•Neutrophil pyroptosis delays re-epithelialization after corneal injury

•Compromised re-epithelialization promotes corneal neovascularization afterinjury

•Inhibition of post-injury pyroptosis could be an effective therapy to promote corneal wound healing.

•AMPK activation induces PGC-1α expression in glioblastoma during nutrient scarcity.

•PGC-1α enables metabolic plasticity by facilitating metabolism of alternative nutrients in glioblastoma.

•PGC-1α expression is inversely correlated with hypoxic tumour regions in human glioblastomas.

•MSI-driven spatial metabolomics preserves metabolite spatial information, enhancing disease analysis and biomarker discovery.

•Advances in MSI technology improve detection sensitivity and accuracy, expanding bioanalytical applications.

•Enhanced visualization techniques refine metabolite identification and spatial distribution analysis.

•Integration of MSI with AI promises to advance precision medicine and accelerate drug development.

•Innovative NKCEs: NK cell engagers (NKCEs) represent a promising new class of immunotherapeutics targeting tumours by activating NK cells.

•Multi-specific formats: The transition from bi-specific to multi-specific NKCEs enhances their versatility and therapeutic efficacy.

•Mechanisms of action: NKCEs have the potential to improve NK cell activation by engaging activating receptors and incorporating cytokines.

•Clinical potential: Current clinical trials demonstrate the safety and efficacy of various NKCEs across different cancer types.

•Future research directions: Optimising NKCE designs and exploring combination therapies are essential for overcoming challenges in cancer treatment.

•Mesothelin expression is significantly higher in gastric and colorectal cancers than normal tissues.

•hYP218 CAR T cells demonstrate strong anti-tumour activity against mesothelin-positive gastric and colorectal carcinomas.

•Activated hYP218 CAR T cells persist in the tumour microenvironment and retain their cytotoxic activity.

•Addition of pembrolizumab in larger tumours enhance CAR T cell efficacy.

•A comprehensive summary of various aspects of DNA methylation, such as its mechanism, detection methods and biomarkers aiding in diagnosis and treatment.

•The role of DNA methylation in regulating hepatocellular carcinoma’s (HCC) malignant progression and sorafenib resistance, alongside elaborating therapeutic effects of DNA methyltransferase inhibitors.

•Deep research on DNA methylation is critical for discovering novel tumour-specific inhibitors for HCC.

•Spatial analyses of melanoma liver metastasis show that adjacent normal hepatocytes have increased collagen-type I levels.

•Melanoma liver metastases tumour cells secrete enhanced levels of TNF-α to stimulate CXCR4/CXCL12 upregulation in adjacent normal hepatocytes.

•Activation of CXCR4 promotes AKT and NF-κB signalling pathways to promote collagen-type I secretion in adjacent normal hepatocytes.

•Elevated collagen levels were associated with reduced tumour-infiltrating lymphocytes

•Lactylation significantly influences tumour metabolism and gene regulation, contributing to cancer progression.

•Advanced sequencing and machine learning reveal widespread lactylation sites in tumours.

•Targeting lactylation enzymes shows promise in enhancing anti-tumour drug efficacy and overcoming chemotherapy resistance.

•This review outlines the clinical implications and future research directions of lactylation in oncology.

•The source of mesenchymal stem cells (MSCs) strongly influences the composition and function of MSC-derived extracellular vesicles (EVs), affecting their therapeutic potential. Adipose-derived MSC-EVs, known for their immunoregulatory properties and ease of isolation, show promise as a treatment for inflammatory bowel disease (IBD).

•MicroRNAs are consistently present in MSC-EVs across cell types and are involved in pathways that are dysregulated in IBD, making them potential therapeutic agents. For example, miR-let-7a is associated with inhibition of apoptosis, miR-100 supports cell survival, miR-125b helps suppress pro-inflammatory cytokines and miR-20 promotes anti-inflammatory M2 macrophage polarisation.

•Preclinical studies in IBD models have shown that MSC-EVs reduce intestinal inflammation by suppressing pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-6) and increasing anti-inflammatory factors (e.g., IL-4, IL-10). They also promote mucosal healing and strengthen the integrity of the gut barrier, suggesting their potential to address IBD pathology.

•Bisphosphonate-induced lymphatic drainage impairment exacerbates bone necrosis.

•Zoledronate acid triggers endoplasmic reticulum stress and apoptosis in lymphatic endothelial cells via the NAD+/SIRT6/XBP1s pathway.

•Novel nanoparticle-loaded Zoledronate acid and rapamycin enhances autophagy, restores lymphatic function, and mitigates bisphosphonates-related osteonecrosis of the jaw progression.

•SCALeBa and its algorithm are developed to study the molecular mechanism underlying human HSPCs identity and function.

•The human HSPCs expressing MYL6B, MYO19, ATP2A2, MDN1, ING3, and PHF20 may have the capability for high stemness.

•The human HSPCs expressing COA3, RIF1, RAB14, and GOLGA4 may have the capability for pluripotent-lineage differentiation.

•The human HSPCs expressing MRPL23 and RBM4 genes may have the capability to differentiate into myeloid and lymphoid lineage respectively in vivo.

•The legitimacy of the identified genes with SCALeBa was validated using biological experiments and a public human HSPCs dataset.

•SCALeBa improves the accuracy of differentiation trajectories in monocle2-based pseudo-time analysis.

•Targeting METTL3 augments tumour cell immunogenicity and sustains T-cell function.

•T cell with METTL3 inhibition can reverse T-cell exhaustion, and promote expression of IFNγ and GzmB, thereby enhancing cytotoxicity in anti-PD-1 therapy.

•YTHDF2 deletion in tumours prolong the lifespan of MHC-I mRNAs.

•The first-ever visualization of cellular distributions in normal and tumor pituitary tissues.

•The inter-and intra-tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed.

•Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.

•Metabolites derived from both gut and intratumoural microbiota play important roles in cancer initiation and progression.

•The dual roles of microbial metabolites pose an obstacle for clinical translations.

•Absolute quantification and tracing techniques of microbial metabolites are essential for addressing the gaps in studies on microbial metabolites.

•Integrating microbial metabolomics with multi-omics transcends current research paradigms.

•Chaperonin TCP1 subunit 6A (CCT6A) plays an oncogenic role in triple-negative breast cancer (TNBC) through the AKT signaling pathway.

•TRIM21 facilitated K48-linked ubiquitination-mediated degradation of CCT6A, thereby impeding TNBC progression.

•Our study collectively underscores the potential of Ipatasertib in conjunction with anti-PD1 therapy as a promising strategy to counteract CCT6A/AKT hyperactivity-driven TNBC progression.

This study explores the role of circSpna2 in depression following traumatic brain injury (TBI). It was found that circSpna2 is significantly downregulated in TBI patients, and its expression levels correlate with depressive symptoms. In TBI mouse models, overexpression of circSpna2 alleviated depression-like behaviours, while its knockdown exacerbated these symptoms, suggesting its potential as both a biomarker and a therapeutic target for post-TBI depression. Mechanistically, circSpna2 regulates the Nrf2-Atp7b signalling pathway by binding to the DGR domain of Keap1, which prevents Nrf2 ubiquitination and enhances Nrf2 activity. This in turn promotes the transcription of Atp7b, a copper transport protein, helping to maintain copper homeostasis and mitigate copper-induced oxidative stress, a key protein of cell death (cuproptosis). The overexpression of circSpna2 also improved mitochondrial function and synaptic integrity, which are typically impaired by copper dysregulation. These findings highlight the therapeutic potential of circSpna2 in managing TBI-related depression through the regulation of oxidative stress and copper homeostasis.