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Maternal gut microbiota influences immune activation at the maternal-fetal interface affecting pregnancy outcome
Meter-scale heterostructure printing for high-toughness fiber electrodes in intelligent digital apparel
Abstract Intelligent digital apparel, which integrates electronic functionalities into clothing, represents the future of healthcare and ubiquitous control in wearable devices. Realizing such apparel necessitates developing meter-scale conductive fibers with high toughness, conductivity, stable conductance under deformation, and mechanical durability. In this study, we present a heterostructure printing method capable of producing meter-scale (~50 m) biphasic conductive fibers that meet these criteria. Our approach involves encapsulating deformable liquid metal particles (LMPs) within a functionalized thermoplastic polyurethane matrix. This encapsulation induces in situ assembly of LMPs during fiber formation, creating a heterostructure that seamlessly integrates the matrix’s durability with the LMPs’ superior electrical performance. Unlike rigid conductive materials, deformable LMPs offer stretchability and toughness with a low gauge factor. Through precise twisting using an engineered annealing machine, multiple fiber strands are transformed into robust, electrically stable meter-scale electrodes. This advancement enhances their practicality in various intelligent digital apparel applications, such as stretchable displays, wearable healthcare systems, and digital controls.
Iron-catalyzed sequential hydrosilylation
Insight predicts subsequent memory via cortical representational change and hippocampal activity
Abstract The neural mechanisms driving creative problem-solving, including representational change and its relation to memory, still remain largely unknown. We focus on the creative process of insight, wherein rapid knowledge reorganization and integration—termed representational change—yield solutions that evoke suddenness, certainty, positive emotion, and enduring memory. We posit that this process is associated with stronger shifts in activation patterns within brain regions housing solution-relevant information, including the visual cortex for visual problems, alongside regions linked to feelings of emotion, suddenness and subsequent memory. To test this, we collect participants’ brain activity while they solve visual insight problems in the MRI. Our findings substantiate these hypotheses, revealing stronger representational changes in visual cortex, coupled with activations in the amygdala and hippocampus—forming an interconnected network. Importantly, representational change and hippocampal effects are positively associated with subsequent memory. This study provides evidence of an integrated insight mechanism influencing memory.
Self-propagating wave drives morphogenesis of skull bones in vivo
Abstract Cellular motion is a key feature of tissue morphogenesis and is often driven by migration. However, migration need not explain cell motion in contexts where there is little free space or no obvious substrate, such as those found during organogenesis of mesenchymal organs including the embryonic skull. Through ex vivo imaging , biophysical modeling, and perturbation experiments, we find that mechanical feedback between cell fate and stiffness drives bone expansion and controls bone size in vivo. This mechanical feedback system is sufficient to propagate a wave of differentiation that establishes a collagen gradient which we find sufficient to describe patterns of osteoblast motion. Our work provides a mechanism for coordinated motion that may not rely upon cell migration but on emergent properties of the mesenchymal collective. Identification of such alternative mechanisms of mechanochemical coupling between differentiation and morphogenesis will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties.
Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer
Two-dimensional materials based two-transistor-two-resistor synaptic kernel for efficient neuromorphic computing
KAT5 regulates neurodevelopmental states associated with G0-like populations in glioblastoma
Abstract Quiescence cancer stem-like cells may play key roles in promoting tumor cell heterogeneity and recurrence for many tumors, including glioblastoma (GBM). Here we show that the protein acetyltransferase KAT5 is a key regulator of transcriptional, epigenetic, and proliferative heterogeneity impacting transitions into G0-like states in GBM. KAT5 activity suppresses the emergence of quiescent subpopulations with neurodevelopmental progenitor characteristics, while promoting GBM stem-like cell (GSC) self-renewal through coordinately regulating E2F- and MYC- transcriptional networks with protein translation. KAT5 inactivation significantly decreases tumor progression and invasive behavior while increasing survival after standard of care. Further, increasing MYC expression in human neural stem cells stimulates KAT5 activity and protein translation, as well as confers sensitivity to homoharringtonine, to similar levels to those found in GSCs and high-grade gliomas. These results suggest that the dynamic behavior of KAT5 plays key roles in G0 ingress/egress, adoption of quasi-neurodevelopmental states, and aggressive tumor growth in gliomas.
Redox-driven photoselective self-assembly
Molecular epidemiology of Ascaris lumbricoides following multiple rounds of community-wide treatment
Abstract Control and elimination of the parasite Ascaris lumbricoides relies on mass drug administration (MDA) using a limited number of anti-helminthics. Whilst these programs have reduced the infection intensity and prevalence within many endemic regions, patterns of transmission remain poorly understood. Reinfection commonly occurs following cessation of treatment due to the absence of acquired immunity post infection. Here, we utilise genomic data to understand parasite transmission within and between households in a community and the genomic impact of repeated MDA. We sequenced 54 whole-genomes from Ascaris worms obtained from individuals in a longitudinal cohort epidemiological study of transmission and drug treatment extending over 6 years. We found that fine-scale population structure exists in spatially distinct clusters of infected individuals with reinfection occurring within or between geographically close households. This observation helps inform the policy for future control in low prevalence settings suggesting more targeted treatment of infection hotspots. We found evidence of positive selection acting on members of gene families previously implicated in reduced drug efficacy but detected no impactful variants. As efforts to eliminate A. lumbricoides intensify, our study provides a foundation for genomic surveillance to help identify both who infects whom and the impact of repeated drug treatment.
Single-transistor organic electrochemical neurons
Abstract Neuromorphic devices that mimic the energy-efficient sensing and processing capabilities of biological neurons hold significant promise for developing bioelectronic systems capable of precise sensing and adaptive stimulus-response. However, current silicon-based technologies lack biocompatibility and rely on operational principles that differ from those of biological neurons. Organic electrochemical neurons (OECNs) address these shortcomings but typically require multiple components, limiting their integration density and scalability. Here, we report a single-transistor OECN (1T–OECN) that leverages the hysteretic switching of organic electrochemical memtransistors (OECmTs) based on poly(benzimidazobenzophenanthroline). By tuning the electrolyte and driving voltage, the OECmTs switch between high- and low-resistance states, enabling action potential generation, dynamic spiking, and logic operations within a single device with dimensions comparable to biological neurons. The compact 1T–OECN design (~180 µm2 footprint) supports high–density integration, achieving over 62,500 neurons/cm2 on flexible substrates. This advancement highlights the potential for scalable, bio-inspired neuromorphic computing and seamless integration with biological systems.
Author Correction: Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank
Spatiotemporal deciphering of dynamic the FUS interactome during liquid-liquid phase separation in living cells
Monitored long-range interacting systems: spin-wave theory for quantum trajectories
Abstract Measurement-induced phases exhibit unconventional dynamics as emergent collective phenomena, yet their behavior in tailored interacting systems – crucial for quantum technologies – remains less understood. We develop a systematic toolbox to analyze monitored dynamics in long-range interacting systems, relevant to platforms like trapped ions and Rydberg atoms. Our method extends spin-wave theory to general dynamical generators at the quantum trajectory level, enabling access to a broader class of states than approaches based on density matrices. This allows efficient simulation of large-scale interacting spins and captures nonlinear dynamical features such as entanglement and trajectory correlations. We showcase the versatility of our framework by exploring entanglement phase transitions in a monitored spin system with power-law interactions in one and two dimensions, where the entanglement scaling changes from logarithm to volume law as the interaction range shortens, and by dwelling on how our method mitigates experimental post-selection challenges in detecting monitored quantum phases.
Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort
Abstract In the global CAPItello-291 randomized phase 3 study (NCT04305496) in patients with hormone receptor-positive/HER2-negative advanced breast cancer and progression during/after aromatase inhibitor treatment, capivasertib–fulvestrant significantly improved progression-free survival (PFS) in the overall population and patients with PIK3CA/AKT1/PTEN-altered tumors versus placebo–fulvestrant. We assessed efficacy and safety of capivasertib–fulvestrant in a prespecified exploratory analysis of a Chinese cohort (n = 24) and extended study with the same protocol (n = 110). Clinically meaningful PFS benefit for capivasertib–fulvestrant was observed in the overall population (median PFS: 6.9 [capivasertib–fulvestrant] versus 2.8 [placebo–fulvestrant] months; hazard ratio 0.51, 95% CI 0.34–0.76), patients with PIK3CA/AKT1/PTEN-altered tumors (n = 46; 5.7 versus 1.9 months; hazard ratio 0.41, 95% CI 0.19–0.85) and PIK3CA/AKT1/PTEN-non-altered tumors (patients with confirmed next-generation sequencing results [n = 68]; 9.2 versus 2.7 months; hazard ratio 0.38; 95% CI 0.21–0.68). The most frequent adverse events (AEs) with capivasertib–fulvestrant were diarrhea (60.6% versus 11.3% with placebo–fulvestrant) and hyperglycemia (57.7% versus 17.7%). AEs leading to capivasertib–fulvestrant discontinuation were reported in 11.3% of patients versus 3.2% for placebo–fulvestrant. The benefit-risk profile of capivasertib–fulvestrant in the Chinese cohort was favorable; further exploration in patients with PIK3CA/AKT1/PTEN-non-altered tumors is warranted.
Microvascular immunity is organ-specific and remodeled after kidney injury in mice
Abstract Many studies analyze tissue-resident or blood-borne leukocytes to monitor disease progression. We hypothesized that the microvasculature serves as a distinct site for immune cell activity. Here, we investigate microvascular leukocyte phenotypes before, during and after acute kidney injury (AKI) in mice, uncovering unique characteristics in the kidney, liver, and lung. Using single-cell sequencing, we identify several immune cells that were up to 100-fold expanded in the kidney vasculature, including macrophages, dendritic cells (DC), and B cells. Regeneration after AKI is characterized by sustained remodeling of the renal microvascular interface. Homeostatic microvascular C1q+ macrophages withdraw from the vascular barrier which is subsequently repopulated by new subsets, including CD11c+F480+ and CD11c+F480− cells. These newly arrived macrophages exhibit enhanced phagocytic activity toward circulating bacteria and secretion of tumor necrosis factor, pointing to maladaptive repair mechanisms after AKI. These data suggest organ- and disease-specific microvascular immune dynamics which are not detectable through conventional blood and tissue analysis.
Examining barriers and facilitators of dental fear treatment adoption: A qualitative study of practicing dentists
Over fifteen percent of the global population experiences dental fear, and although evidence-based treatments exist, adoption of these treatments is almost non-existent. Informed by our prior research examining barriers to adopting face-to-face behavioral treatments in dental operatories, this study examined dentists’ responses to three stepped-care Cognitive Behavioral Therapy for Dental Fear (CBT-DF) formats that use technology. All approaches offer an automated component as the first step (a mobile app) and either an in-person, virtual reality (VR), or video telehealth session as the second step. This study aims to understand which of these approaches would most likely be adopted by private practice dentists and why. Eight focus groups/solo interviews with a total of 13 private practice dentists were conducted with the aim to assess barriers and facilitators to implementing three stepped-care approaches of CBT-DF. The qualitative data obtained from these interviews was coded and analyzed according to Rogers’ framework of innovation (relative advantage, compatibility, complexity, trialability, and observability). The results indicated that participants acknowledged the value of interventions to address dental fear, as they had personal experiences with fearful patients that impacted their practices. Participants responded positively to the automated component of treatment (the app) and were more wary of treatment options requiring office space and staff time (in-person VR and in-person mental health provider). The telehealth option received the most favorable response, although some doubts were expressed regarding relative efficacy and patient accountability. Thus, dissemination of an app-telehealth treatment model that allows dentists to serve as referral partners is promising, given dentists’ incentives to decrease patient fear while avoiding opportunity cost (e.g., occupied chairs and staff time).