Search

MYC is one of the most important oncogenes and is overexpressed in a number of human cancers. The G-quadruplex formed in the MYC oncogene promoter (MycG4) is a transcriptional silencer and amenable to small molecule targeting. G-quadruplexes are noncanonical four-stranded DNA or RNA secondary structures that have emerged as novel therapeutic targets. Indenoisoquinolines are human topoisomerase I inhibitors with improved physicochemical and biological properties as compared to the clinically used camptothecin anticancer drugs. Three indenoisoquinolines, indotecan (LMP400), indimitecan (LMP776), and LMP744, have entered phase I clinical trials in adults with relapsed solid tumors and lymphomas. However, some indenoisoquinolines showed potent anticancer activity without being strong topoisomerase I inhibitors, suggesting additional mechanisms of action. Herein, we demonstrate that a large number of anticancer indenoisoquinolines strongly bind and stabilize MycG4 in vitro, using fluorescence, nuclear magnetic resonance (NMR), and circular dichroism (CD) spectroscopy, as well as gel electromobility shift assay (EMSA). In addition, MycG4-interactive indenoisoquinolines lower MYC mRNA and protein levels in vivo, as shown by western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments. Structure-activity-relationships of MycG4 recognition by indenoisoquinolines were investigated to understand structural requirements for binding. Systemic analysis of indenoisoquinoline derivatives led to the discovery of a synergistic effect of MYC inhibition and topoisomerase I inhibition on anticancer activity. Therefore, these results indicate that targeting the MYC promoter G-quadruplex to downregulate MYC is a new mechanism of action for anticancer indenoisoquinolines. Moreover, our data reveals dual targeting of MycG4 and topoisomerase I as a novel strategy for cancer therapy. Citation Format: Danzhou Yang, Mark Cushman, Kai-Bo Wang, Mohamed S. Elsayed, Guanhui Wu, Adam J. Buric, Mercedes DeMoss. Dual targeting MYC G-quadruplex and topoisomerase I by indenoisoquinolines for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3103.

PDGFR-β (Platelet-Derived Growth Factor Receptor beta) is a receptor tyrosine kinase whose overexpression drives the progression and metastasis of many cancers. It is an established anticancer target and PDGFR-β inhibition via kinase inhibitors has been actively sought-after. However, PDGFR-β kinase inhibitors often lack specificity. The PDGFR-β gene promoter forms DNA G-quadruplexes that are transcription silencer whose stabilization by small molecules represses PDGFR-β expression. Therefore, targeting PDGFR-β promoter G-quadruplexes for transcriptional silencing is a promising alternative strategy for cancer therapy. G-quadruplex is an exciting family of non-canonical DNA secondary structures. DNA G-quadruplex within the PDGFR-β gene promoter forms novel vacancy pockets (vG4) that can be filled-in by guanine metabolites such as dGMP and cGMP. This presents an attractive target for small molecule targeting. Herein, we present the binding of the natural product berberine with the unique PDGFR-β dGMP-vG4 binary complex to form a novel ternary complex, the first case observed in DNA G-quadruplexes. Using circular dichroism, fluorescence, and nuclear magnetic resonance (NMR) spectroscopy, we demonstrated that berberine binds with high affinity and strongly stabilizes the dGMP-fill-in PDGFR-β vG4. Our determined high-resolution NMR structure of this ternary complex in K+-containing solution reveals a 2:1 binding stoichiometry of berberine to the dGMP-fill-in PDGFR-β vG4. Significantly, one berberine directly stacks upon and extensively covers the dGMP. This direct binding mode provides structural basis for targeting the unique PDGFR-β promoter G-quadruplex by small molecules and suggests an intriguing strategy of designing drug-like, guanine-conjugated molecules to selectively silence the PDGFR-β gene. Because vG4 formation and dGMP fill-in is a unique property of the PDGFR-β promoter G-quadruplex, our study provides a structural basis for rationally designing small molecule drugs to specifically target the PDGFR-β promoter G-quadruplex to inhibit oncogenic PDGFR-β for cancer therapeutics. Citation Format: Kai-Bo Wang, Jonathan Dickerhoff, Yichen Han, Danzhou Yang. Berberine recognition of the dGMP-bound PDGFR-β promoter G-quadruplex: Structural insight into specific drug targeting. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3842.

The effect of particle deformation zone (PDZ) on the microstructure and mechanical properties of SiCp/Mg-5Zn composites was studied. Meanwhile, the work hardening and softening behavior of SiCp/Mg-5Zn composites influenced by PDZ size were analyzed and discussed using neutron diffraction under in-situ tensile deformation. The evolution of FWHM (full width at half maximum) extracted from the diffraction pattern of SiCp/Mg-5Zn composites was used to interpret the modification of dislocation density during in-situ tension, which discovered the effect of dislocation on the work hardening behavior of SiCp/Mg-5Zn composites. In addition, the tensile stress reduction (ΔPi) values during in-situ tension test were calculated to analyze the effect of PDZ size on the softening behavior of SiCp/Mg-5Zn composites. The results show that the work hardening rate of SiCp/Mg-5Zn composites increased with the enlargement of PDZ size, which was attributed to the grain size of SiCp/Mg-5Zn composites increased with the enlargement of PDZ size. Moreover, the stress reduction (ΔPi) values increased continuously during in-situ tensile for SiCp/Mg-5Zn composites due to the increased stored energy produced during plastic deformation, which provided a driving force for the softening effect. However, the effect of grain size on the softening behavior is greater than that of the stored energy, which led to the tensile stress reduction (ΔPi) values of P30 (dPDZ = 30 μm) -SiCp/Mg-5Zn composite were higher than that of P60 (dPDZ = 60 μm) -SiCp/Mg-5Zn composite when the eri were 0.25, 0.5, 0.75 and 1, respectively.

Objective To assess the prenatal screening, diagnosis and pregnancy outcomes status with noninvasive prenatal testing (NIPT) in Beijing in 2019. Methods Descriptive statistical methods were used to analyze the screening and diagnosis status by detecting fetal free DNA in maternal peripheral blood in 8 prenatal diagnosis institutions in Beijing. Results A total of 65136 cases of pregnant women accepted NIPT in the 8 institutions in 2019, accounting for 29.8% of the total number of pregnant women (65 136/218 396). The compound coincidence positive predictive rate of 21\18\13-trisomy syndrome was 57.4%(152/265), the coincidence rates of 21-trisomy, 18-trisomy, 13-trisomy, sex chromosomes and other chromosomes were 76.0%(117/154), 38.89%(28/72), 18.0%(7/39), 30.5%(85/279) and 16.4%(30/183), respectively. Among the 65 136 pregnant women, 10 791 cases were suitable for population screening (16.6%); 53 833 cases were used with caution (82.7%); 343 cases were not suitable for population screening (0.5%). By following-up, one case of 21-trisomy and one case of 18-trisomy were found to be false negative cases. The detection rate of 21\18\13-trisomy syndrome was 98.7%(152/154), of 21-trisomy was 99.2%(117/118), of 18-trisomy was 96.6%(28/29), and of 13-trisomy was 100%(7/7). The prenatal diagnosis rate of NIPT was 84.6% for high-risk pregnant women (615/727), of them the prenatal diagnosis rate was 91.7%(243/265) for 21\18\13-trisomy syndrome cases. Conclusions Detection of fetal free DNA in maternal peripheral blood (NIPT) has become one of the important methods of screening 21-trisomy syndrome. In clinical applications, doctors should strictly grasp the test indications, pay attention to genetic counseling before and after testing, improve the prenatal diagnosis rate, strengthen laboratory quality control and improve the quality of testing. DOI: 10.11855/j.issn.0577-7402.2020.12.07

A novel electrochemical method for preparing flower-like nanostructured silver particles using polyvinyl alcohol (PVA) modified carbon cloth as a cathode is reported. The method does not involve the use of any morphological control agents in aqueous solution. The morphology of the silver nanoparticles obtained was studied using scanning electron microscopy (SEM) and X-ray diffractometry (XRD). The effects of the operating conditions on the deposited silver nanoparticles were investigated. It was found that PVA concentration for carbon cloth modification had a significant effect on the deposited silver morphology. With 1% PVA modification, current density of 10 μA cm

Guanine (G)-oxidation to 8-oxo-7,8-dihydroguanine (OG) by reactive oxygen species in genomic DNA has been implicated with various human diseases. G-quadruplex (G4)-forming sequences in gene promoters are highly susceptible to G-oxidation, which can subsequently cause gene activation. However, the underlying G4 structural changes that result from OG modifications remain poorly understood. Herein, we investigate the effect of G-oxidation on the BLM gene promoter G4. For the first time, we show that OG can induce a G-vacancy-containing G4 (vG4), which can be filled in and stabilized by guanine metabolites and derivatives. We determined the NMR solution structure of the cGMP-fill-in oxidized BLM promoter vG4. This is the first complex structure of an OG-induced vG4 from a human gene promoter sequence with a filled-in guanine metabolite. The high-resolution structure elucidates the structural features of the specific 5′-end cGMP-fill-in for the OG-induced vG4. Interestingly, the OG is removed from the G-core and becomes part of the 3′-end capping structure. A series of guanine metabolites and derivatives are evaluated for fill-in activity to the oxidation-induced vG4. Significantly, cellular guanine metabolites, such as cGMP and GTP, can bind and stabilize the OG-induced vG4, suggesting their potential regulatory role in response to oxidative damage in physiological and pathological processes. Our work thus provides exciting insights into how oxidative damage and cellular metabolites may work together through a G4-based epigenetic feature for gene regulation. Furthermore, the NMR structure can guide the rational design of small-molecule inhibitors that specifically target the oxidation-induced vG4s.

Two nonbiaryl axially chiral β-carboline-quinazoline dimers, pegaharmols A (1) and B (2), were isolated from the roots of Peganum harmala. Their planar structures were elucidated by the spectroscopic methods of high-resolution mass spectrometry and 1D and 2D nuclear magnetic resonance (NMR). The stereochemistry was established by a comparison between the experimental data of NMR and electronic circular dichroism and the computed data by quantum mechanical calculations. It is discovered for the first time that the β-carboline at the C-8 position is bonded to the vasicine at the C-9 position. 1 exhibited moderate cytotoxic activity against HL-60 and A549 cell lines.

In this work, the microstructure and mechanical properties of Mg–Al–Ca–Mn alloys with different Ca/Al ratios (0.2, 0.6 and 1.0) have been investigated. The results showed that with the increase of the Ca/Al ratios, the grain sizes of the alloys were significantly refined, and the morphologies and types of main second phases changed from a block Mg17Al12 phase to a semi-continuous Al2Ca (C15) phase and a continuous network (Mg, Al)2Ca (C36) phase. The extruded Mg–2.4Al–2.4Ca–0.6Mn alloy, which was consisted of dynamically recrystallized grains and undynamically recrystallized regions, possessed outstanding mechanical properties with the yield strength of 335.9 MPa, the ultimate tensile strength of 354.7 MPa and the elongation of 8.4%. This was mainly due to the resultant effects of grain refinement strengthening, secondary phases strengthening, texture strengthening and work hardening.

Mechanical properties of microalloying Mg–2.2Zn–1.8Ca–0.5Mn (wt%) matrix composites reinforced by 0.5 wt% TiC nanoparticles before and after extrusion were investigated based on the detailed microstructural analysis. A uniform distribution of TiC nanoparticles was realized in the nanocomposite by the method of ultrasonic-assisted semisolid stirring. The morphology of eutectic Ca2Mg6Zn3 phases changed from plate-like in the free TiC nanoparticles region to lamellar in the dense TiC nanoparticles region for the as-cast nanocomposite. Both the grain structure and precipitates were obviously refined as the extrusion temperature decreased from 350 to 270 °C. The nanocomposite exhibited excellent tensile yield strength (352–428 MPa) which was governed by the extrusion temperature. The grain refinement strengthening with the contribution ratio of ∼80% to this strength increment was much higher relative to thermal expansion effect, Orowan strengthening and dislocation strengthening. Ultrafine recrystallized grain structure with a substantial of fine precipitates appeared in the nanocomposite extruded at 270 °C. The refined grain structure was not only due to dynamic recrystallization, but also the synergistic pinning effect of nano-TiCp, precipitated MgZn2 and α-Mn particles. The tensile toughness value of nanocomposite after extrusion improved with increasing the extrusion temperature. Massive micro-cracks formed along the remnant coarse Ca2Mg6Zn3 led to the structural failure during tension.

A large amount of lamellar phases were precipitated in Mg-9Gd-xAl (x = 0.4, 0.6, 0.8, 1.0, 3.0 wt.%) alloy after solution treatment. In order to explore the composition and formation condition of the lamellar phase, the Mg-9Gd-xAl alloys were subjected to solution treatment at different time, then the influence of lamellar phase on mechanical properties was investigated in Mg-9Gd-xAl alloys. The results indicate that the lamellar phase consists of three elements, Mg, Al, and Gd, and the atomic ratio is close to 1:1:1. It was identified that the lamellar phase is (Mg, Al)2Gd phase which has the same crystal structure with Al2Gd. In addition, the lamellar phases were parallel to each other inside one grain, but the alignment directions inside the adjacent grains were different, which provide strong second phase strengthening effect. After solution treatment, the ultimate tensile strength of Mg-9Gd-0.6Al alloy with abundant lamellar phase is greatly improved to 193 MPa.

TiC nanoparticle-reinforced Mg−4Zn−0.5Ca matrix nanocomposites were processed by combining multidirectional forging (MDF) and extrusion (EX). The grain size of the nanocomposite after MDF+EX multi-step deformation was significantly decreased compared with that processed only by MDF. The average size of the recrystallized grains gradually increased after EX with increasing the number of MDF passes at 270 °C. However, the grain size significantly decreased by MDF processing at 310 °C. Both fine and coarse MgZn2 phases appeared in the (MDF+EX)-processed nanocomposites, and their volume fractions gradually increased with increasing the number of MDF passes before EX. Ultrahigh tensile properties (yield strength of ~404 MPa, ultimate tensile strength of ~450.3 MPa and elongation of ~5.2 %) were obtained in the nanocomposite after three MDF passes at 310 °C followed by EX. This was attributed to the refinement of the recrystallized grains, together with the improved Orowan strengthening provided by the precipitated MgZn2 particles that were generated by MDF+EX multi-step deformation.

The present work mainly focuses on the effect of minor content of Gd element on the microstructure and mechanical properties of Mg-Zn alloy. The Mg-4Zn-xGd (x=0, 0.5, 1, 2) alloys were fabricated and subjected to extrusion at 280°C with the ratio of 25:1. Results revealed that the addition of Gd could inhibit the dynamic recrystallization (DRX) of Mg-4Zn alloy, and both the size and volume fraction of DRXed grains demonstrated a decreasing tendency as the Gd content increased from 0.5 to 2 wt.%. It is the weakening effect on DRX behavior that lead to the smaller amount of fine precipitate and the stronger texture intensity. As compared with the Mg-4Zn alloy, the yield strength and ultimate tensile strength of Mg-4Zn-xGd alloys were improved obviously by the addition of minor content of Gd, however, at the expense of elongation. Excellent tensile properties with the yield strength of ∼369.8 MPa and ultimate tensile strength of ∼400.3 MPa were obtained when the Gd content was 2 wt.%.

A new Mg-2.2 wt% Zn alloy containing 1.8 wt% Ca and 0.5 wt% Mn has been developed and subjected to extrusion under different extrusion parameters. The finest (~ 0.48 μm) recrystallized grain structures, containing both nano-sized MgZn2 precipitates and α-Mn nanoparticles, were obtained in the alloy extruded at 270 °C/0.01 mm s−1. In this alloy, the deformed coarse-grain region possessed a much stronger texture intensity (~ 32.49 mud) relative to the recrystallized fine-grain region (~ 13.99 mud). A positive work hardening rate in the third stage of work hardening curve was also evident in the alloy extruded at 270 °C, which was related to the sharp basal texture and which provided insufficient active slip systems. The high work hardening rate in the fourth stage contributed to the high ductility extruded at 270 °C/1 mm s−1. This alloy exhibited a weak texture, and the examination of fracture surface revealed highly dimpled surfaces. The optimum tensile strength was achieved in the alloy extruded at 270 °C/0.01 mm s−1, and the yield strength, ultimate tensile strength and elongation to failure were ~ 364.1 MPa, ~ 394.5 MPa and ~ 7.2%, respectively. Fine grain strengthening from the recrystallized fine-grain region played the greatest role in the strength increment of this alloy compared with Orowan strengthening and dislocation strengthening in the deformed coarse-grain regions.

A newly developed low Mn and high-Ca containing magnesium alloy, Mg-2.9Zn-1.1Ca-0.5 Mn (wt.%) based alloy was processed by low-temperature extrusion. The average recrystallized grain size decreased from 1.64 to 0.58 μm with a decrease in the extrusion speed from 1 to 0.01 mm s−1, but increased to 2.11 μm with increasing extrusion temperature from 270 to 350 ℃. The finest and uniform recrystallized grain structures with substantial nano-sized MgZn2 precipitates and α-Mn particles were obtained in the 270 ℃/0.01 mm s−1 sample. The texture intensity including basal (0002), prismatic type I (10−10) and prismatic type II (11–20) decreased accompanied by increasing the deformation temperature or extrusion speed. The weakest texture intensity for the 270 ℃/1 mm s−1 sample was derived from high degree of recrystallization, inhomogeneous recrystallized grain structure and the precipitates. Superior uniaxial tensile strength (yield strength of ∼352.5 MPa, ultimate tensile strength of ∼382.3 MPa and elongation of ∼7.1%) were achieved in the 270 ℃/0.01 mm s−1 sample. The improved yield strength was mainly ascribed to fine grain strengthening and precipitates strengthening relative to dislocation strengthening and back stress strengthening. A positive slope of work-hardening rate (dθ⁄dσ > 0) extruded at 270 ℃/0.01 mm s−1 was related to the sharp basal texture and insufficient slip. High θ value at stage IV after extrusion at 270 ℃/1 mm s−1 with abundant dimples and weak texture contributed to high ductility. Massive micro-cracks formed along the twins in the coarse deformed grains led to the failure during tension.

SiCp/Mg composites, where a minor amount of SiCp was added to the pure Mg, were fabricated in this work to eliminate the influence of precipitates and determine the effect of the particle deformation zone on the microstructure, texture and mechanical properties of the Mg matrix. The results show that the dynamically recrystallized ratio in the SiCp/Mg composite obviously improved because SiCp promoted the nucleation of DRX. Compared with those of the pure Mg, the SiCp/Mg composite had finer grain sizes and weaker basal textures. Even when only 1 vol.% SiCp was added to the pure Mg, the yield strength, ultimate tensile strength and elongation of pure Mg could be increased to 247.3 MPa, 260.36 MPa and 6.85%, respectively. Such high strength of the SiCp/Mg composite might attribute to the fine grain size as well as nano-MgO precipitates after the addition of a minor amount of SiCp.

This paper investigates the leader-following formation tracking problem (FTP) for multiple nonholonomic agent systems (MNASs) in the presence of external disturbances and parametric uncertainties, where both the kinematics and dynamics of the agents are taken into consideration. A novel finite-time distributed controller-estimator algorithm (DCEA) is designed to handle such a challenging problem. Based on Lyapunov stability method, the sufficient conditions for finite-time stability of the closed-loop system are derived. Finally, the simulation results are presented to demonstrate the effectiveness and the robustness of the proposed DCEA.

Erosion wear is the main failure cause of the throttling ring in artillery, which will lead to the reduction of the reliability of the throttling ring, which also will lead to degradation of the performance of recoil brake. According to the working conditions and environmental characteristics of the throttling ring, the finite element model of the erosion wear of the throttling ring is established, and the erosion wear simulation test is carried out to study the erosion wear rules of the throttling ring under different influencing factors, so as to evaluate the reliability of the throttling ring reasonably. It is of great theoretical and practical value to obtain the reliability information of the throttling ring under different working conditions and to ensure the normal performance of the recoil brake.

Porous Co/C composite nanofibers were fabricated by combination of electrospinning method and polymer blend. The phase composition, microstructure and electromagnetic characteristics of them were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and vector network analyzer (VNA), and their microwave absorption performances were studied. The results indicate that nanofibers were composited by amorphous carbon and face-centered cubic structured Co nanoparticle after sintering. The addition of PMMA is a key factor of nanofibers morphology and the aperture was improved with the increase of PMMA. When the thickness is 2.0 mm, the samples exhibit the best microwave absorption performance. Their effective absorpt ion bandwidths (RL < 10 dB) are 6.3 GHz, 6.2 GHz and 6.1 GHz, and it’s obviously superior to ordinary morphology nanofibers.

In order to study the corrosion resistance of extruded magnesium alloys, the Mg–4Zn–2Gd–0.5Ca alloy was extruded at the speed of 0.01–0.1 mm/s with the temperature of 280–360 °C in present study. Hot extrusion results show that the volume fraction of precipitates (Vpre), VDRX (the dynamic recrystallization rate) and the average size of DRXed grain (dDRX) decrease with the decrease in extrusion speed, and the corrosion rate of the alloy also shows a downward trend. On the contrary, the values of Vpre, VDRX and dDRX increase with the increase in extrusion temperature, and the corrosion resistance of Mg–4Zn–2Gd–0.5Ca alloy decreases. When the extrusion speed is 0.01 mm/s and the extrusion temperature is 280 °C, the alloy has the best corrosion resistance. The corrosion of extruded Mg–4Zn–2Gd–0.5Ca alloy occurs preferentially on the magnesium matrix around W and I phases in the DRXed zone. With the further corrosion, the corrosion continues to spread along the phase, and the corrosion area gradually increases. Galvanic corrosion plays a leading role in the corrosion process. Moreover, there are a large number of basal plane textures in the unDRXed region, which is conducive to improving the corrosion resistance of magnesium alloys. In addition, the decrease in grain size also makes the corrosion of magnesium alloy more uniform.

In this work, a Mg–Zn–Ca magnesium matrix nanocomposite containing nano-sized TiC particles was firstly processed by multidirectional forging (MDF). With increasing the forging temperature from 230 to 310 °C for 1 MDF pass or the number of MDF passes at 270 °C, both volume fractions and average sizes of recrystallized grains increased. The average sizes of precipitated MgZn2 phases increased with the increase in either the initial forging temperature or MDF passes, and the volume fractions gradually decreased with increasing the initial forging temperature or decreasing the MDF passes. With decreasing the initial MDF temperature, thermal expansion mismatch strengthening slightly decreased while fine-grain strengthening and Orowan strengthening gradually increased, resulting in a gradual increased yield strength. The elongation of the present nanocomposite gradually increased from 8.2% after 1 MDF pass to 22.7% after 6 MDF passes, while both yield strength and ultimate tensile strength did not change significantly. This could be ascribed to that although the fine-grain strengthening gradually reduced, there was no significant change in the Orowan strengthening caused by MgZn2 phases with increasing the number of MDF passes.

Clear cell renal carcinoma (ccRCC) is the most common subtype of renal cancer, accounting for approximately 75% of all histological types of renal cancer, and is the leading cause of death from renal cancer. However, the molecular mechanism of tyrosine kinase binding protein (TYROBP) and sex-determining region Y Box-6 (SOX6) in the ccRCC was not precise.Bioinformatics analysis was performed to explore the hub role of TYROBP and SOX6 on the ccRCC. A total of 6 patients with clear cell renal cell carcinoma (ccRCC) were recruited. HE staining was performed to observe the pathology result of ccRCC. Immunohistochemistry and Immunofluorescence assay was made to detect the protein expression of TYROBP. Total RNA was extracted using TRIzol to examine the mRNA expression of TYROBP via the Real time quantitative polymerase chain reaction. The strong correlation between the expression of TYROBP and the survival time of ccRCC patients was performed by the BP neural network and support vector machine.Compared with the control group, the expression of SOX6 was downregulated in the samples with ccRCC. However, the expression of TYROBP was higher in the samples with ccRCC than in the control group. Compared with the patients with high SOX6 expression, the patients with low SOX6 expression have a poor survival prognosis (HR=0.39, P.05). However, the patients with high TYROBP expression have a shorter survival time than the patients with low TYROBP expression (HR=1.66, P.05). The genes related with TYROBP and SOX6 are mainly enriched in the regulation of cell activation, leukocyte activation, negative regulation of cell activation, myeloid leukocyte activation, positive regulation of response to external stimulus, immune response-regulating signaling pathway. The interaction between TYROBP, SOX6, and kidney neoplasms was drawn, and the inference score of TYROBP and SOX6 on the kidney neoplasms was high.In conclusion, TYROBP is highly expressed in renal clear cell carcinoma, and when this molecule is highly expressed, the survival prognosis of renal carcinoma is poor. TYROBP and SOX6 may be potential targets for diagnosing and treating renal clear cell carcinoma.