NKG2D ligand RAE1ε induces generation and enhances the inhibitor function of myeloid‐derived suppressor cells in mice

Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8⁺ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D‐mediated immune cell activation, such as tumour‐derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down‐regulate the expression of NKG2D on NK cells and CD8⁺ T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b⁺Gr‐1⁺ myeloid‐derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1ε display a robust induction of IL‐10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen‐non‐specific CD8⁺ T‐cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1ε significantly promote CT26 tumour growth in IL‐10‐ and arginase‐dependent manners. RAE1ε moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1ε enhances inhibitory function of CT26‐derived MDSCs and promotes IL‐4 rather than IFN‐γ production from CT26‐derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand⁺ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.     

Growth form and distribution of introduced plants in their native and non-native ranges in Eastern Asia and North America

There is a growing interest in understanding the influence of plant traits on their ability to spread in non-native regions. Many studies addressing this issue have been based on relatively small areas or restricted taxonomic groups. Here, we analyse a large data base involving 1567 plant species introduced between Eastern Asia and North America or from elsewhere to both regions. We related the extent of species distributions in each region to growth form and the distinction between upland and wetland habitats. We identified significant relationships between geographical distribution and plant traits in both native and exotic ranges as well as regional differences in the relationships. Range size was larger for herbaceous graminoids and forbs, especially annuals compared to perennials, than for woody species, and range size also was larger for plants of wetland compared to upland habitats. Distributions were more extensive in North America than in Eastern Asia, although native plants from both regions had broader distributions than non-natives, with exotics from elsewhere intermediate. Growth form and environment explained more of the variance in distribution of plants in North America than in Eastern Asia. The influence of growth form and habitat on distribution suggests that these traits might be related to tolerance of ecological conditions. In addition, the smaller extents of species in non-native compared to native areas suggest roles for dispersal limitation and adaptation to region-specific ecological conditions in determining distribution.     

EPA,not DHA,prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.     

Identification of potentially critical genes in the development of heart failure after ST-segment elevation myocardial infarction (STEMI)

Heart failure (HF) remains a common complication after acute ST-segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post-infarct HF and eight patients without post-infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein-protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow-up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix-receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post-infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.     

典型矿区植被覆盖度时空分布特征及影响因素

植被状况可以直接或间接地反映采煤对生态环境的影响。以长河井工煤矿、离柳井工煤矿、平朔露天煤矿3个典型矿区为研究区域。以Landsat数据为数据源，基于地形调节植被指数的像元二分模型提取植被覆盖度；采用趋势分析、线性回归斜率、稳定性分析方法，分析了3个典型矿区2001-2016年植被覆盖度的时空变化特征；运用"以时间换空间"的方法，采用相关分析方法对植被覆盖度变化的自然影响因素进行了分析。结果表明：（1）近16年3个典型矿区植被覆盖度呈增加趋势，长河、离柳、平朔矿区的增长速率分别为0.09%/10 a、0.10%/10 a、0.08%/10 a（P > 0.05）。（2）空间上，长河、离柳、平朔矿区植被覆盖度变化不明显比例分别占到66.63%，59.90%，62.25%，呈增加趋势的比例仅分别占28.14%、32.55%、27.81%，而呈减少趋势的比例分别占到5.23%、7.55%、9.94%。长河矿区明显改善的区域位于自然植被和耕作区的北部和东北部，离柳矿区明显改善的区域位于以低植被覆盖度为主的北部，平朔矿区明显改善的区域位于复垦的中西部。（3）不区分植被类型时，3个矿区的植被覆盖度变化与高程、高程与温度的交互作用表现出显著相关性（P < 0.01），与各自然因素的相关性总体表现为长河 > 离柳 > 平朔矿区；区分植被类型时，草地与坡度的相关性不显著（P > 0.05），与降雨量、高程存在显著正相关（P < 0.05）；灌木林与温度相关性不显著，与高程和降雨量的交互作用存在显著正相关；旱地与高程、高程与温度的交互作用存在显著相关性；疏林地与坡向、降雨量与坡向坡度的交互作用均没有表现出相关性；有林地与高程降雨量的交互作用表现出显著正相关性。探讨不同植被类型对自然因素的响应，可为矿区植被结构的选择，矿区复垦提供参考依据。     

20-hydroxyecdysone accumulation and regulation in Ajuga lobata D. Don suspension culture

Suspension culture of Ajuga lobata D. Don cells provides a method of synthesis of the phytoecdysteroid 20-hydroxyecdysone (20E) which can regulate the molting process of larvae. We characterized the culture conditions to optimize 20E production. Growth of A. lobata D. Don cells fits the logistic equation curve with a growth cycle of 19 days. Medium conductivity was negatively correlated with dry cell weight and 20E accumulation, thus could be used to determine the optimal time for cell harvest. Continuous subculture reduced 20E synthesis, but supplementing medium with 20E precursors mevalonic (MVA), α-Pinene, and nitric oxide (NO) can significantly promote cell growth and influence 20E accumulation. Combination of α-Pinene, MVA, and SNP significantly elevated 20E accumulation, thus may synergistically enhance 20E synthesis in A. lobata D. Don. The optimal concentrations of α-Pinene, MVA, and NO donor SNP in suspension culture were 50 μL L^?1, 10 mg L^?1, and 80 μmol L^?1.