Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles

The gut microbiota–host co-metabolites are good indicators for representing the cross-talk between host and gut microbiota in a bi-direct manner. There is increasing evidence that levels of aromatic amino acids (AAAs) are associated with the alteration of intestinal microbial community though the effects of long-term microbial disturbance remain unclear. Here we monitored the gut microbiota composition and host–microbiota co-metabolites AAA profiles of mice after gentamicin and ceftriaxone treatments for nearly 4 months since their weaning to reveal the relationship between host and microbiome in long- term microbial disturbances. The study was performed employing targeted LC-MS measurement of AAA-related metabolites and 16S RNA sequence of mice cecal contents. The results showed obvious decreased gut microbial diversity and decreased Firmicutes/Bacteroidetes ratio in the cecal contents after long-term antibiotics treatment. The accumulated AAA (tyrosine, phenylalanine and tryptophan) and re-distribution of their downstreaming metabolites that produced under the existence of intestinal flora were found in mice treated with antibiotics for 4 months. Our results suggested that the long-term antibiotic treatment significantly changed the composition of the gut microbiota and destroyed the homeostasis in the intestinal metabolism. And the urinary AAA could be an indicator for exploring interactions between host and gut microbiota.     

含氮有机物在污水处理过程中的生物转化机制与模型研究进展

随着市政污水处理厂的提标改造,出水总氮浓度逐渐降低,但溶解性有机氮(Dissolved Organic Nitrogen,DON)在总氮中的占比却越来越高,对含氮消毒副产物的生成和受纳水体富营养化的潜在贡献不可忽视。正因如此,近年来有关污水处理系统中DON的研究不断增加。本文重点综述了污水处理厂DON特征、生成转化规律及其生态影响。目前通过混凝沉淀、消毒等物理化学工艺的联合最高可去除70%左右的进水DON,但生物处理单元的微生物代谢活动会生成新的DON,主要包括氨基酸、聚胺等,其藻类生物可利用性较高。在已有DON模型基础上,本文提出了更加完善的ASM3-DON模型,纳入了包括内源呼吸、细胞生长、微生物产物再利用在内的6个过程,可用于对DON生成转化进行更加精确的模拟。未来围绕污水处理过程的DON研究应重点关注DON的快速精确定量分析、生成转化规律探究以及高效去除方法开发。     

Effect of glutamic acid foliar applications on lettuce under water stress

The yield and quality of leafy vegetables can be compromised by reduced water availability. Glutamic acid is involved in different biological processes and among them it plays an important role in chlorophyll and proline biosynthesis. The aim of this work was to evaluate the possible efficacy of glutamic acid in counteracting water stress in romaine lettuce. Lettuce plants were grown in pots filled with substrate and subjected to water deprivation. A glutamic acid solution (1.9 mM) was applied as foliar treatment, both in stressed and non-stressed plants. The effect of the treatment was evaluated at different time points during the experiment in order to evaluate changes at a molecular, physiological, biochemical and agronomic level. Yield was reduced by 35% in stressed plants, while no significant changes in quality parameters were observed, except for nitrate content, which increased under water stress. At a molecular level, the expression of genes encoding for ROS scavenging enzymes was monitored but, apparently, glutamic acid did not significantly prevent the water stress response. Slightly positive effects deriving from glutamic acid application were found for nitrate and proline contents, suggesting that a possible mode of action of glutamic acid would involve a role for these molecules. Further studies are required, also on other crop species, for confirming these results. Different concentrations and application modes should be also tested.     

Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual''s immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.     

脆弱拟杆菌BF839治疗寻常型银屑病：一项单臂、开放初步临床试验

银屑病被认为是一种T细胞主导的炎症性疾病,其发病与肠道菌群失调密切相关。脆弱拟杆菌 (Bacteroides fragilis,BF) 可通过调节T细胞的细胞因子表达起抗炎作用。目前尚无脆弱拟杆菌用于治疗银屑病的相关报道,文中率先探究脆弱拟杆菌BF839对银屑病的治疗效果。选择2019年4月至2019年10月广州医科大学附属第二医院就诊的27例银屑病患者,维持原治疗不变,口服脆弱拟杆菌BF839 12周,对比治疗前后银屑病皮损面积与严重程度指数 (Psoriasis area and severity index,PASI) 评分,统计治疗12周后药物减停率。结果表明,12周试验完成率为96.3% (26/27),12周PASI30 (PASIN定义为治疗后PASI评分下降≥N%的患者比例) 为65.4%,PASI50为42.3%,PASI75为19.2%;治疗前PASI评分为9.1±5.9,治疗12周后PASI评分为5.8±4.9,具有显著统计学差异 (P<0.01);治疗12周后皮肤瘙痒程度用视觉模拟量表 (Visual analog scale,VAS) 评分有效率为42.3%,治疗前VAS评分为2.9±2.2,治疗12周后VAS评分为2.3±2.1,无显著统计学差异 (P>0.05)。患者治疗12周内不良反应率为3.8% (1/26),其中便秘1例,药物减停率为60.0%。以上结果提示脆弱拟杆菌BF839可能对银屑病治疗有一定疗效,可降低PASI评分及药物使用率,不良反应少,值得进一步研究。     

乳酸菌作为药物分子粘膜投递载体的研究进展

乳酸菌是被公认为安全的食品级微生物,广泛地应用于食品生产、保存以及作为益生菌促进人类健康。鉴于发展有效的投递药物分子策略的需要,乳酸菌成为了极有吸引力的用于口服、鼻饲及阴道进行粘膜投递药物分子的活载体。用乳酸菌作为药物分子的投递载体,安全性好,且可直接合成并投递目标蛋白,显著降低药物生产成本。到目前为止,乳酸菌作为粘膜投递载体,已成功地向粘膜组织投递了一系列功能蛋白用以治疗多种疾病。文中综述了近20年的数据,重点聚焦乳酸菌作为药物分子投递载体的发展和应用,为今后乳酸菌作为活载体的临床研究提供一定参考。     

Exploiting nonsystematic covariate monitoring to broaden the scope of evidence about the causal effects of adaptive treatment strategies

In studies based on electronic health records (EHR), the frequency of covariate monitoring can vary by covariate type, across patients, and over time, which can limit the generalizability of inferences about the effects of adaptive treatment strategies. In addition, monitoring is a health intervention in itself with costs and benefits, and stakeholders may be interested in the effect of monitoring when adopting adaptive treatment strategies. This paper demonstrates how to exploit nonsystematic covariate monitoring in EHR‐based studies to both improve the generalizability of causal inferences and to evaluate the health impact of monitoring when evaluating adaptive treatment strategies. Using a real world, EHR‐based, comparative effectiveness research (CER) study of patients with type II diabetes mellitus, we illustrate how the evaluation of joint dynamic treatment and static monitoring interventions can improve CER evidence and describe two alternate estimation approaches based on inverse probability weighting (IPW). First, we demonstrate the poor performance of the standard estimator of the effects of joint treatment‐monitoring interventions, due to a large decrease in data support and concerns over finite‐sample bias from near‐violations of the positivity assumption (PA) for the monitoring process. Second, we detail an alternate IPW estimator using a no direct effect assumption. We demonstrate that this estimator can improve efficiency but at the potential cost of increase in bias from violations of the PA for the treatment process.     

Parental care in the Small Tree Finch Camarhynchus parvulus in relation to parasitism and environmental factors

The parental food compensation hypothesis suggests that parents may compensate for the negative effects of parasites on chicks by increased food provisioning. However, this ability differs widely among host species and may also depend on ecological factors such as adverse weather conditions and habitat quality. Although weed management can improve habitat quality, management measures can bring about a temporary decrease in food availability and thus may reduce parents’ ability to provide their nestlings with enough energy. In our study we investigated the interaction of parasitism and weed management, and the influence of climate on feeding rates in a Darwin’s tree finch species, which is negatively impacted by two invasive species. The larvae of the invasive parasitic fly Philornis downsi ingest the blood and body tissues of tree finch nestlings, and the invasive Blackberry Rubus niveus affects one of the main habitats of Darwin’s tree finches. We compared parental food provisioning of the Small Tree Finch Camarhynchus parvulus in parasitized and parasite‐free nests in three different areas, which differed in invasive weed management (no management, short‐term and long‐term management). In a parasite reduction experiment, we investigated whether the Small Tree Finch increases food provisioning rates to nestlings when parasitized and whether this ability depends on weed management conditions and precipitation. Our results provide no evidence that Small Tree Finches can compensate with additional food provisioning when parasitized with P. downsi. However, we found an increase in male effort in the short‐term management area, which might indicate that males compensate for lower food quality with increased provisioning effort. Furthermore, parental food provisioning was lower during rainfall, which provides an explanation for the negative influence of rain on breeding success found in earlier studies. Like other Darwin’s finches, the Small Tree Finch seems to lack the ability to compensate for the negative effects of P. downsi parasitism, which is one explanation for why this invasive parasite has such a devastating effect on this host species.     

心肺运动试验（CPET）评价个体化精准运动整体方案强化管控心脑血管慢病疗效的临床研究*

目的: 探讨研究症状限制性极限运动心肺运动试验（CPET）评价个体化精准运动整体方案强化管控3月后（简称强化管控）的长期慢病患者整体功能的改善。方法: 选取2014年至2016年由我们团队强化管控的长期心脑血管代谢慢病为主的患者20例,签署知情同意书后完成CPET,根据CPET及连续功能学检测结果制定以个体化适度运动强度为核心的整体管理方案,强化管控3月后再行CPET,个体化分析每例患者强化管控前后CPET指标的变化、计算差值和百分差值。结果: 本研究心脑血管代谢性慢病为主的患者20例（18男2女）,年龄（55.75±10.80,26~73）岁,身高（172.20±8.63,153~190）cm,体重（76.35±15.63,53~105）kg,所有患者CPET和强化管控期间均无任何危险事件发生。①强化管控后患者静态肺功能指标及静息收缩压、心率收缩压乘积和空腹血糖等均显著改善（P<0.05）。②强化管控前峰值摄氧量为（55.60±15.69,34.37~77.45）%pred和无氧阈为（60.11±12.26,43.29~80.63）%pred;强化管控后峰值耗氧量为（71.85±21.04,42.40~102.00）%pred和无氧阈为（74.95±17.03,51.90~99.47）%pred;管控后较管控前峰值摄氧量和无氧阈显著提高分别达（29.09±7.38,17.78~41.80）%和（25.16±18.38,1.77~81.86）%（P均<0.01）;其他核心指标峰值氧脉搏、峰值负荷功率、摄氧通气效率平台和递增功率运动持续时间均显著升高（P均<0.01）,二氧化碳排出通气效率最低值及二氧化碳排出通气斜率也显著好转（P<0.01）。③个体化分析而言,强化管控后15例上述8项CPET核心指标全部改善,另5例7项指标改善;全部病例峰值摄氧量（%pred）提高>15%以上,16例>20%,13例>25%,10例>30%。结论: CPET能安全客观定量地评估人体整体功能状态和治疗效果、指导制定个体化精准运动强度。个体化精准运动整体方案强化管控三个月能安全有效逆转长期心脑血管代谢等慢病患者的整体功能状态和异常指标。