Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority of kidney cancer death worldwide, whose incidence and mortality are not promising. Identifying ideal biomarkers to construct a more accurate prognostic model than conventional clinical parameters is crucial.Methods: Raw count of RNA-sequencing data and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA). Tumor samples were divided into two sets. Differentially expressed genes (DEGs) were screened in the whole set and prognosis-related genes were identified from the training set. Their common genes were used in LASSO and best subset regression which were performed to identify the best prognostic 5 genes. The gene-based risk score was developed based on the Cox coefficient of the individual gene. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess its prognostic power. GSE29609 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to screen independent prognostic parameters to construct a nomogram. The predictive power of the nomogram was revealed by time-dependent ROC curves and the calibration plot and verified in the validation set. Finally, Functional enrichment analysis of DEGs and 5 novel genes were performed to suggest the potential biological pathways.Results: PADI1, ATP6V0D2, DPP6, C9orf135 and PLG were screened to be significantly related to the prognosis of ccRCC patients. The risk score effectively stratified the patients into high-risk group with poor overall survival (OS) based on survival analysis. AJCC-stage, age, recurrence and risk score were regarded as independent prognostic parameters by Cox regression analysis and were used to construct a nomogram. Time-dependent ROC curves showed the nomogram performed best in 1-, 3-and 5-year survival predictions compared with AJCC-stage and risk score in validation sets. The calibration plot showed good agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis suggested several enriched biological pathways related to cancer. Conclusions:In our study, we constructed a gene-based model integrating clinical prognostic parameters to predict prognosis of ccRCC well, which might provide a reliable prognosis assessment tool for clinician and aid treatment decision-making in the clinic. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

No abstract

A strategy is introduced for enhancing the cellular selectivity of Amphotericin B (AmB) and other classes of membrane-disrupting agents. This strategy involves attaching the agent to a molecular umbrella to minimize the disruptive power of aggregated forms. Based on this approach, AmB has been coupled to a molecular umbrella derived from one spermidine and two cholic acid molecules and found to have antifungal activities approaching that of the native drug. However, in sharp contrast to AmB, the hemolytic activity and the cytotoxcity of this conjugate toward HEK293 T cells have been dramatically reduced.

While traditional drug discovery continues to be an important platform for the search of new antibiotics, alternative approaches should also be pursued to complement these efforts. We herein designed a class of molecules that decorate bacterial cell surfaces with the goal of re-engaging components of the immune system toward Escherichia coli and Pseudomonas aeruginosa. More specifically, conjugates were assembled using polymyxin B (an antibiotic that inherently attaches to the surface of Gram-negative pathogens) and antigenic epitopes that recruit antibodies found in human serum. We established that the spacer length played a significant role in hapten display within the bacterial cell surface, a result that was confirmed both experimentally and via molecular dynamics simulations. Most importantly, we demonstrated the specific killing of bacteria by our agent in the presence of human serum. By enlisting the immune system, these agents have the potential to pave the way for a potent antimicrobial modality.

Thus, although TAC inhibits all alloreactive T cells, SRL promotes the differentiation and expansion of donor-specific Tregs without secondary reprogramming to IFN-γFOXP3 and IL-17FOXP3 Treg subsets. These results, although performed in an artificial in vitro model, add clinically applicable information on how these agents affect T-cell subpopulations.

Open-cage fullerene derivatives with an imide moiety above the orifice have been prepared. Rotation of the N-Ar imide bond can tune the orifice to a size large enough to encapsulate H 2 O at r.t. and also to a size small enough to keep H 2 from escaping the cavity rapidly.

The forces that drive lipid raft formation are poorly understood. To date, most of the attention has focused on attractive interactions between cholesterol and high-melting lipids. Remarkably little attention has been paid to repulsive forces. Here, we show that repulsive interactions between an exchangeable mimic of cholesterol and an exchangeable mimic of a low-melting phospholipid in liquid-disordered bilayers can be much stronger than the attractive forces between this same sterol and an exchangeable mimic of a high-melting phospholipid in liquid-ordered bilayers. We conclude that polyunsaturated phospholipids have been largely overlooked as major players in lipid raft formation. This knowledge should stimulate considerable interest in controlling the levels of polyunsaturated phospholipids for the proper functioning of cell membranes.

The gas-phase unimolecular decay kinetics of an anionic, open-cage [60] fullerene derivative encapsulating one water molecule is studied by means of black-body IR radiation induced dissociation (BIRD) in the temperature programmable ion trap of a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. The primary reaction channel observed is escape of the water molecule from the fullerenoid bowl. The rate constants for this water loss as a function of temperature are evaluated using the Arrhenius equation to yield an activation energy of 104 ± 4 kJ mol(-1). A complementary ion mobility spectrometry study contrasting the water-encapsulated and the empty fullerene cages finds identical collision cross sections to within experimental error-supporting the structural assignment of this gas-phase anion as an endohedral (i.e. encapsulated) species. Both experiments were compared with quantum-chemical computations which well-describe the transition state for water desorption and the concomitant binding and activation energies.