Rationale Design for Anchoring Pendant Groups of Zwitterionic Polymeric Medical Coatings.

A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel. Zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized individually with three anchoring monomers of carboxyl acrylamides with different alkyl spacers, including acryloylglycine (2-AE), 6-acrylamidohexanoic acid (6-AH), and 11-acrylamidoundecanoic acid (11-AU). The carboxylic acid groups are responsible for the stable grafting of copolymers onto stainless steel via a coordinative interaction with metal oxides. Due to hydrophobic interaction and hydrogen bonding, the anchoring monomers enable the formation of self-assembling structures in solution and at a metallic interface, which can play an important role in the thin film formation and functionality of the coatings. Therefore, surface characterizations of anchoring monomers on stainless steel were conducted to analyze the packing density and strength of the intermolecular hydrogen bonds. The corresponding copolymers were synthesized, and their aggregate structures were assessed, showing micelle aggregation for copolymers with higher hydrophobic compositions. The synergistic effects of inter/intramolecular interactions and hydrophobicity of the anchoring monomers result in the diversity of the thickness, surface coverage, wettability, and friction of the polymeric coatings on stainless steel. More importantly, the antifouling properties of the coatings against bacteria and proteins were strongly correlated to thin film formation. Ultimately, the key lies in deciphering the molecular structure of the anchoring pendants in thin film formation and assessing the effectiveness of the coatings, which led to the development of medical coatings through the graft-onto approach.

Energy-efficient dispersion compensation for digital micromirror device.

Due to the wave nature of light, the diffraction pattern generated by an optical device is sensitive to the shift of wavelength. This fact significantly compromises the digital micromirror device (DMD) in applications, such as full-color holographic display and multi-color fluorescence microscopy. The existing dispersion compensation techniques for DMD involve adding diffractive elements, which causes a large amount of waste of optical energy. Here, we propose an energy-efficient dispersion compensation method, based on a dispersive prism, for DMD. This method simulates the diffraction pattern of the optical fields reflected from the DMD with an angular spectrum model. According to the simulation, a prism and a set of optical components are introduced to compensate for the angular dispersion of DMD-modulated optical fields. In the experiment, our method reduced the angular dispersion, between the 532 nm and 660 nm light beams, by a factor of ∼8.5.

Analysis of binding and authentic virus-neutralizing activities of immune sera induced by various monkeypox virus antigens.

Monkeypox cases continue to increase globally, and there is an urgent need to develop a highly effective vaccine against monkeypox. This study investigated the binding and authentic-virus neutralizing activities of sera from mice immunized with EEV (extracellularly enveloped viruses) antigens B6R and A35R, and IMV (intrinsic material viruses) antigens M1R, A29L, E8L, and H3L against monkeypox virus. The results showed that immunizations of A35R and E8L could only induce lower titers of binding antibodies, in contrast, immunization of M1R induced the highest titers of binding antibodies, while immunization of B6R, H3L, and A29L induced moderate titers of binding antibodies. For the live monkeypox virus neutralization assay, the results showed that immunization with two doses of EEV antigen B6R did not effectively induce humoral immune responses to neutralize monkeypox live virus, immunization with EEV-A35R only induced weak monkeypox-neutralizing antibodies. In contrast, the immunization of the four types of monkeypox virus IMV antigens can all induce neutralizing antibodies against authentic monkeypox virus, among them, A29L and H3L induced the highest neutralizing antibody titers. The results of this study provide important references for the selection of antigens in the development of the next generation of monkeypox vaccines.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Stroke and frailty index: a two-sample Mendelian randomisation study.

INTRODUCTION: Previous observational studies have found an increased risk of frailty in patients with stroke. However, evidence of a causal relationship between stroke and frailty is scarce. The aim of this study was to investigate the potential causal relationship between stroke and frailty index (FI). METHODS: Pooled data on stroke and debility were obtained from genome-wide association studies (GWAS).The MEGASTROKE Consortium provided data on stroke (N = 40,585), ischemic stroke (IS,N = 34,217), large-vessel atherosclerotic stroke (LAS,N = 4373), and cardioembolic stroke (CES,N = 7 193).Summary statistics for the FI were obtained from the most recent GWAS meta-analysis of UK BioBank participants and Swedish TwinGene participants of European ancestry (N = 175,226).Two-sample Mendelian randomization (MR) analyses were performed by inverse variance weighting (IVW), weighted median, MR-Egger regression, Simple mode, and Weighted mode, and heterogeneity and horizontal multiplicity of results were assessed using Cochran's Q test and MR-Egger regression intercept term test. RESULTS: The results of the current MR study showed a significant correlation between stroke gene prediction and FI (odds ratio 1.104, 95% confidence interval 1.064 - 1.144, P < 0.001). In terms of stroke subtypes, IS (odds ratio 1.081, 95% confidence interval 1.044 - 1.120, P < 0.001) and LAS (odds ratio 1.037, 95% confidence interval 1.012 - 1.062, P = 0.005). There was no causal relationship between gene-predicted CES and FI. Horizontal multidimensionality was not found in the intercept test for MR Egger regression (P > 0.05), nor in the heterogeneity test (P > 0.05). CONCLUSIONS: This study provides evidence for a causal relationship between stroke and FI and offers new insights into the genetic study of FI.

Adhesive Zwitterionic Poly(ionic liquid) with Unprecedented Organic Solvent Resistance.

The resistance of adhesives to organic solvents is of paramount importance in diverse industries. Unfortunately, many currently available adhesives exhibit either weak intermolecular chain interactions, resulting in insufficient resistance to organic solvents, or possess a permanent covalent crosslinked network, impeding recyclability. This study introduces an innovative approach to address this challenge by formulating zwitterionic poly(ionic liquid) (ZPIL) derivatives with robust dipole-dipole interactions, incorporating sulfonic anions and imidazolium cations. Due to its unique dynamic and electrostatic self-crosslinking structure, the ZPIL exhibits significant adhesion to various substrates and demonstrates excellent recyclability even after multiple adhesion tests. Significantly, ZPIL exhibits exceptional adhesion stability across diverse nonpolar and polar organic solvents, including ionic liquids, distinguishing itself from nonionic polymers and conventional poly(ionic liquid)s. Its adhesive performance remains minimally affected even after prolonged exposure to soaking conditions. The study presents a promising solution for the design of highly organic solvent-resistant materials for plastics, coatings, and adhesives.

Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study.

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

Regulation of Photogenerated Redox Species through High Crystallinity Carbon Nitride for Improved C-S Coupling Reactions.

A novel and efficient approach for the synthesis of α, ß-unsaturated sulfones through heterogeneous photocatalyzed C-S coupling reactions have been developed. The use of molten-salt method derived carbon nitride (MCN), a transition metal-free polymeric photocatalyst, combined with enhanced crystallinity and potassium iodide as an additive, effectively modulates photogenerated reactive redox species, markedly increasing the overall reaction selectivity. This method achieves the shortest reaction time (2 h) with high yield (up to 95 %) among the reported heterogeneous catalytic C-S bond formation reactions, matching the efficiency of the homogeneous photocatalysts. Furthermore, the application to challenging alkyne substrates has been demonstrated, underscoring the potential for a broad range of applications in pharmaceutical research and synthetic chemistry.

Ubiquitin-specific protease 5 promotes bladder cancer progression through stabilizing Twist1.

Aberrant activation of the epithelial-mesenchymal transition (EMT) pathway drives the development of solid tumors, which is precisely regulated by core EMT-related transcription factors, including Twist1. However, the expression pattern and regulatory mechanism of Twist1 in the progression of bladder cancer is still unclear. In this study, we explore the role of Twist1 in the progression of bladder cancer. We discovered that the EMT regulon Twist1 protein, but not Twist1 mRNA, is overexpressed in bladder cancer samples using RT-qPCR, western blot and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation (Co-IP) coupled with liquid chromatography and tandem mass spectrometry identified USP5 as a binding partner of Twist1, and the binding of Twist1 to ubiquitin-specific protease 5 (USP5) stabilizes Twist through its deubiquitinase activity to activate the EMT. Further studies found that USP5 depletion reduces cell proliferation, invasion and the EMT in bladder cancer cells, and ectopic expression of Twist1 rescues the adverse effects of USP5 loss on cell invasion and the EMT. A xenograft tumor model was used to reconfirmed the inhibitor effect of silencing USP5 expression on tumorigenesis in vivo. In addition, USP5 protein levels are significantly elevated and positively associated with Twist1 levels in clinical bladder cancer samples. Collectively, our study revealed that USP5-Twist1 axis is a novel regulatory mechanism driving bladder cancer progression and that approaches targeting USP5 may become a promising cancer treatment strategy.

Fatty acid metabolism-related molecular subtypes and a novel model for predicting prognosis in bladder cancer patients.

This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolismrelated molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2-3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.

A computed tomography-based comprehensive standardized adrenal tumor scoring model for predicting the perioperative outcomes of retroperitoneal laparoscopic adrenal surgery.

Background: Many imaging scoring models have been developed for tumor surgery to provide critical guidance for the selection of surgical methods. However, little research has been aimed at developing scoring models for adrenal tumors and retroperitoneal laparoscopic adrenal surgery (RLAS), which has become the primary technique for treating adrenal tumors. The study set out to establish a computed tomography (CT)-based adrenal tumor scoring model for predicting perioperative outcomes in patients with adrenal tumors who have undergone RLAS. Methods: The retrospective analysis included 306 patients with adrenal tumors diagnosed by preoperative unenhanced or enhanced CT from January 2014 to August 2018 in the First Affiliated Hospital of Fujian Medical University. CT images were used to quantify the tumor location and size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the adhesion of periadrenal fat (PF); and the tumor CT enhancement value. We conducted multivariate ordinal logistic regression analysis to screen variables and performed principal component analysis to construct a novel scoring model for RLAS. The perioperative outcomes of RLAS were evaluated according to postoperative length of stay, operative time (OT), intraoperative blood loss (IBL), and postoperative complications. Results: The final scoring model included tumor size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the tumor CT enhancement value; the adhesion of the PF; and the functional status of adrenal tumors. The total score had positive correlations with the OT (rs=0.431), IBL (rs=0.446), and postoperative length (rs=0.180) (all P values <0.001). Compared to any single metric, the total score provided better prediction of OT and IBL. The grading system for RLAS based on the scoring model also performed well in predicting the complexity and difficulty of RLAS. The coincidence rate for these factors was good (all P values <0.001). Conclusions: The developed model is feasible and repeatable in the prediction of the perioperative outcomes, complexity, and difficulty of RLAS.

Robust Vascular Segmentation for Raw Complex Images of Laser Speckle Contrast Based on Weakly Supervised Learning.

Laser speckle contrast imaging (LSCI) is widely used for in vivo real-time detection and analysis of local blood flow microcirculation due to its non-invasive ability and excellent spatial and temporal resolution. However, vascular segmentation of LSCI images still faces a lot of difficulties due to numerous specific noises caused by the complexity of blood microcirculation's structure and irregular vascular aberrations in diseased regions. In addition, the difficulties of LSCI image data annotation have hindered the application of deep learning methods based on supervised learning in the field of LSCI image vascular segmentation. To tackle these difficulties, we propose a robust weakly supervised learning method, which selects the threshold combinations and processing flows instead of labor-intensive annotation work to construct the ground truth of the dataset, and design a deep neural network, FURNet, based on UNet++ and ResNeXt. The model obtained from training achieves high-quality vascular segmentation and captures multi-scene vascular features on both constructed and unknown datasets with good generalization. Furthermore, we intravital verified the availability of this method on a tumor before and after embolization treatment. This work provides a new approach for realizing LSCI vascular segmentation and also makes a new application-level advance in the field of artificial intelligence-assisted disease diagnosis.

Exploring Novel Genome Instability-associated lncRNAs and their Potential Function in Pan-Renal Cell Carcinoma.

OBJECTIVE: Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC). MATERIALS AND METHODS: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation. RESULTS: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance. CONCLUSIONS: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms.

Association of tea and coffee consumption with the risk of all-cause and cause-specific mortality among individuals with metabolic syndrome: a prospective cohort study.

BACKGROUND: The relationship between tea and coffee consumption and mortality among patients with metabolic syndrome (MetS) remains barely explored. Herein, this study aimed to examine the association between tea and coffee consumption and the likelihood of all-cause and cause-specific mortality in patients with MetS. METHODS: A total of 118,872 participants with MetS at baseline from the UK Biobank cohort were included. Information on tea and coffee consumption was obtained during recruitment using a touchscreen questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were determined using Cox proportional hazards models. RESULTS: During a median follow-up of 13.87 years, 13,666 deaths were recorded, with 5913, 3362, and 994 deaths from cancer, cardiovascular diseases (CVD), and respiratory disease (RD), respectively. This research showed a significant inverse association between tea intake and the risk of all-cause and cancer mortality, the respective HRs (95% CI) for consuming tea 2 vs. 0 cup/day were 0.89 (0.84-0.95), and 0.91 (0.83-0.99), and tea intake ≥ 4 cups/day could reduce CVD mortality by 11% (HR 0.89; 95% CI 0.81-0.98). The U-shaped nonlinear association between coffee intake and all-cause/CVD mortality was examined (all p-nonlinear < 0.001). The HRs (95% CI) for coffee consumption 1 vs. 0 cup/day were 0.93 (0.89-0.98) and 0.89 (0.80-0.99), and for ≥ 4 vs. 0 cup/day were 1.05 (1.01-1.11) and 1.13 (1.03-1.25), respectively. Notably, the combined intake of tea and coffee presented a protective effect against all-cause mortality (HR < 1). CONCLUSIONS: The importance of daily tea and moderate coffee consumption in individuals with MetS to optimise health benefits are highlighted.

Mutating BnEOD1s via CRISPR-Cas9 increases the seed size and weight in Brassica napus.

Seed weight, which is highly correlated to seed size, is a critical agronomic trait that determines the yield of Brassica napus. However, there have been limited researches on the genes involved in regulating seed size. In Arabidopsis thaliana, ENHANCER OF DA1 (EOD1), an E3 ubiquitin ligase gene, has been identified as a significant negative regulator in controlling organ size, but the function of its homologs in rapeseed remains unknown. Only two homologous of EOD1, BnaEOD1.A04 and BnaEOD1.C04, have been found in B. napus and were mutated using the CRISPR-Cas9 system. Three T-DNA-free lines, T2-157-1-C8, T2-390-2-B8, and T2-397-2-E2, were identified from the homozygous T2 mutant lines. The BnaEOD1.A04 showed a similar type of editing in these mutants, whereas the BnaEOD1.C04 in T2-397-2-E2 was only missing 26 amino acids, and the translation was not prematurely terminated, which was different from the other two mutants. In parallel, mutation of BnaEOD1s resulted in a noteworthy increase in both seed size and seed weight in the three editing lines. Additionally, there was a significant decline in the number of seeds per silique (SPS) and silique length (SL) in T2-157-1-C8 and T2-390-2-B8, but T2-397-2-E2 did not show any significant changes in the SPS and SL, possibly due to distinct types of editing in the three lines. The above results indicate the conserved function of EOD1 homologs and provides promising germplasm for breeding novel high-yield rapeseed varieties by improving seed size and thousand-seed weight. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01430-z.

The effect of body mass index on quality of life in modified single stoma cutaneous ureterostomy or ileal conduit after radical cystectomy.

OBJECTIVE: To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC). METHODS: Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality-of-life scores and postoperative clinical parameters. RESULTS: Spearman correlation analysis showed that postoperative BMI, late complications and catheter-free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter-free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p<0.05). Patients in Group 2 with significant weight loss had a better Global QoL, a lower rate of stomal stricture and a higher catheter-free state compared with those in Group 1 in both IC and MSSCU patients. MSSCU patients in Group 2 could achieve a comparable Global QoL as to IC patients in Group 1. CONCLUSION: Controlling the substantial increase in body weight after surgery contributes to improving QoL, reducing the occurrence of stomal stricture, and ensuring a postoperative catheter-free state in BCa patients undergoing MSSCU.

Effectiveness, safety and patients' perceptions of an immersive virtual reality-based exercise system for poststroke upper limb motor rehabilitation: A proof-of-concept and feasibility randomized controlled trial.

Objective: This study aimed to examine the effectiveness, safety and patients' perceptions of an immersive virtual reality (VR)-based exercise system for poststroke upper limb rehabilitation. Methods: A proof-of-concept, 2-week randomized controlled trial was conducted. Fifty stroke patients were randomly assigned to either use the immersive VR-based exercise system to perform upper limb exercises for 2 weeks (intervention) or play commercial games (control). Effectiveness, safety and patients' perceptions of the exercise system were assessed at baseline and at 1- and 2-week follow-ups. Results: Intention-to-treat analysis revealed that after 2 weeks, statistically significant improvements in shoulder flexion active range of motion (AROM), shoulder abduction AROM, perceived upper limb motor function and quality of life (QoL) were observed in one or both groups, but not between the groups. Per-protocol analysis showed that after 2 weeks: (i) statistically significant improvement in shoulder abduction AROM was obtained in the intervention group, and the difference in the mean changes between the groups was statistically significant; (ii) statistically significant improvements in coordination/speed (Fugl-Meyer Assessment for Upper Extremity), shoulder flexion AROM, perceived upper limb motor function and QoL were obtained in one or both groups, but not between the groups. Conclusions: The immersive VR-based exercise system is a potentially effective, safe and acceptable approach for supporting poststroke motor rehabilitation. These findings can serve as a basis for larger-scale studies on the application of VR for poststroke exercises.

A novel CD8+ T cell-related gene signature for predicting the prognosis and immunotherapy efficacy in bladder cancer.

OBJECTIVE: To identify CD8+ T cell-related molecular clusters and establish a novel gene signature for predicting the prognosis and efficacy of immunotherapy in bladder cancer (BCa). METHODS: Transcriptome and clinical data of BCa samples were obtained from the Cancer Genome Atlas (TCGA) and GEO databases. The CD8+ T cell-related genes were screened through the CIBERSORT algorithm and correlation analysis. Consensus clustering analysis was utilized to identified CD8+ T cell-related molecular clusters. A novel CD8+ T cell-related prognostic model was developed using univariate Cox regression analysis and Lasso regression analysis. Internal and external validations were performed and the validity of the model was validated in a real-world cohort. Finally, preliminary experimental verifications were carried out to verify the biological functions of SH2D2A in bladder cancer. RESULTS: A total of 52 CD8+ T cell-related prognostic genes were screened and two molecular clusters with notably diverse immune cell infiltration, prognosis and clinical features were developed. Then, a novel CD8+ T cell-related prognostic model was constructed. The patients with high-risk scores exhibited a significantly worse overall survival in training, test, whole TCGA and validating cohort. The AUC was 0.766, 0.725, 0.739 and 0.658 in the four cohorts sequentially. Subgroup analysis suggested that the novel prognostic model has a robust clinical application for selecting high-risk patients. Finally, we confirmed that patients in the low-risk group might benefit more from immunotherapy or chemotherapy, and validated the prognostic model in a real-world immunotherapy cohort. Preliminary experiment showed that SH2D2A was capable of attenuating proliferation, migration and invasion of BCa cells. CONCLUSIONS: CD8+ T cell-related molecular clusters were successfully identified. Besides, a novel CD8+ T cell-related prognostic model with an excellent predictive performance in predicting survival rates and immunotherapy efficacy of BCa was developed.