Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes.

Characterizing the compositional and phenotypic characteristics of tumor-infiltrating B cells (TIBs) is important for advancing our understanding of their role in cancer development. Here, we establish a comprehensive resource of human B cells by integrating single-cell RNA sequencing data of B cells from 649 patients across 19 major cancer types. We demonstrate substantial heterogeneity in their total abundance and subtype composition and observe immunoglobulin G (IgG)-skewness of antibody-secreting cell isotypes. Moreover, we identify stress-response memory B cells and tumor-associated atypical B cells (TAABs), two tumor-enriched subpopulations with prognostic potential, shared in a pan-cancer manner. In particular, TAABs, characterized by a high clonal expansion level and proliferative capacity as well as by close interactions with activated CD4 T cells in tumors, are predictive of immunotherapy response. Our integrative resource depicts distinct clinically relevant TIB subsets, laying a foundation for further exploration of functional commonality and diversity of B cells in cancer.

Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients.

OBJECTIVE: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure. DESIGN: We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation. RESULTS: Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell-cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores. CONCLUSION: Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.

Single-cell meta-analysis of inflammatory bowel disease with scIBD.

Understanding the heterogeneous intestinal microenvironment is critical to uncover the pathogenesis of inflammatory bowel disease (IBD). Recent advances in single-cell RNA sequencing (scRNA-seq) have identified certain cell types and genes that could contribute to IBD; however, a comprehensively integrated analysis of these scRNA-seq datasets is not yet available. Here we introduce scIBD, a platform for single-cell meta-analysis of IBD with interactive and visualization features, which combines highly curated single-cell datasets in a uniform workflow, enabling identifying rare or less-characterized cell types in IBD and dissecting the commonalities, as well as the differences between ulcerative colitis and Crohn's disease. scIBD also incorporates multifunctional information-including regulon activity, GWAS-implicated risk genes and genes targeted by therapeutics-to infer clinically relevant cell-type specificity. Collectively, scIBD is a user-friendly web-based platform for the community to analyze the transcriptome features and gene regulatory networks associated with the pathogenesis and treatment of IBD at single-cell resolution.

Structure and activity alteration in adult highland residents' cerebrum: Voxel-based morphometry and amplitude of low-frequency fluctuation study.

Introduction: People living in highland areas may have factors that allow them to adapt to chronic hypoxia, but these physiological mechanisms remain unclear. This study aimed to investigate the brain mechanism in a cohort of adult residents of Tibet, a well-known plateau section in China, by observing differences in brain structure and function in non-plateau populations. Methods: The study included 27 Tibetan and 27 non-plateau region residents who were matched in age, sex, and education. All participants underwent high-resolution three-dimensional T1 weighted imaging (3D-T1WI) and resting-state functional magnetic resonance imaging (rs-fMRI) scans on a 1.5 Tesla MR. Gray matter volumes and regional spontaneous neuronal activity (SNA) were calculated and compared between the two groups. Results: When comparing gray matter in people living in high altitudes to those living in the flatlands, the results showed positive activation of gray matter in local brain regions (p < 0.05, false discovery rate (FDR) corrected), in the right postcentral [automated atomic labeling (aal)], left postcentral (aal), and right lingual (aal) regions. Comparing the people of high altitude vs. flat land in the brain function study (p < 0.05, FDR corrected), positive activation was found in the right superior motor area (aal) and left superior frontal (aal), and negative activation was found in the right precuneus (aal). Conclusion: In high-altitude individuals, larger regional gray matter volumes and higher SNA may represent a compensatory mechanism to adapt to chronic hypoxia.

A Bioinformatic Framework for Dissecting the Dynamics of T Cells from Single-Cell Transcriptome.

The quantitative tracking of the dynamics of T cells is challenging in human immunology. Although bulk sequencing of T cell receptor (TCR) α- and ß-chains has been widely used for determining the clonality of T cells, such methods are limited in unveiling the phenotypic differences of T cells with the same clonotypes. Here, we describe a bioinformatics framework, STARTRAC, that integrates the single-cell transcriptome and TCR sequences as lineage-specific markers to quantitatively assess the dynamics of T cells, including their clonal expansion, tissue migration, and developmental transition properties.

COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

[Cognition function and its influencing factors among people aged 55 and above in 4 provinces of China from 2018 to 2019].

OBJECTIVE: To analyze the current situation of cognition function of people aged 55 and above in 4 provinces of China, and to explore its influencing factors of demographic characteristics. METHODS: Using the baseline data of the "Community-based Cohort Study on Nervous System Diseases", middle-aged and older populations aged ≥55 years with completed data on demographic and economic factors and the cognitive function scale were selected as study subjects. A total of 5103 subjects were included in the study(male 2294, female 2809, 55-64 years old 1875, 65-74 years old 2197, 75-94 years old 1031). Multi-stage stratified cluster random sampling was adopted, and survey subjects were selected from a total of 32 communities in Hebei, Zhejiang, Shaanxi and Hunan provinces. The baseline data obtained from a face-to-face questionnaire survey was entered using electronic tablets on the spot. Montreal cognitive assessment(MoCA) and activities of daily living scale(ADL) were used to determine mild cognitive impairment(MCI) and its subtypes. Multiple linear regression and multiple Logistic regression model were used to analyze the influencing factors of cognitive function in populations. RESULTS: Among middle-aged and elderly Chinese populations, the score of overall cognitive function and its sub-domains were 21. 79±6. 17, 11. 20±4. 18(memory), 8. 81±3. 31(execution), 5. 33±1. 76(visual-spatial ability), 4. 53±1. 40(language), 13. 32±3. 98(attention) and 5. 54±0. 95(orientation). The prevalence of MCI and its subtypes were 35. 86%, 4. 57%(amnestic MCI single domain, aMCI-SD), 3. 64%(nonamnestic MCI single domain, naMCI-SD), 6. 68%(amnestic MCI multiple domains, aMCI-MD) and 3. 94%(nonamnestic MCI multiple domains, naMCI-MD). Subjects aged ≥55 years, living in rural areas, or with per capita monthly household income less than 1000 yuan had lower score of overall cognitive function and its sub-domains(P<0. 05), and also had lower prevalence of MCI and its subtypes. The OR of MCI, naMCI-SD, aMCI-MD and naMCI-MD was 2. 38(95% CI 1. 98-2. 86), 1. 54(95% CI 1. 01-2. 34), 2. 30(95% CI 1. 65-3. 20) and 3. 11(95% CI 2. 07-4. 69) respectively in subjects aged ≥75 years versus those aged 55-64 years, and of MCI, naMCI-SD and aMCI-MD was 3. 02(95%CI 2. 48-3. 66), 4. 30(95%CI 2. 69-6. 88) and 2. 62(95%CI 1. 81-3. 79) respectively in those living in rural areas versus those living in city areas. Subjects with higher per capita monthly household income had lower ORs of MCI and its subtypes. CONCLUSION: The prevalence rate of MCI among people aged 55 and above in four provinces in China is at a relatively high level. In the studied 4 provinces of China, about 35% of Chinese middle-aged and elderly populations are affected by MCI. The status of overall cognitive function and its sub-domains of subjects aged 75 years and above, living rural areas and with lower per capita monthly household income are poor, and they may have a higher risk of MCI and its subtypes.

Landscape of transcript isoforms in single T cells infiltrating in non-small-cell lung cancer.

Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T-cell differentiation and activation, here, we proposed a computational method named IDEA (Isoform Detection, Enrichment, and functional Annotation) to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq data set of 12,346 T cells from non-small-cell lung cancer (NSCLC). We found that most genes tend to dominantly express one isoform in single T cells, enabling typing T cells based on the isotypes, given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/noncoding switches, transcription start site changes, gains/losses of domains, and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T-cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new light on the regulatory mechanisms of tumor-infiltrating T cells.

[Dandelion clock-like sign on CT for diagnose of COVID-19].

OBJECTIVE: To explore the value of the "dandelion clock-like" sign on chest CT for diagnosis of SARS-CoV-2-associated pneumonia. METHODS: This retrospective analysis was conducted based on the data of 119 cases from the Department of Fever and the Department of Infection undergoing chest high-resolution CT examinations in Sanshui District People's Hospital between January, 24 and February 10, 2020. The cases with no abnormality on chest CT were excluded. Twenty-three patients were diagnosed to have pneumonia, including 9 with SARS-CoV-2-associated pneumonia and 14 with other types of pneumonia. We comparatively analyzed the CT signs, location of the lesions and the dandelion clock-like sign among different types of pneumonia. RESULTS: Among the 23 patients with pneumonia, 9 (39.1%) had common or severe SARS-CoV-2- associated pneumonia with a positive epidemiological history and corresponding respiratory symptoms. Seven of the SARSCoV-2-associated pneumonia patients had multiple lesions in bilateral lungs, compromising mainly the lung field and the subpleural area and showing patchy, lumpy, and umbrella-shaped ground glass opacity, often accompanied by pulmonary vascular thickening and increased microvessels, interlobular septal thickening and fibrosis and lined with grid-like and small-bubble-like "crazy-paving" patterns. The dandelion clock-like sign was found in all the 9 patients with SARSCoV-2-associated pneumonia, with a total of 46 lesions (60.5%, 76 total lesions); 9 of the lesions presented with a "dandelion clek-like" sign and 37 with a "dandelion seed sign". These signs were not found in the 14 patients with other types of pneumonia. CONCLUSIONS: The dandelion clock-like sign is a common and characteristic chest CT finding in patients with SARS-CoV-2-associated pneumonia, and can help to distinguish SARS-CoV-2-associated pneumonia from other types of pneumonia.

Visible-light-mediated deuteration of silanes with deuterium oxide.

Isotopically labeled compounds are highly desirable as they can serve as both mechanistic probes in chemistry and diagnostic tools in medicinal research. Herein, we report an unprecedented visible-light-mediated metal-free deuteration of silanes using D2O as an inexpensive, readily available, and easy to handle deuterium source. A broad range of aryl- and alkyl-substituted silanes were deuterated with high deuterium incorporations and yields. Furthermore, a 100 gram-scale synthesis was demonstrated using continuous-flow micro-tubing reactors, where enhanced reaction efficiency was obtained. The photoredox-catalyzed polarity matched hydrogen atom transfer (HAT) between silanes and the thiol HAT catalyst was responsible for the efficient deuteration.

Tetraphenylethene (TPE) modified polyhedral oligomeric silsesquioxanes (POSS): unadulterated monomer emission, aggregation-induced emission and nanostructural self-assembly modulated by the flexible spacer between POSS and TPE.

Mono-TPE modified POSS molecules, in which the flexible spacers between TPE and POSS moieties control their self-assembly and aggregation, exhibit a unique unadulterated monomer emission in organic solvents as well as an AIE emission in THF/water.