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Nicotinamide adenine dinucleotide (NAD) and its reduced form are indispensable cofactors in life. Diverse NAD mimics have been developed for applications in chemical and biological sciences. Nicotinamide cytosine dinucleotide (NCD) has emerged as a non-natural cofactor to mediate redox transformations, while cells are fed with chemically synthesized NCD. Here, we create NCD synthetase (NcdS) by reprograming the substrate binding pockets of nicotinic acid mononucleotide (NaMN) adenylyltransferase to favor cytidine triphosphate and nicotinamide mononucleotide over their regular substrates ATP and NaMN, respectively. Overexpression of NcdS alone in the model host Escherichia coli facilitated intracellular production of NCD, and higher NCD levels up to 5.0 mM were achieved upon further pathway regulation. Finally, the non-natural cofactor self-sufficiency was confirmed by mediating an NCD-linked metabolic circuit to convert L-malate into D-lactate. NcdS together with NCD-linked enzymes offer unique tools and opportunities for intriguing studies in chemical biology and synthetic biology.
Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.
Adult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.
Efficient low-grade heat recovery can help to reduce greenhouse gas emission as over 70% of primary energy input is wasted as heat, but current technologies to fulfill the heat-to-electricity conversion are still far from optimum. Here we report a direct thermal charging cell, using asymmetric electrodes of a graphene oxide/platinum nanoparticles cathode and a polyaniline anode in Fe2+/Fe3+ redox electrolyte via isothermal heating operation. When heated, the cell generates voltage via a temperature-induced pseudocapacitive effect of graphene oxide and a thermogalvanic effect of Fe2+/Fe3+, and then discharges continuously by oxidizing polyaniline and reducing Fe3+ under isothermal heating till Fe3+ depletion. The cell can be self-regenerated when cooled down. Direct thermal charging cells attain a temperature coefficient of 5.0 mV K-1 and heat-to-electricity conversion efficiency of 2.8% at 70 °C (21.4% of Carnot efficiency) and 3.52% at 90 °C (19.7% of Carnot efficiency), outperforming other thermoelectrochemical and thermoelectric systems.
Self-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.
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