Meta-analysis is fundamental to evidence-based medicine, yet traditional workflows remain labor-intensive and susceptible to bias. Although LLM-based research agents offer opportunities for workflow automation, they often lack the data fidelity and methodological traceability required for rigorous quantitative evidence synthesis, particularly when parsing multimodal scientific charts. To address this challenge, we introduce MacAma, a semi-automated multi-agent framework for protocol-constrained and human-verifiable meta-analysis. MacAma operationalizes selected PRISMA 2020 reporting items, PICOS-based eligibility logic, and SYRCLE risk-of-bias domains as structured prompts, decision rules, output fields, and audit records. Critically, MacAma adopts a risk-aware automation strategy: Lower risk, repetitive, and protocol-driven tasks, such as literature screening and drafting, are delegated to AI agents, whereas high-impact steps that directly affect effect-size estimation and statistical conclusions, such as quantitative chart-data extraction, remain subject to expert verification. In a preclinical radiotherapy case study evaluating tumor-related immune outcomes and metastatic potential mediated by circulating tumor cells, MacAma achieved competitive screening performance in the evaluated benchmark and reduced the manual screening burden by over 80% within the current workflow. The case study further demonstrates how structured agent outputs, predefined criteria, and audit records can support transparent screening, data extraction, statistical synthesis, and manuscript drafting. These results suggest that MacAma may provide a scalable and auditable framework for AI-assisted meta-analysis, although important limitations remain in full-text access, quantitative chart data extraction, and expert interpretation of heterogeneity. MacAma is open-source and available at https://github.com/YilinYuan/MacAma.

As a crucial biological material, the extracellular matrix (ECM) constitutes a major part of the extracellular microenvironment, offering both structural support and essential biological signals to surrounding cells. Research into ECM properties not only deepens our understanding of cellular behavior and metabolism but also opens new avenues for studying disease mechanisms and therapies. In this work, we report a previously unrecognized function of ECM by leveraging a three-dimensional spatial cavity structure. It is termed “Non-contact Transspatial Regulatory” (nCTR), referring to the ECM that remotely regulates cells without traditional direct physical contact. Systematic investigation and validation of key factors reveal that nCTR strongly depends on the 3D spatial distance between ECM and cells, governed by both physical spatial confinement and chemical signaling exchange. The process involves multiple components, pathways, and mechanisms, with macropinocytosis playing a dominant role. This newly identified function of the ECM offers a fresh perspective on cellular behavior and will undoubtedly open a new frontier in the cellular microenvironment studies.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder affecting approximately 3.9% of individuals worldwide over their lifetimes. Since adolescence is characterized by ongoing brain maturation and increased responsiveness to environmental stressors, this developmental stage may provide an important window for PTSD intervention. Growing evidence supports an association between ω-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and the restoration of stress-induced neural damage. However, how ω-3 PUFA supplementation during adolescence affects adult susceptibility to PTSD remains poorly understood. Here, we observed significantly reduced DHA and EPA concentrations in the prefrontal cortex (PFC) and serum of PTSD-susceptible rats. Providing 1.2% DHA and EPA in the adolescent diet significantly reduced PTSD-like phenotypes in adulthood, including excessive fear memory retention, depressive-like and anxiety-like behaviors, while also reducing serum levels of proinflammatory cytokines. These phenotypic and inflammatory improvements were associated with changes in the gut microbiome, including its composition and diversity. DHA/EPA supplementation was also linked to alterations in multiple lipid species, with serum phosphatidylcholine levels showing a significant correlation with fear memory expression. Moreover, we observed dysregulation of the PI3K/AKT/mTOR pathway in the PFC of PTSD-like rats, which was less pronounced in DHA/EPA-supplemented animals. Collectively, these findings provide the first evidence relating adolescent ω-3 PUFA status to PTSD-like phenotypes in adulthood. It further identifies that gut microbiota composition, lipid metabolic profiles (notably phosphatidylcholine), and prefrontal PI3K/AKT/mTOR signaling are correlated with these behavioral outcomes, suggesting that these systems may collectively contribute to trauma resilience.