Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation and the impact of TET2 depletion on anti-PD-L1 therapy were determined in xenograft model experiments. Lymphocyte infiltration and chemokine expression were determined using flow cytometry and qRT-PCR. To determine the downstream targets of TET2, we performed hMeDip-seq and RNA-seq analyses. The molecular mechanism was further confirmed by hMeDip-qPCR, MeDip-qPCR, bisulfite sequencing, Western blotting, qRT-PCR and xenograft model experiments in vitro and in vivo. The present study demonstrated that ascorbic acid enhanced the efficacy of immunotherapy and that the loss of TET2 function enabled renal cancer cells to evade antitumor immunity. Ascorbic acid treatment significantly increased the intratumoral infiltration of T cells and the expression of cytokines and chemokines, while the loss of TET2 impaired the infiltration of T cells and the expression of cytokines and chemokines. TET2 was recruited to IRF1 by IFN-γ-STAT1 signaling, thereby maintaining IRF1 demethylation and ultimately inducing PD-L1 expression. These results suggest a new strategy of stimulating TET activity to improve immunotherapy for renal cell carcinoma.

Objective: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. Materials and methods: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients’ demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. Results: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2–2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4–4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25–22.25 min). Median operating time was 148.5 min (IQR: 178–238.5 min). Median console time was 107 min (IQR: 92.75–149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5–30 min). Median blood loss was 17.5 ml (IQR: 10–50 ml). Conclusions: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Background: The development and implementation of telesurgery are of significant strategic importance for the future expansion and evolution of the surgical robotics industry. Telesurgery has been demonstrated to improve access to advanced medical care but also enhances the overall healthcare delivery in these underserved regions. Here, we presented a telesurgery system that optimized surgical signals via a telesurgery host using real-time signal processing and multi-source signal interaction systems. Additionally, a telesurgery network solution was developed to ensure seamless network switching. Materials and methods: We present the results of the first multi-center human study of robot-assisted laparoscopic telesurgery. Specifically, telesurgeries were performed on 18 patients across four hospitals in China utilizing EDGE MP 1000 tele-surgical systems. The distances between each pair of cities ranged from 450 km to 2200 km. Results: The telesurgery success rate was 100%. The mean real-time round-trip network latency, network jitter, video encoding/decoding latency, code rate, and video display latency were 38.38 ± 13.25 ms, 0.39 ± 0.29 ms, 20.02 ± 0.06 ms, and 12.77 ± 0.57 Mbps, 21.35 ± 3.42 ms, respectively. There was no frame loss during all telesurgeries. Conclusion: Our results indicated that telesurgery using 5G and dedicated line technology was a safe and feasible treatment option for patients with urologic oncology.

CDK12 primarily functions as a transcription regulatory cyclin-dependent kinase (CDK) that controls mRNA elongation, splicing, and polyadenylation. The CDK12 gene is implicated in human cancers since it is frequently mutated and/or deleted in prostate and ovarian cancer but paradoxically amplified in breast cancer. Here, we demonstrate that CDK12 promotes serine-933 phosphorylation of DNA2, a nuclease/helicase critical for replication fork stress regulation, and the phosphorylation subsequently facilitates DNA2 polyubiquitination and degradation mediated by the APC/C ^CDC20 E3 ubiquitin ligase. CDK12 inactivation induces but amplification suppresses genome-wide expression of interferon response and antigen processing and presentation machinery genes in ovarian and breast cancer cells, respectively. Besides causing aberrant DNA2 stabilization, replication stress, genomic instability, and cytosolic double-stranded DNA (dsDNA) accumulation, CDK12 loss also triggers cGAS–STING activation and innate immune response, which can be reversed by forced expression of replication protein A (RPA) subunits or DNA2 depletion. Our findings identify DNA2 as a phosphorylation substrate of CDK12, connecting CDK12 to cell cycle regulation. These data also reveal DNA2 protein destruction as a critical mechanism that dictates genomic instability, cGAS–STING signaling activation, and innate immune response in CDK12-deregulated cancers.

Evidence on the association between anthocyanidin intake and renal cancer risk is limited. The aim of this study was to assess the association of anthocyanidin intake with renal cancer risk in the large prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The cohort for this analysis consisted of 101,156 participants. A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and the 95% confidence intervals (CIs). A restricted cubic spline model with three knots (i.e., 10th, 50th, and 90th percentiles) was used to model a smooth curve. A total of 409 renal cancer cases were identified over a median follow-up of 12.2 years. In the categorical analysis with a fully adjusted model, a higher dietary anthocyanidin consumption was associated with a lower risk of renal cancer (HR_Q4vsQ1: 0.68; 95% CI: 0.51–0.92; p for trend < 0.010). A similar pattern was obtained when anthocyanidin intake was analyzed as a continuous variable. The HR of one-SD increment in the anthocyanidin intake for renal cancer risk was 0.88 (95% CI: 0.77–1.00, p = 0.043). The restricted cubic spline model revealed a reduced risk of renal cancer with a higher intake of anthocyanidins and there was no statistical evidence for nonlinearity (p for nonlinearity = 0.207). In conclusion, in this large American population, a higher dietary anthocyanidin consumption was associated with a lower risk of renal cancer. Future cohort studies are warranted to verify our preliminary findings and to explore the underlying mechanisms in this regard.