Hemorrhagic shock (HS) is a severe condition involving stress proteins, inflammation, and gut microbiota dysbiosis. Understanding whether regulatory proteins influence HS through microbial pathways is crucial for improving therapeutic strategies. We used Mendelian randomization (MR) combined with animal experiments to investigate the role of regulatory proteins in HS. Two-sample...
The complex invasiveness and heterogeneity of glioblastoma multiforme (GBM) hinder the complete eradication of the tumor. The invasion of the basement membrane (BM) occurs before the spread to the meninges and the metastasis of glioma cells, increasing the recurrence rate of the disease, leading to poor patient prognosis. In this study, four cohorts of GBM patients were...
Pseudoexfoliation (PEX) is a complex age-related disorder traditionally considered ocular in origin but increasingly recognized as a systemic condition involving extracellular matrix (ECM) dysregulation, oxidative stress, and cytoskeletal alterations. The disease typically presents as pseudoexfoliation syndrome (PEXS), with a subset of patients progressing to pseudoexfoliation...
Despite decades of therapeutic development, osteosarcoma survival remains poor. Although berberine (BBR) shows anti-tumor activity, its efficacy is limited. We addressed this through structural modification and machine learning-guided discovery, developing a novel derivative: 9-O-methoxyethylberberrubine bromide (B1). In vivo, subcutaneous and orthotopic models were established...
Chimeric antigen receptor (CAR)-T cell therapy has achieved significant progress in the treatment of hematologic cancers but continues to face major obstacles in solid tumors, including antigen heterogeneity, limited infiltration, and an immunosuppressive tumor microenvironment (TME). Oncolytic viruses (OVs) have emerged as promising tools to reshape the TME and improve CAR-T...
Accurate multicancer classification constitutes a cornerstone of modern oncology, offering critical insights into diagnosis, therapeutic decision-making, and prognostication. Numerous existing approaches, however, remain restricted to limited cancer types and typically encode genomic information into a single representational modality. The purpose of this study was to develop and...
Diet and genetic risk are established risk factors for kidney cancer, but their interaction remains unclear. This study aims to systematically investigate the associations between various dietary patterns and kidney cancer risk, as well as to evaluate the combined effects of diet and genetic risk on kidney cancer risk. We conducted a prospective cohort study involving 113,594...
The epidermal growth factor receptor (EGFR) and Yes-associated protein (YAP) signalling pathways are two intrinsic mechanisms that typically control fibrosis. The intracellular molecules that regulate these two pathways remain unclear. Here, we investigated how EGFR and YAP signalling control retinal Müller cell-related diabetic retinal fibrosis in vivo and in vitro. Human...
Inflammation and the nervous system play pivotal roles in cardiac remodeling after myocardial infarction (MI). Recent study showed renal denervation (RDN) could reduce cardiac inflammation, however, the specific mechanism remains unclear. We firstly reanalyzed the previous heart single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to examine the alterations in...
Mitochondria, in addition to their classic role in energy production, have emerged as central hubs in the regulation of innate immunity. Under conditions of cellular stress, mitochondrial dysfunction triggers the release of mitochondrial DNA (mtDNA) into the cytosol or extracellular space, activating potent inflammatory pathways such as cGAS-STING, NLRP3 and TLR9. mtDNA release...
Diabetic retinopathy (DR), a vision-threatening condition spanning non-proliferative and proliferative stages, faces efficacy and safety limitations with current standard care, demanding innovative solutions. We delineate hyperglycemia as the primary driver of DR pathogenesis via sustained oxidative stress, and hypoxia as the critical trigger for PDR transition through...
Apical periodontitis (AP) is one of the most prevalent dental diseases. Its presence can increase systemic inflammatory burden and is associated with cardiometabolic disorders including higher cardiovascular risks and impaired glycaemic control. There is currently a paucity of knowledge showing whether successful endodontic treatment is associated with systemic metabolic...
The lack of response to TNF-α (tumor necrosis factor-alpha) monoclonal antibodies (mAbs) in autoimmune disease poses a considerable clinical challenge. Trigger receptor expressed on myeloid cells 1 (TREM1) has been proposed as a predictor of anti-TNF-α mAb responsiveness in inflammatory bowel disease (IBD), although this remains controversial. We investigated the role of TREM1 in...
Central retinal artery occlusion (CRAO) causes irreversible vision loss through ischemia-reperfusion (I/R) injury, characterized by oxidative stress and retinal ganglion cell (RGC) death. Current therapies are inadequate. This study investigates kynurenine (Kyn)—a tryptophan metabolite—as a novel therapeutic agent targeting dual pathways to combat retinal I/R injury. The...
Nanodynamic therapy (NDT), as an emerging cancer treatment strategy, achieves specific killing of tumor cells by using nanomaterials to generate reactive oxygen species (ROS) under the activation of external energies (e.g. light, acoustic, thermal, and electrical, etc.). This article systematically reviews the classification of NDT and its mechanism of action, including...
This study aims to systematically elucidate the molecular mechanisms underlying idiopathic pulmonary fibrosis (IPF), with a specific focus on the regulatory role of the nucleic acid-binding protein Y-box binding protein 1 (YBX1) in alveolar type II epithelial cells (AT2) and its association with disease progression. Additionally, the study integrates virtual screening and...
Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck...
Atherosclerosis, a progressive inflammatory disease and the leading cause of cardiovascular disease (CVD), remains a global health burden due to the lack of effective early therapeutic interventions. Although growing evidence highlights the involvement of plasma proteins in atherogenesis, their causal contributions to disease pathogenesis are poorly understood. To address this...
HPV status is a key determinant of prognosis and treatment response in head and neck squamous cell carcinoma (HNSCC). To investigate how HPV influences the tumor-immune-stromal landscape, we performed high-dimensional spatial profiling, including its impact on spatial organization, tertiary lymphoid structures (TLSs), and spatially organized cellular neighborhoods. Tumor biopsies...
Preeclampsia (PE), a severe hypertensive disorder during pregnancy, is characterized by dysfunctional placental trophoblasts. This study identifies hsa-miR-518c-5p as a key regulator of trophoblast differentiation and invasion, potentially implicated in PE pathology. In human PE placentae, the expression of hsa-miR-518c-5p was measured, revealing a significant decrease in the...
Mature T/NK-cell lymphoma is a highly heterogeneous, aggressive non-Hodgkin lymphoma. Due to the lack of specific therapeutic targets, treatment outcomes for patients with relapsed/refractory (R/R) disease are limited, and survival rates are low. Therefore, there is an urgent need to explore specific therapeutic targets and treatment strategies based on molecular mechanisms...
Bone maintains a relatively stable bone mass by balancing bone formation and resorption. The development of osteoporosis is closely associated with the disruption of this balance. Muscles and bones, integral components of the musculoskeletal system, are functionally interconnected, and the onset of osteoporosis is frequently linked to the decline in skeletal muscle function...
Diabetes mellitus is a widespread metabolic disorder characterized by chronic hyperglycemia, driven primarily by insulin resistance and β-cell dysfunction. N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotes, has emerged as a critical regulator in diabetes pathogenesis. This review outlines how m6A methylation, mediated by writers (METTL3, METTL14...