A novel prognostic scoring model based on copper homeostasis and cuproptosis which indicates changes in tumor microenvironment and affects treatment response

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A model based on adipose and muscle-related indicators evaluated by CT images for predicting microvascular invasion in HCC patients

Abstract Background and aim The presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC. Methods One hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to data dimensionality reduction and screening. Nomogram was constructed based on the independent variables, and evaluated by external validation, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results Histopathologically identified MVI was found in 101 of 211 patients (47.9%). The preoperative imaging and clinical variables associated with MVI were visceral adipose tissue (VAT) density, intramuscular adipose tissue index (IMATI), skeletal muscle (SM) area, age, tumor size and cirrhosis. Incorporating these 6 factors, the nomogram achieved good concordance index of 0.79 (95%CI: 0.72–0.86) and 0.75 (95%CI: 0.62–0.89) in training and validation cohorts, respectively. In addition, calibration curve exhibited good consistency between predicted and actual MVI probabilities. ROC curve and DCA of the nomogram showed superior performance than that of models only depended on clinical or imaging variables. Based on the nomogram score, patients were divided into high (> 273.8) and low (< = 273.8) risk of MVI presence groups. For patients with high MVI risk, wide-margin resection or anatomical resection could significantly improve the 2-year recurrence free survival. Conclusion By combining 6 preoperative independently predictive factors of MVI, a nomogram was constructed. This model provides an optimal preoperative estimation of MVI risk in HCC patients, and may help to stratify high-risk individuals and optimize clinical decision making

A Positive Climatic Trend in the Global Offshore Wind Power

The climatic variation of offshore wind energy has a close relationship with the long-term plan of energy utilization. However, the work on this aspect is scarce and mainly focuses on the variation of wind power density (WPD). There is little research on the climatic trends of effective wind speed occurrence (EWSO) and occurrence of energy level greater than 200 W/m(2) (rich level occurrence, RLO), which are directly related to the available rate and richness of wind energy. Based on the ERA-Interim wind product from the ECMWF, this study calculated the climatic trends of series of key factors of wind energy in the global oceans, including the WPD, EWSO, and RLO. The results show that the wind energy exhibits a positive trend globally for the past 36 years, with overall annual increasing trends in WPD, EWSO, and RLO, of 0.698 (W/m(2))/yr, 0.076%/yr, and 0.090%/yr separately. The annual trend exhibits evident regional differences. The areas with significant increasing trends are mainly distributed in the mid- low-latitude waters of global oceans and part of the southern hemisphere westerlies. The annual increasing trend of WPD is strongest in the southern westerlies, especially in the extratropical South Pacific (ETSP), of about 1.64 (W/m(2))/yr. The annual increasing trends of EWSO and RLO are strongest in the tropical waters, especially the tropical Pacific Ocean (TPO), of 0.17%/yr and 0.19%/yr separately. The annual and seasonal WPD, EWSO, and RLO in most global oceans have significant increasing trends or no significant variation, meaning that the wind energy trends are rich or stable, which is beneficial for energy development. The climatic trends of wind energy are dominated by different time periods. There is no evident abrupt change of wind energy in the extratropical waters globally and tropical Atlantic Ocean (TAO). The abrupt periods of wind energy in the TIO and TPO occurred in the end of the 20th century and the beginning of the 21st century. The wind energy of the South China Sea, Arabian Sea, and the Bay of Bengal and nino3 index share a common period of approximately 5 years. The offshore wind energy was controlled by an oscillating phenomenon