人造血干/祖细胞多态性的研究:Ⅷ.人正常骨髓 CD34~ 造血细胞体视学的特征

人CD34~ 造血细胞是具有高度自我更新、多向分化及重建长期造血与免疫学功能的独特体细胞。为系统探索CD34~ 造血细胞的形态、细胞化学及超微结构特征,新近我们设计组合并建立了CIMS-100-FACS 440无菌二次分选术,可使所获CD34~ 造血细胞的纯度达100%。在此基础上,本研究采用Cambri-dge Quantimet 970全自动图像分析仪对光学显微镜、扫描电镜及透射电镜下的CD34~ 造血细胞进行了体视学方面的某些探讨,进一步从三维结构信息中深刻揭示CD34~ 造血细胞的形态计量学特征。经扫描→模数转换←阴影校正→图像暂存←统计分析等检测,结果表明:CD34~ 造血细胞的直径3.490—6.741μm,周长11.776—26.240μm,面积9.565—35.686μm~2,形状因子1.048—1.840,核浆比0.58—0.72,平均光密度0.17675—0.65100,积分光密度2717.217—9870.643。由此可见CD34~ 造血细胞的确为非均一细胞群,这可能与CD34~ 造血细胞的功能亚群与分化阶段密切相关。据我们所知,这是国际上首次有关人CD34~ 造血细胞体视学特征的报道。     

The combination therapy of oncolytic HSV-1 armed with anti-PD-1 antibody and IL-12 enhances anti-tumor efficacy

Cancer immunotherapy is a new therapeutic strategy for cancer treatment that targets tumors by improving or restoring immune system function. Therapies targeting immune checkpoint molecules have exerted potent anti-tumor effects and prolonged the overall survival rate of patients. However, only a small number of patients benefit from the treatment. Oncolytic viruses exert anti-tumor effects by regulating the tumor microenvironment and affecting multiple steps of tumor immune circulation. In this study, we engineered two oncolytic viruses that express mouse anti-PD-1 antibody (VT1093M) or mouse IL-12 (VT1092M). We found that both oncolytic viruses showed significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Importantly, the intratumoral combined injection with VT1092M and VT1093M inhibited growth of the primary tumor, prevented growth of the contralateral untreated tumor, produced a vaccine-like response, activated antigen-specific T cell responses and prolonged the overall survival rate of mice. These results indicate that combination therapy with the engineered oncolytic virus may represent a potent immunotherapy strategy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.     

东方蜜蜂微孢子虫侵染过程中nce-miR-34537和靶基因PIP5KI的表达谱

【目的】本研究旨在对前期鉴定到的nce-miR-34537进行表达和序列验证,预测nce-miR-34537的靶基因并明确其分子特性,进而检测nce-miR-34537及其靶基因在东方蜜蜂微孢子虫(Nosema ceranae)侵染意大利蜜蜂(Apis mellifera ligustica)工蜂过程的表达谱,为进一步探究nce-miR-34537调控东方蜜蜂微孢子虫侵染的功能和作用机制提供基础。【方法】通过Stem-loop-RT-PCR和Sanger测序验证nce-miR-34537的表达和序列。通过生物信息学软件预测nce-miR-34537的靶基因PIP5KI(I型磷脂酰肌醇4-磷酸-5-激酶基因)的理化性质等分子特性和保守基序,并构建基于氨基酸序列的系统进化树。采用RT-qPCR检测nce-miR-34537及其靶基因的表达谱。【结果】nce-miR-34537在东方蜜蜂微孢子虫孢子中真实存在和表达。nce-miR-34537共靶向PIP5KI等151个基因。PIP5KI蛋白的分子式为C₈₈₂H_{1 364}N₂₂₆     

福建省多花黄精生态适宜性区划研究

通过研究多花黄精(Polygonatum cyrtonema)的生态适宜性,为其野生资源保护及人工规范化栽培提供依据。收集237份多花黄精分布位置和55个生态因子,导入最大熵(MaxEnt)模型运算,结合地理信息系统(GIS)分析其适合生长区域。结果表明,影响多花黄精生态适宜性的主要生态因子是3月降水量、年均降水量、6月降水量、5月降水量、4月降水量、2月降水量和最冷季降水量,在福建省具有广泛适宜生长区域。模型预测结果可靠,可为多花黄精野生资源保护提供参考,并为其科学种植提供指导。     

泛素化结合酶E2抑制剂对草菇15 ℃保鲜的影响

为了改进草菇低温保鲜方法,在15 ℃贮藏条件下,采用泛素化结合酶E2 (UBEV2)抑制剂对草菇子实体进行处理,并开展相关生理指标和基因表达检测。结果表明,使用100 μmol/L的UBEV2抑制剂L345-0044维持了草菇较好的品质,提高了草菇可溶性糖的含量。低温明显提升抑制剂处理下的碱性蛋白酶和中性蛋白酶活力,并证实了低温胁迫显著提高了抑制剂处理下的一种类型蛋白酶肽基赖氨酸金属内肽酶的表达。本研究证实了草菇可溶性糖和高活性的冷诱导金属内肽酶对于延长草菇的低温保鲜时间是必须的。     

DNA-methylation-mediated silencing of miR-7-5p promotes gastric cancer stem cell invasion via increasing Smo and Hes1

Cancer stem cells are undifferentiated cancer cells that have self-renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence-activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real-time polymerase chain reaction (PCR) revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. The downregulation of miR-7-5p results from the increased DNA methylation in the promoter region using the methylation-specific PCR. Overexpression of miR-7-5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR-7-5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR-7-5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.     

SHORT-ROOT 1 is critical to cell division and tracheary element development in rice roots

The exocyst is a key factor in vesicle transport and is involved in cell secretion, cell growth, cell division and other cytological processes in eukaryotes. EXO70 is the key exocyst subunit. We obtained a gene, SHORT-ROOT 1 (SR1), through map-based cloning and genetic complementation. SR1 is a conserved protein with an EXO70 domain in plants. SR1 mutation affected the whole root-development process: producing shorter radicles, adventitious roots and lateral roots, and demonstrating abnormal xylem development, resulting in dwarfing and reduced water potential and moisture content. SR1 was largely expressed in the roots, but only in developing root meristems and tracheary elements. The shortness of the sr1 mutant roots was caused by the presence of fewer meristem cells. The in situ histone H4 expression patterns confirmed that cell proliferation during root development was impaired. Tracheary element dysplasia was caused by marked decreases in the inner diameters of and distances between the perforations of adjacent tracheary elements. The membrane transport of sr1 mutants was blocked, affecting cell division in the root apical region and the development of root tracheary elements. The study of SR1 will deepen our understanding of the function of EXO70 genes in Oryza sativa (rice) and guide future studies on the molecular mechanisms involved in plant root development.     

草地土壤有机质不同组分氮库对长期氮添加的响应

土壤氮库对生态系统的养分循环至关重要。目前多数研究主要关注氮沉降对土壤总氮的影响, 而对土壤不同有机质组分的氮库对氮沉降响应的研究较为缺乏。该研究基于内蒙古典型草地的长期多水平施氮(0、8、32、64 g·m^-2·a^-1)实验平台, 利用土壤密度分级方法, 探究氮添加处理13年后典型草地中两种土壤有机质组分(颗粒态有机质(POM), 矿质结合态有机质(MAOM))氮含量的变化及调控机制。结果显示: 土壤总碳含量、POM和MAOM的碳含量在施氮处理间均没有显著差异。土壤总氮含量则随着施氮水平增加呈显著增加的趋势, 同时施氮处理下POM的氮含量显著上升, 而MAOM的氮含量没有变化。进一步分析发现, 施氮促进植物地上生物量积累, 增加了凋落物量及其氮含量, 从而导致POM的氮含量增加。由于MAOM主要通过黏土矿物等吸附土壤中小分子有机质形成, 其氮含量受土壤中黏粒与粉粒含量影响, 而与氮添加水平无显著相关关系。该研究结果表明长期氮添加促进土壤氮库积累, 但增加的氮主要分布在稳定性较低的POM中, 受干扰后容易从生态系统中流失。为了更准确地评估和预测氮沉降对陆地生态系统的氮循环过程的影响, 应考虑土壤中不同有机质组分的差异响应。     

Degradation of WTAP blocks antiviral responses by reducing the m6A levels of IRF3 and IFNAR1 mRNA

N ⁶‐methyladenosine (m⁶A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m⁶A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m⁶A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m⁶A modification in type I interferon (IFN‐I) signaling are still largely unknown. Here, we reveal that WT1‐associated protein (WTAP), one of the m⁶A “writers”, is degraded via the ubiquitination‐proteasome pathway upon activation of IFN‐I signaling. With the degradation of WTAP, the m⁶A levels of IFN‐regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP‐IRF3/IFNAR1 axis may serve as negative feedback pathway to fine‐tune the activation of IFN‐I signaling, which highlights the roles of m⁶A in the antiviral response by dictating the fate of mRNAs associated with IFN‐I signaling.