Nature Communications最新文献

Rechargeable Li||I₂ batteries based on liquid organic electrolytes suffer from pronounced polyiodides shuttling and safety concerns, which can be potentially tackled by the use of solid-state electrolytes. However, current all-solid-state Li||I₂ batteries only demonstrate limited capacity based on a two-electron I⁻/I₂ polyiodides chemistry at elevated temperatures, preventing them from rivaling state-of-the-art lithium-ion batteries. Herein, we report a fast, stable and high-capacity four-electron solid-conversion I⁻/I₂/I⁺ chemistry in all-solid-state Li||I₂ batteries at room temperature. Through the strategic use of a highly conductive, chlorine-rich solid electrolyte Li_4.2InCl_7.2 as the catholyte, we effectively activate the I₂/I⁺ redox couple. This activation is achieved through a robust I-Cl interhalogen interaction between I₂ and the catholyte, facilitated by an interface-mediated heterogeneous oxidation mechanism. Moreover, apart from serving as Li-ion conduction pathway, the Li_4.2InCl_7.2 catholyte is demonstrated to show a reversible redox behavior and contribute to the electrode capacity without compromising its conductivity. Based on the I⁻/I₂/I⁺ four-electron chemistry, the as-designed all-solid-state Li||I₂ batteries deliver a high specific capacity of 449 mAh g^-1 at 44 mA g^-1 based on I₂ mass and an impressive cycling stability over 600 cycles with a capacity retention of 91% at 440 mA g^-1 and at 25 °C.

The genetic bases of mosaic pigmentation disorders have increasingly been identified, but these conditions remain poorly characterised, and their pathophysiology is unclear. Here, we report in four unrelated patients that a recurrent postzygotic mutation in GNA13 is responsible for a recognizable syndrome with hypomelanosis of Ito associated with developmental anomalies. GNA13 encodes Gα₁₃, a subunit of αβγ heterotrimeric G proteins coupled to specific transmembrane receptors known as G-protein coupled receptors. In-depth functional investigations revealed that this R200K mutation provides a gain of function to Gα₁₃. Mechanistically, we show that this variant hyperactivates the RHOA/ROCK signalling pathway that consequently increases actin polymerisation and myosin light chains phosphorylation, and promotes melanocytes rounding. Our results also indicate that R200K Gα₁₃ hyperactivates the YAP signalling pathway. All these changes appear to affect cell migration and adhesion but not the proliferation. Our results suggest that hypopigmentation can result from a defect in melanosome transfer to keratinocytes due to cell shape alterations. These findings highlight the interaction between heterotrimeric G proteins and the RHOA pathway, and their role in melanocyte function.

7 billion of 9.2 billion tons of plastic produced becomes waste while conventional catalytic plastic recycling methods are vulnerable with degraded performance and intensive energy input. Here, a hybrid Zn/b-ZnO catalyst, together with the specially-designed microwave reaction system, has achieved fast plastic waste upgrading under atmospheric pressure without using H₂. Bifunctional ZnO acts as a microwave absorber and substrate catalyst, and in-situ formed Zn clusters promote C-C bond cleavage and nearly 100% upcycle landfilled plastic mixtures into lubricant base oil precursors and monomers. Unprecedented turnover number (250 g_plastic g⁻¹_catalyst) of plastic depolymerisation and long-time stability over 50 successive cycles have been demonstrated, together with 8-time higher energy efficiency compared with conventional catalysis, indicating this strategy is an economical approach to efficient upcycling of plastics towards valuable products. Moreover, the catalyst can tolerate high contaminates, even the landfilled plastics can still be converted to lubricant base oil precursors, which has never been reported before.

DNA methylation at cytosine bases (5-methylcytosine, 5mC) is a heritable epigenetic mark regulating gene expression. While enzymes that metabolize 5mC are well-characterized, endogenous signaling molecules that regulate DNA methylation machinery have not been described. We report that physiological nitric oxide (NO) concentrations reversibly inhibit the DNA demethylases TET and ALKBH2 by binding to the mononuclear non-heme iron atom forming a dinitrosyliron complex (DNIC) and preventing cosubstrates from binding. In cancer cells treated with exogenous NO, or endogenously synthesizing NO, 5mC and 5-hydroxymethylcytosine (5hmC) increase, with no changes in DNA methyltransferase activity. 5mC is also significantly increased in NO-producing patient-derived xenograft tumors from mice. Genome-wide methylome analysis of cells chronically treated with NO (10 days) shows enrichment of 5mC and 5hmC at gene-regulatory loci, correlating with altered expression of NO-regulated tumor-associated genes. Regulation of DNA methylation is distinctly different from canonical NO signaling and represents a unique epigenetic role for NO.

Metabolic disturbances are hallmarks of vascular smooth muscle cell (VSMC) phenotypic transitions, which play a critical role in the pathogenesis of aortic dissection (AD). In this study, we identify and characterize glucose metabolism regulatory protein (GMRSP), a protein encoded by lncRNA H19. Using VSMC-specific GMRSP induction in knock-in mice, adeno-associated virus-mediated GMRSP overexpression, and exosomal GMRSP delivery, we demonstrate significant improvements in AD and mitochondrial dysfunction. Mechanistically, GMRSP inhibits heterogeneous nuclear ribonucleoprotein (hnRNP) A2B1-mediated alternative splicing of pyruvate kinase M (PKM) pre-mRNA, leading to reduced PKM2 production and glycolysis. This reprogramming preserves the contractile phenotype of VSMCs and prevents their transition to a proliferative state. Importantly, pharmacological activation of PKM2 via TEPP-46 abrogates the protective effects of GMRSP in vivo and in vitro. Clinical relevance is shown by elevated plasma PKM2 levels in AD patients, which correlate with poor prognosis. Collectively, these findings indicate GMRSP as a key regulator of VSMC metabolism and phenotypic stability, highlighting its potential as a therapeutic target for AD.

Microorganisms must distribute their limited resources among different physiological functions, including those that do not directly contribute to growth. In this study, we investigate the allocation of resources to flagellar swimming, the most prominent and biosynthetically costly of such cellular functions in bacteria. Although the growth-dependence of flagellar gene expression in peritrichously flagellated Escherichia coli is well known, the underlying physiological limitations and regulatory strategies are not fully understood. By characterizing the dependence of motile behavior on the activity of the flagellar regulon, we demonstrate that, beyond a critical number of filaments, the hydrodynamics of propulsion limits the ability of bacteria to increase their swimming by synthesizing additional flagella. In nutrient-rich conditions, E. coli apparently maximizes its motility until reaching this limit, while avoiding the excessive cost of flagella production. Conversely, during carbon-limited growth motility remains below maximal levels and inversely correlates with the growth rate. The physics of swimming may further explain the selection for bimodal resource allocation in motility at low average expression levels. Notwithstanding strain-specific variation, the expression of flagellar genes in all tested natural isolates of E. coli also falls within the same range defined by the physical limitations on swimming and its biosynthetic cost.

Associations between long-term exposure to nitrogen oxides (NO_x) and cause-specific mortality remain insufficiently explored. This study utilizes data from 502,040 participants registered in the UK Biobank. Time-varying Cox regression is used to estimate mortality risks associated with NO_x. Cause-specific mortality risks, including non-accidental, accidental and 15 major disease categories across 103 subcategories, are assessed for each 10 μg/m³ increase in NO_x. Positive associations are observed between NO_x and mortality from all-cause (HR: 1.036; 95% CI: 1.024, 1.049) and non-accidental diseases (HR: 1.032; 95% CI: 1.019, 1.045). We further identify 20 specific diseases related to NO_x, notably respiratory diseases, mental and behavioral disorders, and circulatory diseases, with generally linear exposure-response relationships. Sex and residential areas are potential modifiers of the observed associations. Our findings suggest long-term exposure to NO_x may increase mortality risks from a range of diseases, emphasizing the urgent need for clean air policies to alleviate the health burden.

Childhood maltreatment stands out as a pivotal risk factor for depression, with gene-by-environment interaction serving as a crucial mechanism. Here we perform genome-wide interaction analyzes of childhood maltreatment in the UK Biobank, integrating methylation evidence through colocalization analysis and identifying associated brain structure abnormalities from childhood to adulthood. A genome-wide significant genomic region interacting with childhood maltreatment is identified at 8p11.21 (IDO2 rs7846217, P = 2.02e–08), implicating the tryptophan-kynurenine pathway. Colocalization analysis reveals that IDO2 rs11777027, rs2340953 and rs28631334 are associated with depression in individuals exposed to childhood maltreatment and colocalize with methylation signals in both blood and brain for IDO2. These interactions affect cortical thickness of the left supramarginal gyrus in children (P = 9.72e–04) and adults (P = 1.34e–04), as well as cortical volume in the right angular gyrus in children (P = 1.02e–04). Furthermore, the interactions significantly predict new-onset depression at a 2-year follow-up in children. Stunted increase in cortical thickness of the left middle-anterior cingulate gyrus and sulcus significantly mediates the interaction between childhood maltreatment and IDO2 on childhood depression. These interactions also moderate antidepressant treatment efficacy at 4–6 weeks.

Observations show an increase in the seasonal cycle amplitude of CO₂ in northern latitudes over the past half century. Although multiple drivers contribute, observations and inversion models cannot quantitatively account for the factors contributing to the increased CO₂ amplitude and older versions of Earth System Models (ESMs) do not simulate it. Here we show that several current generation ESMs are closer to the observed CO₂ amplitude and highlight that in the Community Earth System Model (CESM) agricultural nitrogen (N) fertilization increases CO₂ amplitude by 1-3 ppm throughout the Northern Hemisphere and up to 9 ppm in agricultural hotspots. While agricultural N fertilization is the largest contributor to the enhanced amplitude (45%) in Northern Hemisphere land-atmosphere carbon fluxes in CESM, higher CO₂ concentrations and warmer temperatures also contribute, though to a lesser extent (40% and 18% respectively). Our results emphasize the fundamental role of agricultural management in Northern Hemisphere carbon cycle feedbacks and illustrate that agricultural N fertilization should be considered in future carbon cycle simulations.

Multidrug ABC transporters harness the energy of ATP binding and hydrolysis to translocate substrates out of the cell and detoxify them. While this involves a well-accepted alternating access mechanism, molecular details of this interplay are still elusive. Rhodamine6G binding on a catalytic inactive mutant of the homodimeric multidrug ABC transporter BmrA triggers a cooperative binding of ATP on the two identical nucleotide-binding-sites, otherwise michaelian. Here, we investigate this asymmetric behavior via a structural-enzymology approach, solving cryoEM structures of BmrA at defined ATP ratios, highlighting the plasticity of BmrA as it undergoes the transition from inward to outward facing conformations. Analysis of continuous heterogeneity within cryoEM data and structural dynamics, reveals that Rhodamine6G narrows the conformational spectrum explored by the nucleotide-binding domains. We observe the same behavior for the other drug Hœchst33342. Following on these findings, the effect of drug-binding showed an ATPase stimulation and a maximal transport activity of the wild-type protein at the concentration-range where the cooperative transition occurs. Altogether, these findings provide a description of the influence of drug binding on the ATP-binding sites through a change in conformational dynamics.