Holistic metabonomic profiling of urine affords potential early diagnosis for bladder and kidney cancers

The clinical exploration of urinary metabonomic analysis on discriminating between the top-two-incidence urological cancers, bladder and kidney cancers (BC and KC), is still virgin land. In this study, we discovered and evaluated the clinical utility of holistic metabonomic profiling and current single biomarker methods, and ultimately suggested a potential screening test for BC and KC. Urine metabonomic profiling for 19 BC patients, 25 KC patients, and 24 healthy controls was carried out using an LC–MS based platform, which utilized both reversed phase chromatography and hydrophilic interaction chromatography. The holistic method that refers to orthogonal partial least-squares-discriminant analysis based on all qualified profile data, successfully classified BC, KC and healthy control groups, showing 100 % sensitivity and specificity. Taurine, hippuric acid, phenylacetylglutamine and carnitine species contributed most to the BC and KC discrimination. The predictive power of each above metabolite is evaluated using receiver operator characteristic technique. Hippuric acid was found 10-fold decrease in concentration relative healthy controls, and performed the best as a biomarker for BC diagnosis, with its sensitivity and specificity of 78.9 and 86.5 %, respectively. Carnitine C10:3 was found 1.5-fold decrease, and reached 84.0 % of sensitivity and 60.5 % of specificity for KC diagnosis. In view of both sensitivity and specificity, the holistic method is more accurate for detecting BC and KC, than current single metabonomic biomarker methods, and it could be advocated as a prescreen to other forms of more invasive or uncomfortable screening. Moreover, this approach also demonstrates attractive performance in diagnosis of early stage (ES) BC and KC patients.     

Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase

Consumption of plant sterols or stanols (collectively referred to as phytosterols) and their esters results in decreased low-density lipoprotein cholesterol, which is associated with decreased atherosclerotic risk. The mechanisms by which phytosterols impart their effects, however, are incompletely characterized. The objective of the present study is to determine if pancreatic cholesterol esterase (PCE; EC 3.1.1.13), the enzyme primarily responsible for cholesterol ester hydrolysis in the digestive tract, is capable of hydrolyzing various phytosterol esters and to compare the rates of sterol ester hydrolysis in vitro. We found that PCE hydrolyzes palmitate, oleate and stearate esters of cholesterol, stigmasterol, stigmastanol and sitosterol. Furthermore, we found that the rate of hydrolysis was dependent on both the sterol and the fatty acid moieties in the following order of rates of hydrolysis: cholesterol>(sitosterol=stigmastanol)>stigmasterol; oleate>(palmitate=stearate). The addition of free phytosterols to the system did not change hydrolytic activity of PCE, while addition of palmitate, oleate or stearate increased activity. Thus, PCE may play an important but discriminatory role in vivo in the liberation of free phytosterols to compete with cholesterol for micellar solubilization and absorption.     

科尔沁沙地差巴嘎蒿群落及种群生态特征

对科尔沁不同类型沙地上差巴嘎蒿群落内物种重要值、多样性等生态特征进行分析后,将其划分为3个类型：差巴嘎蒿 1年生植物群聚、差巴嘎蒿 禾草类群丛、冷蒿 黄蒿+禾草类群丛,分别分布于流动、半固定和固定沙地上.随着沙地基质固定程度的增加,差巴嘎蒿群落由差巴嘎蒿-1年生植物群聚(先锋群落、盖度＜10%、多样性指数0.33)演替到差巴嘎蒿-禾草类群丛(盖度30%～35%、多样性指数0.56)再演替到冷蒿 黄蒿＋禾草类群丛(草原群落、盖度40%～45%、多样性指数0.59).在差巴嘎蒿群落演替过程中,差巴嗄蒿种群年龄结构的变化趋势是:在流动沙地上为增长型;在半固定和固定沙地上为衰退型.人工种植5年后差巴嘎蒿种群年龄结构为增长型,人工种植18年后为稳定型.     

科尔沁沙地差巴嘎蒿种群生态位适宜度分析

以生长在科尔沁沙地的差巴嘎蒿(Artemisia halodendron)为研究对象,对其在不同类型沙地上的综合活力指数和生态位适宜度进行计算,主要结论如下:1)在生长旺季,差巴嘎蒿种群综合活力指数随着沙地的固定显著下降。2)在同一生长季内,综合生态位适宜度表现为半固定沙地>固定沙地和流动沙地;水分生态位适宜度表现为流动沙地>半固定沙地>固定沙地。随着土壤含水量的变化,土壤水分的限制土层深度也有所不同:7月各类型沙地均为15~30 cm土层;8月随着雨水的下渗,限制土层也有所加深,为45~60 cm土层;9月除流动沙地为15~30 cm外,半固定沙地和固定沙地均为30~45 cm。3)在同一生长季内的不同生境上种群的限制因子(NF_min)不同:在流动沙地上为土壤有机质,而在半固定沙地和固定沙地上为土壤含水量,且土壤有机质和土壤水分的配置关系直接影响综合生态位适宜度值的高低。在一定范围内,二者的比值可直接反映有机质对植物细根的有效性,同时种群通过调节细根生长状况来适应限制因子间的配置关系。     

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

Osteoarthritis (OA) is characterized by cartilage destruction, chronic inflammation, and local pain. Evidence showed that retinoic acid receptor-related orphan receptor-α (RORα) is crucial in cartilage development and OA pathogenesis. Here, we investigated the role and molecular mechanism of RORα, an important member of the nuclear receptor family, in regulating the development of OA pathologic features. Investigation into clinical cartilage specimens showed that RORα expression level is positively correlated with the severity of OA and cartilage damage. In an in vivo OA model induced by anterior crucial ligament transaction, intra-articular injection of si-Rora adenovirus reversed the cartilage damage. The expression of cartilage matrix components type II collagen and aggrecan were elevated upon RORα blockade. RNA-seq data suggested that the IL-6/STAT3 pathway is significantly downregulated, manifesting the reduced expression level of both IL-6 and phosphorylated STAT3. RORα exerted its effect on IL-6/STAT3 signaling in two different ways, including interaction with STAT3 and IL-6 promoter. Taken together, our findings indicated the pivotal role of the RORα/IL-6/STAT3 axis in OA progression and confirmed that RORα blockade improved the matrix catabolism in OA chondrocytes. These results may provide a potential treatment target in OA therapy.Subject terms: Nuclear receptors, Osteoarthritis     

Continuous Removal of Lactic Acid from Wastewater by Candida utilis

Under steady-state conditions, the maximum rate of lactic acid removal was found to be 588 mg/h per liter of continuous culture.