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1.
Gut ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361683

RESUMO

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.

3.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

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.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
4.
Wei Sheng Yan Jiu ; 50(1): 21-36, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33517957

RESUMO

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.


Assuntos
Atividades Cotidianas , Cognição , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
5.
J Genet Genomics ; 47(7): 373-388, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32998846

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Isoformas de Proteínas/genética , Análise de Célula Única , Linfócitos T/metabolismo , Processamento Alternativo/genética , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Éxons/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Isoformas de Proteínas/imunologia , Análise de Sequência de RNA , Linfócitos T/imunologia , Linfócitos T/patologia
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 159-163, 2020 Feb 29.
Artigo em Chinês | MEDLINE | ID: mdl-32376543

RESUMO

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.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Betacoronavirus , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2
7.
Chem Sci ; 10(31): 7340-7344, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31588300

RESUMO

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.

8.
Chem Commun (Camb) ; 52(84): 12478-12481, 2016 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-27711362

RESUMO

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.

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