FEN1是一种结构特异性的多功能核酸酶,具有5''-3''flap核酸内切酶(FEN)、缺口核酸内切酶(GEN)和核酸外切酶(EXO)三大酶切活力.在细胞内,FEN1在多条DNA代谢途径中起着重要作用,包括冈崎片段成熟、长片段碱基切除修复和端粒维持等.鉴于FEN1的复杂功能,细胞内必定存在着一套精确调控机制,以确保FEN1在合适的时间与地点发挥作用.FEN1功能失调将导致基因组的稳定性和完整性下降,最终诱发包括肿瘤在内的多种染色体相关的疾病.本文主要针对FEN1的功能调控、功能失调与肿瘤的关系做一个综述.

Flap endonuclease-1 ( FEN1 ) is a kind of structure-specific multifunctional nuclease which contains 5′->3′flap endonuclease( FEN) activity,gap endonuclease( GEN) activity and exonuclease( EXO) activity. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways,including Okazaki fragment maturation, long-patch base excision repair and telomere maintenance. As such,FEN1 must be precisely regulated to execute each of its functions with the right timing and in a specific subcellular location. FEN1 dysfunction will lead to genomic stability and integrity descend, and eventually induce a variety of chromosomal diseases including tumor. This review mainly targets FEN1’s functional regulation and its link to cancer.

【目的】明确枯草芽胞杆菌Bs916(Bacillus subtilis 916)分泌的脂肽化合物Fengycin操纵子的结构、功能和生物活性,阐明枯草芽孢杆菌Bs916防治真菌病害的分子作用机制。【方法】在Bs916全基因组测序基础上,采用LA-PCR方法克隆Fengycin的操纵子Fen;通过生物信息学方法分析Fen操纵子的遗传特征;运用基质辅助解离质谱法测定Fen操纵子合成的脂肽类化合物中同系物的分子量;采用同源重组方法构建Fengycin突变株BSFG;通过抑菌活性和溶血活性试验测定突变株BSFG的生物活性。【结果】克隆到Bs916基因组DNA中全长约37.67 kb的Fen操纵子,含有5个开放阅读框架分别编码FenA、FenB、FenC、FenD和FenE多功能复合酶;与Bs168对应Fen操纵子的同源性为65%。根据该操纵子特征推测其编码的脂肽类化合物为Fengycin;Fen操纵子负责合成的Fengycin包含5个变异体,分属于两类不同同系物。同系物1的质子化峰分子量分别为1 449.8、1 463.9、1 477.9;属于相差1个(-CH2)亚甲基的同系物,一级结构为[cyclo-([cyclo-(Glu-Orn-Tyr-Thr-Glu-Ala-Pro-GlnTyr-β-amino fatty acid)];同系物2的质子化峰分子量分别为1 491.9和1 505.9,也属于相差1个(-CH2)亚甲基的同系物,相对于同系物1其第6位的Ala氨酸残基变为Val氨酸残基。生物活性测定结果表明突变株BSFG抗菌活性相对于野生型菌株Bs916得到显著下降,但溶血活性的变化不明显。【结论】本研究克隆了生防菌Bs916中合成Fengycin的完整操纵子,通过对操纵子生物信息学分析和生化试验鉴定了Fengycin的5种变异体的化学结构,并阐明了脂肽Fengycin是Bs916抗真菌活性的重要因子之一。

[Objective]The objective of this study is to clone and sequence the Fen operon responsible for synthesis of the fengycin from Bacillus subtilis 916 and determine the structure and biological activities of the Fen operon. [Method]Genome sequence and PCR were performed to clone the Fen operon. Analysis of the Fen operon genetic structure was made by using bioinformatics. The Fen mutant BSFG was constructed by the homologous recombination. Fengycin produced by the Bs916 and mutant was analyzed by the reversed-phase high-performance liquid chromatography (HPLC). The molecular weight of the fengycin was determined by the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MS). The antifungal activities and hemolytic activities were evaluated in the form of a flat plate. [Result]The 37.67 kb Fen operon responsible for synthesis of fengycin was identified and cloned from B. subtilis 916. The operon contained five ORFs designated FenA, FenB, FenC, FenD and FenE, respe

以醋酸铁为前驱体、乙醇为溶剂,通过浸渍、干燥、H2预还原以及NH3氮化,将粒径为100~600nm磁性纳米FexN颗粒植入膨胀石墨(EG)得到FexN-EG复合材料,随氮化温度升高FexN物相主要为Fe4N、Fe2~3N、FeN,所得FexN饱和磁化强度较高,为软磁材料。改变氮化温度可以调控植入的纳米FexN中N原子的比例,从而可以改变FexN的磁性,显著提高复合材料的低频电磁屏蔽效能,使其在较宽的频段内有好的电磁屏蔽效能。结果表明,400℃氮化时磁性颗粒物相以Fe4N为主,此时复合材料的电磁屏蔽效能最好,面密度仅为0.09 g/cm2的试样在300 kHz~1.5 GHz范围的电磁屏蔽效能达68.5~100 dB。

Using iron acetate as precursor and diethyl ether as solvent, FexN-EG composites were prepared by embedding FexN nano-particles in the layers of expanded graphite (EG) by impregnating, drying, pre-reducing in H2 and nitriding in NH3. With increasing the nitriding temperature, FexN mainly consists of Fe4N, Fe2~3N and FeN. The FexN nano-particles exhibt a higher saturation magnetization and particle sizes of mainly 100-600 nm, and are well spread on the layers of EG. N atom percentage of FexN can be regulated by changing nitriding temperature to change the magnetic property of FexN, and resultantly improving shielding effectiveness (SE) for electromagnetic radiations at low frequencies. Since EG is electronically conductive and displays high SE at high frequencies, the composites exhibit good SE at a wide range of frequenciy. The magnetic property of the composites could be monitored through regulating the nitriding temperature, and it was found that the nitrided composites exhibited goo

汾酒具有悠久的历史、深厚的文化底蕴,完全可傲立于白酒产品的最高端。汾酒厂股份公司酿酒工艺应遵循传统、手工酿造,打造高品质的汾酒系列产品;杏花村酒业发展区强调现代机械化、规模化、标准化生产,通过多品牌占领中低端市场,并逐步打造"杏花村"高端产品,与汾酒并驾齐驱。

Fen liquor has a long history and rich cultural heritage, which endow Fen liquor with the most high-end liquor product. Fen Distillery Co., Ltd should follow the traditional manual liquor making process to produce high-quality Fen liquor series; whereas the Xinhuacun Liquor Industry Development District Co. Ltd. should emphasize modern mechanized, large-scale and standardized production to occupy the middle and low-end market with multi-brand liquor, and to gradually build"Xinghuacun"high-end products which are at the same level of Fen liquor.

总结马春芬教授治疗输卵管阻塞性不孕症的经验。方法:随师侍诊,聆听导师教诲,同时收集整理医案,总结其临证经验。结果:马春芬教授在临床治疗中辨证论治,循时用药,内外合治,疗效尤佳。结论:中医治疗输卵管阻塞性不孕症临床效果显著,无创伤,复发率低。

Objective:Experience of Prof. MA Chun-fen for treating tubal obstruction infertility was summarized. Methods:Basic documents were collected. Results:Depending on different time and situation, treating tubal obstruction infertility by Prof. MA Chun-fen in TCM was significant. Conclusion:TCM was effective and come with low recurrence rate on tubal obstruction infertility.