Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure–activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 μg/mL; MIC-MDRTB = 2.0 μg/mL; MIC-RDRTB = 0.25 μg/mL; Mt SD-IC₅₀ = 86.39 μg/mL; and 6g-3, MIC-H37Rv = 1.0 μg/mL; MIC-MDRTB = 4.0 μg/mL; MIC-RDRTB = 2.0 μg/mL; Mt SD-IC₅₀ = 73.57 μg/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance-reversing agents.     

Heavy Metal Level in Human Semen with Different Fertility: a Meta-Analysis

Researches conducted worldwide indicate a frequent deficiency in mineral matters. Due to the increased need during the period of accelerated growth and development, children belong to the group that is exposed to the highest risk of mineral matter deficiency. Our objectives were to determine the iron, zinc, copper, manganese, and calcium intake in the collective diet of the preschool population in the in the northwestern region of Bosnia- in the Republic of Srpska and to estimate the adequacy of the application of the international food composition tables for nutrition planning relating to mineral matters. Samples of food intended for children’s diet were collected in the preschool institution “Radost” (a kindergarten), in the city of Prijedor. In daily portions, Fe, Zn, Cu, Mn, and Ca contents were determined by flame atomic absorption spectrophotometry. Contents of mineral matters in daily meals were also calculated by the food composition tables. An average daily meal contained 2.86 mg of Fe, 1.71 mg of Zn, 0.19 mg of Cu, 0.21 mg of Mn, and 83.5 mg of Ca. With calculation method, contents of all minerals are significantly higher than the experimental data for all used food composition tables. The obtained results indicate a significant deficiency in mineral matters in the collective diet of the preschool population in the Republic of Srpska, a certain non-compliance with the applicable recommendations, and also suggest a need to create food composition tables for food being consumed in our region.     

麋鹿夜间卧息地选择的季节变化

卧息地选择是野生动物对生态环境的行为适应。为了探讨麋鹿(Elaphurus davidianus)夜间卧息地选择的季节变化, 2013年11月至2014年12月, 采用跟踪调查法与直接观察法, 对湖北石首麋鹿国家级自然保护区围栏内麋鹿184个夜间卧息样方和184个对照样方的生态因子信息进行了观测记录。结果表明: 麋鹿春、秋、冬3个季节夜间卧息时均选择隐蔽度较高、草本盖度较高、食物丰富度较高、距隐蔽物(芦苇或树林)较近的林地生境(P < 0.05), 并且春、秋季夜间选择在距道路距离与距居民点距离上的差异不显著(P > 0.05); 夏季夜间选择在草本盖度较低、食物丰富度较低、隐蔽度较低、距隐蔽物较近、距道路与居民点距离较远、距水源较近的滩涂生境卧息(P < 0.05); 冬季夜间选择在风速较小、距道路与居民点较近的生境卧息。判别分析表明: 草本盖度、食物丰富度、距道路距离、隐蔽度、风速、距水源距离以及距隐蔽物距离这7个因子组成的判别函数可区分不同季节麋鹿的夜间卧息地, 且麋鹿在不同季节的夜间卧息地特征存在部分重叠, 这可能与不同季节间食物、水、温度与人为干扰等因子的差异性有关。建议该保护区扩大饲料基地面积、保留麋鹿卧息隐蔽环境、减少人为干扰、控制长江故道水位。     

Production of antioxidant and antitumor metabolites by submerged cultures of <Emphasis Type="Italic">Inonotus obliquus</Emphasis> cocultured with <Emphasis Type="Italic">Phellinus punctatus</Emphasis>

While Inonotus obliquus produces a diverse range of bioactive metabolites in its natural habitats, it accumulates less in its submerged cultures. We show here that coculture of I. obliquus with Phellinus punctatus resulted in less production of mycelial biomass but an increased accumulation of phenolic compounds, melanins, and lanostane-type triterpenoids. Metabolites increased in production by coculture include phelligridin C, phelligridin H, methyl inoscavin A, inoscavin C, inoscavin B, davallialactone, methyl davallialactone, foscoparianol D, 21,24-cyclopentalanosta-3β,21,25-triol-8-en, lanosta-7,9(11),23-triene-3β,22,25-triol, and inotodisaccharide and melanins. Metabolites from coculture also showed an increased potential for scavenging free radicals and inhibiting the proliferation of HeLa 229 cells. Davallialactone, methyl davallialactone, and minor phenolic components are the major contributors for scavenging DPPH and hydroxyl radical in monoculture, and phelligridin C, phelligridin H, methyl inoscavin A, inoscavin C, methyl davallialactone, foscoparianol D, and inotodisaccharide are those for scavenging the tested radicals in coculture. Lanostane-type triterpenoids indicated limited roles in scavenging free radicals. Nearly all the detected metabolites correlate positively with inhibiting proliferation of HeLa 229 cells. Thus, coculture of I. obliquus with other fungi seems to be a cost-effective strategy for upregulating biosynthesis of bioactive metabolites.     

Involvements of <Emphasis Type="Italic">S</Emphasis>-nitrosylation and denitrosylation in the production of polyphenols by <Emphasis Type="Italic">Inonotus obliquus</Emphasis>

Nitric oxide (NO) has been evidenced to mediate biosynthesis of polyphenols in Inonotus obliquus. However, it remains unknown how NO regulates their biosynthesis. Here we show that higher cellular NO levels coincided with higher accumulation of S-nitrosothiols (SNO; the products of NO combined with a specific residue in glutathione or proteins) and polyphenols, and higher activity of denitrosylated S-nitrosoglutathione reductase (GSNOR) and thioredoxin reductase (TrxR). This homeostasis was breached by GSNOR or TrxR inhibitors. Inhibiting GSNOR boosted TrxR activity, but reduced SNO formation, coinciding with an enhanced production of polyphenols. Likewise, inhibiting TrxR increased GSNOR activity and SNO production, but downregulated accumulation of polyphenols. Inhibiting GSNOR or TrxR also modified the polyphenolic profiles of I. obliquus. Suppressing GSNOR-enhanced biosynthesis of phelligridins C and H, inoscavin C and methyl inoscavin B, but reduced that of phelligridin D, methyl inoscavin A, davallialactone and methyl davallialactone, the typical polyphenols in I. obliquus. Similarly, downregulating TrxR increased production of phelligridin D, methyl inoscavin A, davallialactone, and methyl davallialactone, but shrinking that of phelligridins C and H, methyl inoscavin B and inoscavin C. Thus, in I. obliquus, the state of S-nitrosylation and denitrosylation affects not only the accumulation of polyphenols, but also their metabolic profiles.     

多数据库分析肝细胞癌中GLTPD2的表达及临床意义

人类糖脂转运结构域2蛋白(GLTPD2)是糖脂转运蛋白(GLTP)家族的一个新成员.本研究的目的在于通过生物信息学分析,探究GLTPD2在肝细胞癌(LIHC)中的表达及临床意义.利用TCGA数据库的第三方在线工具LinkedOmics分析GLTPD2的表达与LIHC各临床病理特征的关系;利用Ualcan工具分析GLTP...     

块菌人工栽培现状及菌根苗培育方法的研究进展

松露(块菌)是名贵的地下真菌,因其独特的香味和口感享誉全球,具有重要的经济价值、食药用价值和生态价值。块菌必须与宿主植物共生形成外生菌根后才能形成子实体(子囊果)。由于块菌具有较高的经济价值而野生块菌资源被严重破坏,以块菌菌根苗制备技术为基础的人工栽培手段受到广泛关注。本文以块菌菌根苗培育为切入点,阐述了块菌资源面临的较大威胁、人工栽培手段的进步和人工种植园的快速发展,通过综述菌根苗培育前对共生组合的选择,菌根苗培育时使用的基质、接种剂、培养方式、与其他生物间的互作,以及菌根苗培育后进行检测的方法等研究进展,为外生菌根食用菌的菌根苗培育技术和人工栽培推广提供参考。