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Therapist-guided virtual reality exposure therapy for fear of heights: evidence from a multiple-baseline single-case experimental design
Intercellular chemerin-cmklr1 couples epicardial mechanosensing to fibroblasts in pressure overload
Importance of the delivery route for the tolerability and efficacy of immunomodulatory agents for lung cancer
Abstract Although immune checkpoint inhibitors have revolutionized lung cancer treatment, their limited efficacy and significant toxicity highlight the need for improved therapeutic strategies. Immunomodulatory agents are known to enhance anti-tumor immune responses. In this study, we investigated how the route of administration affects the tolerability and immunological impact of these immunostimulants. We demonstrate that airway administration of poly I: C, CpG, and an anti-CD137 antibody in healthy mice results in significantly reduced liver toxicity and systemic inflammation compared with intravenous delivery. This was evidenced by lower AST levels, preserved body weight, and a reduced neutrophil-to-lymphocyte ratio. In addition, airway delivery of immunostimulant promoted dose-dependent recruitment of both myeloid and lymphoid cells as compared to intravenous administration. Using a syngeneic orthotopic mouse model of lung carcinoma, we further showed that local airway administration of anti-CD137 antibody resulted in increased pulmonary infiltration of CD4⁺, CD8⁺, and CD4⁺ TRM cells compared with intravenous injection. This enhanced immune infiltration correlated with improved tumor control. Overall, our findings indicate that local administration of immunostimulants enhances pulmonary adaptive immune responses and tumor suppression while limiting systemic toxicity.
Notch coordinates self-organization of germ layers and axial polarity in sea anemone gastruloids
Abstract Reaggregated early gastrula cells (“gastruloids”) of the sea anemone Nematostella vectensis are able to regenerate into whole polyps within a few days. However, the cellular and molecular mechanisms underlying restoration of body axis and germ layers remains largely unknown. Here, we show that mesodermal cells sort to the periphery of the gastruloid, where they form cell clusters with hitchhiking endodermal cells. One of these clusters immigrates at one pole, forming the future pharynx and inner layer. This morphogenetic behavior that enables the symmetry break of the organizer tissue, requires a Wnt-Notch signaling feedback loop. This highlights a hitherto unknown role of Notch signaling in self-organizing gastruloids. Conservation of Notch-mediated boundary formation between germ layers mirrors similar mechanisms in bilaterians. This demonstrates how adoption of ancestral regulatory networks enables a morphospace converging to similar body plans, thus contributing to evolutionary robustness.
Deep homography-based image stitching with enhanced small object detection
Behavioral correlates of Purkinje cell ensemble covariance
High-value biochar from sunflower husk pyrolysis enhances growth and physiological performance of Spirodela polyrhiza
A continental-scale Eurasian ice sheet 2.4 million years ago
Benchmarking deep learning models for laryngeal cancer staging using the LaryngealCT dataset
Abstract Laryngeal cancer imaging research lacks standardised public datasets to enable reproducible deep learning (DL) model development. We present LaryngealCT, a curated benchmark of 1,029 computed tomography (CT) scans aggregated from six collections from The Cancer Imaging Archive (TCIA). Uniform 1 mm isotropic volumes of interest encompassing the larynx were extracted using a weakly supervised parameter search framework validated by clinical experts. Six 3D DL architectures (custom 3D CNN, ResNet18/50/101, DenseNet121 and MedicalNet-pretrained ResNet50) were benchmarked on (i) early (Tis–T2) vs. advanced (T3–T4) and (ii) T4 vs. non-T4 classification tasks. On the independent test set, the 3D CNN achieved the strongest overall performance across global and per-class metrics (Accuracy = 0.854, F1-macro = 0.841) in early vs. advanced classification. In the T4 task, AU-ROC values exceeded 0.82 for most models, but sensitivity for T4 disease remained limited (≤ 0.412), with ResNet101 showing the most promising calibrated T4 recall (0.706). Model explainability assessed using GradCAM ++ with thyroid cartilage overlays for the T4 classification task revealed anatomically plausible peri-cartilage activations although spatial overlap remained modest. Through open-source data, pretrained models, and integrated explainability tools, LaryngealCT offers a reproducible foundation for AI-driven research to support future clinical decision-making in laryngeal oncology.
Safety and efficacy analysis of in vivo lentiviral gene therapy in pre-clinical ARC syndrome models
Abstract Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a rare inherited disorder caused by defects in the VPS33B trafficking protein, leading to impaired bile flow, progressive liver disease and early death. No effective treatments are currently available. Gene therapy offers a potential approach by restoring the missing VPS33B protein in liver cells. Here, we show that liver-targeted lentiviral gene therapy safely and effectively rescues key features of ARC syndrome in a mouse model following in vivo administration by intravenous injection, combined with transient liver macrophage depletion. To assess the treatment efficacy, disease severity is exacerbated by 0.25% cholic acid diet feeds. A liver-specific vector shows a favourable safety profile over a ubiquitous vector. Mice receiving the safe liver-specific vector display improved survival, growth and liver function, reduced fibrosis and bile canaliculi restoration. These findings support targeted gene therapy as a promising treatment for ARC syndrome and related early-onset liver diseases.
Comprehensive assessment of fragmented fiber shedding from recycled cotton textiles. Part III integrated qualitative and quantitative assessment of released fibers and particles from woven textiles
Ultranarrow nanochannels in a staggered two-dimensional polymer membrane enhance electric double-layer coverage for osmotic energy harvesting
Abstract Two-dimensional framework membranes (2DFMs) hold great promise for sustainable energy-harvesting technologies, yet their performance is often limited by low electric double-layer (EDL) coverage ( ƞ EDL ) arising from large channels and/or low charge densities. Here, we report an ultrathin ( ~ 50 nm), fully crystalline, ABC-stacked viologen-incorporated 2D polymer membrane (sV2DP) featuring vertically aligned triangular nanochannels ( D eff = 1.36 nm) densely decorated with pyridinium sites ( + 22.4 mC m −2 ). Compared with its non-staggered AA-stacked analogue, sV2DP exhibits a 3.2-fold enhancement in ƞ EDL under a 50-fold KCl gradient, combining high anionic selectivity ( t − = 0.85) with remarkable selective current density (14.6 kA m −2 ). Simulations reveal that spirally arranged charges generate a unique “screw-like” anion migration pathway, significantly enhancing transmembrane efficiency relative to non-staggered 2DP analogues. When integrated into micro-aperture osmotic power generators, the sV2DP membrane delivered a peak power density of 243 W m −2 under a 50-fold NaCl gradient, placing it among the highest-performing systems.
Integrated metabolomics, transcriptional, and physicochemical analysis reveals key metabolites and genes associated with somatic embryogenesis in Phyllostachys pubescens
Engineered halohydrin dehalogenase mediates remote enantiocontrolled dehalogenative hydroxylation via an unconventional mechanism
A novel therapeutic strategy against gastric carcinoma: artemisia sieberi-derived biogenic zno nanoparticles inducing intrinsic apoptosis and suppressing AGS cell proliferation
Abstract Gastric carcinoma remains a major cause of cancer-related mortality worldwide, underscoring the need for alternative therapeutic strategies. Zinc oxide nanoparticles (ZnO NPs) have attracted attention in cancer research due to their ability to generate reactive oxygen species (ROS), relative cost-effectiveness, and suitability for green synthesis approaches. In this study, ZnO NPs were synthesized via an eco-friendly biogenic method using Artemisia sieberi , and their anticancer-related effects were evaluated in vitro. ZnO nanoparticles were synthesized using an aqueous extract of Artemisia sieberi and characterized by FE-SEM, DLS, EDS, and XRD. Their biological effects were investigated in human gastric adenocarcinoma (AGS) cells and normal human embryonic kidney (HEK-293) cells. Cytotoxicity was assessed using the MTT assay, apoptosis by flow cytometry, cell migration by a wound healing assay, and gene expression by qRT-PCR. Statistical analysis was performed using one-way ANOVA, with p < 0.05 considered significant. Physicochemical characterization confirmed the formation of spherical to polyhedral ZnO nanoparticles with sizes ranging from 37 to 122 nm. The nanoparticles exhibited concentration-dependent cytotoxicity in AGS cells, with an IC₅₀ of approximately 480 µg/mL, compared to an IC₅₀ of approximately 1250 µg/mL in HEK-293 cells, corresponding to a modest selectivity index (~ 2.6). Flow cytometric analysis demonstrated increased apoptosis in AGS cells, with up to 61.6% apoptotic cells observed at the highest concentration. In addition, ZnO NPs significantly inhibited cancer cell migration. Molecular analysis revealed significant upregulation of p53 , Caspase-9 , and Caspase-3 , suggesting activation of the intrinsic mitochondrial apoptotic pathway. The findings indicate that Artemisia sieberi -derived ZnO nanoparticles can induce apoptosis and inhibit migration in gastric cancer cells in vitro, potentially through a p53-mediated mitochondrial mechanism. Although the observed selectivity toward cancer cells was limited, these results support the preliminary potential of biogenically synthesized ZnO nanoparticles as candidates for further investigation. Additional studies, including in vivo models and broader mechanistic analyses, are required to clarify their therapeutic relevance.
Entropy-driven order-to-disorder transition in perovskite anodes for high-performance solid oxide fuel cells
Abstract Solid oxide fuel cells (SOFCs) enable direct and efficient conversion of transportable hydrocarbons into electricity, offering a scalable pathway for carbon-neutral energy systems. A critical challenge in SOFC development lies in the atomic-scale structural regulation of perovskite-type anodes, which is essential for enhancing hydrocarbon oxidation kinetics while mitigating carbon deposition issues. To overcome this fundamental limitation, we propose an entropy-driven strategy to induce order-to-disorder transitions in perovskite oxides. This strategy is demonstrated in the layered ordered perovskite PrBaFe 2 O 5+δ , where the introduction of five equimolar rare-earth cations at the Pr site results in the formation of a disordered A-site high-entropy perovskite anode with the composition La 0.2 Pr 0.2 Sm 0.2 Gd 0.2 Y 0.2 BaFe 2 O 5+δ (HEP). Such atomic-scale order-to-disorder transitions facilitate oxygen vacancy formation and improve anode hydration capacity, thereby accelerating both hydrocarbon steam reforming and carbon elimination processes. The designed HEP anode exhibits a peak power density of 774.53 mW·cm –2 and stability over 1000 hours under wet methane (3 vol% H 2 O) at 700 °C. The present work contributes a new strategy for controlling ion ordering in perovskite oxides, addressing key challenges in SOFC operating with hydrocarbon fuels.
CWD prions are present in the blood of healthy-appearing, naturally infected free-ranging white-tailed deer
Impact of the local valley splitting on the coherence of conveyor-belt spin shuttling in 28Si/SiGe
Abstract Electron spins in silicon offer a promising path toward scalable, fault-tolerant quantum computing, with the potential to host millions of qubits. However, scaling up dense quantum-dot arrays and enabling qubit interconnections through shuttling are hindered by uncontrolled lateral variations of the valley splitting energy E VS . We map E VS across a 40 nm × 400 nm region of a 28 Si/Si 0.7 Ge 0.3 shuttle device and analyze the spin coherence of a single electron spin transported by conveyor-belt shuttling. We observe that the E VS varies over a wide range from 1.5 μeV to 200 μeV and is dominated by SiGe alloy disorder. In regions of low E VS and at spin-valley resonances, spin coherence is reduced and its dependence on shuttle velocity matches predictions. Rapid and frequent traversal of low- E VS regions induces a regime of enhanced spin coherence explained by motional narrowing. By selecting shuttle trajectories that avoid problematic areas on the E VS map, we achieve transport over tens of microns with coherence limited by the coupling to a static electron spin entangled with the mobile qubit. Our results provide experimental confirmation of the theory of spin decoherence of mobile electron spin-qubits and present practical strategies to integrate conveyor-mode qubit shuttling into silicon quantum chips.
Magnetorheological phase-change McKibben actuators for frequency-controlled actuation and high force output
Abstract State-of-the-art soft robots face a critical trade-off: high-performance pneumatic actuators require bulky external compressors, whereas emerging smart-material actuators often lack sufficient force output. Here, we present a magnetorheological elastomer (MRE)-based phase-change McKibben actuator actuated via induction heating. The inclusion of ferromagnetic particles contributes to improved force output and thermal response of the elastomeric matrix. Furthermore, the design enables wireless operation, where the induction coil’s excitation frequency directly regulates the electromagnetic heating and actuation timing. A multiphysics modeling framework, integrating finite element electromagnetic analysis with analytical fluid-pressurization and structural models, guides the actuator design. Prototypes operating at 127 kHz and 150 kHz are fabricated and tested. They produce up to 70 N blocked force at a 23 g mass, representing an increase over prior phase-change actuators. The force output is 48% higher, with faster heating and cooling times compared to identically dimensioned hyperelastic actuators. Increasing the induction frequency to 150 kHz reduces the time to reach a 35 N load by nearly 25%. With heating times of 10–20 s and wireless operation, this actuator represents a promising platform for lightweight soft robotic systems.
Koopman global linearization of contact dynamics for robot locomotion and manipulation enables elaborate control
Abstract Controlling robots that dynamically engage in contact with their environment is a pressing challenge. Whether a legged robot making-and-breaking contact with a floor, or a manipulator grasping objects, contact is everywhere. Unfortunately, the switching of dynamics at contact boundaries makes control difficult. Predictive controllers face non-convex optimization problems when contact is involved. Here, we overcome this difficulty by applying Koopman operators to subsume the segmented dynamics due to contact changes into a unified, globally-linear model in an embedding space. We show that viscoelastic contact at robot-environment interactions underpins the use of Koopman operators. This methodology enables the convex Model Predictive Control of a legged robot, and the real-time control of a manipulator engaged in dynamic pushing. In this work, we show that our method allows robots to discover elaborate control strategies in real-time over time horizons with multiple contact changes, and the method is applicable to broad fields beyond robotics.