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Central role for fast nociceptors in mechanical nocifensive behavior and sensitization
Abstract Nociceptors, primary afferent nerve fibers that signal noxious stimuli, are broadly divided into slowly conducting unmyelinated C fibers and fast-conducting myelinated A fibers. Whereas C-nociceptors have been extensively studied, considerably less is known about the function of A-nociceptors. Here we demonstrate, combining genetic targeting of these fibers in mice with observations in human participants, a key involvement of A-nociceptors in mechanical nociceptive withdrawal reflexes and affective pain. In mice, optogenetic stimulation induced rapid and precise withdrawal reflexes as well as place aversion and facial expression changes consistent with pain affect, while inhibition strongly impaired mechanical nociceptive withdrawal reflexes. Prolonged A-nociceptor activation induced mechanical pain hypersensitivity and central sensitization. In a rare individual lacking thickly myelinated Aβ fibers, and in healthy participants during preferential Aβ-fiber nerve block, mechanical withdrawal reflexes were absent and mechanical pain perception reduced. Together, these findings identify fast-conducting mechano-nociceptors as essential drivers of nocifensive behaviors in mice and humans.
Short term associations of weather and air quality with ophthalmic outpatient attendance in eastern China
Abstract The magnitude and timing of short-term associations of weather and air quality with ophthalmic attendance remain poorly quantified. We analysed completed attendances from a tertiary ophthalmology department in Jiangsu, China (2015–2025; 3,788 days) using a time-stratified case-crossover design with conditional Poisson regression. Exposures included catchment-weighted meteorology, nitrogen dioxide (NO₂), and fine particulate matter (PM₂.₅); extreme heat, cold, and heavy rainfall were accumulated over 0–3 and 0–7 days. Over 0–3 days, each additional extreme-heat or heavy-rainfall day was associated with lower completed attendance (rate ratios 0.961 [95% CI 0.954–0.967] and 0.937 [95% CI 0.923–0.952], respectively; both p < 0.0001), whereas extreme cold showed no clear association. From a baseline of 293 visits/day, two heat days and two heavy-rainfall days corresponded to approximately 23 and 36 fewer visits/day, respectively. Lag analyses suggested delayed positive rainfall associations compatible with partial compensation, but no comparable heat pattern within 21 days. The retrospective trigger simulation had 39% precision and 59% recall; approximately 61% of triggered days were false alarms. Locally derived heat thresholds and rainfall amount-related estimates may support preparedness planning. Because completed attendance—not underlying ophthalmic need—was measured, real-time use requires prospective validation of safety, equity, and unmet-need outcomes.
Highly stable quasi-solid-state initially anode-free lithium metal batteries enabled by dynamic integrated interface engineering
YOLOv8-based real-time obstacle detection in farmland environments for heavy-load agricultural UAVs
Abstract Heavy-load agricultural UAVs operating at low altitude over farmland often encounter three major difficulties: unreliable recognition of distant small obstacles, unstable localization of elongated targets, and strong interference from cluttered backgrounds. To cope with these challenges, this work introduces a lightweight real-time obstacle detection framework by redesigning YOLOv8n for farmland scenes. In the backbone, SPD-Conv, retained high-resolution $$\:{P}_{2}$$ features, and the DGA-C2f module are jointly used to preserve fine-grained cues for small and slender obstacles. In the feature aggregation stage, a lightweight scale-difference fusion network is constructed, where the LSDF module is embedded into a bidirectional interaction scheme to strengthen cross-level feature collaboration. In the prediction stage, a direction-aware decoupled head is adopted so that orientation modeling can assist localization and improve the regression quality of elongated targets. Experiments on a self-built farmland obstacle dataset show that the resulting model reaches 89.3% Precision, 88.0% Recall, 91.8% mAP@0.5, and 85.0% mAP@0.5:0.95. Compared with YOLOv8n, the proposed model improves Precision, Recall, mAP@0.5, and mAP@0.5:0.95 by 1.5, 1.8, 2.4, and 2.3% points, respectively. It also maintains real-time inference performance with appropriate parameters, 8.9 GFLOPs, and 123 FPS, demonstrating a clear balance among detection accuracy, lightweight complexity, and deployment efficiency for farmland obstacle perception.
Substituent-rebound skeletal editing for precise boron-to-carbon single-atom swapping
Abstract Developing methods that enable single-atom exchange within an aromatic scaffold, while preserving its peripheral substitution, represents an important but highly ambitious goal in synthesis. In principle, such approaches would allow the impact of a single-atom change within a molecular framework to be distinguished from the effects of also altering the peripheral substituents. Yet despite this conceptual power, single-step methodologies for single-atom exchange in aromatic systems remain rare. Herein, we present a boron-to-carbon swapping reaction via a substituent-rebound process, converting 1,2-benzazaborines into the corresponding quinolines. The employment of glyoxylic acid as the carbon-atom source allows the original substituent on the boron atom to be recaptured and incorporated into the quinoline product, representing a rare example of true single-atom skeletal editing. The transformation exhibits high levels of functional group tolerance and is applicable to the late-stage modifications of natural product and pharmaceutical derivatives. Furthermore, comprehensive mechanistic investigations elucidate the intricacies of this process, establishing a foundation for future single-atom editing manifolds that can facilitate the interrogation of structure–function relationships with atom-level precision.
Computational investigation of metal doped coronene for acetophenone adsorption and sensing in wastewater treatment
Abstract Acetophenone (ACT) is a persistent organic pollutant in industrial wastewaters that poses serious risks to human health and the environment. In this study, we evaluated pristine coronene (CRO) and its aluminum- and zinc-doped forms (Al-CRO and Zn-CRO) as adsorbents and potential colorimetric/electrochemical sensing platforms for ACT using B97D/6-31G(d), B97D/LANL2DZ, and ωB97XD/6-31G(d). Statistical comparisons based on mean absolute deviation, root mean square deviation, and Pearson correlation coefficient confirmed the consistency of the main qualitative results at computational levels. Adsorption energy, electronic properties, optical response, and interaction mechanisms were examined using density functional theory (DFT), time-dependent DFT (TD-DFT), quantum theory of atoms in molecules (QTAIM), and NBO, NCI, and ELF/LOL analyses. QTAIM, NCI/RDG, and ELF/LOL analyses consistently identified weak physisorption in CRO@ACT, predominantly noncovalent adsorption with a localized Zn-O contribution in Zn-CRO@ACT, and a strong polarized coordination-type interaction in Al-CRO@ACT. Al-CRO exhibits strong charge-transfer-assisted, coordination-type adsorption, with Eads values from − 47.52 to -48.73 kcal.mol − 1 , accompanied by a reduced HOMO-LUMO gap and a predicted shift in the absorption maximum from 391 to 596 nm upon ACT binding. These results identify Al-CRO as a candidate for strong ACT adsorption/removal and for disposable adsorption-coupled colorimetric/electrochemical sensing due to its extremely long recovery time. Also, according to the theoretical results, Zn-CRO with Eads values from − 10.64 to -12.40 kcal.mol − 1 and faster desorption than Al-CRO (which may facilitate regeneration), along with a shift in the absorption wavelength from 346 to 410 (in the presence of ACT), is a candidate for experimental evaluation in the future.
ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH
Comparative investigation on dry sliding wear behaviour of L-PBF printed tool steel for stamping dies
DICER1-related tumour predisposition mutations increase 3p-miRNA function and HERVH activity
Abstract The DICER1 gene is mutated in cancer, including in DICER1 -related tumour predisposition. Cancer-associated hotspot mutations have been reported in both catalytic domains of DICER and are predicted to disrupt miRNA biogenesis. To understand how these hotspot mutations contribute to cancer development, we generate cell lines harbouring single amino acid substitutions within the catalytic RNase IIIa (S1344L) or RNase IIIb (D1709N) domains of the endogenous DICER1 gene. Here we show that both mutations result in a widespread loss of 5p miRNAs, and an increase in 3p passenger strands loading into AGO2. The shared similarities between both mutants can be attributed to the structural proximity of the S1344 residue to the RNase IIIb catalytic centre. Functionally, we find that changes in the repertoire of miRNAs loaded into AGO2 result in altered gene expression, impacting critical pathways for cancer development. Additionally, our results indicate that inactivating the processing activity of DICER does not result in genomic instability. Instead, mutations cause upregulation of transposable elements, including the human endogenous retrovirus H through miRNA-independent mechanisms. This suggests that both canonical and non-canonical DICER functions are important to understand DICER1 -related tumour predisposition.
Neutrino mass predictions with metaheuristic optimization under $$A_4$$ modular symmetry
Core–sheath coupling controls flagellar curvature and motility in Leptospira
Abstract Spirochaete pathogens are among the most invasive bacteria known, causing syphilis, Lyme disease, and leptospirosis. Their tissue penetration depends on periplasmic flagellar filaments that, unlike other bacterial flagella, are encased in a spirochaete-specific multi-protein sheath and deform the cell body into motile waves. How these filaments achieve the mechanical properties needed for invasive motility has remained unclear. Here we determine complete atomic structures of the Leptospira endoflagellar filament, revealing an elaborate sheath of 9 to 12 distinct asymmetrically arranged proteins. We show that the flagellin variant forming the filament core determines sheath composition, producing curvatures ranging from ~3.5 µm −1 to ~5.6 µm −1 . The lower-curvature architecture, employed by pathogenic Leptospira interrogans , proves essential for motility in viscous environments and during infection. Thus, Leptospira achieves environment-specific motility through modular core–sheath coupling, linking atomic-scale structural plasticity to large-scale changes in swimming behaviour. Conservation of key sheath components suggests this mechanism may extend across spirochaetes.
Deep learning-based adaptive recommendation algorithm for personalized music teaching
Anchoring mechanism-inspired discovery of a bacterial P450 gene conferring resistance to auxin herbicides
Sulfonic acid-functionalized chitosan-Fe3O4/covalent triazine framework as an efficient and reusable magnetic nano-catalyst for fructose conversion into 5-hydroxymethylfurfural
Three-dimensional distribution of amino groups improves perovskite crystallization and defect passivation in high-performance photovoltaics
Abstract Incorporating organic molecules with diverse functional groups to improve film quality has emerged as a crucial strategy for realizing high-performance perovskite solar cells (PSCs). Nevertheless, the role of spatial distribution of those functional groups in governing passivation efficacy and perovskite crystallization remains insufficiently investigated. Here, we introduce three amino-containing molecules, bis(4-aminophenyl)methane (2APM), tris(4-aminophenyl)methane (3APM) and tetrakis(4-aminophenyl)methane (4APM), featuring distinct spatial distributions of amino groups, into the perovskite precursor solution as in-situ regulators. Among them, 4APM exhibits the strongest interactions with PbI 2 and formamidinium iodide (FAI) by virtue of its three-dimensional (3D) distribution of amino groups, most effectively suppressing undercoordinated Pb 2+ defects and enhancing perovskite film crystallinity. As a result, PSCs incorporating 4APM achieve a stabilized power conversion efficiency (PCE) of 26.26%, while retaining over 95% of their initial efficiency after 1000 h of continuous operation at maximum power point under 1-sun illumination in a N 2 atmosphere at 65 °C. Furthermore, 4APM-based perovskite solar modules (PSMs) with an active area of 14.0 cm 2 deliver a PCE of 23.16%. Our findings underscore the critical role of functional group’s spatial distribution in the rational design of molecular passivators for perovskite photovoltaics.
Greenness challenge: a game based learning approach for sustainable analytical chemistry education
Trdn-as directs m6A-dependent transcriptional termination for accurate triadin isoform switching, preventing aberrant dyads and cardiomyopathy
Abstract Heart failure is a leading cause of mortality, and impaired cardiac excitation-contraction coupling represents a potentially fatal trigger for myocardial dysfunction. Long non-coding RNAs (lncRNAs) can contribute to cardiomyopathy, but comprehensive mechanistic insights remain elusive. We demonstrate that reduction of the lncRNA TRDN-AS in human cardiomyopathy or abrogating it in human iPSC-derived cardiomyocytes and mice causes a switch of cardiac TRDN/TRISK32 to skeletal muscle TRDN/TRISK95. Transcription of Trdn-as in cis is essential for stalling RNA Pol II at the 3’ end of the cardiac Trdn transcript, promoting the formation of the cardiac TRDN/TRISK32 isoform. The m6A-methyltransferase METTL3 is crucial for RNA Pol II stalling, enforcing transcriptional termination and proximal polyadenylation of the Trdn transcript. Here, we establish that the switch of TRDN isoforms results in a significantly altered interactome of the cardiac calcium release complex, aberrant calcium handling, altered dyad structure, QT prolongation, and dilated cardiomyopathy in mice and humans.
Association of trajectories and cumulative exposure of modified cardiometabolic index with cardiovascular disease in middle and older adults
Hyperloss from coherent spatial-mode mixing in quantum-correlated networks
Abstract Quantum-correlated networks distribute quantum resources such as squeezed and entangled states. They are central to modern quantum technology, including photonic quantum computing, quantum communications, biological sensing and gravitational-wave detection. Even for squeezed light — the most robust quantum-correlated resource — loss-induced decoherence remains the dominant obstacle to strong quantum advantage. A common design assumption is that spatial-mode mismatch acts as an incoherent loss. Coherent spatial-mode mixing with higher-order modes, however, can produce an apparent loss exceeding the full initial squeezing, a regime we term hyperloss. Here, we show experimentally that a minimal two-node network exhibits hyperloss, with 8 per cent mode mismatch converting 5.8 decibels of observable squeezing into an effectively thermal state, and that the lost correlations can be recovered by tuning differential spatial-mode phases, establishing hyperloss as a practical design constraint for future quantum technologies.