Bacterial extracellular vesicles (BEVs) are actively secreted nanostructures that play a unique role in the pathogenesis of bacterial infections. In this study, we established an intestinal epithelial cell (IEC)/macrophage coculture system and found that Listeria monocytogenes (LM) membrane vesicles (MVs) acted on macrophages and caused intestinal barrier disruption. Further studies revealed that LM MVs not only induced the M1-type polarization in macrophages through the MAPK signaling pathway but also activated AIM2 and NLRP3 inflammasomes in macrophages to induce pyroptosis. The inflammatory factors IFN-α and TNF-α released by macrophages can bind to IFNAR and TNFR in IECs and activate the JAK-STAT3 signaling pathway, disrupting the intestinal barrier. Our study illustrates the role and mechanism of LM MVs in disrupting the intestinal barrier by regulating the inflammatory response of macrophages, which helps understand the function of LM MVs, explains the mechanism of LM-intestinal infection, and may provide new targets for the treatment of intestinal invasive infections with LM.

Gliomas are the most common intracranial tumors characterized by highly malignant behavior. In addition to genetic and epigenetic mutations, the unique cancer microenvironment (CME) plays a pivotal role in glioma progression and resistance to therapy. Among the critical factors in the glioma CME, amino acid metabolism stands out for its significant influence, with specific amino acids suppressing anti-cancer immune responses and promoting an immunosuppressive environment. The human microbiota affect host metabolism and immune functions, with disruptions in microbiota homeostasis leading to metabolic alterations and immune dysfunction in various diseases. Emerging evidence highlights the role of microbiota-derived metabolites, including amino acids, in reprogramming the glioma CME and modulating oncogenic signaling pathways. This review examines the influence of the gut microbiome on specific amino acid metabolism—namely, tryptophan, tyrosine, arginine, and branched-chain amino acids—and evaluates the potential roles of microbiome-derived metabolites in the prognosis and diagnosis of glioma.

As a major cause of death worldwide, heart disease has significant limitations in traditional treatments. However, 3D printing technology, with its personalized, precise, and multifunctional features, provides a new idea for developing cardiac tissue repair materials. This review analyzes the three core advantages of 3D printing technology in cardiac repair materials: the realization of personalized medicine, the intelligent construction of complex tissue structures, and the optimization of the functions of multi-material combinations. Combined with specific research cases, this review reveals the progress of 3D printing in heart valve replacement, heart patches, vascular stent manufacturing, and composite material development, especially the potential of carbon-based conductive materials, biomass-based materials, and bio-based materials in cardiac tissue repair. In addition, this review discusses the innovative applications of advanced 3D printing technologies in the design of prosthetic materials, including coaxial printing, microfluidic extrusion printing, stereospecific rapid prototyping, and two-photon printing. Finally, this review summarizes the significant advantages of 3D printing technology in cardiac tissue repair and proposes future research directions. It emphasizes the importance of combining 3D printing technology with the study of cardiac tissue engineering to further improve the performance and repair effectiveness of cardiac repair materials. Meanwhile, the potentials of single-cell technology, spatial genomics, and protein prediction technology in optimizing the biocompatibility and functionality of repair cardiac repair materials are envisioned to provide scientific support for more efficient cardiac tissue repair through precise regulation of cell behavior, remodeling of the tissue microenvironment, and the development of personalized materials.

The complex relationship between emotions and mental health demands a more comprehensive theoretical framework that can capture its dynamic and multifaceted nature. This perspective article proposes a novel trimodal approach that conceptually integrates three complementary methodologies: Ecological Momentary Assessment, physiological measurements, and Speech Emotion Recognition. By adopting a dynamical system perspective, we argue that the convergence of these methodologies could provide unprecedented insights into emotional dynamics in mental health research and practice. We discuss how this framework could transform our understanding by simultaneously capturing subjective experiences, physiological responses, and linguistic patterns in naturalistic settings. The proposed integration offers a conceptual foundation for developing more sophisticated approaches to mental health monitoring and intervention. We explore the theoretical implications, methodological considerations, and potential future directions of this integrated perspective, highlighting its promise for advancing both research and clinical practice in mental health.

Plant extracellular vesicles (PEVs) are nanoscale vesicles secreted by plant cells with intact membrane architecture, which encapsulate a diverse array of biomolecules, including lipids, proteins and RNA. They are integral to both intra-cellular communication within plants and inter-species signaling. Recently, some PEVs have been regarded as competitive candidates for disease therapy due to their beneficial components and distinctive hollow biomembrane structure. However, the broader applications of PEVs are currently impeded by several challenges of complicated extraction processes, compositional heterogeneity, the lack of reliable biomarkers and unclear therapy mechanisms. A detailed comprehension of their preparation techniques and biological functions is essential for leveraging their potential in clinical medicine. This article first presented a synthesis of the current methodologies for PEV isolation, purification and characterization. Then, it revealed the therapeutic implications of PEVs as medicines in some common diseases based on their bioactive molecules inside, such as cancer, inflammation, and metabolic disorders. We especially explored the emerging role of PEVs with low immunogenicity and the power for biological barriers crossing as drug delivery systems, underscoring their potential for further industry and clinical applications. At last, the bottleneck problems and a vision of PEVs for disease therapy were also presented to evoke more insightful deliberation. This review aims to provide directions for the development of PEV-derived innovative drugs.

Esophageal cancer (EC) is a prevalent malignancy of the digestive tract with high rates of morbidity and mortality. Two main types of EC, Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), differ significantly in their molecular characteristics and response to treatment. Current clinical management primarily involves surgery and chemoradiotherapy; however, the limited efficacy and severe side effects of traditional treatments have led to unsatisfactory outcomes. Recent advancements in molecular classification and precision therapy offer new strategies for improving EC treatment. This article reviews the progress in the molecular classification of EC and its application in precision therapy, providing a theoretical basis and practical guidance for clinical management. We emphasize how multiple omics, such as genomics, transcriptomics and proteomics, enhance our understanding of the molecular characteristics of EC. Additionally, we analyze current clinical research and the effectiveness of targeted therapies and immunotherapies. We found that significant progress has been made in the molecular classification of EC, and studies have revealed the impact of multiple key gene mutations and signaling pathways (e.g., TP53, PIK3CA, EGFR) across different subtypes. Although targeted therapy and immunotherapy have shown good clinical efficacy, challenges such as high heterogeneity and drug resistance persist in current precision therapy. Future research should focus on overcoming drug resistance, finding new biomarkers, and optimizing treatment strategies.

Cancer stem cells exhibit flexible metabolic profiles. However, the underlying mechanisms for differential metabolic pathways affecting stemness maintenance in gastric cancer are poorly understood. Here, we reveal the role of serine hydroxymethyltransferase-2 (SHMT2)/serine-mediated crosstalk between one-carbon metabolism and lipid metabolism in the stemness maintenance of gastric cancer. Clinically, SHMT2 was significantly highly expressed in Gastric cancer cells (GCs) and gastric cancer stem cells, and was associated with clinical malignant features and poor prognosis in gastric cancer patients. Mechanistically, inhibition of SHMT2 expression resulted in diminished serine levels in one-carbon metabolism, which subsequently modified the composition and fluidity of membrane phospholipids, leading to a reduction in lipid rafts within cellular membranes. The remodeling of membrane phospholipids hindered the localization of γ-secretase to lipid rafts, thereby inhibiting the cleavage of CD44 and the subsequent production of CD44-ICD. Consequently, the transcriptional regulation of c-Myc and KLF4 by CD44-ICD was reduced, ultimately disrupting the maintenance of stemness in gastric cancer cells. Together, these results provide compelling evidence for the metabolic adaptability of cancer stem cells, and the SHMT2/serine/lipid rafts signaling axis holds promise as a potential biomarker for the diagnosis and prognosis of gastric cancer. Furthermore, we synthesized HA-Exo-si SHMT2 to investigate targeted therapy for GC, offering a novel approach for the clinical treatment of gastric cancer.

Antibody-drug conjugates are a cutting-edge biotechnology recently attracting wide attention in the medical field. Binding antibodies to drug molecules could deliver drugs precisely to the site of the lesion, which shows great potential in the treatment of tumors and immune diseases. In this paper, we outlined the current popular antibody-coupling techniques and summarized various common antibody-coupling techniques, including antibody-coupled small toxic molecules, antibody-coupled oligenucleotides, antibody-coupled cells, and antibody-coupled polymers. It provided a new therapeutic strategy and means for targeted drug delivery technology. Finally, we discussed the challenges and future development of the antibody-drug conjugates.

Allergic diseases with high recurrence rates have severely threatened human health around the world. Several strategies have been developed including the administration of allergens or neutralizing antibodies, while allergen-specific immunotherapy (AIT) has been considered as a cure for allergic diseases. However, AIT has some drawbacks including the anaphylactic side effects of the native allergen protein during therapy, poor biodistribution of allergen in targeted organs/cells, and unsatisfactory desensitization and long-term unresponsiveness after the treatment. Biomaterials including hydrogels, nanoparticles, polymers and nanoemulsions could improve the pharmacokinetics of allergens and avoid the leakage of free allergens, thereby improving therapeutic efficacy with reduced side effects. This review summarizes the recent advances of engineered biomaterials to alleviate allergic diseases, especially in the combination with AIT. Due to the prevalence of various allergic diseases and the very limited therapeutics for allergic patients, this review will provide new insights into the development of novel biomaterials for the prevention or treatment of allergic diseases with sustained unresponsiveness.

Radiotherapy induced skin defect (RISD) is a severe radiotherapy complication with persistent oxidative stress and recurrent excessive reactive oxygen species (ROS), impeding normal tissue repair processes. Nevertheless, the lack of a standardized animal model severely hinders the progress of related research work. We develop a novel strategy for repairing the RISD microenvironment, which combines initial ROS clearance, subsequent inhibition of ROS production and the repair of proliferation related cell pathways/functions. As a proof of concept, a composite microneedle (MN) patch comprising γ-polyglutamic acid as the base and ruthenium (Ru) clusters modified magnesium silicate nanosheets (MSR NSs) as the enzyme-like component is prepared. The Ru clusters have excellent ROS scavenging ability and help activate the peroxisome proliferators activated receptor signaling pathway confirmed by the sequencing analysis while the magnesium silicate is degraded under physiological conditions to release magnesium ions and silicate ions, enhancing cell proliferation, migration, and angiogenesis ability. The radiation induced skin defect animal model is established to evaluate the RISD repair efficacy of our MSR@MN patch in comparison with γPGA-MSR ointment and commercial product Orgotein. The results show that our MSR@MN patch effectively improves the pathological microenvironment of abnormal ROS accumulation, reduces inflammatory response and promotes mature angiogenesis and tissue remodeling.

Prolonged tooth loss causes a blade-like narrowing of the alveolar bone, severely impairing chewing function and aesthetics and complicating subsequent orthodontic or restorative treatments. Bone morphogenetic protein-2 (BMP-2) is widely used to induce osteogenesis; however, its lack of cellular targeting in complex microenvironments often results in significant side effects. Developing a safe, stable, and osteoblast-targeted drug delivery system is crucial for precise bone regeneration. Nanoparticles, as ideal drug delivery vehicles, offer highly controllable cellular targeting. This study introduces an innovative approach using DNA nanostructure-modified BMP-2-loaded hybrid extracellular vesicles (EVs) formed by fusing liposomes and EVs. Screening identified 180 nm as the optimal particle size for EVs fusion efficiency. The system achieved osteoblast-specific targeting by attaching the DNA aptamer 19S to the hybrid EVs membrane. The hybrid EVs were further combined with a hydrogel sustained-release system, creating a drug delivery platform that effectively repaired alveolar bone defects. This approach demonstrated significant potential for advancing bone tissue repair and regeneration.

Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy characterized by poor prognosis, high relapse rates, and resistance to conventional chemotherapy. The limitations of standard treatments, including systemic toxicity and non-specific drug distribution, highlight the need for novel therapeutic strategies. Nanoparticles (NPs) represent a promising approach for enhancing AML treatment by improving drug solubility, bioavailability, and targeted delivery while simultaneously minimizing adverse effects. Various NPs, including liposomes, polymeric micelles, dendrimers, carbon-based, and metal NPs, have been explored for their ability to selectively target leukemic cells through passive and active targeting mechanisms. Functionalized NPs can exploit the enhanced permeability and retention effect for passive accumulation in leukemia-affected tissues, while ligand-modified NPs enable active targeting of AML-specific biomarkers such as CD33, CD123, and folate receptors. Furthermore, NPs facilitate combination therapies, controlled drug release, and intracellular drug delivery, overcoming multidrug resistance and enhancing therapeutic efficacy. This review discusses the latest advancements in NP-based AML therapies, their targeting strategies, and prospects for clinical translation, emphasizing the potential of nanotechnology in revolutionizing AML treatment.