荒漠微藻的碳氧转换与调控

为了提高微藻的生物燃料生产效率及其在密闭环境中的碳氧转换效率,以两株荒漠微藻BG18-3、BE6-2和一株淡水蓝藻7924为研究对象,对其进行逆境条件培养,发现荒漠微藻BG18-3在各种逆境中表现最佳。在静态培养中,荒漠微藻BG1-3也具有明显的优势,其生物量干重达到0.26 g/L,硝态氮和磷酸盐去除率分别为36%和99%。在荒漠微藻BG18-3的通气培养中,生物干重量最高（3% CO₂通气培养16天）达到2.63 g/L,生物量产率为164.0 mg/L·d,出口CO₂浓度最低降到0.04%,O₂净含量增加0.68%,这表明荒漠微藻BG18-3具有较高的碳氧转化效率,具有生产生物燃料的潜质。最后根据18s rDNA分析结果将荒漠微藻BG18-3鉴定为栅列藻Scenedesmus littoralis。     

Design,synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment

A series of 4′-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ_1–42 aggregation (60.0% and 78.2%, respectively) and Cu²⁺-induced Aβ_1–42 aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.     

Sesquiterpene Lactones with COX‐2 Inhibition Activity from Artemisia lavandulaefolia

Two new sesquiterpene lactones, artelavanolides A ( 1 ) and B ( 2 ), and four known sesquiterpene lactones ( 3 – 6 ) were isolated from the leaves of Artemisia lavandulaefolia. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D‐NMR and HR‐ESI‐MS). The absolute configuration of 1 was determined by the analysis of single‐crystal X‐ray diffraction data. Artelavanolide A ( 1 ) is a rare sesquiterpene lactone possessing an unusual skeleton with the linkage of Me(14)–C(1) that is probably formed through a rearrangement of the guaiane‐type sesquiterpenoids. Artelavanolide B ( 2 ) is a new highly unsaturated guaianolide. Compounds 1 – 6 were tested for activities on the inhibition of COX‐2 enzyme in vitro. All of compounds exhibited inhibitory activity against COX‐2 with IC₅₀ values ranging from 43.29 to 287.07 μm compared with the positive control, celecoxib (IC₅₀ = 18.10 μm ). Among them, 3 showed the best COX‐2 inhibitory activity with an IC₅₀ value of 43.29 μm .     

A context-free encoding scheme of protein sequences for predicting antigenicity of diverse influenza A viruses

Background

The evolution of influenza A viruses leads to the antigenic changes. Serological diagnosis of the antigenicity is usually labor-intensive, time-consuming and not suitable for early-stage detection. Computational prediction of the antigenic relationship between emerging and old strains of influenza viruses using viral sequences can facilitate large-scale antigenic characterization, especially for those viruses requiring high biosafety facilities, such as H5 and H7 influenza A viruses. However, most computational models require carefully designed subtype-specific features, thereby being restricted to only one subtype.

Methods

In this paper, we propose a Context-FreeEncoding Scheme (CFreeEnS) for pairs of protein sequences, which encodes a protein sequence dataset into a numeric matrix and then feeds the matrix into a downstream machine learning model. CFreeEnS is not only free from subtype-specific selected features but also able to improve the accuracy of predicting the antigenicity of influenza. Since CFreeEnS is subtype-free, it is applicable to predicting the antigenicity of diverse influenza subtypes, hopefully saving the biologists from conducting serological assays for highly pathogenic strains.

Results

The accuracy of prediction on each subtype tested (A/H1N1, A/H3N2, A/H5N1, A/H9N2) is over 85%, and can be as high as 91.5%. This outperforms existing methods that use carefully designed subtype-specific features. Furthermore, we tested the CFreeEnS on the combined dataset of the four subtypes. The accuracy reaches 84.6%, much higher than the best performance 75.1% reported by other subtype-free models, i.e. regional band-based model and residue-based model, for predicting the antigenicity of influenza. Also, we investigate the performance of CFreeEnS when the model is trained and tested on different subtypes (i.e. transfer learning). The prediction accuracy using CFreeEnS is 84.3% when the model is trained on the A/H1N1 dataset and tested on the A/H5N1, better than the 75.2% using a regional band-based model.

Conclusions

The CFreeEnS not only improves the prediction of antigenicity on datasets with only one subtype but also outperforms existing methods when tested on a combined dataset with four subtypes of influenza viruses.

     

依那普利叶酸片对高血压伴高同型半胱氨酸血症大鼠左室肥厚干预的研究

目的:观察高同型半胱氨酸对高血压大鼠心肌内质网应激相关因子GRP94、caspase12表达的影响,及依那普利叶酸片(简称依叶片)对其表达的干预作用。方法:30只雄性成年自发性高血压大鼠(SHR),随机分为对照组、模型组和依叶片组,每组10只。对照组给予普通颗粒饲料喂养同时给予双蒸水灌胃,模型组给予含3%蛋氨酸的颗粒饲料喂养同时给予双蒸水灌胃,依叶片组给予含3%蛋氨酸的颗粒饲料喂养同时给予依叶片粉剂20 mg/kg/d灌胃。实验第8周末,用颈动脉插管法测各组大鼠平均动脉压(MAP),同型半胱氨酸检测仪检测血清同型半胱氨酸(homocystein,Hcy)浓度,称取体质量、全心质量及左心室质量计算大鼠心肌肥厚指数HWI及LVEI,通过HE染色观察心肌细胞形态学改变,免疫组化检测大鼠心肌组织中GRP94及caspase12表达水平。结果:①大鼠血清Hcy水平的变化。对照组大鼠血清Hcy值在正常值范围。与对照组相比,模型组大鼠血清Hcy值显著增高(P0.01);与模型组相比,依叶片组大鼠血清Hcy值明显降低(P0.01)。②大鼠HWI、LVEI及MAP的变化。模型组大鼠的HWI及LVEI均明显高于对照组(P0.05);依叶片干预后大鼠的HWI及LVEI均明显降低(P0.05)。对照组与模型组大鼠的MAP均明显增高,但两组大鼠的MAP差异无统计学意义(P0.05);与模型组相比,依叶片干预后大鼠的MAP明显降低(P0.01)。③大鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP94及caspase12表达。对照组及模型组大鼠心肌细胞GRP94及caspase12表达均增高。与对照组相比,模型组大鼠心肌细胞GRP94、caspase12表达增高更为明显(P0.05)。依叶片干预后大鼠心肌细胞GRP94、caspase12表达明显降低(P0.05)。结论:高Hcy通过ERS途径使高血压大鼠左室肥厚程度加重;依叶片可有效降低血清Hcy及血压水平,抑制心肌细胞ERS,从而有效逆转左室肥厚,其对左室肥厚干预的分子机制为"H型"高血压的预防及治疗提供了新的理论依据。     

Effects of aspirin on the development of Helicobacter pylori-induced gastric inflammation and heterotopic proliferative glands in Mongolian gerbils

Background: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti‐inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori‐induced gastritis and the development of heterotopic proliferative glands. Methods: H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E₂ (PGE₂) levels of gastric tissue were determined. Results: H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori‐induced gastritis, but alleviated H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori‐associated apoptosis but decreased H. pylori‐associated cell proliferation. In addition, the increased gastric PGE₂ levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m. Conclusions: Aspirin alleviates H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori‐induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori‐related gastric carcinogenesis.     

血液净化治疗毒鼠强急性中毒的临床研究

目的 观察血液净化治疗对毒鼠强急性中毒的疗效.方法 在内科常规治疗的基础上,采用血液净化救治急性毒鼠强中毒10例,并与单纯常规治疗的12例对照,比较两组的平均住院天数、治愈率以及APACHE Ⅲ评分变化.结果 血液净化治疗组平均住院天数较常规治疗组明显缩短(P＜0.05),治愈率明显提高(P＜0.05);两组治疗后APACHEⅢ评分均较治疗前降低,其中血液净化组治疗后APACHEⅢ评分降低尤为明显(P＜0.05).结论 血液净化是救治毒鼠强急性中毒的有效方法.     

Histone lysine methyltransferases and demethylases in Plasmodium falciparum

Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.