油松天然次生林居群遗传多样性及与产地地理气候因子的关联分析

利用ISSR分子标记技术,分析了中国北部地区10个油松天然次生林居群的遗传多样性,以及与地理环境因子的相关性.研究结果表明:13条ISSR引物对250个个体扩增出137条谱带,平均多态位点百分率60.72％,不同居群的多态位点百分率差异明显;不同地理居群间的期望杂合度指数在0.2824-0.3702之间,平均为0.3210;Shannon多样性指数范围为0.1923-0.2490,平均为0.2165.居群间的遗传变异占居群总的遗传多样性的37.53％.经Mantel检验,居群间的地理距离和遗传距离间不存在显著相关性(r=0.069,p=0.360).聚类分析(UPGMA)表明,河南宝天曼(BTM)、承德大窝铺(DWP)、宁夏苏峪口(SYK)和甘肃冶力关(YLG)居群聚为一组,辽宁医巫闾山(YWL)、山西沁源灵空山(LKS)、陕西蔡家川林场(CJC)、山西和顺云龙公园(YLGY)和山西汶水三道川林场(SDC)居群为一组,山东蒙山(Ms)居群独立为一组.经分析发现,分布于我国地势二级、三级阶梯分界线区域的油松天然林( YWL、BTM、YLGY)遗传多样性水平高,位于分布区东西临界点居群(MS、YLG)遗传多样性水平低.经相关性分析,温度相关因子(年均温、1月均温、极端最低温)、海拔及年降雨量显著影响遗传多样性水平.油松天然居群分子变异存在一定的地理变异规律.     

Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of colorectal cancer by crosstalk with cancer-associated fibroblasts

C-X-C motif chemokine receptor 7 (CXCR7) is a newly discovered atypical chemokine receptor that binds to C-X-C motif chemokine ligand 12 (CXCL12) with higher affinity than CXCR4 and is associated with the metastasis of colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs) have been known to promote tumor progression. However, whether CAFs are involved in CXCR7-mediated metastasis of CRC remains elusive. We found a significant positive correlation between CXCR7 expression and CAF activation markers in colonic tissues from clinical specimens and in villin-CXCR7 transgenic mice. RNA sequencing revealed a coordinated increase in the levels of miR-146a-5p and miR-155-5p in CXCR7-overexpressing CRC cells and their exosomes. Importantly, these CRC cell-derived miR-146a-5p and miR-155-5p could be uptaken by CAFs via exosomes and promote the activation of CAFs through JAK2–STAT3/NF-κB signaling by targeting suppressor of cytokine signaling 1 (SOCS1) and zinc finger and BTB domain containing 2 (ZBTB2). Reciprocally, activated CAFs further potently enhanced the invasive capacity of CRC cells. Mechanistically, CAFs transfected with miR-146a-5p and miR-155-5p exhibited a robust increase in the levels of inflammatory cytokines interleukin-6, tumor necrosis factor-α, transforming growth factor-β, and CXCL12, which trigger the epithelial–mesenchymal transition and pro-metastatic switch of CRC cells. More importantly, the activation of CAFs by miR-146a-5p and miR-155-5p facilitated tumor formation and lung metastasis of CRC in vivo using tumor xenograft models. Our work provides novel insights into CXCR7-mediated CRC metastasis from tumor–stroma interaction and serum exosomal miR-146a-5p and miR-155-5p could serve as potential biomarkers and therapeutic targets for inhibiting CRC metastasis.Subject terms: Cancer microenvironment, Colon cancer     

抗原抗体复合物型治疗性疫苗(乙克)临床研究中患者血清乙型肝炎病毒表面抗原下降的分析与启示

近年来全球慢性乙型肝炎(chronic hepatitis B,CHB)防治指南提出了“功能性治愈”(functional cure)的概念,即患者经过治疗达到血清乙型肝炎病毒表面抗原(hepatitis B virus surface antigen,HBsAg)消失,但现有抗病毒治疗很难实现这一目标。本研究对既往临床试验中经抗原抗体复合物型治疗性疫苗(乙克)治疗后的CHB患者HBsAg下降情况进行了归纳分析,结果显示,经乙克治疗随访后达到乙型肝炎e抗原(hepatitis B e antigen,HBeAg)血清学转换者的HBsAg下降高达0.95log₁₀IU/mL,显著高于未达到HBeAg血清学转换者的0.32log₁₀IU/mL(P<0.01),而经氢氧化铝佐剂治疗随访后发生HBeAg血清学转换(0.49log₁₀IU/mL)者与未发生HBeAg血清学转换者(0.36log₁₀IU/mL)之间HBsAg下降无统计学差异。乙克组治疗过程中,丙氨酸氨基转移酶(alanine aminotransferase,ALT)骤升(ALT flare)在HBsAg下降>1.0log₁₀IU/mL者中较多见,氢氧化铝组未观察到此现象。回归分析显示,乙克治疗后HBsAg下降的影响因素有患者出现HBeAg血清学转换、感染的HBV为B基因型、治疗过程中ALT出现10倍增高,以及基线血清HBsAg为高水平。结果提示,乙克诱导的特异性免疫对降低CHB患者血清HBsAg水平有一定效果,采用“抗病毒药物治疗＋针对HBsAg的中和性抗体被动免疫＋乙克主动免疫”的“三明治”治疗策略可能会提高“功能性治愈”率。     

锌指蛋白的核酸识别特异性研究进展

锌指蛋白是最大的DNA结合蛋白,它能和DNA进行特异性识别,是研究蛋白—DNA相互作用的理想对象。改变锌指元件上的几个保守的氨基酸位点可设计筛选出序列特异的全新锌指蛋白,计算机在锌指蛋白设计方面的应用,使得全新的锌指蛋白识别特异性明显增强。这在基因治疗等方面,具有广阔的应用前景。     

从肿瘤体积到计划靶体积的三维边缘扩展

在适形放疗中需要在肿瘤体积周围加上三维边缘形成计划靶体积。传统的靶体积到计划体积的扩展方法是在组成靶体积的每层轮廓线外手动勾画一个边缘,费时且结果不准确,本文介绍一种新的三维边缘扩展方法,具有思路简洁,结果准确,节约时间等优点。     

添加营养盐对酒精酵母发酵的影响

在以瓜干为原料的酒精生产中,选择添加适量营养盐及其复合物,能改善酵母菌生长环境,提高发酵产物酒精度,缩短发酵周期     

Design,synthesis and biological evaluation of novel hydroxamic acid based histone deacetylase 6 selective inhibitors bearing phenylpyrazol scaffold as surface recognition motif

In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A series of hydroxamic acid derivatives bearing phenylpyrazol moiety were designed and synthesized as HDAC6 inhibitors. Most compounds showed potent HDAC6 inhibition activity. 11i was the most selective compound against HDAC6 with IC₅₀ values of 0.020 µM and selective factor of 101.1. Structure-activity relationship analysis indicated that locating the linker group at 1′ of pyrazol gave the most selectivity. The most compounds 11i (GI₅₀ = 3.63 μM) exhibited 6-fold more potent than vorinostat in HepG2 cells. Considering of the high selectivity against HDAC6 and anti-proliferation activity, such compounds have potential to be developed as anti-cancer agents.