Bridging the Gap: Plant-Endophyte Interactions as a Roadmap to Understanding Small-Molecule Communication in Marine Microbiomes

Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small-molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small-molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans.     

Metallic Nanoparticle-Enabled Sensing of a Drug-of-Abuse: An Attempt at Forensic Application

γ-Hydroxybutyric acid (GHB) functions as a depressant on the central nerve system and serves as a pharmaceutical agent in the treatment of narcolepsy and alcohol withdraw. In recent years, GHB has been misused as a recreational drug due to its ability to induce euphoric feelings. Moreover, it has gained increasing attention as a popular drug of abuse that is frequently related to drug-facilitated sexual assaults. At the moment, detection methods based on chromatography exhibit extraordinary sensitivity for GHB sensing. However, such techniques require complicated sample treatment prior to analysis. Optical sensors provide an alternative approach for rapid and simple analysis of GHB samples. Unfortunately, currently reported probes are mostly based on hydrogen bonding to recognize GHB, and this raises concerns about, for example, the lack of specificity. In this work, we report a bioinspired strategy for selective sensing of GHB. The method is based on specific enzyme recognition to allow highly selective detection of GHB with minimum interference, even in a complex sample matrix (e. g., simulated urine). In addition, the result can be obtained by either quantitative spectroscopy analysis or colorimetric change observed by the naked-eye, thus demonstrating its potential application in drug screening and forensic analysis.     

Quantitative Elemental Analysis of a Single Cell by Using Inductively Coupled Plasma-Mass Spectrometry in Fast Time-Resolved Analysis Mode

The elemental composition of a single yeast, green alga, or red blood cell (RBC) was precisely determined by using inductively coupled plasma-mass spectrometry (ICP-MS) operating in fast time-resolved analysis (TRA) mode. The technique is known as single-cell (SC)-ICP-MS. Phosphorus, sulfur, magnesium, zinc, and iron were detected in the three types of cell. The elemental composition of yeast and green alga obtained by SC-ICP-MS was consistent with results obtained from conventional ICP-MS measurements following acid digestion of the cells. Slight differences were found in the measured values between SC-ICP-MS and the conventional ICP-MS results for RBC. However, the SC-ICP-MS results for S and Fe in RBC were closer to the estimated values for these elements that were calculated from the level of hemoglobin in RBCs. The data suggest that SC-ICP-MS is suitable for the analysis of various cell types, namely, fungus, plant, and animal cells.     

Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario

Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth.     

Advances in Multifunctional Chemotherapeutic Prodrugs for Near-infrared Fluorescence Imaging-guided Therapy

Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor-targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near-infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real-time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo-drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging-guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging-guided therapy are provided.     

Design and Discovery of Plasmepsin II Inhibitors Using an Automated Workflow on Large‐Scale Grids

Novel and potent inhibitors of Plasmodium falciparum plasmepsin II were identified by post‐processing the results of a docking screening with BEAR, a recently reported procedure for the refinement and rescoring of docked ligands in virtual screening. FRET substrate degradation assays performed on the 30 most promising compounds resulted in 26 inhibitors with IC₅₀ values ranging from 4.3 nM to 1.8 μM .