Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1–3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.

Innovations of transistors toward miniaturization and integration aggravate heat accumulation of central processing units (CPUs). Thermal interface materials (TIMs) are critical to remove the generated heat and to guarantee the device reliability. Herein, maltose-assisted mechanochemical exfoliation was proposed to prepare maltose-g-graphene as a structural motif of TIMs. Then, maltose-g-graphene/gelatin composite films with a bilayer structure were prepared by two-step vacuum filtration to construct effective thermally conductive pathways consisting of the directionally arranged and tightly packed maltose-g-graphene. The bilayer composite film exhibited a remarkable in-plane thermal conductivity (30.8 W m −1 K −1 ) and strong anisotropic ratio (∼8325%) at 40 wt % maltose-g-graphene addition. More intriguingly, the cooling effect on CPUs was significantly better for the bilayer composite films than commercial thermal pads as TIMs. The outstanding thermally conductive stability in resistance to instantaneous and prolonged thermal shocks as well as fatigue stability was gathered. Our work offers a valuable reference to design and fabricate highperformance TIMs for CPU cooling to surmount harsh application scenarios.

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Highly crosslinked ultrahigh molecular weight polyethylene (UHMWPE) stabilized by vitamin E (VE) is widely applied in artificial joints as the bearings. Despite the approval, there is a discord that VE lowers the crosslinking efficiency, limiting its use at high concentration. In this work, we aim to obtain highly crosslinked and oxidation resistant UHMWPE through the conjunction of tea polyphenol and chemical crosslinking. We hypothesized that highly incorporated tea polyphenol with multiple reactive sites can ameliorate crosslinking efficiency of chemical crosslinked UHMWPE in comparison to VE. Epigallocatechin gallate (EGCG) as representative tea polyphenol was incorporated into UHMWPE at high concentration (2–8 wt%), followed by chemical crosslinking with 2 wt% organic peroxide. Unlike VE/UHMWPE blends as the control, chemical crosslinking achieved an increasing trend in crosslink density of EGCG/UHMWPE blends with increasing antioxidant concentration. High concentration of EGCG also enhanced the oxidation stability of UHMWPE. Intriguingly, EGCG endowed UHMWPE with an excellent antimicrobial property, which was inefficient in VE/UHMWPE. Cell viability was hardly affected by the high loaded antioxidant and peroxide. The chemically crosslinked UHMWPE blended with EGCG is proved to be a reasonable, cost effective and realistic alternative for use in artificial joints.

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Background/Aim: Body fluids are considered to be a rich source of disease biomarkers. Proteins in many body fluids have potential clinical applications for disease diagnostic and prognostic purposes. The aim of this study was to establish an in-depth multi-body fluid proteome. Materials and Methods: Ten body fluids associated with 8 types of cancers collected from 23 patients involved in 19 common diseases underwent liquid chromatography tandem mass spectrometry (MS) analysis after gel-based protein separation (SDS-PAGE) or peptide-based fractionations. Bioinformatic analysis, including principal component analysis (PCA), consensus clustering, and hierarchical clustering analysis were also performed. The biological function was determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: We profiled the proteome of ten body fluids, including ascites, bile, cerebrospinal fluid (CSF), hydrothorax, knee joint fluid (KJF), plasma, saliva, serum, tears, and urine. A total of 3,396 nonredundant proteins were identified, of which 304 were shared among ten body fluids, with common functions in focal adhesion and complement/coagulation cascades. A total of 41.5% (1,409) of the proteins were detected in only one body fluid and were closely related to their adjacent tissues by function. The functional analysis of the remaining 1,683 proteins showed that similar functions might be shared among different body fluids, which further highlighted the close connection of body fluids in the human body. Conclusion: A deep proteome of multi-body fluids originated from patients diagnosed with 19 common diseases provides a valuable data resource, and might indicate the potential application of body fluids for biomarker discovery.Human body fluids are considered rich sources of potential disease biomarkers because they are in direct contact with a variety of living tissues, which include plasma/serum, saliva, urine, cerebrospinal fluid (CSF), tear fluid, ascites, bile, hydrothorax and knee joint fluid (KJF). It is widely accepted that human body fluids contain disease-associated proteins that are secreted, shed, and emanated from pathological tissues across the body (1). In disease, highly altered protein expression profiles in body fluids may generate undeniable signatures and unwrapped fingerprints, which may provide insight into disease mechanisms. Therefore, body fluids have potential applicability for the early detection of disease, for the monitoring of its progression, and for therapeutic drug efficacy, especially for their adjacent diseased tissue.Proteomics is a powerful method for biomedical research. With the significant advances in mass spectrometry (MS) and proteomics technologies (2, 3), protein biomarker discovery has become one of the central applications of proteomics. In terms of disease diagnosis and prognosis, compared to tissue biopsy, human body fluids (e.g. blood, urine, tears, or saliva) appear to be more easy and attractive because of several key advantages, including lo...

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