The m6A Methyltransferase METTL3-Mediated N6-Methyladenosine Modification of DEK mRNA to Promote Gastric Cancer Cell Growth and Metastasis

Gastric cancer (GC) is the fifth most common cancer and the third deadliest cancer in the world, and the occurrence and development of GC are influenced by epigenetics. Methyltransferase-like 3 (METTL3) is a prominent RNA n6-adenosine methyltransferase (m6A) that plays an important role in tumor growth by controlling the work of RNA. This study aimed to reveal the biological function and molecular mechanism of METTL3 in GC. The expression level of METTL3 in GC tissues and cells was detected by qPCR, Western blot and immunohistochemistry, and the expression level and prognosis of METTL3 were predicted in public databases. CCK-8, colony formation, transwell and wound healing assays were used to study the effect of METTL3 on GC cell proliferation and migration. In addition, the enrichment effect of METTL3 on DEK mRNA was detected by the RIP experiment, the m6A modification effect of METTL3 on DEK was verified by the MeRIP experiment and the mRNA half-life of DEK when METTL3 was overexpressed was detected. The dot blot assay detects m6A modification at the mRNA level. The effect of METTL3 on cell migration ability in vivo was examined by tail vein injection of luciferase-labeled cells. The experimental results showed that METTL3 was highly expressed in GC tissues and cells, and the high expression of METTL3 was associated with a poor prognosis. In addition, the m6A modification level of mRNA was higher in GC tissues and GC cell lines. Overexpression of METTL3 in MGC80-3 cells and AGS promoted cell proliferation and migration, while the knockdown of METTL3 inhibited cell proliferation and migration. The results of in vitro rescue experiments showed that the knockdown of DEK reversed the promoting effects of METTL3 on cell proliferation and migration. In vivo experiments showed that the knockdown of DEK reversed the increase in lung metastases caused by the overexpression of METTL3 in mice. Mechanistically, the results of the RIP experiment showed that METTL3 could enrich DEK mRNA, and the results of the MePIP and RNA half-life experiments indicated that METTL3 binds to the 3’UTR of DEK, participates in the m6A modification of DEK and promotes the stability of DEK mRNA. Ultimately, we concluded that METTL3 promotes GC cell proliferation and migration by stabilizing DEK mRNA expression. Therefore, METTL3 is a potential biomarker for GC prognosis and a therapeutic target.     

橡胶颗粒增强双网络结构堵水冻胶性能研究

目的研究橡胶颗粒增强双网络结构堵水冻胶性能,解决塔河油田为代表的缝洞型油藏在注水开发、注气开发过程中,出水、气窜现象频发的问题。方法选用丙烯酰胺/2-丙烯酰胺-2-甲基丙磺酸二元聚合物和疏水缔合聚合物为主剂,乌洛托品、间苯二酚和有机铬为交联剂,橡胶颗粒为增强剂制备了一种复合冻胶,详细考查了橡胶颗粒对冻胶基液黏度、成胶时间、成胶强度、耐稀释、耐温耐盐性能和封堵效果的影响规律。 结果橡胶颗粒的加入,对冻胶基液黏度和成胶时间没有明显的改变,但对成胶强度、耐温耐盐性能和封堵效果具有明显提高作用。其中,橡胶颗粒质量分数为5%的增强冻胶的屈服应力达326.4 Pa,150 ℃下老化30天,脱水率仅为2.71%,对缝宽1 mm的裂缝岩心进行封堵,盐水突破压力梯度达到3.94 MPa/m。这表明,橡胶颗粒增强的双网络结构冻胶具有优异的封堵能力。结论该研究填补了塔河油田耐高温高盐堵水冻胶的技术空白,为塔河油田堵水技术发展提供了新的研究思路。      

碱金属盐对气基还原铁矿石的催化规律研究

通过气体催化还原氧化铁试验,研究了碱金属盐对气基还原铁氧化物反应的影响规律,对于同一种阳离子的盐催化活性规律为:氟化物＞氯化物＞碘化物＞溴化物;硝酸盐＞氢氧化物＞碳酸盐＞硫酸盐>磷酸盐.并提出了一种新的微观催化机理:添加剂的催化作用在于添加剂的原子改变Fe-O化学键的作用程度;添加剂的催化活性与阳离子、阴离子种类以及化合物的稳定性有关;这三方面因素相互耦合,共同决定添加剂的催化性能;其催化性能用公式表示为:Ψαf(M ) βf(X-)-γ(T)f(MX).     

月桂酸阳离子酯表面活性剂的合成及性能

实验以十二叔胺与环氧氯丙烷合成环氧中间体N-2,3-环氧丙基二甲基十二烷基氯化铵,再与月桂酸反应制备了月桂酸阳离子酯表面活性剂2-羟基-3-十二酰氧丙基-二甲基十二烷基氯化铵(HDAC)。考察了反应条件对产物收率的影响,合成中间体的最佳条件为:反应温度25℃,n(环氧氯丙烷):n(十二叔胺)=1:1,时间约24 h。再用活性中间体与月桂酸在丙酮中以等物质的量比于60℃反应8 h得到柔软性能良好的HDAC,其水溶液的临界胶束浓度为0.85 mmol/L,表面张力为27.38 mN/m。     

A Comprehensive Identification and Function Analysis of Serine/Arginine-Rich (SR) Proteins in Cotton (Gossypium spp.)

As one of the most important factors in alternative splicing (AS) events, serine/arginine-rich (SR) proteins not only participate in the growth and development of plants but also play pivotal roles in abiotic stresses. However, the research about SR proteins in cotton is still lacking. In this study, we performed an extensive comparative analysis of SR proteins and determined their phylogeny in the plant lineage. A total of 169 SR family members were identified from four Gossypium species, and these genes could be divided into eight distinct subfamilies. The domain, motif distribution and gene structure of cotton SR proteins are conserved within each subfamily. The expansion of SR genes is mainly contributed by WGD and allopolyploidization events in cotton. The selection pressure analysis showed that all the paralogous gene pairs were under purifying selection pressure. Many cis-elements responding to abiotic stress and phytohormones were identified in the upstream sequences of the GhSR genes. Expression profiling suggested that some GhSR genes may involve in the pathways of plant resistance to abiotic stresses. The WGCNA analysis showed that GhSCL-8 co-expressed with many abiotic responding related genes in a salt-responding network. The Y2H assays showed that GhSCL-8 could interact with GhSRs in other subfamilies. The subcellular location analysis showed that GhSCL-8 is expressed in the nucleus. The further VIGS assays showed that the silencing of GhSCL-8 could decrease salt tolerance in cotton. These results expand our knowledge of the evolution of the SR gene family in plants, and they will also contribute to the elucidation of the biological functions of SR genes in the future.     

Acute T-Cell-Driven Inflammation Requires the Endoglycosidase Heparanase-1 from Multiple Cell Types

It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, since many redundant proteases can solubilise BM it has been difficult to prove that proteases aid cell migration, particularly in vivo. Recent studies also suggest that other mechanisms allow BM passage of cells. To resolve this issue we exploited heparanase-1 (HPSE-1), the only endoglycosidase in mammals that digests heparan sulfate (HS), a major constituent of BM. Initially we examined the effect of HPSE-1 deficiency on a well-characterised adoptive transfer model of T-cell-mediated inflammation. We found that total elimination of HPSE-1 from this system resulted in a drastic reduction in tissue injury and loss of target HS. Subsequent studies showed that the source of HPSE-1 in the transferred T cells was predominantly activated CD4⁺ T cells. Based on bone marrow chimeras, two cellular sources of HPSE-1 were identified in T cell recipients, one being haematopoiesis dependent and the other radiation resistant. Collectively our findings unequivocally demonstrate that an acute T-cell-initiated inflammatory response is HPSE-1 dependent and is reliant on HPSE-1 from at least three different cell types.