Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response.

BACKGROUND: Finding the oncogene, which was able to inhibit tumor cells intrinsically and improve the immune answers, will be the future direction for renal cancer combined treatment. Following patient sample analysis and signaling pathway examination, we propose p21-activated kinase 4 (PAK4) as a potential target drug for kidney cancer. PAK4 exhibits high expression levels in patient samples and plays a regulatory role in the immune microenvironment. METHODS: Utilizing AI software for peptide drug design, we have engineered a specialized peptide proteolysis targeting chimera (PROTAC) drug with selectivity for PAK4. To address challenges related to drug delivery, we developed a nano-selenium delivery system for efficient transport of the peptide PROTAC drug, termed PpD (PAK4 peptide degrader). FINDINGS: We successfully designed a peptide PROTAC drug targeting PAK4. PpD effectively degraded PAK4 with high selectivity, avoiding interference with other homologous proteins. PpD significantly attenuated renal carcinoma proliferation in vitro and in vivo. Notably, PpD demonstrated a significant inhibitory effect on tumor proliferation in a fully immunocompetent mouse model, concomitantly enhancing the immune cell response. Moreover, PpD demonstrated promising tumor growth inhibitory effects in mini-PDX and PDO models, further underscoring its potential for clinical application. INTERPRETATION: This PAK4-targeting peptide PROTAC drug not only curtails renal cancer cell proliferation but also improves the immune microenvironment and enhances immune response. Our study paves the way for innovative targeted therapies in the management of renal cancer. FUNDING: This work is supported by Research grants from non-profit organizations, as stated in the Acknowledgments.

Measuring Human Auditory Evoked Fields with a Flexible Multi-Channel OPM-Based MEG System.

BACKGROUND: Magnetoencephalography (MEG) is a non-invasive imaging technique for directly measuring the external magnetic field generated from synchronously activated pyramidal neurons in the brain. The optically pumped magnetometer (OPM) is known for its less expensive, non-cryogenic, movable and user-friendly custom-design provides the potential for a change in functional neuroimaging based on MEG. METHODS: An array of OPMs covering the opposite sides of a subject's head is placed inside a magnetically shielded room (MSR) and responses evoked from the auditory cortices are measured. RESULTS: High signal-to-noise ratio auditory evoked response fields (AEFs) were detected by a wearable OPM-MEG system in a MSR, for which a flexible helmet was specially designed to minimize the sensor-to-head distance, along with a set of bi-planar coils developed for background field and gradient nulling. Neuronal current sources activated in AEF experiments were localized and the auditory cortices showed the highest activities. Performance of the hybrid optically pumped magnetometer-magnetoencephalography/electroencephalography (OPM-MEG/EEG) system was also assessed. CONCLUSIONS: The multi-channel OPM-MEG system performs well in a custom built MSR equipped with bi-planar coils and detects human AEFs with a flexible helmet. Moreover, the similarities and differences of auditory evoked potentials (AEPs) and AEFs are discussed, while the operation of OPM-MEG sensors in conjunction with EEG electrodes provides an encouraging combination for the exploration of hybrid OPM-MEG/EEG systems.

Impact of water combined wet ball milling extraction and functional evaluation of dietary fiber from papaya (Carica papaya L).

This study evaluates the structural, physicochemical, functional and rheological properties of papaya dietary fibers (DFs) extracted by alkaline, water and combination of water/wet ball milling. The particle size of DF subjected to water/wet ball milling (WB-DF) was considerably reduced compared to DF extracted by water (W-DF) or alkaline (AL-DF) methods. WB-DF in comparison AL-DF increased the water holding capacity (WHC) by 4.1 folds, oil holding capacity (OHC) by 1.7 folds and water swelling capacity (WSC) by 2.6 folds. WB-DF also improved the cholesterol adsorption capacity (CAC), glucose adsorption (GAC), nitrite-ion adsorption capacity (NIAC) and antioxidant activity. The FT-IR spectra displayed changes in peak intensities observed in the three modified DFs. In addition, WB-DF showed highest viscosity among all smaples. The distributions of monosaccharides in the DFs were affected by the different extractions. Consequently, DFs extracted through the water/wet ball milling exhibit significant potential for applications in the functional food industry.

Mental health and psychosocial interventions to limit the adverse psychological effects of disasters and emergencies in China: a scoping review.

Exposure to disasters and public health emergencies negatively affects mental health. Research documenting the psychosocial responses to these calamities in China increased dramatically after the 2008 Wenchuan earthquake. However, there is no comprehensive assessment of the available literature on China's mental health and psychosocial support (MHPSS) responses to these events. This scoping review systematically maps existing published research and grey literature sources regarding MHPSS to disasters and emergencies in China. We examined relevant literature in English and Chinese from six databases and official websites from Jan 1, 2000, to Aug 13, 2021, and included 77 full-text records in this review. The main types of interventions reported included a) stepped care intervention models, b) individual structured psychotherapy and pharmacotherapy, c) mental health education, d) psychological counselling, and e) government-based policy interventions. Most interventions were evaluated using quantitative methods that assessed the treatment of common mental disorders. The review found that rapid national mobilization, emphasis on resilience-strengthening interventions, and the widespread use of step-care models were essential components of reducing the adverse psychosocial effects of disasters. The review also identified remaining gaps, including a) a lack of integration of disaster-related services with the pre-existing health care system, b) inadequate supervision of MHPSS providers, and c) limited monitoring and evaluation of the services provided. These results show where additional research is needed in China to improve mental health services. It also provides a framework that other countries can adapt when developing and evaluating MHPSS policies and plans in response to disasters.

Incommensurate Spin Density Wave in Antiferromagnetic RuO_{2} Evinced by Abnormal Spin Splitting Torque.

Since the discovery of antiferromagnetism, metallic oxide RuO_{2} has exhibited numerous intriguing spintronics properties such as the anomalous Hall effect and anisotropic spin splitting effect. However, the microscopic origin of its antiferromagnetism remains unclear. By investigating the spin splitting torque in RuO_{2}/Py, we found that metallic RuO_{2} exhibits a spatially periodic spin structure which interacts with the spin waves in Py through interfacial exchange coupling. The wavelength of such structure is evaluated within 14-20 nm depending on the temperature, which is evidence of an incommensurate spin density wave state in RuO_{2}. Our work not only provides a dynamics approach to characterize the antiferromagnetic ordering in RuO_{2}, but also offers fundamental insights into the spin current generation due to anisotropic spin splitting effect associated with spin density wave.

The remediation potential and kinetics of Pb2+ adsorbed by the organic frameworks of Cladophora rupestris.

Cladophora rupestris is ubiquitous in many kinds of waterbodies, and C. rupestris biomass can serve as a carrier for adsorbing and transferring heavy metals. Batch experiments and characterization were performed. Results showed that the organic frameworks of C. rupestris (CROF) had a specific surface area of 2.58 m2/g and an external surface area of 2.06 m2/g. Many mesopores were present in CROF, mainly distributed in 2.5-7.5 nm. The zeta potentials were within the range of - 4.46 to - 13.98 mV in the tested pH of 2.0-9.0. CROF could effectively adsorb Pb2+ in large pH range. The maximum adsorption capacity (qmax) of Pb2+ on CROF was 15.02 mg/g, and 97% of Pb2+ was adsorbed onto CROF after 25 min. CROF had a preferential adsorption of Pb2+. The protein secondary structures and carbon skeletons of CROF all worked in adsorption. The main Pb2+ adsorption mechanisms were pore filling, electrostatic attraction, Pb-π interaction, and surface complexation. Therefore, it is valuable as a biosorbent for the removal of Pb2+ from waterbodies.

Diagnostic accuracy of thoracic CT to differentiate transudative from exudative pleural effusion prior to thoracentesis.

BACKGROUND: Computed tomography (CT) scan is commonly performed for pleural effusion diagnostis in the clinic. However, there are limited data assessing the accuracy of thoracic CT for the separation of transudative from exudative effusions. The study aimed to determine the diagnostic value of thoracic CT in distinguishing transudates from exudates in patients with pleural effusion. METHODS: This is a two-center retrospective analysis of patients with pleural effusion, a total of 209 patients were included from The First Affiliated Hospital of Henan University of Science and Technology as the derivation cohort (Luoyang cohort), and 195 patients from the First Affiliated Hospital of Zhengzhou University as the validation cohort (Zhengzhou cohort). Patients who underwent thoracic CT scan followed by diagnostic thoracentesis were enrolled. The optimal cut-points of CT value in pleural fluid (PF) and PF to blood CT value ratio for predicting a transudative vs. exudative pleural effusions were determined in the derivation cohort and further verified in the validation cohort. RESULTS: In the Derivation (Luoyang) cohort, patients with exudates had significantly higher CT value [13.01 (10.01-16.11) vs. 4.89 (2.31-9.83) HU] and PF to blood CT value ratio [0.37 (0.27-0.53) vs. 0.16 (0.07-0.26)] than those with transudates. With a cut-off value of 10.81 HU, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT value were 0.85, 88.89%, 68.90%, 43.96%, and 95.76%, respectively. The optimum cut-value for PF to blood CT value ratio was 0.27 with AUC of 0.86, yielding a sensitivity of 61.11%, specificity of 86.36%, PPV of 78.57%, and NPV of 73.08%. These were further verified in the Validation (Zhengzhou) cohort. CONCLUSIONS: CT value and PF to blood CT value ratio showed good differential abilities in predicting transudates from exudates, which may help to avoid unnecessary thoracentesis.

Melatonin suppresses tumor proliferation and metastasis by targeting GATA2 in endometrial cancer.

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA-binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development.

Time-Course Transcriptome Analysis of Aquilegia vulgaris Root Reveals the Cell Wall's Roles in Salinity Tolerance.

Salt stress has a considerable impact on the development and growth of plants. The soil is currently affected by salinisation, a problem that is becoming worse every year. This means that a significant amount of salt-tolerant plant material needs to be added. Aquilegia vulgaris has aesthetically pleasing leaves, unique flowers, and a remarkable tolerance to salt. In this study, RNA-seq technology was used to sequence and analyse the transcriptome of the root of Aquilegia vulgaris seedlings subjected to 200 mM NaCl treatment for 12, 24, and 48 h. In total, 12 Aquilegia vulgaris seedling root transcriptome libraries were constructed. At the three time points of salt treatment compared with the control, 3888, 1907, and 1479 differentially expressed genes (DEGs) were identified, respectively. Various families of transcription factors (TFs), mainly AP2, MYB, and bHLH, were identified and might be linked to salt tolerance. Gene Ontology (GO) analysis of DEGs revealed that the structure and composition of the cell wall and cytoskeleton may be crucial in the response to salt stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed a significant enrichment of the pentose and glucuronate interconversion pathway, which is associated with cell wall metabolism after 24 and 48 h of salt treatment. Based on GO and KEGG analyses of DEGs, the pentose and glucuronate interconversion pathway was selected for further investigation. AP2, MYB, and bHLH were found to be correlated with the functional genes in this pathway based on a correlation network. This study provides the groundwork for understanding the key pathways and gene networks in response to salt stress, thereby providing a theoretical basis for improving salt tolerance in Aquilegia vulgaris.

Bidirectional Interphase Modulation of Phosphate Electrolyte Enables Intrinsic Safety and Superior Stability for High-Voltage Lithium-Metal Batteries.

Developing advanced high voltage lithium-metal batteries (LMBs) with superior stability and intrinsic safety is of great significance for practical applications. However, the easy flammability of conventional carbonate solvents and inferior compatibility of commercial electrolytes for both highly reactive Li anodes and high-voltage cathodes severely hinder the implementation process. Hence, we rationally designed an intrinsically nonflammable and low-cost phosphate electrolyte toward stable high-voltage LMBs by bidirectionally modulating the interphases. Benefiting from the synergistic regulation of LiNO3 and DME dual-additives in the 1.5 M LiTFSI/Triethyl phosphate electrolyte, thin, dense and robust electrodes/electrolyte interphases were well constructed simultaneously on the surfaces of Li anode and Ni-rich cathode, dramatically improving the stability and compatibility between electrodes and electrolyte. Consequently, boosted kinetic and high Coulombic efficiency of 98.6% for Li metal plating/stripping over 400 cycles and superior cycling stability of exceeding 4,000 h in Li symmetric cell is achieved. More importantly, the Li∥LiNi0.6Mn0.2Co0.2O2 cell assembled with a thin Li anode and high mass-loading cathode at a high cutoff voltage of 4.6 V retains a 98.4% capacity retention after 500 cycles at 1C. This work affords a promising strategy to develop nonflammable electrolytes enabling the high safety, good cyclability, and low cost of high-energy LMBs.

A Three-Dimensional (3D) Framework of Freestanding Vanadium Nitride Nanowires for Dendrite-Free and Long Life-Span Lithium Metal Anodes.

Lithium (Li) metal is a promising anode candidate for high-energy-density batteries owing to its high theoretical capacity and low electrochemical potential. However, uneven Li nucleation, uncontrollable dendritic growth, infinite voltage change and even safety issues hinder its commercial application. Herein, a three-dimensional (3D) framework of freestanding vanadium nitride nanowires (VN NWs) is established as Li host for dendrite-free Li metal anode. A lithiophilic Li3 N interlayer which in situ formed by the surface reaction between molten Li and VN NWs is utilized to guide a uniform Li nucleation and deposition within the skeleton, as well as avoid the dendrite formation. Meanwhile, VN NWs can decrease local current density, homogenize Li-ion flux and accommodate volume fluctuations of the anode due to its 3D structure with high electron conductivity. Thus, the corresponding composite Li metal anode delivers a long-life span of 500 cycles (1000 h) at a current density of 0.5 mA cm-2 , and exhibits lower nucleation over-potential and voltage hysteresis at different current densities from 0.5~5 mA cm-2 in carbonate electrolyte. In conclusion, this work provides a new type of scaffold with both high electronic conductivity and excellent lithiophilicity for stable Li anodes.

Engineering Proteins for Cell Entry.

Proteins are essential for life, as they participate in all vital processes in the body. In the past decade, delivery of active proteins to specific cells and organs has attracted increasing interest. However, most proteins cannot enter the cytoplasm due to the cell membrane acting as a natural barrier. To overcome this challenge, various proteins have been engineered to acquire cell-penetrating capacity by mimicking or modifying natural shuttling proteins. In this review, we provide an overview of the different types of engineered cell-penetrating proteins such as cell-penetrating peptides, supercharged proteins, receptor-binding proteins, and bacterial toxins. We also discuss some strategies for improving endosomal escape such as pore formation, the proton sponge effect, and hijacking intracellular trafficking pathways. Finally, we introduce some novel methods and technologies for designing and detecting engineered cell-penetrating proteins.

The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome.

The A1762T/G1764A mutations, one of the most common mutations in the hepatitis B virus basal core promoter, are associated with the progression of chronic HBV infection. However, effects of these mutations on HBV replication remains controversial. This study aimed to systematically investigate the effect of the mutations on HBV replication and its underlying mechanisms. Using the prcccDNA/pCMV-Cre recombinant plasmid system, a prcccDNA-A1762T/G1764A mutant plasmid was constructed. Compared with wild-type HBV, A1762T/G1764A mutant HBV showed enhanced replication ability with higher secreted HBV DNA and RNA levels, while Southern and Northern blot indicated higher intracellular levels of relaxed circular DNA, single-stranded DNA, and 3.5 kb RNA. Meanwhile, the mutations increased expression of intracellular core protein and decreased the production of HBeAg and HBsAg. In vitro infection based on HepG2-NTCP cells and mice hydrodynamic injection experiment also proved that these mutations promote HBV replication. 5'-RACE assays showed that these mutations upregulated transcription of pregenomic RNA (pgRNA) while downregulating that of preC RNA, which was further confirmed by full-length transcriptome sequencing. Moreover, a proportion of sub-pgRNAs with the potential to express polymerase were also upregulated by these mutations. The ChIP-qPCR assay showed that A1762T/G1764A mutations created a functional HNF1α binding site in the BCP region, and its overexpression enhanced the effect of A1762T/G1764A mutations on HBV. Our findings revealed the mechanism and importance of A1762T/G1764A mutations as an indicator for management of CHB patients, and provided HNF1α as a new target for curing HBV-infected patients.

Anisotropy and thermal properties in GeTe semiconductor by Raman analysis.

Low-symmetric GeTe semiconductors have attracted wide-ranging attention due to their excellent optical and thermal properties, but only a few research studies are available on their in-plane optical anisotropic nature that is crucial for their applications in optoelectronic and thermoelectric devices. Here, we investigate the optical interactions of anisotropy in GeTe using polarization-resolved Raman spectroscopy and first-principles calculations. After determining both armchair and zigzag directions in GeTe crystals by transmission electron microscopy, we found that the Raman intensity of the two main vibrational modes had a strong in-plane anisotropic nature; the one at ∼88.1 cm-1 can be used to determine the crystal orientation, and the other at ∼124.6 cm-1 can reveal a series of temperature-dependent phase transitions. These results provide a general approach for the investigation of the anisotropy of light-matter interactions in low-symmetric layered materials, benefiting the design and application of optoelectronic, anisotropic thermoelectric, and phase-transition memory devices based on bulk GeTe.

Modification of Ginseng Insoluble Dietary Fiber by Enzymatic Method: Structural, Rheological, Thermal and Functional Properties.

In this study, the effects of enzymatic modification using cellulase/xylanase on the composition and structural and functional properties of ginseng insoluble dietary fiber (G-IDF) were evaluated. Fourier transform infrared spectroscopy and scanning electron microcopy showed that enzymatic extraction treatment caused obvious structural alterations in ginseng-modified (G-MIDF) samples, which exhibited more porous and completely wrinkled surfaces. Comparing the peak morphology of G-MIDF with untreated IDF using X-ray diffractometry, the G-MIDF sample exhibited split peaks at a 2θ angle of 23.71°, along with the emergence of sharp peaks at 28.02°, 31.78°, and 35.07°. Thermo-gravimetric analysis showed that G-MIDF exhibited a specified range of pyrolysis temperature and is suitable for food applications involving processing at temperatures below 300 °C. Overall, it was evident from rheograms that both G-IDF and G-MIDF exhibited a resemblance with respect to viscosity changes as a function of the shear rate. Enzymatic treatment led to significant (p < 0.05) improvement in water holding, oil retention, water swelling, nitrite ion binding, bile acid binding, cholesterol absorption, and glucose absorption capacities.

Inhibition Roles of Calcium in Cadmium Uptake and Translocation in Rice: A Review.

Cadmium (Cd) contamination in rice grains is posing a significant threat to global food security. To restrict the transport of Cd in the soil-rice system, an efficient way is to use the ionomics strategy. Since calcium (Ca) and Cd have similar ionic radii, their uptake and translocation may be linked in multiple aspects in rice. However, the underlying antagonistic mechanisms are still not fully understood. Therefore, we first summarized the current knowledge on the physiological and molecular footprints of Cd translocation in plants and then explored the potential antagonistic points between Ca and Cd in rice, including exchange adsorption on roots, plant cell-wall composition, co-transporter gene expression, and transpiration inhibition. This review provides suggestions for Ca/Cd interaction studies on rice and introduces ionomics research as a means of better controlling the accumulation of Cd in plants.

Nanonitrator: novel enhancer of inorganic nitrate's protective effects, predicated on swarm learning approach.

Inorganic nitrate is an indispensable nutrient that has been used in experimental studies for the prevention and treatment of several diseases. However, the short half-life of nitrate limits its clinical application. To increase the usability of nitrate and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments, we developed a swarm learning-based combination drug prediction system that identified vitamin C as the drug of choice to be combined with nitrate. Employing microencapsulation technology, we used vitamin C, sodium nitrate, and chitosan 3000 as the core materials to prepare a nitrate nanoparticle, which we named Nanonitrator. The long-circulating delivery ability of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in irradiation-induced salivary gland injury, without compromising safety. Nanonitrator at the same dose could better maintain intracellular homeostasis than nitrate (with or without vitamin C), emphasizing its potential for clinical use. More importantly, our work provides a method for incorporating inorganic compounds into sustained-release nanoparticles.

Defect-Enriched Graphene Nanoribbons Tune the Adsorption Behavior of the Mediator to Boost the Lactate/Oxygen Biofuel Cell.

Owing to the high efficiency and specificity in moderate conditions, enzymatic biofuel cells (EBFCs) have gained significant interest as a promising energy source for wearable devices. However, the instability of the bioelectrode and the lack of efficient electrical communication between the enzymes and electrodes are the main obstacles. Herein, defect-enriched 3D graphene nanoribbons (GNRs) frameworks are fabricated by unzipping multiwall carbon nanotubes, followed by thermal annealing. It is found that defective carbon shows stronger adsorption energy towards the polar mediators than the pristine carbon, which is beneficial to improving the stability of the bioelectrodes. Consequently, the EBFCs equipped with the GNRs exhibit a significantly enhanced bioelectrocatalytic performance and operational stability, delivering an open-circuit voltage and power density of 0.62 V, 70.7 µW/cm2, and 0.58 V, 18.6 µW/cm2 in phosphate buffer solution and artificial tear, respectively, which represent the high levels among the reported literature. This work provides a design principle according to which defective carbon materials could be more suitable for the immobilization of biocatalytic components in the application of EBFCs.

TRABID overexpression enables synthetic lethality to PARP inhibitor via prolonging 53BP1 retention at double-strand breaks.

53BP1 promotes nonhomologous end joining (NHEJ) over homologous recombination (HR) repair by mediating inactivation of DNA end resection. Ubiquitination plays an important role in regulating dissociation of 53BP1 from DNA double-strand breaks (DSBs). However, how this process is regulated remains poorly understood. Here, we demonstrate that TRABID deubiquitinase binds to 53BP1 at endogenous level and regulates 53BP1 retention at DSB sites. TRABID deubiquitinates K29-linked polyubiquitination of 53BP1 mediated by E3 ubiquitin ligase SPOP and prevents 53BP1 dissociation from DSBs, consequently inducing HR defects and chromosomal instability. Prostate cancer cells with TRABID overexpression exhibit a high sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. Our work shows that TRABID facilitates NHEJ repair over HR during DNA repair by inducing prolonged 53BP1 retention at DSB sites, suggesting that TRABID overexpression may predict HR deficiency and the potential therapeutic use of PARP inhibitors in prostate cancer.

EZH2-regulated immune risk score prognostic model predicts outcome of clear cell renal cell carcinoma.

Background: The enhancer of zeste homolog 2 (EZH2) plays an important role in the tumor microenvironment (TME), and EZH2 in shaping the epigenetic landscape of CD8+ T cell fate and function, with a particular emphasis on cancer. Here, high EZH2 expression always leads to less CD8+ T cell infiltration. However, clear cell renal cell carcinoma (ccRCC) is reportedly a "hot" tumor, with contradictory high EZH2 expression. Our goal was to construct a EZH2-regulated immune risk score prognostic model to predict ccRCC outcomes, and provide a prospect of clinical EZH2 inhibitors in fine-tuning T cell responses with immune therapy. Methods: We downloaded and analyzed The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), TISIDB database, and WebGestalt for ccRCC patients, EZH2-related tumor-infiltrating lymphocytes and immunomodulators. R packages "limma", "BiocManager", and "preprocessCore", etc. were downloaded to prepare CIBERSORT files, immune cells heatmap, multivariable Cox model and survival analysis. The EZH2-regulated immune risk model's prognostic ability was calculated by receiver operating characteristic (ROC) and area under the curve (AUC) analyses in R studio. Results: EZH2 was highly expressed and related to poor outcome in ccRCC. However, high-expression EZH2 was not related to a "cool" tumor. Of the 49 immunomodulators significantly regulated by EZH2, forest plot showed 26 immunomodulators signatures independently associated with overall survival. The EZH2-regulated immune-risk score prognostic model was an independent prognostic factor (AUC =0.816), especially combined with clinicopathologic parameters in ccRCC overall survival prediction. Conclusions: The EZH2-regulated immune-risk score prognostic model was an independent prognostic factor, with good accuracy and predictability, and could provide experimental data to the clinical area.