Inhibitory factors affecting the process of enhanced biological phosphorus removal (EBPR) – A mini-review

Enhanced biological phosphorus removal (EBPR) technology has been widely considered as a key strategy in preventing eutrophication and recognized as the advancing front of research in wastewater treatment. The key to keep its high efficiency in biological phosphorus removal is to optimize the operation and management of the system. Previous research in this field has undoubtedly improved understanding of the factors hindered overall efficiency of EBPR. However, it is obvious that much remains to be learnt. This paper attempts to review the fundamental understanding in factors inhibiting the stability and reliability of the EBPR systems in the state-of-the-art research. In view of modeling the EBPR systems, an appropriate extension of the current mechanistic models with these inhibitory factors is recommended in order to better simulate and predict the behavior of full-scale and lab-scale EBPR plants. From the perspectives of the further mechanistic and multi-factors study, the direction of denitrifying dephosphatation and granules/biofilms are also discussed. This comprehensive overview will not only help us to understand the overall mechanism of the EBPR process, but also benefit the researchers and engineers to consider all the possible factors affecting the process in the urban sewage treatment plants.     

Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca²⁺ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca²⁺ permeability (P_Ca/P_Na) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca²⁺ conductance, because neither Na⁺ conductance nor Ca²⁺-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca²⁺ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca²⁺ permeability.     

基于网络药理学探讨皂角刺治疗乳痈的作用机制

摘要 目的：基于网络药理学探讨皂角刺治疗乳痈的作用机制。方法：通过建立皂角刺药物靶点数据集、乳痈相关疾病靶点数据集，构建皂角刺治疗急性乳腺炎的蛋白互作（PPI）网络，构建并分析"皂角刺活性成分-潜在靶点-急性乳腺炎"网络。开展基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，探讨皂角刺治疗乳痈的可能机制。结果：共得到皂角刺活性成分11个，筛选出活性成分所对应的不重复靶点共97个，其中1个活性成分无对应靶点。通过搜集GeneCards 和OMIM数据库，共得到292个急性乳腺炎的相关靶点基因。将疾病靶点基因与药物活性成分所对应的靶点进行比对后，得到10个交集靶点，即皂角刺治疗急性乳腺炎的潜在靶点。皂角刺活性成分按degree值排前3名的依次为槲皮素（quercetin）、漆黄素（fisetin）、山奈酚（kaempferol），其中皂角刺治疗乳痈的靶点包括白细胞介素-6（IL-6）、表皮生长因子受体（EGFR）、酪氨酸激酶受体2（ERBB2）、细胞间黏附分子-1（ICAM1）、雌激素受体1（ESR1）等5个关键靶点，主要涉及乳腺癌疾病通路、TNF信号通路和雌激素信号通路等3条信号通路。结论：皂角刺治疗乳痈的作用机制可能与机体的炎症反应以及雌激素水平变化等密切相关。     

A possible mechanism for the increased oxidation of choline after chronic ethanol ingestion

An attempt has been made to determine the location of the site at which the metabolism of ethanol interacts with that of choline to produce an increase in the oxidation of choline. The first enzyme in the oxidation pathway for choline, choline dehydrogenase, was assayed using a newly developed spectro-photometric assay and freshly isolated intact rat liver mitochondria. No changes were observed in either the ‘apparent’ V or the ‘apparent’ K_m values of choline dehydrogenase for choline after ethanol ingestion. However, when the choline oxidase system was assayed, a 28% decrease in ‘apparent’ K_m for choline and a 53% increase in ‘apparent’ V was observed. The effects of ATP on choline oxidase were studied further, and a 29.4% decrease was observed in mitochondrial ATP levels from freshly isolated mitochondria from the ethanoltreated rats. In vitro aging of mitochondria further decreased the level of ATP, and the rate of decrease was considerably faster during the first hour in the mitochondria from the ethanol-treated animals. The decreases in ATP from both control and experimental mitochondria were accompanied by increases in choline oxidase activity. The initial decrease in ATP was correlated with an increase in mitochondrial ATPase activity which may be related to an increase in mitochondrial Mg²⁺. Because chronic ethanol ingestion has resulted in decreased oxidation rates of succinate and β-hydroxybutyrate while at the same time increasing the oxidation rates of choline, the studies reported here suggest that the effect of chronic ethanol ingestion is primarily on a step that is unique to choline and which probably exists prior to the electron transport chain.     

Honey: Single food stuff comprises many drugs

Honey is a natural food item produced by honey bees. Ancient civilizations considered honey as a God gifted prestigious product. Therefore, a huge literature is available regarding honey importance in almost all religions. Physically, honey is a viscous and jelly material having no specific color. Chemically, honey is a complex blend of many organic and inorganic compounds such as sugars, proteins, organic acids, pigments, minerals, and many other elements. Honey use as a therapeutic agent is as old as human civilization itself. Prior to the appearance of present day drugs, honey was conventionally used for treating many diseases. At this instant, the modern research has proven the medicinal importance of honey. It has broad spectrum anti-biotic, anti-viral and anti-fungal activities. Honey prevents and kills microbes through different mechanism such as elevated pH and enzyme activities. Till now, no synthetic compound that works as anti-bacterial, anti-viral and anti-fungal drugs has been reported in honey yet it works against bacteria, viruses and fungi while no anti-protozoal activity has been reported. Potent anti-oxidant, anti-inflammatory and anti-cancerous activities of honey have been reported. Honey is not only significant as anti-inflammatory drug that relieve inflammation but also protect liver by degenerative effects of synthetic anti-inflammatory drugs. This article reviews physico-chemical properties, traditional use of honey as medicine and mechanism of action of honey in the light of modern scientific medicinal knowledge.     

长链非编码RNA及其与疾病相关性的研究进展*

人类基因组中,用于蛋白质编码的核酸序列约占1.5%,另外98.5%的非蛋白编码基因被视为"噪音"序列,并未引起人们的注意。随着测序技术的发展,人们发现大部分的基因被转录成RNA,其中多数为长度大于200nt且不编码蛋白质的长链非编码RNA(Long non-coding RNA, lncRNA),其作用机制包括支架分子、引导分子等,广泛参与细胞发育、增殖及迁移过程,且其水平的改变又与肿瘤、代谢性疾病等相关。本文主要对lncRNA的分类、作用机制及涉及的疾病等进行综述,为进一步研究lncRNA的功能机制奠定基础。     

不同剂量瑞舒伐他汀钙治疗脑梗死患者的临床疗效及机制研究

目的:探讨不同剂量瑞舒伐他汀钙治疗脑梗死患者的临床疗效,并分析其疗效机制。方法:将2015年2月至2018年2月医院诊治的脑梗死患者84例按随机数字表法分为观察组(42例)及对照组(42例)。所有患者入院后均给予降血压、降血糖、稳定颅内压以及改善微循环等基本治疗,在此基础上,对照组口服瑞舒伐他汀钙10 mg/d,观察组口服瑞舒伐他汀钙20 mg/d,两组疗程均为14 d。比较两组疗效、治疗前后美国国立卫生研究所卒中量表(NIHSS)评分以及日常生活能力量表(Barthel指数)变化,并比较两组血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、高迁移率族蛋白-1(HMGB1)和超敏C反应蛋白(hs-CRP)水平,分析血清HMGB1、IL-6、IL-8和hs-CRP之间的相关性,记录两组患者治疗过程中不良反应发生情况。结果:观察组治疗总有效率为95.24%(40/42),明显高于对照组的80.95%(34/42)(P0.05)。两组治疗后NIHSS评分均低于治疗前,Barthel指数高于治疗前,同时,观察组NIHSS评分降低程度大于对照组,Barthel指数升高程度大于对照组(P0.05)。治疗后两组患者血清IL-6、IL-8、HMGB1、hs-CRP明显降低,且观察组血清IL-6、IL-8、HMGB1、hs-CRP明显低于对照组(P0.05)。Person相关性分析表明患者血清HMGB1与IL-6、IL-8、hs-CRP呈正相关(r=0.306,0.428,0.367,均P0.05),IL-6与IL-8、hs-CRP呈正相关(r=0.327,0.385,P0.05),IL-8与hs-CRP亦呈正相关(r=0.430,P0.05)。治疗期间两组不良反应发生率比较无统计学差异(P0.05)。结论:高剂量瑞舒伐他汀钙治疗脑梗死能够促进神经功能恢复,提高日常生活能力,临床疗效显著,其机制可能与降低脑梗死急性期炎症反应有关。     

Recent advances in natural antifungal flavonoids and their derivatives

The resistance of pathogenic fungi and failure of drug therapy increased dramatically. Numerous studies have reported the individual or synergistic antifungal potency of natural and synthesized flavonoids, especially against drug-resistant fungi. This brief review summarizes the structure and individual or synergistic antifungal activity of natural and synthesized flavonoids (literatures mainly cover the past 10 years 2009–2019), with a special focus on the antifungal spectra, structure–activity relationship and mechanisms of actions. These may contribute to a better understanding of flavonoids as multi-target agents in the treatment of mycoses and provide some ideas on the development of novel flavonoids-based antifungals.