T cells are central drivers of inflammation across autoimmune and inflammatory diseases, yet current therapies inadequately target pathogenic T-cell pathways, limiting durable disease control. Here, we identified a novel, targetable transcriptional-metabolic axis that sustains inflammatory T-cell responses, characterized by NFATc1-regulated activation of MTHFD2-dependent one...
Cellular protein homeostasis, or proteostasis, underpins the integrity, adaptability, and survival of all cells by balancing protein synthesis, folding, trafficking, and degradation. This multilayered network is sustained by coordinated actions of molecular chaperones, the ubiquitin‒proteasome system, autophagy-lysosomal pathways, and organelle-specific quality control programs...
This open-label, multicenter, phase 1b/2 trial assessed the safety and efficacy of toripalimab plus cetuximab in patients with platinum-refractory (Cohort A) or previously untreated programmed cell death-ligand 1 (PD-L1)-positive (Cohort B) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Patients received toripalimab 240 mg intravenously (IV) every 3...
Premature termination codons (PTCs) are a major class of pathogenic variants that underlie rare inherited disorders, including forms of childhood blindness. Therapeutic suppression of these “nonsense mutations” offers a gene- and position-agnostic strategy to restore protein function. Our previous work established that the W53X PTC in the KCNJ13 gene causes Leber congenital...
Glioblastoma remains one of the most lethal brain tumors. Although immunotherapy and other therapeutic modalities has achieved significant therapeutic success in several malignancies, its efficacy in glioblastoma remains limited primarily due to the complex tumor microenvironment (TME) and physiological barriers such as the blood–brain barrier (BBB). In this context, nanomedicine...
Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone...
Cold tumors, including epithelial ovarian cancer (EOC), mostly arise from sporadic factors, particularly hormonal and environmental influences, and are characterized by limited immune cell infiltration. Growth differentiation factor 15 (Gdf15) is increasingly recognized as a prognostic marker for EOC, but its role in harsh tumor environments, including immune surveillance and...
Galectins are glycan-binding proteins that interact with diverse glycoconjugates and protein networks to regulate intracellular and extracellular signaling pathways governing fundamental biological processes. Increasing evidence implicates galectins in the pathogenesis of major human diseases, including cancer, cardiovascular disorders, neurodegeneration, metabolic disorders, and...
Tumor heterogeneity presents a major clinical challenge. Reactivation of telomerase (hTERT) is a near-universal hallmark of cancer, yet direct inhibition of hTERT has shown limited therapeutic benefit. To uncover tractable telomerase-related vulnerabilities, we applied a synthetic dosage lethality (SDL) strategy to identify genes required only when hTERT is overexpressed. We...
Autophagy is a tightly regulated catabolic process that is essential for cellular homeostasis, stress adaptation, and metabolic balance. Its dysregulation has been implicated in a wide range of diseases, including cancer, neurodegenerative disorders, metabolic syndromes, muscular diseases, and infections. Recent studies have revealed the central roles of transcription factors...
In triple-negative breast cancer (TNBC), chemotherapy-induced immunogenic cell death (ICD) often fails to trigger truly effective antitumor immunity. This failure primarily stems from the simultaneous release of damage-associated molecular patterns (DAMPs) and immunosuppressive prostaglandin E2 (PGE2), creating an intrinsic NOT-AND signaling conflict. This barrier hinders...
The integration of multiomics technologies with artificial intelligence (AI) has become a transformative force in modern precision medicine, particularly within drug discovery. Multiomics approaches, including genome-wide association studies, transcriptomic profiling, proteomic interaction mapping, and metabolomic sequencing, provide unparalleled insights into the molecular...
Human papillomavirus (HPV)-associated cervical diseases pose significant health risks to women worldwide. Current clinical interventions face challenges in achieving complete viral clearance and controlling disease progression, with limited efficacy and recurrence risks. To address this unmet need, we developed an innovative nanovaccine (HM-NPs@LP) designed to codeliver tumor...
Autism spectrum disorders (ASD) affect approximately 1.0% of children worldwide with still increasing global prevalence. The fact that genetic factors contribute to less than 50% of ASD suggests some critical yet enigmatic roles of non-genetic factors in ASD etiology. Here, we reported that montelukast (MTK), a cysteinyl leukotriene receptor antagonist and one of the most...
LAG3 is a critical inhibitory receptor that is highly enriched on exhausted T cells within the tumor microenvironment (TME), where it acts as a key driver of T-cell exhaustion—an archetypal barrier to robust antitumor immunity. In a colon cancer model, LAG3+CD8+ tumor-infiltrating lymphocytes (TILs) constitute the predominant type of tumor-specific T cells but exhibit defective...
The integration of molecular computation with nanomedicine holds transformative potential for precision cancer theranostics. However, achieving an intelligent, multi-input decision-making process within living cells remains a formidable challenge because of the complexity of intracellular signaling networks. Here, we present a set of DNA tetrahedron logic processors that enable...
Aging is a complex biological process characterized by progressive functional decline, driving the incidence of age-related diseases such as neurodegeneration, metabolic disorders, and cardiovascular diseases. Therapeutic strategies targeting aging hallmarks can delay aging and mitigate disease risk. Emerging interventions focus on modulating core aging mechanisms, including...
As immunoregulatory cells, regulatory T cells (Tregs) play pivotal roles in maintaining immune tolerance and preventing autoimmunity. However, Tregs exhibit distinct functions across different diseases. In cancer, Tregs are most likely to suppress antitumor immune responses and promote tumor immune evasion, whereas in inflammatory diseases, functionally competent Tregs mitigate...
Acute myeloid leukemia (AML) is a rapidly progressive malignancy with poor prognosis. To date, chimeric antigen receptor (CAR) T-cell therapy in AML has been limited by the lack of antigens with high specificity for AML cells. Here, we developed a synthetic T-cell receptor and antigen receptor-T (STAR-T) cell therapy targeting LILRB4, an immunosuppressive receptor highly...
Breast cancer (BC) is the most common type of cancer among women worldwide and underlies relapse, disease progression, and metastasis. Resistance to chemotherapy and programmed cell death (PCD), including apoptosis, strongly affects BC therapy success and remains a major challenge. Although necroptosis, a lytic, and via damage-associated molecular patterns (DAMP) release, highly...
Patients diagnosed with limited-stage small cell lung cancer (LS-SCLC) face dismal long-term outcomes, as relapse occurs frequently even after standard concurrent chemoradiotherapy. Integrating immune checkpoint blockade into chemoradiotherapy regimens may enhance sustained disease control, yet prospective evidence for this strategy in LS-SCLC remains sparse. In this single-arm...