A Cross-linked n-Type Conjugated Polymer with Polar Side Chains Enables Ultrafast Pseudocapacitive Energy Storage.

Pseudocapacitors bridge the performance gap between batteries and electric double-layer capacitors by storing energy via a combination of fast surface/near-surface Faradaic redox processes and electrical double-layer capacitance. Organic semiconductors are an emerging class of pseudocapacitive materials that benefit from facile synthetic tunability and mixed ionic-electronic conduction. Reported examples are mostly limited to p-type (electron-donating) conjugated polymers, while n-type (electron-accepting) examples remain comparatively underexplored. This work introduces a new cross-linked n-type conjugated polymer, spiro-NDI-N, strategically designed with polar tertiary amine side chains. This molecular design aims to synergistically increase the electroactive surface area and boost ion transport for efficient ionic-electronic coupling. Spiro-NDI-N demonstrates excellent pseudocapacitive energy storage performance in pH-neutral aqueous electrolytes, with specific capacitance values of up to 532 F g-1 at 5 A g-1 and stable cycling over 5000 cycles. Moreover, it maintains a rate capability of 307 F g-1 at 350 A g-1. The superior pseudocapacitive performance of spiro-NDI-N, compared to strategically designed structural analogues lacking either the cross-linked backbone or polar side chains, validates the essential role of its molecular design elements. More broadly, the design and performance of spiro-NDI-N provide a novel strategy for developing high-performance organic pseudocapacitors.

An anti-mycobacterial conjugated oligoelectrolyte effective against Mycobacterium abscessus.

Infections caused by nontuberculous mycobacteria have increased more than 50% in the past two decades and more than doubled in the elderly population. Mycobacterium abscessus (Mab), one of the most prevalent of these rapidly growing species, is intrinsically resistant to numerous antibiotics. Current standard-of-care treatments are not satisfactory, with high failure rate and notable adverse effects. We report here a potent anti-Mab compound from the flexible molecular framework afforded by conjugated oligoelectrolytes (COEs). A screen of structurally diverse, noncytotoxic COEs identified a lead compound, COE-PNH2, which was bactericidal against replicating, nonreplicating persisters and intracellular Mab.COE-PNH2 had low propensity for resistance development, with a frequency of resistance below 1.25 × 10-9 and showed no detectable resistance upon serial passaging. Mechanism of action studies were in line with COE-PNH2 affecting the physical and functional integrity of the bacterial envelope and disrupting the mycomembrane and associated essential bioenergetic pathways. Moreover, COE-PNH2 was well-tolerated and efficacious in a mouse model of Mab lung infection. This study highlights desirable in vitro and in vivo potency and safety index of this COE structure, which represents a promising anti-mycobacterial to tackle an unmet medical need.

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

AIM: To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). METHODS: This cross-sectional study included 50 healthy adolescents, aged 14-18 years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. RESULTS: The mean age of all participants was 15.9 years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53 ± 0.04 mm vs 0.47 ± 0.02 mm, p = 0.001). Among adolescents with a parental history of PCAD, those with ≥ 3 CRFs had significantly higher IMT values (0.56 mm) than those with < 3 CRFs (0.52 mm) and controls (0.48 mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. CONCLUSION: Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥ 3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Conjugated Polyelectrolyte Thin Films for Pseudocapacitive Applications.

A subclass of organic semiconductors known as conjugated polyelectrolytes (CPEs) is characterized by a conjugated backbone with ionic pendant groups. The water solubility of CPEs typically hinders applications of thin films in aqueous media. Herein, it is reported that films of an anionic CPE, namely CPE-K, drop cast from water produces single-component solid-state pseudocapacitive electrodes that are insoluble in aqueous electrolyte. That X-ray diffraction experiments reveal a more structurally ordered film, relative to the as-obtained powder from chemical synthesis, and dynamic light scattering measurements show an increase in aggregate particle size with increasing [KCl] indicate that CPE-K films are insoluble because of tight interchain contacts and electrostatic screening by the electrolyte. CPE-K film electrodes can maintain 85% of their original capacitance (84 F g-1 ) at 500 A g-1 and exhibit excellent cycling stability, where a capacitance retention of 93% after 100 000 cycles at a current density of 35 A g-1 . These findings demonstrate that it is possible to use initially water soluble ionic-organic materials in aqueous electrolytes, by increasing the electrolyte concentration. This strategy can be applied to the application of conjugated polyelectrolytes in batteries, organic electrochemical transistors, and electrochemical sensors, where fast electron and ion transport are required.

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.

Recyclable Conjugated Polyelectrolyte Hydrogels for Pseudocapacitor Fabrication.

In alignment with widespread interest in carbon neutralization and sustainable practices, we disclose that conjugated polyelectrolyte (CPE) hydrogels are a type of recyclable, electrochemically stable, and environmentally friendly pseudocapacitive material for energy storage applications. By leveraging ionic-electronic coupling in a relatively fluid medium, one finds that hydrogels prepared using a fresh batch of an anionic CPE, namely, Pris-CPE-K, exhibit a specific capacitance of 32.6 ± 6.6 F g-1 in 2 M NaCl and are capable of 80% (26.1 ± 6.5 F g-1) capacitance retention after 100,000 galvanostatic charge-discharge (GCD) cycles at a current density (J) of 10 A g-1. We note that equilibration under a constant potential prior to GCD analysis leads to the K+ counterions in the CPE exchanging with Na+ and, thus, the relevant active material Pris-CPE-Na. It is possible to remove the CPE material from the electrochemical cell via extraction with water and to carry out a simple purification through dialysis to produce a recycled material, namely Re-CPE-Na. The recycling workup has no significant detrimental impact on the electrochemical performance. Specifically, Re-CPE-Na hydrogels display an initial specific capacitance of 26.3 ± 1.2 F g-1 (at 10 A g-1) and retain 77% of the capacitance after a subsequent 100,000 GCD cycles. Characterization by NMR, FTIR, and Raman spectroscopies, together with XPS and GPC measurements, revealed no change in the structure of the backbone or side chains. However, rheological measurements gave evidence of a slight loss in G' and G''. Overall, that CPE hydrogels display recyclability argues in favor of considering them as a novel materials platform for energy storage applications within an economically viable circular recycling strategy.

From nuclear track characterization to machine learning based image classification in neutron autoradiography for boron neutron capture therapy.

Knowledge of the 10B microdistribution is of great relevance in BNCT studies. Since 10B concentration assesment through neutron autoradiography depends on the correct quantification of tracks in a nuclear track detector, image acquisition and processing conditions should be controlled and verified, in order to obtain accurate results to be applied in the frame of BNCT. With this aim, an image verification process was proposed, based on parameters extracted from the quantified nuclear tracks. Track characterization was performed by selecting a set of morphological and pixel-intensity uniformity parameters from the quantified objects (area, diameter, roundness, aspect ratio, heterogeneity and clumpiness). Their distributions were studied, leading to the observation of varying behaviours in images generated by different samples and acquisition conditions. The distributions corresponding to samples coming from the BNC reaction showed similar attributes in each analyzed parameter, proving to be robust to the experimental process, but sensitive to light and focus conditions. Considering those observations, a manual feature extraction was performed as a pre-processing step. A Support Vector Machine (SVM) and a fully dense Neural Network (NN) were optimized, trained, and tested. The final performance metrics were similar for both models: 93%-93% for the SVM, vs 94%-95% for the NN in accuracy and precision respectively. Based on the distribution of the predicted class probabilities, the latter had a better capacity to reject inadequate images, so the NN was selected to perform the image verification step prior to quantification. The trained NN was able to correctly classify the images regardless of their track density. The exhaustive characterization of the nuclear tracks provided new knowledge related to the autoradiographic images generation. The inclusion of machine learning in the analysis workflow proves to optimize the boron determination process and paves the way for further applications in the field of boron imaging.

Amidine-Based Cationic Conjugated Oligoelectrolytes with Antimicrobial Activity against Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that can cause high-morbidity infections. Due to its robust, flexible genome and ability to form biofilms, it can evade and rapidly develop resistance to antibiotics. Cationic conjugated oligoelectrolytes (COEs) have emerged as a promising class of antimicrobials. Herein, we report a series of amidine-containing COEs with high selectivity for bacteria. From this series, we identified 1b as the most active compound against P. aeruginosa (minimum inhibitory concentration (MIC) = 2 µg/mL) with low cytotoxicity (IC50 (HepG2) = 1024 µg/mL). The activity of 1b was not affected by known drug-resistant phenotypes of 100 diverse P. aeruginosa isolates. Moreover, 1b is bactericidal with a low propensity for P. aeruginosa to develop resistance. Furthermore, 1b is also able to inhibit biofilm formation at subinhibitory concentrations and kills P. aeruginosa in established biofilms. The in vivo efficacy of 1b was demonstrated in biofilm-associated murine wound infection models.

Structural modulation of membrane-intercalating conjugated oligoelectrolytes decouples outer membrane permeabilizing and antimicrobial activities.

We report a series of membrane-intercalating conjugated oligoelectrolytes (MICOEs) to probe how structural features impact bacterial membrane integrity and antibiotic activity. Minimum inhibitory concentrations (MICs) and outer membrane (OM) permeability correlated to different structural parameters suggesting that the antimicrobial mechanism is not related to OM permeabilization. However, lipid order parameters and MICs correlated to the same structural feature suggesting a possible link.

Interstellar photovoltaics.

The term 'Solar Cell' is commonly used for Photovoltaics that convert light into electrical energy. However, light can be harvested from various sources not limited to the Sun. This work considers the possibility of harvesting photons from different star types, including our closest neighbor star Proxima Centauri. The theoretical efficiency limits of single junction photovoltaic devices are calculated for different star types at a normalized light intensity corresponding to the AM0 spectrum intensity with AM0 = 1361 W/m2. An optimal bandgap of > 12 eV for the hottest O5V star type leads to 47% Shockley-Queisser photoconversion efficiency (SQ PCE), whereas a narrower optimal bandgap of 0.7 eV leads to 23% SQ PCE for the coldest red dwarf M0, M5.5Ve, and M8V type stars. Organic Photovoltaics (OPVs) are the most lightweight solar technology and have the potential to be employed in weight-restricted space applications, including foreseeable interstellar missions. With that in mind, the Sun's G2V spectrum and Proxima Centauri's M5.5Ve spectrum are considered in further detail in combination with two extreme bandgap OPV systems: one narrow bandgap system (PM2:COTIC-4F, Eg = 1.14 eV) and one wide bandgap system (PM6:o-IDTBR, Eg = 1.62 eV). Semi-empirically modeled JV-curves reveal that the absorption characteristics of the PM2:COTIC-4F blend match well with both the G2V and the M5.5Ve spectrum, yielding theoretical PCEs of 22.6% and 12.6%, respectively. In contrast, the PM6:o-IDTBR device shows a theoretical PCE of 18.2% under G2V illumination that drops sharply to 0.9% under M5.5Ve illumination.

Single-cell lineage capture across genomic modalities with CellTag-multi reveals fate-specific gene regulatory changes.

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to endoderm progenitors, we identify core regulatory programs underlying on-target and off-target fates. Furthermore, we reveal the transcription factor Zfp281 as a regulator of reprogramming outcome, biasing cells toward an off-target mesenchymal fate. Our results establish CellTag-multi as a lineage-tracing method compatible with multiple single-cell modalities and demonstrate its utility in revealing fate-specifying gene regulatory changes across diverse paradigms of differentiation and reprogramming.

Single-cell lineage tracing reveals hierarchy and mechanism of adipocyte precursor maturation.

White adipose tissue is crucial in various physiological processes. In response to high caloric intake, adipose tissue may expand by generating new adipocytes. Adipocyte precursor cells (progenitors and preadipocytes) are essential for generating mature adipocytes, and single-cell RNA sequencing provides new means to identify these populations. Here, we characterized adipocyte precursor populations in the skin, an adipose depot with rapid and robust generation of mature adipocytes. We identified a new population of immature preadipocytes, revealed a biased differentiation potential of progenitor cells, and identified Sox9 as a critical factor in driving progenitors toward adipose commitment, the first known mechanism of progenitor differentiation. These findings shed light on the specific dynamics and molecular mechanisms underlying rapid adipogenesis in the skin.

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 .

Increased Nitrogenase Activity in Solar-Driven Biohybrids Containing Non-photosynthetic Bacteria and Conducting Polymers.

A conductive polymer-based photosynthetic biohybrid is constructed to enhance biological nitrogen fixation by increasing nitrogenase activity in the non-photosynthetic bacterium Azotobacter Chroococcum (A. Chroococcum). The light-harvesting cationic poly(fluorene-alt-phenylene) (PFP) electrostatically binds to the surface of the bacteria and possesses satisfactory conductivity to facilitate electron transfer to the bacterium, promoting the nitrogen fixation pathway through redox proteins on the surface of the bacteria when under illumination. Therefore, the nitrogenase activity, hydrogen, NH4 + -N and L-amino acids production are increased by 260 %, 37 %, 44 %, and 47 %, respectively. The expression levels of nifD and nifK encoding molybdenum-iron (MoFe) protein and relevant nitrogen-fixing proteins are up-regulated. These photoactive conductive polymer-bacteria biohybrids provide a new method for improving the biological nitrogen fixation capability of non-photosynthetic nitrogen-fixing bacteria.

An n-Type Conjugated Oligoelectrolyte Mimics Transmembrane Electron Transport Proteins for Enhanced Microbial Electrosynthesis.

Interfacing bacteria as biocatalysts with an electrode provides the basis for emerging bioelectrochemical systems that enable sustainable energy interconversion between electrical and chemical energy. Electron transfer rates at the abiotic-biotic interface are, however, often limited by poor electrical contacts and the intrinsically insulating cell membranes. Herein, we report the first example of an n-type redox-active conjugated oligoelectrolyte, namely COE-NDI, which spontaneously intercalates into cell membranes and mimics the function of endogenous transmembrane electron transport proteins. The incorporation of COE-NDI into Shewanella oneidensis MR-1 cells amplifies current uptake from the electrode by 4-fold, resulting in the enhanced bio-electroreduction of fumarate to succinate. Moreover, COE-NDI can serve as a "protein prosthetic" to rescue current uptake in non-electrogenic knockout mutants.

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.

Impact of COVID-19 vaccination in post-COVID cardiac complications.

BACKGROUND: After the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms. METHODS: All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis. RESULTS: From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17-0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40-0.69, p<0.001). CONCLUSION: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.

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.

A broad-spectrum synthetic antibiotic that does not evoke bacterial resistance.

BACKGROUND: Antimicrobial resistance (AMR) poses a critical threat to public health and disproportionately affects the health and well-being of persons in low-income and middle-income countries. Our aim was to identify synthetic antimicrobials termed conjugated oligoelectrolytes (COEs) that effectively treated AMR infections and whose structures could be readily modified to address current and anticipated patient needs. METHODS: Fifteen chemical variants were synthesized that contain specific alterations to the COE modular structure, and each variant was evaluated for broad-spectrum antibacterial activity and for in vitro cytotoxicity in cultured mammalian cells. Antibiotic efficacy was analyzed in murine models of sepsis; in vivo toxicity was evaluated via a blinded study of mouse clinical signs as an outcome of drug treatment. FINDINGS: We identified a compound, COE2-2hexyl, that displayed broad-spectrum antibacterial activity. This compound cured mice infected with clinical bacterial isolates derived from patients with refractory bacteremia and did not evoke bacterial resistance. COE2-2hexyl has specific effects on multiple membrane-associated functions (e.g., septation, motility, ATP synthesis, respiration, membrane permeability to small molecules) that may act together to negate bacterial cell viability and the evolution of drug-resistance. Disruption of these bacterial properties may occur through alteration of critical protein-protein or protein-lipid membrane interfaces-a mechanism of action distinct from many membrane disrupting antimicrobials or detergents that destabilize membranes to induce bacterial cell lysis. INTERPRETATION: The ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. These COE features enable the construction of a spectrum of compounds with the potential for development as a new versatile therapy for an imminent global health crisis. FUNDING: U.S. Army Research Office, National Institute of Allergy and Infectious Diseases, and National Heart, Lung, and Blood Institute.

Water-soluble extracellular vesicle probes based on conjugated oligoelectrolytes.

We developed a series of transmembrane conjugated oligoelectrolytes (COEs) with tunable optical emissions from the UV to the near IR to address the false-positive problem when detecting nanometer-sized extracellular vesicles (EVs) by flow cytometry. The amphiphilic molecular framework of COEs is defined by a linear conjugated structure and cationic charged groups at each terminal site. Consequently, COEs have excellent water solubility and the absence of nanoaggregates at concentrations up to 50 µM, and unbound COE dyes can be readily removed through ultrafiltration. These properties enable unambiguous and simple detection of COE-labeled small EVs using flow cytometry with negligible background signals. We also demonstrated the time-lapsed tracking of small EV uptake into mammalian cells and the endogenous small EV labeling using COEs. Briefly, COEs provide a class of membrane-targeting dyes that behave as biomimetics of the lipid bilayer and a general and practical labeling strategy for nanosized EVs.