Challenges of clinical translation from single-cell sequencing to measures in clinical biochemistry of haematology: Definition of immune cell identities.

Peripheral immune cells play important roles in the maintenance of systemic and microenvironmental hemostasis. Measurements of circulating blood cells by single-cell RNA sequencing (scRNA-seq) were proposed as one of the routine measures in clinical biochemistry of hematology. Out of translational challenges, defining precise identities of cell subsets and states is more difficult, due to the complexity of immune cell development, location, regulation, function, and metabolism.

Discovery in clinical and translational medicine.

With the rapid development of biotechnologies and deep improvement of knowledge, "Discovery" is the initial period and source of innovation of clinical and translational medicine. The international journal of Clinical and Translational Discovery serves to highlight unknown or unclear aspects of clinical and translational medicine-associated knowledge, technologies, mechanisms, and therapies (https://onlinelibrary.wiley.

Clinical significance of spatiotemporal transcriptional bursting and control.

The rapid development of technologies provides the potential to perform real-time visualization of transcriptional bursting patterns, superenhancer formation and sensitivity to perturbation, and interactions between enhancers, promoters, and regulators during the burst. The transcriptional bursting-induced fluctuation can modify cell capacities, cell-cell communications, cell responses to microenvironmental changes, and forms of cell death. A large number of clinical and translational studies describe the existence of heterogeneity among cells, tissues, and organs but mechanism-based understanding of how and why the heterogeneity exists and how it is formed.

Significance of clinical phenomes of patients with COVID-19 infection: A learning from 3795 patients in 80 reports.

A new coronavirus SARS-CoV-2 has caused outbreaks in multiple countries and the number of cases is rapidly increasing through human-to-human transmission. Clinical phenomes of patients with SARS-CoV-2 infection are critical in distinguishing it from other respiratory infections. The extent and characteristics of those phenomes varied depending on the severities of the infection, for example, beginning with fever or a mild cough, progressed with signs of pneumonia, and worsened with severe or even fatal respiratory difficulty in acute respiratory distress syndrome.

Acute lung injury in patients with COVID-19 infection.

During the 2020 Spring Festival in China, the outbreak of a novel coronavirus, named COVID-19 by WHO, brought on a worldwide panic. According to the clinical data of infected patients, radiologic evidence of lung edema is common and deserves clinical attention. Lung edema is a manifestation of acute lung injury (ALI) and may progress to hypoxemia and potentially acute respiratory distress syndrome (ARDS).

Off-target genome editing: A new discipline of gene science and a new class of medicine.

With an increasing growth of genome editing, off-target effects such as non-specific genetic modifications resulting from the designed process of genome editing become a new discipline of gene science and new class medicine. The degree of short-term and long-term side effects and toxicity or dynamics of the primary and secondary off-target genome editing varies with the application of different methodologies of gene editing and measuring, readouts of genetic modifications, or comparison reference. Measurements of dynamic off-target effects caused directly or indirectly by genome editing are critical in clinical application of gene editing.

A tour of 3D genome with a focus on CTCF.

The complex three-dimensional (3D) structure of the genome plays critical roles in the maintenance of genome stability, organization, and dynamics and in regulation of gene expression for understanding molecular mechanisms and diseases. Chromatin maintains biological functions and transcriptional activities through long distance interaction and interactions between loops and enhancers-promoters. We firstly overview the architecture and biology of chromatin and loops, topologically associated domains (TADs) and interactions, and compartments and functions.

Genome dimensions control biological and toxicological functions; myth or reality?

The multidimensional genome offers a new perspective to understand molecular mechanisms of genotoxicity and provide deeper knowledge of how genome organization and reorganization in dimensions can alter cell sensitivity, tolerance, resistance, or toxicity to drugs, whether drugs per se can influence the 3D architecture of the genome directly or indirectly through transcriptional factors, and how we can improve cell sensitivity to drugs through the reorganization of genome and regulation of gene expression. We address roles of 3D genome organization and reorganization in the pathogenesis and progression of disease by evaluating various methodologies of studying the 3D genome, and in the genome integrity and stability susceptible to chemicals as mechanisms of genotoxicity. We discuss the value of imaging, visualizing, and nuclear proximity ligation-based methods of 3D genome organization to measure spatial proximity and visualize spatial distances between genomic loci.

Lung Cancer Heterogeneity and New Strategies for Drug Therapy.

Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system.

Genome analyses identify the genetic modification of lung cancer subtypes.

Lung cancer is a highly intricate and heterogeneous disease with genomic diversity in each subtype. Global analyses of gene expression and sequencing provided us new understanding of the genetic variation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), including adenocarcinoma (ADC), and squamous cell carcinoma (SCC). The genetic variations of lung cancer subtypes in genomic studies were integrated and further analyzed using bioinformatics methods.

Roles of tumor heterogeneity in the development of drug resistance: A call for precision therapy.

The drug resistance limits the optimal efficacy of drugs during target therapies for lung cancer and requires the development of precision medicine to identify and develop new highly selective drugs and more precise tailoring of medicine to the target population. Lung cancer heterogeneity as a potential cause of drug resistance to targeted therapy may foster tumor evolution and adaptation and fade personalized-medicine strategies. The present review elucidates the influence of tumor heterogeneity on drug efficacy and resistance, and discusses potential strategies to combat heterogeneity for cancer treatment.

Tomorrow's genome medicine in lung cancer.

Tomorrow's genome medicine in lung cancer should focus more on the homogeneity and heterogeneity of lung cancer which play an important role in the development of drug resistance, genetic complexity, as well as confusion and difficulty of early diagnosis and therapy. Chromosome positioning and repositioning may contribute to the sensitivity of lung cancer cells to therapy, the heterogeneity associated with drug resistance, and the mechanism of lung carcinogenesis. The CCCTC-binding factor plays critical roles in genome topology and function, increased risk of carcinogenicity, and potential of lung cancer-specific mediations.

Genomic mechanisms of transformation from chronic obstructive pulmonary disease to lung cancer.

Genetic variations in COPD and lung cancer may be one of the molecular mechanisms responsible for COPD-lung cancer transformation. The present review highlights main genetic variations co-existed in COPD and lung cancer and integrates the varied genes into four molecular mechanisms, e.g.

Detection of single cell heterogeneity in cancer.

Single cell heterogeneity has already been highlighted in cancer classification, diagnosis, and treatment. Recent advanced technologies have gained more ability to reveal the heterogeneity on single cell level. In this review, we listed various detection targets applied in single cell study, including tumor tissue cells, circulating tumor cells (CTCs), disseminated tumor cells (DTCs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cancer stem cells (CSCs).

Role of epigenetics in lung cancer heterogeneity and clinical implication.

Lung cancer, as a highly heterogeneous disease, can be initiated and progressed through the interaction between permanent genetic mutations and dynamic epigenetic alterations. However, the mediating mechanisms of epigenetics in cancer heterogeneity remain unclear. The evolution of cancer, the existence of cancer stem cells (CSCs) and the phenomenon of epithelial-mesenchymal transition (EMT) have been reported to be involved in lung cancer heterogeneity.

Correlation between mucin biology and tumor heterogeneity in lung cancer.

Mucins (MUC) are a family consisting of large O-glycoproteins whose primary functions are to protect and lubricate cell epithelial surfaces and contribute to intra- and inter-cellular signal pathways, cell proliferation, growth and apotosis. With the development of new technologies, MUCs begin to be identified as an effective marker in evaluating the tumor heterogeneity in lung cancer. MUCs' diverse expressions in subtypes of lung cancer indicate the inter-tumor heterogeneity.

Systems heterogeneity: An integrative way to understand cancer heterogeneity.

The concept of systems heterogeneity was firstly coined and explained in the Special Issue, as a new alternative to understand the importance and complexity of heterogeneity in cancer. Systems heterogeneity can offer a full image of heterogeneity at multi-dimensional functions and multi-omics by integrating gene or protein expression, epigenetics, sequencing, phosphorylation, transcription, pathway, or interaction. The Special Issue starts with the roles of epigenetics in the initiation and development of cancer heterogeneity through the interaction between permanent genetic mutations and dynamic epigenetic alterations.

Potentials of single-cell biology in identification and validation of disease biomarkers.

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location.

Effects of anti-human T lymphocyte immune globulins in patients: new or old.

Multiple studies demonstrated that anti-human T lymphocyte immune globulins (ATG) can decrease the incidence of acute and chronic graft rejection in cell or organ transplants. However, further in-depth study indicates that different subgroups may benefit from either different regimes or alteration of them. Studies among renal transplant patients indicate that low immunological risk patients may not gain the same amount of benefit and thus tilt the risk versus benefit consideration.

Regulatory T cells and potential inmmunotherapeutic targets in lung cancer.

Lung cancer and metastasis are two of the most lethal diseases globally and seldom have effective therapies. Immunotherapy is considered as one of the powerful alternatives. Regulatory T cells (Tregs) can suppress the activation of the immune system, maintain immune tolerance to self-antigens, and contribute to immunosuppression of antitumor immunity, which is critical for tumor immune evasion in epithelial malignancies, including lung cancer.

Prediction of dynamical drug sensitivity and resistance by module network rewiring-analysis based on transcriptional profiling.

Revealing functional reorganization or module rewiring between modules at network levels during drug treatment is important to systematically understand therapies and drug responses. The present article proposed a novel model of module network rewiring to characterize functional reorganization of a complex biological system, and described a new framework named as module network rewiring-analysis (MNR) for systematically studying dynamical drug sensitivity and resistance during drug treatment. MNR was used to investigate functional reorganization or rewiring on the module network, rather than molecular network or individual molecules.

Single-cell transcriptome in the identification of disease biomarkers: opportunities and challenges.

Single cell transcriptome defined as the entire RNA or polyadenylated products of RNA polymerase II on a cell can describe the gene regulation networks responsible for physiological functions, behaviours, and phenotypes in response to signals and microenvironmental changes. Single cell transcriptome/sequencing has the special power to investigate small groups of differentiating cells, circulating tumour cells, or tissue stem cells. A large number of factors may influence the extent of single-cell heterogeneity within a system.

Effects of phosphoinositide 3-kinase on protease-induced acute and chronic lung inflammation, remodeling, and emphysema in rats.

Background: Phosphoinositide 3-kinase (PI3K) plays an important role in tissue inflammatory reactions and fibrotic processes. The objective of this study was to evaluate the potential mechanism and therapeutic effects of PI3K inhibitor on pancreatic elastase (PE)-induced acute and chronic lung inflammation, edema, and injury.

Methods: Rats were terminated at 7 or 28 days after an intratracheal challenge with PE and intranasal instillation with a PI3K inhibitor, SHBM1009.