Clinical and translational values of spatial transcriptomics.

The combination of spatial transcriptomics (ST) and single cell RNA sequencing (scRNA-seq) acts as a pivotal component to bridge the pathological phenomes of human tissues with molecular alterations, defining in situ intercellular molecular communications and knowledge on spatiotemporal molecular medicine. The present article overviews the development of ST and aims to evaluate clinical and translational values for understanding molecular pathogenesis and uncovering disease-specific biomarkers. We compare the advantages and disadvantages of sequencing- and imaging-based technologies and highlight opportunities and challenges of ST.

Clinical challenges of tissue preparation for spatial transcriptome.

Spatial transcriptomics is considered as an important part of spatiotemporal molecular images to bridge molecular information with clinical images. Of those potentials and opportunities, the excellent quality of human sample preparation and handling will ensure the precise and reliable information generated from clinical spatial transcriptome. The present study aims at defining potential factors that might influence the quality of spatial transcriptomics in lung cancer, para-cancer, or normal tissues, pathological images of sections and the RNA integrity before spatial transcriptome sequencing.

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery.

Background: The number of patients receiving anaesthesia is increasing, but the impact of general anaesthesia on the patient's immune system remains unclear. The aim of the present study is to investigate dynamics of systemic immune cell responses to anaesthesia during perioperative period at a single-cell solution.

Methods: The peripheral blood mononuclear cells (PBMCs) and clinical phenomes were harvested and recorded 1 day before anaesthesia and operation, just after anaesthesia (0 h), and 24 and 48 h after anaesthesia.

Spatial omics: Navigating to the golden era of cancer research.

The idea that tumour microenvironment (TME) is organised in a spatial manner will not surprise many cancer biologists; however, systematically capturing spatial architecture of TME is still not possible until recent decade. The past five years have witnessed a boom in the research of high-throughput spatial techniques and algorithms to delineate TME at an unprecedented level. Here, we review the technological progress of spatial omics and how advanced computation methods boost multi-modal spatial data analysis.

Roles of pulmonary telocytes in airway epithelia to benefit experimental acute lung injury through production of telocyte-driven mediators and exosomes.

Background: Telocytes (TCs) are experimentally evidenced as an alternative of cell therapies for organ tissue injury and repair. The aims of the present studies are to explore direct roles of TCs and the roles of TC-derived exosomes in support of experimental acute lung injury (ALI) in vivo or in vitro.

Materials And Methods: The roles of TCs in experimental ALI were firstly estimated.

Elevated circulating high-sensitivity cardiac troponin t and cardiac remodeling in obesity.

Background: It is well established that body mass index (BMI) and troponins are independently associated. However, whether the obesity could cause myocardial injury independent of coronary heart disease (CHD) remains unclear. This study focuses on the relationship between BMI and troponins, and whether this relationship is being attenuated when CHD is accounted for.

Can single cell RNA sequencing reshape the clinical biochemistry of hematology: New clusters of circulating blood cells.

scRNA-seq is on track for use as a routine measurement of clinical biochemistry and to assist in clinical decision-making and guide the performance of molecular medicine, but there are still a large number of challenges to be overcome. In conclusion, scRNA-seq-based clusters and differentiation of circulating blood cells have been examined and informative in patients with various diseases, although the information generated from scRNA-seq varies between different conditions, technologies, and diseases. Most of the clinical studies published have focused on the landscape of circulating immune cells, disease-specific patterns of new clusters, understanding of potential mechanisms, and potential correlation between cell clusters, differentiations, cell interactions, and circulating and migrated cells.

New focuses on roles of communications between endoplasmic reticulum and mitochondria in identification of biomarkers and targets.

The communication between endoplasmic reticulum (ER) and mitochondria (Mt) plays important roles in maintenance of intra- and extra-cellular microenvironment, metabolisms, signaling activities and cell-cell communication. The present review aims to overview the advanced understanding about roles of ER-Mt structural contacts, molecular interactions and chemical exchanges, signal transmissions and inter-organelle regulations in ER-Mt communication. We address how the ER-Mt communication contributes to the regulation of lipid, amino acid and glucose metabolisms by enzymes, transporters and regulators in the process of biosynthesis.

A cellular census of human peripheral immune cells identifies novel cell states in lung diseases.

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study.

Potential biomarkers and targets of mitochondrial dynamics.

Mitochondrial dysfunction contributes to the imbalance of cellular homeostasis and the development of diseases, which is regulated by mitochondria-associated factors. The present review aims to explore the process of the mitochondrial quality control system as a new source of the potential diagnostic biomarkers and/or therapeutic targets for diseases, including mitophagy, mitochondrial dynamics, interactions between mitochondria and other organelles (lipid droplets, endoplasmic reticulum, endosomes, and lysosomes), as well as the regulation and posttranscriptional modifications of mitochondrial DNA/RNA (mtDNA/mtRNA). The direct and indirect influencing factors were especially illustrated in understanding the interactions among regulators of mitochondrial dynamics.

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.

Regulatory roles of osteopontin in human lung cancer cell epithelial-to-mesenchymal transitions and responses.

Background: Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial-to-mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the regulatory mechanism of internal and external OPN in the development of lung cancer.

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation.

Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer.

Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment-naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B-cell antigen presentation, distinct regulatory T-cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC.

Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples.

Genomic studies of cancer cell alterations, such as mutations, copy number variations (CNVs), and translocations, greatly promote our understanding of the genesis and development of cancers. However, the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties. To explore the 3D genome structure in clinical lung cancer, we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer, combining with RNA sequenceing analysis.

How to breakthrough mitochondrial DNA methylation-associated networks.

Mitochondrial DNA (mtDNA) plays an important role in regulating mitochondrial homeostasis, transcription, cell metabolism, and drug sensitivity. Patterns and regulations of mtDNA methylation vary among cell types, species, functions, and diseases. High-resolution mtDNA methylation maps of human and animal mitochondrial genomes addressed that the light (L)-strand non-CpG methylation of mtDNA varied among species, developing stages, and ages.

Obesity-induced excess of 17-hydroxyprogesterone promotes hyperglycemia through activation of glucocorticoid receptor.

Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR.

Molecular mechanisms, off-target activities, and clinical potentials of genome editing systems.

Methodologies of genome editing are rapidly developing with the improvement of gene science and technology, mechanism-based understanding, and urgent needs. In addition to the specificity and efficiency of on-target sites, one of the most important issues is to find and avoid off-targets before clinical application of gene editing as a therapy. Various algorithms, modified nucleases, and delivery vectors are developed to localize and minimize off-target sites.

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).