Oogenesis involves transduction of mechanical forces from the cytoskeleton to the nuclear envelope (NE). In Caenorhabditis elegans , oocyte nuclei lacking the single lamin protein LMN-1 are vulnerable to collapse under forces mediated through LINC (linker of nucleoskeleton and cytoskeleton) complexes. Here, we use cytological analysis and in vivo imaging to investigate the balance of forces that drive this collapse and protect oocyte nuclei. We also use a mechano-node-pore sensing device to directly measure the effect of genetic mutations on oocyte nuclear stiffness. We find that nuclear collapse is not a consequence of apoptosis. It is promoted by dynein, which induces polarization of a LINC complex composed of Sad1 and UNC-84 homology 1 (SUN-1) and ZYGote defective 12 (ZYG-12). Lamins contribute to oocyte nuclear stiffness and cooperate with other inner nuclear membrane proteins to distribute LINC complexes and protect nuclei from collapse. We speculate that a similar network may protect oocyte integrity during extended oocyte arrest in mammals.

Preliminary analyses of asteroid Ryugu samples show kinship to aqueously altered CI (Ivuna-type) chondrites, suggesting similar origins. We report identification of C-rich, particularly primitive clasts in Ryugu samples that contain preserved presolar silicate grains and exceptional abundances of presolar SiC and isotopically anomalous organic matter. The high presolar silicate abundance (104 ppm) indicates that the clast escaped extensive alteration. The 5 to 10 times higher abundances of presolar SiC (~235 ppm), N-rich organic matter, organics with N isotopic anomalies (1.2%), and organics with C isotopic anomalies (0.2%) in the primitive clasts compared to bulk Ryugu suggest that the clasts formed in a unique part of the protoplanetary disk enriched in presolar materials. These clasts likely represent previously unsampled outer solar system material that accreted onto Ryugu after aqueous alteration ceased, consistent with Ryugu’s rubble pile origin.

Robots typically interact with their environments via feedback loops consisting of electronic sensors, microcontrollers, and actuators, which can be bulky and complex. Researchers have sought new strategies for achieving autonomous sensing and control in next-generation soft robots. We describe here an electronics-free approach for autonomous control of soft robots, whose compositional and structural features embody the sensing, control, and actuation feedback loop of their soft bodies. Specifically, we design multiple modular control units that are regulated by responsive materials such as liquid crystal elastomers. These modules enable the robot to sense and respond to different external stimuli (light, heat, and solvents), causing autonomous changes to the robot’s trajectory. By combining multiple types of control modules, complex responses can be achieved, such as logical evaluations that require multiple events to occur in the environment before an action is performed. This framework for embodied control offers a new strategy toward autonomous soft robots that operate in uncertain or dynamic environments.

Cognitive performance varies widely across animal species, but the processes underlying cognitive evolution remain poorly known. For cognitive abilities to evolve, performance must be linked to individual fitness benefits, but these links have been rarely studied in primates even though they exceed most other mammals in these traits. We subjected 198 wild gray mouse lemurs to four cognitive and two personality tests and subsequently monitored their survival in a mark-recapture study. Our study revealed that survival was predicted by individual variation in cognitive performance as well as body mass and exploration. Because cognitive performance covaried negatively with exploration, individuals gathering more accurate information enjoyed better cognitive performance and lived longer, but so did heavier and more explorative individuals. These effects may reflect a speed-accuracy trade-off, with alternative strategies yielding similar overall fitness. The observed intraspecific variation in selective benefits of cognitive performance, if heritable, can provide the basis for the evolution of cognitive abilities in members of our lineage.

Quasar-driven outflows on galactic scales are a routinely invoked ingredient for galaxy formation models. We report the discovery of ionized gas nebulae surrounding three luminous red quasars at z ~ 0.4 from Gemini integral field unit observations. All these nebulae feature unprecedented pairs of “superbubbles” extending ~20 kpc in diameter, and the line-of-sight velocity difference between the red- and blueshifted bubbles reaches up to ~1200 km/s. Their spectacular dual-bubble morphology (in analogy to the galactic “Fermi bubbles”) and their kinematics provide unambiguous evidence for galaxy-wide quasar-driven outflows, in parallel with the quasi-spherical outflows similar in size from luminous type 1 and type 2 quasars at concordant redshift. These bubble pairs manifest themselves as a signpost of the short-lived superbubble “break-out” phase, when the quasar wind drives the bubbles to escape the confinement from the dense environment and plunge into the galactic halo with a high-velocity expansion.

Autoproteolysis has been discovered to play key roles in various biological processes, but functional autoproteolysis has been rarely reported for transmembrane signaling in prokaryotes. In this study, an autoproteolytic effect was discovered in the conserved periplasmic domain of anti-σ factor RsgIs from Clostridium thermocellum , which was found to transmit extracellular polysaccharide-sensing signals into cells for regulation of the cellulosome system, a polysaccharide-degrading multienzyme complex. Crystal and NMR structures of periplasmic domains from three RsgIs demonstrated that they are different from all known proteins that undergo autoproteolysis. The RsgI-based autocleavage site was located at a conserved Asn-Pro motif between the β1 and β2 strands in the periplasmic domain. This cleavage was demonstrated to be essential for subsequent regulated intramembrane proteolysis to activate the cognate SigI, in a manner similar to that of autoproteolysis-dependent activation of eukaryotic adhesion G protein–coupled receptors. These results indicate the presence of a unique prevalent type of autoproteolytic phenomenon in bacteria for signal transduction.

The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized neuronal components, such as ionotropic receptors at the postsynapse and voltage-gated ion channels at the axon initial segment, often requiring additional antigen-exposing techniques to detect their authentic signals. To solve this problem, we used glyoxal, a two-carbon atom di-aldehyde. We found that glyoxal fixation greatly improved antibody penetration and immunoreactivity, uncovering signals for buried molecules by conventional immunohistochemical procedures at light and electron microscopic levels. It also enhanced immunosignals of most other molecules, which are known to be detectable in formaldehyde-fixed sections. Furthermore, we unearthed several specific primary antibodies that were once judged to be unusable in formaldehyde-fixed tissues, allowing us to successfully localize so far controversial synaptic adhesion molecule Neuroligin 1. Thus, glyoxal is a highly effective fixative for immunostaining, and a side-by-side comparison of glyoxal and formaldehyde fixation is recommended for routine immunostaining in neuroscience research.

Nuclear localization signal (NLS) of HIV-1 integrase (IN) is implicated in nuclear import of HIV-1 preintegration complex (PIC). Here, we established a multiclass drug-resistant HIV-1 variant (HIV KGD ) by consecutively exposing an HIV-1 variant to various antiretroviral agents including IN strand transfer inhibitors (INSTIs). HIV KGD was extremely susceptible to a previously reported HIV-1 protease inhibitor, GRL-142, with IC 50 of 130 femtomolar. When cells were exposed to HIV KGD IN–containing recombinant HIV in the presence of GRL-142, significant decrease of unintegrated 2-LTR circular cDNA was observed, suggesting that nuclear import of PIC was severely compromised by GRL-142. X-ray crystallographic analyses revealed that GRL-142 interacts with NLS’s putative sequence (DQAEHLK) and sterically blocks the nuclear transport of GRL-142–bound HIV KGD ’s PIC. Highly INSTI-resistant HIV-1 variants isolated from heavily INSTI-experienced patients proved to be susceptible to GRL-142, suggesting that NLS-targeting agents would serve as salvage therapy agents for highly INSTI-resistant variant–harboring individuals. The data should offer a new modality to block HIV-1 infectivity and replication and shed light on developing NLS inhibitors for AIDS therapy.

Colloidal quantum dot (CQD)–based photodetectors are promising alternatives to bulk semiconductor-based detectors to be monolithically integrated with complementary metal-oxide semiconductor readout integrated circuits avoiding high-cost epitaxial growth methods and complicated flip-bonding processes. To date, photovoltaic (PV) single-pixel detectors have led to the best performance with background-limit infrared photodetection performance. However, the nonuniform and uncontrollable doping methods and complex device configuration restrict the focal plane array (FPA) imagers to operate in PV mode. Here, we propose a controllable in situ electric field–activated doping method to construct lateral p-n junctions in the short-wave infrared (SWIR) mercury telluride (HgTe) CQD–based photodetectors with a simple planar configuration. The planar p-n junction FPA imagers with 640 × 512 pixels (15-μm pixel pitch) are fabricated and exhibit substantially improved performance compared with photoconductor imagers before activation. High-resolution SWIR infrared imaging is demonstrated with great potential for various applications including semiconductor inspection, food safety, and chemical analysis.

Membrane technologies that enable the efficient purification of impaired water sources are needed to address growing water scarcity. However, state-of-the-art engineered membranes are constrained by a universal, deleterious trade-off where membranes with high water permeability lack selectivity. Current membranes also poorly remove low–molecular weight neutral solutes and are vulnerable to degradation from oxidants used in water treatment. We report a water desalination technology that uses applied pressure to drive vapor transport through membranes with an entrapped air layer. Since separation occurs due to a gas-liquid phase change, near-complete rejection of dissolved solutes including sodium chloride, boron, urea, and N -nitrosodimethylamine is observed. Membranes fabricated with sub-200-nm-thick air layers showed water permeabilities that exceed those of commercial membranes without sacrificing salt rejection. We also find the air-trapping membranes tolerate exposure to chlorine and ozone oxidants. The results advance our understanding of evaporation behavior and facilitate high-throughput ultraselective separations.

Cytokinetic abscission, the last step of cell division, is regulated by the ESCRT machinery. In response to mitotic errors, ESCRT proteins, namely, ALIX, CHMP4B, and CHMP4C, accumulate in the cytosolic compartments termed “abscission checkpoint bodies” (ACBs) to delay abscission and prevent tumorigenesis. ALIX contributes to the biogenesis and stability of ACBs via an unknown mechanism. We show that ALIX phase separates into nondynamic condensates in vitro and in vivo, mediated by the amyloidogenic portion of its proline-rich domain. ALIX condensates confined CHMP4 paralogs in vitro. These condensates dissolved and reformed upon reversible tyrosine phosphorylation of ALIX, mediated by Src kinase and PTP1B, and sequestration of CHMP4C altered their Src-mediated dissolution. NMR analysis revealed how ALIX triggers the activation of CHMP4 proteins, which is required for successful abscission. These results implicate ALIX’s phase separation in the modulation of ACBs. This study also highlights how posttranslational modifications can control protein phase separation.

Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin ( Spp1 ). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3 + macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3 + phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3 + macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and reveal Spp1 as a major regulator of macrophage and stromal progenitor interactions.

Prior knowledge facilitates our perception and goal-directed behaviors, particularly when sensory input is lacking or noisy. However, the neural mechanisms underlying the improvement in sensorimotor behavior by prior expectations remain unknown. In this study, we examine the neural activity in the middle temporal (MT) area of visual cortex while monkeys perform a smooth pursuit eye movement task with prior expectation of the visual target’s motion direction. Prior expectations discriminately reduce the MT neural responses depending on their preferred directions, when the sensory evidence is weak. This response reduction effectively sharpens neural population direction tuning. Simulations with a realistic MT population demonstrate that sharpening the tuning can explain the biases and variabilities in smooth pursuit, suggesting that neural computations in the sensory area alone can underpin the integration of prior knowledge and sensory evidence. State-space analysis further supports this by revealing neural signals of prior expectations in the MT population activity that correlate with behavioral changes.

The biogeochemical sulfur cycle plays a central role in fueling microbial metabolisms, regulating the Earth’s redox state, and affecting climate. However, geochemical reconstructions of the ancient sulfur cycle are confounded by ambiguous isotopic signals. We use phylogenetic reconciliation to ascertain the timing of ancient sulfur cycling gene events across the tree of life. Our results suggest that metabolisms using sulfide oxidation emerged in the Archean, but those involving thiosulfate emerged only after the Great Oxidation Event. Our data reveal that observed geochemical signatures resulted not from the expansion of a single type of organism but were instead associated with genomic innovation across the biosphere. Moreover, our results provide the first indication of organic sulfur cycling from the Mid-Proterozoic onwards, with implications for climate regulation and atmospheric biosignatures. Overall, our results provide insights into how the biological sulfur cycle evolved in tandem with the redox state of the early Earth.

The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics–based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth.

Pressure-overloaded left ventricular remodeling in young population is progressive and readily degenerate into heart failure. The aims of this study were to identify a plasma metabolite that predicts and is mechanistically linked to the disease. Untargeted metabolomics determined elevated plasma kynurenine (Kyn) in both the patient cohorts and the mice model, which was correlated with remodeling parameters. In vitro and in vivo evidence, combined with single-nucleus RNA sequencing (snRNA-seq), demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by activating aryl hydrocarbon receptors (AHR) to up-regulate hypertrophy- and fibrosis-related genes. Shotgun metagenomics and fecal microbiota transplantation revealed the existence of the altered gut microbiota-Kyn relationship. Supplementation of selected microbes reconstructed the gut microbiota, reduced plasma Kyn, and alleviated ventricular remodeling. Our data collectively discovered a gut microbiota–derived metabolite to activate AHR and its gene targets in remodeling young heart, a process that could be prevented by specific gut microbiota modulation.

Morphogenesis of living systems involves topological shape transformations which are highly unusual in the inanimate world. Here, we demonstrate that a droplet of a nematic liquid crystal changes its equilibrium shape from a simply connected tactoid, which is topologically equivalent to a sphere, to a torus, which is not simply connected. The topological shape transformation is caused by the interplay of nematic elastic constants, which facilitates splay and bend of molecular orientations in tactoids but hinders splay in the toroids. The elastic anisotropy mechanism might be helpful in understanding topology transformations in morphogenesis and paves the way to control and transform shapes of droplets of liquid crystals and related soft materials.

While analog neural network (NN) accelerators promise massive energy and time savings, an important challenge is to make them robust to static fabrication error. Present-day training methods for programmable photonic interferometer circuits, a leading analog NN platform, do not produce networks that perform well in the presence of static hardware errors. Moreover, existing hardware error correction techniques either require individual retraining of every analog NN (which is impractical in an edge setting with millions of devices), place stringent demands on component quality, or introduce hardware overhead. We solve all three problems by introducing one-time error-aware training techniques that produce robust NNs that match the performance of ideal hardware and can be exactly transferred to arbitrary highly faulty photonic NNs with hardware errors up to five times larger than present-day fabrication tolerances.

Water-based lubricants provide lubrication of rubbing surfaces in many technical, biological, and physiological applications. The structure of hydrated ion layers adsorbed on solid surfaces that determine the lubricating properties of aqueous lubricants is thought to be invariable in hydration lubrication. However, we prove that the ion surface coverage dictates the roughness of the hydration layer and its lubricating properties, especially under subnanometer confinement. We characterize different hydration layer structures on surfaces lubricated by aqueous trivalent electrolytes. Two superlubrication regimes are observed with friction coefficients of 10 −4 and 10 −3 , depending on the structure and thickness of the hydration layer. Each regime exhibits a distinct energy dissipation pathway and a different dependence to the hydration layer structure. Our analysis supports the idea of an intimate relationship between the dynamic structure of a boundary lubricant film and its tribological properties and offers a framework to study such relationship at the molecular level.

The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO − and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA . It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO − penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.