Lysine methyltransferase 5C increases the proliferation and metastatic abilities of clear cell renal cell carcinoma via aerobic glycolysis.

Among all types of renal cancer, clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype and is associated with a high risk of metastasis and recurrence. Histone modifications regulate several biological processes that are fundamental to the development of cancer. Lysine methyltransferase 5C (KMT5C; also known as SUV420H2) is an epigenetic modifier responsible for the trimethylation of H4K20, which drives critical cellular events, including genome integrity, cell growth and epithelial­mesenchymal transition (EMT), in various types of cancer. However, the role of KMT5C in ccRCC remains unclear. As such, the expression and function of KMT5C in ccRCC were investigated in the present study. KMT5C expression was significantly increased in ccRCC tissues compared with normal tissues (P<0.0001), and it was closely associated with the overall survival rate of patients with ccRCC. By establishing ccRCC cell lines with KMT5C expression knockdown, the role of KMT5C in the maintenance of aerobic glycolysis in ccRCC cells via the regulation of several vital glycolytic genes was identified. Additionally, KMT5C promoted the proliferation and EMT of ccRCC cells by controlling crucial EMT transcriptional factors. Together, these data suggested that KMT5C may act as an oncoprotein, guide molecular diagnosis, and shed light on novel drug development and therapeutic strategies for patients with ccRCC.

DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma.

The KEAP1-NRF2 axis is the principal regulator of cellular responses to oxidative and electrophilic stressors. NRF2 hyperactivation is frequently observed in many types of cancer and promotes cancer initiation, progression, metastasis, and resistance to various therapies. Here, we determined that dipeptidyl peptidase 9 (DPP9) is a regulator of the KEAP1-NRF2 pathway in clear cell renal cell carcinoma (ccRCC). DPP9 was markedly overexpressed at the mRNA and protein levels in ccRCC, and high DPP9 expression levels correlated with advanced tumor stage and poor prognosis in patients with ccRCC. Protein affinity purification to identify functional partners of DPP9 revealed that it bound to KEAP1 via a conserved ESGE motif. DPP9 disrupted KEAP1-NRF2 binding by competing with NRF2 for binding to KEAP1 in an enzyme-independent manner. Upregulation of DPP9 led to stabilization of NRF2, driving NRF2-dependent transcription and thereby decreasing cellular reactive oxygen species levels. Moreover, DPP9 overexpression suppressed ferroptosis and induced resistance to sorafenib in ccRCC cells, which was largely dependent on the NRF2 transcriptional target SLC7A11. Collectively, these findings indicate that the accumulation of DPP9 results in hyperactivation of the NRF2 pathway to promote tumorigenesis and intrinsic drug resistance in ccRCC. SIGNIFICANCE: DPP9 overcomes oxidative stress and suppresses ferroptosis in ccRCC by binding to KEAP1 and promoting NRF2 stability, which drives tumor development and sorafenib resistance.

Leafhopper-inspired reversibly switchable antireflection coating with sugar apple-like structure arrays.

Optical coatings with reversibly tunable antireflective characteristics hold a tremendous potential for next generation optical energy-related applications. Bioinpsired by the camouflage behavior of small yellow leafhoppers, silica hollow sphere/shape memory polymer composites are self-assembled using a non-lithography-based approach. The average visible transmittance of the as-patterned hierarchical structure array-covered substrate is increased by ca. 6.3% at normal incident, and even improved by more than 20% for an incident angle of 75°. Interestingly, the broadband omnidirectional antireflection performance can be reversibly erased and recovered by applying external stimuli under ambient conditions. To gain a better understanding, its reversibility, mechanical robustness, and the structure-shape effect on the antireflective properties are systematically investigated in this research.

Development of a novel resin for provisional prostheses using hyperbranched polyurethane acrylate and triethylene glycol dimethacrylate - An in vitro study.

PURPOSE: To develop a novel resin for provisional prostheses using hyperbranched polyurethane acrylate (HBPUA) and triethylene glycol dimethacrylate (TEGDMA) with promising mechanical properties and low volumetric shrinkage. METHODS: Four groups including TIH3-0 (100 wt% TEGDMA), TIH3-30 (30 wt% HBPUA + 70 wt% TEGDMA), TIH3-60 (60 wt% HBPUA + 40 wt% TEGDMA), and TB-60 (60 wt% bisphenol A-glycidyl dimethacrylate + 40 wt% TEGDMA) were prepared and commercial Luxatemp (DMG) was used for comparison. Fourier transform infrared spectroscopy and gel permeation chromatography were used for material characterization. Mechanical properties including microhardness, flexural strength, flexural modulus, and load energy were measured before and after water immersion. Physical properties measurement included weight changes, solubility, water absorption, surface hydrophobicity, and volumetric shrinkage. Finally, biocompatibility was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. RESULTS: The number- and weight-average molecular weights of the HBPUA were approximately 870 and 1480, respectively. The addition of HBPUA to TEGDMA increased the mechanical strength considerably. Although the weight changes and water absorption of TIH3-60 were higher than those of Luxatemp, the microhardness, flexural strength, flexural modulus, load energy, solubility, shrinkage, and biocompatibility of TIH3-60 were either comparable or superior to those of Luxatemp. CONCLUSION: Based on the findings of the present study, TIH3-60 has potential for development as a new provisional material.

Construction of an Immune Escape-Related Signature in Clear Cell Renal Cell Carcinoma and Identification of the Relationship between IFNAR1 and Immune Infiltration by Multiple Immunohistochemistry.

BACKGROUND: In the past decade, immunotherapy has been widely used in the treatment of various tumors, such as PD-1/PD-L1 inhibitors. Although clear cell renal cell carcinoma (ccRCC) has been shown to be sensitive to immunotherapy, it is effective only in several cases, which brings great obstacles to anti-tumor therapy for patients. Lawson et al. have successfully identified 182 "core cancer innate immune escape genes" whose deletion makes cancer cells more sensitive or resistant to T-cell attack. METHODS: In this research, we sought to explore genes closely associated with ccRCC among the 182 core cancer innate immune escape genes. We used online databases to screen mutated genes in ccRCC, and then used ConsensusClusterPlus to cluster clinical samples to analyze differences in clinical prognosis and immune components between the two subgroups. In addition, the immune escape score was calculated using lasso cox regression, and a stable tumor immune escape-related nomogram was established to predict the overall survival of patients. RESULTS: Higher immune escape score was significantly correlated with shorter survival time. Meanwhile, through the validation of the external cohort and the correlation analysis of the immune microenvironment, we proved that IFNAR1 is the key gene regulating immune escape in ccRCC, and we also found that the function of IFNAR1 in promoting immune activation is achieved by facilitating the infiltration of CD4+ T cells and CD8+ T cells. IFNAR1 regulates the malignant behavior of ccRCC by inhibiting the proliferation and migration properties. CONCLUSIONS: IFNAR1 may become a key biomarker for evaluating the efficacy of ccRCC immunotherapy and may also be a potential target for immunotherapy.

Thin-Film Coated Plastic Wrap for Food Packaging.

In this study, the antimicrobial property and food package capability of polymethylpentene (PMP) substrate with silicon oxdie (SiOx) and organic silicon (SiCxHy) stacked layers deposited by an inductively coupled plasma chemical vapor deposition system were investigated. The experimental results show that the stacked pair number of SiOx/SiCxHy on PMP is limited to three pairs, beyond which the films will crack and cause package failure. The three-pair SiOx/SiCxHy on PMP shows a low water vapor transmission rate of 0.57 g/m²/day and a high water contact angle of 102°. Three-pair thin-film coated PMP demonstrates no microbe adhesion and exhibits antibacterial properties within 24 h. Food shelf life testing performed at 28 °C and 80% humidity reports that the three-pair thin-film coated PMP can enhance the food shelf-life to 120 h. The results indicate that the silicon-based thin film may be a promising material for antibacterial food packaging applications to extend the shelf-life of food products.