Pan-cancer Analysis Reveals m6A Variation and Cell-specific Regulatory Network in Different Cancer Types.

As the most abundant messenger RNA (mRNA) modification in mRNA, N  6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the function and role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called "m6A-express", we predicted m6A-regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin, and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A for cancer precision medicine for patients with different cancer types.

An Exo III-powered closed-loop DNA circuit architecture for biosensing/imaging.

With their regulated Boolean logic operations in vitro and in vivo, DNA logic circuits have shown great promise for target recognition and disease diagnosis. However, significant obstacles must be overcome to improve their operational efficiency and broaden their range of applications. In this study, we propose an Exo III-powered closed-loop DNA circuit (ECDC) architecture that integrates four highly efficient AND logic gates. The ECDC utilizes Exo III as the sole enzyme-activated actuator, simplifying the circuit design and ensuring optimal performance. Moreover, the use of Exo III enables a self-feedback (autocatalytic) mechanism in the dynamic switching between AND logic gates within this circulating logic circuit. After validating the signal flow and examining the impact of each AND logic gate on the regulation of the circuit, we demonstrate the intelligent determination of miR-21 using the carefully designed ECDC architecture in vitro. The proposed ECDC exhibits a linear detection range for miR-21 from 0 to 300 nM, with a limit of detection (LOD) of approximately 0.01 nM, surpassing most reported methods. It also shows excellent selectivity for miR-21 detection and holds potential for identifying and imaging live cancer cells. This study presents a practical and efficient strategy for monitoring various nucleic acid-based biomarkers in vitro and in vivo through specific sequence modifications, offering significant potential for early cancer diagnosis, bioanalysis, and prognostic clinical applications.

GutUDB: A comprehensive multiomics database for intestinal diseases.

Gut Universe Database (GutUDB) provides a comprehensive, systematic, and practical platform for researchers, and is dedicated to the management, analysis, and visualization of knowledge related to intestinal diseases. Based on this database, eight major categories of omics data analyses are carried out to explore the genotype-phenotype characteristics of a certain intestinal disease. The first tool for comprehensive omics data research on intestinal diseases will help each researcher better understand intestinal diseases.

Improving aromatic higher alcohol acetates in wines by co-fermentation of Pichia kluyveri and Saccharomyces cerevisiae: growth interaction and amino acid competition.

BACKGROUND: Higher alcohol acetates (HAAs) are potent aroma-active esters that impart desirable fruity and floral aromas. However, the conversion of higher alcohol precursors into HAAs is extremely low in winemaking. To investigate the underlying yeast-yeast interaction on targeted improvement of aromatic HAAs, we evaluated fermentation activity, cell viability, amino acid consumption and HAA production when Pichia kluyveri and Saccharomyces cerevisiae were inoculated concurrently or sequentially. RESULTS: Pichia kluyveri PK-21 possessed the ability to survive and increased HAA level up to 5.2-fold in mixed fermentation. Such an increment may benefit from the efficient conversion of higher alcohol precursors into HAAs (>27-fold higher than S. cerevisiae). During mixed fermentation, the two yeasts exhibited crucial interactions regarding cell growth and amino acid competition. Saccharomyces cerevisiae dominated over the co-inoculated P. kluyveri by efficient uptake of amino acids and biomass production. However, this dominance decreased in sequential fermentation, where P. kluyveri growth increased due to the consumption of preferred amino acids prior to S. cerevisiae. Pearson correlation analysis indicated that phenylalanine and aspartic acid may act as positive amino acids in boosting P. kluyveri growth and HAA production. Laboratory-scale winemaking validated the fermentation performance of P. kluyveri in sequential inoculum, resulting in a balanced aroma profile with enhanced floral and tropical fruity characteristics in the final wines. CONCLUSION: This study proposes a microbial, non-genetically engineered approach for targeted increase of HAA production in winemaking and the findings provide new insights into yeast-yeast interactions. © 2024 Society of Chemical Industry.

The application of impulse oscillometry system based on machine learning algorithm in the diagnosis of chronic obstructive pulmonary disease.

Objective. Diagnosing chronic obstructive pulmonary disease (COPD) using impulse oscillometry (IOS) is challenging due to the high level of clinical expertise it demands from doctors, which limits the clinical application of IOS in screening. The primary aim of this study is to develop a COPD diagnostic model based on machine learning algorithms using IOS test results.Approach. Feature selection was conducted to identify the optimal subset of features from the original feature set, which significantly enhanced the classifier's performance. Additionally, secondary features area of reactance (AX) were derived from the original features based on clinical theory, further enhancing the performance of the classifier. The performance of the model was analyzed and validated using various classifiers and hyperparameter settings to identify the optimal classifier. We collected 528 clinical data examples from the China-Japan Friendship Hospital for training and validating the model.Main results. The proposed model achieved reasonably accurate diagnostic results in the clinical data (accuracy = 0.920, specificity = 0.941, precision = 0.875, recall = 0.875).Significance. The results of this study demonstrate that the proposed classifier model, feature selection method, and derived secondary feature AX provide significant auxiliary support in reducing the requirement for clinical experience in COPD diagnosis using IOS.

Alternative Polyadenylation Regulatory Factors Signature for Survival Prediction in Kidney Renal Cell Carcinoma.

Background: Alternative polyadenylation (APA) plays a vital regulatory role in various diseases. It is widely accepted that APA is regulated by APA regulatory factors. Objective: Whether APA regulatory factors affect the prognosis of renal cell carcinoma remains unclear, and this is the main topic of this study. Methods: We downloaded the transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database. We used the Lasso regression system to construct an APA model for analyzing the relationship between common APA regulatory factors and renal cell carcinoma. We also validated our APA model using independent GEO datasets (GSE29609, GSE76207). Results: It was found that the expression levels of 5 APA regulatory factors (CPSF1, CPSF2, CSTF2, PABPC1, and PABPC4) were significantly associated with tumor gene mutation burden (TMB) score in renal clear cell carcinoma, and the risk score constructed using the expression level of 5 key APA regulatory factors could be used to predict the outcome of renal clear cell carcinoma. The TMB score is associated with the remodeling of the immune microenvironment. Conclusions: By identifying key APA regulatory factors in renal cell carcinoma and constructing risk scores for key APA regulatory factors, we showed that key APA regulators affect prognosis of renal clear cell carcinoma patients. In addition, the risk score level is associated with TMB, indicating that APA may affect the efficacy of immunotherapy through immune microenvironment-related genes. This helps us better understand the mRNA processing mechanism of renal clear cell carcinoma.

CS/CoFe2O4 nanocomposite as a high-effective and steady chainmail catalyst for tetracycline degradation with peroxymonosulfate activation: performance and mechanism.

Tetracycline becomes a crucial measure for managing and treating communicable diseases in both human and animal sectors due to its beneficial antibacterial properties and cost-effectiveness. However, it is important not to trivialize the associated concerns of environmental contamination following the antibiotic's application. In this study, cobalt ferrate (CoFe2O4) nanoparticles were loaded into chitosan (CS), which can avoid the agglomeration problem caused by high surface energy and thus improve the catalytic performance of cobalt ferrate. And it can avoid the problem of secondary contamination caused by the massive leaching of metal ions. The resulting product was used as a catalyst to activate peroxymonosulfate (PMS) for the degradation of tetracycline (TC). To determine the potential effects on TC degradation, various factors such as PMS dosing, catalyst dosing, TC concentration, initial solution pH, temperature, and inorganic anions (Cl-, H2PO4- and HCO3-) were investigated. The CS/CoFe2O4/PMS system exhibited superior performance compared to the CoFe2O4-catalyzed PMS system alone, achieving a 92.75% TC removal within 120 min. The catalyst displayed high stability during the recycling process, with the efficiency observed after five uses remaining at a stable 73.1%, and only minor leaching of dissolved metal ions from the catalyst. This confirms the high stability of the catalyst. The activation mechanism study showed that there are free radical and non-free radical pathways in the reaction system to degrade TC together, and SO4•- and 1O2 are the primary reactive oxygen radicals involved in the reaction, allowing for effective treatment of contaminated water by TC.

Applying the extended parallel process model to understand households' responses to tornado and earthquake risks in Oklahoma.

Oklahoma is a multihazard environment where both natural (e.g., tornadoes) and technological hazards (e.g., induced seismicity) are significant, making Oklahoma a unique setting to better understand how to manage and prepare for multiple hazards. While studies have attempted to understand drivers of hazard adjustments, few have focused on the overall number of adjustments undertaken instead of individual adjustments or adjustments in a multihazard environment. To address these gaps, we employ a survey sample of 866 households in Oklahoma to understand households' danger control responses (protective hazard adjustments) for tornado and earthquake risks in Oklahoma. We apply the extended parallel processing model (EPPM) to categorize respondents according to their relative level of perceived threat and efficacy of protective actions in predicting the number of hazard adjustments they intend to or have adopted in response to tornadoes and induced earthquakes. In line with the EPPM, we found that households have the highest number of danger control responses when their perceived threat and efficacy are both high. Counter to the EPPM literature, we found low threat coupled with high efficacy moved some individuals toward the adoption of danger control responses in response to both tornadoes and earthquakes. When households have high efficacy, threat appraisals matter in tornado danger control responses but not in earthquake danger control responses. This EPPM categorization opens new research approaches for studies of natural and technological hazards. This study also provides information for local officials and emergency managers making mitigation and preparedness investments and policies.

Osteosarcoma Explorer: A Data Commons With Clinical, Genomic, Protein, and Tissue Imaging Data for Osteosarcoma Research.

PURPOSE: Osteosarcoma research advancement requires enhanced data integration across different modalities and sources. Current osteosarcoma research, encompassing clinical, genomic, protein, and tissue imaging data, is hindered by the siloed landscape of data generation and storage. MATERIALS AND METHODS: Clinical, molecular profiling, and tissue imaging data for 573 patients with pediatric osteosarcoma were collected from four public and institutional sources. A common data model incorporating standardized terminology was created to facilitate the transformation, integration, and load of source data into a relational database. On the basis of this database, a data commons accompanied by a user-friendly web portal was developed, enabling various data exploration and analytics functions. RESULTS: The Osteosarcoma Explorer (OSE) was released to the public in 2021. Leveraging a comprehensive and harmonized data set on the backend, the OSE offers a wide range of functions, including Cohort Discovery, Patient Dashboard, Image Visualization, and Online Analysis. Since its initial release, the OSE has experienced an increasing utilization by the osteosarcoma research community and provided solid, continuous user support. To our knowledge, the OSE is the largest (N = 573) and most comprehensive research data commons for pediatric osteosarcoma, a rare disease. This project demonstrates an effective framework for data integration and data commons development that can be readily applied to other projects sharing similar goals. CONCLUSION: The OSE offers an online exploration and analysis platform for integrated clinical, molecular profiling, and tissue imaging data of osteosarcoma. Its underlying data model, database, and web framework support continuous expansion onto new data modalities and sources.

Breeding Behavior, Nestling Growth, and Begging Behavior in the Plain Laughingthrush (Garrulax davidi): Implications for Parent-Offspring Conflict.

Investigation on food allocation among nestlings of altricial birds is crucial in understanding parent-offspring conflicts within avian families. However, there is no consensus in empirical studies regarding whether parents or offspring determine the food allocation pattern within a brood. In the Plain Laughingthrush (Garrulax davidi), we examine the relationship between parental feeding strategies and nestling begging behaviors. Due to hatching asynchrony, larger nestlings have a competitive advantage in food acquisition over their smaller brood-mates; nevertheless, if the initial food-receivers were already satiated and did not immediately consume the food, parents would retrieve the food and re-allocate it to another nestling. This re-feeding tactic employed by parents reduced the likelihood of early-hatched nestlings monopolizing the food solely due to their larger body size. Our findings indicate that parents primarily allocated food based on nestling begging intensity, while their re-feeding tactic is determined by whether the first food-receivers have consumed the food. To date, our research demonstrates that while parental food allocation primarily hinges on the begging intensity of the nestlings, the decision to re-feed is contingent upon whether the initial recipients of the food ingest it immediately.

Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration.

Synaptotagmin-1 and synaptotagmin-7 are two prominent calcium sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding calcium, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examine the biophysical properties of these two synaptotagmin isoforms and compare their interactions with phospholipid membranes. We discover that synaptotagmin-1-membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a super-penetrator. We exploit these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to calcium.

Characteristics and risk factors for readmission in HIV-infected patients with Talaromyces marneffei infection.

OBJECTIVES: Talaromyces marneffei (T. marneffei) is an opportunistic fungal infection (talaromycosis), which is common in subtropical regions and is a leading cause of death in HIV-1-infected patients. This study aimed to determine the characteristics and risk factors associated with hospital readmissions in HIV patients with T. marneffei infection in order to reduce readmissions. METHODS: We conducted a retrospective study of admitted HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from 2012 to 2019. Kaplan-Meier analyses and Principal component analysis (PCA) were used to evaluate the effects of T. marneffei infection on patient readmissions. Additionally, univariate and multifactorial analyses, as well as Propensity score matching (PSM) were used to analyze the factors associated with patient readmissions. RESULTS: HIV/AIDS patients with T. marneffei-infected had shorter intervals between admissions and longer lengths of stay than non-T. marneffei-infected patients, despite lower readmission rates. Compared with non-T. marneffei-infected patients, the mortality rate for talaromycosis patients was higher at the first admission. Among HIV/AIDS patients with opportunistic infections, the mortality rate was highest for T. marneffei at 16.2%, followed by cryptococcus at 12.5%. However, the readmission rate was highest for cryptococcus infection (37.5%) and lowest for T. marneffei (10.8%). PSM and Logistic regression analysis identified leukopenia and elevated low-density lipoprotein (LDL) as key factors in T.marneffei-infected patients hospital readmissions. CONCLUSIONS: The first admission represents a critical window to intervene in the prognosis of patients with T. marneffei infection. Leukopenia and elevated LDL may be potential risk factors impacting readmissions. Our findings provide scientific evidence to improve the long-term outcomes of HIV patients with T. marneffei infection.

Quantum-sized topological insulators/semimetals enable ultrahigh and broadband saturable absorption.

Two-dimensional topological insulators/semimetals have recently attracted much attention. However, quantum-sized topological insulators/semimetals with intrinsic characteristics have never been reported before. Herein, we report the high-yield production of topological insulator (i.e., Bi2Se3 and Sb2Te3) and semimetal (i.e., TiS2) quantum sheets (QSs) with monolayer structures and sub-4 nm lateral sizes. Both linear and nonlinear optical performances of the QSs are investigated. The QS dispersions present remarkable photoluminescence with excitation wavelength-, concentration-, and solvent-dependence. The solution-processed QSs-poly(methyl methacrylate) (PMMA) hybrid thin films demonstrate exceptional nonlinear saturation absorption (NSA). Particularly, Bi2Se3 QSs-PMMA enables record-high NSA performance with a broadband feature. Specifically, the (absolute) modulation depths up to 71.6 and 72.4% and saturation intensities down to 1.52 and 0.49 MW cm-2 are achieved at 532 and 800 nm, respectively. Such a phenomenal NSA performance would greatly facilitate their applications in mode-locked lasers and related fields.

A Fast Calibration Method for Pneumotachograph with a 3L Syringe.

The pneumotachograph (PNT), a commonly used flowmeter in pulmonary function diagnostic equipment, is the required frequency calibration to maintain high accuracy. Aiming to simplify calibration steps, we developed a fast calibration system with a commercially available 3L syringe to provide a real output flow waveform. The acquisition of the real output flow waveform is based on the reliable measurement of in-cylinder pressure and the real-time detection of plunger speed. To improve the calibration accuracy, the tapping position for measuring in-cylinder pressure was optimized by CFD dynamic-mesh updating technique. The plunger speed was obtained by tracking the handle of the plunger with a smart terminal. Then, the real output flow was corrected using a compensation model equation. The calibration system was verified by the pulmonary waveform generator that the accuracy satisfied the requirements for respiratory flow measurement according to ATS standardization. The experimental results suggest that the developed method promises the fast calibration of PNT.

The moderating role of depression in the association between hypertension during pregnancy and birth outcomes.

OBJECTIVE: Investigate how hypertension during pregnancy (HDP) and depression during pregnancy (DDP) independently and jointly affect infant birth outcomes. METHODS: This population-based, retrospective cohort study included a sample of 68,052 women who participated in PRAMS 2016-2018 survey. Poisson regression was used for adjusted relative risks (aRRs). RESULTS: Compared to women without HDP and DDP, aRRs for PTB and LBW among women with both HDP and DDP are 2.04 (95% CI 1.73, 2.42) and 2.84 (95% CI 2.27, 3.56), respectively, albeit lower than the expected joint effect of risk. CONCLUSION: DDP may modify the association between HDP and PTB, LBW.

Leveraging Ligand and Composition Effects: Morphology-Tailorable Pt-Bi Bimetallic Aerogels for Enhanced (Photo-)Electrocatalysis.

Metal aerogels (MAs) are emerging porous materials displaying unprecedented potential in catalysis, sensing, plasmonic technologies, etc. However, the lack of efficient regulation of their nano-building blocks (NBBs) remains a big hurdle that hampers the in-depth investigation and performance enhancement. Here, by harmonizing composition and ligand effects, Pt- and Bi-based single- and bimetallic aerogels bearing NBBs of controlled dimensions and shapes are obtained by facilely tuning the metal precursors and the applied ligands. Particularly, by further modulating the electronic and optic properties of the aerogels via adjusting the content of the catalytically active Pt component and the semiconducting Bi component, both the electrocatalytic and photoelectrocatalytic performance of the Pt-Bi aerogels can be manipulated. In this light, an impressive catalytic performance for electro-oxidation of methanol is acquired, marking a mass activity of 6.4-fold higher under UV irradiation than that for commercial Pt/C. This study not only sheds light on in situ manipulating NBBs of MAs, but also puts forward guidelines for crafting high-performance MAs-based electrocatalysts and photoelectrocatalysts toward energy-related electrochemical processes.

Chloroquine Protects Hypoxia/Ischemia-Induced Neonatal Brain Injury in Rats by Mitigating Blood-Brain Barrier Disruption.

Neonatal hypoxic-ischemic (H/I) brain damage (HIBD) is a devastating condition for which there are presently no effective therapeutic strategies against its severe neurological deficits in neonates and young children. Traditionally, H/I induces the compromise of the blood-brain barrier (BBB), which causes neuronal cell death, eventually resulting in brain secondary injury. In addition to neonatal HIBD, chloroquine (CQ) has been proved to exert a protective effect on BBB disruption in several brain injury models. The main purpose of this research was to study whether CQ protects the BBB from H/I insult and confers beneficial neuroprotection in the neonatal Rice-Vannucci rat model. Herein, we reported that CQ administration significantly reduced brain damage and improved behavioral dysplasia after H/I injury. Moreover, we demonstrated the protective effects of CQ on BBB integrity, evidenced by ameliorating brain edema and Evans blue extravasation, inhibiting the degeneration of the tight junction and adherens junction proteins, and improving pericyte survival in neonatal rats after HIBD. These findings indicated that CQ administration protected the BBB against H/I injury, thereby ameliorating brain damage and promoting neurofunctional recovery. Collectively, our data demonstrated that CQ played a crucial role in BBB integrity after neonatal H/I injury, which sheds light on the development of therapeutic agents to treat HIBD.

Weighted gene co-expression network analysis revealed T cell differentiation associated with the age-related phenotypes in COVID-19 patients.

The risk of severe condition caused by Corona Virus Disease 2019 (COVID-19) increases with age. However, the underlying mechanisms have not been clearly understood. The dataset GSE157103 was used to perform weighted gene co-expression network analysis on 100 COVID-19 patients in our analysis. Through weighted gene co-expression network analysis, we identified a key module which was significantly related with age. This age-related module could predict Intensive Care Unit status and mechanical-ventilation usage, and enriched with positive regulation of T cell receptor signaling pathway biological progress. Moreover, 10 hub genes were identified as crucial gene of the age-related module. Protein-protein interaction network and transcription factors-gene interactions were established. Lastly, independent data sets and RT-qPCR were used to validate the key module and hub genes. Our conclusion revealed that key genes were associated with the age-related phenotypes in COVID-19 patients, and it would be beneficial for clinical doctors to develop reasonable therapeutic strategies in elderly COVID-19 patients.

Enhanced π-π Stacking between Dipole-Bearing Single Molecules Revealed by Conductance Measurement.

Dipoles are widely involved in π-π interactions and are central to many chemical and biological functions, but their influence on the strength of π-π interactions remains unclear. Here, we report a study of π-π interaction between azulene-based, polar single molecules and between naphthalene-based, nonpolar single molecules. By performing scanning tunneling microscopy break junction measurements of single-molecule conductance, we show that the π-stacked dimers formed by the azulene-based, polar aromatic structures feature higher electrical conductivity and mechanical stability than those formed by the naphthalene-based, nonpolar molecules. Mechanical control of π-π interactions in both rotational and translational motion reveals a sensitive dependence of the stacking strength on relative alignment between the dipoles. The antiparallel alignment of the dipoles was found to be the optimal stacking configuration that underpins the observed enhancement of π-π stacking between azulene-based single molecules. Density functional theory calculations further explained the observed enhancement of stacking strength and the corresponding charge transport efficiency. Our experimental and theoretical results show that the antiparallel alignment of the dipole moments significantly enhances the electronic coupling and mechanical stability of π-π stacking. In addition, in the formation of single-molecule junctions, the azulene group was experimentally and theoretically proved to form a Au-π contact with electrodes with high charge transport efficiency. This paper provides evidence and interpretation of the role of dipoles in π-π interactions at the single-molecule level and offers new insights into potential applications in supramolecular devices.

Cluster analysis of patients with chronic rhinosinusitis and asthma after endoscopic sinus surgery.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps and asthma (CRSwAS) are highly heterogenous in severity and prognosis. The clinical phenotypes and inflammatory endotypes of CRSwAS and their association with outcomes of endoscopic sinus surgery (ESS) have not been fully studied yet. OBJECTIVE: We aimed to find out the clinical phenotypes of CRSwAS and explore their relationship with ESS outcomes using cluster analysis. METHODS: We recruited 103 consecutive adult patients with CRSwAS who had undergone ESS and been followed up for more than 1 year. For cluster analysis, we collected the data from 63 variables pertaining to demographic characteristics, preoperative disease status, surgical techniques, postoperative medical treatment, and outcomes. Eosinophilic CRS was defined as greater than or equal to 10 eosinophils/high-power field, and sinus computed tomography was evaluated by Lund-Mackay sinus computed tomography score (LM score). RESULTS: We screened 92 eligible patients and 13 preoperative variables for balanced iterative reducing and clustering using hierarchies cluster analysis. Patients with CRSwAS were divided into 4 clusters with distinct ESS outcomes: (1) cluster 1, characterized by aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (2) cluster 2, characterized as having female dominance (66.67%), non-aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (3) cluster 3, characterized as having female dominance (95.83%), noneosinophilic CRS, low preoperative LM score, moderate asthma, and controlled CRS after ESS; and (4) cluster 4, characterized as men-only, smoker, noneosinophilic CRS, low preoperative LM score, mild asthma, and controlled CRS after ESS. CONCLUSION: CRSwAS has distinct clusters, each corresponding to unique clinical and inflammatory characteristics and ESS outcomes.