Browse Articles

The origin of spontaneous oxidation in a floating oil nanofilm

Nanoscale geometries can profoundly alter chemical reactivity, yet platforms that isolate and control this regime remain limited primarily to microdroplets. Here, we introduce a simple, surfactant-free method to generate a floating oil nanofilm by trapping a gas bubble at the interface between immiscible aqueous and organic phases. This geometry produces a stable, suspended organic film approximately 100 nm thick with a surface-area-to-volume ratio of 10 7 m −1 , mimicking a droplet with a radius of 300 nm, bounded by closely spaced gas|liquid and liquid|liquid interfaces without a solid substrate. Using electrochemistry combined with finite-element modeling, we quantitatively characterize the nanofilm thickness and show that it enables spontaneous oxidation chemistry that is greatly accelerated compared to bulk systems. Decamethylferrocene undergoes pronounced oxidation within the nanofilm within seconds, in contrast to 10 s of hours required at bulk liquid|liquid interfaces. This behavior is absent under oxygen-free conditions and can be tuned by selective ion transfer across the interface, implicating charge compensation as an important factor in enhanced interfacial chemistry. By accelerating redox processes that are otherwise slow or inaccessible in bulk systems, the floating liquid nanofilm establishes a distinct regime of interfacial reactivity and provides a versatile platform for probing chemical transformations under nanoscale confinement.

Immune cell–intrinsic STING activation drives tumor ferroptosis via AA-mediated suppression of ACSL4 lactylation in colorectal cancer

Ferroptosis has emerged as a key effector mechanism in antitumor immunity, yet the transcellular metabolic cross talk that modulates ferroptotic sensitivity in colorectal cancer (CRC) remains incompletely understood. Here, we describe an integrative regulatory axis linking immune cell–intrinsic Stimulator of Interferon Genes (STING) signaling to tumor ferroptosis through coordinated lipid metabolism and posttranslational modifications (PTMs). Mechanistically, STING activation in immune cells triggers TANK-binding kinase 1 (TBK1)-dependent phosphorylation of cytosolic phospholipase A 2 (cPLA 2 ) at Ser505, thereby releasing arachidonic acid (AA) into the tumor microenvironment (TME). This immune-derived AA is taken up by adjacent CRC cells, where it promotes ACSL4-dependent ferroptosis by inhibiting EP300-mediated lactylation of ACSL4 at lysine 426 (K426). In vivo, pharmacological activation of STING enhances AA release and facilitates ferroptosis-mediated tumor suppression. Notably, STING agonist synergizes with PD-1 checkpoint blockade to inhibit tumor progression, which is reversed by the ferroptosis inhibitor. Collectively, our findings establish an integrative and transcellular immunometabolic framework linking innate immune sensing to tumor ferroptosis, providing a strong rationale for combinatorial therapeutic strategies in CRC.

Atlantic to Pacific: Outbreak of bivalve transmissible neoplasia detected in hybridizing soft-shell clams and eDNA in Puget Sound

Bivalve transmissible neoplasias (BTNs) are transmissible cancers that have arisen in multiple bivalve species, including Eastern soft-shell clam ( Mya arenaria ) populations on the East Coast of North America. Two sublineages of a single clone (termed MarBTN) currently circulate at low enzootic levels (1 to 5%) in New England, the United States, and Prince Edward Island, Canada, but MarBTN has not previously been observed in soft-shell clams on the West Coast. In 2022, we collected soft-shell clams in Puget Sound, Washington, and unexpectedly found MarBTN in two sites. Prevalence increased in subsequent years, surpassing 75% at both sites in 2024, while remaining undetectable in other populations, suggesting the early stages of a severe disease outbreak. Based on the presence of somatic transposon insertion sites found only in the USA-sublineage, the cancer was likely recently transplanted from New England. We also found that soft-shell clams in multiple Puget Sound locations are hybridizing populations of M. arenaria and Mya japonica . M. japonica may have decreased susceptibility to this cancer, though further sampling will be needed to confirm this hypothesis. We further developed a sensitive environmental DNA (eDNA) assay, targeting somatic mutations in the MarBTN mitogenome. Using this assay, we surveyed 51 sites throughout Puget Sound, detecting cancer at high levels at sites where MarBTN-positive clams were observed and in the surrounding area. These results identify a severe outbreak of transmissible cancer in a hybridizing population, due to transfer of disease from another ocean, and demonstrate the utility of eDNA methods to track BTN through the environment.

Detecting silent whales using seabed fiber-optic cables

Distributed acoustic sensing (DAS) has emerged as a powerful tool for passive whale monitoring, enabling both the detection of vocalizations and the simultaneous tracking of multiple individuals. However, a fundamental limitation of passive acoustic monitoring is that most methods rely on acoustic data, which is only available when whales vocalize. This clearly demonstrates the need for new sensing methods that can detect silent whales. In this paper, we detect hydrodynamic pressure and velocity fields in the low-frequency DAS data induced by a whale’s motion and develop methods to analyze these signals. First, we use ships as proxies to demonstrate and calibrate the proposed method. Then, we show that a simple fluid mechanical model can be adapted to understand how whale swimming can be detected and analyzed using DAS. We detect multiple silent whales simultaneously, estimate their characteristics, and show that whale motion signals decay as one over distance cubed. Moreover, we demonstrate that we can observe hydrodynamic pressure and velocity signals from a cruise ship at 413 m water depth, and up to 550 m from the fiber cable. In comparison, the smaller blue whales can be observed when diving within 40 m of the fiber-optical cable. This sensing method enables an approach to monitoring one of the world’s most endangered species.

Cultivation enhances warming sensitivity of redox-driven carbon pulses in black soils: The overlooked role of anaerobic legacy effects

Wetlands on the world’s most fertile black soil serve as critical yet vulnerable carbon reservoirs, yet their stability is threatened by redox fluctuations intensified by climate change and human activities. However, how cultivation modulates this process and its temperature sensitivity remains poorly understood. Here, we integrated field surveys of 10 black soils with mechanistic experiments on three contrasting soils along a cultivation gradient, including microbial inoculation, sterilization, radical quenching, and mineral chelation, to demonstrate that rice cultivation fundamentally reshaped the coupled biotic-abiotic process governing temperature sensitivity of carbon pulses under redox fluctuations. We found that rice cultivation enhanced iron-reducing capacity and shifted microbial metabolic pathways toward catabolism, establishing a persistent anaerobic legacy that amplified the warming sensitivity of aerobic carbon pulses. Mechanistically, ferrous mineral–catalyzed oxidation through both direct catalytic oxidation and • OH-mediated pathways dominated the aerobic pulse in cultivated soils (>44 to 61% of CO 2 yields). This pathway was dependent on anaerobic legacies, including activated mineral catalytic potential and accumulated dissolved organic carbon, and was further intensified by warming. Across 10 soils, paddies exhibited stronger ferrous mineral catalytic capacity for aerobic CO 2 pulses than natural wetlands, with warming further amplifying this divergence. These findings reveal a bio-abiotic coupling mechanism, where antecedent anaerobic microbial processes establish a functional legacy that governs subsequent abiotic mineral catalysis, that is currently underrepresented in ecosystem models.

A guardian role of TagA in protecting <i>Mycobacterium tuberculosis</i> from nitrosative killing

Upon activation, macrophages generate substantial levels of reactive nitrogen species, which can induce alkylating damage in the DNA of intracellular Mycobacterium tuberculosis ( Mtb ) and thereby restrict bacterial replication. However, the molecular mechanisms by which Mtb repairs such DNA lesions remain poorly understood. Here, we identified genes required for Mtb survival in distinct macrophage subsets using transposon insertion sequencing. Among these, tagA displayed a specialized role in Mtb survival in M1-polarized macrophages, as well as in mice at 4 wk postinfection, a stage when macrophages are biased toward an M1-polarized state. Mechanistically, TagA conferred resistance to the DNA alkylating agent methyl methanesulfonate through its 3-methyladenine (3-MA) excision activity with Glu48 serving as a key catalytic residue for substrate binding. Critically, TagA was found to protect the Mtb genome from alkylation damage caused by nitrosative stress—a hallmark of the M1-polarized macrophage microenvironment. Furthermore, pharmacological inhibition of inducible nitric oxide synthase (iNOS) with S-methylisothiourea sulfate in mice or genetic deletion of nos2a in zebrafish markedly rescued the survival defect of Δ tagA . Together, these findings reveal a previously unappreciated mechanism by which the DNA repair enzyme TagA protects Mtb against 3-MA DNA damage under nitrosative stress, thereby promoting bacterial survival in M1-polarized macrophages and during in vivo infection.

Counterselection against β-lactamase-expressing bacteria via an activatable photosensitizer that accumulates in resistant pathogens

The rapid global spread of antimicrobial resistance via β-lactamase (bla) demands targeted strategies that selectively eliminate resistant pathogens without exacerbating resistance. Herein, we report BIN-3I , a photosensitizer (PS) that enables bla-selective activation and—more importantly—covalent retention and accumulation within resistant bacteria, allowing potent photodynamic eradication of bla-expressing pathogens and exerting counter-selection pressure. BIN-3I adopts an enzyme-triggered "one-to-multi" design: Upon bla hydrolysis, it undergoes a hydrophilic-to-hydrophobic and low-to-high permeability transition, facilitating uptake and generating a reactive quinone methide intermediate that covalently binds intracellular proteins, leading to &gt;2,000-fold accumulation within resistant bacteria, thiol depletion and light-triggered reactive oxygen species generation. In vitro, BIN-3I demonstrated bla-specific activation, selective enrichment in bla-expressing MRSA, and potent photodynamic killing (&gt;99.999% reduction), outperforming the corresponding uncaged photosensitizer. Crucially, it selectively eradicates bla-producing MRSA within mixed populations, exerting counter-selection pressure against resistant strains. The PS also activates and accumulates in bla-expressing Gram-negative Enterobacter cloacae , albeit with reduced killing efficiency compared to Gram-positive bacteria. In vivo, it exhibited prolonged retention at infection sites and targeted imaging capability in murine myositis and abscess models. Notably, BIN-3I -mediated photodynamic therapy effectively cleared MRSA infections across multiple models—including thigh infection, wound, and biofilm-associated infections—achieving &gt;5-log reduction in bacterial load and surpassing vancomycin in efficacy. This work presents a targeted antimicrobial platform that exploits bacterial resistance mechanisms to achieve species-specific eradication, offering a promising strategy to combat multidrug-resistant infections and alleviate the selection pressure that drives the enrichment of resistant strains.

A broadly conserved gram-positive lipoprotein regulates cell elongation

The cell wall peptidoglycan (PG) protects virtually all bacteria from osmotic lysis and specifies cell shape. Synthesis of this exoskeleton is carried out by enzymes that polymerize glycan strands and transpeptidases that crosslink them into the existing cell wall matrix. In many bacteria, a broadly conserved cell wall synthesis complex known as the Rod complex or elongasome plays an essential role in cell growth. To investigate whether there are undiscovered Rod complex components, we combined high-throughput genetics with AlphaFold-Multimer screens. The two approaches converged on the lipoprotein ClcR (formerly, YerH or CamS). ClcR is broadly conserved among gram-positive bacteria and is predicted to interact with the Rod complex transpeptidases. We find that ClcR contributes to proper cell wall synthesis in Bacillus subtilis and Staphylococcus aureus and is essential for proper elongation and cell shape in Bacillus anthracis . We show that ClcR orthologs interact with their cognate transpeptidases and function as positive regulators of Rod complex activity in a distinct pathway from that of the known regulators MreCD. Altogether, our data define a broadly conserved component of the cell wall elongation machinery. As part of this study, we built a webtool to facilitate visualization and analysis of transposon-sequencing datasets. Our findings and accompanying resources provide a framework for uncovering biologically relevant protein–protein interactions that pairs genetic and in silico approaches.

Three centuries of technological innovation: Opportunity is the mother of invention

What socioecological conditions nurture the ingenuity and collaborative interactions underlying transformative technological innovations? We compiled a dataset on more than 400 major technological inventions from 1690 to 1990 spanning seven categories (agriculture, armaments, information and communication, household, industry, medical, and transportation) and performed inductive macroecological analyses to address how attributes of inventors, teams, and their social and geographic environments contributed to the innovation of new technologies that have changed the way people live. The vast majority of inventions were attributed to single inventors of various ages. The frequency, size, and cultural diversity of teams increased in the 20th Century, as did the proportion of inventions attributed to women and immigrants. A wide variety of environments acted as innovation hubs, including rural areas as well as specialized institutions and large cities. Invention rate (number of inventions per time period) peaked during the 1800s in cities, rural areas, and most categories but continued increasing over time in institutional environments and medical and communication technologies. The overall pattern across ages, genders, team attributes, environments, technological categories, and time periods supports the conclusion that opportunity, ingenuity, and environment all play key roles in the inventiveness phase of the innovation process: creative individuals in particular ecological environments and social settings come up with novel solutions to specific practical problems. Similar innovation patterns have been observed for tool use among nonhuman primates, highlighting unifying processes of innovation. Our macroecological approach offers valuable insights into the emergence and drivers of innovation and material culture.

Fasting primes small intestinal regeneration after damage via a microbiome–metabolite–chromatin axis

Fasting enhances small intestinal regeneration after radiation, but the contribution of the gut microbiome to this process remains uncharacterized. We identify Akkermansia muciniphila ( AKK ) as a key mediator of this response. AKK was enriched in fasted mice and its antibiotic depletion abrogated radioprotection, whereas reintroduction restored both organismal survival and intestinal integrity. Fasting elevated propionic acid, consistent with AKK ’s metabolic output. AKK -conditioned medium and propionate induced histone H3 acetylation in intestinal stem cell cultures while in vivo fasting induced AKK -dependent H3K27ac and H3K9ac, remodeling promoter–enhancer landscapes in crypt epithelial cells. Epigenetic profiling revealed a rewired core regulatory program enriched for pioneer transcription factors (Foxa, Gata, Klf), architectural organizers (Ctcf, Boris), and lineage-defining and metabolic regulators (Cdx2, Hnf4). This program supports expansion of a population of primed persister cells characterized by open chromatin accessibility at key stem and regenerative-associated loci including Clu , Olfm4 , Lgr5, Ascl2, Lrig1, Sox9, Rnf43, and Axin2. These findings define a fasting-induced microbiome–metabolite–chromatin axis that epigenetically primes highly plastic persister cells for rapid regeneration of the intestinal epithelium following radiation-induced injury.

Vaccination elicits HIV broadly neutralizing antibodies in primates

Protein-enhanced small molecule disruptors of ordered membrane domains

Membrane order and fluidity influence many biological processes. However, tools to manipulate membranes under physiological conditions have been limited. In the process of high-throughput screening for molecules that shift the phase partitioning between ordered and disordered membrane phases of the tetraspan membrane protein peripheral myelin protein 22 (PMP22), we identified two chemically similar compounds, VU0615562 and VU0619195, that shift PMP22 toward the disordered phase and destabilize the “lipid raft”-like ordered phase. Follow-up experiments showed that this latter activity is, counterintuitively, enhanced by the presence of PMP22, which normally stabilizes the ordered phase. Biophysical studies indicate that these compounds reduce raft stability through a mechanism that involves both direct interactions with proteins and the disruption of lipid packing. We further observed that acute treatment of live cells with VU0619195 modulated membrane fluidity and TRPM8 channel function while both compounds altered KCNQ1 channel activity, providing examples of practical applications for these compounds. These protein-enhanced raft modulators reveal distinct lipid and protein-based forces that destabilize membrane order and may be useful as pharmacological tools for manipulating and probing the biological roles of ordered membrane domains in cells.

Enhanced B cell priming induces broadly neutralizing HIV-1 apex antibodies

Modeling framework to demonstrate elimination of a vector population: Tsetse elimination in Chad

Every year, over 700,000 people, particularly children under five, die from vector-borne diseases worldwide. Effectively controlling endemics and preventing new outbreaks requires an integrated approach that can lead to the elimination of both vectors and diseases. In the last two decades, integrating medical interventions and vector control has significantly reduced the incidence of Gambian Human African Trypanosomiasis (g-HAT), with the World Health Organization validating eight countries as having eliminated the disease as a public health problem. However, elimination of the tsetse vector has not been confirmed, leaving the possibility of re-emergence. We developed a six-step modeling framework to assess vector elimination by calculating: i) the probability of vector capture; ii) the probability of observing a series of zero catches, even without actual elimination; iii) the probability of natural elimination; iv) the probability of failing to detect a rebound; v) the reinvasion risk; and vi) the sensitivity analysis. Our case study is g-HAT in Mandoul, Chad, and the elimination of Glossina fuscipes fuscipes. We used vector control from 2014 to 2025 with no tsetse detected since 2018. We cannot yet conclude, with over 90% confidence, that tsetse has been eliminated from Mandoul, nor that any remnant population will be naturally eliminated. However, since vector control stopped in April 2025, we estimate that with continued sampling over the next 2 y, and no tsetse detected, elimination could be demonstrated with 99% confidence. Our multistep modeling framework can be applied to other vectors, providing policymakers with guidelines for ongoing and future efforts.

Retraction Note: NSD2 targeting reverses plasticity and drug resistance in prostate cancer

Daring few, patient many: Division of labor in decentralized foraging collectives

How can social animals divide labor to forage effectively without a leader? Effective foraging requires balancing individual exploration costs against collective information gains, but without central coordination. This balance must emerge from the distributed decisions of group members. We address this challenge using a collective foraging model in which individuals share information and rewards but each must choose whether to bear the cost of exploring or to remain idle. We show that decentralized collectives can match the performance of centrally controlled groups through a division of labor with a small exploratory minority bearing the cost of foraging in lean times, continuously gathering information to enable a synchronized majority to exploit favorable conditions. This division of labor is inherently adaptive because fixed individual thresholds produce flexible collective behavior without central adjustment of roles. Information redundancy causes the optimal number of explorers to grow logarithmically with group size, so larger groups need proportionally fewer explorers. We find that the ideal level of group heterogeneity is maximized at intermediate ecological pressures, whereas optimal groups are homogeneous under extreme conditions. Collective responses to environmental changes are asymmetric and detecting improving conditions is slower than detecting deteriorating ones, as the exploratory minority needed to signal recovery is costly to maintain. We thus show how a division of labor based on simple individual threshold rules leads to optimal collective performance without central coordination, and predict when ecological pressures favor heterogeneous vs. uniform group composition.

Intracellular delivery of full-length antibodies via organ-targeted lipid nanoparticles

Antibodies are proteins prized for their ability to bind to extracellular antigens with exceptionally high affinities and specificities. These features have motivated researchers to utilize antibody–antigen binding to inhibit intracellular disease targets in the proteome, yet delivery of antibodies into the cytosol of cells has long been a considerable challenge. Here, we outline the development of a lipid nanoparticle (LNP) platform for delivering antibodies into cells to selectively inhibit disease-relevant cytosolic targets. This approach efficiently delivers various therapeutic antibodies into multiple cancer cell lines, inhibiting key transcription factors in inflammatory and cancer signaling pathways. We further demonstrate systemic delivery of therapeutic antibodies in disease models, including α-synuclein-specific antibodies for Parkinson’s disease and RelA-specific Immunoglobulins for acute lung injury using targeted LNP formulations. This work establishes a promising method for using LNPs for the delivery of antibody and antibody-derived therapeutics intracellularly to treat numerous proteome targets.

Natural variation of <i>CTS1</i> confers cold tolerance and blast resistance in rice

Improving multistress resilience in crops is essential for sustainable agriculture, yet the genetic mechanisms coordinating abiotic and biotic stress responses remain poorly understood. This study identifies CTS1 ( Cold Tolerance at the Seedling stage1 ), encoding the transcription factor OsWRKY74, as a key pleiotropic regulator that mediates both cold tolerance and blast resistance in rice. Through genome-wide association study, we found that CTS1 negatively regulates cold tolerance at the seedling stage. The natural allele CTS1 Hap1 confers greater cold tolerance than CTS1 Hap2 by mildly repressing the expression of CTB2 , thereby maintaining sterol glycoside homeostasis and membrane stability. Furthermore, during Magnaporthe oryzae infection, CTS1 activates the expression of OsHSP90 and upregulates pathogenesis-related genes, thereby enhancing blast resistance. Our findings reveal a dual-function mechanism of CTS1 in stress adaptation and provide valuable alleles for breeding multistress resilient rice varieties.

Early television set impresses Nature editors — but will it catch on?

Restriction–modification systems are required for <i>Neisseria gonorrhoeae</i> pilin antigenic variation

Neisseria gonorrhoeae (Gc) pilin antigenic variation is a diversity-generating system that uses gene conversion to produce numerous PilE protein variants, the major subunit of the Type IV pilus (T4p). Pilin antigenic variation allows the bacteria to escape immune surveillance by expressing a variant but functional pilus, and can also alter T4p expression. While pilin antigenic variation requires many conserved homologous recombination and DNA repair factors, the pattern of sequence changes leading to pilin antigenic variants resembles that of an annealing reaction, rather than the expected long recombination tracts usually found in homologous recombination. We demonstrate that two paralogous restriction–modification modules cleave specific, unmodified sequences within the expressed and silent pilin loci and that cleavage is an important process for pilin antigenic variation. Moreover, expression of these restriction activities in a subset of the bacterial population affects the fitness. These findings partially explain the patchwork recombination patterns of pilin antigenic variants and show a unique mechanism for generating diversity.