Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin–dependent (canonical) or –independent (noncanonical) signaling

The demand for mechanically robust polymer-based electrolytes is increasing for applications to wearable devices. Young’s modulus and breaking energy are essential parameters for describing the mechanical reliability of electrolytes. The former plays a vital role in suppressing the short circuit during charge-discharge, while the latter indicates crack propagation resistance. However, polymer electrolytes

Staphylococcus epidermidis expresses glycerol phosphate wall teichoic acid (WTA), but some health care–associated methicillin-resistant S. epidermidis (HA-MRSE) clones produce a second, ribitol phosphate (RboP) WTA, resembling that of the aggressive pathogen Staphylococcus aureus . RboP-WTA promotes HA-MRSE persistence and virulence in bloodstream infections. We report here that the TarM enzyme of

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas with limited treatment options, and new effective therapeutic strategies are desperately needed. We observe antiproliferative potency of genetic depletion of PTPN11 or pharmacological inhibition using the SHP2 inhibitor (SHP2i) TNO155. Our studies into the signaling response to SHP2i reveal that resistance

Field-induced superconductivity is a rare phenomenon where an applied magnetic field enhances or induces superconductivity. Here, we use applied stress as a control switch between a field-tunable superconducting state and a robust non–field-tunable state. This marks the first demonstration of a strain-tunable superconducting spin valve with infinite magnetoresistance. We combine tunable uniaxial stress

Patients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD. Our data showed a hypertrophic response

Eggs accumulate thousands of translationally repressed mRNAs that are translated into proteins after fertilization to direct diverse developmental processes. However, molecular mechanisms underlying the translation of stored mRNAs after fertilization remain unclear. Here, we report a previously unknown RNA processing of 3′ end sequences of mature mRNAs that activates the translation of stored mRNAs

Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules is crucial for rational development of immunotherapies and vaccines targeting CD4 + T cell activation. So far, most prediction methods for HLA class II antigen presentation have focused on HLA-DR because of limited availability of immunopeptidomics data for HLA-DQ and HLA-DP while not taking into account

Distinct from the dynamical phase, in a cyclic evolution, a system’s state may acquire an additional component, a.k.a. geometric phase. Recently, it has been demonstrated that geometric phases can be induced by a sequence of generalized measurements implemented on a single qubit. Furthermore, it has been predicted that these geometric phases may exhibit a topological transition as a function of the

Red snow caused by blooms of microalgae darkens the surface of summer snowfields, increasing snowmelt. To assess the contribution of red snow to supraglacial snowmelt in northwestern North America, we systematically mapped the 2019–2022 distribution of blooms by applying supervised classification to 6158 satellite images. Blooms occurred on 5% of the total glaciated area, heavily affecting many glaciers

Summer monsoon frontal rainfall in East Asia (EA) is crucial for water resources and flood hazards in densely populated areas. Recent studies have documented the increasing intensity of summer frontal rainfall over recent decades. However, the extent of ongoing climate change on the intensification of the EA frontal precipitation system remains uncertain. Using an objective method for detecting frontal

Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA–mRNA network of inflamed motor neurons by leveraging cell type–specific miRNA and

Diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG) signaling by converting DAG to phosphatidic acid, thereby suppressing pathways downstream of T cell receptor signaling. Using a dual DGKα/ζ inhibitor (DGKi), tumor-specific CD8 T cells with different affinities (TRP1 high and TRP1 low ), and altered peptide ligands, we demonstrate that inhibition of DGKα/ζ can lower the signaling threshold

Biallelic genetic variants in N -acetylneuraminic acid synthase ( NANS ), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that NANS mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical

Metastable phases present a promising route to expand the functionality of complex materials. Of particular interest are light-induced metastable phases that are inaccessible under equilibrium conditions, as they often host new, emergent properties switchable on ultrafast timescales. However, the processes governing the trajectories to such hidden phases remain largely unexplored. Here, using time-

Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO Ascites ) in cancer progression and use modified exosomes as resources for cancer therapy. EXO Ascites from patients

Unlike reef-building, scleractinian corals, Caribbean soft corals (octocorals) have not suffered marked declines in abundance associated with anthropogenic ocean warming. Both octocorals and reef-building scleractinians depend on a nutritional symbiosis with single-celled algae living within their tissues. In both groups, increased ocean temperatures can induce symbiont loss (bleaching) and coral death

Cross-linked elastomers are stretchable materials that typically are not recyclable or biodegradable. Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are soft and ductile, making these bio-based polymers good candidates for biodegradable elastomers. Elasticity is commonly imparted by a cross-linked network structure, and covalent adaptable networks have emerged as a solution to prepare recyclable

2LiX-GaF 3 (X = Cl, Br, I) electrolytes offer favorable features for solid-state batteries: mechanical pliability and high conductivities. However, understanding the origin of fast ion transport in 2LiX-GaF 3 has been challenging. The ionic conductivity order of 2LiCl-GaF 3 (3.20 mS/cm) > 2LiBr-GaF 3 (0.84 mS/cm) > 2LiI-GaF 3 (0.03 mS/cm) contradicts binary LiCl (10 −12 S/cm) < LiBr (10 −10 S/cm) <

Endozoicomonas are often predominant bacteria and prominently important in coral health. Their role in dimethylsulfoniopropionate (DMSP) degradation has been a subject of discussion for over a decade. A previous study found that Endozoicomonas degraded DMSP through the dddD pathway. This process releases dimethyl sulfide, which is vital for corals coping with thermal stress. However, little is known

Thin-film ferroelectrics have been pursued for capacitive and nonvolatile memory devices. They rely on polarizations that are oriented in an out-of-plane direction to facilitate integration and addressability with complementary metal-oxide semiconductor architectures. The internal depolarization field, however, formed by surface charges can suppress the out-of-plane polarization in ultrathin ferroelectric

Generation and manipulation of three-dimensional (3D) optical polarization structures have received considerable interest because of their distinctive optical features and potential applications. However, the realization of multiple 3D polarization structures in a queue along the light propagation direction has not yet been reported. We propose and experimentally demonstrate a metalens to create longitudinally

Transcriptional dysregulation is a recurring pathogenic hallmark and an emerging therapeutic vulnerability in ovarian cancer. Here, we demonstrated that ovarian cancer exhibited a unique dependency on the regulatory machinery of transcriptional termination, particularly, cleavage and polyadenylation specificity factor (CPSF) complex. Genetic abrogation of multiple CPSF subunits substantially hampered

We envision programmable matters that can alter their physical properties in desirable manners based on user input or autonomous sensing. This vision motivates the pursuit of mechanical metamaterials that interact with the environment in a programmable fashion. However, this has not been systematically achieved for soft metamaterials because of the highly nonlinear deformation and underdevelopment

Chemical shift assignment is vital for nuclear magnetic resonance (NMR)–based studies of protein structures, dynamics, and interactions, providing crucial atomic-level insight. However, obtaining chemical shift assignments is labor intensive and requires extensive measurement time. To address this limitation, we previously proposed ARTINA, a deep learning method for automatic assignment of two-dimensional

Investigation into the nexus of human-environmental behavior has seen increasing collaboration of archaeologists, historians, and paleo-scientists. However, many studies still lack interdisciplinarity and overlook incompatibilities in spatiotemporal scaling of environmental and societal data and their uncertainties. Here, we argue for a strengthened commitment to collaborative work and introduce the

Understanding the fundamentals and applications of chirality relies substantially on the amplification of chirality through hierarchical assemblies involving various weak interactions. However, a notable challenge remains for metal clusters chiral assembly driven by halogen bonding, despite their promising applications in lighting, catalysis, and biomedicine. Here, we used halogen bonding–driven assembly

Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation

Osteosarcoma is a highly aggressive cancer and lacks effective therapeutic targets. We found that L3MBTL2 acts as a tumor suppressor by transcriptionally repressing IFIT2 in osteosarcoma. L3MBTL2 recruits the components of Polycomb repressive complex 1.6 to form condensates via both Pho-binding pockets and polybasic regions within carboxyl-terminal intrinsically disordered regions; the L3MBTL2-induced

Genetically encoded voltage indicators (GEVIs) allow the direct visualization of cellular membrane potential at the millisecond time scale. Among these, red-emitting GEVIs have been reported to support multichannel recordings and manipulation of cellular activities with reduced autofluorescence background. However, the limited sensitivity and dimness of existing red GEVIs have restricted their applications

Despite great advances in protein structure analysis, label-free and ultrasensitive methods to obtain the natural and dynamic three-dimensional (3D) structures are still urgently needed. Surface-enhanced Raman spectroscopy (SERS) can be a good candidate, whereas the complexity originated from the interactions between the protein and the gradient surface electric field makes it extremely challenging

Chromatin regulation plays a pivotal role in establishing and maintaining cellular identity and is one of the top pathways disrupted in autism spectrum disorder (ASD). The hippocampus, composed of distinct cell types, is often affected in patients with ASD. However, the specific hippocampal cell types and their transcriptional programs that are dysregulated in ASD are unknown. Using single-nucleus

Human infants acquire language with notable ease compared to adults, but the neural basis of their remarkable brain plasticity for language remains little understood. Applying a scaling analysis of neural oscillations to address this question, we show that newborns’ electrophysiological activity exhibits increased long-range temporal correlations after stimulation with speech, particularly in the prenatally

Adaptation to low levels of oxygen (hypoxia) is a universal biological feature across metazoans. However, the unique mechanisms how different species sense oxygen deprivation remain unresolved. Here, we functionally characterize a novel long noncoding RNA (lncRNA), LOC105369301 , which we termed hypoxia-induced lncRNA for polo-like kinase 1 (PLK1) stabilization ( HILPS ). HILPS exhibits appreciable

BMP15 is a conserved regulator of ovarian development and maintenance in vertebrates. In humans, premature ovarian insufficiency is caused by autoimmunity and genetic factors, including mutation of BMP15. The cellular mechanisms underlying ovarian failure caused by BMP15 mutation and immune contributions are not understood. Using zebrafish, we established a causal link between macrophage activation

The biological role of the repetitive DNA sequences in the human genome remains an outstanding question. Recent long-read human genome assemblies have allowed us to identify a function for one of these repetitive regions. We have uncovered a tandem array of conserved primate-specific retrogenes encoding the protein Elongin A3 (ELOA3), a homolog of the RNA polymerase II (RNAPII) elongation factor Elongin

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone–collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients

The electronic and nuclear dynamics inside molecules are essential for chemical reactions, where different pathways typically unfold on ultrafast timescales. Extreme ultraviolet (XUV) light pulses generated by free-electron lasers (FELs) allow atomic-site and electronic-state selectivity, triggering specific molecular dynamics while providing femtosecond resolution. Yet, time-resolved experiments are

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder

Animals and plants worldwide are structured in global biogeographic regions, which were shaped by major geologic forces during Earth history. Recently, humans have changed the course of events by multiplying global pathways of introduction for nonindigenous species and propagating local species extirpations. Here, we report on how introductions and extirpations have changed the distributions of freshwater

Organic aerosol (OA) is an air pollutant ubiquitous in urban atmospheres. Urban OA is usually apportioned into primary OA (POA), mostly emitted by mobile sources, and secondary OA (SOA), which forms in the atmosphere due to oxidation of gas-phase precursors from anthropogenic and biogenic sources. By performing coordinated measurements in the particle phase and the gas phase, we show that the alkylperoxy

Taste systems encode chemical cues that drive vital behaviors. We have elucidated noncanonical features of taste coding using an unconventional kind of electrophysiological analysis. We find that taste neurons of Drosophila are much more sensitive than previously thought. They have a low spontaneous firing frequency that depends on taste receptors. Taste neurons have a dual function as olfactory neurons:

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here, we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of α-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in α-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent

Leukotrienes, a class of inflammatory bioactive lipids, are well studied in the periphery, but less is known of their importance in the brain. We identified that the enzyme leukotriene A4 hydrolase (LTA4H) is expressed in healthy mouse neurons, and inhibition of LTA4H in aged mice improves hippocampal dependent memory. Single-cell nuclear RNA sequencing of hippocampal neurons after inhibition reveals

Energy deprivation triggers food seeking to ensure homeostatic consumption, but the neural coding of motivational vigor in food seeking during physical hunger remains unknown. Here, we report that ablation of dopamine (DA) neurons in zona incerta (ZI) but not ventral tegmental area potently impaired food seeking after fasting. ZI DA neurons and their projections to paraventricular thalamus (PVT) were

Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock

Embryonic stem cells (ESCs) have transcriptionally permissive chromatin enriched for gene activation–associated histone modifications. A striking exception is DOT1L-mediated H3K79 dimethylation (H3K79me2) that is considered a positive regulator of transcription. We find that ESCs are depleted for H3K79me2 at shared locations of enrichment with somatic cells, which are highly and ubiquitously expressed

Atmospheric rivers (ARs) bring concentrated rainfall and flooding to the western United States (US) and are hypothesized to have supported sustained hydroclimatic changes in the past. However, their ephemeral nature makes it challenging to document ARs in climate models and estimate their contribution to hydroclimate changes recorded by time-averaged paleoclimate archives. We present new climate model

Aberrant activation of Ras/Raf/mitogen-activated protein kinase (MAPK) signaling is frequently linked to metastatic prostate cancer (PCa); therefore, the characterization of modulators of this pathway is critical for defining therapeutic vulnerabilities for metastatic PCa. The lysine methyltransferase SET and MYND domain 3 (SMYD3) methylates MAPK kinase kinase 2 (MAP3K2) in some cancers, causing enhanced

Carbon dioxide and methane emissions are the two primary anthropogenic climate-forcing agents and an important source of uncertainty in the global carbon budget. Uncertainties are further magnified when emissions occur at fine spatial scales (<1 km), making attribution challenging. We present the first observations from NASA’s Earth Surface Mineral Dust Source Investigation (EMIT) imaging spectrometer

Parkinson’s disease (PD) is characterized by conversion of soluble α-synuclein (αS) into intraneuronal aggregates and degeneration of neurons and neuronal processes. Indications that women with early-stage PD display milder neurodegenerative features suggest that female sex partially protects against αS pathology. We previously reported that female sex and estradiol improved αS homeostasis and PD-like

Simulations of nuclear magnetic resonance (NMR) experiments can be an important tool for extracting information about molecular structure and optimizing experimental protocols but are often intractable on classical computers for large molecules such as proteins and for protocols such as zero-field NMR. We demonstrate the first quantum simulation of an NMR spectrum, computing the zero-field spectrum

The Mid-Pliocene represents the most recent interval in Earth history with climatic conditions similar to those expected in the coming decades. Mid-Pliocene sea level estimates therefore provide important constraints on projections of future ice sheet behavior and sea level change but differ by tens of meters due to local distortion of paleoshorelines caused by mantle dynamics. We combine an Australian

Iron deficiency (ID) is a widespread condition concomitant with disease and results in systemic dysfunction of target tissues including skeletal muscle. Activated by ID, ferritinophagy is a recently found type of selective autophagy, which plays an important role in various physiological and pathological conditions. In this study, we demonstrated that ID-mediated ferritinophagy impeded myogenic differentiation

Gross primary productivity (GPP) is the key determinant of land carbon uptake, but its representation in terrestrial biosphere models (TBMs) does not reflect our latest physiological understanding. We implemented three empirically well supported but often omitted mechanisms into the TBM CABLE-POP: photosynthetic temperature acclimation, explicit mesophyll conductance, and photosynthetic optimization

The large Kuiper Belt object Eris is tidally locked to its small companion Dysnomia. Recently obtained bounds on the mass of Dysnomia demonstrate that Eris must be unexpectedly dissipative for it to have despun over the age of the solar system. Here, we show that Eris must have differentiated into an ice shell and rocky core to explain the dissipation. We further demonstrate that Eris’s ice shell must

Hydrovoltaic technology has achieved notable breakthroughs in electric output via using the moving boundary of electric double layer, but the output voltage induced by droplets is saturated around 350 volts, and the underlying mechanism remains to be further clarified. Here, we show that falling water droplets can stably spark an unprecedented voltage up to 1200 volts within microseconds that they

Protein misfolding and aggregation is a characteristic of many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. The oligomers generated during aggregation are likely involved in disease pathogenesis and present promising biomarker candidates. However, owing to their small size and low concentration, specific tools to quantify and characterize aggregates in complex biological

The advent of implantable bioelectronic devices offers prospective solutions toward health monitoring and disease diagnosis and treatments. However, advances in power modules have lagged far behind the tissue-integrated sensor nodes and circuit units. Here, we report a soft implantable power system that monolithically integrates wireless energy transmission and storage modules. The energy storage unit