An Enzymatic Antibiotic Adjuvant Modulates the Infectious Microenvironment to Overcome Antimicrobial Resistance of Pathogens

The emergence and evolution of antimicrobial resistance (AMR) pose a significant challenge to the current arsenal to fight infection. Antibiotic adjuvants represent an appealing tactic for tackling the AMR of pathogens, however, their practical applications are greatly constrained by the harsh infectious microenvironment. Herein, it is found that silver nanoclusters (Ag NCs) can possess tunable enzymatic activities to modulate infectious microenvironments. Based on this finding, an enzymatic nanoadjuvant (EnzNA) self-assembled from Ag NCs, which is inert under neutral physiological conditions but can readily disassemble into isolated Ag NCs exhibiting biofilm destructive oxidase-mimetic activity in the acidic biofilm microenvironment, is developed. Once internalized into the neutral cytoplasm of bacteria, Ag NCs switch to reveal the thiol oxidase-mimetic activity to suppress ribosomal biogenesis for AMR reversal and evolution inhibition of pathogens. Consequently, EnzNAs revitalize various existing antibiotics against methicillin-resistant Staphylococcus aureus, and potentiate the antibiotic efficacy against biofilm-mediated skin infection and lethal lung infection in mice. These findings highlight the capability of enzyme-mimetic nanomaterials to modulate the infectious microenvironment and potentiate antibiotics, providing a paradigm shift for anti-infection therapy.     

Efficient and Durable Vaccine against Intimin β of Diarrheagenic E. Coli Induced by Clay Nanoparticles

Improved strategies are urgently required to control infections with enterohemorrhagic Escherichia coli and enteropathogenic E. coli, two dominant zoonotic enteric pathogens responsible for a wide spectrum of illnesses as well as deaths of human being, with tremendous financial cost worldwide. The present study investigates the capacity of two clay nanoparticles (NPs) with opposite surface charges, namely synthetic layered double hydroxide (LDH) and hectorite (HEC) NPs as adjuvants to promote strong immune responses against the infections. Here both LDH and HEC NPs are showed to be able to carry an appreciable amount of Intimin β (1.1 and 4.4 mg per mg clay nanomaterials, respectively) and significantly facilitate antigen uptake by antigen‐presenting cells. Remarkably, these clay NPs induce strong antibody and cell‐mediated immune responses, which are much higher than that by the potent adjuvant, QuilA. Furthermore, these strong immune responses are well maintained for at least four months in the mouse model, during which there are no changes in histopathology of the animal organs. Collectively these data demonstrate the suitability of LDH and HEC NPs as useful adjuvants in new‐generation vaccine formulations to control various infectious diseases.     

Structure–Function Studies on IMD-0354 Identifies Highly Active Colistin Adjuvants

Infections caused by multidrug-resistant (MDR) bacteria, particularly Gram-negative bacteria, are an escalating global health threat. Often clinicians are forced to administer the last-resort antibiotic colistin; however, colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-negative infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising orthogonal approach to the development of new antibiotics. We recently disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this study, we explore the structure–activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin-resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae.     

Ionic-Liquid-Based Safe Adjuvants

Adjuvants play a critical role in the design and development of novel vaccines. Despite extensive research, only a handful of vaccine adjuvants have been approved for human use. Currently used adjuvants are mostly composed of components that are non-native to the human body, such as aluminum salt, bacterial lipids, or foreign genomic material. Here, a new ionic-liquid-based adjuvant is explored, synthesized using two metabolites of the body, choline and lactic acid (ChoLa). ChoLa distributes the antigen efficiently upon injection, maintains antigen integrity, enhances immune infiltration at the injection site, and leads to a potent immune response against the antigen. Thus, it can serve as a promising safe adjuvant platform that can help to protect against pandemics and future infectious threats.     

Adjuvant properties of mesoporous silica particles tune the development of effector T cells

Alum is the most frequently used adjuvant today, primarily inducing Th2 responses. However, Th1‐type responses are often desirable within immune therapy, and therefore the development of new adjuvants is greatly needed. Mesoporous silica particles with a highly ordered pore structure have properties that make them very interesting for future controlled drug delivery systems, such as controllable particle and pore size; they also have the ability to induce minor immune modulatory effects, as previously demonstrated on human‐monocyte‐derived dendritic cells (MDDCs). In this study, mesoporous silica particles are shown to be efficiently engulfed by MDDCs within 2 h, probably by phagocytic uptake, as seen by confocal microscopy and transmission electron microscopy. A co‐culture protocol is developed to evaluate the capability of MDDCs to stimulate the development of naïve CD4⁺ T cells in different directions. The method, involving ELISpot as a readout system, demonstrates that MDDCs, after exposure to mesoporous silica particles (AMS‐6 and SBA‐15), are capable of tuning autologous naïve T cells into different effector cells. Depending on the size and functionalization of the particles added to the cells, different cytokine patterns are detected. This suggests that mesoporous silica particles can be used as delivery vehicles with tunable adjuvant properties, which may be of importance for several medical applications, such as immune therapy and vaccination.     

不同农药助剂的初级生物降解性研究

以新型复配农药助剂——松脂基表面活性剂1号和2号以及传统农药助剂壬基酚聚氧乙烯醚、松香酸聚乙二醇酯和直链十二醇聚氧乙烯醚为目标物,通过实验考察了不同类型农药助剂的初级生物降解特性。8 d的生物降解实验结果表明,松脂基表面活性剂1号的初级生物降解度为79.1%,松脂基表面活性剂2号的初级生物降解度为82.4%,松香酸聚乙二醇酯的初级生物降解度为84.2%,壬基酚聚氧乙烯醚的初级生物降解度为91.1%,直链十二醇聚氧乙烯醚的初级生物降解度大于99%。新型复配农药助剂的组成结构更为复杂,其初级生物降解度要低于直链醇类、酚类的聚氧乙烯醚及单一结构酸类的聚乙二醇酯等农药助剂。     

GC-MS/MS法测定乳油和可溶液剂型液体农药制剂中3种高风险吡咯烷酮类农药助剂

建立了气相色谱-串联质谱（GC-MS/MS）法同时测定乳油和可溶液剂型液体农药制剂中3种高风险吡咯烷酮类农药助剂。农药制剂经甲醇稀释,20 ℃下以8 000 r/min离心5 min,取上清液,过0.22 μm滤膜后检测分析。采用VF-WAXms毛细管柱（60 m×0.25 mm×0.25 μm）分离,多反应监测（MRM）模式测定,外标法定量。结果表明,3种农药助剂在1.0~40.0 mg/L浓度范围内线性关系良好,相关系数（R²）均大于0.999,方法定量限为3.1~6.8 mg/kg,乳油型和可溶液剂型农药样品平均加标回收率分别为98.2%~108.9%和98.1%~111.7%,相对标准偏差分别为0.4%~2.6%和0.4%~3.4%（n=6）。采用该方法检测市售94份乳油型和27份可溶液剂型农药制剂样品,其中6份检出N-甲基吡咯烷酮（含量范围0.022%~11.328%）,2份检出2-吡咯烷酮（含量范围0.018%~0.023%）。该方法具有操作简便、灵敏度高、准确度好等优点,适用于同时测定乳油和可溶液剂型液体农药制剂中3种高风险吡咯烷酮类农药助剂。     

农药桶混助剂的选择原理

桶混助剂通过改善农药在植物叶面上的附着，展布或吸收而能够极大地提高药效，介并非任何助剂对任何农药均有效。如果说提高药液附着对所有农药均有利，那么获得卓越的药液展布性对保护性杀菌剂尤为重要。表面活性剂对农药叶面吸收的影响更复杂，与其亲水基及亲脂基结构以及浓度均有关系。因此选择桶混助剂时，既要考虑农药本身的理化性质，又要考虑靶标植物的叶片表面特征。     

农药助剂的环境毒理研究进展

文章阐述了农药助剂环境毒理研究的重要性,介绍了国外对农药助剂环境毒理研究取得的进展,以期为其他研究者的进一步研究提供帮助。