不同树龄水曲柳半同胞家系生长性状变异研究

为筛选优质的水曲柳种质资源,以吉林省三岔子林业局国家水曲柳良种基地的16年生水曲柳子代测定林75个半同胞家系为材料,分别在第4、11和16年对其树高、地径（胸径）和材积进行测定。方差分析结果表明,不同变异来源各指标均达极显著差异水平（P<0.01）;各指标表型变异系数变化范围为22.20%~63.30%,家系遗传力变化范围为0.796~0.981;相关性分析结果表明各指标间均呈极显著正相关;以材积为评价指标,按10%入选率对家系进行评价选择,初步筛选8个优良家系,入选的家系材积平均值比总平均值高0.007 m³,遗传增益为36.03%;该研究选出的优良家系可为良种登记提供基础,也可为种子园的改建提供材料。     

磁性纳米材料的生物医学应用进展

以四氧化三铁为代表的医用磁性纳米材料具有独特的磁学性能、表面易功能化、良好的生物学相容性等特点,在纳米医学相关领域展现出巨大的应用前景,特别是近年来它作为可介导外场的智能材料,在材料设计和生物医学应用方面均取得了突破性的进展.鉴于此,本文围绕磁性氧化铁纳米材料的生物医学应用,着重介绍近年来其在磁共振影像探针、磁热和磁力效应的生物医学应用、诊疗一体化以及纳米酶催化等领域的研究进展,并对磁性纳米材料在生物医学领域未来的发展方向进行了展望.     

Using focus ion beam to prepare crystal lamella for electron diffraction

Electron diffraction provides a powerful tool to solve the structures of small protein crystals. However, strong interactions between the electrons and the materials limit the application of the electron crystallographic method on large protein crystals with micrometer or larger sizes. Here, we used the focused ion beam (FIB) equipped on the scanning electron microscope (SEM) to mill a large crystal to thin lamella. The influences of the milling on the crystal lamella were observed and investigated, including radiation damage on the crystal surface during the FIB imaging, deformation of the thin crystal lamella, and variation in the diffraction intensities under electron radiation. These observations provide important information to optimize the FIB milling, and hence is important to obtain high-quality crystal samples for routine structure determination of protein crystals using the electron cryo-microscope.     

人中鼻甲来源嗅鞘细胞培养与鉴定的初步研究

目的探索一种从人中鼻甲分离培养嗅鞘细胞的方法并鉴定所获得的细胞。 方法通过手术获取人中鼻甲黏膜组织,随后进行两步消化并剥离黏膜上皮组织,得到体积较小的组织块,再进行组织块原代（传代）培养并加压筛选,最终得到双极或多极样细胞并对获得的细胞进行免疫荧光鉴定。上皮样细胞比例、S100β和p75阳性细胞比例用 ±s表示,组间比较采用独立样本t检验。 结果将不剥离上皮层与剥离上皮层培养的原代细胞中上皮样细胞的比例进行对比,发现上皮层组上皮样细胞比例为（92.23±3.93）%高于剥离上皮层组上皮样细胞的比例（77.63±2.97）%,差异具有统计学意义（t = 5.129,P = 0.007）。采用剥离上皮层法培养原代细胞,经过加压筛选的细胞呈现双极或多极样,符合嗅鞘细胞形态学特点。免疫荧光染色发现,S100β阳性细胞占总细胞量的（8.1±1.7）%,而p75阳性细胞占总细胞量的5%以下,达到国内外研究同等水平。 结论通过使用两步消化法和加压筛选联合的方法从人中鼻甲粘膜组织中成功获得了人中鼻甲嗅鞘细胞,相比较传统方法,细胞分离培养周期明显缩短。     

In vivo surveillance and elimination of teratoma-forming human embryonic stem cells with monoclonal antibody 2448 targeting annexin A2

This study describes the use of a previously reported chimerised monoclonal antibody (mAb), ch2448, to kill human embryonic stem cells (hESCs) in vivo and prevent or delay the formation of teratomas. ch2448 was raised against hESCs and was previously shown to effectively kill ovarian and breast cancer cells in vitro and in vivo. The antigen target was subsequently found to be Annexin A2, an oncofetal antigen expressed on both embryonic cells and cancer cells. Against cancer cells, ch2448 binds and kills via antibody-dependent cell-mediated cytotoxicity (ADCC) and/or antibody-drug conjugate (ADC) routes. Here, we investigate if the use of ch2448 can be extended to hESC. ch2448 was found to bind specifically to undifferentiated hESC but not differentiated progenitors. Similar to previous study using cancer cells, ch2448 kills hESC in vivo either indirectly by eliciting ADCC or directly as an ADC. The treatment with ch2448 post-transplantation eliminated the in vivo circulating undifferentiated cells and prevented or delayed the formation of teratomas. This surveillance role of ch2448 adds an additional layer of safeguard to enhance the safety and efficacious use of pluripotent stem cell-derived products in regenerative medicine. Thereby, translating the use of ch2448 in the treatment of cancers to a proof of concept study in hESC (or pluripotent stem cell [PSC]), we show that mAbs can also be used to eliminate teratoma forming cells in vivo during PSC-derived cell therapies. We propose to use this strategy to complement existing methods to eliminate teratoma-forming cells in vitro. Residual undifferentiated cells may escape in vitro removal methods and be introduced into patients together with the differentiated cells.     

Inhibition mechanisms of CRISPR-Cas9 by AcrIIA17 and AcrIIA18

Mobile genetic elements such as phages and plasmids have evolved anti-CRISPR proteins (Acrs) to suppress CRISPR-Cas adaptive immune systems. Recently, several phage and non-phage derived Acrs including AcrIIA17 and AcrIIA18 have been reported to inhibit Cas9 through modulation of sgRNA. Here, we show that AcrIIA17 and AcrIIA18 inactivate Cas9 through distinct mechanisms. AcrIIA17 inhibits Cas9 activity through interference with Cas9-sgRNA binary complex formation. In contrast, AcrIIA18 induces the truncation of sgRNA in a Cas9-dependent manner, generating a shortened sgRNA incapable of triggering Cas9 activity. The crystal structure of AcrIIA18, combined with mutagenesis studies, reveals a crucial role of the N-terminal β-hairpin in AcrIIA18 for sgRNA cleavage. The enzymatic inhibition mechanism of AcrIIA18 is different from those of the other reported type II Acrs. Our results add new insights into the mechanistic understanding of CRISPR-Cas9 inhibition by Acrs, and also provide valuable information in the designs of tools for conditional manipulation of CRISPR-Cas9.