recycling the spent supernatants of the SSELP process, which could reduce enzyme consumption and wastewater discharge. Conclusions The SSELP process was superior to other processes in terms of converting alkaline-pretreated corn stover into lipids by C. curvatus, as it required less cellulolytic enzymes and had a higher lipid coefficient. Moreover, the process facilitated easy enzyme recycling that should lead to further reduction of enzyme consumption. These results provide valuable information for cost-effective lipid production from lignocelluloses, which should be particularly important in achieving a sustainable production of biodiesel. [ABSTRACT FROM AUTHOR]

Background: The α2-adrenoreceptor agonist dexmedetomidine is known to provide renoprotection against ischemia and reperfusion (I/R) injury. However the underlying molecular mechanisms remain unclear. The purpose of this study was to investigate whether the Janus kinase and signal transducer and activator of transcription (JAK/ STAT) signaling pathway plays a role in dexmedetomidine's renoprotection. Methods: I/R model was induced by bilateral renal pedicle clamping for 45 min followed by 48 h of reperfusion in male Wistar rat. Sham laparotomy served as controls. Animals received dexmedetomidine (50 μg/kg, i.p.) in the absence or presence of atipamezole (250 μg/kg, i.p.), or vehicle (DMSO) in the absence or presence of selective JAK2 inhibitor tyrphostin AG490 (10 mg/kg, i.p.) before ischemia. Renal function, histology, apoptosis, expression of cleaved caspase 3 protein, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and phosphorylations of JAK2, STAT1 and STAT3 were assessed. Results: The animals treated with either dexmedetomidine or AG490 exhibited an improved renal functional recovery, attenuated histological lesions and reduced number of apoptotic tubular epithelial cells. Either dexmedetomidine or AG490 inhibited the phosphorylations of JAK2 and its downstream molecule STAT1 and STAT3, accompanied by down-regulation the expression of cleaved caspase 3, ICAM-1 and MCP-1 proteins, and significantly ameliorated renal I/R injury. Conclusions: Dexmedetomidine protects kidney against I/R injury, at least in part, through its inhibitory effects on injury-induced activation of JAK/STAT signaling pathway. If our data can be extrapolated to clinical setting, then dexmedetomidine may therefore serve as a clinical strategy to treat/prevent perioperative renal I/R injury. [ABSTRACT FROM AUTHOR]

Background: Microbial lipid production by using lignocellulosic biomass as the feedstock holds a great promise for biodiesel production and biorefinery. This usually involves hydrolysis of biomass into sugar-rich hydrolysates, which are then used by oleaginous microorganisms as the carbon and energy sources to produce lipids. However, the costs of microbial lipids remain prohibitively high for commercialization. More efficient and integrated processes are pivotal for better techno-economics of microbial lipid technology. Results: Here we describe the simultaneous saccharification and enhanced lipid production (SSELP) process that is highly advantageous in terms of converting cellulosic materials into lipids, as it integrates cellulose biomass hydrolysis and lipid biosynthesis. Specifically, Cryptococcus curvatus cells prepared in a nutrient-rich medium were inoculated at high dosage for lipid production in biomass suspension in the presence of hydrolytic enzymes without auxiliary nutrients. When cellulose was loaded at 32.3 g/L, cellulose conversion, cell mass, lipid content and lipid coefficient reached 98.5%, 12.4 g/L, 59.9% and 204 mg/g, respectively. Lipid yields of the SSELP process were higher than those obtained by using the conventional process where cellulose was hydrolyzed separately. When ionic liquid pretreated corn stover was used, both cellulose and hemicellulose were consumed simultaneously. No xylose was accumulated over time, indicating that glucose effect was circumvented. The lipid yield reached 112 mg/g regenerated corn stover. This process could be performed without sterilization because of the absence of auxiliary nutrients for bacterial contamination. Conclusions: The SSELP process facilitates direct conversion of both cellulose and hemicellulose of lignocellulosic materials into microbial lipids. It greatly reduces time and capital costs while improves lipid coefficient. Optimization of the SSELP process at different levels should further improve the efficiency of microbial lipid technology, which in turn, promote the biotechnological production of fatty acid-derived products from lignocellulosic biomass. [ABSTRACT FROM AUTHOR]