A ZBP1 isoform blocks ZBP1-mediated cell death.

ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy.

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold. The ligand designed with lipophilic small-sized scaffolds bearing multipositive charges targeting the unique feature of high mitochondrial membrane potential (MMP) is lacking and most mitochondria-selective ligands are not G4-targeting. Herein, we report a new small-sized dicationic lipophilic ligand to target MMP and mitochondrial DNA G4s to enhance drug delivery for anticancer. The ligand showed marked alteration of mitochondrial gene expression and substantial induction of ROS production, mitochondrial dysfunction, DNA damage, cellular senescence, and apoptosis. The ligand also exhibited high anticancer activity against HCT116 cancer cells (IC50, 3.4 µM) and high antitumor efficacy in the HCT116 tumor xenograft mouse model (∼70% tumor weight reduction).

Antennal Transcriptome Evaluation and Analysis for Odorant-Binding Proteins, Chemosensory Proteins, and Suitable Reference Genes in the Leaf Beetle Pest Diorhabda rybakowi Weise (Coleoptera: Chrysomelidae).

Diorhabda rybakowi Weise is one of the dominant pests feeding on Nitraria spp., a pioneer plant used for windbreaking and sand fixation purposes, and poses a threat to local livestock and ecosystems. To clarify the key olfactory genes of D. rybakowi and provide a theoretical basis for attractant and repellent development, the optimal reference genes under two different conditions (tissue and sex) were identified, and the bioinformatics and characterization of the tissue expression profiles of two categories of soluble olfactory proteins (OBPs and CSPs) were investigated. The results showed that the best reference genes were RPL13a and RPS18 for comparison among tissues, and RPL19 and RPS18 for comparison between sexes. Strong expressions of DrybOBP3, DrybOBP6, DrybOBP7, DrybOBP10, DrybOBP11, DrybCSP2, and DrybCSP5 were found in antennae, the most important olfactory organ for D. rybakowi. These findings not only provide a basis for further in-depth research on the olfactory molecular mechanisms of host-specialized pests but also provide a theoretical basis for the future development of new chemical attractants or repellents using volatiles to control D. rybakowi.

Glutamine inhibition combined with CD47 blockade enhances radiotherapy-induced ferroptosis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a formidable cancer type that poses significant treatment challenges, including radiotherapy (RT) resistance. The metabolic characteristics of tumors present substantial obstacles to cancer therapy, and the relationship between RT and tumor metabolism in HNSCC remains elusive. Ferroptosis is a type of iron-dependent regulated cell death, representing an emerging disease-modulatory mechanism. Here, we report that after RT, glutamine levels rise in HNSCC, and the glutamine transporter protein SLC1A5 is upregulated. Notably, blocking glutamine significantly enhances the therapeutic efficacy of RT in HNSCC. Furthermore, inhibition of glutamine combined with RT triggers immunogenic tumor ferroptosis, a form of nonapoptotic regulated cell death. Mechanistically, RT increases interferon regulatory factor (IRF) 1 expression by activating the interferon signaling pathway, and glutamine blockade augments this efficacy. IRF1 drives transferrin receptor expression, elevating intracellular Fe2+ concentration, disrupting iron homeostasis, and inducing cancer cell ferroptosis. Importantly, the combination treatment-induced ferroptosis is dependent on IRF1 expression. Additionally, blocking glutamine combined with RT boosts CD47 expression and hinders macrophage phagocytosis, attenuating the treatment effect. Dual-blocking glutamine and CD47 promote tumor remission and enhance RT-induced ferroptosis, thereby ameliorating the tumor microenvironment. Our work provides valuable insights into the metabolic and immunological mechanisms underlying RT-induced ferroptosis, highlighting a promising strategy to augment RT efficacy in HNSCC.

A facile N-doped NiFe(B) (Oxy)hydroxide monolithic electrode for enhanced water oxidation.

N-doped NiFe(B) (oxy)hydroxide can promote the catalytic activity for an alkaline oxygen evolution reaction (OER) significantly, but fabrication is difficult. Herein, we introduced a B-induction route to the N-NiFe(B) (oxy)hydroxide monolithic electrode under a relatively low temperature. We observed an excellent catalytic performance benefiting from an optimal electronic structure, enlarged surface area and improved hydrophilicity. Moreover, this mild protocol could be extended to fabricate an S-doped NiFe-based catalyst. This research could aid large-scale manufacture.

Live Cell Imaging and Real-Time Monitoring of Nucleolus Morphology and Mitophagy with a Red Fluorescent and Photostable rRNA-Specific Probe in Human Cancer Cells.

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy. Currently, only a few rRNA-selective probes have been developed, and most of them encounter the drawbacks of low water solubility, poor nuclear membrane permeability, short emission wavelength, low stability against photobleaching, and high cytotoxicity. These unfavorable properties of rRNA probes limit their potential applications. In the present study, we reported a new rRNA-selective and near-infrared fluorescent turn-on probe, 4MPS-TO, capable of tracking rRNA in live human cancer cells. The real-time monitoring performance in nucleolus morphology and mitochondrial autophagy is demonstrated in HeLa cells. The probe shows great application potential for being used as a rRNA-selective, sensitive, and photostable imaging tool in chemical biology study and drug screening.

Unveiling the importance of VOCs from pesticides applicated in main crops for elevating ozone concentrations in China.

Volatile organic compounds (VOCs) are considered as important precursors of ozone in the air, while the contribution of VOCs from pesticide application (PVOCs) to ozone production is unknown. Utilizing data from the Ministry of Agriculture and Rural Affairs of the People's Republic of China and ChinaCropPhen1km, this paper developed PVOC emission inventories with a resolution of 1 km for the main crops (rice, maize, and wheat) from 2012 to 2019 in China. The results revealed that pesticide application is an important VOC emission source in China. Specially, the PVOC emissions from the major grain-producing regions in June accounted for approximately 30% of the annual total PVOC emissions in the local regions. The simulation with the Weather Research and Forecasting Community Multiscale Air Quality model (WRF-CMAQ) indicated that the PVOC emissions increased the mean maximum daily 8-hour average (MDA8) ozone concentration across China by 2.5 ppb in June 2019. During the same period, PVOCs in the parts of North China Plain contributed 10% of the ozone formation. Under the comprehensive emission reduction scenario, it is anticipated that by 2025, the joint implementation of measures including reducing pesticide application, improving pesticide utilization efficiency and promoting solvent substitution will decrease PVOC emissions by 60% compared with 2019, thereby mitigating ozone pollution.

A method of gas-related pollution source layout based on multi-source data: A case study of shaanxi province, China.

The location and layout of enterprises have an important impact on local air quality. However, a few studies on exploring of the optimal layout of gas-related enterprises from the perspective of optimizing the layout of air pollution sources. This study developed a method for the evaluation of air pollution source layout based on air pollutant emission inventory data, atmospheric self-purification capacity data, and satellite remote sensing air quality data. Taking Shaanxi Province as an example, the Moran's I index and GIS spatial analysis techniques were used to evaluate the layout of air pollution sources, analyze the spatial variation characteristics of air pollution sources, and propose specific countermeasures to optimize the layout of air pollution sources. Results showed that northern Shaanxi and Guanzhong Plain are the most unsuitable for the distribution of NOx and CO sources, accounting for 13.78% and 21.77% of the total area, respectively. The most suitable area for the distribution of NOx is southern Shaanxi, accounting for 65.77% of the total area, mainly concentrated in Hanzhong and Ankang regions. The most suitable area for the distribution of CO is southern Shaanxi, accounting for 40.97% of the total area, mainly concentrated in Hanzhong and Shangluo regions. The findings of this study could supplement and improve the evaluation of the layout of industrial enterprises in China from technical and methodological aspects, and provide new insight for local governments to adjust and optimize the layout of air pollution sources.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of TFAP2 Family Members in Bladder Cancer from Database and FFPE Sample.

Background: Bladder cancer (BLCA) is one of the common malignant tumors worldwide. Recent studies have shown that Transcription factor activating protein-2(TFAP2) family proteins plays a bidirectional regulatory role in the process of tumorigenesis versus evolution by regulating the expression of tumor associated genes. However, little is known about the function of distinct TFAP2s proteins in patient with BLCA. Methods: Formalin-fixed paraffin-embedded (FFPE) sample tissues and clinical data of 240 patients with bladder cancer were collected for immunohistochemical analysis. The Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), Shiny Methylation Analysis Resource Tool (SMART), Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, TIMER and CIBERSORT were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of TFAP2 family in patients with BLCA. Results: Our study found that TFAP2 family proteins are generally expressed higher in BLCA tissues than in normal tissues. However, they show different trends in the growth, metastasis and survival prognosis of BLCA. TFAP2A and TFAP2C was associated with worse clinical stage and prognosis in BLCA patients, while TFAP2B, TFAP2D and TFAP2E showed the opposite trend. Importantly, the functions of the differentially expressed TFAP2s were primarily related to the developmental process, reproductive process, response to stimulus and immune system process, etc. Moreover, TFAP2 family was significantly correlated with the infiltration of six immune cell types and might regulate TAM polarization. Conclusion: TFAP2 family might be an important regulator of immune cell infiltration and a valuable prognostic biomarker in patients with BLCA.

Health effects of future dioxins emission mitigation from Chinese municipal solid waste incinerators.

Dioxins (including 2,3,7,8-tetrachlorodibenzo-p-dioxin, as Group 1 Carcinogen) in the atmosphere mainly originate from incomplete combustion during municipal solid waste (MSW) incineration. To significantly reduce dioxins emission from the MSW incineration industry, China has promulgated a set of ambitious plans regulating MSW-related pollution; however, the emission reduction potentials and concomitant environmental and health impacts associated with the implementation of these programs on a national scale remain unknown. Here, we use real measurements from official environmental impact assessment systems and continuous emissions monitoring systems (covering 96.6% of national MSW incinerators) to estimate unit-level dioxins emission and concomitant environmental and health impacts. We find that in 2018, 99.3% and 66.7% of Chinese incinerators met such concentration and temperature standards, respectively, controlling the total emissions to 19.6 g toxic equivalency quantity and maintaining carcinogenic and noncarcinogenic risks significantly below safety levels nationwide. Fully achieving both current standards and future regulations will reduce emissions and health risks by 67.7% and 62.6%, respectively, with waste sorting program contributing the majority. This study reveals substantial benefits from curbing MSW-related dioxins pollution and underscores the promise of ongoing management.

Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.

Sphingosine kinases (SphK), including SphK1 and SphK2, are important enzymes promoting progression of prostate cancer. SKI-178 is a novel and highly potent SphK1/2 dual inhibitor. We here tested the potential anti-prostate cancer cell activity of SKI-178. Bioinformatics analyses and results from local tissues demonstrated that that both SphK1 and SphK2 are upregulated in human prostate cancer tissues. Ectopic overexpression of SphK1 and SphK2, by lentiviral constructs, promoted primary prostate cancer cell proliferation and migration. In primary human prostate cancer cells and immortalized cell lines, SKI-178 potently inhibited cell viability, proliferation, cell cycle progression and cell migration, causing robust cell death and apoptosis. SKI-178 impaired mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production and ATP depletion.SKI-178 potently inhibited SphK activity and induced ceramide production, without affecting SphK1/2 expression in prostate cancer cells. Further, SKI-178 inhibited Akt-mTOR activation and induced JNK activation in prostate cancer cells. Contrarily, a constitutively-active Akt1 construct or the pharmacological JNK inhibitors attenuated SKI-178-induced cytotoxicity in prostate cancer cells. In vivo, daily intraperitoneal injection of a single dose of SKI-178 potently inhibited PC-3 xenograft growth in nude mice. SphK inhibition, ceramide production, ATP depletion and lipid peroxidation as well as Akt-mTOR inactivation and JNK activation were detected in PC-3 xenograft tissues with SKI-178 administration. Together, targeting SphK1/2 by SKI-178 potently inhibited prostate cancer cell growth in vitro and in vivo.

[Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis].

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor ß1 (TGF-ß1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-ß1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.

Cost-benefits analysis of ultra-low emissions standard on air quality and health impact in thermal power plants in China.

As China's largest energy infrastructure, thermal power plant consumed approximately half of China's coal over the past decade and threatened air quality, human health and socioeconomic development. Thus, a series of control policies have been implemented to alleviate those impacts in China. Particularly, China has witnessed unprecedented declines in air pollutant emissions from thermal power plants since the ultra-low emissions (ULE) standards were implemented. In contrast, the effect of the ULE policy on air quality, health and cost benefits remains poorly understood. Therefore, this study estimates the improved air quality and associated health and economic benefits under the ULE standards in the thermal power sector by using a measure-specific approach, combining a bottom-up emission inventory, an atmospheric model, a health assessment model and a cost analysis model. The results show that all the control measures lead to reduced air pollution, and renovating pre-existing units (RPU) is the most effective. Compared to without implementing the ULE policy, the population-weighted average PM2.5 and O3 concentrations decreased by 1.50 µg/m3 and 0.87 ppm, and 67,831 premature deaths could be avoided nationally. Furthermore, the results also show the net economic benefits of combining health benefits and costs due to control measures are 109.92 billion Yuan (in 2015 value) in China. The comprehensive results reveal that the health benefits outweigh the direct policy. Based on these empirical findings and the specific circumstances of China, we suggest that RPU should be further promoted to the entire of China, and if necessary, establish a long-term compensation mechanism for inter-provincial interests and institute and enforce comprehensive policies that carefully consider the health impacts of policies. This study provides strong arguments for China's policy-making and considering tightening emission standards for thermal power plants worldwide.

RNA-Selective Small-Molecule Ligands: Recent Advances in Live-Cell Imaging and Drug Discovery.

RNA structures, including those formed from coding and noncoding RNAs, alternative to protein-based drug targets, could be a promising target of small molecules for drug discovery against various human diseases, particularly in anticancer, antibacterial and antivirus development. The normal cellular activity of cells is critically dependent on the function of various RNA molecules generated from DNA transcription. Moreover, many studies support that mRNA-targeting small molecules may regulate the synthesis of disease-related proteins via the non-covalent mRNA-ligand interactions that do not involve gene modification. RNA-ligand interaction is thus an attractive approach to address the challenge of "undruggable" proteins in drug discovery because the intracellular activity of these proteins is hard to be suppressed with small molecule ligands. We selectively surveyed a specific area of RNA structure-selective small molecule ligands in fluorescence live cell imaging and drug discovery because the area was currently underexplored. This state-of-the-art review thus mainly focuses on the research published within the past three years and aims to provide the most recent information on this research area; hopefully, it could be complementary to the previously reported reviews and give new insights into the future development on RNA-specific small molecule ligands for live cell imaging and drug discovery.

Application of machine learning to predict hospital visits for respiratory diseases using meteorological and air pollution factors in Linyi, China.

Urbanization and industrial development have resulted in increased air pollution, which is concerning for public health. This study evaluates the effect of meteorological factors and air pollution on hospital visits for respiratory diseases (pneumonia, acute upper respiratory infections, and chronic lower respiratory diseases). The test dataset comprises meteorological parameters, air pollutant concentrations, and outpatient hospital visits for respiratory diseases in Linyi, China, from January 1, 2016 to August 20, 2022. We use support vector regression (SVR) to build models that enable analysis of the effect of meteorological factors and air pollutants on the number of outpatient visits for respiratory diseases. Spearman correlation analysis and SVR model results indicate that NO2, PM2.5, and PM10 are correlated with the occurrence of respiratory diseases, with the strongest correlation relating to pneumonia. An increase in the daily average temperature and daily relative humidity decreases the number of patients with pneumonia and chronic lower respiratory diseases but increases the number of patients with acute upper respiratory infections. The SVR modeling has the potential to predict the number of respiratory-related hospital visits. This work demonstrates that machine learning can be combined with meteorological and air pollution data for disease prediction, providing a useful tool whereby policymakers can take preventive measures.

Identification of Disease-Associated MicroRNAs Via Locality-Constrained Linear Coding-Based Ensemble Learning.

Clinical trials indicate that the dysregulation of microRNAs (miRNAs) is closely associated with the development of diseases. Therefore, predicting miRNA-disease associations is significant for studying the pathogenesis of diseases. Since traditional wet-lab methods are resource-intensive, cost-saving computational models can be an effective complementary tool in biological experiments. In this work, a locality-constrained linear coding is proposed to predict associations (ILLCEL). Among them, ILLCEL adopts miRNA sequence similarity, miRNA functional similarity, disease semantic similarity, and interaction profile similarity obtained by locality-constrained linear coding (LLC) as the priori information. Next, features and similarities extracted from multiperspectives are input to the ensemble learning framework to improve the comprehensiveness of the prediction. Significantly, the introduction of hypergraph-regular terms improves the accuracy of prediction by describing complex associations between samples. The results under fivefold cross validation indicate that ILLCEL achieves superior prediction performance. In case studies, known associations are accurately predicted and novel associations are verified in HMDD v3.2, miRCancer, and existing literature. It is concluded that ILLCEL can be served as a powerful tool for inferring potential associations.

KGLRR: A low-rank representation K-means with graph regularization constraint method for Single-cell type identification.

Single-cell RNA sequencing technology provides a tremendous opportunity for studying disease mechanisms at the single-cell level. Cell type identification is a key step in the research of disease mechanisms. Many clustering algorithms have been proposed to identify cell types. Most clustering algorithms perform similarity calculation before cell clustering. Because clustering and similarity calculation are independent, a low-rank matrix obtained only by similarity calculation may be unable to fully reveal the patterns in single-cell data. In this study, to capture accurate single-cell clustering information, we propose a novel method based on a low-rank representation model, called KGLRR, that combines the low-rank representation approach with K-means clustering. The cluster centroid is updated as the cell dimension decreases to better from new clusters and improve the quality of clustering information. In addition, the low-rank representation model ignores local geometric information, so the graph regularization constraint is introduced. KGLRR is tested on both simulated and real single-cell datasets to validate the effectiveness of the new method. The experimental results show that KGLRR is more robust and accurate in cell type identification than other advanced algorithms.

CTLA-4 blockade induces tumor pyroptosis via CD8+ T cells in head and neck squamous cell carcinoma.

Immune checkpoint blockade (ICB) treatment has demonstrated excellent medical effects in oncology, and it is one of the most sought after immunotherapies for tumors. However, there are several issues with ICB therapy, including low response rates and a lack of effective efficacy predictors. Gasdermin-mediated pyroptosis is a typical inflammatory death mode. We discovered that increased expression of gasdermin protein was linked to a favorable tumor immune microenvironment and prognosis in head and neck squamous cell carcinoma (HNSCC). We used the mouse HNSCC cell lines 4MOSC1 (responsive to CTLA-4 blockade) and 4MOSC2 (resistant to CTLA-4 blockade) orthotopic models and demonstrated that CTLA-4 blockade treatment induced gasdermin-mediated pyroptosis of tumor cells, and gasdermin expression positively correlated to the effectiveness of CTLA-4 blockade treatment. We found that CTLA-4 blockade activated CD8+ T cells and increased the levels of interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) cytokines in the tumor microenvironment. These cytokines synergistically activated the STAT1/IRF1 axis to trigger tumor cell pyroptosis and the release of large amounts of inflammatory substances and chemokines. Collectively, our findings revealed that CTLA-4 blockade triggered tumor cells pyroptosis via the release of IFN-γ and TNF-α from activated CD8+ T cells, providing a new perspective of ICB.

A Cytoplasm-Specific Fluorescent Ligand for Selective Imaging of RNA G-Quadruplexes in Live Cancer Cells.

The development of site-specific, target-selective and biocompatible small molecule ligands as a fluorescent tool for real-time study of cellular functions of RNA G-quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm-specific and RNA G4-selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA. These G4s are recognized as human cancer hallmarks. Moreover, intracellular competition studies with BRACO19 and PDS, and the colocalization study with G4-specific antibody (BG4) in HeLa cells may support that the ligand selectively binds to G4s in cellulo. Furthermore, the ligand was demonstrated for the first time in the visualization and monitoring of dynamic resolving process of RNA G4s by the overexpressed RFP-tagged DHX36 helicase in live HeLa cells.

Exosomal miR-93-5p as an important driver of bladder cancer progression.

Background: Tumor-derived exosomes are involved in the process of tumor metastasis and angiogenesis. MicroRNAs (miRNAs) are the most widely investigated factors in exosomes. Therefore, we hope to find a new therapeutic target in bladder cancer (BLCA), which has high incidence rate and mortality. Methods: Exosomal microRNA(miR)-93-5p expression level, downstream target molecules, and biological functions were examined with bioinformatics technology. Exosomes were extracted by sequential differential centrifugation and verified by transmission electron microscopy. The exosomal miR-93-5p on cell proliferation, invasion, and angiogenesis abilities in 5637 and T24 cells was determined by Cell Counting Kit 8 (CCK-8), colony-forming assay, Transwell assay, and vascular ring formation assay. A mouse xenograft model with intratumor injection was adopted to evaluate the correlation between BLCA-derived exosomes and tumor growth in vivo. Results: The results revealed that exosomes play an important role in the biological progression of BLCA, with miR-93-5p being a particularly important molecule. Compared to normal cells, more malignant cells release more exosomal miR-93-5p, and tumor-derived exosomal miR-93-5p could significantly promote cell proliferation, invasion, and angiogenesis in vitro and in vivo. We identified phosphatase and tensin homolog (PTEN) as the most significant target of miR-93-5p in BLCA and human umbilical vein endothelial cells. Conclusions: Our study successfully revealed the biological role and mechanism of BLCA-derived exosomes in tumor progression. Target at tumor exosomes and exosomal miR-93-5p may be an effective treatment in BLCA.