Design of Cryptococcus neoformans multi-epitope vaccine based on immunoinformatics method.

Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.

A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.

A novel mRNA multi-epitope vaccine of Acinetobacter baumannii based on multi-target protein design in immunoinformatic approach.

Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.

Design of a cryptococcus neoformans vaccine by subtractive proteomics combined with immunoinformatics.

The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

AIMS: The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. METHODS AND RESULTS: A two-stage (decision + Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5 year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2 years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468 462, £28 910, €26 045, and $71 199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. CONCLUSIONS: MitraClip + guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines.

The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications. Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, "LbL-CoV19". These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The "plug-and-play" platform technology is well suited to preparedness for future pandemics and disease outbreaks.

Optimization of doping design for planar P-N homologous junction perovskite solar cells.

In this study, we used the solar cell capacitance simulator (SCAPS) to analyse numerically the performance of perovskite solar cells (PSCs) containing CH3NH3PbI3. The findings indicate that P-N homologous junction processing based on traditional P-I-N PSCs can enhance the photoelectric conversion efficiency (PCE). Furthermore, the authors analyzed the effect of uniform P-N doping of CH3NH3PbI3, concluding that the photoelectric efficiency can be improved from 16.10% to 19.03% after doping. In addition, the optical properties of PSCs under solar irradiation are simulated using finite difference time-domain (FDTD) software under AM1.5. This method is applied to investigate the effect of the P-N uniform junction on the internal electric field generated within the cell. The generation of this electric field promotes carrier separation and transmission, ultimately increasing the open circuit voltage (VOC) of the solar cell from 1.03 to 1.12 V. The usage of P-N junctions enhances PSCs performance and exhibits vast potential for designing and developing PSCs.

A Study on the Surface Quality and Damage Properties of Single-Crystal Silicon Using Different Post-Treatment Processes.

Detecting subsurface defects in optical components has always been challenging. This study utilizes laser scattering and photothermal weak absorption techniques to detect surface and subsurface nano-damage precursors of single-crystal silicon components. Based on laser scattering and photothermal weak absorption techniques, we successfully establish the relationship between damage precursors and laser damage resistance. The photothermal absorption level is used as an important parameter to measure the damage resistance threshold of optical elements. Single-crystal silicon elements are processed and post-processed optimally. This research employs dry etching and wet etching techniques to effectively eliminate damage precursors from optical components. Additionally, detection techniques are utilized to comprehensively characterize these components, resulting in the successful identification of optimal damage precursor removal methods for various polishing types of single-crystal silicon components. Consequently, this method efficiently enhances the damage thresholds of optical components.

The Impact of Contrast-Associated Acute Kidney Injury on All-Cause Mortality in Older Patients After Coronary Angiography:A 7.5-year Follow-Up.

Older patients (≥75 years) after coronary angiography constitute an increasing proportion, but only limited data are available regarding the prognosis of geriatric contrast-associated acute kidney injury (CA-AKI). Patients (≥75 years) undergoing coronary angiography between December 2010 and September 2013 were consecutively enrolled. CA-AKI was defined as an increase in serum creatinine of 25% or .5 mg/dL from the baseline within 48-72 h of contrast exposure. All-cause mortality was assessed during median 7.5 years (interquartile range [IQR] 6.7-8.7 years) follow-up period. In total, 571 patients aged >75 years undergoing coronary angiography were enrolled in a single center study; 82 (14.4%) patients had CA-AKI. The all-cause mortality during the median 7.5 years follow-up period was 22.0% in patients with CA-AKI and 13.1% in patients without CA-AKI (P = .015). After adjusting for potential confounding factors, the multivariable analysis indicated that CA-AKI was related to an increased risk of all-cause mortality during the median 7.5-year follow-up (hazard ratio [HR]: 2.46; 95% CI: 1.29-4.7; P = .006). CA-AKI is a significant and independent predictor of long-term mortality for patients aged over 75 years who underwent coronary angiography.

Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.

Developing a safe and effective preventive for HIV-1 remains the hope for controlling the global AIDS epidemic. Recently, mRNA vaccines have emerged as a promising alternative to conventional vaccine approaches, primarily due to their rapid development and potential for low-cost manufacture. Despite the advantages of mRNA vaccines, challenges remain, especially due to the adverse effects of the delivery vehicle and low delivery efficiency. As a result, Luna Labs is developing a short carbon nanotube-based delivery platform (NanoVac) that can co-deliver mRNA and HIV-1 glycoproteins to the immune system efficiently with negligible toxicity. Surface chemistries of NanoVac were optimized to guide antigen/mRNA loading density and presentation. Multiple formulations were engineered for compatibility with both intramuscular and intranasal administration. NanoVac candidates demonstrated immunogenicity in rabbits and generated human-derived humoral and cellular responses in humanized mice (HIS). Briefly, 33% of the HIV-1-infected HIS mice vaccinated with NanoVac-mRNA was cleared of virus infection by 8-weeks post-infection. Finally, NanoVac stabilized the loaded mRNA against degradation under refrigeration for at least three months, reducing the cold chain burden for vaccine deployment.

Simulation Optimization of AlGaN/GaN SBD with Field Plate Structures and Recessed Anode.

This study investigated several AlGaN/GaN Schottky Barrier Diodes (SBDs) with different designs to achieve device optimization. First, the optimal electrode spacing, etching depth, and field plate size of the devices were measured using Technology Computer-Aided Design (TCAD) software by Silvaco, and analysis of the electrical behavior of the device was based on the simulation results, and several AlGaN/GaN SBD chips were designed and prepared. The experimental results revealed that the recessed anode can increase the forward current and reduce the on-resistance. An etched depth of 30 nm could obtain a turn-on voltage of 0.75 V and a forward current density of 216 mA/mm. A breakdown voltage of 1043 V and a power figure of merit (FOM) value of 572.6 MW/cm2 was obtained with a 3 µm field plate. Experiments and simulations confirmed that the recessed anode and field plate structure could increase the breakdown voltage and forward current and improve the FOM value, resulting in higher electrical performance and a wider range of application scenarios.

Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity.

Purpose: This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM. Methods: GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart. Results: A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts. Conclusion: Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.

Does the patellar tendon reflex affect the postural stability in stroke patients with blocked vision?

Background: Stroke patients often show postural instability. The patellar tendon reflex is a basic physical examination for stroke patients. This study aimed to explore the correlation between patellar tendon reflex grade and postural stability among stroke patients. Methods: A total of 37 elderly stroke patients, each with the same quadriceps muscle strength but different patellar tendon reflex levels, were tested on a force platform under eyes-open (EO) and eyes-closed (EC) conditions. Parametric analysis, detrended fluctuation analysis (DFA), and power spectral density (PSD) analysis were used in centre of pressure (COP) signal processing. The correlation between the results of measured data processing and the level of patellar tendon reflex was analysed. Results: All three parameters of COP (the length of the sway trajectory, the mean range of the sway trajectory in the mediolateral [ML] direction [R x ], and the mean range of the sway trajectory in the anterior-posterior [AP] directions [R y ]) were negatively correlated with the patient's patellar tendon reflex grade under the EC condition. The DFA results showed that a higher grade of patellar tendon reflex was associated with a smaller value of the crossover point in the AP direction. Only the PSD values of each frequency band in the AP direction were negatively correlated with patellar tendon reflex grade with EO and became negatively correlated in both AP and ML directions with EC. Overall, the results showed a strong correlation between patellar tendon reflex and postural stability in stroke patients when vision was blocked. Significance: The strong correlation with EC may provide insights into clinic evaluation and treatment for rehabilitation or fall risks of stroke patients.

Prediabetes and all-cause mortality in young patients undergoing coronary artery angiography: a multicenter cohort study in China.

BACKGROUND: The prevalence of prediabetes is increasing in young adults and patients undergoing coronary angiography. However, whether prediabetes is a considerable risk factor for all-cause mortality remains undetermined in young patients undergoing coronary angiography. METHODS: In this study, we retrospectively included 8868 young patients (men aged < 45 years, women aged < 55 years) who underwent coronary angiography (CAG). Patients were categorized as normoglycemic, prediabetes and diabetes according to the HbA1c level or documented history of diabetes. The association of all-cause mortality with diabetes and prediabetes was detected by Cox proportional hazards regression analysis. RESULTS: A total of 3240 (36.5%) among 8868 young patients receiving CAG were prediabetes and 2218 (25.0%) were diabetes. 728 patients died during a median follow-up of 4.92 years. Compared to the normoglycemic group, prediabetes increased the risk of all-cause mortality in young CAG patients by 24%(adjusted HR: 1.24, 95% CI: 1.04-1.49, p = 0.019) and diabetes increased the risk of all-cause mortality by 46%(adjusted HR:1.46, 95% CI:1.2-1.79, p < 0.001). Subgroup analysis showed that diabetes and prediabetes increased the risk of death mainly in patients without comorbidities. CONCLUSION: Prediabetes accounts for more than one-third of the young adults undergoing CAG and was associated with an increased risk of all-cause mortality, active prevention strategy should be considered for these patients.

Wall Motion Score Index Predicts Persistent Moderate or Severe Secondary Mitral Regurgitation and its Prognostic Role in Patients Undergoing Percutaneous Coronary Intervention.

Background: Patients with secondary mitral regurgitation (sMR) often present with greater mortality and comorbidity, which may be predicted by some risk factors. This study was designed to investigate the prognostic meaning of the echocardiographically detected wall motion score index (WMSI) in coronary artery disease (CAD) patients with moderate or severe baseline sMR who underwent percutaneous coronary intervention (PCI) therapy. Methods: The present study was a multi-center and prospective cohort of consecutive CAD patients with baseline moderate or severe sMR who underwent PCI. All underwent echocardiography at baseline and at follow-up after PCI to assess sMR and WMSI. The primary endpoint was the persistence of moderate or severe sMR after the second echocardiographic measurement. Logistic and Cox proportional hazards models were constructed for the primary (persistent moderate or severe sMR) and secondary (worsening heart failure [HF]; all-cause mortality; cardiovascular-specific mortality; and major adverse cardiovascular events [MACE]) endpoints. Results: Among 920 participants, 483 had WMSI values of ≥ 1.47, and 437 were less. Of all the participants, 366 (39.8%) continued to have moderate or severe sMR after the second echocardiogram measurement. After full adjustment for confounders, elevated WMSI after PCI was independently associated with the primary endpoint during 3-12 month follow-up. Similarly, elevated WMSI was associated with increased risk of worsening HF, all-cause mortality, cardiovascular-specific mortality, and MACE. Conclusions: Persistent moderate or severe sMR is common (approximately 40%) in PCI patients. Elevated WMSI in CAD patients after PCI is a predictor of persistent moderate or severe sMR and has independent negative prognostic value. Patients with CAD and sMR should be monitored for WMSI to identify those at higher risk of mortality and comorbidity.

Intermediate Hyperglycemia Increases the Risk of All-Cause Mortality in Premature Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention.

Background: Hyperglycemia has been associated with an adverse prognosis in patients with premature coronary artery disease (CAD). However, whether the intermediate hyperglycemia status affects the risk of mortality in premature CAD patients treated with percutaneous coronary intervention (PCI), remains unclear. Methods: We retrospectively included 14,585 premature CAD patients undergoing PCI from 2007 to 2020. Patients were divided into normal glycemia ( < 6%), intermediate hyperglycemia (6%-6.5%), and hyperglycemia ( ≥ 6.5%) according to hemoglobin A1c (HbA1c) level in whole blood. Follow-up all-cause mortality was defined as a primary outcome, and Cox proportional regression analysis was used to assess the association between glycemia status and the primary outcome. Results: Among 14,585 premature CAD patients undergoing PCI (mean age 43.6 ± 7.6 years, 28.1% female), 2856 (19.6%) were diagnosed with intermediate hyperglycemia. Over a median follow-up of 4.62 years (2.72-7.19 years), patients with hyperglycemia were correlated with higher risk (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.19-1.54, p < 0.001) while patients with intermediate hyperglycemia were associated with intermediate mortality risk from all causes (HR 1.17, 95% CI 1.0-1.36, p = 0.049). Conclusions: Intermediate hyperglycemia was positively associated with all-cause mortality risk in patients with premature CAD undergoing PCI. Active glucose-lowering therapy may be considered in these patients. Clinical Trial Registration: NCT05050877.

Mucosal Delivery of HIV-1 Glycoprotein Vaccine Candidate Enabled by Short Carbon Nanotubes.

The HIV-1 envelope glycoprotein spike is the target of antibodies, and therefore represents the main viral antigen for antibody-based vaccine design. One of the challenges in HIV-1 vaccine development is finding efficient ways for the immune system to recognize and respond to HIV-1 without establishing an infection. Since HIV-1 enters the body at mucosal surfaces, induction of immune response at these sites is a preferred preventive approach. Nasal administration is a very effective route for mucosal immunization since it can stimulate mucosal immune responses both locally and distantly. In this paper, Luna develops a safe, short carbon nanotube (CNT)-based, needle-free delivery platform known as "CNTVac". The size of short CNT was controlled to possess HIV-1 particle-like morphology (100-200 nm) capable of efficiently delivering a broad range of antigens intranasally. PEG-Lipid served as the antigen conformation protector and mucosal barrier penetration enhancer (Schematic Figure) was localized between V1V2 antigens, which caused highly enhanced local IgA and systemic antibody IgG responses in mice and rabbits. The short CNT incorporated with PEG-Lipid could not only serve as efficient delivery system but also reduce the amount of lipid usage in order to balance the vaccine dosage in order to eliminate the potential adverse effect. These data suggest a promising platform technology for vaccine delivery.

Layer-by-Layer Delivery of Multiple Antigens Using Trimethyl Chitosan Nanoparticles as a Malaria Vaccine Candidate.

Developing a safe and effective malaria vaccine is critical to reducing the spread and resurgence of this deadly disease, especially in children. In recent years, vaccine technology has seen expanded development of subunit protein, peptide, and nucleic acid vaccines. This is due to their inherent safety, the ability to tailor their immune response, simple storage requirements, easier production, and lower expense compared to using attenuated and inactivated organism-based approaches. However, these new vaccine technologies generally have low efficacy. Subunit vaccines, due to their weak immunogenicity, often necessitate advanced delivery vectors and/or the use of adjuvants. A new area of vaccine development involves design of synthetic micro- and nano-particles and adjuvants that can stimulate immune cells directly through their physical and chemical properties. Further, the unique and complex life cycle of the Plasmodium organism, with multiple stages and varying epitopes/antigens presented by the parasite, is another challenge for malaria vaccine development. Targeting multistage antigens simultaneously is therefore critical for an effective malaria vaccine. Here, we rationally design a layer-by-layer (LbL) antigen delivery platform (we called LbL NP) specifically engineered for malaria vaccines. A biocompatible modified chitosan nanoparticle (trimethyl chitosan, TMC) was synthesized and utilized for LbL loading and release of multiple malaria antigens from pre-erythrocytic and erythrocytic stages. LbL NP served as antigen/protein delivery vehicles and were demonstrated to induce the highest Plasmodium falciparum Circumsporozoite Protein (PfCSP) specific T-cell responses in mice studies as compared to multiple controls. From immunogenicity studies, it was concluded that two doses of intramuscular injection with a longer interval (4 weeks) than traditional malaria vaccine candidate dosing would be the vaccination potential for LbL NP vaccine candidates. Furthermore, in PfCSP/Py parasite challenge studies we demonstrated protective efficacy using LbL NP. These LbL NP provided a significant adjuvant effect since they may induce innate immune response that led to a potent adaptive immunity to mediate non-specific anti-malarial effect. Most importantly, the delivery of CSP full-length protein stimulated long-lasting protective immune responses even after the booster immunization 4 weeks later in mice.

Immunoinformatic screening of Marburgvirus epitopes and computational investigations of epitope-allele complexes.

Marburgvirus (MARV), a member of the Filovirus family, causes severe hemorrhagic fever in humans. Currently, there are no approved vaccines or post exposure treatment methods available against MARV. With the aim of identifying vaccine candidates against MARV, we employ different sequence-based computational methods to predict the MHC-I and MHC-II T-cell epitopes as well as B-cell epitopes for the complete MARV genome. We analyzed the variations in the predicted epitopes among four MARV variants, the Lake Victoria, Angola, Musoke, and Ravn. We used a consensus approach to identify several epitopes, including novel epitopes, and narrowed down the selection based on different parameters such as antigenicity and IC50 values. The selected epitopes can be used in various vaccine constructs that give effective antibody responses. The MHC-I epitope-allele complexes for GP and NP with favorably low IC50 values were investigated using molecular dynamics computations to determine the molecular details of the epitope-allele complexes. This study provides information for further experimental validation of the potential epitopes and the design and development of MARV vaccines.

The U-Shaped Relationship Between Serum Uric Acid and Long-Term All-Cause Mortality in Coronary Artery Disease Patients: A Cohort Study of 33,034 Patients.

Background: Associations between high serum uric acid (SUA) and cardiovascular diseases have been reported. However, few studies have been conducted to explore the relationship between SUA and long-term all-cause mortality in coronary artery disease (CAD) patients. Our study aims to investigate the relationship between SUA and long-term all-cause mortality in patients with CAD. Methods: From January 2007 to December 2018, we divided 33,034 patients with CAD admitted in the Guangdong Provincial People's Hospital into five groups (quintile 1: SUA <5.05 mg/dl, quintile 2: 5.05 mg/dl ≤ SUA <5.59 mg/dl, quintile 3:5.59 mg/dl ≤ SUA <6.8 mg/dl, quintile 4, 6.8 mg/dl ≤ SUA <7.93 mg/dl, and quintile 5, SUA ≥7.93 mg/d;). This study used Kaplan-Meier survival analysis to evaluate patient outcomes with different ranges of SUA. Cox proportional hazards regression models and restricted cubic spline were applied to determine the association between serum uric and long-term all-cause mortality. Results: A total of 33,034 participants were recruited, including 24,780 (75.01%) men and 8,254 (24.99) women in this cohort study. Median follow-up was 4.91 years. We found that SUA is an independent risk factor of long-term all-cause mortality according to the result of Cox proportional hazards models. This study also illustrated an approximate U-shape association between SUA and all-cause mortality when compared with 5.95 mg/lL ≤ SUA <6.8 mg/dl, SUA <5.0 5mg/dl (adjusted hazard ratio (aHR) =1.13, 95% CI: 1.01-1.26, p = 0.03), and SUA ≥8 mg/dL (aHR = 1.18, 95% CI: 1.06-1.32, p = 0.003). Conclusion: Our study indicated a U-shaped relationship between SUA and long-term all-cause mortality in patients with CAD. No matter whether SUA is too high or too low, it increased the all-cause mortality in the CAD population, which deserves to be closely monitored.