Molecular bases of eukaryotic circadian clocks mainly rely on transcriptional-translational feedback loops (TTFLs), while epigenetic codes also play critical roles in fine-tuning circadian rhythms. However, unlike histone modification codes that play extensive and well-known roles in the regulation of circadian clocks, whether DNA methylation (5mC) can affect the circadian clock, and the associated underlying molecular mechanisms, remains largely unexplored in many organisms. Here we demonstrate that global genome DNA hypomethylation can significantly lengthen the circadian period of Arabidopsis. Transcriptomic and genetic evidence demonstrate that SUPPRESSOR OF drm1 drm2 cmt3 (SDC), encoding an F-box containing protein, is required for the DNA hypomethylation-tuned circadian clock. Moreover, SDC can physically interact with another F-box containing protein ZEITLUPE (ZTL) to diminish its accumulation. Genetic analysis further revealed that ZTL and its substrate TIMING OF CAB EXPRESSION 1 (TOC1) likely act downstream of DNA methyltransferases to control circadian rhythm. Together, our findings support the notion that DNA methylation is important to maintain proper circadian pace in Arabidopsis, and further established that SDC links DNA hypomethylation with a proteolytic cascade to assist in tuning the circadian clock.

We previously identified three putative prophenoloxidase-activating proteinase (mdPAP1, mdPAP2, and mdPAP3) genes from housefly Musca domestica by transcriptomic analysis. In this study, mdPAP1 cDNA was cloned, and the function of its encoded protein was analyzed. The cDNA of mdPAP1 was 1358 bp, and it contained a single open reading frame of 1122 bp encoding a predicted MdPAP1 protein of 373 amino acids. The estimated molecular weight of MdPAP1 was 41267.08 Da with an isoelectric point of 6.25. The deduced amino acid sequence of MdPAP1 exhibited high similarity to known PAPs of insects. mdPAP1 was detected in larvae, pupae, and adult housefly, and the expression level of mdPAP1 was upregulated in bacterial challenged larvae. The recombinant protein of MdPAP1 expressed in Escherichia coli could cleave the prophenoloxidase into phenoloxidase in M. domestica hemolymph infected by bacteria and result in a significant increase of the total phenoloxidase activity. In addition, RNA interference-mediated gene silencing of mdPAP1 significantly increased the mortality of M. domestica larvae. Results indicated that mdPAP1 was involved in the activation of the prophenoloxidase against bacterial infection in M. domestica.

Identifying genetic disease-susceptible individuals through population screening is considered as a promising approach for disease prevention. DNA mismatch repair (MMR) genes including MLH1, MSH2, MSH6 and PMS2 play essential roles in maintaining microsatellite stability through DNA mismatch repair, and pathogenic variation in MMR genes causes microsatellite instability and is the genetic predisposition for cancer as represented by the Lynch syndrome. While the prevalence and spectrum of MMR variation has been extensively studied in cancer, it remains largely elusive in the general population. Lack of the knowledge prevents effective prevention for MMR variation-caused cancer. In the current study, we addressed the issue by using the Chinese population as a model.

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

Chimeric antigen receptor T (CAR-T) cells targeting CD19 came into clinical practice for the treatment of B cell lymphoma in 2018. However, patients being treated for B cell lymphoma often suffer from comorbidities such as chronic pain, cardiovascular diseases and arthritis. Thus, these patients frequently receive concomitant medications that include nonsteroidal anti-inflammatory drugs (NSAIDs) like cyclooxygenase (COX) inhibitors. Celecoxib, a selective COX-2 inhibitor, and aspirin, a non-selective COX-1 and COX-2 inhibitor, are being used as anti-inflammatory, analgesic and anti-pyretic drugs. In addition, several studies have also focused on the anti-neoplastic properties of COX-inhibitors. As the influence of COX-inhibitors on CD19.CAR-T cells is still unknown, we investigated the effect of celecoxib and aspirin on the quantity and quality of CD19.CAR-T cells at different concentrations with special regard to cytotoxicity, activation, cytokine release, proliferation and exhaustion. A significant effect on CAR-T cells could be observed for 0.1 mmol/L of celecoxib and for 4 mmol/L of aspirin. At these concentrations, we found that both COX-inhibitors could induce intrinsic apoptosis of CD19.CAR-T cells showing a significant reduction in the ratio of JC-10 red to JC-10 green CAR-T cells from 6.46 ± 7.03 (mean ± SD) to 1.76 ± 0.67 by celecoxib and to 4.41 ± 0.32 by aspirin, respectively. Additionally, the ratios of JC-10 red to JC-10 green Daudi cells were also decreased from 3.41 ± 0.30 to 0.77 ± 0.06 by celecoxib and to 1.26 ± 0.04 by aspirin, respectively. Although the cytokine release by CD19.CAR-T cells upon activation was not hampered by both COX-inhibitors, activation and proliferation of CAR-T cells were significantly inhibited via diminishing the NF-ĸB signaling pathway by a significant down-regulation of expression of CD27 on CD4+ and CD8+ CAR-T cells, followed by a clear decrease of phosphorylated NF-ĸB p65 in both CD4+ and CD8+ CAR-T cells by a factor of 1.8. Of note, COX-inhibitors hampered expansion and induced exhaustion of CAR-T cells in an antigen stress assay. Collectively, our findings indicate that the use of COX-inhibitors is a double-edged sword that not only induces apoptosis in tumor cells but also impairs the quantity and quality of CAR-T cells. Therefore, COX-inhibitors should be used with caution in patients with B cell lymphoma under CAR-T cell therapy.

Cyclin-dependent kinases (CDKs) are protein kinases regulating important cellular processes such as cell cycle and transcription. Many CDK genes also play a critical role during adipogenic differentiation, but the role of CDK gene family in regulating bovine adipocyte differentiation has not been studied. Therefore, the present study aims to characterize the CDK gene family in bovine and study their expression pattern during adipocyte differentiation.

Pseudomonas syringae pv. actinidiae (Psa) is a phytopathogen that causes canker in kiwifruit. Few conventional control methods are effective against this bacterium. Therefore, alternative approaches, such as phage therapy are warranted. In this study, a lytic bacteriophage (PN09) of Psa was isolated from surface water collected from a river in Hangzhou, China in 2019. Morphologically, PN09 was classified into the Myoviridae family, and could lyse all 29 Psa biovar 3 strains. The optimal temperature and pH ranges for PN09 activity were determined as 25 to 35 ∘C and 6.0 to 9.0, respectively. The complete genome of PN09 was found to be composed of a linear 99,229 bp double-stranded DNA genome with a GC content of 48.16%. The PN09 endolysin (LysPN09) was expressed in vitro and characterized. LysPN09 was predicted to belong to the Muraidase superfamily domain and showed lytic activity against the outer-membrane-permeabilized Psa strains. The lytic activity of LysPN09 was optimal over temperature and pH ranges of 25 to 40 ∘C and 6.0 to 8.0, respectively. When recombinant endolysin LysPN09 was combined with EDTA, Psa strains were effectively damaged. All these characteristics demonstrate that the phage PN09 and its endolysin, LysPN09, are potential candidates for biocontrol of Psa in the kiwifruit industry.

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC50 values of 135.75, 128.26, 142.65, 155.73 and 111.60 μM, respectively. In U87 and U251 cells, TMZ (200 μM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg-1·d-1, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.

Intramuscular fat (IMF) is one of the most critical parameters affecting meat quality and mainly affected by genetic factors. MicroRNA as an important regulatory factor, which is still a lack of research in the development of sheep IMF deposition. We used RNA sequencing (RNA-seq) and cell-level validation to explore the role of miRNA in IMF deposition. As for this purpose, longissimus thoracis et lumborum (LTL) samples of 2 month-old (Mth-2) and 12 months-old (Mth-12) Aohan fine-wool sheep (AFWS) were used to identified miRNAs expression. We found 59 differentially expressed miRNAs (DE-miRNA) between these age groups and predicted their 1,796 target genes. KEGG functional enrichment analysis revealed eight pathways involved in lipid metabolism-related processes, including fatty acid elongation and the AMPK signaling pathway. A highly expressed DE-miRNA, miR-193a-5p, was found to serve a function in 3T3-L1 preadipocyte differentiation. Luciferase assay demonstrated that miR-193a-5p directly binds to the 3'-UTR region of ACAA2. By constructing mimics and inhibitor vector transfecting into 3T3-L1 cells to explore the effect of miR-193a-5p on cell proliferation and differentiation, we demonstrated that overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte proliferation, as evidenced by decreased mRNA and protein expression of CDK4 and CyclinB. CCK-8 assay showed that miR-193a-5p significantly inhibited cell proliferation. Similarly, the overexpression of miR-193a-5p inhibited 3T3-L1 preadipocyte differentiation and adipocyte-specific molecular markers' expression, leading to a decrease in PPARγ and C/EBPα and ACAA2. Inhibition of miR-193a-5p had the opposite effects. Our study lists the miRNAs associated with intramuscular lipid deposition in sheep and their potential targets, striving to improve sheep meat quality.

The pore-forming protein perforin is one of the effectors of cell-mediated killing via the granule exocytosis pathway. In this study, a genome-wide association study was conducted in Vibrio harveyi disease-resistant and disease-susceptible families of half smooth tongue sole (Cynoglossus semilaevis) to determine the genes accounting for host resistance, and a perforin homologue was identified, designated perforin-1 like (CsPRF1l). The full-length cDNA of CsPRF1l is 1835 bp, and encodes 514 amino acids. The CsPRF1l gene consists of 10 exons and 9 introns, spanning approximately 7 kb. The amino acid sequence of CsPRF1l shows 60.35, 54.03, 41.92, and 34.17% identities to Morone saxatilis PRF1l, Oryzias melastigma PRF1l, Danio rerio PRF1.5 and Homo sapiens PRF, respectively. Sequence analysis revealed the presence of membrane attack complex/perforin (MACPF) and C2 domains in CsPRF1l. Quantitative real-time PCR showed that CsPRF1l presented a higher intestinal expression level in disease-resistant families than in susceptible families. Tissue expression pattern analysis showed that CsPRF1l is present in most of the tested tissues and highly expressed in the intestine, brain, stomach and gills. After challenge with V. harveyi, CsPRF1l mRNA was markedly upregulated in the liver, spleen, kidney, intestine, gills and skin. In addition, the recombinant CsPRF1l protein exhibited obvious antimicrobial activity against V. harveyi in vitro and in a zebrafish model. Collectively, these data indicate that CsPRF1l modulates host immune defense against V. harveyi invasion and provide clues about the efficacy of rCsPRF1l in fish that will give rise to useful therapeutic applications for V. harveyi infection in C. semilaevis.

The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O'Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects.

This study aimed to evaluate the biodistribution and kinetics of [18F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI).

Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs' toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human-hamster hybrid (AL) cells showed that p53, PI3k-Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.

There is an emerging body of literature suggesting that unlike the chronic neuroinflammatory response, acute neuroinflammation is self-regulated and is beneficial for central nervous system homeostasis and cognitive integrity. However, the neurophysiological alterations upon acute neuroinflammation and their implications on cognitive function remain poorly understood. In the present study, we reliably established a mouse model of acute and self-limiting neuroinflammation by administering a single intraperitoneal injection of low-dose lipopolysaccharide, which induced reversible sickness behavior and increased pro-inflammatory cytokine expression in the medial prefrontal cortex (mPFC). During acute neuroinflammation, fast-spiking parvalbumin-expressing interneurons (PV interneurons) in the mPFC exhibited a hyperexcitable phenotype exemplified by increased input resistance, decreased rheobase current, and a higher frequency of action potentials. Furthermore, PV interneurons in the prelimbic subregion of the mPFC were excessively recruited into circuits supporting novel object recognition memory, which remained intact after acute neuroinflammation. Together, our findings suggest that alterations in PV neuronal excitability resulting from acute neuroinflammation may mediate neuronal recruitment and confer a beneficial outcome on functional integrity of NOR circuit in the mPFC.

Extracellular matrix (ECM) material with good biological activity is essential to simulate cell growth microenvironment, induce cell infiltration and angiogenesis, and promote the repair of large area acute skin wound. In this study, tilapia skin acellular dermal matrix (TADM) was prepared to simulate ECM microenvironment, which can promote substantial area acute wound healing in rats. The main component of TADM is type I collagen, which has good physical and chemical properties, biological activity and cell adhesion. TADM is a form of biomaterial with low immunogenicity, low risk of prion infection and lower economic cost than other related materials such as mammalian collagen biomaterials. Our results show that TADM can guide cell infiltration, angiogenesis, regulate the expression and secretion of inflammatory and skin repair correlated factors to promote tissue healing.

Immunotherapy is a novel hotspot for the treatment of pancreatic adenocarcinoma (PAAD). However, potential biomarkers which could identify the inflamed tumor microenvironment (TME) are urgently required.

Atrial fibrillation (AF) is a chronic and progressive disease, with advancing age, the morbidity of which will increase exponentially. Circular ribonucleic acids (RNAs; circRNAs) have gained a growing attention in the development of AF in recent years. The purpose of this study is to explore the mechanism of circRNA regulation in AF, in particular, the intricate interactions among circRNA, microRNA (miRNA), and messenger RNA (mRNA). Three datasets (GSE129409, GSE68475, and GSE79768) were obtained from the Gene Expression Omnibus database to screen differentially expressed (DE) circRNAs, DE miRNAs, and DE mRNAs in AF, respectively. Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competing endogenous RNAs (ceRNAs) network was built. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of DE mRNAs in the network were performed and protein-protein interaction (PPI) networks were established to identify hub genes. Finally, a circRNA-miRNA-hub gene subnetwork was constructed. A total of 103 DE circRNAs, 16 DE miRNAs, and 110 DE mRNAs were screened in AF. Next, ceRNAs network in AF was constructed with 3 upregulated circRNAs, 2 downregulated circRNAs, 2 upregulated miRNAs, 2 downregulated miRNAs, 17 upregulated mRNAs, and 24 downregulated mRNAs. Thirty GO terms and 6 KEGG pathways were obtained. Besides, 6 hub genes (C-X-C chemokine receptor type 4 [CXCR4], C-X-C chemokine receptor type 2 [CXCR2], C-X-C motif chemokine 11 [CXCL11], neuromedin-U, B1 bradykinin receptor, and complement C3) were screened from constructing a PPI network. Finally, a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes was constructed to describe the interactions among the differential circRNAs, miRNA, and hub genes. We speculated that hsa_circRNA_0056281/hsa_circRNA_0006665 -hsa-miR-613-CXCR4/CXCR2/CXCL11 regulatory axes and hsa_circRNA_0003638-hsa-miR-1207-3p-CXCR4 regulatory axis may be associated with the pathogenesis of AF.

Cationic cell-penetrating peptides (CPPs), such as transactivator of transcription (TAT) peptide, have been proposed as effective drug carriers to improve intracellular delivery of biological macromolecules. Amphibian skin-derived Kunitz-type trypsin inhibitors (KTIs), short counterparts of KTIs from plant sources, were found to possess potent serine protease inhibitory activity. However, poor transmembrane permeability of these molecules has largely hindered the study of the full spectrum of their biological actions. As a result, this study aimed to extend the biological activities of amphibian KTIs by their conjugation to cationic CPPs. Herein, a novel peptide (kunitzin-OV2) and its phenylalanine-substituted analogue F9-kunitzin-OV2 (F9-KOV2) were evaluated for inhibition of trypsin/chymotrypsin and showed weak antibacterial activity against Escherichia coli (E. coli). As expected, the conjugation to TAT peptide did not increase membrane lysis compared with the original kunitzin-OV2, but effectively assisted this complex to enter cells. TAT-kunitzin-OV2 (TAT-KOV2) exhibited a 32-fold increase in antibacterial activity and an enhanced bactericidal rate against E. coli. In addition, the conjugation enabled the parent peptides to exhibit antiproliferative activity against cancer cells. Interestingly, TAT-F9-kunitzin-OV2 (TAT-F9-KOV2) showed stronger antiproliferative activity against human breast cancer (MCF-7) and human glioblastoma (U251MG) cell lines, which TAT-KOV2 did not possess. Moreover, TAT-F9-KOV2 showed a 20-25-fold increase in antiproliferative capacity against human lung cancer (H157, H460) cell lines compared with TAT-KOV2. Therefore, the conjugation of CPPs effectively solves the problem of cell penetration that short KTIs lack and provides evidence for new potential applications for their subsequent development as new antibacterial and anticancer agents.

Immune-related genes play a key role in regulating the cancer immune microenvironment, influencing the overall survival of patients with hepatocellular carcinoma (HCC). Along with the rapid development of immunotherapy, identifying immune-related genes with prognostic value in HCC has attracted increasing attention. Here, we aimed to develop a prognostic signature based on immune-related genes. By investigating the transcriptome landscape of 374 HCC and 160 non-HCC samples in silico, a total of 2251 differentially expressed genes were identified. Among which, 183 differentially expressed immune-related genes were subjected to a univariate Cox proportional hazard model to screen for genes with possible prognostic significance. A 10-gene prognostic signature, including HLA-G, S100A9, S100A10, DCK, CCL14, NRAS, EPO, IL1RN, GHR and RHOA, was generated employing a multivariate Cox proportional hazard model. Kaplan-Meier and Receiver Operator Characteristic (ROC) curves were used to evaluate the prognostic utility of the 10-gene signature. Moreover, the underlying mechanisms of these genes were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. According to the Tumor Immune Estimation Resource (TIMER) database, our prognostic signature was significantly associated with tumor-infiltrating B cells, CD4 T cells, dendritic cells, macrophages and neutrophils. Our study provides a novel prognostic signature based on immune-related genes associated with clinical outco mes of HCC.

Background: The effects of fatty acid metabolism in many tumors have been widely reported. Due to the diversity of lipid synthesis, uptake, and transformation in clear cell renal cell carcinoma (ccRCC) cells, many studies have shown that ccRCC is associated with fatty acid metabolism. The study aimed was to explore the impact of fatty acid metabolism genes on the prognosis and immunotherapy of ccRCC. Methods: Two subtypes were distinguished by unsupervised clustering analysis based on the expression of 309 fatty acid metabolism genes. A prognostic model was constructed by lasso algorithm and multivariate COX regression analysis using fatty acid metabolism genes as the signatures. The tumor microenvironment between subtypes and between risk groups was further analyzed. The International Cancer Genome Consortium cohort was used for external validation of the model. Results: The analysis showed that subtype B had a poorer prognosis and a higher degree of immune infiltration. The high-risk group had a poorer prognosis and higher tumor microenvironment scores. The nomogram could accurately predict patient survival. Conclusion: Fatty acid metabolism may affect the prognosis and immune infiltration of patients with ccRCC. The analysis was performed to understand the potential role of fatty acid metabolism genes in the immune infiltration and prognosis of patients. These findings have implications for individualized treatment, prognosis, and immunization for patients with ccRCC.