Methyl-CpG binding protein 2 (MeCP2) is a chromatin-associated transcriptional regulator that modulates neuronal gene programs in response to environmental stimuli. Although MeCP2 has been implicated in stress responses and depression, its cell-type-specific functions within defined limbic circuits remain incompletely understood. Here, using a chronic restraint stress (CRS) model...
The development of compounds triggering intestinal stem cells (ISCs) proliferation represents a promising strategy to alleviate irradiation (IR)-induced gastrointestinal syndrome. Here, cannabidiol (CBD)-a nonpsychotomimetic phytocannabinoid derived from the Cannabis sativa plant-was found to dramatically improve body weight loss of mice and stimulate Lgr5+ ISCs proliferation...
DNA topoisomerase II-binding protein 1 (TopBP1) plays a critical role in V(D)J recombination and DNA damage repair during B and T cell development. However, its role in the development of conventional dendritic cells (cDCs) remains unexplored. Mice with DC-specific depletion of TopBP1 (TopBP1cKO) exhibited accelerated tumor progression due to impaired anti-tumor immunity, which...
Psoriasis is a chronic inflammatory disease characterized by dysregulated interactions between keratinocytes (KCs) and immune cells. However, the details of KCs orchestrating the immune cell infiltration, particularly for natural killer (NK) cells, remain unclear. Here NK cell infiltration is significantly increased in psoriatic skin lesions, and the application of anti-MHC-II...
Lactate has been recognized as a major fuel substrate and also a lactyl-group donor for histone lysine lactylation. Hepatocytes act as lactate-consuming cells owing the high oxidative capability especially during exercise, a primary nonpharmacological intervention for alleviating metabolic dysfunction-associated steatotic liver diseases including steatohepatitis (MASLD/MASH...
N-terminal (Nt) methionine formylation, once thought restricted to bacteria and organelles, is now recognized as a stress-inducible initiator modification in the eukaryotic cytosol. Under metabolic or environmental stress, mitochondrial methionyl-transfer RNA (tRNA) formyltransferase mislocalizes to the cytosol, generating formylated initiator tRNA (fMet-tRNAi) that initiates...
Muscle-invasive bladder cancer (MIBC) presents with variable clinical and pathological features, leading to inconsistent responses to standard treatments such as neoadjuvant chemotherapy (NAC). Although transcriptome profiling has shown differences in NAC response, reliable predictors of treatment outcome remain elusive. Here this study aimed to improve NAC response prediction by...
Growth differentiation factor-15 (GDF15), a stress-responsive cytokine of the transforming growth factor-β superfamily, is elevated in cancer cachexia, chemotherapy-induced nausea, and hyperemesis gravidarum, making it both a biomarker and a therapeutic target. Here, we developed high-affinity GDF15 binders using an artificial intelligence-driven protein design framework. To...
The tumor microenvironment harbors diverse immunosuppressive cell populations—including regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages and other tolerogenic subsets—that drive immune evasion and therapeutic resistance. These cells are metabolically reprogrammed to sustain their suppressive function and survive under conditions of hypoxia...
Peripheral nerve injury presents a major therapeutic challenge owing to limited endogenous repair and incomplete functional recovery. Schwann cells (SCs), the principal glia of the peripheral nervous system, support axonal integrity and regeneration, but the post-transcriptional mechanisms regulating their development and reparative function remain poorly defined. Here, we...
The mitochondrial calcium uniporter (Mcu) mediates calcium influx into the mitochondrial matrix, playing an essential role in cellular energy metabolism and survival. Although Mcu has been studied in various physiological contexts, its role in skeletal homeostasis remains poorly understood. Here we investigate how Mcu deficiency affects osteoblast differentiation and bone...
Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been implicated in cardiovascular diseases, yet its role in vascular remodeling remains incompletely understood. Here we investigated the contribution of EHMT2 to vascular smooth muscle cell (VSMC) proliferation, migration and neointima formation following vascular injury using carotid artery injury models and in vitro...
Knee osteoarthritis is a degenerative joint disease, with no fundamental cure beyond pain relief and anti-inflammation. This phase I, multicenter, open-label, dose-escalation trial evaluated the safety, tolerability, and preliminary efficacy of OSCA, an intra-articular injection co-formulation of osiramestrocel (allogeneic mesenchymal stromal cells) and cartilage acellular matrix...
Intervertebral disc degeneration (IDD), a leading cause of low back pain, involves progressive dysfunction of nucleus pulposus (NP) cells and extracellular matrix degradation. The pathological mechanisms underlying IDD remain complex and lack comprehensive elucidation. This study identifies the RNA-binding protein TDP43 as a central driver of IDD pathogenesis through analysis of...
Restoring cardiac function after myocardial infarction remains a major challenge, as current pharmacological and interventional therapies primarily mitigate symptoms and slow disease progression without addressing the irreversible loss of functional myocardium. Although a diverse range of biologically active agents has been developed to modulate inflammation, angiogenesis...
Zinc (Zn²⁺) is an essential trace element that supports a vast array of cellular processes, including enzymatic catalysis, gene expression, immune regulation and signaling. Its unique redox-inert properties and ability to bind diverse proteins make it indispensable for cellular homeostasis. Zinc is dynamically distributed within cells, where its compartmentalization across...
Rheumatoid arthritis (RA) is a leading cause of disability globally. Although iron accumulation in arthritic lesions has been observed in patients with RA, its specific contribution to disability outcomes remains unclear. Here we demonstrate a comprehensive multiomics approach to elucidate the impact and underlying mechanisms of iron overload in RA. First, clinical radiology in...
Metastasis is the main cause of cancer-related death. The liver is an organ with high metastatic tropism for various malignancies. Hepatic-resident macrophage Kupffer cells are the major non-parenchymal cells in the liver that phagocytize disseminated tumor cells to restrict liver metastasis. However, the critical molecules that modulate phagocytosis of tumor cells by Kupffer...
Astroglia, an extended class of homeostatic and defensive cells of the central nervous system (CNS), contribute to the pathogenesis of all known neurological and neuropsychiatric disorders. The pathophysiology of astrocytes is complex, mutable, disease and disease-stage specific. In neuroinflammatory lesions and in various chronic conditions, astrocytes undergo an evolutionary...
The rapid and accurate detection of multiple cancers presents considerable challenges, especially for stage I disease, due to the low concentration and heterogeneous nature of circulating tumor DNA. Here we introduce an enhanced multicancer screening assay that integrates whole-genome methylation sequencing with an innovative multimodal analytical framework for cell-free DNA. The...
Here we aim to elucidate the role of the p300/CBP-associated factor (PCAF) in pathological cardiac remodeling. Specifically, we explore how PCAF-mediated acetylation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) influences AMPK signaling, thereby regulating cardiac hypertrophy and dysfunction under pathological stress. A genetically engineered PCAF-knockout (KO...
Excessive fibrogenesis is associated with adverse cardiac remodeling and heart failure. Myofibroblast, primarily derived resident fibroblast, is the effector cell type in cardiac fibrosis. The mechanism whereby fibroblast–myofibroblast transition is driven remains incompletely understood. In the present study, we investigated the role and targetability of vascular adhesion...
The ovaries are vital components of the female reproductive system. Ovarian aging, driven by oxidative stress, chronic inflammation and hormonal dysregulation, severely compromises female fertility. The receptor for advanced glycation end products (RAGE) serves as a critical regulator of ovarian physiology and pathology. linking metabolic dysfunction to reproductive decline. This...
Aging arises not only from intrinsic cellular decline but also from systemic alterations in circulating factors that govern tissue maintenance and regeneration. Recent multi-omics advances — including plasma proteomics, metabolomics, and single-cell immunomics — highlight blood as both a mirror and a modulator of organismal aging. Circulating proteins and metabolites reflect not...