Search

Effective optical absorption is highly desirable for numerous applications in energy harvesting and optoelectronics. Bifacial absorbers can significantly enhance light absorption by capturing albedo light from the environment. Here, we experimentally demonstrate that free-standing silica-silver core–shell nano-resonator arrays allow bifacial and omnidirectional optical absorption across the visible spectrum. Specifically, resonator arrays can highly absorb light (>80%) with all polarizations from a directional range (−40° to 40°) on both front and rear sides of a surface. Numerical simulations reveal that such bifacial and omnidirectional light absorption results from hybridized excitation of surface plasmons and whispering gallery modes in a symmetrical configuration. The absorption band can be flexibly adjusted by changing the silica core size. In addition, the absorbed optical energy quickly decays as the excitation of plasmonic hot electrons as observed using transient absorption spectroscopy. Our work provides a bifacial absorber for many optoelectronic applications in photodetection, photovoltaics, and photocatalysis. [ABSTRACT FROM AUTHOR]

With the expansion of the gene circuits scale and its application, traditional approaches to design gene circuits for synthetic biology are faced with new challenges. The construction of the new synthetic genetic circuits requires a long experimental cycle with huge cost of trial and error, so it is difficult to get satisfying results in a short time by simply relying on experiments. The iGEM software design competition aims to make the design and prediction of genetic circuits more efficient and automatic. In order to understand the software design better and acquire new design ideas, the projects of iGEM software teams of recent years are summarized, where the background, purpose, design scheme, and application of the projects were investigated. After comparison and summarization, these projects could be classified into four categories according to their functions: 1 auxiliary design, 2 data sharing, 3 cooperation and communication, and 4 data analysis. The review could provide new ideas for the future iGEM software design, and the development of systematic genetic circuit design automation for synthetic biology. [ABSTRACT FROM AUTHOR]

In the present study, the effects of levamlodipine benzenesulfonate on the development of fertile Sprague-Dawley (SD) rats, their embryos, and littermates were assessed using an embryo-fetal developmental toxicity test. Maternal body weight reduction was observed at a dose of 20 mg/kg, but it recovered after treatment cessation. The 20 mg/kg dose group showed a skewed sex ratio in fetal rats, with a higher proportion of males. While some effects on fetal sternum development were observed at 20 mg/kg, no skeletal malformations were observed. No significant gross morphological abnormalities were detected in the dams (mothers), no significant embryotoxicity or foetotoxicity in fetal rats and no significant effects on fetal length and weight development at doses of 5 and 10 mg/kg. Genotoxicity was evaluated using a combination of the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration assay, and the ICR mouse bone marrow micronucleus test. The Ames test results indicated substantial bacteriostatic effects at doses of 500 and 5000 mg/dish, with no mutagenicity observed at doses of 0.5, 5, and 50 mg/dish. No significant effect on the aberration rate of CHO cell chromosomes was found at doses of 2.8, 5.6, and 11.2 mg/mL. In the ICR mouse micronucleus test, no micronucleus-inducing effect was observed at doses of 3.125, 6.25, and 12.5 mg/kg in each treatment group. In conclusion, under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for developmental toxicity of levamlodipine benzenesulfonate in fertile SD rats, their embryos, and littermates was established to be 10 mg/kg/day. Levamlodipine benzenesulfonate did not exhibit significant genotoxicity. • First evaluation of the embryo-fetal developmental toxicity of levamlodipine benzenesulfonate compound I in SD rats. • The genotoxicity of levamlodipine benzenesulfonate compound I was evaluated for the first time. • The NOAEL of levamlodipine benzenesulfonate compound I in pregnant SD rats, embryos and fetuses was higher than 10 mg/kg/day. [ABSTRACT FROM AUTHOR]

Efficient forward stimulated Raman scattering (SRS) was observed along 400-nm femtosecond (fs) laser filaments in water. SRS conversion dominated over self-phase modulation induced continuum generation as the input pulse energy was above 4 μJ (∼30 Pcr), implying that plasma in the aqueous filamentation channel played an important role in compensating for the group velocity walk-off between the pump and Stokes pulses. By overlapping two synchronous fs 400-nm filaments to form plasma grating in water, significant enhancement of SRS conversion was observed. Such a SRS enhancement originated from the ultrahigh plasma density in the intersection region of the preformed plasma grating. [ABSTRACT FROM AUTHOR]

Micro‐scale soft actuators with controllable shape‐morphing are the focus of advanced technological fields, ranging from advancing sensing, industrial robotics, and digital manufacturing to medical devices. Particularly, there is a growing interest in the scientific community to leverage liquid crystal polymers (LCPs) to fabricate such soft actuators, because LCPs can offer reversible, programmable deformations under external stimuli. However, pattern micromachining of LCPs into micro‐scale remains a daunting challenge. Herein, a femtosecond laser direct writing (FsLDW) method for cross‐linked LCP (CLCP) microstructure construction is reported that enables arbitrary pattern machining with a minimum size of 40 µm and average heat‐affected zone (HAZ) below 8 µm through optimization of processing parameters. Light‐driven behaviors of CLCP microstructures are systematically characterized through analyzing the effects of film thickness, length‐width ratio, light irradiation time, incident angle, light intensity, and cutting direction on bending and twisting behaviors. Finally, a light‐driven micromirror system is demonstrated, which can achieve not only a controllable swing but also a rotation of the mirror surface with a maximum scanning frequency of ≈2 Hz. [ABSTRACT FROM AUTHOR]

New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobacterial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria. We prepared compounds that potently inhibit the growth of Mycobacterium tuberculosis (Mtb) and other mycobacteria in cell culture. The cryoelectron microscopy (cryo-EM) structure of mycobacterial MmpL3 in complex with one of these compounds (ST004) was determined using lipid nanodiscs at an overall resolution of 3.36 Å. The structure reveals the binding mode of ST004 to MmpL3, with the S4 and S5 subsites of the inhibitor-binding pocket in the proton translocation channel playing vital roles. These data are a promising starting point for the development of anti-tuberculosis drugs that target MmpL3. [Display omitted] • Compounds with antibacterial activity that target MmpL3 are reported • Compound ST004 potently inhibits the growth of Mtb as well as other mycobacteria • Cryo-EM structure of MmpL3 in complex with ST004 is determined in lipid nanodiscs • The scaffolds at the S4 and S5 subsites are important for the efficacy of the compounds MmpL3 is an important target for TB drug discovery. Hu et al. report the structure-based development of potent compounds that target MmpL3. These data are a promising starting point for the development of anti-mycobacterial drugs targeting MmpL3. [ABSTRACT FROM AUTHOR]

A novel coronavirus [severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo–electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified b-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp. [ABSTRACT FROM AUTHOR]

The human pathogen, Mycobacterium tuberculosis (Mtb) relies heavily on trehalose for both survival and pathogenicity. The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the only trehalose import pathway in Mtb. Conformational dynamics of ABC transporters is an important feature to explain how they operate, but experimental structures are determined in a static environment. Therefore, a detailed transport mechanism cannot be elucidated because there is a lack of intermediate structures. Here, we used single-particle cryo-electron microscopy (cryo-EM) to determine the structure of the Mycobacterium smegmatis (M. smegmatis) trehalose-specific importer LpqY-SugABC complex in five different conformations. These structures have been classified and reconstructed from a single cryo-EM dataset. This study allows a comprehensive understanding of the trehalose recycling mechanism in Mycobacteria and also demonstrates the potential of single-particle cryo-EM to explore the dynamic structures of other ABC transporters and molecular machines. [Display omitted] • Structures of LpqY-SugABC in complex with trehalose and ATP • Five structures of LpqY-SugABC have been determined from a single cryo-EM dataset • The intermediate structures reveal the trehalose import mechanism in Mycobacteria The LpqY-SugABC complex is the only trehalose import pathway in mycobacteria, and it plays an important role in the survival of these bacteria. Liang et al. determine the structures of Mycobacterium smegmatis LpqY-SugABC complex in five different comformations, providing a comprehensive understanding of the trehalose import mechanism in Mycobacteria. [ABSTRACT FROM AUTHOR]

Biological energy currency ATP is produced by F 1 F o -ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures reveal that the release of ADP occurs when the β subunit of F 1 F o -ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis. The accommodation of the symmetry mismatch between F 1 and F o motors is resolved by the torsional flexing of the entire complex, especially the γ subunit, and the rotational substep of the c subunit. Water molecules are identified in the inlet and outlet half-channels, suggesting that the proton transfer in these two half-channels proceed via a Grotthus mechanism. Clinically relevant mutations are mapped to the structure, showing that they are mainly located at the subunit-subunit interfaces, thus causing instability of the complex. [Display omitted] • A complete structure of the human ATP synthase complex • ADP release occurs when the β subunit is in the open conformation • Water molecules are defined in the inlet and outlet proton half-channels • Clinically relevant mutations cause the instability of the complex Lai et al. determine the complete structures of human ATP synthase in three main rotational states and one substate, providing mechanistic insights into the structure and function of the ATP synthase complexes and laying a foundation for target-based drug discovery. [ABSTRACT FROM AUTHOR]

To enhance the signal intensity of magnetostrictive position sensor (MPS), a new method of bipolar pulse excitation (BPE), and a new structure of single-end damper (SED) are proposed in this paper. Two torsion strain waves, named as W1 and W2 waves, are generated by the BPE, and the W1 wave is reflected (changed into RW1) by the SED. Based on the principle of wave superposition, the interference between RW1 and W2 is realized by adjusting the structure parameters of the sensor. Therefore, the MPS signal is strengthened 1.8 times approximately as well as the measuring range. The notable difference between the new strategy and the conventional one lies in the reflection wave. In conventional MPS, the smaller the reflection wave is, the better the signal will be. However, the reflection wave should be as strong as possible in the new strategy. After the explanation of BPE and SED, a new model is presented. The validity and feasibility of the proposed strategy are verified by experiments. Finally, the characteristics of BPE and SED, such as the measured object, the polar of excitation pulse, and the limit of signal, are discussed in detail. Research results indicate that the proposed BPE method and SED structure are innovative development to conventional MPS, and are of great practical value. [ABSTRACT FROM PUBLISHER]

Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here, we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre- and post- translocated polymerase complexes. Compared with the apo complex, the structures show notable structural rearrangements happening to nsp12 and its co-factors nsp7 and nsp8 to accommodate the nucleic acid, whereas there are highly conserved residues in nsp12, positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanism of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription and replication machinery. • Structures of SARS-CoV-2 RNA polymerase in complexes with RNA revealed • Conformational changes in nsp8 and its interaction with the exiting RNA are observed • Incorporation and delayed-chain-termination mechanism of remdesivir is elucidated • Transition model from primase complex to polymerase complex is proposed Cryo-EM structures of the SARS-CoV-2 RNA polymerase in complexes with RNA, before and after RNA translocation, reveals structural rearrangements that the RNA-dependent RNA polymerase (RdRp) nsp12 and its co-factors (nsp7 and nsp8) undergo to accommodate nucleic acid binding. Further insights into how the complex is inhibited by remdesivir, and into the primase to polymerase transition, are also presented. [ABSTRACT FROM AUTHOR]