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11. Corrigendum to “Discovery of a potent, selective and cell active inhibitor of m6A demethylase ALKBH5” [Eur. J. Med. Chem. 238 (2022) 114446]

Author

Fang, Zhen, primary, Mu, Bo, additional, Liu, Yang, additional, Guo, Nihong, additional, Xiong, Liang, additional, Guo, Yinping, additional, Xia, Anjie, additional, Zhang, Rong, additional, Zhang, Hailin, additional, Yao, Rui, additional, Fan, Yan, additional, Li, Linli, additional, Yang, Shengyong, additional, and Xiang, Rong, additional

Published
2023
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12. Discovery of a Potent and Cell-Active Inhibitor of DNA 6mA Demethylase ALKBH1

Author

Xiong, Liang, Li, Feng, Guo, Yinping, Zhang, Jian, Xu, Ke, Xiong, Zijie, Tong, Aiping, Li, Linli, and Yang, Shengyong

Abstract

N6-Methyladenine (6mA) of DNA has emerged as a novel epigenetic mark in eukaryotes, and several 6mA effector proteins have been identified. However, efforts to selectively inhibit the biological functions of these effector proteins with small molecules are unsuccessful to date. Here we report the first potent and selective small molecule inhibitor (13h) of AlkB homologue 1 (ALKBH1), the only validated 6mA demethylase. 13hshowed an IC50of 0.026 ± 0.013 μM and 1.39 ± 0.13 μM in the fluorescence polarization (FP) and enzyme activity assay, respectively, and a KDof 0.112 ± 0.017 μM in the isothermal titration calorimetry (ITC) assay. The potency of 13hwas well explained by the cocrystal structure of the 13h-ALKBH1 complex. Furthermore, 13hdisplayed excellent selectivity for ALKBH1. In cells, compound 13hand its derivative 16were able to engage ALKBH1 and modulate the 6mA levels. Collectively, our study identified the first potent, isoform selective, and cell-active ALKBH1 inhibitor, providing a tool compound for exploring the biological functions of ALKBH1 and DNA 6mA.

Published
2024
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20. Effect of Cerebral Small Vessel Disease Burden on Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment

Author

Huang, Hao, primary, Zong, Weifeng, additional, Tong, Xu, additional, Tian, Xue, additional, Wang, Anxin, additional, Jia, Baixue, additional, Zhao, Jing, additional, Wu, Lingshan, additional, Zhou, Xirui, additional, Guo, Yinping, additional, Zhang, Yi, additional, Yu, Zhiyuan, additional, Wang, Yilong, additional, Wang, Yongjun, additional, Luo, Xiang, additional, and Miao, Zhongrong, additional

Published
2022
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21. Association of Excessive Daytime Sleepiness with Cerebral Small Vessel Disease in Community-Dwelling Older Adults

Author

Zhao,Jing, Kong,Qianqian, Wang,Minghuan, Huang,Hao, Zhou,Xirui, Guo,Yinping, Zhang,Yi, Wu,Lingshan, Yu,Zhiyuan, Luo,Xiang, Zhao,Jing, Kong,Qianqian, Wang,Minghuan, Huang,Hao, Zhou,Xirui, Guo,Yinping, Zhang,Yi, Wu,Lingshan, Yu,Zhiyuan, and Luo,Xiang

Abstract

Jing Zhao, Qianqian Kong, Minghuan Wang, Hao Huang, Xirui Zhou, Yinping Guo, Yi Zhang, Lingshan Wu, Zhiyuan Yu, Xiang Luo Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xiang Luo, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 27-83663337, Email flydottjh@163.comPurpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD.Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55– 85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD.Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p < 0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p < 0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p < 0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p < 0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564).Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associa

Published
2022

27. Impact of Inclusive Leadership on Innovative Work Behavior: The Mediating Role of Job Crafting.

Author

Guo, Yinping, Jin, Junge, and Yim, Sang-Hyuk

Subjects
INCLUSIVE leadership, JOB performance, STRUCTURAL equation modeling, EMPLOYEE motivation
Abstract

The study aims to examine the mediating role of job crafting between inclusive leadership and innovative work behavior. The data were collected from 314 workers employed in China's small and medium-sized industries. The data collection was done through survey design. The data analysis was done using Spss 26.0 and through structural equation modeling by Mplus 8. Inclusive leadership was found to be related to job crafting and innovative work behavior of the employees. Job crafting was found to be mediating between inclusive leadership and innovative work behavior. The study delineated the link mechanism between inclusive leadership and innovative work behavior. Studying inclusive leadership in the context of Chinese culture is a powerful complement to inclusive leadership theory. This paper provides the managers of SMEs with significant managerial insights into how inclusive leadership can effectively motivate employees' innovative work behaviors. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Developing a rapid and highly efficient cowpea regeneration, transformation and genome editing system using embryonic axis explants

Author

Che, Ping, primary, Chang, Shujun, additional, Simon, Marissa K., additional, Zhang, Zhifen, additional, Shaharyar, Ahmed, additional, Ourada, Jesse, additional, O’Neill, Dennis, additional, Torres‐Mendoza, Mijael, additional, Guo, Yinping, additional, Marasigan, Kathleen M., additional, Vielle‐Calzada, Jean‐Philippe, additional, Ozias‐Akins, Peggy, additional, Albertsen, Marc C., additional, and Jones, Todd J., additional

Published
2021
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37. RNA-seq and microarray complement each other in transcriptome profiling

Author

Kogenaru Sunitha, Qing Yan, Guo Yinping, and Wang Nian

Subjects
RNA-seq, Microarray, Transcriptome profiling, Pathogenic bacteria, Virulence, Type 3 secretion system, Effectors, HrpX, Xanthomonas, Citrus canker disease, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background RNA-seq and microarray are the two popular methods employed for genome-wide transcriptome profiling. Current comparison studies have shown that transcriptome quantified by these two methods correlated well. However, none of them have addressed if they complement each other, considering the strengths and the limitations inherent with them. The pivotal requirement to address this question is the knowledge of a well known data set. In this regard, HrpX regulome from pathogenic bacteria serves as an ideal choice as the target genes of HrpX transcription factor are well studied due to their central role in pathogenicity. Results We compared the performance of RNA-seq and microarray in their ability to detect known HrpX target genes by profiling the transcriptome from the wild-type and the hrpX mutant strains of γ-Proteobacterium Xanthomonas citri subsp. citri. Our comparative analysis indicated that gene expression levels quantified by RNA-seq and microarray well-correlated both at absolute as well as relative levels (Spearman correlation-coefficient, rs > 0.76). Further, the expression levels quantified by RNA-seq and microarray for the significantly differentially expressed genes (DEGs) also well-correlated with qRT-PCR based quantification (rs = 0.58 to 0.94). Finally, in addition to the 55 newly identified DEGs, 72% of the already known HrpX target genes were detected by both RNA-seq and microarray, while, the remaining 28% could only be detected by either one of the methods. Conclusions This study has significantly advanced our understanding of the regulome of the critical transcriptional factor HrpX. RNA-seq and microarray together provide a more comprehensive picture of HrpX regulome by uniquely identifying new DEGs. Our study demonstrated that RNA-seq and microarray complement each other in transcriptome profiling.

Published
2012
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38. Developing a rapid and highly efficient cowpea regeneration and transformation system using embryonic axis explants

Author

Che, Ping, primary, Chang, Shujun, additional, Simon, Marissa K., additional, Zhang, Zhifen, additional, Shaharyar, Ahmed, additional, Ourada, Jesse, additional, O’Neill, Dennis, additional, Torres-Mendoza, Mijael, additional, Guo, Yinping, additional, Marasigan, Kathleen M., additional, Vielle-Calzada, Jean-Philippe, additional, Ozias-Akins, Peggy, additional, Albertsen, Marc C., additional, and Jones, Todd J., additional

Published
2019
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40. Thromboelastography predicts dual antiplatelet therapy-related hemorrhage in patients with acute ischemic stroke

Author

He, Dan, Guo, Yinping, Zhang, Yi, Zhao, Jing, Wu, Lingshan, Yu, Zhiyuan, Qu, Wensheng, and Luo, Xiang

Abstract

BackgroundStratification of the risk of hemorrhage in patients with acute ischemic stroke following dual antiplatelet therapy (DAPT) is challenging. It remains unclear whether thromboelastography (TEG) can be used to predict DAPT-related hemorrhagic events.ObjectiveThe present study aims to discover predictors for hemorrhage events after DAPT based on parameters such as TEG.MethodsA total of 859 patients with acute ischemic stroke who received DAPT were recruited consecutively. Demographic, clinical, and neuroimaging characteristics were evaluated at baseline; TEG parameters were obtained 7 days later after DAPT. Hemorrhagic events were monitored about 1 month after the stroke.ResultsOf the patients, 61 (7.1%) had hemorrhagic events. Patients in the hemorrhage group had a lower adenosine diphosphate (ADP)-induced platelet-fibrin clot maximum amplitude and a higher ADP inhibition rate (ADP%) than those in the non-hemorrhage group (p<0.05). ADP% was confirmed as an independent predictor of hemorrhagic events with an optimal cut-off point of 83.3% (area under the curve (AUC) = 0.665, 95% CI 0.573 to 0.767, p<0.01). We constructed a logistic model based on D-dimer, National Institutes of Health Stroke Scale scores, and ADP% to predict hemorrhagic events in patients with acute ischemic stroke during DAPT (AUC=0.720, 95% CI 0.625 to 0.858, p<0.01), with a sensitivity of 72.1% and a specificity of 76.5%.ConclusionsMonitoring changes of TEG parameters helps to guide personalized DAPT for patients with ischemic stroke. A 30–82.3% range of ADP% is recommended for DAPT treatment.

Published
2022
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49. Structural Optimization and Structure-Activity Relationship of 1 H -Pyrazole-4-carboxylic Acid Derivatives as DNA 6mA Demethylase ALKBH1 Inhibitors and Their Antigastric Cancer Activity.

Author

Li F, Xiong L, Zhang J, Guo Y, Xu K, Xiong Z, Wang Y, Ji S, Tong A, Li L, and Yang S

Subjects
Humans, Structure-Activity Relationship, Animals, Mice, Cell Line, Tumor, Carboxylic Acids chemistry, Carboxylic Acids pharmacology, Carboxylic Acids chemical synthesis, Cell Proliferation drug effects, Molecular Structure, Molecular Docking Simulation, Mice, Nude, Mice, Inbred BALB C, AlkB Homolog 1, Histone H2a Dioxygenase metabolism, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology, Pyrazoles pharmacology, Pyrazoles chemistry, Pyrazoles chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Enzyme Inhibitors pharmacology, Enzyme Inhibitors chemistry, Enzyme Inhibitors chemical synthesis
Abstract

DNA N 6 -methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1 H -pyrazole-4-carboxylic acid derivative 29 . The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29 , we prepared a prodrug of 29 ( 29E ), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E . Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.

Published
2024
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50. Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain.

Author

Guo Y, Mao X, Xiong L, Xia A, You J, Lin G, Wu C, Huang L, Wang Y, and Yang S

Subjects
Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Histone-Lysine N-Methyltransferase metabolism, Humans, Models, Molecular, Molecular Structure, Drug Discovery, Enzyme Inhibitors pharmacology, Histone-Lysine N-Methyltransferase antagonists & inhibitors
Abstract

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1), we discovered the first potent and selective small molecule SETDB1-TTD inhibitor (R,R)-59 through stepwise structure-guided optimization. (R,R)-59 showed a K D value of 0.088±0.045 μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biological functions of SETDB1-TTD., (© 2021 Wiley-VCH GmbH.)

Published
2021
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