❌

Normal view

Inhalable carrier-free self-assembled leonurine-ursolic acid nanoaggregates ameliorate acute lung injury by suppressing TLR4/MyD88-NET axis

Mater Today Bio. 2026 Aug 18;40:103583. doi: 10.1016/j.mtbio.2026.103583. eCollection 2026 Oct.

ABSTRACT

TLR4 activation and the cascade of neutrophil extracellular trap (NET) formation exacerbate excessive inflammation and organ damage in the pathogenesis of acute lung injury (ALI), yet effective pharmacological interventions remain unavailable. Nanoaggregates derived from natural products offer promising avenue by leveraging synergistic anti-inflammatory effects. In this study, we surprisingly discovered that leonurine and ursolic acid spontaneously self-assemble into nanoparticles (LUNP) through non-covalent interactions, achieving a drug loading capacity of 100%. The LUNP platform exhibits superior biophysical properties, including enhanced mucus penetration, pH-responsive drug release, improved cellular uptake, and prolonged retention within inflamed lung tissue. Mechanistically, LUNP ameliorates ALI by dampening TLR4/MyD88/NF-κB-driven inflammatory activation, thereby remodeling the microenvironment to limit NOX4-PAD4-mediated NET formation. Notably, inhalational LUNP exhibits outstanding biosafety with minimal off-target distribution. Overall, this work introduces a synergistic self-assembled nanoplatform for precise pulmonary intervention in ALI, showcasing its ability to safely and effectively orchestrate the coordinated modulation of multiple pathological pathways. In summary, by inhibiting both TLR4 activation and NET formation, the synergistic LUNP platform offers an efficient, safe, and easily accessible therapeutic strategy for ALI, providing a promising solution for clinical translation.

PMID:42750707 | PMC:PMC13577835 | DOI:10.1016/j.mtbio.2026.103583

VBVR-Pro: A Scalable and Verifiable Suite for Native Visual Reasoning

arXiv:2608.26105v2 Announce Type: replace-cross Abstract: Native visual reasoning treats visual generation as the medium of reasoning itself: visual states (i.e. images and videos) are not merely inputs to be understood or outputs to be rendered, but first-class substrates for problem solving beyond language. Yet progress remains bottlenecked by the lack of scalable training tasks, reliable feedback, and controlled comparisons across generative substrates. In this work, we introduce VBVR-Pro, a closed-loop testbed that makes native visual reasoning through generation trainable, verifiable, optimizable, and experimentally controllable. 1) Task scaling. VBVR-Pro turns visual reasoning into a controlled task space of 300 procedurally generated tasks. Models trained on VBVR-Pro show strong transfer beyond the proposed suite across seven external visual reasoning benchmarks such as RISE-Video, MME-CoF-Pro, and BabyVision. 2) Verifiable rewards. VBVR-Pro provides verifiable reward scorers for task-grounded evaluation. Through a systematic study of leading MLLMs as judges, we identify recurring failure modes of the prevalent VLM-as-a-judge paradigm. In contrast, the proposed scorers are grounded in deterministic, task-specific rules, achieve fine-grained alignment with human judgments. Importantly, they serve as reliable reward signals for large-scale multi-task reinforcement learning and demonstrate stronger post-RL performance across visual reasoning tasks. 3) Mechanism study. VBVR-Pro enables controlled modality studies across more than 30 image, video, and interleaved generators. Our analysis shows that video generation remains strongest for tasks requiring persistent spatiotemporal state tracking, while interleaved generation provides a compute-efficient alternative. Critically, ablations and probing suggest the presence of vision-native trajectories that are crucial to visual reasoning. We release all data, models, scorers, and code.

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. Objective: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. Methods: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the ² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] −4.52, 95% CI −8.38 to −0.67, PI −9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%‐2.11%, PI 1.85%‐2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98‐35.24, PI −16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (=.07). Certainty of evidence ranged from moderate to high. Conclusions: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base. Trial Registration: PROSPERO CRD420251038603; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251038603

A SAUR gene enhances maize drought resilience by promoting silk elongation

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10566-9

The Small Auxin Up RNA (SAUR) protein ZmSAUR72 in maize (Zea mays) promotes silk growth via regulation of H+-ATPase activity, and is a key determinant of the anthesis-silking interval and thus resilience to drought.

Improving Safety Alignment via Balanced Direct Preference Optimization

arXiv:2603.22829v1 Announce Type: new Abstract: With the rapid development and widespread application of Large Language Models (LLMs), their potential safety risks have attracted widespread attention. Reinforcement Learning from Human Feedback (RLHF) has been adopted to enhance the safety performance of LLMs. As a simple and effective alternative to RLHF, Direct Preference Optimization (DPO) is widely used for safety alignment. However, safety alignment still suffers from severe overfitting, which limits its actual performance. This paper revisits the overfitting phenomenon from the perspective of the model's comprehension of the training data. We find that the Imbalanced Preference Comprehension phenomenon exists between responses in preference pairs, which compromises the model's safety performance. To address this, we propose Balanced Direct Preference Optimization (B-DPO), which adaptively modulates optimization strength between preferred and dispreferred responses based on mutual information. A series of experimental results show that B-DPO can enhance the safety capability while maintaining the competitive general capabilities of LLMs on various mainstream benchmarks compared to state-of-the-art methods. \color{red}{Warning: This paper contains examples of harmful texts, and reader discretion is recommended.

A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk

J Int Med Res. 2026 Mar;54(3):3000605261430163. doi: 10.1177/03000605261430163. Epub 2026 Mar 16.

ABSTRACT

ObjectiveTo explore the potential involvement of PANoptosis-related genes in gastric cancer susceptibility through multiomics analyses.MethodsSummary-data-based Mendelian randomization was performed by integrating blood-derived methylation, gene expression, and protein quantitative trait loci data with genome-wide association study results. The findings were further evaluated in The Cancer Genome Atlas cohort, followed by protein-protein interaction analysis, drug prediction, and molecular docking.ResultsSummary-data-based Mendelian randomization and colocalization analyses identified several traits suggestively associated with gastric cancer risk. Genetically predicted higher expression of apoptosis and caspase activation inhibitor (AVEN) and hepatocyte growth factor (HGF) as well as higher HGF protein levels were associated with increased risk, whereas higher levels of protein phosphatase 2 regulatory subunit B beta (PPP2R2B) appeared to be protective. Multiomics integration suggested epigenetic regulation of HGF and PPP2R2B. The Cancer Genome Atlas analysis corroborated the dysregulation of these candidates, with high AVEN expression associated with poorer survival. Protein-protein interaction and drug prediction analyses highlighted functional networks and potential therapeutics, supported by molecular docking demonstrating strong HGF-binding affinities. However, these associations did not reach statistical significance in the independent validation cohort, possibly due to limited statistical power.ConclusionsThis study identified AVEN, HGF, and PPP2R2B as potential candidate genes for gastric cancer. These findings require further validation in larger cohorts.

PMID:41840829 | DOI:10.1177/03000605261430163

LR-SGS: Robust LiDAR-Reflectance-Guided Salient Gaussian Splatting for Self-Driving Scene Reconstruction

arXiv:2603.12647v1 Announce Type: cross Abstract: Recent 3D Gaussian Splatting (3DGS) methods have demonstrated the feasibility of self-driving scene reconstruction and novel view synthesis. However, most existing methods either rely solely on cameras or use LiDAR only for Gaussian initialization or depth supervision, while the rich scene information contained in point clouds, such as reflectance, and the complementarity between LiDAR and RGB have not been fully exploited, leading to degradation in challenging self-driving scenes, such as those with high ego-motion and complex lighting. To address these issues, we propose a robust and efficient LiDAR-reflectance-guided Salient Gaussian Splatting method (LR-SGS) for self-driving scenes, which introduces a structure-aware Salient Gaussian representation, initialized from geometric and reflectance feature points extracted from LiDAR and refined through a salient transform and improved density control to capture edge and planar structures. Furthermore, we calibrate LiDAR intensity into reflectance and attach it to each Gaussian as a lighting-invariant material channel, jointly aligned with RGB to enforce boundary consistency. Extensive experiments on the Waymo Open Dataset demonstrate that LR-SGS achieves superior reconstruction performance with fewer Gaussians and shorter training time. In particular, on Complex Lighting scenes, our method surpasses OmniRe by 1.18 dB PSNR.

AriadneMem: Threading the Maze of Lifelong Memory for LLM Agents

arXiv:2603.03290v1 Announce Type: cross Abstract: Long-horizon LLM agents require memory systems that remain accurate under fixed context budgets. However, existing systems struggle with two persistent challenges in long-term dialogue: (i) \textbf{disconnected evidence}, where multi-hop answers require linking facts distributed across time, and (ii) \textbf{state updates}, where evolving information (e.g., schedule changes) creates conflicts with older static logs. We propose AriadneMem, a structured memory system that addresses these failure modes via a decoupled two-phase pipeline. In the \textbf{offline construction phase}, AriadneMem employs \emph{entropy-aware gating} to filter noise and low-information message before LLM extraction and applies \emph{conflict-aware coarsening} to merge static duplicates while preserving state transitions as temporal edges. In the \textbf{online reasoning phase}, rather than relying on expensive iterative planning, AriadneMem executes \emph{algorithmic bridge discovery} to reconstruct missing logical paths between retrieved facts, followed by \emph{single-call topology-aware synthesis}. On LoCoMo experiments with GPT-4o, AriadneMem improves \textbf{Multi-Hop F1 by 15.2\%} and \textbf{Average F1 by 9.0\%} over strong baselines. Crucially, by offloading reasoning to the graph layer, AriadneMem reduces \textbf{total runtime by 77.8\%} using only \textbf{497} context tokens. The code is available at https://github.com/LLM-VLM-GSL/AriadneMem.
❌