No abstract

Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

During dire conditions, the channelling of resources into reproduction ensures species preservation. This strategy of survival through the next generation is particularly important for plants that are unable to escape their environment but can produce hardy seeds. Here, we describe the multiple roles of OXIDATIVE STRESS 2 (OXS2) in maintaining vegetative growth, activating stress tolerance, or entering into stress-induced reproduction. In the absence of stress, OXS2 is cytoplasmic and is needed for vegetative growth; in its absence, the plant flowers earlier.Upon stress, OXS2 is nuclear and is needed for stress tolerance; in its absence, the plant is stress sensitive. OXS2 can activate its own gene and those of floral integrator genes, with direct binding to the floral integrator promoter SOC1. Stress-induced SOC1 expression and stress-induced flowering are impaired in mutants with defects in OXS2 and three of the four OXS2-like paralogues. The autoactivation of OXS2 may be a commensurate response to the stress intensity, stepping up from a strategy based on tolerating the effects of stress to one of escaping the stress via reproduction.

Numerous efforts have been devoted to boost the efficiency of thermally activated delayed fluorescence (TADF) devices; however, strategies to suppress the device efficiency roll-off are still in urgent need. Here, a general and effective approach to suppress the efficiency roll-off of TADF devices is proposed, that is, utilizing TADF materials as the hosts for TADF emitters. Bearing small singlet-triplet splitting (ΔE) with donor and acceptor units, TADF materials as the hosts possess the potential to achieve matched frontier energy levels with the adjacent transporting layers, facilitating balanced charge injection as well as bipolar charge transport mobilities beneficial to the balanced charges transportation. Furthermore, an enhanced Förster energy transfer from the host to the dopant can be anticipated, helpful to reduce the exciton concentration. Based on the principles, a new TADF material based on indeno[2,1-b]carbazole/1,3,5-triazin derivation is synthesized and used as the universal host for the full-color TADF devices. Remarkable low efficiency roll-off was achieved with above 90% of the maximum external quantum efficiencies (EQE's) maintained even at a brightness of 2000 cd/m, along with EQE's of 23.2, 21.0, and 19.2% for orange, green, and sky-blue TADF devices, respectively. Through computational simulation, we identified the suppressed exciton annihilation rates compared with devices adopting conventional hosts. The state-of-the-art low efficiency roll-off of those TADF devices manifests the great potential of such host design strategy, paving an efficient strategy toward their practical application.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has lasted more than 2 years with over 260 million infections and 5 million deaths worldwide as of November 2021. To combat the virus, monoclonal antibodies blocking the virus binding to human receptor, the angiotensin converting enzyme 2 (ACE2), have been approved to treat the infected patients. Inactivated whole virus or the full-length virus spike encoding adenovirus or mRNA vaccines are being used to immunize the public. However, SARS-CoV-2 variants are emerging. These, to some extent, escape neutralization by the therapeutic antibodies and vaccine-induced immunity. Thus, breakthrough infections by SARS-CoV-2 variants have been reported in previously virus-infected or fully vaccinated individuals. The receptor binding domain (RBD) of the virus spike protein reacts with host ACE2, leading to the entry of the virus into the cell. It is also the major antigenic site of the virus, with more than 90% of broadly neutralizing antibodies from either infected patients or vaccinated individuals targeting the spike RBD. Therefore, mutations in the RBD region are effective ways for SARS-CoV-2 variants to gain infectivity and escape the immunity built up by the original vaccines or infections. In this review, we focus on the impact of RBD mutations in SARS-CoV-2 variants of concern (VOC) and variants of interest (VOI) on ACE2 binding affinity and escape of serum antibody neutralization. We also provide protein structure models to show how the VOC and VOI RBD mutations affect ACE2 binding and allow escape of the virus from the therapeutic antibody, bamlanivimab.

SUMMARYReactive oxygen species (ROS) are signaling molecules, but how they are perceived in plants remains unclear. This study showed that cortex proliferation in the Arabidopsis root can be induced by hydrogen peroxide and that the receptor kinase ERECTA and one of its ligands, STOMAGEN, are involved in a signaling pathway that couples ROS sensing with redox-mediated cortex proliferation. This study also revealed a new role for SPINDLY (SPY), a putative O-GlcNAc transferase, in cellular redox homeostasis.

White organic light-emitting diodes (WOLEDs) with thermally activated delayed fluorophor sensitized fluorescence (TSF) have aroused wide attention, considering their potential for full exciton utilization without noble-metal containing phosphors. However, performances of TSF-WOLEDs with a singleemissive-layer (SEL) still suffer from low exciton utilization and insufficient blue emission for proper white balance. Here, by modulating Förster and Dexter interactions in SEL-TSF-WOLEDs, high efficiencies, balanced white spectra, and extended lifetimes are realized simultaneously. Given the different dependencies of Förster and Dexter interactions on intermolecular distances, sterically shielded blue thermally activated delayed fluorescence (TADF) emitters and orange conventional fluorescent dopants (CFDs) with electronically inert peripheral units are adopted to enlarge distances of electronically active chromophores, not only blocking the Dexter interaction to prevent exciton loss but also finely suppressing the Förster one to guarantee balanced white emission with sufficient blue components. It thus provides the possibility to maximize device performances in a large range of CFD concentrations. A record high maximum external quantum efficiency/power efficiency of 19.6%/52.2 lm W −1 , Commission Internationale de L'Eclairage coordinate of (0.33, 0.45), and prolonged half-lifetime of over 2300 h at an initial luminance of 1000 cd m −2 are realized simultaneously for SEL-TSF-WOLEDs, paving the way toward practical applications.

A high triplet energy (T) is usually taken as the prerequisite of the good exciton confinement of electron transporting materials (ETMs); however, there is usually a tradeoff with large mobility and stability. Here, we demonstrated that good exciton confinement can also be realized utilizing a low-T ETM with a sterically shielding low-T unit. Given the short-range interaction of the Dexter energy transfer, the large steric side groups of the low-T ETM can effectively hinder the T of the emitters from being quenched by increasing the intermolecular distance. Based on this concept, a maximum external quantum efficiency (EQE) as high as 21.3% was observed in the sky-blue thermally activated delayed fluorescence device using a low-T ETM, with the EQE remaining at 21.2% at 1000 cd/m and 17.8% at 5000 cd/m. Further, an EQE as high as 25.5%, a low turn-on voltage of 2.3 V, as well as a long T of over 400 h at an initial luminance of 5000 cd/m were achieved for green phosphorescent devices. This work highlights a viable strategy for developing high-performance ETMs, paving their way toward practical applications.