LSH, a homologue of the ISWI/SNF2 family of chromatin remodelers, is required in vivo for deposition of the histone variants macroH2A1 and macroH2A2 at specific genomic locations. However, it remains unknown whether LSH is directly involved in this process or promotes other factors. Here we show that recombinant LSH interacts in vitro with macroH2A1–H2B and macroH2A2–H2B dimers, but not with H2A.Z–H2B dimers. Moreover, LSH catalyzes the transfer of macroH2A into mono-nucleosomes reconstituted with canonical core histones in an ATP dependent manner. LSH requires the ATP binding site and the replacement process is unidirectional leading to heterotypic and homotypic nucleosomes. Both variants macroH2A1 and macroH2A2 are equally well incorporated into the nucleosome. The histone exchange reaction is specific for histone variant macroH2A, since LSH is not capable to incorporate H2A.Z. These findings define a previously unknown role for LSH in chromatin remodeling and identify a novel molecular mechanism for deposition of the histone variant macroH2A.

Background: Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC). Methods: Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients’ clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers. Results: We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors. Conclusions: Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.

In recent years, nanoparticle-based drug delivery systems have demonstrated significant potential in the diagnosis and treatment of urologic malignancies. Common urinary system tumors, including prostate cancer, bladder cancer, and renal cell carcinoma, are characterized by high recurrence rates, strong drug resistance, and limited diagnostic sensitivity, posing substantial challenges to effective clinical management. Compared with conventional therapeutic approaches, nanoparticles—through enhanced permeability and retention (EPR) effects, surface ligand modifications, and controlled release capabilities—enable precise drug accumulation at tumor sites, thereby enhancing efficacy while minimizing systemic toxicity. This review provides a comprehensive summary of recent advances in inorganic (e.g., gold, silver, magnetic, mesoporous silica), organic (e.g., liposomes, PLGA, dendrimers), and hybrid nanoparticle platforms for urologic cancers. It highlights their multifaceted roles in targeted chemotherapy, immunotherapy, gene delivery, photothermal/photodynamic therapy, multimodal imaging, and integrated theranostic strategies. Additionally, the article critically analyzes key challenges in clinical translation, including long-term biocompatibility, immune activation, in vivo clearance, and scalable production. Finally, it discusses future directions such as stimuli-responsive nanoplatforms, personalized precision medicine, and synergistic multimodal technologies. This review aims to provide a theoretical foundation and technical reference for the clinical transformation of nanomedicine in urologic oncology.

With the rising global incidence of cancer and the limitations of traditional treatment methods, the integration of three-dimensional (3D) printing technology with drug delivery systems offers a promising solution for precision medicine. 3D printing, with its high flexibility and precise production control, allows for the accurate modulation of drug delivery systems, particularly in terms of targeted delivery and controlled drug release rates, thus significantly enhancing therapeutic efficacy and reducing side effects. This review focuses on the applications of various drug delivery forms, such as microneedle patches, implants, and tablets, in the treatment of cancers including breast cancer, melanoma, osteosarcoma, cervical cancer, colorectal cancer, and prostate cancer. Furthermore, the review explores the synergistic effects of combination therapies, such as photothermal therapy, chemotherapy, and immunotherapy, within 3D-printed drug delivery systems, and assesses their potential in addressing tumor recurrence, drug resistance, and treatment-related side effects. Despite the substantial promise of 3D printing technology in cancer treatment, challenges remain in material selection, process optimization, and production standardization. As technology continues to evolve and multidisciplinary collaborations deepen, 3D printing is expected to play an increasingly significant role in the future of precision medicine and personalized cancer therapy.

Coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is still threatening the human life and society throughout the world. For those critically ill patients, mechanical ventilation (MV) is essential to provide life support during treatment. However, both the virus infection and MV disrupt the balance between secretion and elimination of airway mucus and lead to mucus accumulation in the lung. Postmortem examination verified that the lungs in patients died of COVID-19 are indeed filled with sticky mucus, suggesting a great need to improve airway mucus clearance in critically ill COVID-19 patients. Therefore, it may be helpful to comprehensively review the current understanding regarding the changes of biochemical and rheological features of airway mucus associated with the disease, as well as the physiological principles and algorithm to decide airway clearance techniques suitable for the critically ill COVID-19 patients. Based on these considerations, optimized strategies may be developed to eliminate the airway mucus accumulated in the airways of critically ill COVID-19 patients.

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