Mesenchymal Stromal Cell Secretome Up-Regulates 47 kDa CXCR4 Expression,and Induce Invasiveness in Neuroblastoma Cell Lines

Neuroblastoma accounts for 15% of childhood cancer deaths and presents with metastatic disease of the bone and the bone marrow at diagnosis in 70% of the cases. Previous studies have shown that the Mesenchymal Stromal Cell (MSC) secretome, triggers metastases in several cancer types such as breast and prostate cancer, but the specific role of the MSC factors in neuroblastoma metastasis is unclear. To better understand the effect of MSC secretome on chemokine receptors in neuroblastoma, and its role in metastasis, we studied a panel of 20 neuroblastoma cell lines, and compared their invasive potential towards MSC-conditioned-RPMI (mRPMI) and their cytokine receptor expression profiles. Western blot analysis revealed the expression of multiple CXCR4 isoforms in neuroblastoma cells. Among the five major isoforms, the expression of the 47 kDa isoform showed significant correlation with high invasiveness. Pretreatment with mRPMI up-regulated the expression of the 47 kDa CXCR4 isoform and also increased MMP-9 secretion, expression of integrin α3 and integrin β1, and the invasive potential of the cell; while blocking CXCR4 either with AMD 3100, a CXCR4 antagonist, or with an anti-47 kDa CXCR4 neutralizing antibody decreased the secretion of MMP-9, the expression of integrin α3 and integrin β1, and the invasive potential of the cell. Pretreatment with mRPMI also protected the 47 kDa CXCR4 isoform from ubiquitination and subsequent degradation. Our data suggest a modulatory role of the MSC secretome on the expression of the 47 kDa CXCR4 isoform and invasion potential of the neuroblastoma cells to the bone marrow.     

Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes

Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (ABCA1, GCKR, BAZ1B, TOMM40, DOCK7, HNF1A, and HNF4A) were genotyped. After adjusting for multiple covariates, SNPs in ABCA1, GCKR, BAZ1B, TOMM40, and HNF1A were identified as significantly associated with triglyceride levels in T2D patients (P < 0.05). The associations between the SNPs in ABCA1 (rs3890182), GCKR (rs780094), and BAZ1B (rs2240466) remained significant even after correction for multiple testing (P = 8.85×10⁻³, 7.88×10⁻⁷, and 2.03×10⁻⁶, respectively). BAZ1B (rs2240466) also was associated with the total cholesterol level (P = 4.75×10⁻²). In addition, SNP rs157580 in TOMM40 was associated with the low-density lipoprotein cholesterol level (P = 6.94×10⁻³). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.     

Virulence phenotypes of Shigella flexneri 2a avirulent mutant 24570 can be complemented by the plasmid-coded positive regulator virF gene

Avirulent mutation of an opaque colony variant of Shigella flexneri 2a designated 24570 has been believed to be linked with the glpK locus of the chromosome. However, avirulent phenotypes of the 24570 strain could be complemented by the invasion plasmid-coded virF gene, a positive regulator for invasion genes. The 24570 strain had a DNA structural alteration upstream of the virF gene.     

Enrichment of AT-TA transversion at 5′-CAG-3′ motif is not a unique mutational signature of aristolochic acid

<正>Aristolochic acids, mutational signature, and hepatocellular carcinoma Aristolochic acids (AA) are the etiologic agents of aristolochic acid nephropathy (AAN) and contribute to the global prevalence of chronic kidney disease and urothelial cancer (Grollman et al., 2007). DNA adducts formed by AA generate a unique AT transversions mutation spectrum at     

基于多尺度协同的长沙市生态网络构建与层级优化

城市化背景下人类与自然环境的矛盾呈现出多尺度、层级化特征，而传统生态网络的构建方式较少考虑不同尺度下生态要素的关系，无法从区域落实到中心城区，难以形成系统性的解决方案。研究在综合梳理各尺度生态网络构建方法的基础上，以长沙市为例，基于形态学空间格局分析（Morphological Spatial Pattern Analysis，MSPA）、景观连通性原理和生态斑块重要性评价识别生态源地，并通过多层级生态阻力面的确定，综合运用最小费用路径（Least-cost path method，LCP）、电路理论、层级传导理论、尺度嵌套等方法对市域、都市区、中心城区的生态网络进行了协同构建和层级优化，最后基于不同尺度生态网络的特点应用并落实到多层级的国土空间规划体系中。研究结果表明：（1）长沙市域生态网络和都市区生态网络具有较好的层级嵌套特征；共识别两尺度生态叠合源地14个、生态叠合廊道15条，主要通过中心城区内的湘江、浏阳河和捞刀河部分河段与外围生态绿圈相衔接，形成"外环内楔"的空间格局。（2）确定市域重要廊道、市域潜在廊道、生态叠合廊道、都市区重要廊道、都市区潜在廊道的核心保护面积共501.14 km²，并提取位于生态廊道核心保护区范围内的生态夹点和生态障碍点，以进一步落实生态保护修复策略。（3）得到具有重要生态连通功能的中心城区生态绿道长度441.2 km，生态修复单元56个，并结合生态阻力值划分为5级进行针对性修复。（4）基于不同尺度生态网络的衔接、嵌套，最终构建"市域总体生态安全格局-都市区城市生态空间发展格局-以城市绿道为基础的中心城区生态修复单元"，并与不同层级的国土空间规划体系相对应。研究结果将为以大城市为中心的跨尺度生态系统修复和生态安全格局构建提供科学参考。     

Effects of Photoperiod and Maturity Genes on Plant Growth, Partitioning, Radiation Use Efficiency, and Yield in Soyabean [Glycine max(L.) Merrill] 'Clark'

Plants of four isolines of soyabean [Glycine max(L.) Merrill]‘Clark’, viz‘L71-920’ (maturity genecomplemente₁e₂e₃ ), ‘L80-5914’ (E₁e₂e₃), ‘Clark’(e₁E₂E₃), and ‘L65-3366’ (E₁E₂E₃), were grown inshort (12.25 h d ^{- 1}natural light) and long days (12.25 h d^{- 1}natural light supplemented with 2.75 h d ^{- 1}low-irradianceartificial light) from first flowering to maturity in a polythenetunnel maintained at 30/24°C (day/night). Whereas therewere few differences among the isolines grown in short days,in long days the dominant alleles increased crop duration, biomassand seed yield substantially. Increases in biological and economicyield were not solely a consequence of longer crop duration:the dominant alleles also increased crop growth rate and radiationuse efficiency in long days (from 1.3 g MJ ^{- 1}total radiationine₁e₂e₃ to 2.8 g MJ ^{- 1}inE₁E₂E₃ ). Greater radiation use efficiencyresulted from a relatively longer leaf area duration, betterdistribution and orientation of a larger mass of leaves withinthe canopy, and smaller partitioning of assimilates to reproductivestructures. The work reveals the substantial effects of thethree lociE₁ / e₁, E₂/ e₂and E₃/e₃ on the response of plantgrowth, as well as development, to environment. Their relevanceto crop adaptation is discussed. Copyright 2000 Annals of BotanyCompany Glycine max(L.) Merrill, soyabean, maturity genes, flowering, phenology, growth, yield     

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

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Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short‐chain fatty acids metabolism and GPR41/43 expression in β‐lactoglobulin–sensitized mice

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.