Cardiac ischemia‒reperfusion (I/R) injury is a leading cause of disability and mortality worldwide, but the underlying mechanism remains largely unknown. Despite the emerging recognition of circular RNAs (circRNAs) as pivotal regulators of cardiac development and disease, their roles in cardiac I/R injury have yet to be thoroughly investigated. In this study, we identified a...
COVID-19 resulting from SARS-CoV-2 infection has presented significant challenges to global health over the past several years. Animal models are essential for studying the pathogenic mechanisms of SARS-CoV-2 and facilitating the development of therapeutic strategies. Transgenic hACE2 mouse models are widely used to explore the mechanisms responsible for severe and lethal COVID...
Nanoparticle-based phototherapy represents a paradigm shift in precision medicine, harnessing light-activated mechanisms to modulate cellular pathways across a spectrum of diseases. By integrating nanoparticles, phototherapeutic modalities achieve enhanced light absorption and improved targeting and amplification effects, such as reactive oxygen species generation in photodynamic...
Pyroptosis, which rapidly releases cellular contents through pyroptotic pores, is an ideal method for inducing in situ cancer vaccines, evoking systemic antitumor immunity, and suppressing primary and metastatic tumors. However, the clinical translation of pyroptosis-based therapy is hindered by the inability to spatially control the activation of inert precursors and the...
The gut-brain axis is increasingly recognized as a critical contributor to Parkinson’s disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor...
Calcific aortic valve disease (CAVD) is a prevalent age-related valvulopathy characterized by high morbidity and mortality. CAVD pathogenesis involves maladaptive differentiation of valvular interstitial cells (VICs) into profibrotic and osteogenic phenotypes, yet the underlying mechanisms remain unclear. Emerging evidence implicates cyclic guanosine monophosphate (cGMP)-protein...
Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapies have demonstrated remarkable efficacy in hematologic malignancies; however, their clinical performance in solid tumors remains limited due to suboptimal tumor infiltration, antigen heterogeneity, and immunosuppressive tumor microenvironments (TME). Invariant natural killer T (NKT) cells have recently emerged as a...
Despite advances in therapeutic regimens for managing cancer progression, ovarian cancer (OVC) still depends on platinum-based chemotherapy as its first-line treatment. Acquired resistance is accompanied by abnormal alterations in epigenetic regulation; however, in-depth mechanistic studies on cisplatin-resistant OVC are lacking. Herein, we show that abnormal overexpression of...
This prospective phase 1 pilot study evaluated the safety and efficacy of GS001, an adeno-associated virus serotype 8 (AAV8)-based vector encoding B-domain–deleted factor VIII with exploratory assessment of prophylactic immunosuppression. Twelve adult severe hemophilia A participants were enrolled. Participants received GS001 at either 2×10¹² (low dose cohort) or 4×10¹² (high...
Chimeric antigen receptor natural killer (CAR-NK) cell therapy has emerged as a promising immunotherapeutic modality with potent cytotoxicity and a favorable safety profile. However, its therapeutic efficacy is often limited by poor infiltration into tumors and the profoundly immunosuppressive tumor microenvironment (TME). In hepatocellular carcinoma (HCC), one of the leading...
Chimeric antigen receptor (CAR)-T cell therapy exerts limited therapeutic efficacy in solid tumors including digestive tract cancer (DTC), which is largely attributable to the suppressive tumor microenvironment (TME) and the functional deficits of CAR-T cells. Herein, we generated fourth-generation CAR-T cells engineered to target Claudin18.2 (CLDN18.2) with concurrent secretion...
Oxidative stress and excessive inflammatory responses are major drivers of atherosclerosis (AS) formation and progression. In this study, we report a nature-inspired nanoreactor (named USPB@SeDMSN@NM) with superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) multienzymatic activities for targeted atherosclerosis therapy. The confined cascade nanocatalyst...
Fibrosis is a maladaptive pathophysiological process characterized by excessive deposition of extracellular matrix resulting from dysregulated tissue repair responses. Fibrosis can affect nearly all organ systems, such as the lung, heart, liver, and kidney. Persistent fibrotic remodeling leads to architectural distortion, loss of function, organ failure, and ultimately increased...
The broader clinical application of Bispecific T-cell engagers (BiTEs) is hindered by their short half-life, on-target off-tumor toxicity, and limited therapeutic effect for solid tumors. Herein, we constructed a bimetallic-enriched triple-kill nanobomb manganese/Co2+-dopamine@BiTE/HPT (MnO2/Co-DA@BiTE/HPT) based on metal-polyphenol to improve the immunosuppressive tumor...
Effective precision oncology demands integration of pharmacokinetics/pharmacodynamics (PK/PD) profiling with tumor-specific genomic features. Here, we present a personalized treatment model using a patient-derived Networking Organoid Culture System (NOCS) composed of intestinal, liver, and kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of an NF1...
Osteoarthritis (OA) is a debilitating joint disorder that causes chronic pain, inflammation, and detrimental bone alterations. Despite significant advances in understanding OA pathogenesis, current therapeutic strategies remain inadequate in halting disease progression or providing effective pain relief, highlighting unmet clinical needs. Recent insights into OA nociceptive...
Immunotherapy with immune checkpoint blockade (ICB) in epithelial ovarian carcinoma (EOC) shows limited clinical benefit only for a small subset of patients. Overall response rates are low, so that overcoming immunotherapy resistance and improved stratification are key. In this study, we investigated the immunometabolic landscape of EOC with a focus on omental metastases...
Dendritic cells (DCs) regulate both innate and adaptive immunity during sepsis. Prostaglandins (PGs), small lipid molecules derived from arachidonic acid via COX enzymes, are crucial regulators of immune homeostasis and inflammation. However, their role in sepsis pathogenesis remains poorly defined. In this study, we identified a significant negative correlation between DC...
Transcriptional activity perturbation holds promise for selectively modulating harmful transcriptional networks, but its therapeutic potential remains largely unexplored. We employed a network-based analysis of single-cell heart transcriptomes to identify transcription factor activities linked to pathological cardiomyocytes in vivo. This analysis revealed that transcriptional...
Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is a leading cause of cancer death. G protein-coupled receptor 54 (GPR54) plays a role in cancer development by interacting with its endogenous ligand kisspeptin encoded by the KISS1 gene. However, the role of GPR54 in NSCLC development is not yet fully understood. Here, we demonstrate that GPR54 regulates...
Bofanglutide is a novel biweekly (once every two weeks; Q2W) glucagon-like peptide-1 receptor agonist. We evaluated the efficacy and safety of bofanglutide in Chinese adults with overweight or obesity in a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov, NCT06256562). Adults with overweight (body mass index [BMI] ≥24, <28 kg/m2) and at least one...