IGF2BP3 promotes progression of head and neck cancers through the circHECTD2/hsa_miR_4310/7157-5p/Smad2 signaling axis in an m6A modification-dependent manner.

Transcriptional control of lysosome biogenesis is an important mechanism underlying cellular adaptation to stress. It is largely unclear how cell surface changes or signals induce alteration in lysosome numbers. By developing a Caenorhabditis elegans-based heterologous TFE3 activation system, we here identify the non-receptor tyrosine kinases SRC-1/-2 (C. elegans) and FGR (mammals) as critical regulators of lysosome biogenesis. In C. elegans, inactivation of src-1/-2 leads to nuclear enrichment of ectopically expressed TFE3 and increased intensity of lysosomal markers. In mammalian cells, FGR inhibition or deficiency similarly results in TFEB/TFE3-dependent lysosomal increase. FGR acts through AKT2 by promoting the activation of the latter. FGR associates with the plasma membrane but is internalized onto endosomes and reaches lysosomes along the endosome-lysosome pathway following endocytosis. Lysosomal FGR promotes AKT2 recruitment to lysosomes, where it phosphorylates TFEB/TFE3 to prevent their activation. Together, these findings reveal a plasma membrane-to-lysosome signaling axis that is required for endocytosis-associated lysosome homeostasis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by chronic inflammation and immune dysregulation, with neutrophils playing a critical role in disease pathogenesis. In this study, we elucidated the involvement of the CXCL2-PI3K/AKT/NF-κB signalling axis in the abnormal activation of neutrophils in SLE using transcriptome analysis and functional experiments. Transcriptomic profiling revealed that CXCL2 expression is significantly upregulated in SLE patients, contributing to the activation of key inflammatory pathways and the expression of pro-inflammatory cytokines and chemokines. Invitro and invivo experiments confirmed that CXCL2 promotes the transcription of inflammatory factors by activating the PI3K/AKT/NF-κB pathway, and inhibitors targeting this signalling axis effectively reduced inflammation. Furthermore, neutrophils from SLE patients exhibited a 'pre-activated' state under CXCL2 stimulation, potentially due to epigenetic or metabolic alterations. The functional relevance of CXCL2 was further validated invivo, where knockout of CXCL2 or depletion of neutrophils reduced tissue damage and inflammatory responses. This study highlights the importance of the CXCL2-PI3K/AKT/NF-κB signalling axis in SLE and suggests that targeting CXCL2 or neutrophil-specific markers could provide novel therapeutic strategies for managing SLE. Future research should explore the heterogeneity of neutrophil subpopulations in SLE and the role of metabolic reprogramming in exacerbating inflammation, further refining potential targeted therapies.

Glucocorticoid signaling mitigates colitis-associated visceral hypersensitivity by suppressing 5-HT release in enterochromaffin cells via a GR-PI3K-SGK1 axis.

Ginsenoside Rh2 and luteolin synergistically induce cellular senescence to suppress hepatocellular carcinoma progression through oxidative stress-mediated mechanisms.

Duhuo mitigates intervertebral disc degeneration by activating PI3K/AKT to inhibit ferroptosis in nucleus pulposus cells.

Emodin induces oxidative stress and Ferroptosis in hepatocellular carcinoma cells through the miR-4465/NFE2L3/HMGCR/GPX4 signaling axis.

Compressive stress induces cartilage endplate degeneration through the Piezo1/YAP-TEAD/NLRP3 axis.

Exercise-derived irisin prevents bone loss via Nrf2 activation and inhibition of STING/NF-κB signaling.

TRAF6 mediates vascular remodeling via endoplasmic reticulum stress-mitophagy in hypoxic pulmonary hypertension.

The MafG/Bach1-Lcn2 transcriptional axis drives ferroptosis in sepsis-induced acute lung injury via disrupting redox homeostasis.

Inhibiting Arachidonate-5-lipoxygenase expression ameliorates osteoarthritis progression by suppressing ferroptosis via the JAK2/STAT3 signaling pathway.

Targeting PPP1R15B and ATF4 axis in hepatocellular carcinoma: A novel strategy for overcoming lenvatinib-tolerant persister cells through GPX4-mediated ferroptosis induction.

Atractylodes macrocephala Koidz. water extract alleviates exercise-induced fatigue by activating mitochondrial biogenesis via the PGC-1α/NRF1/TFAM axis.

HHcy promotes hypertension by activating ferroptosis via suppression of the renal H₂S-SLC7A11/GPX4 axis.

PLA2R1-mediated ERK-Dependent ferroptosis: A key pathogenic mechanism in epileptic neuronal injury.

Crosstalk between cGAS-STING and pyroptosis: From molecular mechanisms to therapeutic strategies.

Oxidative stress impairs the expansion of regulatory T cells in active vitiligo via dysregulated CGRP-RAMP1-Gαi3 signaling.

ZIP10 drives radioresistance and malignant progression in lung adenocarcinoma by inhibiting the Hippo pathway via a Zinc-LATS axis.

Shenling Baizhu powder alleviates pyrotinib-induced diarrhea via CFTR-activated chloride secretion.