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Resonant and non-resonant driving of linearly-polarized excitons in Cd3P2 magic-size clusters
DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB.
Abstract Neuroinflammation is a major pathogenic mechanism underlying neurodegenerative diseases. Understanding how neuroinflammation is regulated is critical to therapeutic development. Here, we report that dynaminrelated protein 1 (DRP1), well-recognized for its role in mitochondrial fission, also functions as a transcription factor that regulates neuroinflammation. Using multiple inflammatory models, we demonstrate that upon stimulation with pro-inflammatory lipopolysaccharides (LPS), DRP1 translocates from the cytosol to the nucleus, where it binds to the promoter region of Rela (encoding NF-κB p65) to activate its gene products and other downstream inflammatory cytokines. Our data further reveal a significant role of the proinflammatory lipocalin-2 in the brain. In combination, this study identifies a previously unrecognized function of DRP1 in mediating neuroinflammation via the NF-κB-lipocalin-2 axis and highlights DRP1-mediated pathways as potential therapeutic targets for neurodegenerative and other inflammation-related diseases.
Illuminating cell states by a comprehensive and interpretable single cell foundation model
Durvalumab and cediranib with and without olaparib in recurrent ovarian cancer: a phase II proof-of-concept study
Abstract Here we report the efficacy and translational findings of durvalumab, olaparib, and cediranib (D + O + C) and of durvalumab plus cediranib (D + C) from the recurrent ovarian cancer cohort within a single-center, multi-arm, non-randomized, multi-cohort phase I/II trial (NCT02484404). Sixty-eight patients were enrolled (39 in D + O + C, 29 in D + C). The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. ORR was 19.4% (95% CI, 9.5-43.5) for D + O + C and 29.6% (95% CI, 13.8-46.9) for D + C; D + C met the primary endpoint while D + O + C did not. Median PFS was 4.5 months in both arms, with four exceptional responders (PFS ≥ 12 months) per arm. Toxicity was manageable. Pre- and on-treatment biopsies and blood samples were collected for prespecified transcriptomic and immunophenotypic profiling; signature analyses and preclinical studies were conducted post hoc and were exploratory. Baseline tumors from exceptional responders and patients with clinical benefit (partial response or stable disease with PFS ≥ 4 months) demonstrated enrichment of immune activation and metabolic pathways, whereas tumors with no clinical benefit (NCB; progressive disease or stable disease with PFS < 4 months) exhibited upregulation of vascular adaptation and cytoskeletal remodeling pathways. These findings support the proof-of-concept clinical activity of D + O + C and D + C and identify molecular signatures with potential predictive value in subsets of recurrent ovarian cancer.
Light-programmable mechanical computing via polyaniline composite film
Abstract Mechanical computing represents a highly promising paradigm for environment-adaptive information processing. However, existing implementations are generally constrained by limited architectural scalability, and their modes of application in practical scenarios remain insufficiently defined. Here, we develop a light-programmable mechanical computing system that not only performs scalable logic operations but also enables environment-adaptive optical camouflage. The system is based on a polyaniline composite film (PCF) that integrates light-responsive expansion–contraction elements with a flexible conductive layer. Light illumination dynamically modulates the conductive pathways, giving rise to optically controlled single-pole single-throw (SPST) and single-pole double-throw (SPDT) relays that reconfigure signal transmission routes. Interconnecting these relays enables the construction of basic logic gates and 2-bit full-adder circuits, establishing a scalable paradigm for light-programmable mechanical computation. Moreover, we implement an adaptive camouflage function that senses environmental textures and generates matching optical patterns, demonstrating potential for intelligent skin applications capable of environmental interaction. This work establishes a light-programmable, pathway-reconfigurable mechanical computing framework, expanding possibilities for autonomous and adaptive intelligent systems.
Bridging the latency gap with a continuous stream evaluation framework in event-driven perception
Large megathrust earthquakes in cold mantle wedge corners under lawsonite blueschist facies
Conditional survival rates after neoadjuvant chemoradiotherapy combined with surgery in intermediate-low locally advanced rectal cancer based on two-centre retrospective analysis
Semantic similarity across languages reflects neurocognitive dimensions shaped by climate
Abstract Human languages differ widely, yet they share systematic regularities in the underlying semantic representations being expressed. How such similarities and differences arise remains unclear, in part because semantic theories often lack a principled link to neurocognitive constraints. Drawing on neurocognitive accounts in which semantic knowledge is grounded in biologically salient information dimensions, we examine how environmental factors shape conceptual representations in language. Here we show that word meanings across languages are organized along shared neurocognitive dimensions, while systematic variation along these dimensions is associated with climate. Using word embeddings from 53 languages and behavioral ratings from speakers of 8 languages, we find converging evidence that climatic variables explain semantic variation beyond commonly considered sociocultural factors. Complementary exploratory brain data further suggest climate-related modulation of activity patterns in the right anterior temporal lobe. Together, these findings indicate that semantic representations in language reflect biologically grounded dimensions that are flexibly shaped by long-term environmental conditions.
Frontispiece: Spatial Mapping of Membrane Protein Interactions Using a DNA Origami Rubbing
Single-cell and bulk transcriptomic analyses uncover immune subtypes associated with programmed cell death features in intrahepatic cholangiocarcinoma
Prediction of thermally driven quasi-1D superionic states in carbon hydride under giant planetary conditions
Adaptive state-feedback echo state networks for temporal sequence learning
Abstract Echo State Networks are recurrent neural networks that leverage a random reservoir’s dynamics, training only a simple readout layer. This approach is computationally efficient but limits network performance. By introducing state or output-feedback connections, the reservoir dynamics can be shaped to enhance the network’s ability to capture complex temporal dependencies. Here we propose AFRICO (Adaptive Feedback, Readout and Input with Connectivity Optimisation), a novel training framework for Echo State Networks that adapts input and state-feedback weights via an Extended Kalman Filter, followed by optimisation of a sparse readout layer that selectively connects reservoir states to the output. The key novelty lies in jointly adapting input and state-feedback pathways to shape reservoir dynamics, while separately constructing a sparse task-specific readout. This approach enables the Echo State Network to capture both the internal dynamics and output mapping of the target system. We evaluate AFRICO on synthetic linear and nonlinear systems, as well as in vivo electrophysiological recordings from fly photoreceptors, demonstrating its versatility for general-purpose input–output time-series modelling across both engineering and biological domains. Across varied hyperparameter initialisations, AFRICO achieves up to 88% reduction in Normalised Mean Squared Error compared to Echo State Networks with fixed output-feedback, while maintaining modest computational effort relative to fully trained Recurrent Neural Networks.
Structural basis of lipid-linked galactan export by the mycobacterial ABC transporter Wzm-Wzt
Abstract Mycobacteria, including Mycobacterium tuberculosis , possess a unique cell envelope containing arabinogalactan, a heteropolysaccharide critical for cell wall integrity and target of several tuberculosis drugs. The cytosolic precursor of arabinogalactan, lipid-linked galactan (LLG), is translocated across the plasma membrane by the essential ABC transporter Wzm-Wzt through a molecular mechanism that is poorly understood. Here, we present a series of cryo-EM structures of Wzm-Wzt from Mycobacterium abscessus , representing different conformations of the transport cycle. Conserved residues lining the proposed LLG translocation pathway were investigated by three orthologous functional assays, revealing that the cytosolic gate helix (GH) plays a key functional role in polysaccharide transport. Our data suggests that the hydrophobic polyprenyl-moiety is translocated first, followed by the galactan-polysaccharide, which requires Wzm-Wzt to open a continuous channel through which the sugar chain is ratcheted at the expense of ATP hydrolysis. Our results provide a rational basis for the development of drugs that inhibit mycobacterial cell wall biosynthesis.
Physiological medium and 3-hydroxybutyrate modulate autophagy-linked organelle remodeling in human external urethral sphincter myoblasts
Abstract Autophagy-linked organelle remodeling is essential for skeletal muscle differentiation and is closely linked to the metabolic environment. The ketone body 3-hydroxybutyrate (3HB) serves as an alternative energy substrate and signaling molecule that modulates organelle function and myogenic programs. This study investigated how extracellular metabolic conditions and 3HB regulate autophagy-linked organelle remodeling in human external urethral sphincter (hEUS) myoblasts. Immortalized hEUS myoblasts (US2-KD) were differentiated under four conditions combining high-glucose Dulbecco’s modified Eagle’s medium (HG-DMEM) or low-glucose physiologically formulated minimum essential medium (LG-MEM) with or without 3HB. Metabolomic profiling revealed that the medium composition predominantly shaped energy and amino acid pathways, whereas 3HB induced subtler, context-dependent shifts in metabolites related to autophagy and mitochondrial function. At the cellular level, LG-MEM accelerated myogenic differentiation compared to HG-DMEM, with earlier induction of MYOG and MYH7 and faster maturation of myotubes. LG-MEM also altered LC3B expression patterns, while transmission electron microscopy showed fewer excess autophagosomes and autolysosomes along with more prominent myofibril-like ultrastructure, consistent with more efficient autophagic activity and organelle remodeling. These findings suggest that a physiological metabolic environment facilitates autophagy-linked organelle remodeling in hEUS myoblasts and that 3HB acts as a fine-tuning signal, potentially supporting metabolism-oriented approaches for stress urinary incontinence.