Activation of Notch-1 enhances epithelial-mesenchymal transition in gefitinib-acquired resistant lung cancer cells

Despite an initial response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer, most patients eventually become resistant and result in treatment failure. Recent studies have shown that epithelial to mesenchymal transition (EMT) is associated with drug resistance and cancer cell metastasis. Strong multiple gene signature data indicate that EMT acts as a determinant of insensitivity to EGFR-TKI. However, the exact mechanism for the acquisition of the EMT phenotype in EGFR-TKI resistant lung cancer cells remains unclear. In the present study, we showed that the expression of Notch-1 was highly upregulated in gefitinib-resistant PC9/AB2 lung cancer cells. Notch-1 receptor intracellular domain (N1IC), the activated form of the Notch-1 receptor, promoted the EMT phenotype in PC9 cells. Silencing of Notch-1 using siRNA reversed the EMT phenotype and restored sensitivity to gefitinib in PC9/AB2 cells. Moreover, Notch-1 reduction was also involved in inhibition of anoikis as well as colony-formation activity of PC9/AB2 cells. Taken together, these results provide strong molecular evidence that gefitinib-acquired resistance in lung cancer cells undergoing EMT occurs through activation of Notch-1 signaling. Thus, inhibition of Notch-1 can be a novel strategy for the reversal of the EMT phenotype thereby potentially increasing therapeutic drug sensitivity to lung cancer cells.     

Response of CH4 and N2O Emissions and Wheat Yields to Tillage Method Changes in the North China Plain

The objective of this study was to quantify soil methane (CH₄) and nitrous oxide (N₂O) emissions when converting from minimum and no-tillage systems to subsoiling (tilled soil to a depth of 40 cm to 45 cm) in the North China Plain. The relationships between CH₄ and N₂O flux and soil temperature, moisture, NH₄ ⁺-N, organic carbon (SOC) and pH were investigated over 18 months using a split-plot design. The soil absorption of CH₄ appeared to increase after conversion from no-tillage (NT) to subsoiling (NTS), from harrow tillage (HT) to subsoiling (HTS) and from rotary tillage (RT) to subsoiling (RTS). N₂O emissions also increased after conversion. Furthermore, after conversion to subsoiling, the combined global warming potential (GWP) of CH₄ and N₂O increased by approximately 0.05 kg CO₂ ha⁻¹ for HTS, 0.02 kg CO₂ ha⁻¹ for RTS and 0.23 kg CO₂ ha⁻¹ for NTS. Soil temperature, moisture, SOC, NH₄ ⁺-N and pH also changed after conversion to subsoiling. These changes were correlated with CH₄ uptake and N₂O emissions. However, there was no significant correlation between N₂O emissions and soil temperature in this study. The grain yields of wheat improved after conversion to subsoiling. Under HTS, RTS and NTS, the average grain yield was elevated by approximately 42.5%, 27.8% and 60.3% respectively. Our findings indicate that RTS and HTS would be ideal rotation tillage systems to balance GWP decreases and grain yield improvements in the North China Plain region.     

全球转基因大豆专利信息分析与技术展望

转基因大豆作为目前转基因作物推广种植面积最广的作物,在保障人类油料与饲料供给上发挥着重要作用。基于智慧芽数据库(PatSnap)对欧盟、美国及中国等国家地区1985~2016年收录的全球转基因大豆技术领域专利文献进行统计分析,得出全球转基因大豆专利信息的总体发展趋势、研发热点及技术分布与格局,并对比分析了我国转基因大豆研发的竞争力,对未来转基因大豆的产业发展提出了展望。     

Enhanced chemiluminescence enzyme‐linked immunoassay for the determination of DNA methyltransferase 1 in human serum

The occurrence of many diseases is closely related to the high expression of DNA methyltransferase 1 (DNMT1). However, most studies are focused on the detection of DNMT1 activity, a few are concerned with the detection of DNMT1 content. In this study, we developed a simple and highly sensitive chemiluminescence (CL) assay for the detection of DNMT1 content. In this method, anti‐DNMT1 monoclonal antibody was coated on a polystyrene microplate to capture DNMT1. Then anti‐DNMT1 polyclonal antibody and goat anti‐rabbit immunoglobulin G with horseradish peroxidase (IgG‐HRP) were respectively added to combine with captured DNMT1 to form a sandwich structure. Finally, the HRP could catalyze CL substrate and achieve CL signal response. Based on this novel sensitive strategy, the recovery percents were in the ranges from 71.5% to 91.0%. The precision of intra‐assays and inter‐assays were 5.45%–11.29% and 7.03%–11.25%, respectively. The method was successfully applied for the determination of DNMT1 in human serum. The detection results of serum samples showed that the proposed assay had a high correlation with enzyme‐linked immunosorbent assay (ELISA) kit. Compared with the ELISA kit (limit of detection = 0.1 ng/mL), the method has a lower limit of detection of 0.042 ng/mL. Therefore, our method has the potential for the detection of DNMT1 content in clinical diagnosis.     

Comprehensive metabolomic,proteomic and physiological analyses of grain yield reduction in rice under abrupt drought–flood alternation stress

Abrupt drought–flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought–flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought–flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought–flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought–flood alteration stress, which are factors that leads to the rice grain yield reduction.     

The Adverse Effects of Se Toxicity on Inflammatory and Immune Responses in Chicken Spleens

Selenium (Se) is an essential trace element, but excessive intake of Se could induce Se poisoning, and result in various health problems. NF-κB regulated many molecules of the immune response and the inflammatory response, and Th1/Th2 balance played a key in the regulation of immune response. The aim of this study is to investigate the role of NF-κB pathway and Th1/Th2 imbalance in the adverse influence of Se poisoning on chicken spleens. In the current study, 90 chickens were randomly divided into two groups (n?=?45 per group). The chickens were maintained either on a basal diet (the control group) containing 0.2 mg/kg Se or a high supplemented diet (the Se group) containing 15 mg/kg Se for 45 days. Then, we observed the pathohistology of spleen cells and detected NO content, iNOS activity, and the expression of NF-κB, iNOS, COX-2, PTGE, IL-6, TNF-α, Foxp3, IL-4, and IFN-γ in chicken spleens. In chicken spleens of the Se group, the result showed typical characteristics of inflammation: the content of NO and the activity of iNOS were increased, and the expression of NF-κB, iNOS, COX-2, PTGE, IL-6, TNF-α, and IL-4 was enhanced and that of Foxp3 and IFN-γ was decreased. Our study showed that Se toxicity could promote inflammation via NF-κB pathway, impairing the immune function, and changing Th1/Th2 balance in the chicken spleens.     

Diversity and conservation of Chinese wild begonias

Begonia, one of the most diverse plant taxa and the fifth or sixth largest angiosperm genus, consists of over 1800 accepted species. The number of species recognized within this genus has greatly increased over the past 20 years, rising from 80 to 200 species in China alone. Based on recent field surveys, the number of begonia species in China is predicted to be between 250 and 300. Given the large number of begonia species that still remain to be described, further taxonomical work is urgently required. This is especially true for Chinese Begonia, in which there is a huge diversity of habitat, habit, plant size, leaf type, flower and fruit morphology, and most species are narrowly distributed in isolated habitats that are subject to negative disturbances from climate change, as well as agricultural and industrial activities. Although the conservation status for the majority of species has been evaluated using the standards of the International Union for Conservation of Nature, the results don't represent the truth in many species, and also about 11.5% of which are data-absent. In addition, illegal collection and over-harvesting of wild begonias for ornamental or medicinal use has increased due to the rapid development of internet commerce. Far more often than predicted, these species should be categorized as rare and endangered and require immediate protection. Ex situ conservation of Chinese begonias started in 1995 and over 60% of the total species have been so far introduced into cultivation by several major botanical gardens in China. However, only few research institutions, limited funds and human resources have been involved in Begonia conservation; moreover, no project has conducted reintroduction. Therefore, more conservation-based work remains to be done. Improved conservation of Chinese begonias in the future depends on further field survey, an improved understanding of population diversity, and integrative approaches, including in situ and ex situ conservation, seed banking, and plant reintroduction. Speciestargeted conservation zones should be established for endangered species excluded from the existing nature reserves. Additionally, laws pertaining to plant protection should be extended to prevent the illegal collection and transaction of wild plants, particularly for those species with unique habitats and small populations.     

太白山针叶林的Fuzzy分类研究

应用模糊聚类分析法和模糊图论分析对太白山针叶林进行了数量分类比较研究。将２６个样地分为两大类共７个群落类型。研究结果表明,两种方法在植物群落分类研究中,不但是可行的,而且所分类的实际结果是等价的,与实际观测情况也是吻合的。其中的图论法直接依据模糊相似系数得到树状图,简便易行,显示出更大的适用性。     

K-77(2)雄性不育小麦花粉壁结构特征

K-77(2)不育花粉内壁比保持系厚将近一倍。在保持系花粉内壁中,有径向排列的、断断续续的、着色深的管状结构。而不育花粉内壁中则没有管状结构,且在不育花粉内壁中形成许多小泡。在花粉粒后期,往往在Z层与内壁连接处断开。推测,由于花粉内壁结构被破坏,影响了正常的营养运输和萌发所需酶的合成而抑制花粉发育。     

Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels

Protein palmitoylation is rapidly emerging as an important determinant in the regulation of ion channels, including large conductance calcium-activated potassium (BK) channels. However, the enzymes that control channel palmitoylation are largely unknown. Indeed, although palmitoylation is the only reversible lipid modification of proteins, acyl thioesterases that control ion channel depalmitoylation have not been identified. Here, we demonstrate that palmitoylation of the intracellular S0-S1 loop of BK channels is controlled by two of the 23 mammalian palmitoyl-transferases, zDHHC22 and zDHHC23. Palmitoylation by these acyl transferases is essential for efficient cell surface expression of BK channels. In contrast, depalmitoylation is controlled by the cytosolic thioesterase APT1 (LYPLA1), but not APT2 (LYPLA2). In addition, we identify a splice variant of LYPLAL1, a homolog with ～30% identity to APT1, that also controls BK channel depalmitoylation. Thus, both palmitoyl acyltransferases and acyl thioesterases display discrete substrate specificity for BK channels. Because depalmitoylated BK channels are retarded in the trans-Golgi network, reversible protein palmitoylation provides a critical checkpoint to regulate exit from the trans-Golgi network and thus control BK channel cell surface expression.