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Article ; Online: Controversial treatments: An updated understanding of the coronavirus disease 2019.

Zhang, Cantong / Huang, Shaoying / Zheng, Fengping / Dai, Yong

2020 Volume 92, Issue 9, Page(s) 1441–1448

Abstract: An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the ... ...

Abstract	An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/therapy ; Chloroquine ; Extracorporeal Membrane Oxygenation ; Glucocorticoids/therapeutic use ; Humans ; Liver, Artificial ; Ribavirin
Chemical Substances	Antiviral Agents ; Glucocorticoids ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Ribavirin (49717AWG6K) ; Chloroquine (886U3H6UFF) ; Alanine (OF5P57N2ZX)
Keywords	covid19
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25788
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Article ; Online: Exploration and Biological Evaluation of 1,3-Diamino-7

Zhu, Zihao / Chen, Cantong / Zhang, Jie / Lai, Fangfang / Feng, Jing / Wu, Guangxu / Xia, Jie / Zhang, Wenxuan / Han, Zunsheng / Zhang, Chi / Yang, Qingyun / Wang, Yuchen / Liu, Bo / Li, Tianlei / Wu, Song

Journal of medicinal chemistry

2023 Volume 66, Issue 20, Page(s) 13946–13967

Abstract: Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR ... ...

Abstract	Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7
MeSH term(s)	Mice ; Animals ; Folic Acid Antagonists ; Structure-Activity Relationship ; Methicillin-Resistant Staphylococcus aureus ; Disease Models, Animal ; Neoplasms ; Tetrahydrofolate Dehydrogenase/metabolism
Chemical Substances	Folic Acid Antagonists ; Tetrahydrofolate Dehydrogenase (EC 1.5.1.3)
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c00891
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Article ; Online: Analyzing the gene regulatory network in hepatitis B patients by single-cell ATAC sequencing

Xu, Huixuan / Yu, Haiyan / Zheng, Fengping / Zhang, Cantong / Cai, Wanxia / Zhang, Xinzhou / Tang, Donge / Dai, Yong

Clin Rheumatol. 2022 Nov., v. 41, no. 11, p. 3513-3524

2022 , Page(s) 3513–3524

Abstract: OBJECTIVE: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing. BACKGROUND: Hepatitis B virus ( ...

Abstract	OBJECTIVE: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing. BACKGROUND: Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory responses. The exact mechanism is unknown. As such, there is an urgent need to address this problem and study the relationship between aberrant peripheral blood mononuclear cell (PBMC) immune response and progression of liver disease. METHOD: The sequencing of the chromatin accessibility of 8016 cells from the whole venous blood of normal control (NC) individuals and CHB patients was performed through assay for transposase-accessible chromatin in single-cell sequencing (ScATAC-seq). Unsupervised clustering and annotation analyses were performed by Signac (version 1.7.0) and Seurat clustering to identify different cell types. Then, TF motif enrichment analysis and differentially expressed peak analysis were performed to identify cell-type-specific candidate open chromatins related to CHB. RESULT: We identified 12 leukocytic clusters corresponding to five cell types. The specific cell types associated with CHB were found to be located in B-0 and T-3. We have drawn the regulatory network of the hepatitis B signal pathway composed of genes linked to the differentially expressed peaks of these two CHB disease-specific cell types. Further, we profoundly explored the potential mechanisms of B-0-associated TF motif IRF2 and T-3-associated TF motif FOXC2 in the occurrence of CHB. CONCLUSION: We have drawn a systematic and distinguishing gene regulatory network of CHB-related PBMCs. Key Points • Peripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. • We draw a systematic and distinctive gene regulatory network of CHB-related PBMC through ScATAC-seq.
Keywords	Hepatitis B virus ; chromatin ; chronic hepatitis B ; gene expression regulation ; gene regulatory networks ; immune response ; liver ; mononuclear leukocytes ; pathophysiology ; signal transduction
Language	English
Dates of publication	2022-11
Size	p. 3513-3524
Publishing place	Springer International Publishing
Document type	Article ; Online
ZDB-ID	604755-5
ISSN	0770-3198
ISSN	0770-3198
DOI	10.1007/s10067-022-06310-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Analyzing the gene regulatory network in hepatitis B patients by single-cell ATAC sequencing.

Xu, Huixuan / Yu, Haiyan / Zheng, Fengping / Zhang, Cantong / Cai, Wanxia / Zhang, Xinzhou / Tang, Donge / Dai, Yong

Clinical rheumatology

2022 Volume 41, Issue 11, Page(s) 3513–3524

Abstract: Objective: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing.: Background: Hepatitis B ... ...

Abstract	Objective: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing. Background: Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory responses. The exact mechanism is unknown. As such, there is an urgent need to address this problem and study the relationship between aberrant peripheral blood mononuclear cell (PBMC) immune response and progression of liver disease. Method: The sequencing of the chromatin accessibility of 8016 cells from the whole venous blood of normal control (NC) individuals and CHB patients was performed through assay for transposase-accessible chromatin in single-cell sequencing (ScATAC-seq). Unsupervised clustering and annotation analyses were performed by Signac (version 1.7.0) and Seurat clustering to identify different cell types. Then, TF motif enrichment analysis and differentially expressed peak analysis were performed to identify cell-type-specific candidate open chromatins related to CHB. Result: We identified 12 leukocytic clusters corresponding to five cell types. The specific cell types associated with CHB were found to be located in B-0 and T-3. We have drawn the regulatory network of the hepatitis B signal pathway composed of genes linked to the differentially expressed peaks of these two CHB disease-specific cell types. Further, we profoundly explored the potential mechanisms of B-0-associated TF motif IRF2 and T-3-associated TF motif FOXC2 in the occurrence of CHB. Conclusion: We have drawn a systematic and distinguishing gene regulatory network of CHB-related PBMCs. Key Points • Peripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. • We draw a systematic and distinctive gene regulatory network of CHB-related PBMC through ScATAC-seq.
MeSH term(s)	Chromatin/metabolism ; Gene Regulatory Networks ; Hepatitis B/genetics ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/genetics ; Humans ; Leukocytes, Mononuclear/metabolism ; Transposases/genetics ; Transposases/metabolism
Chemical Substances	Chromatin ; Transposases (EC 2.7.7.-)
Language	English
Publishing date	2022-07-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	604755-5
ISSN	1434-9949 ; 0770-3198
ISSN (online)	1434-9949
ISSN	0770-3198
DOI	10.1007/s10067-022-06310-z
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Article ; Online: Machine learning-based intradialytic hypotension prediction of patients undergoing hemodialysis: A multicenter retrospective study.

Dong, Jingjing / Wang, Kang / He, Jingquan / Guo, Qi / Min, Haodi / Tang, Donge / Zhang, Zeyu / Zhang, Cantong / Zheng, Fengping / Li, Yixi / Xu, Huixuan / Wang, Gang / Luan, Shaodong / Yin, Lianghong / Zhang, Xinzhou / Dai, Yong

Computer methods and programs in biomedicine

2023 Volume 240, Page(s) 107698

Abstract: Background and objective: Intradialytic hypotension (IDH) is closely associated with adverse clinical outcomes in HD-patients. An IDH predictor model is important for IDH risk screening and clinical decision-making. In this study, we used Machine ... ...

Abstract	Background and objective: Intradialytic hypotension (IDH) is closely associated with adverse clinical outcomes in HD-patients. An IDH predictor model is important for IDH risk screening and clinical decision-making. In this study, we used Machine learning (ML) to develop IDH model for risk prediction in HD patients. Methods: 62,227 dialysis sessions were randomly partitioned into training data (70%), test data (20%), and validation data (10%). IDH-A model based on twenty-seven variables was constructed for risk prediction for the next HD treatment. IDH-B model based on ten variables from 64,870 dialysis sessions was developed for risk assessment before each HD treatment. Light Gradient Boosting Machine (LightGBM), Linear Discriminant Analysis, support vector machines, XGBoost, TabNet, and multilayer perceptron were used to develop the predictor model. Results: In IDH-A model, we identified the LightGBM method as the best-performing and interpretable model with C- statistics of 0.82 in Fall30Nadir90 definitions, which was higher than those obtained using the other models (P<0.01). In other IDH standards of Nadir90, Nadir100, Fall20, Fall30, and Fall20Nadir90, the LightGBM method had a performance with C- statistics ranged 0.77 to 0.89. As a complementary application, the LightGBM model in IDH-B model achieved C- statistics of 0.68 in Fall30Nadir90 definitions and 0.69 to 0.78 in the other five IDH standards, which were also higher than the other methods, respectively. Conclusion: Use ML, we identified the LightGBM method as the good-performing and interpretable model. We identified the top variables as the high-risk factors for IDH incident in HD-patient. IDH-A and IDH-B model can usefully complement each other for risk prediction and further facilitate timely intervention through applied into different clinical setting.
MeSH term(s)	Retrospective Studies ; Hypertension/etiology ; Renal Dialysis/adverse effects ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/therapy ; Machine Learning ; Humans ; Male ; Female ; Adult ; Middle Aged ; Risk Adjustment
Language	English
Publishing date	2023-06-25
Publishing country	Ireland
Document type	Multicenter Study ; Journal Article
ZDB-ID	632564-6
ISSN	1872-7565 ; 0169-2607
ISSN (online)	1872-7565
ISSN	0169-2607
DOI	10.1016/j.cmpb.2023.107698
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Article: Controversial treatments: An updated understanding of the coronavirus disease 2019

Zhang, Cantong / Huang, Shaoying / Zheng, Fengping / Dai, Yong

J. med. virol

Abstract	An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #17542
Database	COVID19

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Article ; Online: Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis.

Xu, Huixuan / Yu, Haiyan / Liu, Lixiong / Wu, Hongwei / Zhang, Cantong / Cai, Wanxia / Hong, Xiaoping / Liu, Dongzhou / Tang, Donge / Dai, Yong

Frontiers in immunology

2021 Volume 12, Page(s) 760381

Abstract: Objective: Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.: Methods: We integrated single-cell ... ...

Abstract	Objective: Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot. Methods: We integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis. Results: We identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene Conclusions: Our results revealed a possible mechanism by which
MeSH term(s)	Adult ; Chromatin Immunoprecipitation Sequencing ; Female ; Gene Expression ; Humans ; Leukocytes, Mononuclear/cytology ; Male ; RNA-Seq ; Single-Cell Analysis ; Spondylitis, Ankylosing/genetics ; Spondylitis, Ankylosing/immunology ; Transcription Factors/genetics ; Young Adult
Chemical Substances	Transcription Factors
Language	English
Publishing date	2021-11-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.760381
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Article ; Online: The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease.

Zheng, Fengping / Xu, Huixuan / Huang, Shaoying / Zhang, Cantong / Li, Shanshan / Wang, Kang / Dai, Weier / Zhang, Xinzhou / Tang, Donge / Dai, Yong

Nephron

2021 Volume 145, Issue 6, Page(s) 760–769

Abstract: Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood ... ...

Abstract	Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood monocytes (PBMCs) of patients with ESRD. Method: We combined TMT labeling with LC-MS/MS analysis to compare Khib modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of Khib, and the bioinformatics analysis was conducted to analyze the pathology of these Khib-modified proteins. Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 Khib sites on 324 upregulated proteins and 287 Khib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the Khib protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients. Conclusion: In this study, we found that Khib-modified proteins correlated with the occurrence and progression of ESRD.
MeSH term(s)	Adult ; Case-Control Studies ; Computational Biology ; Down-Regulation ; Female ; Humans ; Kidney Failure, Chronic/blood ; Lysine/analogs & derivatives ; Lysine/metabolism ; Male ; Middle Aged ; Monocytes/metabolism ; Proteomics ; Up-Regulation
Chemical Substances	2-hydroxyisobutyryl-lysine ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-09-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000518424
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Article ; Online: Immune cell and TCR/BCR repertoire profiling in systemic lupus erythematosus patients by single-cell sequencing.

Zheng, Fengping / Xu, Huixuan / Zhang, Cantong / Hong, Xiaoping / Liu, Dongzhou / Tang, Donge / Xiong, Zuying / Dai, Yong

Aging

2021 Volume 13, Issue 21, Page(s) 24432–24448

Abstract: The immune cells and the repertoire of T cells and B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Exploring their expression and distribution in SLE can help us better understand this lethal autoimmune disease. ... ...

Abstract	The immune cells and the repertoire of T cells and B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Exploring their expression and distribution in SLE can help us better understand this lethal autoimmune disease. In this study, we used a single-cell 5' RNA sequence and single-cell T cell receptor (TCR)/B cell receptor (BCR) to study the immune cells and the repertoire from ten SLE patients and the paired normal controls (NC). The results showed that 9732 cells correspondence to 12 cluster immune cell types were identified in NC, whereas 11042 cells correspondence to 16 cluster immune cell types were identified in SLE. The results demonstrated that neutrophil, macrophage, and dendritic cells were accumulated in SLE by annotating the immune cell types. Besides, the bioinformatics analysis of differentially expressed genes (DEGs) in these cell types indicates their role in inflammation response. In addition, patients with SLE showed increased TCR and BCR clonotypes compared with the healthy controls. Furthermore, patients with SLE showed biased usage of TCR and BCR V(D)J genes. Taken together, we characterized the transcriptome and TCR/BCR immune repertoire profiles of SLE patients, which may provide a new avenue for the diagnosis and treatment of SLE.
MeSH term(s)	Adult ; B-Lymphocytes/immunology ; Humans ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/metabolism ; Middle Aged ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Single-Cell Analysis ; T-Lymphocytes/immunology ; Transcriptome/genetics
Chemical Substances	Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2021-11-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203695
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Article ; Online: Gene regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells.

Zhang, Cantong / Hong, Xiaoping / Yu, Haiyan / Xu, Huixuan / Qiu, Xiaofen / Cai, Wanxia / Hocher, Berthold / Dai, Weier / Tang, Donge / Liu, Dongzhou / Dai, Yong

Modern rheumatology

2022 Volume 33, Issue 4, Page(s) 739–750

Abstract: Objectives: Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the ... ...

Abstract	Objectives: Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of rheumatoid arthritis (RA) at a single-cell resolution using epigenetic technology. Methods: Peripheral blood mononuclear cells of seven RA patients and seven natural controls were extracted nuclei suspensions for library construction. Subsequently, scATAC-seq was performed to generate a high-resolution map of active regulatory DNA for bioinformatics analysis. Results: We obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in RA pathogenesis by regulating the activity of mitogen-activated protein kinase. Consequently, two genes (PTPRC and SPAG9) regulated by 10 key TFs were found, which may be associated with RA disease pathogenesis, and these TFs were obviously enriched in RA patients (P < .05, fold change value > 1.2). With further quantitative polymerase chain reaction validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs [ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), and MEF2B], showing highly accessible binding sites in RA patients. Conclusions: These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived peripheral blood mononuclear cells, providing insights into therapy from an epigenetic perspective.
MeSH term(s)	Humans ; Gene Regulatory Networks ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/pathology ; Chromatin ; Leukocytes, Mononuclear ; Case-Control Studies ; Transcription Factors ; Chromatin Immunoprecipitation Sequencing ; Adult ; Middle Aged ; Aged ; Male ; Female
Chemical Substances	Chromatin ; Transcription Factors
Language	English
Publishing date	2022-07-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roac072
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