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Toward trustworthy chatbots: a protocol for red teaming for health related conversations
The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons
Abstract The N-terminal acetyltransferase B (NatB) acetylates ~20% of the eukaryotic proteome. However, the role of NatB-mediated N-terminal acetylation (NTA) for the regulation of the proteome fate remains unclear in eukaryotes. In this study, we demonstrate that CRISPR-Cas9-mediated deletion of NatB activity in plants results in significantly lowered global protein turnover due to decreased ubiquitin-proteasome system (UPS) activity and protein translation. Quantitative proteomics uncovers that NatB substrates are significantly enriched in the fraction of stabilized proteins in natb mutants. We provide direct evidence that the absent NTA of KIN11, a subunit of the autophagy-controlling energy sensor SnRK1, protects it from UPS-mediated destruction. The resulting accumulation of KIN11 is responsible for the increased resistance of natb mutants to energy limitation induced by prolonged darkness. Our findings establish NatB as a central regulator of UPS–autophagy interplay and highlight its role in maintaining proteome stability and enabling dynamic stress responses in plants.
Correction: The influence of structured reporting on the accuracy of head and neck sonographies
Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions
Abstract White matter hyperintensities (WMHs) are neuroimaging markers widely interpreted as caused by cerebral small vessel disease, yet emerging evidence suggests that a subset may have a neurodegenerative etiology. Current imaging methods have lacked the specificity to disentangle biological processes underlying WMHs in vivo. Here, we used voxel-level normative modeling and seven microstructural MRI markers with complementary biophysical sensitivities to generate single-subject high-resolution WMH pathophysiology maps in a large cohort ( n = 32,526). We calculated data-driven spatial patterns of similar WMHs, revealing distinct periventricular, posterior, and anterior clusters. We identified a reproducible WMH signature linked to dementia and Alzheimer’s disease, characterized by a posterior predominance and a pathophysiological pattern indicative of selective fiber degeneration. Posterior WMHs connected cortical regions vulnerable to tau pathology. Our framework helps parsing vascular and neurodegenerative contributions of WMHs in vivo, which could alter the course of treatment strategies and provide nuanced interpretations of research findings.
The control mechanisms of clearance ratio on squeeze film dampers performance
Single-molecule dynamics reveal ATP binding alone powers substrate translocation by an ABC transporter
Abstract ATP-binding cassette (ABC) transporters are molecular machines involved in diverse physiological processes, including antigen processing by TAP, a key component of adaptive immunity. TAP and its bacterial homolog TmrAB use ATP to translocate peptides across membranes, yet the precise mechanism linking ATP binding to substrate movement remains unclear. Here, we employ a single-molecule FRET sensor to visualize single translocation events by individual ABC transporters and thereby overcome the limitations of ensemble averaging. This approach reveals that substrate transport is driven by a conformational switch from the inward- to the outward-facing state. Using a slow-turnover TmrAB variant, we demonstrate that ATP binding alone, even in the absence of Mg 2+ , is sufficient to drive a single round of peptide translocation. Cryo-EM structures of wild-type and slow-turnover TmrAB show that ATP binding induces the outward-facing conformation even without Mg 2+ . In wild-type TmrAB, this conformational transition supports a single translocation event, whereas Mg 2+ -dependent ATP hydrolysis is required to reset the transporter. These findings establish a direct mechanistic link between ATP binding and substrate translocation at single-molecule resolution and provide insight into the catalytic cycle of ABC transporters.
Spatiotemporal differentiation and dynamics simulation of China’s industrial soot and dust emissions
CXCR3 is associated with T-cell-induced heart damage in acute rheumatic fever
Urban theft prediction via LLM-empowered spatiotemporal transformer
Abstract With the deepening of urbanization, the spatiotemporal heterogeneity of theft crimes in New York City has become prominent, creating a demand for more accurate prediction. Existing models face limitations in capturing nonlinear correlations, integrating multi-source data, and generalizing to dynamic scenarios. This study proposes an LLM-enhanced Spatiotemporal Transformer (LLM-STT) model, which integrates multi-source spatiotemporal features (including taxi passenger flow proxy) and Gemma3-12B embeddings, with a lightweight fine-tuning scheme for Gemma3-1B. Its main explorations include LLM-based semantic encoding, quantifying feature coupling, and balancing performance and deployment feasibility. Experiments on hourly neighborhood-scale theft prediction in New York City show the model achieves an AUC of 0.91 and an F1 score of 0.83, demonstrating competitive performance against baselines. LLM embeddings and dynamic population features contribute positively, and the lightweight fine-tuned model outperforms the random baseline. These findings offer preliminary support for targeted crime prevention in similar urban contexts, with broader generalization requiring further validation.
A statistical understanding of oxygen vacancies in distorted high-entropy perovskite oxides
Vibrational and electronic properties of Np$$_2$$O$$_5$$ from experimental spectroscopy and first principles calculations
Abstract High-valence actinide oxides are critical to understanding the behavior of 5 f -electrons, yet their structural and electronic properties remain poorly understood due to challenges in synthesis and handling. We report the first Raman spectroscopic study of single-crystalline Np $$_2$$ O $$_5$$ and the first scanning tunneling spectroscopy (STS) measurement on any neptunium-containing material. Hydrothermally synthesized crystals were structurally verified by X-ray diffraction. Raman spectra revealed sharply resolved vibrational features, including previously unreported low-frequency modes. STS measurements revealed a band gap of 1.5 eV. Density functional theory (DFT) enables vibrational mode assignments, reveals neptunium-dominated low-frequency phonons, oxygen-dominated high-frequency modes, and predicts an indirect band gap of 1.68 eV. This predicted value is in excellent agreement with the experimentally measured STS gap. This combined Raman, DFT, and STS approach provides a robust framework for correlating lattice dynamics and electronic structure in actinide materials, providing benchmark data for Np $$_2$$ O $$_5$$ , and opening new avenues for probing structure–property relationships in complex f -electron materials.
Mapping human pre-rRNA processing and modification at single nucleotide resolution using long read nanopore sequencing
Abstract Ribosome biogenesis requires the synthesis and sequential processing of precursor rRNAs (pre-rRNAs) into mature rRNAs. Traditional methods such as northern blotting and metabolic labeling provide limited resolution. Here, we present NanoRibolyzer, a nanopore-based long-read sequencing approach that enables ab initio identification and quantification of rRNA precursors while simultaneously mapping RNA modifications. Using supervised and unsupervised mapping, we detect both known and previously uncharacterized pre-rRNAs and delineate cleavage events at single-nucleotide resolution. A simple cell-fractionation protocol further separates nuclear and cytoplasmic pre-rRNAs, allowing spatial deconvolution of processing pathways. By projecting each sequenced molecule in a two-dimensional space using its starting and ending coordinates, we generate an intuitive representation in which the activity of the 5′ → 3′ and 3′ → 5′ exoRNases can be tracked as they mature pre-rRNAs one nucleotide at a time. Targeted knockdowns of ribosome-assembly factors quantify accumulation of intermediates and reveal condition-specific processing “fingerprints” with biomarker potential. High-resolution re-analysis of known factors uncovers unexpected functions. Additionally, pseudouridine mapping shows that the primary 47S transcript is extensively modified, whereas aberrant intermediates (34S and 36S-C) are hypomodified. With its high resolution and unique discovery mode, NanoRibolyzer provides new insights into rRNA processing and modification, greatly advancing our understanding of ribosome biogenesis.
Double flower is associated with defects in a Phantastica-like gene in Catharanthus roseus
A prospective multicenter trial of deep learning auto-segmentation for organs at risk in thoracic radiotherapy
Disorder suppression and tunable localization in ultrathin SrIrO3 films via SrTiO3 capping
Fluorescence-based mapping of condensate dielectric permittivity uncovers hydrophobicity-driven membrane interactions
Abstract Biomolecular condensates, essential for cellular organization, possess mesoscale properties largely governed by hydrophobicity, influencing molecule partitioning and material characteristics like viscosity, surface tension, and hydration. While hydrophobicity’s role is increasingly recognized, its impact on membrane-condensate interactions remains unexplored. Here, we combine hyperspectral imaging of an environment-sensitive dye and phasor analysis, to quantitatively map the local dielectric permittivity of both condensates and their environment with pixel resolution. This robust method senses the immediate molecular vicinity of the dye and reveals a surprisingly broad range of condensate permittivities, spanning from oil-like to water-like values. Importantly, we uncover that membrane affinity is not dictated by condensate permittivity itself, but by the permittivity contrast with their surroundings. Indeed, membrane wetting affinity is found to scale linearly with this permittivity contrast, unveiling a unifying dielectric principle governing condensate-membrane interactions. Compatible with live-cell and in vitro imaging, this technique provides quantitative insights into condensate biophysics and function and opens new avenues for studying biomolecular condensate biology.
Effect of insurance status on mortality following surgical treatment of colorectal cancers in the United States
Abstract Healthcare disparities in colorectal cancer, driven by insurance status and socioeconomic factors, lead to delayed diagnoses and poor surgical outcomes. We sought to examine the impact of insurance status on presentation, treatment, and in-hospital mortality among CRC patients undergoing colectomy using the Nationwide Inpatient Sample (NIS) database. We included patients aged 18–65 years diagnosed with colon cancer and undergoing colectomy, as identified by ICD-9-CM codes. We classified them as those with private insurance, Medicaid, or no insurance during the period January 1, 2005, through December 31, 2014. The primary independent variable was insurance status, and the primary outcome was in-hospital postoperative death. Associations between this outcome and insurance status were analyzed using the Cox proportional hazard model, both in the full cohort as well as in a subset of patients with low comorbidity, with models stratified by hospitals to account for clustering effects from variations in access to care. The study cohort included 301,304 patients, of whom 238,158 (79.0%) were privately insured, 40,417 (13.4%) on Medicaid, and 22,729 (7.6%) were uninsured. Most patients were White (71.6%), followed by African American (12.6%), Hispanic (8.4%), Asian/Pacific Islander (3.8%), and Native American (0.5%). A total of 55.4% of cases took place in teaching hospitals. In the unadjusted analysis, the mortality rate for privately insured patients was 0.7% (95% CI 0.6–0.7%) compared with 2.1% for uninsured patients (95% CI 1.7–2.5%) and 1.5% for Medicaid recipients (95% CI 1.2–1.8%; p = 0.001). After adjusting for patient characteristics and stratifying by hospital in patients with low comorbidity, uninsured patients still had a higher risk of experiencing in-hospital death (HR, 1.60; 95% CI 1.24–2.07) compared with privately insured patients, while no significant disparity was found in Medicaid recipients (HR, 0.95; 95% CI 0.75–1.22). Uninsured patients undergoing colectomy for colon cancer experienced the highest in-hospital mortality, a disparity not fully explained by overall health differences. These findings underscore the critical role of insurance coverage in improving surgical outcomes and highlight the need for policy interventions to reduce mortality disparities.
Developing a novel index for neighborhood social determinants of cardiovascular diseases in the CARDIA study
Tampa scale for kinesiophobia in individuals with knee osteoarthritis: a cross-sectional psychometric evaluation using item-level and exploratory factor analyses
Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis
Abstract Convergence and extension (C&E) cell movements that elongate the primary embryonic axis are precisely timed during vertebrate gastrulation, but mechanisms controlling their onset remain unknown. Using zebrafish embryonic explants that recapitulate C&E and its timing, we identified sulfatase modifying factor 2 ( sumf2 ) as a candidate trigger gene for C&E onset. sumf2 and its paralog sumf1 encode negative and positive sulfatase regulators, respectively, whose expression levels invert and increase heparan sulfate sulfation during gastrulation. Overexpressing sumf1 or sumf2 causes delayed or precocious C&E, respectively, whereas their loss shifts C&E timing in the opposite direction. We identified Sulf1, a modifier of heparan sulfate proteoglycans (HSPGs), as their key downstream effector and found that altering heparan sulfate sulfation levels shifts C&E onset and suppresses sumf1 and sumf2 mutant phenotypes. This work supports a model in which sumf2 expression reduces sulfatase activity, rewriting HSPG sulfation patterns to promote the onset of C&E morphogenesis.