Multiomics biomarkers were not superior to clinical variables for pan-cancer screening.

Background: Cancer screening tests are considered pivotal for early diagnosis and survival. However, the efficacy of these tests for improving survival has recently been questioned. This study aims to test if cancer screening could be improved by biomarkers in peripheral blood based on multi-omics data.

An interactive atlas of genomic, proteomic, and metabolomic biomarkers promotes the potential of proteins to predict complex diseases.

Multiomics analyses have identified multiple potential biomarkers of the incidence and prevalence of complex diseases. However, it is not known which type of biomarker is optimal for clinical purposes. Here, we make a systematic comparison of 90 million genetic variants, 1453 proteins, and 325 metabolites from 500,000 individuals with complex diseases from the UK Biobank.

Transcript and protein signatures derived from shared molecular interactions across cancers are associated with mortality.

Background: Characterization of shared cancer mechanisms have been proposed to improve therapy strategies and prognosis. Here, we aimed to identify shared cell-cell interactions (CCIs) within the tumor microenvironment across multiple solid cancers and assess their association with cancer mortality.

Methods: CCIs of each cancer were identified by NicheNet analysis of single-cell RNA sequencing data from breast, colon, liver, lung, and ovarian cancers.

DNA G-Quadruplex in NRP1 Promoter Facilitates SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to raise concerns worldwide. Numerous host factors involved in SARS-CoV-2 infection have been identified, but the regulatory mechanisms of these host factor remain unclear. Here, we report the role of G-quadruplexes (G4s) located in the host factor promoter region in SARS-CoV-2 infection.

scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases.

Background: Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs.

Methods: Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data.

An interactive atlas of genomic, proteomic, and metabolomic biomarkers promotes the potential of proteins to predict complex diseases.

Multiomics analyses have identified multiple potential biomarkers of the incidence and prevalence of complex diseases. However, it is not known which type of biomarker is optimal for clinical purposes. Here, we make a systematic comparison of 90 million genetic variants, 1,453 proteins, and 325 metabolites from 500,000 individuals with complex diseases from the UK Biobank.

Targeting LEF1-mediated epithelial-mesenchymal transition reverses lenvatinib resistance in hepatocellular carcinoma.

Acquired resistance is a significant hindrance to clinical application of lenvatinib in unresectable hepatocellular carcinoma (HCC). Further in-depth investigation of resistance mechanisms can help to develop additional therapeutic strategies to overcome or delay resistance. In our study, two lenvatinib-resistant (LR) HCC cell lines were established by treatment with gradient increasing concentration of lenvatinib, named Hep3B-LR and HepG2-LR.

Co-overexpression of BRD4 and CDK7 promotes cell proliferation and predicts poor prognosis in HCC.

Aberrant expression of critical components of the -acting super-enhancers (SE) complex contributes to the continuous and robust transcription of oncogenes in human cancers. Small-molecule inhibitors targeting core-transcriptional components such as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7) have been developed and are currently undergoing preclinical and clinical testing in several malignant cancers. By analysis of TCGA data and clinical specimens, we demonstrated that BRD4 and CDK7 were frequently overexpressed in human HCCs and were associated with the poor prognosis.

Construction of Mn doped CuS nanozymes for synergistic tumor therapy in NIR-I/II bio-windows.

In photothermal therapy (PTT) and chemodynamic therapy (CDT) of cancer, poor performance of nanoagents severely impaired the therapeutic effect of cancer. To solve the problem, we proposed and constructed a novel Mn doped CuS phothermal nanoagent both in the first near-infrared (NIR-I) and the second near- infrared (NIR-II) windows in this work, which exhibited high photothermal conversion efficiency of 40.3% at 808 nm (NIR-I window) and 33.

scDrugPrio: A framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases.

Background: Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs.

Methods: Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data.

Multi-organ single-cell analysis reveals an on/off switch system with potential for personalized treatment of immunological diseases.

Prioritization of disease mechanisms, biomarkers, and drug targets in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions between thousands of genes. Our multi-organ single-cell RNA sequencing of a mouse IMID model, namely collagen-induced arthritis, shows highly complex and heterogeneous expression changes in all analyzed organs, even though only joints showed signs of inflammation. We organized those into a multi-organ multicellular disease model, which shows predicted molecular interactions within and between organs.

A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets.

Background: Medical digital twins are computational disease models for drug discovery and treatment. Unresolved problems include how to organize and prioritize between disease-associated changes in digital twins, on cellulome- and genome-wide scales. We present a dynamic framework that can be used to model such changes and thereby prioritize upstream regulators (URs) for biomarker- and drug discovery.

Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation.

Parkinson's disease is a neurodegenerative disorder in which activated microglia may appear prior to motor symptoms, but the specific therapeutic mechanisms remain unclear. This study investigated the potential effects of Edaravone (EDA) on M1/M2 polarization of microglia in rats with dopaminergic neurons damage induced by lipopolysaccharide (LPS) and its mechanism. Rats were randomly grouped as the following ( = 10): Control, EDA alone (10 mg/kg), LPS-model (LPS 5 μg), LPS + EDA (5 mg/kg) and LPS + EDA (10 mg/kg).

TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p.

Hepatocellular carcinoma (HCC) is among the most common malignancies and has an unfavorable prognosis. The hepatitis B virus-encoded X (HBx) protein is closely associated with hepatocarcinogenesis. Sorafenib is a unique targeted oral kinase inhibitor for advanced HCC.

Computational fluid dynamics simulation of time-resolved blood flow in Budd-Chiari syndrome with inferior vena cava stenosis and its implication for postoperative efficacy assessment.

Background: This study aimed to adopt computational fluid dynamics to simulate the blood flow dynamics in inferior vena cava stenosis based on time-dependent patient-specific models of Budd-Chiari syndrome as well as a normal model. It could offer valuable references for a retrospective insight into the underlying mechanisms of Budd-Chiari syndrome pathogenesis as well as more accurate evaluation of postoperative efficacy.

Methods: Three-dimensional inferior vena cava models of Budd-Chiari syndrome patient-specific (preoperative and postoperative) and normal morphology model were reconstructed as per magnetic resonance images using Simpleware.

Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis.

Background: Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells.

Digital twins to personalize medicine.

Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.

Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pathways in peripheral blood and arthritic joints complicates biomarker discovery.

Background: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint.

Inhibition of CXCL1-CXCR2 axis ameliorates cisplatin-induced acute kidney injury by mediating inflammatory response.

One of the limiting side effects of cisplatin use in cancer chemotherapy is nephrotoxicity. Inflammation is now believed to play a major role in the pathogenesis of cisplatin-induced acute kidney injury (AKI), and the mediators of inflammation contribute to it. CXCL1 was recently reported to be involved in renal physiology and pathology in ischemia mouse model; however, its roles and mechanisms in cisplatin-induced AKI are completely unknown.

An algorithm-based meta-analysis of genome- and proteome-wide data identifies a combination of potential plasma biomarkers for colorectal cancer.

Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. Painstaking research has led to the identification of a large number of different types of biomarkers, few of which are in general clinical use. Here, we searched for highly accurate combinations of biomarkers by meta-analyses of genome- and proteome-wide data from CRC tumors.

A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases.

Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets.

Generation of Cas9 transgenic zebrafish and their application in establishing an ERV-deficient animal model.

Objectives: To investigate the effect of endogenous Cas9 on genome editing efficiency in transgenic zebrafish.

Results: Here we have constructed a transgenic zebrafish strain that can be screened by pigment deficiency. Compared with the traditional CRISPR injection method, the transgenic zebrafish can improve the efficiency of genome editing significantly.

Injection of an SV40 transcriptional terminator causes embryonic lethality: a possible zebrafish model for screening nonhomologous end-joining inhibitors.

Introduction: DNA repair by the nonhomologous end joining (NHEJ) pathway promotes tumor recurrence after chemotherapy and radiotherapy. Discovery of rapid and high-throughput techniques to screen for an effective NHEJ inhibitor drug is imperative for the suppression of NHEJ during tumor treatment. However, traditional screening methods are too cumbersome to meet the current need.