Real-Time Monitoring of Mitochondrial Damage Using Conjugated Oligoelectrolytes.

Conjugated oligoelectrolytes (COEs) comprise a class of fluorescent reporters with tunable optical properties and lipid bilayer affinity. These molecules have proven effective in a range of bioimaging applications; however, their use in characterizing specific subcellular structures remains restricted. Such capabilities would broaden COE applications to understand cellular dysfunction, cell communication, and the targets of different pharmaceutical agents. Here, we disclose a novel COE derivative, COE-CN, which enables the visualization of mitochondria, including morphological changes and lysosomal fusion upon treatment with depolarizing agents. COE-CN is characterized by the presence of imidazolium solubilizing groups and an optically active cyanovinyl-linked distyrylbenzene core with intramolecular charge-transfer characteristics. Our current understanding is that the relatively shorter molecular length of COE-CN leads to weaker binding within lipid bilayer membranes, which allows sampling of internal cellular structures and ultimately to different localization relative to elongated COEs. As a means of practical demonstration, COE-CN can be used to diagnose cells with damaged mitochondria via flow cytometry. Coupled with an elongated COE that does not translocate upon depolarization, changes in ratiometric fluorescence intensity can be used to monitor mitochondrial membrane potential disruption, demonstrating the potential for use in diagnostic assays.

A Broad Light-Harvesting Conjugated Oligoelectrolyte Enables Photocatalytic Nitrogen Fixation in a Bacterial Biohybrid.

We report a rationally designed membrane-intercalating conjugated oligoelectrolyte (COE), namely COE-IC, which endows aerobic N2 -fixing bacteria Azotobacter vinelandii with a light-harvesting ability that enables photosynthetic ammonia production. COE-IC possesses an acceptor-donor-acceptor (A-D-A) type conjugated core, which promotes visible light absorption with a high molar extinction coefficient. Furthermore, COE-IC spontaneously associates with A. vinelandii to form a biohybrid in which the COE is intercalated within the lipid bilayer membrane. In the presence of L-ascorbate as a sacrificial electron donor, the resulting COE-IC/A. vinelandii biohybrid showed a 2.4-fold increase in light-driven ammonia production, as compared to the control. Photoinduced enhancement of bacterial biomass and production of L-amino acids is also observed. Introduction of isotopically enriched 15 N2 atmosphere led to the enrichment of 15 N-containing intracellular metabolites, consistent with the products being generated from atmospheric N2 .

Antimicrobial Conjugated Oligoelectrolytes Containing Triphenylphosphonium Solubilizing Groups.

Invited for the cover of this issue is the group of Guillermo C. Bazan, Kaixi Zhang and co-workers at the National University of Singapore The image depicts the activity of lead compound DM6P acting on a model bacteria membrane. Read the full text of the article at 10.1002/chem.202203803.

Antimicrobial Conjugated Oligoelectrolytes Containing Triphenylphosphonium Solubilizing Groups.

Conjugated oligoelectrolytes (COEs) are an emerging class of amphiphilic antimicrobial compounds with a modular molecular framework suitable for simple chemical derivatization. Here, a series of COE derivatives with a stilbene-conjugated segment and triphenylphosphonium (TPP) pendant groups was designed and synthesized to understand how lipophilic cationic groups impact antimicrobial activity. In vitro evaluations against ESKAPE pathogens showed broad-spectrum activity towards multi-drug resistant (MDR) bacteria and mycobacteria, with TPP groups enhancing antimicrobial activity towards clinically relevant Gram-negative strains compared to their ammonium analogues. We studied the interactions of DM6P, the most active TPP-COE compound, with various membrane assays. Treatment of bacterial cells with DM6P showed enhanced permeability of cell membranes without inducing the development of significant bacterial resistance. Moreover, DM6P eliminated 99.99 % of methicillin-resistant Staphyloccocus aureus (MRSA) in an in vivo wound model. These results represent a promising chemical strategy for increasing the activity spectrum of membrane-active COE antibiotics to tackle challenging drug-resistant targets.

MOF-derived ruthenium-doped amorphous molybdenum dioxide hybrid for highly efficient hydrogen evolution reaction in alkaline media.

Ruthenium-doped amorphous molybdenum dioxide coupled with a reduced graphene oxide hybrid (Ru-MoO2@PC/rGO) is synthesized using polyoxometalate-based MOFs/GO as a precursor. Benefitting from the synergistic effect of numerous exposed active sites, Ru dopants and the introduction of GO, the designed catalyst shows exceptional electrocatalytic performance toward the HER in alkaline media.

Diffusion tensor imaging of the structural integrity of white matter correlates with impulsivity in adolescents with internet gaming disorder.

INTRODUCTION: Internet gaming disorder (IGD) is usually defined as the inability of an individual to control internet gaming resulting in serious negative consequences, and trait impulsivity has been viewed as a hallmark feature of IGD. Recent studies have suggested that the structural integrity of the white matter (WM) plays an important role in the neuromediation of an individual's impulsivity. However, no study has examined the association between WM integrity and impulsivity in IGD adolescents. METHODS: In this study, 33 adolescents with IGD and 32 healthy controls (HCs) were recruited, and the intergroup differences in the relationships between impulsivity and fractional anisotropy (FA) values across the whole brain WM were investigated using voxel-wise correlation analyses. RESULTS: Our results revealed significant intergroup differences in the correlations between impulsivity and the FA values of the right corticospinal tract (CST) and the right occipital WM. Region of interest-based tests revealed that the FA values of these clusters were positive or insignificantly correlated with impulsivity in the IGD adolescents contrasted to the significantly negative correlation in the HCs. CONCLUSIONS: This altered correlations in the IGD adolescents might reflect potential WM microstructural changes which may be associated with the greater impulsivity of IGD adolescents and provide possible therapeutic targets for interventions in this population.

Comparative Transcriptomics of Buzura suppressaria (Lepidoptera: Geometridae) Assembled De Novo Yield Insights Into Response After Buzura suppressaria Nuclear Polyhedrosis Virus Infection.

Buzura suppressaria Guenee (Lepidoptera: Geometridae) is a defoliator that seriously harms eucalyptus trees in South China. Buzura suppressaria nuclear polyhedrosis virus (BsNPV) is a baculovirus that infects B. suppressaria with high specificity and efficiency. Transcriptomes of B. suppressaria were sequenced before and after BsNPV infection using an Illumina-based platform to probe for differentially expressed genes (DEGs) of B. suppressaria after viral infection. On average, ∼57.4 million high-quality clean reads were generated and assembled de novo into 69,761 unigenes. The NCBI nonredundant protein, Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Cluster of Orthologous Groups databases were used to annotate unigenes through NCBI BLAST; 33,575 unigenes (48.1%) were then mapped to at least one of these databases, and 4,366 unigenes (6.3%) were mapped to all databases. Differential expression analysis showed that 25,212 unigenes were upregulated and 22,880 unigenes were downregulated in at least one pairwise comparison. Control versus 48 h had more DEGs than other two pairwise comparisons in either the GO or KEGG database, because the number of regulated gene would increase as BsNPV infected more tissues and would decrease as more tissues were disabled. To ascertain B. suppressaria immune response to BsNPV infection, DEGs were annotated to the GO and KEGG databases. In total, 89 GO categories are related to immune response and 1,007 DEGs are annotated to these GO categories. Furthermore, 7 downregulated DEGs and 37 upregulated were obtained simultaneously in all three groups. These DEGs were considered to possess a central role throughout viral infection.

Adsorption of plasma proteins and fibronectin on poly(hydroxylethyl methacrylate) brushes of different thickness and their relationship with adhesion and migration of vascular smooth muscle cells.

The surface-grafted poly(hydroxylethyl methacrylate) (PHEMA) molecules were demonstrated to show a brush state regardless of their molecular length (molecular weight). Adsorption of proteins from 10% fetal bovine serum (FBS), fibronectin (Fn) and bovine serum albumin (BSA) was quantified by ellipsometry, revealing that the amounts of FBS and Fn decreased monotonously along with the increase of PHEMA thickness, whereas not detectable for BSA when the PHEMA thickness was larger than 6 nm. Radio immunoassay found that the adsorption of Fn from 10% FBS had no significant difference regardless of the PHEMA thickness. However, ELISA results showed that the Arg-Gly-Asp (RGD) activity of adsorbed Fn decreased with the increase of PHEMA thickness. By comparison of cellular behaviors of vascular smooth muscle cells (VSMCs) being cultured in vitro in the normal serum-containing medium and the Fn-depleted serum-containing medium, the significant role of Fn on modulating the adhesion and migration of VSMCs was verified. Taking account all the results, the Fn adsorption model and its role on linking the biomaterials surface to the VSMCs behaviors are proposed.

Molecular interactions of different size AuNP-COOH nanoparticles with human fibrinogen.

Protein adsorption influences greatly the performance of materials used in biotechnology and biomedicine. The binding of fibrinogen (Fg) to nanoparticles (NPs) can result in protein unfolding and exposure of cryptic epitopes that subsequently interact with cell surface receptors. The response and its degree are dependent on the size, charge, and concentration of the NPs. In this study the binding kinetics of human Fg to negatively charged 11-mercaptoundecanoic acid-functionalized gold nanoparticles (AuNPs-COOH) ranging from 5.6 to 64.5 nm were examined. The larger NPs bound Fg with a larger number of proteins per square unit and a higher dissociation rate (Kd'), but with decreased affinity. By contrast, the 5.6 nm AuNPs-COOH behaved in a cooperative manner for Fg adsorption. In the presence of excess Fg, only the 64.5 nm AuNPs-COOH showed severe aggregation, whose degree was alleviated in a dilute Fg solution. The Fg is adsorbed through a side-on configuration and both side-on and end-on configurations on the smaller (5.6 and 14.2 nm) and 31.5 nm AuNPs-COOH, respectively. It also retains the native conformation. By contrast, on the 64.5 nm AuNPs-COOH the Fg adopts the end-on configuration and loses most of the secondary structure.