Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice

Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4⁺ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner.     

Effects of Psychological Stress on Hypertension in Middle-Aged Chinese: A Cross-Sectional Study

We examined the effect and relative contributions of different types of stress on the risk of hypertension. Using cluster sampling, 5,976 community-dwelling individuals aged 40–60 were selected. Hypertension was defined according to the Seventh Report of the Joint National Committee, and general psychological stress was defined as experiencing stress at work or home. Information on known risk factors of hypertension (e.g., physical activity levels, food intake, smoking behavior) was collected from participants. Logistic regression analysis was used to determine the associations between psychological stress and hypertension, calculating population-attributable risks and 95% confidence intervals (CIs). General stress was significantly related to hypertension (odds ratio [OR] = 1.247, 95% CI [1.076, 1.446]). Additionally, after adjustment for all other risk factors, women showed a greater risk of hypertension if they had either stress at work or at home: OR = 1.285, 95% CI (1.027, 1.609) and OR = 1.231, 95% CI (1.001, 1.514), respectively. However, this increased risk for hypertension by stress was not found in men. General stress contributed approximately 9.1% (95% CI [3.1, 15.0]) to the risk for hypertension. Thus, psychological stress was associated with an increased risk for hypertension, although this increased risk was not consistent across gender.     

光照强度驱动典型阴生植物三七的生理生态响应特征

为探究阴生植物三七(Panax notoginseng)对不同光照强度的生理生态响应特征,研究5种透光率(46.5% LT、21.8% LT、9.70% LT、5.10% LT、2.80% LT)下三七生理、形态和生长等各项指标的变化特征,并对其相关指标进行相关性、可塑性和主成分分析。结果表明:三七在高光(46.5% LT和21.8% LT)和低光(5.10% LT和2.80% LT)条件下各形态特征(株高、茎粗、单株叶面积)、生物量及相对生长速率(RGR)均有所降低;随着光照强度的降低,根生物量比(RMR)、最大净光合速率(P_n-max)、气孔导度(G_s)、光补偿点(LCP)和暗呼吸速率(R_d)都随之下降,而叶面积比(LAR)、比叶面积(SLA)、茎生物量比(SMR)和叶生物量比(LMR)却呈现升高的趋势。这些变化能够减少三七在高光下的光能捕获及消耗,而低光下的光能捕获和消耗则会得到加强。此外,阴生植物三七的形态特征表型可塑性指数均小于0.5,而光合生理(P_n-max、G_s、LCP、R_d)、LAR和根部生物量的表型可塑性指数则大于0.5,其可塑性较强,且P_n-max、G_s、LCP与RGR的相关系数分别高达0.581、0.558、0.574,这些结果表明光照强度驱动三七的响应特征主要为光合生理特性、LAR和根部生物量的变化。研究还发现三七在10%左右的透光率下生长发育较好。而在低光条件下,三七主要采取保守策略进行缓慢的碳获取和碳消耗,高光条件下则主要采取快速碳获取和碳消耗的冒险策略。研究阐明了三七对不同光照环境的响应策略,为三七的优质高效种植提供理论依据。     

香菇原生质体融合及融合子的鉴定

以香菇（Ｌｅｎｔｉｎｕｓｅｄｏｄｅｓ）种内不同株一对亲和的单核菌丝（７４０２〈２〉和９１０１〈１２〉）为亲本,以碘乙酰胺失活７４０２〈２〉作为筛选标记,经过原生质体制备、ＰＥＧ融合及融合子再生等步骤,选育得融合子。融合子与双亲无拮抗性,在菌丝形态,核数目及可溶性蛋白质图谱、酯酶同工酶谱和过氧化物酶谱上均与双亲单核菌丝及担孢子杂交子有区别。将Ｋｎｏｗｌｔｏｎ等于１９８４年建立的一种分离高频再生衍生株的方法首次运用至食用菌中,使原生质体再生率提高２－３倍,为融合操作提供了方便。     

Discovery of N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents

Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant S. aureus (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified AG-690/11765367, or f1, as a novel and potent inhibitor of the target protein (IC₅₀: 1.21 µM). Structural modification was used to further identify two more potent GyrB inhibitors: f4 (IC₅₀: 0.31 µM) and f14 (IC₅₀: 0.28 µM). Additional experiments indicated that compound f1 is more potent than the others in terms of antibacterial activity against MRSA (MICs: 4–8 µg/mL), non-toxic to HUVEC and HepG2 (CC₅₀: approximately 50 µM), and metabolically stable (t_1/2: > 372.8 min for plasma; 24.5 min for liver microsomes). In summary, this study showed that the discovered N-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides are novel GyrB-targeted antibacterial agents; compound f1 is promising for further development.     

降解尿酸乳酸菌复合菌系的筛选与菌株组合提升降解效果

【背景】高尿酸症由血液中尿酸含量明显升高而导致,利用乳酸菌对人体的益生作用缓解高尿酸血症越来越受到关注。【目的】获得具有降解尿酸能力的乳酸菌复合菌系与纯培养菌株。【方法】以泡菜为样品来源,以尿酸为底物,采用MRS培养基筛选降解尿酸的乳酸菌复合菌系,通过高效液相色谱法测定复合菌系对尿酸的降解能力。【结果】得到一组乳酸菌复合菌系,当培养温度为37 °C、pH值为6.20、静置培养72 h后复合菌系对尿酸的降解率为12.08%;通过优化培养条件,当该菌系在以牛肉膏为单一氮源、初始pH值为5.00、温度为35 °C的条件下培养72 h,尿酸降解率上升至17.19%,降解率比优化前提高了42.3%;从该菌系中分离出两株具有尿酸降解能力的菌株UA-1与UA-2,它们的尿酸降解率分别为10.85%和8.65%;通过形态学观察和16S rRNA基因序列分析,经鉴定两株菌均为布氏乳杆菌(Lactobacillus buchneri)。将两株单菌组合降解尿酸试验发现,UA-1与UA-2比例为2:1的尿酸降解率为20.2%,比原复合菌系的降解能力提高了67.22%。【结论】研究证明了乳酸菌复合菌系对尿酸的降解能力优于单个菌株,为后续利用乳酸菌复合菌系应用提供了数据支持。     

蛇足石杉内生细菌多样性北大核心CSCD

【目的】探索国家二级保护野生药用植物蛇足石杉内生细菌的物种和生理活性多样性,发现并收集药用植物内生菌资源。【方法】分别从四川和福建等不同生态环境采集蛇足石杉植株,运用纯培养手段,对经过表面消毒处理的蛇足石杉样品进行内生菌的分离、培养;根据菌株16S r RNA基因信息,计算从蛇足石杉不同区系分离获得的内生细菌间的Jaccard指数、多样性指数、优势度指数与均匀度指数等,分析内生菌物种多样性;应用6种筛选模型对分离得到的内生菌进行生理活性测定,初步评价蛇足石杉内生细菌的生理活性多样性和药用价值。【结果】从12份蛇足石杉植物样品中分离获得356株内生菌菌株,菌株16S r RNA基因序列信息显示,分离得到的蛇足石杉内生细菌隶属于放线菌门、厚壁菌门和变形菌门等3个门的26个科、41个属,来源于蛇足石杉地上和地下部位的菌株数目、多样性指数等无明显差异。从中发现了分属于拟无枝酸菌属(Amycolatopsis)、Angustibacter、节杆菌属(Arthrobacter)、短小杆菌属(Curtobacterium)、Frondihabitans、Glaciihabitans、Jatrophihabitans、Luteimicrobium、Massilia、Naumannella和Tardiphaga等11个属的11个潜在新物种,以及皮生球菌科(Dermacoccaceae)的1个新属。在抗菌活性筛选中,356株纯培养物抗粪肠球菌、抗肺炎克雷伯菌、抗耻垢分枝杆菌以及抗水稻白叶枯病菌的阳性率分别是9.0%、1.4%、2.2%、0.8%;抑制SS04生长的降血脂药物筛选模型上的阳性率是8.1%;抗HIV-1的初筛阳性率为4.5%。共计74株菌在一个或多个筛选模型中显示出活性,初筛总阳性率为20.8%。【结论】蛇足石杉内生细菌具有丰富的物种多样性和生理活性多样性,是进一步发掘新型天然产物的理想菌种资源。