Nature Communications最新文献

Correction to: Nature Communications https://doi.org/10.1038/s41467-024-50424-8, published online 16 July 2024

Cellular responses to stimuli underpin discoveries in drug development, synthetic biology, and general life sciences. We introduce a library comprising 6144 synthetic promoters, each shorter than 250 bp, designed as transcriptional readouts of cellular stimulus responses in massively parallel reporter assay format. This library facilitates precise detection and amplification of transcriptional activity from our promoters, enabling the systematic development of tunable reporters with dynamic ranges of 50−100 fold. Our library proved functional in numerous cell lines and responsive to a variety of stimuli, including metabolites, mitogens, toxins, and pharmaceutical agents, generating robust and scalable reporters effective in screening assays, biomarkers, and synthetic circuits attuned to endogenous cellular activities. Particularly valuable in therapeutic development, our library excels in capturing candidate reporters to signals mediated by drug targets, a feature we illustrate across nine diverse G-protein coupled receptors (GPCRs), critical targets in drug development. We detail how this tool isolates and defines discrete signaling pathways associated with specific GPCRs, elucidating their transcriptional signatures. With its ease of implementation, broad utility, publicly available data, and comprehensive documentation, our library will be beneficial in synthetic biology, cellular engineering, ligand exploration, and drug development.

Salicylic acid (SA) production in Brassicaceae plants is uniquely accelerated from isochorismate by EPS1, a newly identified enzyme in the BAHD acyltransferase family. We present crystal structures of EPS1 from Arabidopsis thaliana in both its apo and substrate-analog-bound forms. Integrating microsecond-scale molecular dynamics simulations with quantum mechanical cluster modeling, we propose a pericyclic rearrangement lyase mechanism for EPS1. We further reconstitute the isochorismate-derived SA biosynthesis pathway in Saccharomyces cerevisiae, establishing an in vivo platform to examine the impact of active-site residues on EPS1 functionality. Moreover, stable transgenic expression of EPS1 in soybean increases basal SA levels, highlighting the enzyme’s potential to enhance defense mechanisms in non-Brassicaceae plants lacking an EPS1 ortholog. Our findings illustrate the evolutionary adaptation of an ancestral enzyme’s active site to enable a novel catalytic mechanism that boosts SA production in Brassicaceae plants.

Quantum sensors based on solid-state defects, in particular nitrogen-vacancy (NV) centers in diamond, enable precise measurement of magnetic fields, temperature, rotation, and electric fields. Cavity quantum electrodynamic (cQED) readout, in which an NV ensemble is hybridized with a microwave mode, can overcome limitations in optical spin detection and has resulted in leading magnetic sensitivities at the pT-level. This approach, however, remains far from the intrinsic spin-projection noise limit due to thermal Johnson-Nyquist noise and spin saturation effects. Here we tackle these challenges by combining recently demonstrated spin refrigeration techniques with comprehensive nonlinear modeling of the cQED sensor operation. We demonstrate that the optically-polarized NV ensemble simultaneously provides magnetic sensitivity and acts as a heat sink for the deleterious thermal microwave noise background, even when actively probed by a microwave field. Optimizing the NV-cQED system, we demonstrate a broadband sensitivity of 576 ± 6 fT/(sqrt{{{{rm{Hz}}}}}) around 15 kHz in ambient conditions. We then discuss the implications of this approach for the design of future magnetometers, including near-projection-limited devices approaching 3 fT/(sqrt{{{{rm{Hz}}}}}) sensitivity enabled by spin refrigeration.

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss. Elevation of OXM, under basal and postprandial conditions, and similar metabolic adaptations after G49 treatment were found in plasma from patients with obesity early after metabolic bariatric surgery. These results identify G49 as a potential pharmacological alternative sharing with bariatric surgery hormonal and metabolic pathways.

The development of efficient and stable electrocatalysts for water oxidation in acidic media is vital for the commercialization of the proton exchange membrane electrolyzers. In this work, we successfully construct Ru–O–Ir atomic interfaces for acidic oxygen evolution reaction (OER). The catalysts achieve overpotentials as low as 167, 300, and 390 mV at 10, 500, and 1500 mA cm⁻² in 0.5 M H₂SO₄, respectively, with the electrocatalyst showing robust stability for >1000 h of operation at 10 mA cm⁻² and negligible degradation after 200,000 cyclic voltammetry cycles. Operando spectroelectrochemical measurements together with theoretical investigations reveal that the OER pathway over the Ru–O–Ir active site is near-optimal, where the bridging oxygen site of Ir–O_BRI serves as the proton acceptor to accelerate proton transfer on an adjacent Ru centre, breaking the typical adsorption-dissociation linear scaling relationship on a single Ru site and thus enhancing OER activity. Here, we show that rational design of multiple active sites can break the activity/stability trade-off commonly encountered for OER catalysts, offering good approaches towards high-performance acidic OER catalysts.

Precipitation hardening has been recently validated as a new mechanism for domain wall pinning and mechanical loss reduction in piezoelectrics. While anisometric precipitates have high pinning strengths, there is limited knowledge about the electrical anisotropy of the precipitation-hardened piezoceramics. In the present work, we successfully orient the precipitates in Li_0.18Na_0.82NbO₃ piezoceramics by applying a uniaxial stress during the aging and studied its electrical anisotropy. Predicted by mechanical simulation and verified by transmission electron microscopy, it is demonstrated that the precipitate variant with its long axis perpendicular to the applied stress is energetically favored. The electrical anisotropy of the stress-assisted aged Li_0.18Na_0.82NbO₃ is studied by applying electrical fields parallel or perpendicular to the stress axis. The domain wall contribution to permittivity is found to vary by more than a factor of two depending on orientation. In addition, the domain walls are more difficult to be activated by increasing the temperature when the electric field is perpendicular to the stress axis. Our work highlights the precipitate variant selection induced by stress-assisted aging and the related electrical anisotropy in piezoceramics. This technique enables the precipitate orientation in piezoceramics and the utilization of its anisotropy, providing fundamental insight into precipitate-domain-wall interactions and setting the ground for leveraging precipitation hardening effect in piezoceramics.

Understanding abiotic carbon fixation provides insights into early Earth’s carbon cycles and life’s emergence in terrestrial hot springs, where iron sulfide (FeS), similar to cofactors in metabolic enzymes, may catalyze prebiotic synthesis. However, the role of FeS-mediated carbon fixation in such conditions remains underexplored. Here, we investigate the catalytic behaviors of FeS (pure and doped with Ti, Ni, Mn, and Co), which are capable of H₂-driven CO₂ reduction to methanol under simulated hot spring vapor-zone conditions, using an anaerobic flow chamber connected to a gas chromatograph. Specifically, Mn-doped FeS increases methanol production five-fold at 120 °C, with UV−visible light (300–720 nm) and UV-enhanced light (200–600 nm) further increasing this activity. Operando and theoretical investigations indicate the mechanism involves a reverse water-gas shift with CO as an intermediate. These findings highlight the potential of FeS-catalyzed carbon fixation in early Earth’s terrestrial hot springs, effective with or without UV light.

The stereoselectivity of enzymes plays a central role in asymmetric biocatalytic reactions, but there remains a dearth of evolution-driven biochemistry studies investigating the evolutionary trajectory of this vital property. Imine reductases (IREDs) are one such enzyme that possesses excellent stereoselectivity, and stereocomplementary members are pervasive in the family. However, the regulatory mechanism behind stereocomplementarity remains cryptic. Herein, we reconstruct a panel of active ancestral IREDs and trace the evolution of stereoselectivity from ancestors to extant IREDs. Combined with coevolution analysis, we reveal six historical mutations capable of recapitulating stereoselectivity evolution. An investigation of the mechanism with X-ray crystallography shows that they collectively reshape the substrate-binding pocket to regulate stereoselectivity inversion. In addition, we construct an empirical fitness landscape and discover that epistasis is prevalent in stereoselectivity evolution. Our findings emphasize the power of ASR in circumventing the time-consuming large-scale mutagenesis library screening for identifying mutations that change functions and support a Darwinian premise from a molecular perspective that the evolution of biological functions is a stepwise process.

High-quality (Q)-factor optical resonators with extreme temporal coherence are of both technological and fundamental importance in optical metrology, continuous-wave lasing, and semiconductor quantum optics. Despite extensive efforts in designing high-Q resonators across different spectral regimes, the experimental realization of very large Q-factors at visible wavelengths remains challenging due to the small feature size that is sensitive to fabrication imperfections, and thus is typically implemented in integrated photonics. In the pursuit of free-space optics with the benefits of large space-bandwidth product and massive parallel operations, here we design and fabricate a near-visible-wavelength etch-free metasurface with minimized fabrication defects and experimentally demonstrate a million-scale ultrahigh-Q resonance. A new laser-scanning momentum-space-resolved spectroscopy technique with extremely high spectral and angular resolution is developed to characterize the record-high Q-factor as well as the dispersion of the million-Q resonance in free space. By integrating monolayer WSe₂ into our ultrahigh-Q meta-resonator, we further demonstrate laser-like highly unidirectional and narrow-linewidth exciton emission, albeit without any operating power density threshold. Under continuous-wave laser pumping, we observe pump-power-dependent linewidth narrowing at room temperature, indicating the potential of our meta-optics platform in controlling coherent quantum light-sources. Our result also holds great promise for applications like optical sensing, spectral filtering, and few-photon nonlinear optics.