用于高分辨率成像的肺器官芯片构建及肺炎模型应用研究

肺是人体呼吸系统的重要组成部分,气道上皮是肺与外界接触的第一道屏障,参与抵御外来的颗粒物、病原体等,可将异物以痰的形式排出体外,对维护呼吸道正常功能起到至关重要的作用.常用的体外细胞培养模型和哺乳动物模型尚不能完全模拟人体肺-气道微环境,在人体细胞与病原体相互作用研究和药物研发应用方面具有一定的局限性.该研究设计制作了...     

Structural Considerations for Building Synthetic Glycoconjugates as Inhibitors for Pseudomonas aeruginosa Lectins

Pseudomonas aeruginosa is a pathogenic bacterium, responsible for a large portion of nosocomial infections globally and designated as critical priority by the World Health Organisation. Its characteristic carbohydrate-binding proteins LecA and LecB, which play a role in biofilm-formation and lung-infection, can be targeted by glycoconjugates. Here we review the wide range of inhibitors for these proteins (136 references), highlighting structural features and which impact binding affinity and/or therapeutic effects, including carbohydrate selection; linker length and rigidity; and scaffold topology, particularly for multivalent candidates. We also discuss emerging therapeutic strategies, which build on targeting of LecA and LecB, such as anti-biofilm activity, anti-adhesion and drug-delivery, with promising prospects for medicinal chemistry.     

芳樟醇对莓实假单胞菌的抑菌活性及机制

食品在生产、运输和贮藏过程中易受致病菌污染而引起食源性疾病。芳樟醇具有抗菌作用,但其作用机制尚不明确。研究芳樟醇对莓实假单胞菌的抑菌活性及作用机制,可为其作为天然食品防腐剂的开发提供理论依据。通过测定最小抑菌浓度、绘制细菌生长曲线评价芳樟醇的抑菌活性;通过扫描电子显微镜观察、结晶紫染色实验、二乙酸荧光素染色实验以及测定电导率、核酸泄漏、呼吸代谢活力和呼吸链脱氢酶活性的变化探究芳樟醇的抑菌机制。结果表明：芳樟醇对莓实假单胞菌具有较强的抑制作用,最小抑菌浓度为1.5 mL/L;芳樟醇能破坏莓实假单胞菌细胞的结构形态和细胞膜的完整性,增加细胞膜的通透性,导致胞内物质泄漏、膜外电导率升高;能抑制呼吸代谢活力和呼吸链脱氢酶活性,破坏呼吸链,导致胞内代谢紊乱。研究认为,芳樟醇可通过破坏莓实假单胞菌的细胞结构和抑制其呼吸代谢而发挥抑菌作用,有望作为天然防腐剂应用于食品的防腐保鲜。     

Microbiologically Influenced Corrosion Behavior of Fe40(CoCrMnNi)60 and Fe60(CoCrMnNi)40 Medium Entropy Alloys in the Presence of Pseudomonas Aeruginosa

In this work, the microbiologically influenced corrosion (MIC) of Fe₄₀(CoCrMnNi)₆₀ and Fe₆₀(CoCrMnNi)₄₀ medium entropy alloys (MEAs) induced by Pseudomonas aeruginosa (P. aeruginosa) was investigated. Corrosion behaviors during 14 days of immersion in sterile and P. aeruginosa-inoculated culture media are presented. Under sterile conditions, both MEAs exhibited good corrosion resistance against the culture medium solution. In the presence of P. aeruginosa, the pitting corrosion of MEAs was promoted. The results of inductively coupled plasma‒mass spectrometry (ICP‒MS) and potentiodynamic polarization tests showed that the presence of P. aeruginosa promoted the selective dissolution of passive film and accelerated the corrosion of MEAs. The results of X-ray photoelectron spectroscopy (XPS) and Mott-Schottky measurements further demonstrated the degradation effect of P. aeruginosa on the passive film. Compared with Fe₆₀(CoCrMnNi)₄₀, Fe₄₀(CoCrMnNi)₆₀ manifested better resistance to the MIC caused by P. aeruginosa, which may be attributed to more Cr oxides and fewer Fe oxides of the passive film.     

饮用水中铜绿假单胞菌全基因组分析与分子溯源

目的：为湖南省饮用水中铜绿假单胞菌的溯源研究和污染防治提供数据支持。方法：按GB 8538—2016检验湖南省部分市县随机采集的桶装水，对分离鉴定的18株铜绿假单胞菌进行全基因组测序、分子溯源以及毒力基因和耐药基因分析。结果：通过系统进化树分析可知，18株铜绿假单胞菌有明显的聚类分布，清晰反映了样本菌株的亲缘远近情况；通过统计分析毒力基因和耐药基因，证实4株铜绿假单胞菌在地域分布、同源性、致病基因和耐药基因型上呈现一致性，推测为同一来源。结论：基于全基因测序、16S rRNA和单拷贝直系同源分析，可实现饮用水中铜绿假单胞菌的溯源、毒力基因及耐药基因分析。     

包装饮用水中铜绿假单胞菌定性检测方法构建

该研究构建包装饮用水中铜绿假单胞菌定性检测方法并开展应用效果评价。通过低菌浓度接种，选取合适培养条件及增菌基础肉汤，通过单因素试验优化增菌液配方，通过多重比较优化选择分离培养基配方。以GB 8538-2022方法为对照，选取市售包装饮用水加入不同类别、菌量标准菌后，使用臭氧发生器分别通气0、30、60、90 min后，再进行膜过滤富集增菌-选择划线分离-MALDI-TOF MS仪鉴定的定性测试，比较两者的灵敏度、选择性、特异性，并选取不同类别样品进行应用效果测试。该研究构建的定性检测方法第一步增菌选取TSB添加甘露醇4 g/L配方，42 ℃培养6~8 h；第二步选择分离选取CN添加丙酮酸钠0.20 g/L配方，42 ℃培养24~48 h，利用MALDI-TOF MS仪对可疑菌可实现准确、快速、高通量鉴定。该法对铜绿假单胞菌的最低识别限为3 CFU/250 mL，可识别1 000~10 000 CFU/250 mL干扰菌，对不同样品的检测识别效果较现行国标差异显著（x2=25.45，P<0.05），相对现有方法，具有灵敏度高、特异性强、简便安全、高效等技术优势。     

StyS激酶自磷酸化对Pseudomonas putida B3中靛蓝生物合成的调节作用

在恶臭假单胞菌Pseudomonas putida B3中,靛蓝生物合成关键酶基因styAB上游存在一个二元调控系统StyS-StyR.StyS蛋白属于激酶家族,是磷酸化信号转导的重要媒介,但激酶StyS的自磷酸化传导机制对靛蓝生物合成的调节作用尚未探明,因此,研究以Pseudomonas putida B3中激酶蛋白StyS作为研究对象,发现了两个磷酸化结合位点,构建了磷酸化位点突变株.通过分析野生菌株P.putida B3、styS基因缺失菌株P.putida B3-△styS、styS基因回补菌株P.putida B3-△styS-8和磷酸化位点突变株P.putida B3-△styS-1之间的靛蓝产量及酶活发现,P.putida B3产量为10.14 mg/L,P.putida B3-△styS-8产量为3.63 mg/L,磷酸化位点突变菌株无激酶活性且失去了产生靛蓝的能力.结果表明,StyS自磷酸化作用在靛蓝发酵体系中起重要作用.研究结果将为靛蓝生物合成途径的进一步研究提供参考.     

Tetraphenylporphyrin Enters the Ring: First Example of a Complex between Highly Bulky Porphyrins and a Protein**

Tetraphenylporphyrin (TPP) is a symmetrically substituted synthetic porphyrin whose properties can be readily modified, providing it with significant advantages over naturally occurring porphyrins. Herein, we report the first example of a stable complex between a native biomolecule, the haemoprotein HasA, and TPP as well as its derivatives. The X-ray crystal structures of nine different HasA-TPP complexes were solved at high resolutions. HasA capturing TPP derivatives was also demonstrated to inhibit growth of the opportunistic pathogen Pseudomonas aeruginosa. Mutant variants of HasA binding FeTPP were shown to possess a different mode of coordination, permitting the cyclopropanation of styrene.     

一步热分解法形成的MoO3在无光条件下的抗菌性能

生物污损是威胁海工材料安全高效服役的重要因素，因此开发环保、成本低廉的防污材料非常必要。本文通过一步热分解法分别在450 ℃和750 ℃制备α-MoO3粉末材料，即S450和S750。采用X射线衍射（XRD）、扫描电子显微镜（SEM）、红外光谱（FTIR）对样品进行表征。结果显示，450 ℃和750 ℃获得的α-MoO3分别表现为纳米级板状结构和微米级长板状结构。利用平板计数法评价两种材料在无光条件下对铜绿假单胞菌（P. aeruginosa）的抗菌性能。结果显示，S450和S750在浓度为0.25，0.5，0.75，和1 mg/ml时，其抗菌率分别为27.3%，99%，100%，100%和16.1%，30.1%，52.3%，73.6%。表明两个条件下获得的α-MoO3在无光条件下均表现出良好的抗菌性能，并且溶液pH值随α-MoO3样品浓度的升高而降低，Mo离子溶出量随α-MoO3样品浓度的升高而增加。α-MoO3在无光条件下的抗菌活性源于H3O+和Mo离子溶出的协同作用影响。与S750相比，S450表现出更高的抗菌率，这可能源于S450在溶液中具有更高的溶解度，因而导致更多的H3O+和Mo离子溶出。