Body temperature-responsive Janus patches accelerate diabetic wound regeneration via coupling mechanical transduction and biochemical pathways.

A bilayer hydrogel enables spatiotemporal delivery of distinct hepcidin forms to reprogram macrophage responses for repair of infected bone defect.

Breaking the oncogene-immune suppression cycle through dual HER2 silencing and innate immune activation by biomineralized DNA nanocomplexes.

Scutebarbatine A inhibits M2 macrophage polarization via blocking PI3K/AKT signaling to impair cell stemness, metastasis, and angiogenesis in non-small cell lung cancer.

Regulatory role of MRTF-A in macrophage polarization and the therapeutic mechanism of Bushen Wenyang Huayu decoction in endometriosis.

Luteolin inhibits IL-33/ST2L-induced M2 macrophage polarization in endometriosis.

Targeting the Fra2/LCN2 axis attenuates PM2.5-aggravated asthma by suppressing M2 macrophage ferroptosis.

Background Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with a poor survival rate despite advances in therapy. Metabolic reprogramming, particularly involving lactate transport, plays a critical role in HCC progression. Monocarboxylate transporter 4 (MCT4) is a key lactate exporter often overexpressed in cancers, yet its precise role in HCC pathogenesis and immune modulation remains incompletely defined. Methods We integrated bioinformatic analyses of multiple datasets (TCGA-LIHC, GSE46408, GSE36411) with experimental validation in HCC cell lines (Huh7, MHCC97-H) and a murine xenograft model. Functional assays including wound healing, Transwell invasion, Western blot, and flow cytometry were employed. Immune cell infiltration and polarization were analyzed via CIBERSORT and single-cell RNA sequencing data (GSE282701). Results MCT4 was identified as a prognostic hub gene among lactate metabolism-related genes (LMRGs) and was significantly upregulated in HCC tissues, correlating with advanced tumor stage and poor survival. Gene Set Enrichment Analysis (GSEA) revealed a strong association between MCT4 expression and matrix metalloproteinase (MMP) pathways. In vitro , MCT4 knockdown downregulated MMP1, MMP2, and MMP9 expression and suppressed HCC cell migration and invasion. Furthermore, high MCT4 expression was linked to an immunosuppressive tumor microenvironment characterized by M2 macrophage polarization. In vivo , MCT4 knockdown inhibited tumor growth and reduced infiltration of CD206 + M2 macrophages. Conclusions Our findings demonstrate that MCT4 drives HCC progression through two complementary mechanisms: enhancing MMP-mediated invasion and metastasis, and promoting immunosuppressive M2 macrophage polarization. These results nominate MCT4 as a promising therapeutic target for restoring antitumor immunity and inhibiting metastasis in HCC.

Lipoteichoic acid as a key wound healing mediator in Gram-positive bacteria.

Integrated bioinformatics and experimental validation identifies CLIC6 as a novel tumor suppressor regulating NF-κB signaling and immune microenvironment in nasopharyngeal carcinoma.

Modulation of M1 macrophage polarization by Fe3O4@Cu2-xS engineering for improved tumor immunotherapy and MRI.

Role of uridine triggering M2 macrophage polarization to alleviate LPS-induced acute lung injury through the STAT6 signaling pathway.

Erchen decoction promotes inguinal white adipose tissue browning via the M2 macrophage-sympathetic axis to ameliorate obesity in mice.

Severe acute pancreatitis (SAP) often leads to incomplete tissue repair and prolonged exocrine dysfunction. Acinar-to-ductal metaplasia (ADM) is a critical regenerative process postinjury, but persistent ADM impedes functional recovery. Axl and Mertk belong to the TAM family of receptor tyrosine kinases, which are expressed primarily in macrophages to mediate efferocytosis and promote pro-resolving macrophage polarization, and have been implicated in tissue repair. However, their roles in resolving ADM and restoring exocrine function remain unclear. We utilized cerulein-induced SAP models in mice with either global or cell-specific deletion of Axl and Mertk. Pancreatic repair was assessed by histology, transcriptomics, and functional assays. Coculture of primary acinar cells with bone marrow-derived macrophages. The expression of AXL and MERTK in the pancreas was upregulated on Day 4 during pancreatic repair after SAP. Global deletion of Axl and Mertk similarly delayed tissue repair, resulting in persistent ADM, impaired acinar redifferentiation, and defective restoration of exocrine function. Transcriptomics revealed aberrant activation of developmental signaling pathways, including Hedgehog, Wnt, and Notch, and sustained suppression of acinar digestive enzyme genes. In vitro coculture experiments showed that M2 macrophages lacking Axl and Mertk promoted persistent ADM, in contrast to M1 macrophages. AXL and MERTK in macrophages are crucial regulators of pancreatic regeneration after SAP, facilitating ADM resolution and exocrine recovery through interactions between acinar cells and M2 macrophages. These findings highlight that macrophage AXL and MERTK could act as a potential therapeutic target for enhancing long-term restoration of pancreatic function following SAP.NEW & NOTEWORTHY Deleting Axl and Mertk in myeloid cells disrupts the healing process, resulting in persistent ductal structures and failure to recover exocrine function. This repair failure is linked to the abnormal persistence of developmental signaling pathways and is mediated by interactions between acinar cells and macrophages, emphasizing the importance of AXL and MERTK in macrophages in pancreatic functional recovery.

SUMO-conjugating enzyme UBE2I inhibition alleviates asthma progression: effects on BHLHE40 and M2 macrophage polarization.

Nucleotide (NT) supplementation is an efficient practice for enhancing growth and immune performance in farmed aquatic species. However, the NT mode of use, optimal dosage and metabolic effects in different species remain poorly understood. This study investigated the effects of exposing zebrafish ( Danio rerio ) and gilthead seabream ( Sparus aurata ) embryos and larvae to different concentrations of a blend of NTs directly through the water. Embryos and larvae were exposed for 96 h, starting at 24 h post fertilisation. The developmental and physiological parameters assessed included survival, hatching rate, morphology, swimming behaviour, expression of growth-related genes, and macrophage cell status. In zebrafish, survival and hatching rate were unaffected up to 200 mg L −1 (>90%). Morphological analysis revealed that zebrafish exposed to NT at 20–40 mg L −1 exhibited the most significant enhancements in growth (+5% compared to controls), while behavioural tests and gene expression analysis indicated increased swimming activity and significant modulation of key growth-related genes at 10 mg L −1 . Furthermore, immunological assays demonstrated a significant increase in the prevalence of pro-healing M2 macrophages in the gut of larvae at this NT concentration. In gilthead seabream, NT-treated larvae at 10 mg L −1 exhibited a significant increase in standard body length (+4% compared to controls), with no adverse effects on survival or hatching rate up to this level (>75%). Overall, these findings demonstrate that NT exposure promotes larval growth and modulates immune and metabolic activity in zebrafish and gilthead seabream, supporting the application of NT blends as sustainable bioactive additives in aquaculture. • Waterborne nucleotide enhance zebrafish and gilthead seabream larval growth. • Nucleotide exposure boosts zebrafish swimming activity and expression of growth-related genes. • Nucleotides increase pro-healing M2 macrophages in the gut of transgenic zebrafish. • Zebrafish serves as an efficient model for testing bioactive compounds in aquaculture.

Inflammation-targeted nanoaggregates encapsulated triptolide and hyperoside for M2 macrophage repolarization and oxidative stress reversal in rheumatoid arthritis therapy.

On-site self-assembly of glycopeptide triggered by bioorthogonal ligation to metabolically labeled bacteria for promoting tissue regeneration in methicillin-resistant Staphylococcus aureus (MRSA)-Infected wounds.

Construction of ammonia death-related lncRNA prognostic signature model and immunomodulatory effect in glioblastoma multiforme.

Biomimetic hydrogel strategy inspired by sea cucumbers: Integrating antibacterial, osteoimmune, and osteogenic functions for infected bone repair.