Nature Communications
<p><em>Nature Communications</em> is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical and Earth sciences. Papers published by the journal aim to represent important advances of significance to specialists within each field.</p> <p>We are committed to providing an efficient service for both authors and readers. Our team of independent editors make rapid and fair publication decisions. Prompt dissemination of accepted papers to a wide readership and beyond is achieved through a programme of continuous online publication. </p>
The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length. The authors show that telomere length resetting in embryos, a key determinant of healthy aging, is established by mitochondrial function at conception.
Wearable thermoelectric devices, capable of converting body heat into electrical energy, provide the potential driving power for the Internet of Things, artificial intelligence, and soft robotics. However, critical parameters have long been overlooked for these practical applications. Here, we report a three-dimensional flexible thermoelectric device with a structure featuring an inner rigid and outer flexible woven design. Such a structure includes numerous small static air pockets that create a stable out-of-plane temperature difference, enabling precise temperature signal detection (accuracy up to 0.02 K). Particularly, this structure exhibits excellent multi-signal decoupling capability, excellent elasticity (>10,000 compression cycles), ultra-fast compression response (20 ms), stable output signal under 50% compressive strain, high breathability (1300 mm s−1), and washability. All these metrics achieve the highest values currently reported, fully meeting the requirements for body heat and moisture exchange, as demonstrated in our designed integrated smart mask and smart glove systems based on vector machine learning technology. This work shows that our three-dimensional flexible thermoelectric device has broad applicability in wearable electronics. Wearable thermoelectric devices are promising, though fabricating a breathable, sensitive, and washable devices has been a challenge. This report shows a woven thermoelectric fabric, incorporating rigid and flexible layers, for smart wearable devices.
Astrocytes are closely linked to depression, and the prefrontal cortex (PFC) is an important brain region involved in major depressive disorder (MDD). However, the underlying mechanism by which astrocytes within PFC contribute to MDD remains unclear. Using single-nucleus RNA sequencing analyses, we show a significant reduction in astrocytes and attenuated pleiotrophin-protein tyrosine phosphatase receptor type Z1 (PTN-PTPRZ1) signaling in astrocyte-to-excitatory neuron communication in the PFC of male MDD patients. We find reduced astrocytes and PTN in the dorsomedial PFC of male mice with depression induced by chronic restraint and social defeat stress. Knockdown of astrocytic PTN induces depression-related responses, which is reversed by exogenous PTN supplementation or overexpression of astrocytic PTN. The antidepressant effects exerted by astrocytic PTN require interaction with PTPRZ1 in excitatory neurons, and PTN-PTPRZ1 activates the AKT signaling pathway to regulate depression-related responses. Our findings indicate the PTN-PTPRZ1-AKT pathway may be a potential therapeutic target for MDD. Astrocytes in the prefrontal cortex are closely linked to depression, but the underlying mechanisms remain unclear. Here, the authors show that reduction of astrocytic pleiotrophin in the dorsomedial prefrontal cortex contributes to depression-like phenotype in male mice.
Early life stress (ELS) can increase vulnerability to psychiatric disorders, but also trigger resilience. FKBP51 has been associated with an increased risk for developing psychiatric disorders, specifically in interaction with ELS exposure. Here, the contribution of FKBP51 in glutamatergic forebrain neurons to the long-term consequences of ELS was investigated in both sexes. In female wild-type Fkbp5lox/lox mice, ELS exposure led to an anxiolytic phenotype and improved memory performance in a stressful context, however this ELS effect was absent in Fkbp5Nex mice. These interactive FKBP51 x ELS effects in female mice were also reflected in reduced brain region volumes, and on structural and electrophysiological properties of CA1 pyramidal neurons of the dorsal hippocampus. In contrast, the behavioral, structural and functional effects in male ELS mice were less pronounced and independent of FKBP51. RNA sequencing of the hippocampus revealed the transcription factor 4 (TCF4) as a potential regulator of the female interactive effects. Cre-dependent viral overexpression of TCF4 in female Nex-Cre mice led to similar beneficial effects on behavior as the ELS exposure. This study demonstrates a sex-specific role for FKBP51 in mediating the adaptive effects of ELS on emotional regulation, cognition, and neuronal function, implicating TCF4 as a downstream effector. Early life stress can induce lasting changes in brain function and behavior. Here, authors show that glutamatergic FKBP51 specifically in females mediates adaptive stress effects on anxiety and cognition via TCF4.
Chiral organic-inorganic hybrid metal halides as promising circularly polarized luminescence (CPL) emitter candidates hold great potential for high-definition displays and future spin-optoelectronics. The recent challenge lies primarily in developing high-performance red CPL emitters. Here, coupling the f-f transition characteristics of trivalent europium ions (Eu3+) with chirality, we construct the chiral Eu-based halides, (R/S-3BrMBA)3EuCl6, which exhibit strong and predictable red emission with large photoluminescence quantum yield (59.8%), narrow bandwidth (≈2 nm), long lifetime (≈2 ms), together with large dissymmetry factor |glum| of 1.84 × 10−2. Compared with the previously reported chiral metal halides, these chiral Eu-based halides show the highest red CPL brightness. Furthermore, the degree of photoluminescence polarization in (R/S-3BrMBA)3EuCl6 can be manipulated by the external magnetic field. Particularly, benefiting from the field-generated Zeeman splitting and spin mixing at exciton states, an anomalously positive magneto-photoluminescence was observed at room temperature. This work provides an efficient strategy for constructing both high-performance and pure-red CPL emitters. It also opens the door for chiral rare-earth halides toward chiral optoelectronic and spintronic applications. Chiral organic-inorganic perovskites are promising materials for circularly polarized luminescence. Here the authors present chiral europium halides leading to red circularly polarized luminescence with large dissymmetry factor and strong magneto-chiroptical properties.
Anticipating and addressing resistance is essential for maximizing the potential of an oncology target and effectively addressing clinical needs. In this study, we aimed to proactively outline the resistance mechanisms of USP7 inhibitors. We discovered a key treatment-emergent heterozygous mutation (V517F) in USP7 in the binding pocket of compounds as the primary cause of resistance to the USP7 inhibitor USP7-797. Our structural analysis, supported by AlphaFold2 predictions, indicates that the V517F mutation altered the conformation of the compound binding pocket, causing steric hindrance and reducing the affinity between USP7 and its inhibitors. Consistent with these predictions, the affinity between V517F mutant and USP7 inhibitors was found to reduce significantly. Conversely, substitutions at position V517 with smaller side chains, such as V517G, V517A, and V517I, do not significantly impact binding affinity. In contrast, replacement with the bulkier side chain V517Y leads to reduced binding affinity and diminished inhibitor efficacy. Furthermore, the engineered cell lines harboring the V517F mutation exhibited substantial resistance to USP7 inhibition. These data provide rationales for patient selection and the development of next-generation USP7 inhibitors designed to overcome treatment-emergent mutations. Drug resistance is inevitable and pervasive. Here, the authors identify the V517F mutation as a significant contributor to USP7-mediated inhibitor resistance. This discovery offers valuable insights for the development of next-generation USP7 inhibitors.
Programmable metasurface holds big promise in wireless communications by virtue of its powerful capability in controlling electromagnetic waves. However, challenges exist for the programmable metasurface in achieving self-sufficient renewable energy supply and flexible and reliable multi-domain information transmissions. Here, we report a solar-powered light-modulated microwave programmable metasurface (SLMPM) by integrating a photovoltaic module to acquire information from modulated light and energy from sunlight simultaneously. Such an SLMPM enables direct, real-time, and reliable information transmissions from light to microwave domains under direct sunlight exposure, with the flexibility to implement various modulation schemes. Its low power consumption and on-board energy harvesting capability allows for 24 hours of light-to-microwave information transmission with 8 hours of sole sunlight energy input. A hybrid wireless communication system for real-time image transmission is demonstrated to show the outstanding features of SLMPM. We believe that SLMPM can contribute to the sustainable advancement of future wireless communications, rendering them more cost-effective, energy-efficient, environment-friendly, and ubiquitous. Achieving sustainability in wireless communications is crucial yet poses significant challenges. To address this, the authors propose and demonstrate a solar-powered programmable metasurface enabling hybrid light-to-microwave wireless communications.
China is facing a severe groundwater quality crisis amid economic development and climate change, yet the extent and trajectory of this crisis remain largely unknown. Here we developed a machine-learning model, incorporating natural and social-economic factors, to construct annual probabilistic maps of poor groundwater quality (PGQ, i.e., Class V based on the Chinese groundwater quality standard) across China from 1980 to 2100. Alarmingly, our findings indicate a concerning escalation in PGQ area ratio, rising from 17.3% in 1980 to 30.1% in 2000, and surging to 40.8% by 2020, adversely affecting 6.8%, 17.5%, and 36.0% of the Chinese population, respectively. The predominant drivers of this degradation were identified as agricultural discharge (contributing to 10.7% growth in PGQ area ratio), followed by groundwater exploitation (5.6%), industrial discharge (5.3%), domestic discharge (1.7%), climate change (0.5%), and land use change (-0.3%). By 2050, the PGQ area ratio could range from 37.9% to 48.3% under different socio-economic and climate scenarios. Our study highlights the urgent need for effective water resources management and conservation measures to mitigate the deteriorating trend of groundwater quality and address the challenges posed by socio-economic development and climate change, thereby safeguarding water security for China and the global community. This paper uses machine learning and extensive groundwater survey data to predict the evolution of groundwater quality across China. It integrates both natural and socio-economic factors.
Nature Communications - Author Correction: Segregation-dislocation self-organized structures ductilize a work-hardened medium entropy alloy
Nature Communications - Author Correction: Unveiling mechanisms and onset threshold of humping in high-speed laser welding
Nature Communications - Author Correction: Coherent coupling between vortex bound states and magnetic impurities in 2D layered superconductors
Nature Communications - Author Correction: The role of climate and population change in global flood exposure and vulnerability
Nature Communications - Addendum: Trade-off between critical metal requirement and transportation decarbonization in automotive electrification
Nature Communications - Author Correction: Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans
In contrast to allyl palladium complexes, propargylic/allenylic palladium species display complex reactivities that limit their implementation in polymer chemistry, especially for chain-growth polymerizations. Here we report an example of controlled chain-growth polymerization via propargyl/allenyl palladium intermediates. Vinylidenecyclopropane 1,1-dicarboxylate (VDCP), a unique allenylic electrophile, selectively reacts via the σ-allenyl palladium complex rather than the more common π-propargyl pathway, thereby unlocking a chain-growth process. Based on this concept, precise synthesis of alkyne-backbone polymers is realized, featuring fast rate, high molecular weight, narrow dispersity, high chemoselectivity, and excellent end-group fidelity. We demonstrate preparation of unsaturated macromolecules with advanced sequences and architectures using this method, including block, gradient, and graft copolymers. In contrast to allyl palladium complexes, propargylic/allenylic palladium species display complex reactivities that limit their implementation in polymer chemistry. Here, the authors report an example of controlled chain-growth polymerization via propargyl/allenyl palladium intermediates.
A ring contraction of easily available cyclic compounds to smaller cycles that are valuable but difficult to synthetically access is one of important skeletal editing strategies. Pyrrolidine synthesis via a ring contraction of pyridines, which are abundant, cheap, and readily available bulk chemicals in chemical industry, is highly promising to accelerate drug discovery and development research due to the great demand of pyrrolidine skeletons in medicinal molecules. Herein we report a photo-promoted ring contraction of pyridines with silylborane to afford pyrrolidine derivatives bearing a 2-azabicyclo[3.1.0]hex-3-ene skeleton. The reaction demonstrates broad substrate scope with high functional group compatibility, realizing facile access to 6-silyl-2-azabicyclo[3.1.0]hex-3-ene derivatives that work as powerful synthons for the synthesis of functionalized pyrrolidines and nitrogen-containing compounds. The reaction mechanism is clarified to proceed via 2-silyl-1,2-dihydropyridine and vinylazomethine ylide as intermediates, which are connected via photochemical or thermal silyl migration. Ring contraction of easily available cyclic compounds to smaller cycles that are valuable but difficult to synthetically access is an important skeletal editing strategy. Here, the authors report a photo-promoted ring contraction of pyridines with silylborane to afford pyrrolidine derivatives bearing a 2- azabicyclo[3.1.0]hex-3-ene skeleton.
Fully triggering the deep-seated potential of traditional nanomaterials, such as the classic spinel family, is of paramount importance in the field of materials science, which is yet believed to heavily depend on advanced conceptual designs and synthetic strategies. Herein, a type of inorganic–organic hybrid spinel oxide is designed using a π-conjugated azobenzene single-tooth coordination method to overcome their stubborn problems of moderate activity and phase instability in electrocatalytic reactions. Taking spinel Co3O4 nanocubes as a pre-catalyst, after subtle etching of the cube surfaces, some oxygen atoms in the tetrahedral Co–O coordination field are replaced and selectively linked to weakly polar azo-extended π-conjugated units (π*–N=N–π*) via electrophilic carboxyl groups. The π-conjugation structure in Co3O4 suppresses the covalency competition between the tetrahedral and octahedral Co–O coordination fields, successfully preventing the phase transition during the electrocatalytic process and improving the electrocatalytic activity and durability. This study not only expands the spinel family but also provides useful guidelines for developing advanced functional materials. Unlocking the potential of traditional nanomaterials like spinel oxides is crucial for improving the catalytic oxygen evolution reaction. Here, the authors report an inorganic–organic hybrid spinel oxide that enhances both catalytic activity and structural stability through a coordination method.
Nature Communications - Author Correction: Ultrafast signatures of merocyanine overcoming steric impedance in crystalline spiropyran
Nature Communications - Author Correction: Ballistic superconductivity in semiconductor nanowires
Increasing attention has been paid to silacyclobutanes because of their wide application in ring opening and ring extension reactions. However, the synthesis of functionalized silacyclobutanes remains an unmet challenge because of the limited functional group tolerance of the reactions with organometallic reagents and chlorosilacyclobutanes. Herein, we report a conceptually different solution to this end through a visible-light-induced metal-free hydrosilylation of unactivated alkenes with hydrosilacyclobutanes. A wide range of unactivated alkenes with diverse functional groups including the base-sensitive acid, alcohol and ketones participated in this reaction smoothly. In particular, the first hydrosilylation reaction of alkenes with dihydrosilacyclobutane provides a facile access to various functionalized alkyl monohydrosilacyclobutanes. Unsymmetrical dialkyl silacyclobutanes have also been synthesized through consecutive hydrosilylation with dihydrosilacyclobutane in one pot. The mechanism study reveals that the Lewis basic solvent could promote the generation of strained silyl radicals by direct light irradiation without a redox-active photocatalyst and the thiol catalyst plays an important role in accelerating the reaction. Silacyclobutanes have wide applications in ring opening and ring extension reactions, but functionalization remains challenging. Herein, the authors report visible-light-induced metal-free hydrosilylation of unactivated alkenes with hydrosilacyclobutanes.
Producing room temperature phosphorescent (RTP) materials from biomass resources using a solvent free method is essential but hard to achieve. Here, we discovered that lignin dissolved well in the liquid monomer, 2-hydroxyethyl acrylate (HEA), due to extensive hydrogen bonding and non-bonding interactions between lignin and HEA. Motivated by this discovery, we developed a solvent free system consisting of HEA and urethane dimethacrylate (UDMA) for converting lignin into RTP materials. With this design, lignin generated radicals upon UV irradiation, which initiated the polymerization of HEA (as monomer) and UDMA (as crosslinker). The as-obtained polymer network rigidifies lignin and activates the humidity/water-resistant RTP of lignin with a lifetime of 202.9 ms. Moreover, the afterglow color was successfully tuned to red after loading with RhB via energy transfer (TS-FRET). Using these properties, the as-developed material was used as photocured multiple-emission RTP inks, luminescent coatings and a smart anti-counterfeiting logo for a medicine bottle. Preparing room temperature phosphorescent materials from biomass is important but challenging. Here, the authors report the use of liquid monomer 2-hydroxyethyl acrylate for dissolution of lignin and subsequent solvent-free preparation of lignin-based RTP materials.
The modern view of industrial heterogeneous catalysis is evolving from the traditional static paradigm where the catalyst merely provides active sites, to that of a functional material in which dynamics plays a crucial role. Using machine learning-driven molecular dynamics simulations, we confirm this picture for the ammonia synthesis catalysed by BaH2. Recent experiments show that this system acts as a highly efficient catalyst, but only when exposed first to N2 and then to H2 in a chemical looping process. Our simulations reveal that when first exposed to N2, BaH2 undergoes a profound change, transforming into a superionic mixed compound, BaH2−2x(NH)x, characterized by a high mobility of both hydrides and imides. This transformation is not limited to the surface but involves the entire catalyst. When this compound is exposed to H2 in the second step of the looping process, ammonia is readily formed and released, a process greatly facilitated by the high ionic mobility. Once all the nitrogen hydrides are hydrogenated, the system reverts to its initial state, ready for the next looping cycle. Our microscopic analysis underlines the dynamic nature of this heterogeneous catalyst, which does not merely serve as static platform for reactions, rather it is a dynamic entity that evolves under reaction conditions. The traditional view of industrial heterogeneous catalysis is shifting from a static to a dynamic paradigm. Here, the authors show that BaH2 does not merely serve as static platform for reactions during ammonia synthesis, but rather it is a dynamic entity that evolves under reaction conditions.
Ground-state charge transfer plays a vital role in improving the photocatalytic performance of D-A type covalent organic frameworks. However, limited studies have explored the modulation of photocatalytic performance in COFs-based photocatalysts through ground-state charge transfer. Here we show the formation of extremely intense ground-state charge transfer via a unique covalent bonding approach. We transform three-dimensional stacked COF-based S-scheme heterojunctions (FOOCOF-PDIU) into co-planar single-molecule junctions (FOOCOF-PDI). This co-planar single-molecule junction structure exhibits strong ground-state charge transfer compared to the traditional randomly stacked heterojunctions and individual COFs. Ground-state charge transfer induces charge redistribution and dipole moment formation, which enhances the built-in electric field intensity in single-molecule junctions. This enhanced built-in electric field promotes exciton dissociation and charge separation, resulting in improved photocatalytic efficiency. Therefore, a stable molecule-decorated COF with broad light absorption has been successfully obtained, whose hydrogen evolution rate can reach 265 mmol g−1 h−1. This work opens an avenue for exploiting photocatalytic mechanisms in COFs based on ground-state charge transfer effects. Ground state charge transfer is important for improving the photocatalytic performance of donor-acceptor type covalent organic frameworks (COFs), but it has been underexplored. Here, the authors report a COF with enhanced charge transfer, achieving a hydrogen evolution rate of 265 mmol g−1 h−1.
Ionic actuators with capability of electro-mechanical transduction are emerging as a useful platform for artificial intelligence and modern medical instruments. However, the insufficient ion transport inside material interfaces usually leads to limited energy transduction efficiency and energy density of actuators. Here, we report a polyrotaxane interface with adjustable ion transport based on sliding-ring effect for highly-efficient ionic actuators. The switch status of ion channels is synchronous with actuation strains, and energy barrier of interfacial ion transfer is reduced. As a result, the electro-mechanical transduction efficiency of actuators gets significantly improved. The as-delivered energy density of devices is stronger than that of mammalian skeletal muscle. Based on the high actuation performances, we demonstrate a fiber-shape soft actuator that can be directly injected into biological tissue just using syringe. The injectable actuator is promising for surgical navigation and physiological monitoring. Traditional capacitive mechanism for ionic actuators suffers from low energy transduction efficiency. Here, the authors report a sliding ring actuation mechanism for ionic actuators with high energy transduction efficiency and large energy density.
We experience countless pieces of new information each day, but remembering them later depends on firmly instilling memory storage in the brain. Numerous studies have implicated non-rapid eye movement (NREM) sleep in consolidating memories via interactions between hippocampus and cortex. However, the temporal dynamics of this hippocampal-cortical communication and the concomitant neural oscillations during memory reactivations remains unclear. To address this issue, the present study used the procedure of targeted memory reactivation (TMR) following learning of object-location associations to selectively reactivate memories during human NREM sleep. Cortical pattern reactivation and hippocampal-cortical coupling were measured with intracranial EEG recordings in patients with epilepsy. We found that TMR produced variable amounts of memory enhancement across a set of object-location associations. Successful TMR increased hippocampal ripples and cortical spindles, apparent during two discrete sweeps of reactivation. The first reactivation sweep was accompanied by increased hippocampal-cortical communication and hippocampal ripple events coupled to local cortical activity (cortical ripples and high-frequency broadband activity). In contrast, hippocampal-cortical coupling decreased during the second sweep, while increased cortical spindle activity indicated continued cortical processing to achieve long-term storage. Taken together, our findings show how dynamic patterns of item-level reactivation and hippocampal-cortical communication support memory enhancement during NREM sleep. Here, the authors demonstrate how targeted memory reactivation during NREM sleep enhances memory consolidation through repeated reactivations, characterized by increased hippocampal ripples, cortical spindles, and dynamic hippocampal-cortical interactions.
An increasing number of real-world interventions aim to preemptively protect or inoculate people against misinformation. Inoculation research has demonstrated positive effects on misinformation resilience when measured immediately after treatment via messages, games, or videos. However, very little is currently known about their long-term effectiveness and the mechanisms by which such treatment effects decay over time. We start by proposing three possible models on the mechanisms driving resistance to misinformation. We then report five pre-registered longitudinal experiments (Ntotal = 11,759) that investigate the effectiveness of psychological inoculation interventions over time as well as their underlying mechanisms. We find that text-based and video-based inoculation interventions can remain effective for one month—whereas game-based interventions appear to decay more rapidly—and that memory-enhancing booster interventions can enhance the diminishing effects of counter-misinformation interventions. Finally, we propose an integrated memory-motivation model, concluding that misinformation researchers would benefit from integrating knowledge from the cognitive science of memory to design better psychological interventions that can counter misinformation durably over time and at-scale. Interventions to increase resilience to misinformation work but decay over time. Here, the authors show that memory—which can be strengthened—is a key predictor for the longevity of intervention effects, more so than motivation.
Molecular design using data-driven generative models has emerged as a promising technology, impacting various fields such as drug discovery and the development of functional materials. However, this approach is often susceptible to optimization failure due to reward hacking, where prediction models fail to extrapolate, i.e., fail to accurately predict properties for designed molecules that considerably deviate from the training data. While methods for estimating prediction reliability, such as the applicability domain (AD), have been used for mitigating reward hacking, multi-objective optimization makes it challenging. The difficulty arises from the need to determine in advance whether the multiple ADs with some reliability levels overlap in chemical space, and to appropriately adjust the reliability levels for each property prediction. Herein, we propose a reliable design framework to perform multi-objective optimization using generative models while preventing reward hacking. To demonstrate the effectiveness of the proposed framework, we designed candidates for anticancer drugs as a typical example of multi-objective optimization. We successfully designed molecules with high predicted values and reliabilities, including an approved drug. In addition, the reliability levels can be automatically adjusted according to the property prioritization specified by the user without any detailed settings. Molecular design using data-driven generative models faces the problem of reward hacking in multiobjective settings. Here, authors propose a framework to automatically adjust reliability levels for each objective to design promising molecules.
Lanthanide-based luminescent materials have shown great capabilities in addressing scientific problems encountered in diverse fields. However, achieving full-color switchable output under single-wavelength irradiation has remained a daunting challenge. Here we report a conceptual model to realize this aim by the temporal control of full upconversion evolution in a multi-layer core-shell nanostructure upon a single commercial 980-nm laser, instead of two or more excitation wavelengths as reported previously. We show that it is able to realize the red-to-green color change (from Er3+) under non-steady state excitation by constructing the cooperative modulation effect in the Er-Tm-Yb triple system, and single out the blue light (from Tm3+) by filtering out the short-decay emissions via a time-gating technique. The key role of Tm3+ in manipulating up-transition dynamics of Er3+ is further demonstrated. Our results present a deep insight into the photophysics of lanthanides, and help develop new generation of smart luminescent materials toward emerging photonic applications. Multi-color emission in upconversion nanoparticles usually requires multiple wavelengths to excite different lanthanide ions. Here the authors show color tuning from a single excitation wavelength through modulating energy transfer and time gating.
Glycine transporter 1 (GlyT1) is a key player in shaping extracellular glutamatergic signaling processes and holds promise for treating cognitive impairments associated with schizophrenia by inhibiting its activity and thus enhancing the function of NMDA receptors. Despite its significant role in physiological and pharmacology, its modulation mechanism by clinical drugs and internal lipids remains elusive. Here, we determine cryo-EM structures of GlyT1 in its apo state and in complex with clinical trial drugs iclepertin and sarcosine. The GlyT1 in its apo state is determined in three distinct conformations, exhibiting a conformational equilibrium of the transport cycle. The complex structures with inhibitor iclepertin and sarcosine elucidate their unique binding poses with GlyT1. Three binding sites of cholesterol are determined in GlyT1, two of which are conformation-dependent. Transport kinetics studies reveal that a delicate binding equilibrium for cholesterol is crucial for the conformational transition of GlyT1. This study significantly enhances our understanding of the physiological and pharmacological aspects of GlyT1. GlyT1 critically regulates excitatory neurotransmission and has thus emerged as a therapeutic target for schizophrenia. This study delineates the binding sites of the clinically trialed drugs iclepertin and sarcosine and elucidates how cholesterol modulates GlyT1 activity.
Optical-based terahertz sources are important for many burgeoning scientific and technological applications. Among such applications is precision spectroscopy of molecules, which exhibit rotational transitions at terahertz frequencies. Stemming from precision spectroscopy is frequency discrimination (a core technology in atomic clocks) and stabilization of terahertz sources. Because many molecular species exist in the gas phase at room temperature, their transitions are prime candidates for practical terahertz frequency references. We demonstrate the stabilization of a low phase-noise, dual-wavelength Brillouin laser (DWBL) terahertz oscillator to a rotational transition of carbonyl sulfide (OCS). We achieve an instability of $$1.2\times 1{0}^{-12}/\sqrt{\tau }$$ , where τ is the averaging time in seconds. The signal-to-noise ratio and intermodulation limitations of the experiment are also discussed. We thus demonstrate a highly stable and spectrally pure terahertz frequency source. Our presented architecture will likely benefit metrology, spectroscopy, precision terahertz studies, and beyond. This author’s experiment demonstrated a stabilized low phase-noise optical terahertz source (dual-wavelength Brillouin laser) to the quantum rotational transition of a molecule (OCS) and achieved a fractional frequency instability of 5 × 10−12 after 100ms of averaging.
The heterogeneity of major depressive disorder (MDD) has hindered clinical translation and neuromarker identification. Biotyping facilitates solving the problems of heterogeneity, by dissecting MDD patients into discrete subgroups. However, interindividual variations suggest that depression may be conceptualized as a “continuum,” rather than as a “category.” We use a Bayesian model to decompose structural MRI features of MDD patients from a multisite cross-sectional cohort into three latent disease factors (spatial pattern) and continuum factor compositions (individual expression). The disease factors are associated with distinct neurotransmitter receptors/transporters obtained from open PET sources. Increases cortical thickness in sensory and decreases in orbitofrontal cortices (Factor 1) associate with norepinephrine and 5-HT2A density, decreases in the cingulo-opercular network and subcortex (Factor 2) associate with norepinephrine and 5-HTT density, and increases in social and affective brain systems (Factor 3) relate to 5-HTT density. Disease factor patterns can also be used to predict depressive symptom improvement in patients from the longitudinal cohort. Moreover, individual factor expressions in MDD are stable over time in a longitudinal cohort, with differentially expressed disease controls from a transdiagnostic cohort. Collectively, our data-driven disease factors reveal that patients with MDD organize along continuous dimensions that affect distinct sets of regions. Li et al. identify three latent patterns of brain abnormalities in MDD using an unsupervised machine learning technique, and quantify their expression level for each patient.
Biomolecular condensates formed by proteins and nucleic acids are critical for cellular processes. Macromolecule-based coacervate droplets formed by liquid-liquid phase separation serve as synthetic analogues, but are limited by complex compositions and high molecular weights. Recently, short peptides have emerged as an alternative component of coacervates, but tend to form metastable microdroplets that evolve into rigid nanostructures. Here we present programmable coacervates using binary mixtures of diphenylalanine-based short peptides. We show that the presence of different short peptides stabilizes the coacervate phase and prevents the formation of rigid structures, allowing peptide coacervates to be used as stable adaptive compartments. This approach allows fine control of droplet formation and dynamic morphological changes in response to physiological triggers. As compartments, short peptide coacervates sequester hydrophobic molecules and enhance bio-orthogonal catalysis. In addition, the incorporation of coacervates into model synthetic cells enables the design of Boolean logic gates. Our findings highlight the potential of short peptide coacervates for creating adaptive biomimetic systems and provide insight into the principles of phase separation in biomolecular condensates. Study of coacervates can give insights into biomolecular condensates, but peptide-based systems generally form microdroplets which evolve into rigid nanostructures. Here, the authors report programmable coacervates from binary mixtures of diphenylalanine-based short peptides.
Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding oligomerization domain (NOD)-like receptors widely distributed in immune systems across animals and plants. EfAvs5, a type 5 Avs from Escherichia fergusonii, contains an N-terminal SIR2 effector domain, a NOD, and a C-terminal sensor domain, conferring protection against diverse phage invasions. Despite the established roles of SIR2 and STAND in prokaryotic and eukaryotic immunity, the mechanism underlying their collaboration remains unclear. Here we present cryo-EM structures of EfAvs5 filaments, elucidating the mechanisms of dimerization, filamentation, filament bundling, ATP binding, and NAD+ hydrolysis, all of which are crucial for anti-phage defense. The SIR2 and NOD domains engage in intra- and inter-dimer interaction to form an individual filament, while the outward C-terminal sensor domains contribute to bundle formation. Filamentation potentially stabilizes the dimeric SIR2 configuration, thereby activating the NADase activity of EfAvs5. Furthermore, we identify the nucleotide kinase gp1.7 of phage T7 as an activator of EfAvs5, demonstrating its ability to induce filamentation and NADase activity. Together, we uncover the filament assembly of Avs5 as a unique mechanism to switch enzyme activities and perform anti-phage defenses. Bacterial antiviral STANDs (Avs) protect against phage invasions. Here, the authors reveal that EfAvs5 forms clustered filaments for NAD+ hydrolysis and can be activated by phage gp1.7 protein, elucidating its antiviral mechanism.
Structural variations (SVs) are diverse forms of genetic alterations and drive a wide range of human diseases. Accurately genotyping SVs, particularly occurring at repetitive genomic regions, from short-read sequencing data remains challenging. Here, we introduce SVLearn, a machine-learning approach for genotyping bi-allelic SVs. It exploits a dual-reference strategy to engineer a curated set of genomic, alignment, and genotyping features based on a reference genome in concert with an allele-based alternative genome. Using 38,613 human-derived SVs, we show that SVLearn significantly outperforms four state-of-the-art tools, with precision improvements of up to 15.61% for insertions and 13.75% for deletions in repetitive regions. On two additional sets of 121,435 cattle SVs and 113,042 sheep SVs, SVLearn demonstrates a strong generalizability to cross-species genotype SVs with a weighted genotype concordance score of up to 90%. Notably, SVLearn enables accurate genotyping of SVs at low sequencing coverage, which is comparable to the accuracy at 30× coverage. Our studies suggest that SVLearn can accelerate the understanding of associations between the genome-scale, high-quality genotyped SVs and diseases across multiple species. Accurately genotyping structural variations (SVs) from short-read sequencing data is challenging. Here, the authors introduce SVLearn for precise genotyping of bi-allelic SVs, demonstrating robust cross-species generalizability across multiple coverage levels.
Thermokarst lakes, serving as significant sources of methane (CH4), play a crucial role in affecting the feedback of permafrost carbon cycle to global warming. However, accurately assessing CH4 emissions from these lakes remains challenging due to limited observations during lake ice melting periods. In this study, by integrating field surveys with machine learning modeling, we offer a comprehensive assessment of present and future CH4 emissions from thermokarst lakes on the Tibetan Plateau. Our results reveal that the previously underestimated CH4 release from lake ice bubble and water storage during ice melting periods is 11.2 ± 1.6 Gg C of CH4, accounting for 17 ± 4% of the annual total release from lakes. Despite thermokarst lakes cover only 0.2% of the permafrost area, they annually emit 65.5 ± 10.0 Gg C of CH4, which offsets 6.4% of the net carbon sink in alpine grasslands on the plateau. Considering the loss of lake ice, the expansion of thermokarst lakes is projected to lead to 1.1–1.2 folds increase in CH4 emissions by 2100. Our study allows foreseeing future CH4 emissions from the rapid expanding thermokarst lakes and sheds new lights on processes controlling the carbon-climate feedback in alpine permafrost ecosystems. Methane emissions from thermokarst lakes on the Tibetan Plateau have likely been underestimated, according to the integration of field surveys with machine learning
Managing junctional hemorrhage is challenging due to ineffective existing techniques, with the groin being the most common site, accounting for approximately 19.2% of potentially survivable field deaths. Here, we report a bicomponent nano- and microfiber aerogel (NMA) for injection into deep, narrow junctional wounds to effectively halt bleeding. The aerogel comprises intertwined poly(lactic acid) nanofibers and poly(ε-caprolactone) microfibers, with mechanical properties tunable through crosslinking. Optimized aerogels demonstrate improved resilience, toughness, and elasticity, enabling rapid re-expansion upon blood contact. They demonstrate superior blood absorption and clotting efficacy compared to commercial products (i.e., QuikClot® Combat Gauze and XStat®). Most importantly, in a lethal swine junctional wound model (Yorkshire swine, both male and female, n = 5), aerogel treatment achieved immediate hemostasis, a 100% survival rate, no rebleeding, hemodynamic stability, and stable coagulation, hematologic, and arterial blood gas testing. Deep wounds with severe bleeding are a prominent cause of preventable deaths. Here, Shahriar et al. report a bicomponent nano- and microfiber aerogel that effectively halts bleeding in deep junctional wounds, outperforming FDA-approved hemostatic materials in a lethal swine model.
The microenvironment regulation of Fe-N4 single atom catalysts (SACs) critically governs peroxymonosulfate (PMS) activation. Although conventional heteroatom substitution in primary coordination enhances activity, it disrupts Fe-N4 symmetry and compromises stability. Herein, we propose oxygen doping in the secondary coordination shell to construct Fe-N4-C6O2 SAC, which amplifies the localized electric field while preserving the pristine coordination symmetry, thus trading off its activity and stability. This approach suppresses Fe-N bond structural deformation (bond amplitude reduced from 0.875–3.175 Å to 0.925–2.975 Å) during PMS activation by lowering Fe center electron density to strengthen Fe-N bond, achieving extended catalytic durability (>240 h). Simultaneously, the weakened coordination field lowers the Fe=O σ* orbital energy, promoting electrophilic σ-attack of high-valent iron-oxo towards bisphenol A, and increasing its degradation rate by 41.6-fold. This work demonstrates secondary coordination engineering as a viable strategy to resolve the activity-stability trade-off in SAC design, offering promising perspectives for developing environmental catalysts. Heteroatom substitution in SAC’s first coordination boosts activity but weakens stability, limiting its practical application. Here, authors show that doping O in secondary shell enhances catalytic durability (>240 h) and FeIV = O activity (41.6-fold), resolving the activity-stability trade-off.
Nature Communications - Author Correction: Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline
Nature Communications - Author Correction: Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications
Nature Communications - Publisher Correction: Muscle abnormalities in Long COVID
We see unprecedented weather causing widespread impacts across the world. In this perspective, we provide an overview of methods that help anticipate unprecedented weather hazards that can contribute to stop being surprised. We then discuss disaster management and climate adaptation practices, their gaps, and how the methods to anticipate unprecedented weather may help build resilience. We stimulate thinking about transformative adaptation as a foundation for long-term resilience to unprecedented weather, supported by incremental adaptation through upgrading existing infrastructure, and reactive adaptation through short-term early action and disaster response. Because in the end, we should take responsibility to build resilience rather than being surprised by unprecedented weather. Unprecedented weather events are increasingly impacting societies worldwide. This Perspective explores methods to anticipate such hazards, and it highlights the role of transformative, incremental, and reactive adaptation strategies to achieve enhanced resilience.
An exciton–polariton condensate is a state of matter with collective coherence leading to many fascinating macroscopic quantum effects. Recently, optical bound states in the continuum (BICs) have been demonstrated as peculiar topological states capable of imparting novel characteristics onto the polariton condensates. Organic semiconductors featuring robust Frenkel excitons and high physicochemical tunability potentially offer a promising platform to explore topologically engineering of BIC polariton condensates at room temperature. However, a universal physical mechanism for engineering organic BIC systems has remained elusive, hindering the demonstration of BIC polariton condensates with topologically tunable macroscopic quantum effects. Here we report topologically reconfigurable room-temperature polariton condensates by systematically engineering the BICs in organic semiconductor metasurfaces. Two-dimensional organic metasurfaces are designed to support two polariton BICs with different topological charges. The organic Frenkel excitons with large binding energies allow for non-equilibrium polariton condensation at BICs at room-temperature. By virtue of the excellent physicochemical tunability of organic materials, we further explore the dynamic topological engineering of polariton lasers by manipulating the BICs in situ. Our results fundamentally promote the innovative design and topological engineering of polaritonic materials and devices. Here the authors demonstrate topologically reconfigurable room-temperature polariton condensates by systematically engineering the BICs in organic semiconductor metasurfaces achieving dynamic engineering of polariton lasing
Baleen whales migrate from productive high-latitude feeding grounds to usually oligotrophic tropical and subtropical reproductive winter grounds, translocating limiting nutrients across ecosystem boundaries in their bodies. Here, we estimate the latitudinal movement of nutrients through carcasses, placentas, and urea for four species of baleen whales that exhibit clear annual migration, relying on spatial data from publicly available databases, present and past populations, and measurements of protein catabolism and other sources of nitrogen from baleen whales and other marine mammals. Migrating gray, humpback, and North Atlantic and southern right whales convey an estimated 3784 tons N yr−1 and 46,512 tons of biomass yr−1 to winter grounds, a flux also known as the “great whale conveyor belt”; these numbers might have been three times higher before commercial whaling. We discuss how species recovery might help restore nutrient movement by whales in global oceans and increase the resilience and adaptative capacity of recipient ecosystems. Baleen whales migrate from high latitude feeding grounds to subtropical reproductive winter grounds, translocating limiting nutrients across ecosystems. This study estimates the latitudinal movement of nutrients from carcasses, placentas and urea for four species of baleen whales that exhibit annual migrations.
Computational pathology, utilizing whole slide images (WSIs) for pathological diagnosis, has advanced the development of intelligent healthcare. However, the scarcity of annotated data and histological differences hinder the general application of existing methods. Extensive histopathological data and the robustness of self-supervised models in small-scale data demonstrate promising prospects for developing foundation pathology models. Here we show BEPH (BEiT-based model Pre-training on Histopathological image), a foundation model that leverages self-supervised learning to learn meaningful representations from 11 million unlabeled histopathological images. These representations are then efficiently adapted to various tasks, including patch-level cancer diagnosis, WSI-level cancer classification, and survival prediction for multiple cancer subtypes. By leveraging the masked image modeling (MIM) pre-training approach, BEPH offers an efficient solution to enhance model performance, reduce the reliance on expert annotations, and facilitate the broader application of artificial intelligence in clinical settings. The pre-trained model is available at https://github.com/Zhcyoung/BEPH . Yang et al. developed a new method, BEPH, a foundation model trained on TCGA WSI images. BEPH improves cancer recognition, classification, and survival prediction across subtypes, potentially reducing reliance on expert annotations.
The synergistic Cu0-Cu+ sites is regarded as the active species towards NH3 synthesis from the nitrate electrochemical reduction reaction (NO3-RR) process. However, the mechanistic understanding and the roles of Cu0 and Cu+ remain exclusive. The big obstacle is that it is challenging to effectively regulate the interfacial motifs of Cu0-Cu+ sites. In this paper, we describe the tunable construction of Cu0-Cu+ interfacial structure by modulating the size-effect of Cu2O nanocube electrocatalysts to NO3-RR performance. We elucidate the formation mechanism of Cu0-Cu+ motifs by correlating the macroscopic particle size with the microscopic coordinated structure properties, and identify the synergistic effect of Cu0-Cu+ motifs on NO3-RR. Based on the rational design of Cu0-Cu+ interfacial electrocatalyst, we develop an efficient paired-electrolysis system to simultaneously achieve the efficient production of NH3 and 2,5-furandicarboxylic acid at an industrially relevant current densities (2 A cm−2), while maintaining high Faradaic efficiencies, high yield rates, and long-term operational stability in a 100 cm2 electrolyzers, indicating promising practical applications. It is challenging to regulate the interfacial motifs of Cu0-Cu+ sites to understand roles of Cu0 and Cu+ for nitrate electrochemical reduction reaction. Here, the authors report a tunable construction of Cu0-Cu+ interfacial structure by modulating the size-effect of Cu2O electrocatalysts.
Harnessing the power of immune system to treat cancer has become a core clinical approach. However, rewiring of intrinsic circuitry by genomic alterations enables tumor cells to escape immune surveillance, leading to therapeutic failure. Uncovering the molecular basis of how tumor mutations induce therapeutic resistance may guide the development of intervention approaches to advance precision immunotherapy. Here we report the identification of the Liver Kinase B1 (LKB1)-Inhibitor of Apoptosis Protein (IAP)- Janus Kinase 1 (JAK1) dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells. LKB1 alteration exposes a critical dependency of lung cancer cells on IAP for their immune resistance. Indeed, pharmacological inhibition of IAP re-establishes JAK1-regulated Stimulator of interferon genes (STING) expression and DNA sensing signaling, enhances cytotoxic immune cell infiltration, and augmentes immune-dependent anti-tumor activity in an LKB1-mutant immune-competent mouse model. Thus, IAP-JAK1-targeted strategies, like IAP inhibitors, may offer a promising therapeutic approach to restore the responsiveness of immunologically-cold LKB1-mutant tumors to immune checkpoint inhibitors or STING-directed therapies. LKB1-mut has been shown as a major genetic driver of primary resistance to immune checkpoint inhibitors. Here this group reports the identification of the LKB1-IAP-JAK dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells.
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