Extracellular vesicles (EVs) are promising cell-free therapeutics for diabetic wound healing due to their immunomodulatory and proangiogenic properties. Nonetheless, challenges in ensuring long-term stability and achieving targeted delivery continue to impede clinical translation. Herein, we developed a 3-dimensional bioprinted methacrylated decellularized umbilical cord matrix (MDUM) patch enabling the sustained delivery of telomerase-immortalized umbilical cord mesenchymal stem cell-derived EVs (TMSC-EVs). TMSC-EVs encapsulated in MDUM maintained their structural integrity and biological functionality for more than 30 d under 4 °C storage, outperforming those encapsulated in gelatin methacryloyl (P < 0.01). In a diabetic murine wound model, our data demonstrated that MDUM could enhance the retention and delivery of TMSC-EVs and further augment the therapeutic effects for diabetic wound healing as revealed by attenuating proinflammatory cytokine levels, enhancing neovascularization, and accelerating collagen deposition. This study pioneers the integration of biomaterial engineering with immortalized cell-derived EVs, establishing a translatable platform for regenerative therapies in chronic wound management.

A full reproductive cycle (pregnancy followed by lactation and involution) imprints long-lived CD8⁺ tissue-resident-memory-like T cells in the breast. These cells restrain tumor growth in mice and are linked to a more inflamed tumor microenvironment and better outcomes in human triple-negative breast cancer.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a major and unavoidable environmental contaminant that poses serious risks to intestinal health. Lycopene (LYC), a natural carotenoid with potent antioxidant properties, has been reported to exert protective effects against oxidative stress. Phosphoglycerate mutase family member 5 (PGAM5) acts as a key signaling hub to control mitochondrial dynamics and mitophagy. This study aimed to elucidate the potential role of LYC in DON-induced intestinal damage and clarify the contribution of PGAM5. We established intestinal porcine epithelial cell models to explore the effects of DON and LYC on intestinal barrier integrity, mitochondrial function, mitophagy, and ferroptosis through assessments of cell viability, oxidative stress, iron accumulation, and autophagic activity. Mechanistic insights were validated using RNA sequencing, molecular docking, Western blotting, and immunofluorescence analyses. PGAM5 expression was modulated via plasmids and small interfering RNA. Our results demonstrated that DON disrupted barrier integrity, reduced cell motility, and induced cytoskeletal disorganization, accompanied by excessive mitophagy, lipid peroxidation, and ferrous iron accumulation, ultimately leading to ferroptosis. Notably, LYC alleviated DON-induced intestinal damage by inhibiting mitophagy and ferroptosis. Importantly, PGAM5 overexpression abolished the protective effects of LYC, indicating that PGAM5-mediated mitophagy-dependent ferroptosis plays a critical role in DON-induced intestinal damage. These findings suggest that LYC may serve as a potential therapeutic strategy for treating mycotoxin-induced intestinal disorders.

In this study, we have designed a full-function interferometer OB (optical bench) for the Taiji program and, for the first time, provided detailed parameter specifications for its interferometer system. Additionally, we constructed a first-generation Taiji interferometer OB and ground test system and conducted preliminary testing and calibration. A comprehensive analysis was carried out on the various noise sources impacting the interferometer system, including laser frequency noise, laser power noise, thermal drift noise, and angular jitter noise. The results revealed that the noise level of the interferometer system reached 1.1 pm/Hz^1/2 at 1 Hz, 5 pm/Hz^1/2 at 0.1 Hz, and 8 pm/Hz^1/2 at 0.01 Hz; these levels satisfied the requirements of the Taiji-2 mission. This work marks the first step in transitioning the Taiji program’s interferometer system from a principle prototype to an engineering prototype, playing a critical role in its future development.

The mammillary body (MB) has traditionally been regarded as a relay station for the hippocampus and plays a pivotal role in the Papez circuit. However, its molecular and cellular organization remains inadequately characterized. This study focuses on the horizontally symmetrically distributed neurotensin (Nts)-expressing and nitric oxide synthase 1 (Nos1)-expressing neurons in the MB, demonstrating that Grik4 (encoding a high-affinity kainate receptor subunit) underlies their distinct electrophysiological properties. Within neural circuits, Nts and Nos1 neurons receive excitatory inputs from the ventral subiculum and send parallel excitatory projections to the dorsomedial and ventrolateral subdivisions of the anteroventral thalamus (AV). These 2 cell type-specific circuits are essential for working memory and exhibit selective activation during the maintenance phase with a marked temporal difference. Together, our findings establish a direct link from molecular identity to circuit architecture and cognitive processing by demonstrating that molecularly distinct Nts and Nos1 neurons constitute differential circuits with convergent inputs, divergent outputs, and dissociable roles in working memory maintenance. This work thus reveals a fundamental cross-scale organizational principle—molecule, cell, circuit, function—within the MB.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host immune response to infection, initiated by an excessive inflammatory cascade that frequently progresses to immunoparalysis characterized by immune cell dysfunction. In this review, we first provide an overview of the key elements and stages in the onset and progression of sepsis. Subsequently, we discuss the recent advances of biomaterial-based nanomedicine (including organic nanomaterials, inorganic nanomaterials, and natural bio-inspired nanomaterials) in the treatment of sepsis. The elimination of pathogens and the modulation of the immune response within the sepsis microenvironment through the design of diverse biomaterial systems were specifically summarized. Finally, we discuss the challenges and opportunities for biomaterial-based nanomedicine in the treatment of sepsis.

Effective therapy for ischemic diseases requires not only timely restoration of perfusion but also protection of ischemic tissues from secondary insults, particularly oxidative-stress-induced injury. Here, we propose the concept of “proangiogenic nanozymes” and develop an efficient screening platform by doping angiogenic elements (Mg, Co, Cu, Zn, Sr, or Eu) into an archetypal antioxidative nanozyme, Prussian blue. Systematic assessment of catalytic activity and proangiogenic performance identified Cu-doped Prussian blue (CuPB) as the lead candidate. In addition to efficiently decomposing multiple reactive oxygen species, thereby attenuating oxidative stress, reducing apoptosis, and protecting ischemic tissues from secondary injury, CuPB nanozymes also stimulated angiogenesis, thereby accelerating tissue repair. In murine models of hind limb ischemia and myocardial infarction, CuPB conferred therapeutic benefits after both local and systemic administration, underscoring its translational potential. This proangiogenic nanozyme strategy offers an integrated and effective approach to ischemic tissue regeneration, bridging catalytic nanomedicine and vascular repair.

Adipose tissue has evolved from a passive lipid store to a dynamic, heterogeneous endocrine organ, whose dysfunction is closely linked to a cluster of chronic metabolic diseases. While early studies focused on overall adiposity, emerging evidence demonstrates that depot-specific adipose tissue traits outperform body mass index alone in predicting various disease risks. Adipose tissue heterogeneity refers to the inherent differences across distinct adipose depots, which manifest at anatomical, cellular, and molecular levels, alongside functional specialization. Moving beyond descriptive characterization, this review proposes a multiscale, functionally grounded framework that translates adipose heterogeneity into precision risk management and depot-targeted therapies. We provide a holistic update to cover previously underappreciated adipose depots (perivascular, epicardial, and bone marrow adipose tissues) and integrate recent single-cell sequencing discoveries of novel cell subsets in adipose tissues. We systematically summarize the core hallmarks of adipose heterogeneity and depot-specific roles in health and disease, while assessing the strength of evidence linking cellular subsets to functional outcomes. We also discuss how emerging technologies such as spatial transcriptomics, organoid technology, and artificial intelligence-driven imaging analysis resolve pathogenic niches and build translatable risk models. Finally, we propose a translational framework to overcome key bottlenecks from preclinical validation to clinical implementation, aiming to advance personalized management of diseases related to adipose tissue dysfunction.