Recent research has indicated that cuprotosis, or copper induced cell death, is a novel type of cell death that could be utilized as a new weapon for cancer management. However, the characteristics ...and implications of such signatures in cancers, especially in clear cell renal cell cancer (ccRCC), remain elusive.
Expression, methylation, mutation, clinical information, copy number variation, functional implication, and drug sensitivity data at the pan-cancer level were collected from The Cancer Genome Atlas. An unsupervised clustering algorithm was applied to decipher ccRCC heterogeneity. Immune microenvironment construction, immune therapy response, metabolic pattern, and cancer progression signature between subgroups were also investigated.
Cuprotosis related genes were specifically downregulated in various cancer tissues compared with normal tissues and were correlated with hypermethylation and copy number variation. Cuprotosis scores were also dysregulated in tumor tissues, and we found that such a signature could positively regulate oxidative phosphorylation and Myc and negatively regulate epithelial mesenchymal translation and myogenesis pathways. CPCS1 (cuprotosis scores high) and CPCS2 (cuprotosis scores low) in ccRCC displayed distinctive clinical profiles and biological characteristics; the CPCS2 subtype had a higher clinical stage and a worse prognosis and might positively regulate cornification and epidermal cell differentiation to fuel cancer progression. CPCS2 also displayed a higher tumor mutation burden and low tumor stemness index, while it led to a low ICI therapy response and dysfunctional tumor immunity state. The genome-copy numbers of CPCS2, including arm- gain and arm- loss, were higher than those of CPCS1. The prognostic model constructed based on subgroup biomarkers exerted satisfactory performance in both the training and validation cohorts. In addition, overexpression of the copper death activator DLAT suppressed the malignant ability, including cell migration and proliferation, of renal cell lines in vitro and in vivo. Finally, activation of cuprotosis in tumors could enhance antitumor immunity through dsDNA-cGAS-STING signaling in ccRCC.
The activation of cuprotosis might function as a promising approach among multiple cancers. The cuprotosis related signatures could reshape tumor immunity in the ccRCC microenvironment via cGAS-STING signal, thus activating tumor antigen-presenting process. Upregulation of DLAT expression in ccRCC cell lines could reactivate the copper death pattern and be treated as a suitable target for ccRCC.
Pyroptosis is essential for tumorigenesis and progression of neoplasm. However, the heterogeneity of pyroptosis and its relationship with the tumor microenvironment (TME) in clear cell renal cell ...carcinoma (ccRCC) remain unclear. The purpose of the present study was to identify pyroptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.
First, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model established by LASSO regression was verified by the ICGC database. Then, the clinical significance, functional status, immune infiltration, cell-cell communication, genomic alteration, and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.
Two heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in the C2 subgroup was lower than that in the C1 subgroup. Pyroptosis-related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters
the pyroptosis-related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while the characteristics of C2 were alterations in SPEN and ROS1 mutation. Finally, a robust and promising pyroptosis-related prediction model for ccRCC was constructed and validated.
Two heterogeneous pyroptosis subtypes were identified and compared in multiple omics levels, and five pyroptosis-related signatures were applied to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.
•Aggregation occurs to protein after phosphorylation with particle size increases.•The addition of STP and TSPP decreased the gelling characteristics of egg white.•The secondary structure of gel ...changed regularly after STP and TSPP were added.•Phosphorylated egg white gel shows larger pores and reticulated microstructures.•The addition of STP/TSPP reduced salt and solvent sensitivity of egg white gel.
In this study, sodium tripolyphosphate (STP) and tetrasodium pyrophosphate (TSPP) were utilized to modify duck egg white protein (EWP). The phosphorylated EWP was prepared as egg white gel (EWG) by adding sodium hydroxide. The phosphorus content of EWP reached 2.18 mg/g and 2.07 mg/g with the addition of STP and TSPP, respectively, after 2 h phosphorylation. The average particle size, absolute zeta potential value, and surface hydrophobicity of EWP increased significantly during phosphorylation. FTIR results indicate that phosphorylation reduced the random structure and α-helical content while increasing the content of β-sheets and β-turn. The mechanical and rheological properties of EWG decreased obviously after phosphorylation. A three-dimensional porous network microstructure was formed, and the gel with added TSPP had larger pores. Adding STP and TSPP to EWG weakened its salt and solvent sensitivity. The findings provide a direction for the exploration of gel properties after protein modification.
Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA-
) data. However, it cannot ...detect the exact cellular and molecular changes in tumor cells. This study aimed to construct a prognostic model for LUAD using single-cell RNA-
(scRNA-
) and traditional RNA-
data.
Bulk RNA-
data were downloaded from The Cancer Genome Atlas (TCGA) database. LUAD scRNA-
data were acquired from Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Weighted Gene Correlation Network Analysis (WGCNA) was utilized to identify key modules and differentially expressed genes (DEGs). The non-negative Matrix Factorization (NMF) algorithm was used to identify different subtypes based on DEGs. The Cox regression analysis was used to develop the prognostic model. The characteristics of mutation landscape, immune status, and immune checkpoint inhibitors (ICIs) related genes between different risk groups were also investigated.
scRNA-
data of four samples were integrated to identify 13 clusters and 9cell types. After applying differential analysis, NK cells, bladder epithelial cells, and bronchial epithelial cells were identified as significant cell types. Overall, 329 DEGs were selected for prognostic model construction through differential analysis and WGCNA. Besides, NMF identified two clusters based on DEGs in the TCGA cohort, with distinct prognosis and immune characteristics being observed. We developed a prognostic model based on the expression levels of six DEGs. A higher risk score was significantly correlated with poor survival outcomes but was associated with a more frequent
mutation rate, higher tumor mutation burden (TMB), and up-regulation of
. Two independent external validation cohorts were also adopted to verify our results, with consistent results observed in them.
This study constructed and validated a prognostic model for LUAD by integrating 10× scRNA-
and bulk RNA-
data. Besides, we observed two distinct subtypes in this population, with different prognosis and immune characteristics.
In this paper, two novel algorithms are developed to design sparse linear-phase (LP) FIR filters. Compared to traditional design methods, they can jointly optimize coefficient sparsity and order of ...an LP FIR filter, so as to achieve a balance between filtering performance and implementation efficiency. The design problem under consideration is formally cast as a regularized l 0 -norm minimization problem, which is then tackled by two different design algorithms. In the first proposed algorithm, the objective function of the original design problem is replaced by its upper bound, which leads to a weighted l 0 -norm minimization problem, while in the second one a group of auxiliary variables are introduced such that the original design problem can be equivalently transformed to another weighted l 0 -norm minimization problem. The iterative-reweighted-least-squares (IRLS) algorithm is employed with appropriate modifications to solve both weighted l 0 -norm minimization problems. Simulation results show that, compared to traditional approaches, the proposed algorithms can achieve comparable or better design results in terms of both sparsity and effective filter order.
Carbapenem-resistant
strains are a major clinical problem because of the lack of effective alternative antibiotics. However, viruses that lyze bacteria, called bacteriophages, have potential ...therapeutic applications in the control of antibiotic-resistant bacteria. In the present study, a lytic bacteriophage specific for
isolates, designated vB_EaeM_φEap-3, was characterized. Based on transmission electron microscopy analysis, phage vB_EaeM_φEap-3 was classified as a member of the family
(order,
). Host range determination revealed that vB_EaeM_φEap-3 lyzed 18 of the 28
strains tested, while a one-step growth curve showed a short latent period and a moderate burst size. The stability of vB_EaeM_φEap-3 at various temperatures and pH levels was also examined. Genomic sequencing and bioinformatics analysis revealed that vB_EaeM_φEap-3 has a 175,814-bp double-stranded DNA genome that does not contain any genes considered undesirable for the development of therapeutics (e.g., antibiotic resistance genes, toxin-encoding genes, integrase). The phage genome contained 278 putative protein-coding genes and one tRNA gene, tRNA-Met (AUG). Phylogenetic analysis based on large terminase subunit and major capsid protein sequences suggested that vB_EaeM_φEap-3 belongs to novel genus "Kp15 virus" within the T4-like virus subfamily. Based on host range, genomic, and physiological parameters, we propose that phage vB_EaeM_φEap-3 is a suitable candidate for phage therapy applications.
Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to ...fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients.
This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.
A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3-4 (odds ratio OR = 6.08, 95% confidence interval CI: 2.04-18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11-6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21-5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22-4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03-6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve AUC: 0.759), calibration ability, and net clinical benefit.
Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PBRM1 is a tumor suppressor frequently mutated in clear cell renal cell carcinoma. However, no effective targeted therapies exist for ccRCC with PBRM1 loss. To identify novel therapeutic approaches ...to targeting PBRM1-deficient renal cancers, we employed a synthetic lethality compound screening in isogenic PBRM1+/+ and PBRM1-/- 786-O renal tumor cells and found that a DNMT inhibitor 5-Fluoro-2’-deoxycytidine (Fdcyd) selectively inhibit PBRM1-deficient tumor growth. RCC cells lacking PBRM1 show enhanced DNA damage response, which leads to sensitivity to DNA toxic drugs. Fdcyd treatment not only induces DNA damage, but also re-activated a pro-apoptotic factor XAF1 and further promotes the genotoxic stress-induced PBRM1-deficient cell death. This study shows a novel synthetic lethality interaction between PBRM1 loss and Fdcyd treatment and indicates that DNMT inhibitor represents a novel strategy for treating ccRCC with PBRM1 loss-of-function mutations.
Cancer cells reprogram their metabolism to meet their growing demand for bioenergy and biosynthesis. The metabolic profile of cancer cells usually includes dysregulation of main nutritional metabolic ...pathways and the production of metabolites, which leads to a tumor microenvironment (TME) having the characteristics of acidity, hypoxic, and/or nutrient depletion. Therapies targeting metabolism have become an active and revolutionary research topic for anti-cancer drug development. The differential metabolic vulnerabilities between tumor cells and other cells within TME provide nanotechnology a therapeutic window of anti-cancer. In this review, we present the metabolic characteristics of intrinsic cancer cells and TME and summarize representative strategies of nanoparticles in metabolism-regulating anti-cancer therapy. Then, we put forward the challenges and opportunities of using nanoparticles in this emerging field.
Pentachlorophenol (PCP) is a ubiquitous emerging persistent organic pollutant detected in the environment and foodstuffs. Despite the dietary intake of PCP being performed using surveillance data, ...the assessment does not consider the bioaccessibility and bioavailability of PCP. Pork, beef, pork liver, chicken and freshwater fish
-fortified by three levels of PCP were processed by RIVM and the Caco-2 cell model after steaming, boiling and pan-frying, and PCP in foods and digestive juices were detected using isotope dilution-UPLC-MS/MS. The culinary treatment and food matrix were significantly influenced (
< 0.05) in terms of the bioaccessibility and bioavailability of PCP. Pan-frying was a significant factor (
< 0.05) influencing the digestion and absorption of PCP in foods, with the following bioaccessibility: pork (81.37-90.36%), beef (72.09-83.63%), pork liver (69.11-78.07%), chicken (63.43-75.52%) and freshwater fish (60.27-72.14%). The bioavailability was as follows: pork (49.39-63.41%), beef (40.32-53.43%), pork liver (33.63-47.11%), chicken (30.63-40.83%) and freshwater fish (17.14-27.09%). Pork and beef with higher fat content were a key factor in facilitating the notable PCP bioaccessibility and bioavailability (
< 0.05). Further, the exposure of PCP to the population was significantly reduced by 42.70-98.46% after the consideration of bioaccessibility and bioavailability, with no potential health risk. It can improve the accuracy of risk assessment for PCP.
PDF
