Maternal education was strongly correlated with adolescent brain morphology, cognitive performances, and mental health. However, the molecular basis for the effects of maternal education on the structural neurodevelopment remains unknown. Here, we conducted gene-environment-wide interaction study using the Adolescent Brain Cognitive Development cohort. Seven genomic loci with significant gene-environment

The role of tumor microenvironment (TME)–associated inadequate protein modification and trafficking due to insufficiency in Golgi function, leading to Golgi stress, in the regulation of T cell function is largely unknown. Here, we show that disruption of Golgi architecture under TME stress, identified by the decreased expression of GM130, was reverted upon treatment with hydrogen sulfide (H 2 S) donor

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of molecular features. These approaches distill cancer histologic images into high-level features, which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom

Glucose has long been considered the primary fuel source for the brain. However, glucose levels fluctuate in the brain during sleep or circuit activity, posing major metabolic stress. Here, we demonstrate that the mammalian brain uses pyruvate as a fuel source, and pyruvate can support neuronal viability in the absence of glucose. Nerve terminals are sites of metabolic vulnerability, and we show that

Controlling electron density in two-dimensional semiconductors is crucial for both comprehensive understanding of fundamental material properties and their technological applications. However, conventional electrostatic doping methods exhibit limitations, particularly in addressing electric field–induced drift and subsequent diffusion of electrons, which restrict nanoscale doping. Here, we present

Elementary reaction mechanisms constitute a fundamental infrastructure for chemical processes as a whole. However, while these mechanisms are well understood for second-period elements, involving those of the third period and beyond can introduce unorthodox reactivity. Combining crossed molecular beam experiments with electronic structure calculations and molecular dynamics simulations, we provide

The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness

B cell adapter for PI 3-kinase (BCAP) is an adaptor molecule associated with signaling through multiple immune receptors, including the B cell receptor (BCR). However, B cell–intrinsic role of BCAP in antibody responses is unclear. We investigated the role of BCAP in B cell response to viral particles and found a previously unidentified mechanism by which BCAP regulates antigen-specific responses.

Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had an antitumoral effect in SM1 melanoma and CT26 colon cancer models and increased the efficacy of anti–programmed cell death protein 1 treatment, leading to complete remission in melanoma and increased

Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes

Morphogen gradients instruct cells to pattern tissues. Although the mechanisms by which morphogens transduce chemical signals have been extensively studied, the roles and regulation of the physical communication between morphogen-receiver cells remain unclear. Here, we show that the Wnt/β-catenin–morphogen gradient, which patterns the embryonic anterior-posterior (AP) axis, generates intercellular

Microbial communities are shaped by cell-cell interactions. Although archaea are often found in associations with other microorganisms, the mechanisms structuring these communities are poorly understood. Here, we report on the structure and function of haloarchaeal contractile injection systems (CISs). Using a combination of functional assays and time-lapse imaging, we show that Halogeometricum borinquense

N 6 -methyladenosine (m 6 A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m 6 A modification and SG stability remains unclear. Here, we presented a spatiotemporal m 6 A imaging system (SMIS) that can monitor the m 6 A modification and the translation of mRNAs with high specificity and sensitivity in

Morphological features of organismal body plans are often highly conserved within large taxa. For example, segmentation is a shared and defining feature of all insects. Screens in Drosophila identified genes responsible for the development of body segments, including the “pair-rule” genes (PRGs), which subdivide embryos into double-segment units in a previously unexpected pre-patterning step. Here

Geological storage and mineralization of CO 2 in mafic/ultramafic reservoirs faces challenges including limited effective porosity, permeability, and rock reactivity; difficulties in using seawater for CO 2 capture; and uncontrolled carbonation. This study introduces a CO 2 capture, storage, and mineralization approach with the utilization of biobased biodegradable chelating agents and seawater. An

The establishment of Tasmanian Palawa/Pakana communities ~40 thousand years ago (ka) was achieved by the earliest and farthest human migrations from Africa and necessitated migration into high-latitude Southern Hemisphere environments. The scarcity of high-resolution paleoecological records during this period, however, limits our understanding of the environmental effects of this pivotal event, particularly

Future changes to the year-to-year swings between active and inactive North Atlantic tropical cyclone (TC) seasons have received little attention, yet may have great societal implications in areas prone to hurricane landfalls. This work investigates past and future changes in North Atlantic TC activity, focusing on interannual variability and evaluating the contributions from anthropogenic forcing

C points, circular polarization in momentum space, play crucial roles in chiral wave manipulations. However, conventional approaches of achieving intrinsic C points using photonic crystals with broken symmetries suffer from a low Q factor and high sensitivity to structural geometry, rendering them fragile and susceptible to perturbations and disorders. We report magneto-optical (MO) bound states in

B cell maturation depends on cognate interactions between the T and B cells. Upon interaction with CD40 ligand (CD40L) on T cells, CD40 delivers costimulatory signals alongside B cell antigen receptor (BCR) signaling to regulate affinity maturation and antibody class switch. Mutations affecting CD40-CD40L interactions cause abnormal antibody responses in immunodeficiencies known as X-linked hyper-IgM

Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of Bacillus subtilis and identified a Mg 2+ -dependent physiological cost. Coculture competition experiments show that Mg 2+ limitation hinders the growth of the L22*

Cloud microphysics studies include how tiny cloud droplets grow and become rain. This is crucial for understanding cloud properties like size, life span, and impact on climate through radiative effects. Small weak-updraft clouds near the haze-to-cloud transition are especially difficult to measure and understand. They are abundant but hard to capture by satellites. Köhler’s theory explains initial

Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly 1000 human hearts profiled by RNA sequencing

Noncentrosymmetric (NCS) pnictides are indispensable for nonlinear optics, ferroelectrics, magnetic Weyl electronics, etc., areas, yet their structure design remains a substantial challenge. By using asymmetric ionic unit–driven covalent groups orienting and rigidity-flexibility coupling dual strategy, we successfully design and synthesize four NCS pnictides: [Sr 4 Br] 2 [M II 3 Si 25 P 40 ] (M II

PARP inhibitors (PARPi) represent a game-changing treatment for patients with ovarian cancer with tumors deficient for the homologous recombination (HR) pathway treated with platinum (Pt)–based therapy. PARPi exert their cytotoxic effect by both trapping PARP1 on the damaged DNA and by restraining its enzymatic activity (PARylation). How PARP1 is recruited and trapped at the DNA damage sites and how

Bioarchaeology uses human skeletal remains to reconstruct varied experiences of individuals and populations in the past, including patterns of health across time periods and cultural contexts. In the past three decades, bioarchaeological studies have highlighted the concept of “frailty,” operationalizing it as increased risk of mortality or cumulative phenotypes. Using data from medieval London cemeteries

Nonlinear optical microscopy provides elegant means for label-free imaging of biological samples and condensed matter systems. The widespread areas of application could even be increased if resolution was improved, which the famous Abbe diffraction limit now restrains. Super-resolution techniques can break the diffraction limit but most rely on fluorescent labeling. This makes them incompatible with

The discrimination of quantum operations has long been an intriguing challenge, with theoretical research notably advancing our understanding of the quantum features in discriminating quantum objects. This challenge is closely related to the discrimination of quantum states, and proof-of-principle demonstrations of the latter have already been realized using optical photons. However, the experimental

The capture of CO 2 is of high interest in our society representing an essential tool to mitigate man-made climate warming. Membrane technology applied for CO 2 capture offers several advantages in terms of energy savings, simple operation, and easy scale-up. Glassy membranes are associated with low gas permeability that negatively affect on their industrial implementation. Oppositely, rubbery membranes

Developing instant detection systems with disease diagnostic capabilities holds immense importance for remote or resource-limited areas. However, the task of creating these systems—which are simultaneously easy to operate, rapid in detection, and cost-effective—remains a challenge. In this study, we present a compact highly sensitive photothermal reverse transcriptase–loop-mediated isothermal amplification

Fast and accurate assessment of skin mechanics holds great promise in diagnosing various epidermal diseases, yet substantial challenges remain in developing simple and wearable strategies for continuous monitoring. Here, we present a design concept, named active near-infrared spectroscopy patch (ANIRP) for continuously mapping skin mechanics. ANIRP addresses these challenges by integrating near-infrared

Cometary comae are a mixture of gas and ice-covered dust. Processing on the surface and in the coma change the composition of ice on dust grains relative to that of the nucleus. As the ice on dust grains sublimates, the local coma composition changes. Rosetta observations of 67P/Churyumov-Gerasimenko previously reported one of the highest D/H values for a comet. However, reanalysis of more than 4000

Nucleoporins (nups) in the nuclear pore complex (NPC) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptor (NTR)–bound cargos. Recent studies have shown that the NPC may dilate and constrict, but how altering the NPC diameter affects its selective barrier properties remains unclear. Here, we build DNA nanopores with

Heterozygosity for inverted formin-2 (INF2) mutations causes focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth disease. A key question is whether the disease is caused by gain-of-function effects on INF2 or loss of function (haploinsufficiency). Despite established roles in multiple cellular processes, neither INF2 knockout mice nor mice with a disease-associated point mutation

More than 110,000 Europeans died as a result of the record-breaking temperatures of 2022 and 2023. A new generation of impact-based early warning systems, using epidemiological models to transform weather forecasts into health forecasts for targeted population subgroups, is an essential adaptation strategy to increase resilience against climate change. Here, we assessed the skill of an operational

The relative amount of scattering and absorbing aerosols is essential in determining the aerosol radiative and climate effects. Using reanalysis datasets and climate simulations, here, we show that changes in the relative amount of scattering and absorbing aerosols in the Northern Hemisphere (NH) high latitudes, manifested as long-term decreasing trends in aerosol single-scattering albedo (SSA), have

Ring resonator (RR) devices are closed-loop waveguides where waves circulate only at the resonant frequencies. They have been used in sensor technology and optical tweezers, but controlling micron-scale particles with optical RR tweezers is challenging due to insufficient force, short working distances, and photodamage. To overcome these obstacles, an acoustofluidic RR-based tweezing method is developed

The coastal circulation around Southern Greenland transports fresh, buoyant water masses from the Arctic and Greenland Ice Sheet near regions of convection, sinking, and deep-water formation in the Irminger and Labrador Seas. Here, we track the pathways and fate of these fresh water masses by initializing synthetic particles in the East Greenland Coastal Current on the Southeast Greenland shelf and

Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3′-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically

CD8 + T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2’s role in exhausted T cell (T EX ) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell–like T EX progenitors toward terminally

Ekman’s theory of wind-driven ocean currents on a rotating planet is central to our understanding of why surface currents are deflected to the right of the winds in the Northern Hemisphere and to the left of the winds in the Southern Hemisphere. The theory admits solutions for currents deflected in the opposite direction at periods shorter than the local inertial period, but Ekman did not mention these

The timescale of animal diversification has been a focus of debate over how evolutionary history should be calibrated to geologic time. Molecular clock analyses have invariably estimated a Cryogenian or Tonian origin of animals while unequivocal animal fossils first occur in the Ediacaran. However, redating of key Ediacaran biotas and the discovery of several Ediacaran crown-Metazoa prompt recalibration

We use Coupled Model Intercomparison Project Phase 6 (CMIP6) coupled and Atmospheric Model Intercomparison Project (AMIP) climate models, dynamical analyses, and observations to investigate interactions between summer Arctic sea ice concentration (SIC) variations and the Summer North Atlantic Oscillation (SNAO). Observations suggest that SIC-SNAO relationships mainly come from the East Siberian to

Two-dimensional (2D) van der Waals (vdW) semiconductors play a key role in developing nanoscale nonlinear optical devices. 2D Ruddlesden-Popper lead halide perovskites (RPPs) expand the potential of using 2D vdW semiconductors in nonlinear optical applications because they exhibit electrically switchable and chiral second-order optical nonlinearity originating from the emergence of ferroelectricity

Early-life experience influences subsequent maturation and function of the adult brain, sometimes even in a sex-specific manner, but underlying molecular mechanisms are poorly understood. We describe here how juvenile experience defines sexually dimorphic synaptic connectivity in the adult Caenorhabditis elegans nervous system. Starvation of juvenile males disrupts serotonin-dependent activation of

Shifts in cytosolic pH have been recognized as key signaling events and mounting evidence supports the interdependence between H + and Ca 2+ signaling in eukaryotic cells. Among the cellular pH-stats, K + /H + exchange at various membranes is paramount in plant cells. Vacuolar K + /H + exchangers of the NHX (Na + ,K + /H + exchanger) family control luminal pH and, together with K + and H + transporters

Micro- and nanostructured surfaces offer the potential to enhance two-phase heat transfer. However, the mechanisms behind these enhancements are not well-understood due to insufficient diagnostic methods, leading to reliance on trial-and-error surface development. We introduce in situ boroscopy to investigate microscale bubble dynamics during flow boiling nucleation and subsequent flow regime development

Patients suffering from chronic stress develop numerous symptoms, including emotional and cognitive deficits. The precise circuit mechanisms underlying different symptoms remain poorly understood. We identified two distinct basal forebrain cholinergic subpopulations in mice projecting to the dorsal hippocampus (dHPC) or ventral hippocampus (vHPC), which exhibited distinct input organizations, electrophysiological

Stomata respond slowly to changes in light when compared with photosynthesis, undermining plant water-use efficiency (WUE). We know much about stomatal mechanics, yet efforts to accelerate stomatal responsiveness have been limited despite the breadth of potential targets for manipulation. Here, we use mechanistic modeling to establish a hierarchy of putative targets affecting stomatal kinetics. Counterintuitively

Tailoring the losses of optical systems within the frame of non-Hermitian physics has appeared very fruitful in the past few years. In particular, the description of exceptional points (EPs) with coupled resonators has become widespread. The on-chip realization of these functionalities is crucial for integrated nanophotonics but requires fine control techniques of the nanodevice properties. Here, we

Coronavirus-infected cells contain double-membrane vesicles (DMVs) that are key for viral RNA replication and transcription, perforated by hexameric pores connecting the vesicular lumen to the cytoplasm. How pores form and traverse two membranes, and how DMVs organize RNA synthesis, is unknown. Using structure prediction and functional assays, we show that the nonstructural viral membrane protein nsp4

Human foragers avoid noncommunicable diseases that are leading causes of mortality, partly because physically active lifestyles promote healthy aging. High activity levels also promote tissue damage accumulation from wear-and-tear, increase risk of injury and disability which compromise productivity, and reduce energetic investments in somatic maintenance given constrained energy expenditure. Constraints

We analyzed the evolution of extreme annual surface air temperature and rainfall on Earth, based on the recurrence rate of record-breaking events, and found the highest recurrence rates for record-high annual temperatures in the tropics, as opposed to the polar regions with the fastest warming. Both recurrence rates and the global surface area fraction with daily mean surface air temperatures exceeding

Solar-warmed surface waters subduct beneath Antarctica’s ice shelves as a result of wind forcing, but this process is poorly observed and its interannual variability is yet to be assessed. We observe a 50-meter-thick intrusion of warm surface water immediately beneath the Ross Ice Shelf. Temperature in the uppermost 5 meters decreases toward the ice base in near-perfect agreement with an exponential

Specific regions in the cognitive cerebellum are connected to distinct cerebral association networks. Do these cerebellar regions exhibit functional specialization similar to the cerebral cortex? Here, we mapped the cerebellum within intensively studied participants ( N = 15) first using connectivity to estimate regions linked to specific networks and then prospectively testing functional response

Introducing heteroatoms into graphene is a powerful strategy to modulate its catalytic, electronic, and magnetic properties. At variance with the cases of nitrogen (N)– and boron (B)–doped graphene, a scalable method for incorporating transition metal atoms in the carbon (C) mesh is currently lacking, limiting the applicative interest of model system studies. This work presents a during-growth synthesis

Rapidly increasing human-nature interactions exacerbate the risk of exposure to wildfires for human society. The wildland-urban interface (WUI) represents the nexus of human-nature interactions, where the risk of exposure to natural hazards such as wildfire is most pronounced. However, quantifying long-term global WUI change and the corresponding driving factors at fine resolution remain challenging

Identifying mechanisms driving the substantial dissolution of biogenic CaCO 3 (60 to 80%) in surface and mesopelagic waters of the global ocean is critical for constraining the surface ocean’s alkalinity and inorganic carbon budgets. We examine microzooplankton grazing on coccolithophores, photosynthetic calcifying algae responsible for a majority of open-ocean CaCO 3 production, as a mechanism driving

The role of the Arctic Ocean in the global climate system during the last climatic cycles remains conjectural, but radiocarbon-based chronologies and proxy data provide reliable information about the present interglacial. In the western Arctic, paleoceanographic data demonstrate a linkage between increasing Pacific water fluxes, resulting from the postglacial submergence of the Bering Strait, and the

PANoptosis has recently emerged as a potential approach to improve the immune microenvironment. However, current methods for inducing PANoptosis are limited. Herein, through biological screening, the rational use of the nutrient metal ions Cu 2+ and Zn 2+ had great potential to induce PANoptosis. Inspired by these findings, we successfully developed hydrazided hyaluronic acid–modified zinc copper oxide

Human forecasting accuracy improves through the “wisdom of the crowd” effect, in which aggregated predictions tend to outperform individual ones. Past research suggests that individual large language models (LLMs) tend to underperform compared to human crowd aggregates. We simulate a wisdom of the crowd effect with LLMs. Specifically, we use an ensemble of 12 LLMs to make probabilistic predictions